These 4708 Ganz

Rsum e e
La nano-structuration topographique des surfaces est un concept prometteur, notamment pour amliorer la bio-intgration des proth`ses orthopdiques en tie e e e tane. Dans cette optique, une nouvelle mthode de nano-structuration des surfaces e de titane anodis a t dveloppe. e ee e e Des asprits ordonnes de lordre de quelques dizaines de nanom`tres de e e e e hauteur ont t cres en anodisant du titane lectropoli en prsence de partie e ee e e cules polymriques dposes en mono-couches. Pour ce faire, un procd existant e e e e e dlctropolissage du titane a t adapt et optimis, permettant la production ee ee e e de surfaces de dpart extrmement lisses. Le contact entre les particules et le e e substrat a t mesur, modlis et nalement modi par le biais de traitements ee e e e e plasma, thermiques et par vapeurs chimiques, et son inuence sur la topographie de la couche doxyde anodique a t examine. ee e Dirents types de structures ordonnes ont ainsi t produits, puis carace e ee triss par microscopie ` force atomique (AFM) et par microscopie lectronique e e a e a balayage (SEM). Leet des conditions danodisation sur la topographie et la ` morphologie de la surface a t tudi. eee e An dacqurir une meilleure comprhension des phnom`nes ` luvre, une e e e e a exprience mod`le utilisant la lithographie lectronique a t conue. Des ranges e e e ee c e de masques polymriques de diam`tre croissant ont t dposes sur le titane e e ee e e an de simuler la prsence de particules de tailles correspondantes. Leet de ces e masques sur la topographie de la couche doxyde a ensuite t mesur par AFM, ee e SEM et tomographie FIB. Certains aspects des phnom`nes de structuration e e prcdemment observs avec les particules ont ainsi t claircis, en particulier e e e eee ltendue de la propagation de la couche anodise sous les masques. e e Enn, la modlisation numrique par lments nis a t utilise pour simuler e e ee ee e la phase initiale de croissance de la couche anodique autour de masques isolants,
permettant ainsi une meilleure comprhension de la formation de certaines des e structures topographiques observes. e En parall`le ` ces travaux sur la structuration de surfaces, des particules mule a tifonctionnelles de silice msoporeuse ont t produites. Elles taient destines a e ee e e ` lorigine ` servir dalternative aux particules polymriques utilises pour crer nos a e e e structurations. Leur procd de synth`se, fond sur la formation de particules par e e e e sol-gel dans une minimulsion, a t mis a lchelle et optimis, permettant la proe ee ` e e duction de particules submicroniques troitement distribues avec un important e e volume de micropores et une forte charge de nanoparticules fonctionnelles. Ces particules se sont avres inadaptes pour la structuration de surfaces, ee e mais leur potentiel pour dautres applications a t sond, en fonction du type de ee e nanoparticles incorpor dans la matrice de silice. e En combinaison avec des nanoparticlules doxyde de fer superparamagne tiques, elles ont t values en tant que vecteur magntique de mdicament. ee e e e e Le chargement et le relarguage du mdicament anti-cancer paclitaxel dans les e particules ont t analys sur ce syst`me mod`le, par lexprimentation et la siee e e e e mulation. Le relarguage du mdicament sest avr tr`s lent, restreint par une e ee e grande dirence de potentiel chimique entre la molcule en solution et celle ade e sorbe dans les pores. e Des nanoparticules dalumine dope au chrome (rubis) ont t synthtises e ee e e et caractrises pour une ventuelle application en tant que marqueurs uorese e e cents pour limagerie biomdicale. Leurs proprits de photoluminescence dans le e ee proche infrarouge ont t mesures et se sont rvles susamment intenses pour ee e e ee tre dtectes en microscopie par uorescence en champ large et en microscopie e e e confocale ` balayage laser. Elle nont pas pu en revanche tre incorpores dans a e e les particules multifonctionnelles lors de la synth`se par glication en mulsion. e e e Des nanoparticules uorescentes de sulfure de zinc dop au mangan`se ont e e galement t incorpores dans de la silice mesoporeuse, an de constituer le mae ee e triau de base de surfaces uorescentes multicolores. Par le biais dun traitement e thermique local par laser, la longueur donde dmission du matriau a t moe e ee die avec succ`s. Une programmation adquate du laser a ensuite permis de e e e raliser des images uorescentes multicolores. e
Mots clefs : titane, nano-structuration, topographie, silice mesoporeuses, particules multifonctionnelles.
iv
Abstract
Topographic nanostructuring of surfaces is a promising concept, in particular to improve the bio-integration of titanium orthopedic implants. In this context, a new method for the nanostructuring of anodised titanium surfaces was developed. Ordered topographic features in the tens of nanometre in height were created by anodising electropolished titanium in the presence of polymeric particles deposited as monolayers. To do so, an existing electropolishing method for titanium was applied and optimised, allowing the production of extremely smooth starting surfaces. The particle-substrate contact was mesured, modeled and nally modied by plasma, thermal and chemical vapour treatments and its eect on the topography of the anodic oxide layer was investigated. Dierent types of ordered structures were produced, and characterised by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The inuence of the anodisation conditions on the topography and morphology of the surface was studied. To gain deeper understanding of the mechanisms at play, a model experiment using electron beam lithography was designed. Circular masks of increasing diameters were deposited on the surface to simulate the presence of particles of corresponding sizes, and the eect on the topography of the oxide layer was characterised. Some aspects of the structuring phenomena observed with the particles were thus cleared up, in particular the extent of oxide layer growth underneath the masks. Finally, numerical nite element modeling was applied to simulate the initial stages of anodic oxide growth around masks, leading to a better understanding of the formation of some of the topographic features observed. In parallel to this work on surface structuring, mesoporous silica particles containing dierent functional nanoparticles were produced. They were originally destined to serve as an alternative to the polymeric particles used to create
our structurations. Their synthesis process, based on the formation of particles by sol-gel in a miniemulsion, was scaled-up and optimised to obtain narrowly distributed submicron particles with a high micropore volume and a high functional nanoparticle loading. These multifunctional particles were nally found to be unadapted for surface structuring but were assessed for various other applications, depending on the type of nanoparticles incorporated in the silica matrix. In combination with superparamagnetic iron oxide nanoparticles (SPIONS), they were evaluated as potential magnetic drug delivery vehicles. Drug loading and release of the anticancer drug paclitaxel was studied as a model system by simulation and experiment. The release kinetics was found to be very slow, restricted by the large chemical potential dierence between the molecule in solution and the molecule adsorbed inside micropores. Chromium doped alumina (ruby) nanoparticles were synthesised and characterised for potential application as near-IR uorescent markers for biomedical imaging. Their photoluminescent properties were studied and were found to be suciently intense for bright-eld uorescence microscopy and confocal laser scanning microscopy. They could however not be incorporated in the multifunctional particles during the gel emulsion synthesis. Manganese doped zinc sulphide quantum dots were also encapsulated in a mesoporous silica matrix and used as the basis material for the production of multicolour uorescent surfaces. Localised laser thermal treatment of the material was successfully realised, causing a shift in its uorescence emission wavelength. Multicolour uorescent images could thus be drawn by programing the laser appropriately. Keywords: titanium, nanostructuring, topography, anodisation, mesoporous silica, multifunctional particles.
` A Gabrielle et a Joseph. ` Life, oh life, oh life. . . Desree
Acknowledgements
I want to thank my thesis director, Pr. Hofmann for his support, guidance and trust, and for the great freedom he left me. I hope it was put to good use. I also thank Pr. Alke Fink for her moral support throughout the years. I would also like to thank the Entwicklungsfond fr Seltene Metalle u (ESM) for their nancial support of this project. Futhermore, I would like to thank the following people:
The other members of my thesis jury, Pr. Marcus Textor, Pr.
Thomas Graule and Dr. Pierre-Franois Chauvy for their very c constructive review of the present work.
Michael Stuer and Amlie Bazzoni for their commitment in their e
semester theses, as well as Pr. Patrick Homann, Bamdad Afra for their expertise and their time.
Pr. Stefano Mischler, Jean-Daniel Neuvecelle and Julien Perret of
LMCH for their help with electrochemistry and their equipment.

The people at the atelier MX, Pierre-Andr Desponts, Werner e
Bronnimann, Yves Ruschetta and Adrien Grisendi, for their help and for their competence.
Pr. Jacques Lemaitre and Dr. Paul Bowen for their help with
experimental methodology and particle size measurements

All the people at LTP, for their friendship and for making these
three and a half years a very pleasant time.
Contents
List of Figures List of Tables 1 Introduction 1.1 1.2 1.3 Context of the work . . . . . . . . . . . . . . . . . . . . . . . . . . Objectives of the project . . . . . . . . . . . . . . . . . . . . . . . Structure of the thesis . . . . . . . . . . . . . . . . . . . . . . . . ix xv 1 2 3 6 7 8 8 9 9 9 9 11 11 11 12 12 13 14 15 16
2 Multifunctional mesoporous silica particles 2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.1 2.1.2 State of the art . . . . . . . . . . . . . . . . . . . . . . . . Functional nanoparticles used . . . . . . . . . . . . . . . . 2.1.2.1 2.1.2.2 2.1.2.3 2.2 2.2.1 2.2.2 2.2.3 Superparamagnetic iron oxide nanoparticles . . . Chromium doped alumina nanoparticles . . . . . Manganese doped zinc sulphide nanoparticles . .
Gel emulsion synthesis . . . . . . . . . . . . . . . . . . . . . . . . Principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . Previous work . . . . . . . . . . . . . . . . . . . . . . . . . Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.3.1 2.2.3.2 2.2.3.3 2.2.3.4 2.2.4 Emulsions . . . . . . . . . . . . . . . . . . . . . . Coarsening of emulsions . . . . . . . . . . . . . . The AOT-octane-water system . . . . . . . . . . Sol-gel process . . . . . . . . . . . . . . . . . . .
Materials and methods . . . . . . . . . . . . . . . . . . . .
iii
CONTENTS
2.2.5
Results and discussion . . . . . . . . . . . . . . . . . . . . 2.2.5.1 2.2.5.2 2.2.5.3 Scale-up of the emulsion . . . . . . . . . . . . . . Kinetic evolution . . . . . . . . . . . . . . . . . . Optimisation of emulsion parameters . . . . . . .
17 17 19 21 25 25 25 30 30 31 31 31 31 32 33 33 35 37 43 44 44 44 45 45 49 51 53 55 55 58 58
2.3
Materials characterisation . . . . . . . . . . . . . . . . . . . . . . 2.3.1 2.3.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results and discussion . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and methods . . . . . . . . . . . . . . . . . . . . 2.4.2.1 2.4.2.2 2.4.2.3 2.4.2.4 2.4.3 2.4.3.1 2.4.3.2 2.4.3.3 2.4.4 Paclitaxel loading . . . . . . . . . . . . . . . . . . Paclitaxel release . . . . . . . . . . . . . . . . . . Instrumentation and measurements . . . . . . . . Simulation . . . . . . . . . . . . . . . . . . . . . Paclitaxel adsorption . . . . . . . . . . . . . . . . Simulation . . . . . . . . . . . . . . . . . . . . . Paclitaxel release . . . . . . . . . . . . . . . . . .
2.4
Mesoporous silica spheres as drug delivery vehicles . . . . . . . . . 2.4.1 2.4.2
Results and discussion . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and methods . . . . . . . . . . . . . . . . . . . . Results and discussion . . . . . . . . . . . . . . . . . . . . 2.5.3.1 2.5.3.2 2.5.3.3 2.5.3.4 Materials characterisation . . . . . . . . . . . . . Characterisation of uorescence . . . . . . . . . . Eect of chromium concentration and annealing time on uorescence . . . . . . . . . . . . . . . . Fluorescence imaging . . . . . . . . . . . . . . . . Eect of SPIONS on uorescence . . . . . . . . . Synthesis of MS-SPION-Ruby multifunctional particles . . . . . . . . . . . . . . . . . . . . . . . . .
2.5
Chromium doped alumina . . . . . . . . . . . . . . . . . . . . . . 2.5.1 2.5.2 2.5.3
2.5.4
Application to multifunctional particles . . . . . . . . . . . 2.5.4.1 2.5.4.2
2.5.5
Conclusion and outlook . . . . . . . . . . . . . . . . . . . .
iv
CONTENTS
2.6
Laser annealing of silica coated ZnS:Mn2+ nanoparticles . . . . . . 2.6.1 2.6.2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6.2.1 2.6.2.2 2.6.3 2.6.4 Silica coated ZnS:Mn2+ nanoparticles . . . . . . . Eect of annealing . . . . . . . . . . . . . . . . .
59 59 59 59 61 61 64 64 65 70 72 77 78 78 78 78 79 80 83 83 84 86 86 87 87 87 87 89 90 90 91 91
Materials and methods . . . . . . . . . . . . . . . . . . . . Results and discussion . . . . . . . . . . . . . . . . . . . . 2.6.4.1 2.6.4.2 2.6.4.3 Oven annealing . . . . . . . . . . . . . . . . . . . Laser annealing . . . . . . . . . . . . . . . . . . . Cathodoluminescence . . . . . . . . . . . . . . .
2.6.5
Conclusion and outlook . . . . . . . . . . . . . . . . . . . .
3 Titanium surface structuring 3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.1 3.1.2 Titanium . . . . . . . . . . . . . . . . . . . . . . . . . . . Electrochemical properties . . . . . . . . . . . . . . . . . . 3.1.2.1 3.1.2.2 3.2 3.3 Passivity . . . . . . . . . . . . . . . . . . . . . . Anodic oxide lm growth . . . . . . . . . . . . .
Structuring of titanium surface . . . . . . . . . . . . . . . . . . . Electrochemical polishing of titanium . . . . . . . . . . . . . . . . 3.3.1 3.3.2 3.3.3 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and Methods . . . . . . . . . . . . . . . . . . . . 3.3.3.1 3.3.3.2 3.3.3.3 3.3.3.4 3.3.3.5 3.3.3.6 3.3.3.7 3.3.3.8 3.3.4 3.3.4.1 Electrolyte . . . . . . . . . . . . . . . . . . . . . Sample preparation . . . . . . . . . . . . . . . . . Rotating disc electrode . . . . . . . . . . . . . . . Multisample rotating electrode . . . . . . . . . . Electrochemical cell . . . . . . . . . . . . . . . . Multisample electrochemical cell . . . . . . . . . Roughness measurements . . . . . . . . . . . . . Roughness parameter . . . . . . . . . . . . . . . Experiment plan . . . . . . . . . . . . . . . . . .
Experimental optimisation of polishing . . . . . . . . . . .
CONTENTS
3.3.4.2 3.3.5 3.3.5.1 3.3.5.2 3.3.5.3 3.3.6 3.3.6.1 3.3.6.2 3.4 3.4.1 3.4.2 3.4.3
Results and discussion . . . . . . . . . . . . . . . Eect of water. . . . . . . . . . . . . . . . . . . . Sources of water contamination. . . . . . . . . . . Non-anodic current limitations. . . . . . . . . . . Rotating electrode setups . . . . . . . . . . . . . Fixed electrode setups . . . . . . . . . . . . . . .
91 95 95 96 97 98 98 98
Other factors aecting polishing. . . . . . . . . . . . . . .
Assessment of the dierent polishing setups. . . . . . . . .
Particle-substrate contact . . . . . . . . . . . . . . . . . . . . . . 101 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 101 Materials and methods . . . . . . . . . . . . . . . . . . . . 101 Results and discussion . . . . . . . . . . . . . . . . . . . . 102 3.4.3.1 3.4.3.2 3.4.3.3 Pristine particles . . . . . . . . . . . . . . . . . . 102 Eect of heat . . . . . . . . . . . . . . . . . . . . 104 Eect of acetone . . . . . . . . . . . . . . . . . . 109
3.5
Particle deposition . . . . . . . . . . . . . . . . . . . . . . . . . . 111 3.5.1 3.5.2 3.5.3 3.5.4 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 111 Materials and methods . . . . . . . . . . . . . . . . . . . . 112 Dip coating . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Drop drying . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Air plasma for particle deposition . . . . . . . . . . . . . . 116 Air plasma for SAM preparation . . . . . . . . . . . . . . 116 Air plasma for cleaning . . . . . . . . . . . . . . . . . . . . 118 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Materials and methods . . . . . . . . . . . . . . . . . . . . 121 Results and discussion . . . . . . . . . . . . . . . . . . . . 122 3.7.3.1 3.7.3.2 3.7.3.3 3.7.3.4 3.7.4 Inuence of the contact radius . . . . . . . . . . . 122 Eect of particle deposition . . . . . . . . . . . . 127 Inuence of the anodisation voltage . . . . . . . . 129 Inuence of the anodisation prole . . . . . . . . 131
3.6
Air plasma treatments . . . . . . . . . . . . . . . . . . . . . . . . 116 3.6.1 3.6.2 3.6.3
3.7
Surface structuring with polystyrene particles . . . . . . . . . . . 121 3.7.1 3.7.2 3.7.3
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
vi
CONTENTS
3.8
Model experiment using e-beam lithography . . . . . . . . . . . . 133 3.8.1 3.8.2 3.8.3 Aim of the experiment . . . . . . . . . . . . . . . . . . . . 133 Materials and methods . . . . . . . . . . . . . . . . . . . . 135 Results and discussion . . . . . . . . . . . . . . . . . . . . 136 3.8.3.1 3.8.3.2 3.8.3.3 3.8.3.4 3.8.3.5 E-beam lithography . . . . . . . . . . . . . . . . 136 Eect of the masks on topography . . . . . . . . 138 Eect of anodisation parameters . . . . . . . . . 141 Cross-sections by focused ion beam . . . . . . . . 144 Conclusion . . . . . . . . . . . . . . . . . . . . . 146
3.9
Finite element modeling . . . . . . . . . . . . . . . . . . . . . . . 149 3.9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 149 3.9.2 3.9.3 3.9.4 3.9.5 Single physic model . . . . . . . . . . . . . . . . . . . . . . 149 Two physics model . . . . . . . . . . . . . . . . . . . . . . 151 Results and discussion . . . . . . . . . . . . . . . . . . . . 153 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 157 159
4 Conclusion and outlook Bibliography
vii
CONTENTS
viii
List of Figures
1.1 1.2 Envisaged process ows for surface structuring with sacricial polystyrene (PS) particles as template. . . . . . . . . . . . . . . . . . . . . . . Envisaged process ows for surface structuring with multifunctional particles as inclusions in the oxide layer. . . . . . . . . . . . 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 Scheme of the emulsication process. . . . . . . . . . . . . . . . . Phase diagram for the AOT-octane-water system. . . . . . . . . . High shear rotor stator homogeniser. . . . . . . . . . . . . . . . . Kinetic evolution the emulsion by dynamic light scattering. . . . . Kinetic evolution of the emulsion by dynamic light scattering. . . Experimental values and values predicted by the statistical model (Adjusted values) for all the dierent treatments. . . . . . . . . . Eect of the factors on the particles mean volume diameter. . . . SEM micrographs of composite silica-SPION particles. . . . . . . Particle size distribution of composite silica-SPION particles. . . . 22 22 25 27 28 29 30 33 38 40 41 42 4 11 14 18 19 20 3
2.10 Nitrogen adsorption and desorption isotherms. . . . . . . . . . . . 2.11 Incremental pore diameter distribution in volume. . . . . . . . . . 2.12 Paclitaxel molecule. . . . . . . . . . . . . . . . . . . . . . . . . . . 2.13 Adsorption isotherm of paclitaxel on silica-SPION particles. . . . 2.14 Paclitaxel release prole in water. . . . . . . . . . . . . . . . . . . 2.15 Conguration of paclitaxel in a 2 nm diameter pore . . . . . . . . 2.16 Schematic representation of the chemical potential gradient at the pore opening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.17 Calculated paclitaxel concentration prole inside the pores. . . . .
ix
LIST OF FIGURES
2.18 Cumulative particle size distribution in volume for pristine HT-100 Condea powder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.19 Cumulative and frequency particle size distribution in volume for annealed chromium doped alumina after attrition. . . . . . . . . . 2.20 X-ray diraction spectrum of chromium doped alumina annealed at 900 C. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.21 Excitation and emission spectra of chromium doped alumina particles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 50 51 52 53 54 55 56 57 60 62 64 65 67 68 69 70 71 2.22 Emission intensity decay over time. . . . . . . . . . . . . . . . . . 2.23 Bi-factorial plan for the uorescence response of chromium doped alumina. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.24 Fluorescence response surface for chromium doped alumina: inuence of annealing time and chromium concentration. . . . . . . . . 2.25 Fluorescence microscopy images of chromium doped alumina agglomerate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.26 Fluorescence microscopy images of chromium doped alumina. . . . 2.27 Eect of SPION concentration on the uorescence emission intensity of chromium doped alumina. . . . . . . . . . . . . . . . . . . 2.28 Relative uorescence intensity for dierent SPION concentrations. 2.29 Phase diagram between iron oxide and chromium oxide. . . . . . . 2.30 Jablonski diagram for ZnS. . . . . . . . . . . . . . . . . . . . . . . 2.31 Dierent sample preparation methods for laser annealing. . . . . . 2.32 Colours obtained after annealing of ZnS:Mn2+ @SiO2 at dierent temperatures and in dierent atmospheres. . . . . . . . . . . . . . 2.33 Emission spectra of annealed ZnS:Mn2+ @SiO2 samples. . . . . . . 2.34 Array of laser impact points. . . . . . . . . . . . . . . . . . . . . . 2.35 Laser annealing of ZnS:Mn @SiO2 powder in dierent conditions. 2.36 EPFL logo drawn by IR laser on a bed of ZnS:Mn2+ @SiO2 . . . . . 2.37 Emission spectra of the laser treated and non treated zones by cathodoluminescence. . . . . . . . . . . . . . . . . . . . . . . . . . 2.38 Cathodoluminescence of ZnS:Mn2+ @SiO2 before and after laser treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2+
47 47 48
LIST OF FIGURES
2.39 SE image of compacted ZnS:Mn2+ @SiO2 surface and chemical mapping of the surface. . . . . . . . . . . . . . . . . . . . . . . . . . . 2.40 SE image of laser treated ZnS:Mn @SiO2 surface and chemical mapping of the surface. . . . . . . . . . . . . . . . . . . . . . . . . 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 Pourbaix diagram for titanium in aqueous environment. . . . . . . Levelling eect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Titanium sample before polishing. 75 79 84 86 88 89 92 92 94 96 99
2+
74
Rotating electrode setups. . . . . . . . . . . . . . . . . . . . . . . Multisample electrochemistry cell. . . . . . . . . . . . . . . . . . . Results: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Eect of the factors. . . . . . . . . . . . . . . . . . . . . . . . . . Response surface at 20 V. . . . . . . . . . . . . . . . . . . . . . . AFM-Typical polishing defects caused by small amounts of water in the electrolyte. . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.10 Multiscale roughness measurement from AFM proles for samples polished before and after optimisation. . . . . . . . . . . . . . . . 3.11 AFM-Polished titanium surface. . . . . . . . . . . . . . . . . . . . 100 3.12 Contact diameter measurement. . . . . . . . . . . . . . . . . . . . 102 3.13 Linear plot of the contact radius a0 against the square root of the particle radius. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 3.14 Eect of heat on the contact diameter. . . . . . . . . . . . . . . . 105 3.15 Geometry of a deformed elastic sphere. . . . . . . . . . . . . . . 106 3.16 Elastic, surface and total energies for the spreading of 200 nm and 500 nm PS particles at 150 C. . . . . . . . . . . . . . . . . . . . . 108 3.17 500 and 200 nm deformed particles (150 C for 5 minutes). . . . . 109 3.18 Capillary condensation around a spherical particle in presence of a vapour. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 3.19 Eect of acetone capillary condensation. . . . . . . . . . . . . . . 110 3.20 Schematic illustration of the phenomenon of particle diusion toward the meniscus encountered in processes such as dip coating and drop-drying. . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 3.21 Dierent deposits obtained by dip coating of 200 nm particle. . . 114
xi
LIST OF FIGURES
3.22 Self assembled monolayers by drop drying. . . . . . . . . . . . . . 115 3.23 Dense monolayer of 500 nm particles before (A) and after (B) 2 minutes oxygen plasma treatment. . . . . . . . . . . . . . . . . . . 117 3.24 Ordered array of hemispherical PS particles. . . . . . . . . . . . . 117 3.25 200 nm diameter particles after 2 minutes plasma treatment. . . . 118 3.26 Deformed particle after dierent plasma treatment times. . . . . . 119 3.27 Deformed particle array after dierent plasma treatment times. . 120 3.28 Structuring with particles. . . . . . . . . . . . . . . . . . . . . . . 122 3.29 Sample coated with 200 nm particles. . . . . . . . . . . . . . . . . 123 3.30 AFM image of anodised samples. . . . . . . . . . . . . . . . . . . 124 3.31 Topography prole across protrusions. . . . . . . . . . . . . . . . 124 3.32 Eect of heat deformed particles on the topography. . . . . . . . . 125 3.33 Surface structuring with deformed particles. . . . . . . . . . . . . 125 3.34 Prole across the imprint of a deformed particle. . . . . . . . . . . 126 3.35 Surface structuring with self-assembled monolayers of deformed particles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 3.36 Regular honeycomb structurations caused by SAMs of deformed particles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 3.37 Details of structurations by SAMs. . . . . . . . . . . . . . . . . . 128 3.38 Imprint of deformed particles after anodisation at dierent voltages.129 3.39 Height of topographic features as a function of anodisation voltage. 130 3.40 Structure of the oxide layer underneath the particles. . . . . . . . 131 3.41 Scheme of the dierent anodisation treatments. . . . . . . . . . . 132 3.42 Process ow and pattern for e-beam lithography. . . . . . . . . . . 134 3.43 Overview of the e-beam patterns for dierent electron dosages. . . 136 3.44 Arrays of masks by e-beam lithography. . . . . . . . . . . . . . . . 137 3.45 Tilt view of the 4 m, 800 nm, 400 nm and 100 nm masks. . . . . 137 3.46 2 m mask at dierent stages of the process. . . . . . . . . . . . . 138 3.47 SEM image of the e-beam sample after anodisation and removal of the masks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 3.48 Tilt SEM image of the e-beam sample after anodisation and removal of the masks. . . . . . . . . . . . . . . . . . . . . . . . . . . 139
xii
LIST OF FIGURES
3.49 AFM topography of the e-beam sample after anodisation and cleaning. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 3.50 AFM topography of the e-beam sample after anodisation and cleaning. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 3.51 Height proles across the dierent masks. . . . . . . . . . . . . . . 141 3.52 Eect of mask diameter on the edge structure. . . . . . . . . . . . 142 3.53 Eect of the anodisation parameters. . . . . . . . . . . . . . . . . 142 3.54 Proles across the dierent masks for dierent anodisation conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 3.55 Damage through a 100 m mask after anodisation at 55 V. . . . . 144 3.56 Dierent steps of the FIB technique. . . . . . . . . . . . . . . . . 145 3.57 FIB cross-sections across dierent e-beam imprint. . . . . . . . . . 148 3.58 Scheme of the model system. . . . . . . . . . . . . . . . . . . . . . 150 3.59 Current density around a mask. . . . . . . . . . . . . . . . . . . . 151 3.60 Oxide layer with mask. . . . . . . . . . . . . . . . . . . . . . . . . 152 3.61 Oxide layer growth around a mask. . . . . . . . . . . . . . . . . . 153 3.62 Detail of the edges at dierent anodisation times. . . . . . . . . . 154 3.63 Oxide growth between two adjacent masks. . . . . . . . . . . . . . 154
xiii
LIST OF FIGURES
xiv
List of Tables
2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Structure of the emulsion experiment plan. . . . . . . . . . . . . . List of emulsication experiments. . . . . . . . . . . . . . . . . . . Typical material characteristics. . . . . . . . . . . . . . . . . . . . Fitting parameters for Langmuirs isotherm. . . . . . . . . . . . . Calculated dierential adsorption enthalpies. . . . . . . . . . . . . Diusion coecients for dierent cases. . . . . . . . . . . . . . . . Material properties of chromium doped alumina. . . . . . . . . . . List of parameters tested. . . . . . . . . . . . . . . . . . . . . . . Structure of the experiment plan. . . . . . . . . . . . . . . . . . . 21 21 27 34 35 36 48 68 91
List of experiments. . . . . . . . . . . . . . . . . . . . . . . . . . . 93 Properties of polystyrene. . . . . . . . . . . . . . . . . . . . . . . 103 Contact radii predicted by the JKR model vs. measured contact radii. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 Calculated Youngs modulus according to the Lau et al. model. . 108 Electrical conductivities. . . . . . . . . . . . . . . . . . . . . . . . 150 Boundary conditions. . . . . . . . . . . . . . . . . . . . . . . . . . 152
xv
LIST OF TABLES
xvi
1 Introduction
1. INTRODUCTION
1.1
Context of the work
Surface structuring of titanium oxide surfaces is a promising concept that nds applications in various elds, such as biomedical engineering [64, 77, 128] and micro-systems applications [10, 55]. In this context, The aim of this work is to create a versatile technology platform making it possible to create precise and reproducible surface topographic structures in the nanometer range (10 to a few hundred nanometer in height) on titanium surfaces by an electrochemical route. Such a platform, together with the understanding of the underlying science, could eventually open new elds of application. Most attempts at nanostructuring titanium surfaces were done either by topdown methods such as microcontact printing and lithography, or by anodisation of titanium in dierent electrolytes, yielding characteristic structures such as titanium oxide nanotubes for anodisation in the presence of uorine ions, or more or less controlled pore structures in other types of electrolytes [42, 50, 109, 121, 128]. These features are dicult to control and to order satisfactorily and such processes often result in a more or less random topography. Another possibility is to create topographical structures by anodisation of titanium in the presence of particles. This approach can potentially present several advantages. Provided one achieves a good control of the particle size distribution on the one hand, and a good understanding of particle deposition processes on surfaces on the other, one can create arrays of adsorbed particles with a high degree of order and well dened characteristic length scales. It is a bottom-up approach (self-assembly of particles on surfaces) and therefore promises be comparatively cheap, quick and easy compared to expensive top-down processes such as traditional lithography techniques. These adsorbed particles then act as masks, allowing a selective exposure of the surface, to anodic oxidation in our case. In a related theme, the functionalisation of surfaces by adsorption of functional microparticles has been realised, for example to confer antiseptic properties to implant surfaces in order to prevent septic implant loosening [25]. Alternatively,
1.2 Objectives of the project
Figure 1.1: Envisaged process ows for surface structuring with sacricial polystyrene (PS) particles as template. Anodisation and removal of the particles.
encoded uorescent microparticles have been immobilised on surfaces for biosensor applications [22, 60]. An interesting concept would be to link these two ideas, and to perform particle lithography using adsorbed multifunctional microparticles, so as to make use of their structural properties in the lithography process, and then keep them adsorbed on the surface, and make use of their other properties, such as for example drug elution or uorescence.
1.2
Objectives of the project
The original aim of this project was to explore the feasibility of achieving ordered structuring of titanium surfaces by anodisation in the presence of particles. The purpose was not so much to optimise a process of a particular application as to nd creative ways to achieve new types of surface structures on the nanometer scale, and attempt to understand the phenomena observed. Two concepts were originally considered:
1. INTRODUCTION
The rst one was to perform the anodisation of a titanium surface covered with polymeric submicron particle in the hope that the particles would act as masks, locally preventing the growth of the oxide lm, and that the lm would then grow around the particles, partially or completely embedding them inside the newly formed oxide layer. This would create, after thermal removal of the particles, a more or less structured topography on the titanium surface, with a typical features height of the order of the layer thickness, as illustrated on gure 1.1 The second concept considered was to anodise the titanium surface in the presence of mesoporous silica (MS) composite multifunctional particles in the hope that they could be embedded inside the oxide layer during anodisation, and remain there. These particles are composed of a mesoporous silica matrix in which dierent functional nanoparticles (superparamagnetic iron oxide nanoparticles, uorescent quantum dots) are encapsulated. Thus, in addition to the topographic eect, the inclusion of these particles in the surface could confer it a whole new range of desirable properties (gure 1.2).
Figure 1.2: Envisaged process ows for surface structuring with multifunctional particles as inclusions in the oxide layer. Embedded particles retain their functionalities such as drug elution, uorescence or magnetic properties in addition to topographic structuring.
These two directions were developed in parallel, on one side attempting to
1.2 Objectives of the project
understand, by characterisation and modeling, the phenomena a play during anodisation in the presence of model commercial polymeric particle, and on the other synthesising multifunctional particles with dierent properties that could eventually be applied to surface structuring. The combination of these two research directions was however found to be unrealistic. The advances and experience gained in surface structuring by anodisation made it gradually clear that both the growth mechanism of the oxide layer and the properties of the synthesised multifunctional particles rendered the idea irrelevant. Our results showed that when anodisation was performed in the presence of adsorbed particles of the order of size of the oxide layer thickness (<5 m), the oxide layer did not grow around the particles leaving an hole, as illustrated on gure 1.1 and as was originally conjectured. Instead, the oxide layer grew unhindered underneath the particles, lifting them up with the rest of the surface. As a result, the idea of embedding multifunctional particles inside the oxide layer was not achievable by anodisation. Furthermore, the eect of adsorbed particles on the topography of the anodic layer was shown to be dependent on the particle-substrate contact area. In the case of the model polymeric particles used, this contact area could be increased by a heat treatment, causing a softening of the particles and their spreading on the surface. This spreading was however nor feasible with the silica based multifunctional particles, due to their mechanical properties, and the particlesubstrate contact area could not be increased in that case. Consequently, both research directions were carried on independently and no combination of the two technologies was attempted in the end. SPION-loaded MS particles were studied for potential application in drug delivery. In this perspective, an existing gel-emulsion synthesis method was studied and optimised to improve the production yield as well as the particle size distribution. In addition, two other types of functional nanoparticles were studied in combination with mesoporous silica. Near IR uorescent chromium-doped alumina nanoparticles were investigated as potential uorescent labels in bioimaging, and manganese doped zinc sulphide nanoparticles were applied in the production of multicolour uorescent displays.
1. INTRODUCTION
1.3
Structure of the thesis
The structure of the thesis reects what is explained above, and is divided into two main chapters. All aspects related to the synthesis, characterisation and application of the multifunctional particles are treated in chapter two, and all the work done on surface structuring of titanium is presented in chapter three.
2 Multifunctional mesoporous silica particles
2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES
2.1
2.1.1
Introduction
State of the art
Mesoporous silica (MS), thanks to its high pore volume, tunable pore size, high specic surface area and chemical inertness has been widely applied as a support material in various areas such as enzyme immobilization, drug and gene delivery, chromatography, adsorbents and catalysis [3, 38, 96, 111]. A notable trend is the combination of the porous properties of MS with functional nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONS) and/or uorescent semi-conductor nanoparticles (Quantum dots) to form multifunctional particles [53, 125]. The challenge for any synthesis and envisaged application is to achieve simultaneous control of the pore morphology, of the macroscopic morphology (particle size and size distribution) and of the functional nanoparticle loading. While pore morphology can be controlled by appropriate synthesis conditions and the use of self assembled surfactant templates, control of the macroscopic morphology is dicult and has been an important hurdle in the development of these materials [5]. Methods such as modied Stber processes, or microemulsion synthesis o can yield very narrow submicron size distributions and homogeneous, tunable pore diameter and are often used to produce well characterized core shell type nanoparticles [5, 62, 76, 106, 119, 125]. They are however less adapted to achieve high nanoparticle loading inside the MS sphere, which is important to enhance the desired functionalities. Other methods, such as the one presented here, rely on metastable morphology templates to form the desired product. In aerosolassisted synthesis and inverse miniemulsion synthesis, the droplets of liquid in air or of liquid in liquid determine the nal morphology of the particles [58, 90]. The main advantage of these methods is that they allow the encapsulation of large amounts of functional nanoparticles by dispersing them in the silica precursor, whilst retaining the porous properties of MS silica. Their main disadvantage is that they make it dicult to control the particle size and size distribution. They typically produce particles diameters in the tens of micrometer range with broad distributions.
2.1 Introduction
The challenge is therefore to produce well dened, narrowly distributed submicron mesoporous particles with well dened pore diameter and high functional nanoparticle loading.
2.1.2
2.1.2.1
Functional nanoparticles used

Superparamagnetic iron oxide nanoparticles
SPIONS have been used for separation techniques, site specic drug delivery, hyperthermia and are a powerful contrast agent for magnetic resonance imaging (MRI) [28, 75, 93, 114]. Magnetic Carrier Systems (MCS) combining their magnetic properties with those of MS have been increasingly studied and used in industry, particularly in diagnostics and bioseparation [78, 96]. A variety of synthesis approaches are found in the literature. Hematite nanoparticles were provided with a mesoporous silica shell, again using a sol-gel approach [76, 124]. Studies exist where the iron oxide nanoparticles have been precipitated in situ in the pore volume of the pre-formed silica particles, making it possible to achieve a high magnetic content (19 wt%) inside monodisperse particles, at the expense however of the pore volume [74]. Shao et al. [96] have formed magnetic silica particles through a direct miniemulsion of tetraethyl orthosilicate (TEOS) in water, with hydrophobic SPIONS dispersed in the TEOS phase, achieving high magnetic loading (10 to 30 wt%) and narrow size distribution, without however paying particular attention to the porosity. 2.1.2.2 Chromium doped alumina nanoparticles
Chromium doped alumina nanoparticles were investigated for potential application as a near IR uorescent markers for bio-imaging applications. 2.1.2.3 Manganese doped zinc sulphide nanoparticles
ZnS:Mn2+ nanoparticles were extensively studied as uorescent markers by B. Steitz at LTP, who attempted to combine them to SPION containing systems
[100]. Their optical interaction with SPIONS however quenches most of their uorescence, which limits the interest of such an association. In this study, laser thermal annealing of these uorescent nanoparticles in silica was attempted for the fabrication of uorescent displays. .
10
2.2 Gel emulsion synthesis
2.2
2.2.1
Gel emulsion synthesis

Principle
The synthesis of multifunctionnal MS particles by a gel emulsion process consists in dispersing an aqueous silica precursor into a non-miscible oil phase in order to form a homogeneous miniemulsion. Functional nanoparticles are present as colloids in the dispersed phase.
Figure 2.1: Scheme of the emulsication process.
The silica precusor is then caused to undergo a polycondensation reaction and form amorphous mesoporous silica. The miniemulsion droplets act as a morphology template for the formation of solid spherical MS particles. The functional nanoparticles suspended in the silica precursor are thus encapsulated inside the particles.
2.2.2
Previous work
The formulation of the emulsion system used was developed by F. Krauss and B. Steitz [51] in the framework of a masters thesis at EPFL. The emulsication was
11
performed in their case using an ultrasound horn on small volumes of emulsion (up to 5 ml).
2.2.3
2.2.3.1
Theory
Emulsions
Emulsions are a type of colloid consisting in the mixture of two immiscible liquids such as water and oil [11]. They are macroscopically homogeneous but microscopically heterogeneous as they are composed of two separate phases, one phase generally dispersed in the other in the form of spherical droplets. There are both oil-in-water emulsions (oil droplets in water, also called direct emulsions) and water-in-oil emulsions, droplets of water dispersed in oil, also called reverse emulsions). The mixture can be stabilised by a third component class called surfactants. A surfactant is a chemical compound which is preferentially adsorbed at a surface or at an interface and which modies its physico-chemical properties. It is a so-called amphiphilic molecule, composed of a hydrophobic and a hydrophilic group. The presence of surfactants in an emulsion tends to decrease the interfacial energy between the two phases, and slow down its separating back into a macroscopic two-phase system. Surfactants tend to for self-assembled aggregates in solution [29]. The simplest and best understood type of aggregate is the micelle, a spherical aggregate of surfactant molecules (see gure 2.1). As one increases the surfactant concentration in an emulsion, the oil-water interface is gradually populated by surfactant molecules, decreasing the interfacial energy, until at last it becomes saturated. At this concentration, known as the critical micelle concentration (CMC), the interfacial energy does not change signicantly anymore and the extra surfactant molecules start forming micelles in solution. Microemulsions are a specic subset of emulsion that have droplet with diameters in the range of 1 to 20 nm. The main particularity of this class of emulsion is that they are thermodynamically stable systems, as opposed to classical emulsions, which are metastable and have a tendency to be destroyed in time. They
12
are formed without extensive mechanical work. The surfactant micelles present in the continuous phase can swell up to a certain extent and accommodate a small amount of the other phase in their center in a process called micellar solubilisation. These micellar solutions are usually clear homogeneous liquids. Miniemulsions are metastable emulsions with a droplet size usually comprised between 50 and 500 nm. They are formed by applying high shear to the mixture using various techniques such as ultrasonication, high pressure homogenisers or high shear rotor stator turbines. 2.2.3.2 Coarsening of emulsions
There are four main mechanism for the coarsening and eventual destruction of metastable emulsions: Creaming and sedimentation is caused by a mismatch in the densities of the two phases, which causes the dispersed phase to either oat (creaming) or sink (sedimentation). This phenomenon is faster with increasing droplets or droplet ocs diameter. Coalescence is the rupture of the interfacial lm between two droplets causing them to merge into a single large droplet. Proximity of the droplets due to sedimentation, creaming or occulation increases the risk of coalescence. Ostwalds ripening is the gradual coarsening of larger droplets to the expense of smaller ones. The driving force behind it is the dierence in free surface energy between droplets of dierent sizes. It consists in a transfer of matter from small droplets to larger ones through the continuous phase. This is aggravated by the small residual solubility of the dispersed phase in the continuous phase. Flocculation is the aggregation of droplets due to insucient colloidal stabilisation forces. Flocs and single droplets can coexist at equilibrium in suspension [57].
13
2.2.3.3
The AOT-octane-water system
Sodium-bis(2 ethylhexyl) sulfosuccinate (or aerosol OT, AOT) is a surfactant with a polar head and two apolar tails. Phase diagrams could not be found in literature for the exact AOT-octane-water system, but several publications have studied similar systems in particular AOT-isooctane-water [104, 122] or AOTdecane-water [14] systems. The general aspect of these phase diagrams being quite alike, an approximate ternary phase diagram can be drawn for our system (gure 2.2)
Figure 2.2: Phase diagram for the AOT-octane-water system.
The location of our formulation is near the top corner of the triangle, at low water and AOT contents, in the two phases zone. The critical micelle concentration in octane is of the order of 1 103 mol/l [72].
14
2.2.3.4
Sol-gel process
Sol-gel processes are a type of wet chemical process by which a suspension of colloidal particles, or a solution of monomer, assemble to create a solid loose 3D network (gel). Typical sol-gel systems involve metal alkoxides, such as tetramethyl orthosilicate (TMOS), a widely used silica precursor, and the starting chemical used throughout this study. The sol -gel reaction comprises two successive steps, namely a hydrolysis reaction followed by a polycondensation reaction. The hydrolysis reaction consists in the replacement of a methoxide group of the TMOS1 by a hydroxyl group with the production of methanol. Si O CH3 + H2 O Si O H + CH3 OH (2.1)
The second reaction consists in a polycondensation between either two hydrolysed TMOS molecules with the production of water, or alternatively between one hydrolysed and one non-hydrolysed molecule, with the production of methanol. Si OH + HO Si Si O Si + H2 O (2.2)
Si O CH3 + HO Si Si O Si + CH3 OH
(2.3)
The gelation speed of the solution depends on both hydrolysis and condensation. In acidic conditions, the rate determining step is condensation, hydrolysis being quite fast. In basic conditions, the opposite is true. As a result, the morphology of the gel produced in each condition is quite dierent. Chain formation is favoured in acidic conditions and the gel obtained is softer and its porosity tends to collapse upon drying [105], whereas denser spherical particles will rather be formed at high pH. To obtain a fast gelation inside the emulsion droplets, the TMOS can be prehydrolysed in acidic conditions, and then, though the addition of a base, fast polycondensation of the gel can be induced [117]. Gels formed in such conditions have a larger SSA and a stier structure that prevents collapse of the porosity.
1
The triple bond symbol in (2.1) represents the three remaining methoxide groups.
15
TMOS is not readily water soluble, which presents a problem for the prehydrolysation step. Methanol is therefore used as a solvent. In the conditions used, the gelation time is around 10 to 15 minutes.
2.2.4
Materials and methods
Based on the formulation established by F. Krauss. Aqueous suspensions of polyvinyl alcohol (PVA) coated iron oxide nanoparticles containing 10.75 mg iron/ml and 2 mg PVA/ml were prepared as described previously [15]. Octane fraction (purum), tetramethyl orthosilicate (TMOS, p.a.), methanol (puriss.), hydrochloric acid (HCl, p.a.), sodium-bis(2 ethylhexyl) sulfosuccinate (AOT, 98 %) and tetramethyl ammonium hydroxide (puriss) were purchased from Fluka. 4 ml of methanol, 545 l of 0.2 M HCl, and 680 l of TMOS were mixed together for 10 minutes under continuous stirring to pre-hydrolyze the TMOS (molar ratio TMOS:methanol:H2 0=1:22:6). 2.5 ml of this pre-hydrolysed TMOS and 2.5 ml of PVA coated iron oxide dispersion were added to 514 ml of a 0.0054 M solution of AOT in octane fraction in a thermostatic reactor (20 C) and emulsied vigorously using a high shear rotor-stator homogenizer (Polytron PT DA 3030, see gure 2.3) for 30 minutes at 16000 rpm. 250 l of tetramethyl ammonium hydroxide at 2.5% v/v in DI water were nally added into the reactor and the mixture was emulsied for 5 more minutes. The emulsion droplets were left to harden into solid particles for 30 minutes and were then sedimented magnetically using a permanent FeNdB magnet (Maurer Magnets, 5x5x2.5 cm, BR 0.5 T), the AOT-octane supernatant was discarded, and the particles re-suspended in dichloromethane (DCM). They were washed three times by successive magnetic sedimentation, discarding of the supernatant and re-suspension in fresh DCM. Dynamic light scattering was on a Malvern mastersizer with a 633 nm He-Ne
laser on emulsions without addition of base.
16
2.2.5
2.2.5.1
Results and discussion

Scale-up of the emulsion
Three strategies were pursued, sometimes in combination, to increase the amount of particles produced: 1. to increase the volume of the reactor whilst keeping the same emulsion composition 2. to increasing the water-to-oil ratio 3. to set up a continuous emulsication system Increasing the volume of the reactor has been attempted by F. Krauss [51] using the ultrasound horn without much success as the power of the device is not sucient to homogenize volumes larger than 5 ml. To address this issue, a more powerful emulsication setup was adopted, namely a high shear rotor-stator homogeniser [71]. It consists in a turbine rotating in a toothed stator, resulting in a turbulent ow. This system allows the emulsication of larger volumes (up to 1 l) with comparable power per volume unit as the ultrasound horn. This system was used for all emulsication experiments. The second strategy consisting in increasing the volume of the dispersed phase is not successful, as the emulsion is destroyed before the particles harden. Good results are however obtained when emulsions with up to 4% dispersed phase are diluted immediately after the emulsication step by addition of AOT-octane solution at the CMC. The composition of this diluted emulsion can then be set to be equal to the original formulation (around 1%) and the colloidal stability is preserved suciently for the droplets to harden. A continuous emulsication method was not achieved because of the diculty of matching the average residence time in the reactor with the hardening time of the droplets. The emulsication process by turbine requires at least a few minutes, and the gelation time should not be inferior to the emulsication time. In such a case, the hardening gel starts sticking to the reactors walls and to the turbine shaft and does not form particles. This is a major dierence between ultrasound
17
Figure 2.3: High shear rotor stator homogeniser. The reactor is connected to a thermostatic circulator.
18
treatment and high shear turbine. In the former case, the emulsication time can exceed the gelation time without catastrophic consequence on the product as the hardening droplets remain in suspension. This caused some diculty when the change was made between the two methods. Continuous emulsication could be attempted with a high pressure homogeniser (HPH), which would yield more reproducible results and could be set up in line. 2.2.5.2 Kinetic evolution
In order to understand the phenomena involved in the colloidal stability of the emulsion, the kinetic evolution of the emulsion was investigated. Depending on the synthesis parameters (AOT concentration, rotation speed of the turbine, or water/oil ratio) the destruction of the emulsion can occur within a few minutes, before complete hardening of the droplets. To monitor the evolution of the droplet size, dynamic light scattering was implemented on an emulsion in which no base was added, so as to prevent the gelation of the droplets.
Figure 2.4: Kinetic evolution the emulsion by dynamic light scattering. The main mechanism at play is the occulation and subsequent sedimentation of the droplets.
The diculty of the DLS method in the case of emulsions, is that the concentration of droplets is a very inuent parameter of the kinetic behaviour of the system. It is however also an important parameter for the light scattering
19
experiment, as the scattered intensity is directly dependant on it and has to be sucient for the measurement. On gure 2.4, the main peak corresponding to single droplets is well visible around 500 nm. The top of the peak hardly shifts from this position during the time of the experiment, but it becomes broader towards the larger sizes, and new broad peaks appear in the tens of m range. These results are a clear indication that the single droplets do not undergo signicant Oswald ripening in the rst four hours after the end of emulsication, but are very prone to occulation, followed necessarily by sedimentation. The resistance of the droplets against coalescence once they are agglomerated in ocks is low, and the emulsion is quickly destroyed.
Figure 2.5: Kinetic evolution of the emulsion by dynamic light scattering. Single droplet evolution.
Colloidal stability in inverse emulsions is dicult to achieve. The absence of electrostatic charges to act as repulsive forces leave only steric hindrance as a possible mechanism for colloidal stabilisation. In this case two steps can be taken to improve the colloidal stability of the droplets. The water to oil ratio must be kept low (in our case 1 % volume) and the surfactant concentration must be kept to a minimum. At surfactant concentrations above the critical micelle concentration, micelles are present, and cause an additional attractive depletion interaction between the droplets [70].
20
2.2.5.3
Optimisation of emulsion parameters
The inuence of emulsication parameters were studied in an experiment plan including three parameters on two levels with two repetitions. The composition of the emulsion was kept constant as described in section 2.2.4, but on a total emulsion volume of 30 ml. Factor Levels (-1) (+1) A Temperature [ C] 15 20 B Time [min] 10 20 C Rotation speed [rpm] 12000 16000 Denition
Table 2.1: Structure of the emulsion experiment plan.
Treatment Experiment n Temperature [ C] Time [min.] Rot. speed [rpm] (1) 1 15 10 12000 A 2 20 10 12000 B 3 15 20 12000 AB 4 20 20 12000 C 5 15 10 16000 AC 6 20 10 16000 BC 7 15 20 16000 ABC 8 20 20 16000
Table 2.2: List of emulsication experiments.
The particles mean volume diameter was measured by centrifuge particle sizer (see section 2.3.1 for more detail) after hardening of the particles and redispersion in water. This represents a total of 16 dierent experiments, realised in random order so as to rule out block or sequence eects. The result of the experiments can be seen on gure 2.6. The reproducibility of the experiments is poor due to the inherent thermodynamic instability of the system. As can be seen on gure 2.7, the size of the droplets depends primarily on the emulsication conditions. The rotation speed,
21
Figure 2.6: Experimental values and values predicted by the statistical model (Adjusted values) for all the dierent treatments.
Figure 2.7: Eect of the factors on the particles mean volume diameter. These three eects account for 83.4 % of the experimental variation.
22
which determines the shear rate, is the most important factor inuencing the fractionation process. Slight dierences in the positioning of the turbine can aect the state of the vortex created, or modify the circulation of the emulsion inside the reactor, thus inducing variance in the droplet sizes. Eorts in methodology were made during this study to understand and eliminate the sources of variance, but although progress was made to an extent allowing the conduct of a pertinent experiment plan, it still remains too large to deduce physical models. Only three factors were retained as signicant (time B, rotation speed C and the interaction ABC), which alone account for 83.4 % of the total experimental variability, the remaining being considered as experimental error. This rather important experimental error is, as explained above, quite credible for such a system and this interpretation of the results seems therefore safe and consistent. We can see that higher shear rates produce smaller droplets in the range investigated, which perhaps leaves the possibility of further increasing the rotation speed (the maximum is 24000 rpm) to diminish the mean diameter. Emulsication time has a signicant inuence on droplet diameter in the range measured, and even at 12000 rpm, the system does not reach a steady state after only ten minutes of treatment. This means that destructive processes (coalescence, Ostwald ripening) which lead to a coarsening of the emulsion are not fast enough to entirely counteract the eect of the mechanical energy brought to the system, and the droplet size continues to decrease after this time. The span was used as a measure of the width of the particle size distribution. It is dened as follows: DV 90 DV 10 DV 50
Span =
(2.4)
The eect of the parameters on the span of the particles size distribution is small with respect to experimental error, as only one parameter, the temperature, has a statistically signicant eect. A 5 C temperature increase reduces the span by approximately 7 % the width of the distribution. This is probably due to a faster gelation of the TMOS after the end of the emulsication step. Optimal
23
conditions for the production of small particles with a narrow size distribution would therefore be those of experiment 8 (table 2.2).
24
2.3 Materials characterisation
2.3
2.3.1
Materials characterisation
Methods
Specic surface area measurements and porosimetry were realized by nitrogen adsorption, using a Micromeritics ASAP 2010 machine at 77K. The specic surface areas were calculated by the Brunauer-Emmet-Teller (BET) method, and the pore diameter distributions and total pore volume were derived from the adsorption branch by the Barrett-Joyner-Halenda (BJH) method. Density measurements were done on a Micromeritics Acupyc 1330 helium pycnometer. The particles were dried and degassed for 24 h at 200 C in vacuum prior to the measurements. Scanning electron microscopy (SEM) images were acquired on a FEI XLF30-FEG. Samples were prepared by drying a drop of the suspension on a polished titanium plate. Particle size measurements were done on a disc photocentrifuge particle sizer, CPS Model DC24000, using 470 nm light in a gradient of 8% to 24% sucrose solution. The particles were re-suspended in DI water. The results obtained were compared to the individual measurement of 536 particles from SEM pictures using ImageJ image analysis program.
2.3.2
The morphology of the particles is homogeneously spherical (gure 2.8) and their size is in the sub-micron range.
Figure 2.8: SEM micrographs of composite silica-SPION particles.
25
Their surface is rough, due to the presence of SPIONS and open porosity. The particles are neither coalesced nor agglomerated, which shows that the colloidal stability of the emulsion is good in the time range needed for the hardening of the particles. Light centrifuge techniques require a precise measurement of the hydrodynamic density of the material, as well as a correct estimate of its refractive index. The hydrodynamic density is determined mainly in our case by the pycnometric density of the material and the total pore volume. It was calculated by combining helium pycnometry with nitrogen adsorption porosimetry, assuming that the pore volume was fully lled with the dispersion medium (water). To calculate the refractive index of the composite material constituting our particles, the refractive index of each component, silica, iron oxide, PVA and the water in the pores was multiplied by its volume fraction in the particles and added up to yield a composite refractive index of 1.55. The CPS (gure 2.9) shows a normal size distribution with a mean volume diameter of 479 nm and a standard deviation of 106 nm, which corresponds to a dispersion of 22%. These results concur with SEM images, indicating that the method is valid, and that the hydrodynamic density was measured accurately. The size distribution is narrow compared to other systems using metastable morphology templates, such as aerosol assisted synthesis and other mini-emulsions systems [2, 90]. The helium pycnometer density value of 2.28 g/cm3 (table 2.3) is in good accordance with what can be calculated on the basis of the composition of the particles. The hydrodynamic density was calculated to be 1.77 g/cm3 with a measured pore volume of 0.291 cm3 /g. Mesoporous silica particles obtained by the Stber method or microemulsion o synthesis can be virtually monodisperse and present homogeneous, tunable pore diameters [45, 120]. Our particles have a broader size distribution but can contain up to 20 %wt of functional nanoparticles, thus enhancing the desired functionality whilst retaining the porous properties of the silica. Such a high nanoparticle content cannot to our knowledge be obtained with the abovementioned methods, which are more adapted for producing well characterized core shell type nanoparticles-silica composites with low nanoparticle loads.
26
Figure 2.9: Particle size distribution of composite silica-SPION particles. Volume distribution measured by centrifuge particle sizer (CPS).
Specic surface area (by BET): 720 m2 /g Average pore diameter (4V/A by BET): 2.6 nm Total pore volume 0.291 cm3 /g Porosity 0.4 He Pycnometer density 2.28 g/cm3 Hydrodynamic density 1.74 g/cm3 SiO2 content 86.6 %wt SPION content 11.1 %wt PVA content 2.3 %wt
Table 2.3: Typical material characteristics.
27
The particles have a high specic surface area (SSA) of 720 m2 /g, which is close to values reported in literature for mesoporous silica prepared from pre-hydrolyzed TMOS in basic conditions [105], bearing in mind that they are made up of only 86 wt% silica. The BJH adsorption-desorption isotherm (gure 2.10) has shape of a Brunnauers type I/type II combination, with a steep rise a low partial pressure, due to the lling of micropores, a second regime corresponding to the lling of small mesoporosity, and a plateau at higher partial pressure (P/P 0 = 0.45) [91, 116, 120].
Figure 2.10: Nitrogen adsorption and desorption isotherms. Before and after paclitaxel adsorption (see section 2.4).
It shows another steep rise around P/P 0 = 1 due to capillary condensation in the inter-particle spaces [2, 66]. The nitrogen volume adsorbed due to this eect was not considered in the calculation of the total pore volume. The isotherm also shows no hysteresis, which indicates the absence of an ink bottle eect: all the pores have access to the surface of the particle either directly, or through a larger pore [79]. The pore diameter distribution (gure 2.11) shows that 87 % of the total pore volume is constituted of pores smaller than 5 nm in diameter, narrowly distributed around an average pore diameter of 2.62 nm, which is realistic for TMOS based gels condensed in basic conditions [105].
28
Figure 2.11: Incremental pore diameter distribution in volume. Before and after paclitaxel adsorption (see section 2.4).
29
2.4
Mesoporous silica spheres as drug delivery vehicles
2.4.1
Introduction
The applicability of MS multifunctional particles for drug delivery applications was assessed using the anti-cancer drug paclitaxel as a model compound. Paclitaxel (or Taxol) is an anti-tumor agent that specically binds to the microtubules of cells during mitosis, thus blocking cellular division. Because cancer cells divide more frequently than healthy cells, the tumors are aected in priority. Paclitaxel has attracted much interest for the treatment of ovarian and breast cancers. The dimensions of the molecules (see gure 2.12) compared to our porosity, as well as the expertise developed at LTP by K. Dittmar [27] for the handling and measurement of paclitaxel solutions by HPLC, made it a good candidate for this study. It is however a very dangerous substance because of its strong antimitotic properties at very low concentrations, and requires to be handled with care.
Figure 2.12: Paclitaxel molecule.
The loading capacity of the drug in the particles was measured, as well as the release kinetics in water. Finally, simulations of the molecule in silica micropores were run using molecular dynamics.
30
2.4 Mesoporous silica spheres as drug delivery vehicles
2.4.2
2.4.2.1

Paclitaxel loading
Known masses of MS-SPION particles were suspended in dierent concentrations of paclitaxel in dichloromethane (DCM). Corresponding reference solutions without particles were prepared at the same time. The paclitaxel was left to adsorb on the particles for 48h at 4 C in the dark. The particles were then magnetically sedimented, the supernatant was pipetted out and its paclitaxel concentration was measured by high performance liquid chromatography (HPLC). The concentration in the references was measured at the same time. The amount of paclitaxel adsorbed was calculated on the basis of the concentration dierence between the samples and the references solutions. The experiment was done in triplicates. Sample preparation for nitrogen adsorption measurement on paclitaxel loaded samples was adapted from Hata et al. [35]. 2.4.2.2 Paclitaxel release
3.4 mg of MS-SPION particles were suspended for 48h in 10 ml of 100 g/ml solution of paclitaxel in DCM. They were then magnetically sedimented, supernatant was discarded, and the particles were left 1 minute in air for the remaining DCM to dry. The particles were re-suspended in 10 ml DI water under stirring. At dierent times, the particles were magnetically sedimented, and the supernatant was entirely sampled out for measurement and replaced by 10 ml of fresh DI water. At all times, the supernatant concentration of paclitaxel was kept well below the saturation concentration. The paclitaxel concentration in the samples was measured by HPLC. 2.4.2.3 Instrumentation and measurements
The HPLC system consisted of an Alliance 2690 pump module (Waters) connected to the analytical column ODS-3 (Inertsil
, particle size 5 m; 4.6 x 150 mm), which was protected with an ODS-3 conventional guard column (Inertsil ,
particle size 5 m; 4.6 x 50 mm). The analysis procedure applied in this study was adapted from literature [4, 110]. The mobile phase consisted of UP-water
31
and acetonitrile in a gradient elution. The ow rate was set to 1 ml/min. Detection was performed at 227 nm with a Photodiode Array Detector 996 (Waters) with connection to the Millenium 3.05.01 software data station (Waters). 100
l of each sample were injected for analysis via autosampler. The absorption of
paclitaxel as a function of retention time was recorded in the chromatograms. 2.4.2.4 Simulation
All simulations were carried out with Dr. Ulrich Aschauer using the Discover module within the Material Studio [1] modelling software package using the COMPASS forceeld. Amorphous SiO2 glass structures provided with this package have been used for surface calculations and as the starting point for pores. For pore generation, all atoms within a given radius of the center of the simulation box were removed, while retaining the stoichiometry of the simulation box. After the nano-pore atoms were xed to retain periodicity, the molecule was placed in the pore and DCM solvent molecules were allowed to diuse into the pore during an NPT (constant pressure) simulation from a reservoir until equilibrium was reached [65]. The reservoir was then disconnected, all atoms allowed to move in subsequent NVT (constant volume) simulations. The simulation timestep was chosen as 1 ps and Nose-Hoover and Andersen thermo- and barostats were applied as needed. Information about the total simulation time are given along with the results. Adsorption enthalpies were calculated using (2.5), where the letters S, A and L denote the substrate, the adsorbent and the liquid respectively. Hads = HSAL (HSL + HAL HL ) (2.5)
This equation compares the state (SAL) where the paclitaxel is adsorbed to the substrate (surface or pore), with the states of just the substrate (SL) or the paclitaxel (AL) in contact with the solvent. The self interaction energy within the solvent (L) has to be subtracted due to double counting in both SL and AL terms. Diusion coecients were calculated from the mean square displacement (MSD) as given by equation 2.6 and Einsteins equation as given by (2.7).
32
MSD(t) = |r(t = 0) r(t)|2
(2.6)
MSD(t) (2.7) t Mt Where the vectors r are the atom positions at time t and the average being D = lim taken over all atoms of the diusing molecule and M is a dimensionality number, which is 6 for a 3D situation and 2 for a 1D situation.
2.4.3
2.4.3.1

Paclitaxel adsorption
The amount of paclitaxel adsorbed on the particles increases with the supernatant concentration until a saturation plateau is reached (gure 2.13).
Figure 2.13: Adsorption isotherm of paclitaxel on silica-SPION particles. The data is tted with Langmuirs adsorption isotherm.
Nitrogen adsorption porosimetry (gure 2.11) realized on the particles after saturation with paclitaxel shows a decrease in specic pore volume of 0.19 cm3 /g, principally in the pores with diameters smaller than 5 nm. The average pore diameter is decreased from 2.62 nm to 2.3 nm, indicating that the paclitaxel is
33
a 8.03 105 mol/g b 2.63 104 l/mol

Table 2.4: Fitting parameters for Langmuirs isotherm.
indeed adsorbed as a dense layer inside the larger micropores. The decrease in pore volume is too large to be entirely accounted for by the presence of paclitaxel. The total volume of paclitaxel adsorbed can be calculated to be 0.091 cm3 /g using using the value calculated by Huynh et al. for the density of paclitaxel [39]. Alternatively, is can be estimated geometrically from the decrease in the average pore diameter to be 0.15 cm3 /g. Between these two estimates, the adsorbed paclitaxel volume represents only between 45 and 60 % of the total pore volume decrease, which can be explained by assuming that the molecules partially or completely block the opening of pores, leaving large volumes inaccessible to the adsorbing nitrogen. This is supported by the fact that the nitrogen adsorption-desorption isotherm on paclitaxel-lled particles presents an hysteresis which was not seen for the pristine particles: the partial obstruction of pore openings by the molecules results in an ink bottle structure and could account for this dierence. Park et al. [80] measured the adsorption isotherm of paclitaxel on mesoporous silica in a HPLC column and found Langmuirs adsorption isotherm to be a suitable model. The paclitaxel adsorption data was tted with a Langmuir isotherm of the form: abC (2.8) 1+bC with Q the quantity adsorbed, a the quantity adsorbed at saturation, b the Q= gradient of the curve at the origin and C the equilibrium concentration of paclitaxel in the supernatant. Our data points are also well described by this model. Table 2.4 shows the values of the tting parameters obtained. The t is satisfactory, with a goodness of t close to 1 and less than 5% standard error for the quantity adsorbed at saturation, and 18% for the slope at the origin. The dierential free adsorption energy can be calculated from b the slope of Langmuirs isotherm at the origin using the following relation [63]: G = RT ln(b C0 ) ads (2.9)
34
Structure Hads [kJ/mol] Surface -779 2.0 nm pore diameter -2633 1.5 nm pore diameter -460
Table 2.5: Calculated dierential adsorption enthalpies.
Where R is the universal gas constant, T is the absolute temperature and C0 is the standard concentration dened as 1 mol/l. The G obtained from our measurements is -23.5 kJ/mol 0.4. This is ads a reasonable order of magnitude for a free dierential adsorption enthalpy, and indicates that the adsorption of paclitaxel on silica is spontaneous and stable. For comparison, in a dierent yet similar system, the value that can be derived from Langmuirs isotherm measured by Park et al. [80] for paclitaxel on mesoporous silica with an average pore diameter of 6 nm in hexane-methanol mixture is equal to -9.31 kJ/mol. The systems and the methods are dierent, but it is interesting to see that both values lie in the same order of magnitude. 2.4.3.2 Simulation
Adsorption of paclitaxel was calculated onto a at surface and in pores approximately 1.5 nm and 2 nm in diameter, larger pores not being realisable with available computer resources at the present time. All structures were allowed to evolve freely for 1ns and the average energy to be used in the adsorption energy calculations was evaluated over the last 100 ps. The obtained adsorption enthalpies are given in table 2.5. As simulated values are very large compared to those measured experimentally direct comparision is impossible and only relative values should be considered. The reasons for the discrepancy between simulation and experiment are complex and not fully explained, but several factors are worth noting. The simulation assumes an ideal situation, without impurities or contamination, simple pore and surface geometries and computes a nite number of conformations which are not necessarily statistically representative. The real pore morphology and topology of the material is dierent and cannot be considered as an interconnected network
35
Case D[m2 /s] Pore total 7.4 1011 Pore in axis 5.0 1011 Free total 4.9 1010
Table 2.6: Diusion coecients for dierent cases. In axis: M=2, others: M=6 (see (2.7).
of perfect cylindrical pore. It was found by Coasne et al. [20] that the simulated adsorption isotherm of molecular uids in porous media diered substantially when using simple geometry pores models versus realistic pore models. Another important point is that standard molecular dynamics simulations do not take into account entropic eects. The result is given as an interaction enthalpy, and not as a free energy, as is the case for the results calculated from Langmuirs adsorption isotherm, although this is not enough in itself to account for such a dierence. The results obtained by simulation, tough not directly applicable quantitatively, do however show the general tendencies that can be expected for this system. Adsorption is more favourable in the 2.0 nm pore than on a at surface. Santhong et al. [92] found in their molecular dynamics simulations that the adsorption enthalpy of hexane in mesoporous silica increased with decreasing pore diameter. The adsorption of paclitaxel is however less favourable in the 1.5 nm pore than in the 2 nm pore. Hata et al. [35] found that paclitaxel was not adsorbed inside silica pores smaller than 1.6 nm. This is most likely due to molecular distortions as a result of connement, the size of the paclitaxel molecule being approximately 1.8 nm. Diusion simulations in the pure solvent and the solvent lled pore were run for 1 nanosecond. The diusion coecients (table 2.6) for the dierent cases result from a linear t of the mean squared displacement curves as a function of time. The free diusion coecient calculated by simulation can be compared with the one that can be obtained from the Stokes-Einstein equation [24].
36
Dfree =
kB T 6rm
(2.10)
Where kB is the Bolzmann constant, the dynamic viscosity of the solvent and rm the radius of the solute. The Dfree obtained for paclitaxel (rm = 81010 m) in DCM ( = 4.1 104 Pas) is 6.3 1010 m2 /s, which is consistent with the Dfree of 4.9 1010 m2 /s calculated in our simulation. Veith et al. [108] have studied the diusion of small aroma molecules inside mesoporous silica. Their phenomenological model can be applied to evaluate our simulation results. The eective pore diusion coecient Dpore can be related to the free diusion coecient using the following relation [61]: Dpore p = F () Dfree p Where
p
(2.11)
is the porosity of the particle, p is the tortuosity of the pore network,
F () is a restrictive factor accounting for steric hindrance and is the ratio between the molecule radius and the pore radius. The medium through which diusion takes place in our simulation is a single innite cylindrical pore. The porosity as well as the tortuosity can therefore both be considered as equal to 1, and so only the steric hindrance factor F () is taken into account. It is in our case for mesoporous silica [47]: F () = (1 1.83 + 4.182 ) exp(6.52) (2.12)
With = 0.6, Dpore in this case is equal to 1.77 1011 m2 /s, which also compares well with the simulated value of 5 1011 m2 /s. 2.4.3.3 Paclitaxel release
The release prole in water (gure 2.14) shows a burst release in the rst few minutes which decreases to zero after approximately 100 minutes. The experiment was carried on for 72 h and no further release could be detected during that time. The total paclitaxel amount released corresponds to 36% of the total quantity originally adsorbed, indicating that the majority of the
37
Figure 2.14: Paclitaxel release prole in water.
substance in not eluted and remains inside the pores. The eluted paclitaxel probably comes from the largest pores and the outer surface of the particles. This is consistent with elution results in water obtained by Hata et al. [35]. The release rate determining step could be determined by the diusion rate out of the porous structure, the dissolution kinetics of paclitaxel in water, the speed of liquid penetration inside the pores, the desorption kinetics of paclitaxel from the silica surface or nally the existence of a chemical driving force counteracting diusion. Using the following empirical relations established for mesoporous silica [103]:
p = With
p
+ 1.5(1
p)
(2.13)
= 0.4, we can calculate from (2.11) Dpore to be 5.45 1012 m2 /s.
The average time thus needed for a paclitaxel molecule to travel the distance from the center of a MS-SPION particle to its surface (240 nm) can be calculated to be of the order of one hundredth of a second. The release experiment having run for over 72h, diusion limitations cannot explain this retention eect. The dissolution kinetics of paclitaxel in water limits the burst release rate as is the case in most paclitaxel eluting devices in water [21, 46, 86]. This initial burst release is caused by the dissolution of the drug not directly adsorbed on
38
the silica, but as multilayers either in larger pores or at the surface. It does not however explain why most of the drug remains inside the particles. The desorption kinetics of the drug on the silica could be a rate limiting factor, but our diusion simulations inside the pore do not show any stable adsorption but diusion limited transport (gure 2.15). The substantial dierence in adsorption enthalpy between pores and the at surface, and between the at surface and the solution means that a molecule exiting a small pore into a larger pore or into the solution goes through a strong chemical potential gradient, and as a result experiences a force in the opposite direction to the diusion. The simulations only show a diusion driven transport mechanism because it is conducted in an innite cylindrical pore. There is no widening of the pore radius and thus no inuence of the chemical potential on the transport of the molecule. Rough calculations of this eect in DCM show that the majority of paclitaxel is retained inside the pores. Assuming cylindrical pores, the chemical potential prole inside the particles is constant and constitutes a potential well with respect to that of free paclitaxel in solution. The chemical potential increases steeply at the opening of the pore. As a rst approximation, the length scale over which this occurs is in the order of magnitude of the pore diameter, as illustrated in gure 2.16. The force on the molecule is thus: F = Gads dA (2.14)
Where Gads is the dierential free enthalpy of adsorption obtained from Langmuirs isotherm, d is the average pore diameter and A is Avogadros constant. Using the Nernst-Einstein equation we can calculate the ux JF due to this force [83]: v Dpore = F kT (2.15) (2.16)
JF = v c(x)
Where v is the time-averaged speed of the paclitaxel molecules and c(x) is the concentration.
39
Figure 2.15: Conguration of paclitaxel in a 2 nm diameter pore at various equilibration times.
40
Figure 2.16: Schematic representation of the chemical potential gradient at the pore opening.
We can compare JF to the diusion ux Jdi : Jdi = Dpore dc dx (2.17)
When a steady state is reached, the two uxes equilibrate and the total net ux is zero. In that case, the following is true: Dpore dc = v c(x) dx (2.18)
The solution to this dierential equation is a Bolzmann distribution of the form: c(x) = const. exp (x)/kT (2.19)
Where (x) is the chemical potential prole, taken as linear in this case. We can thus plot the concentration prole inside the pore. The y-intercept on gure 2.17 is the minimal concentration in the solution for which a steady state is reached. This equilibrium solution concentration is determined by : cs = cp e
G ads RT
(2.20)
Where cs is the equilibrium concentration in the solution, cp is the equilibrium concentration in the pores. In the case of release in water, given the poor solubility of paclitaxel, G is larger than in DCM, and cs is probably under ads the detection limit of HPLC which explains why no release can be detected after
41
Figure 2.17: Calculated paclitaxel concentration prole inside the pores. x = 0 represents the pore opening
the burst release. With this argument, and knowing our HPLCs detection limit for paclitaxel in water, we can estimate using (2.20) a minimum G in water: ads with G < 29 kJ/mol, any paclitaxel release is undetectable with our setup. ads This value seems reasonable compared to the one measured in DCM. The paclitaxel is thus released from the particles, but comes to equilibrium with the solution at low concentrations (cs < 2.0 107 mol/l) and then remains trapped inside the particles. Finally, the penetration speed of water into the pore could be a limiting factor, and can be calculated using the following relation [34]: v= rp LV cos c 1 4 l (2.21)
With v the meniscus speed, rp the pore diameter, LV (0.0728 N/m) the surface tension of water, and c (70 ) [27] is the contact angle between paclitaxel and water and l is the distance between the meniscus and the opening of the pore. The meniscus speed is low in such small pores, especially as the surface is covered with a hydrophobic drug. It decreases to 7.6 102 m/s near the center of the particle. The particles are however so small that the time needed
42
for water penetration is negligible. Equation (2.21) is however valid for pores as narrow as 27 nm in diameter, and it is quite possible that the penetration of water in smaller pores could be hindered not merely by a kinetic problem, but be thermodynamically unfavourable under a certain diameter. In this case, our main porosity could be too small for water to penetrate, especially when coated with an hydrophobic drug, which would explain the retention of the drug in the particles, as approximately 65 % of the drug is situated inside these pores.
2.4.4
Conclusion
Our particles have successfully been loaded with the anti-cancer drug paclitaxel and their loading capacity was measured. An credible estimate for the free differential adsorption enthalpy of paclitaxel on our mesoporous silica particles was obtained from the adsorption isotherm. The drug release properties were found to be extremely slow after an initial burst release, which could either be caused by a high anity between the paclitaxel and the silica, or by the inability for water to enter the micropores. Such a slow release is a concern for drug delivery applications, but could be an asset for purication applications using magnetically separable adsorbent particles. The pore size distribution of the silica matrix could be optimised to improve and control the release kinetics by pore templating using surfactants.
43
2.5
2.5.1
Chromium doped alumina

Introduction
IR radiations penetrate living tissues much better than UV or visible light, and are therefore indicated for use in medical imaging. The necessity of nding an inorganic uorescent marker emitting in the IR has been partially addressed by the discovery of heavy metal quantum dots. These are however inherently toxic and little is known about their long term eects on health [13]. In order to address that issue, chromium doped alumina, also known as ruby, in the form of colloidal nanoparticles was investigated. The main advantage of this material is its low toxicity, being based on a biologically inert material and containing heavy metal only in low concentrations (< 3% w/w). The uorescence response and the particle size distribution of the materials were characterised and optimised. Conventional and confocal uorescence microscopy were performed to assess the quality of the signal to noise ratio and contrast that could be obtained for bioimaging applications. Finally, the particles were used in the gel-emulsion synthesis in order to combine them to MS particles, alone or in the presence of SPIONS.
2.5.2
HT-100 boehmite powder (Condea, Germany) was suspended as a 13% w/w suspension into a 0.014 M solution of chromium nitrate (Merck, p.a.) in 2 % w/w acetic acid (AA) to yield in the end product a chromium concentration (Cr2 O3 to Al2 O3 ) of 0.7 % w/w. This suspension was then freeze dried 50 C @ 0.08-0.1 mbar, Alpha 1-4, Christ, Germany). Thermal treatments were done on the freeze-dried powder in a Naber 1400 oven (Nabertherm, Germany). The annealed powder was crushed in a mortar before attrition milling to break large agglomerates and resuspended at 30% w/w powder in 2% AA. Attrition milling was performed on a 30%w/w suspension of the annealed powder in an attrition mill with 400 g of 1.25 mm diameter 3YSZ grinding spheres (Tosoh, Japan) at 1500 rpm for 3 hours.
44
2.5 Chromium doped alumina
The attrited suspension was retrieved by 10 fold dilution in 2% AA. To remove larger agglomerates, centrifugation was performed on this diluted suspension in a GR 20 22 Jouan ultracentrifuge. The concentration of chromium doped alumina particles is estimated to be (after dilution centrifugation) maximum 2% w/w. Particle size distributions were acquired on a CPS 24000 (see 2.3.1) centrifuge particles sizer at 11000 rpm using n=1.624 [99] for the refractive index and =3.82 g/cm3 for the density. X-ray diraction was realised on a Philips Xpert diractometer with a Cu K radiation. Fluorescence spectroscopy was done on a Tecan Innite M200 well plate
reader. The powders were packed into the 5 mm wells of polystyrene 96-well plates. The uorescence was measured from the bottom of the well. Fluorescence microscopy was done on a ZEISS LSM 700 upright microscope (objective plan-apochromat 20x/0.80 in air) using a 639 nm solid state excitation laser and a 655 to 715 nm band pass lter. The uorescent particle suspension was dried on a glass sample holder and imaged directly. Confocal uorescence imaging was done on a LEICA SP2 AOBS inverted confocal laser scanning microscope (objective HCX PL APO 63x/1.40-0.60 in oil) with an excitation laser at 633 nm and a 662 to 737 nm band pass lter. A drop of non-attrited suspension was placed between two glass plates, which were sealed with nail polish.
2.5.3
2.5.3.1

Materials characterisation
The starting material (HT-100, Condea, Germany) is a high surface area pseudoboehmite. Pseudoboehmite, or gelatinous boehmite, is a highly hydrated, poorly crystallised form of mineral boehmite (AlOOH), a major constituent of many naturally occuring bauxites [112]. It is supplied as a spray dried powder with 5 to 15 m granules, but is easily dispersed in 2 % acetic acid. It has a very small particle size, which requires it to
45
be handled with special safety precautions1 , a narrow size distribution and few agglomerates. Table 2.7 shows some materials characteristics of the pristine powder and the chromium doped alumina. The BET equivalent spherical particle diameter dBET is calculated from the specic surface area (SSA) of the powder and its pycnometric density () according to: 6 dBET = (2.22) SSA It gives an indication on the average size of the primary particles of a powder irrespective of its level of agglomeration. The agglomeration factor FAG is given as the ratio of the mean volume diameter dV to dBET . There is no substantial primary particle growth during annealing, as can be seen from the nitrogen adsorption data. The density of the material increases substantially during the process, while the SSA decreases accordingly, due to the thermal dehydroxilation of boehmite into alumina (Al2 O3 ) starting at around 300 C. The powder becomes yellowish during annealing and undergoes severe agglomeration, which creates the necessity of an attrition treatment. After attrition milling, the agglomeration factor remains over three time greater than before the treatment but the mean volume diameter is now low enough to envisage the inclusion of the particles inside MS multifunctional beads. The particles size distributions of the pristine powder and of our material after annealing and attrition are shown on gures 2.18 and 2.19. The polymorph of alumina obtained from pseudoboehmite after calcination at 900 C is -alumina, a transition alumina closely related to tetragonal -alumina [112]. This is conrmed by X-ray diraction analysis (gure 2.20), although signicant peak broadening is observed, caused by the small size of the crystallites (see table 2.7) and poor long range order of the material which makes it dicult to dierentiate these two quite similar forms.
Because of its small size, and its potential adverse health eects, all manipulations of the dry powder were done in a specially dedicated underpressurised room wearing protective gear and a breathing mask.
1
46
Figure 2.18: Cumulative particle size distribution in volume for pristine HT-100 Condea powder. From the work of Staiger, Bowen et al. [99]. Dierent PSD characterisation methods are compared: X-ray disc centrifuge (XRD), photon correlation spectroscopy (PCS) and cuvette photocentrifuge (CAPA)
Figure 2.19: Cumulative and frequency particle size distribution in volume for annealed chromium doped alumina after attrition. The particles are strongly agglomerated compared to the pristine powder.
47
Properties Pristine powder [99] After annealing and attrition SSA [m2 /g] 214 156 3 [g/cm ] 3.01 3.82 dBET [nm] 9.3 10 dV [nm] 17 58 V [nm] 4 28 FAG 1.7 5.8
Table 2.7: Material properties of chromium doped alumina. Annealing at 900 C.
Figure 2.20: X-ray diraction spectrum of chromium doped alumina annealed at 900 C. The crystal structure is that of - or -alumina.
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2.5.3.2
Characterisation of uorescence
Figure 2.21: Excitation and emission spectra of chromium doped alumina particles. A and C: Excitation and emission spectra for ex = 580 nm, em = 700 nm, integration time = 2000 s; B and D: Excitation and emission spectra for ex = 610 nm, em = 800 nm, integration time = 40 s.
At 2000 s integration time our material shows an excitation peak at 580 nm and an emission peak at 700 nm. When acquired with a shorter (40 s) integration time however, the excitation and the emission undergo a red-shift with peaks at 610 nm (red) and 800 nm (near IR) respectively (see gure 2.21). This indicates that there are at least two dierent uorescence phenomena, emitting at dierent wavelengths with dierent characteristic decay times. To investigate the time dependency of the uorescence emission, a series of emission spectra were acquired with a constant acquisition time of 40 s, and a variable lag time of 0 to 900 s. The uorescence intensity for two wavelengths (700 nm and 800 nm) were plotted against the lag time, yielding uorescence decay curves for each phenomenon (see gure 2.22).
49
One can thus separate one broadband short lived emission with a peak around 810 nm, and one more dened peak at 700 nm, characterised by a longer uorescence lifetime.
Figure 2.22: Emission intensity decay over time. For = 700 nm and = 800 nm.
Bulk ruby (-alumina) has two well known emission peaks at = 693.2 nm and 694.5 nm [40]. These so-called R emission bands are caused by Cr3 + ions substituted to Al3+ on octahedral sites. At high Cr3+ concentration (> 1%), asymmetric peak broadening of these Rlines is observed, and a broadband emission peak appears at = 750 nm caused by pair and cluster interaction between chromium ions [41]. At room temperature however, and contrary to our observations, the uorescence lifetime of these phenomena are identical. This indicates that while chromium pair and cluster interactions cannot be ruled out, they cannot explain the short lived uorescence phenomenon observed. Patra et al. [82] found that in -alumina, the two discrete R-lines found in -alumina tend to convolute of into a single broader emission band ranging from 690 to 720 nm. They attribute this eect to the distortion of octahedral sites in the -lattice.
50
Pillonet et al. have characterised the uorescence of chromium doped - and -alumina calcinated from boehmites or via a sol-gel route [84]. They also observe a short lived (time constant in the tens of s range) broadband IR radiation with an excitation peak at 607 nm and an emission peak around 820 nm in addition to the convoluted R-lines. They attribute this phenomenon to Cr3+ ions located in weak crystal eld sites, in the vicinity of cation vacancies. The exact time constant related to each event cannot however adequately be measured with our setup. The Tecan microplate reader is indeed more adapted to the automatic measurement of multiple samples in solution than to the precise, time-resolved characterisation of optical phenomena in solids. 2.5.3.3 Eect of chromium concentration and annealing time on uorescence
The eects of chromium concentration and annealing time on the uorescence intensity of chromium doped alumina were investigated using a bi-factorial approach. The annealing temperature chosen was 900 C. The levels of the factors were chosen as shown on gure 2.23.
Figure 2.23: Bi-factorial plan for the uorescence response of chromium doped alumina. Inuence of annealing time and chromium concentration.
Annealing time has a negative inuence on the uorescence signal, while high chromium concentrations is benecial.
51
Figure 2.24: Fluorescence response surface for chromium doped alumina: inuence of annealing time and chromium concentration. em = 800 nm, ex = 615 nm
52
2.5.3.4
Fluorescence imaging
The powder could be imaged on a confocal laser scanning microscope, despite the long time constant of the main emission peak. The signal was however very weak even with a high gain and an integration time pushed to upper the limit (a few microseconds/pixel). The eect was to increase the noise and the acquisition time, given the large number of points needed to create an image. These problems cannot be easily resolved and reduce the applicability of chromium doped alumina for CLSM. The long uorescence lifetime is however not a disadvantage in the case of classical wideeld uorescence microscopy, where both the excitation and the acquisition occur in a continuous way. The signal in this case is strong, with a good contrast and little noise. Figure 2.26 is a uorescence microscopy image of the drop of suspension after drying, reconstructed automatically by the machine from an array of smaller images. This techniques makes it possible to images such large objects.
Figure 2.25: Fluorescence microscopy images of chromium doped alumina agglomerate.
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Figure 2.26: Fluorescence microscopy images of chromium doped alumina. Dried suspension drop
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2.5.4
Application to multifunctional particles
The applicability of these uorophores in multifunctional particles for biomedical applications was assessed by combining them with SPIONS in a mesoporous silica matrix. 2.5.4.1 Eect of SPIONS on uorescence
In order to assess the functional compatibility between SPIONS and chromium doped alumina nanoparticles (ruby), their optical interactions were measured in suspension. SPIONS and ruby suspensions were mixed together in various proportions in order to measure the loss of uorescence caused by the SPIONS. The SPION concentration was varied between zero and the concentration typically found in our multifunctional particles, i.e. approximately 5 mg Fe/ml.
Figure 2.27: Eect of SPION concentration on the uorescence emission intensity of chromium doped alumina. Even at SPION concentrations equal to those present in the particles, 70% of the uorescence signal is still detected.
The relative intensity in gure 2.27 is given as the ratio of intensities between the suspension with SPION and the one without SPIONS. At 5 mg Fe/ml, the uorescence signal decreases by approximately 30 % with respect to a SPION-free suspension. The optical interactions between the two particles is thus relatively benign, as most of the signal can still be detected. Furthermore, the decrease is not linear, as SPIONS seem to absorb only a certain part of the spectrum ( < 550 nm) but not all of it.
55
Another strategy was also attempted to combine both types of particles in a silica matrix, while limiting agglomeration of the boehmite during annealing. The idea was to directly incorporate the pristine boehmite powder and chromium ions inside the MS matrix alongside SPIONS, and only then perform the annealing step. The boehmite is well dispersed in the silica matrix, and remains so during annealing. Dierent quantities of SPIONS in prehydrolysed TMOS were thus mixed to HT-100 boehmite suspension in chromium nitrate solution. This mixture was allowed to form a gel by addition of a base, and then annealed at 900 C for one hour. The SPION concentrations are given here as a percentage of the mass of SPIONS to the mass of boehmite present in the sample (see gure 2.28).
Figure 2.28: Relative uorescence intensity for dierent SPION concentrations. A: No SPIONS; B: 0.25 % SPIONS; C: 7.55 % SPIONS
The uorescence signal is strongly reduced (55 %) with 0.25 % SPIONS, and decreases to zero with 7.5 % SPIONS. If one compares this to gure 2.27, where the SPION concentrations reaches maximum 25 % (5 mg Fe/ml) without a major loss in signal, we can deduce that absorbance is not the key phenomenon at play
56
here. It is more likely that SPIONS interfere with the synthesis of chromium doped alumina. Chromium and iron oxide have a high anity and form mixed oxides together over a wide range of concentrations, as can be seen from the Fe2 O3 -Cr2 O3 phase diagram (gure 2.29). Iron oxide nanoparticles have even been used to purify drinking water from chromium contamination [126].
Figure 2.29: Phase diagram between iron oxide and chromium oxide. C = corundum structure; CC = chromium rich corundum; FC = iron rich corundum. From [73].
If one synthesises the chromium doped alumina nanoparticles separately, they can be combined to SPIONS at high concentrations without catastrophic loss of functionality. When they are synthesised in the presence of SPIONS however, the chromium ions seem to combine preferentially with the iron oxide and very low levels of uorescence of alumina are observed. This closes the door to transforming well dispersed boehmite nanoparticles into so many -alumina particles directly inside the already formed MS-SPION beads, which would have the great advantage of conserving its excellent particle size distribution.
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2.5.4.2
Synthesis of MS-SPION-Ruby multifunctional particles
The encapsulation of chromium doped alumina particles alongside SPIONS inside mesoporous silica particles was attempted using chromium doped alumina. The experimental procedure is identical to the one described in section 2.3.1 except that the PVA-SPIONS suspension in the emulsion were replaced with a 1:1 vol:vol mixture of PVA-SPION suspension and chromium doped alumina suspension. No uorescence could be detected on the particles, and the continuous phase of the emulsion seemed to be slighlty yellow. This indicates that the ruby particles did not remain in the dispersed phase but were extracted into the oil. The SPIONS on the other hand remained, as observed before, inside the particles. Attempts using PVA-coated ruby particles yielded identical results: the particles could not be kept inside the emulsion droplets.
2.5.5
Conclusion and outlook
The applicability of chromium doped alumina nanoparticles as near-IR uorescent markers is promising, although most aspects investigated here, from characterisation to synthesis, would need to be completed and optimised. The quantum yield of the material should be measured. This aspect was not addressed in this study, but would be a necessary characterisation to have an idea of the intrinsic value of this uorophore for imaging applications. The synthesis of well dened, homogeneously doped alumina nanoparticles cannot without great diculties and tedious processes (attrition milling, centrifugation), be achieved from a commercial powder. A good approach would be a bottom-up synthesis via, for example organic alumina precusors. Zhou et al. have for example synthesised -alumina nanocrystals from aluminum acetylacetonate in nonaqueous media [127]. One could imagine to adapt this synthesis and perform it in the presence of chromium species. It might even be possible to inuence the relative intensity of each uorescence phenomenon, as well as to improve the quantum yield, by controlling the synthesis conditions.
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2.6 Laser annealing of silica coated ZnS:Mn2+ nanoparticles
2.6
Laser annealing of silica coated ZnS:Mn2+ nanoparticles
2.6.1
Introduction
This section investigates the applicability of silica-coated manganese-doped zinc sulphide (ZnS:Mn2+ @SiO2 ) as multicolor luminescent material for display applications. Localized annealing of compacted ZnS:Mn2+ @SiO2 powder was attempted by heating the material with dierent lasers, so as thermally induce uorescence color changes at desired sites on the surface. These thermally aected zones were characterized by SEM, photoluminescence and cathodoluminescence. The applicability of the method to the production of multicolour luminescent images was assessed. This work was conducted with the assistance of two successive students of the material science master program, Michael Stuer and Amlie Bazzoni [8, 102]. e
2.6.2
2.6.2.1
Theory
Silica coated ZnS:Mn2+ nanoparticles
ZnS:Mn quantum dots are uorescent have an orange emission peak (595 nm) which is due to the T1 (G)-A1 (G) Mn2+ d-d transition [9] (see gure 2.30), and a size dependant excitation peak which is around 300 nm (UV) for our synthesis route. Pure nanosized ZnS has an emission peak at 420 to 450 nm, but doping with transition metals such as Mn2+ , Cu2+ or Eu3+ creates dierent emission peaks in the visible spectrum [87, 118]. ZnS nanocrystals have a cubic zinc blende structure, also called sphalerite, which consists in primitive cubic sulphur lattice with zinc occupying half the tetrahedral sites. Wurtzite is a high temperature polymorph of ZnS, thermodynamically stable above 1020 C, but also found as a metastable phase at room temperature in reductive conditions. It consists in an hexagonal close-packed sulphur lattice with zinc occupying half the tetrahedral sites. The special optical properties of these nanosized semiconductor crystals mainly come from the connement in space of their conduction band electrons and va-
59
Figure 2.30: Jablonski diagram for ZnS. Possible transitions and corresponding colours in ZnS with or without manganese doping.
lence band holes, to dimensions approaching the exciton Bohr diameter. This connement causes an increase in the uorescence eciency, a shortening of the uorescence lifetime, and an increase in the width of the band gap compared to the bulk material. Photoluminescence (PL) properties, as well as other physical properties such as crystal structure and defect density [32, 33], are also strongly dependant on the condition of the nanocrystals surface. The presence of surface defects or transition metal impurities near the surface, which act as surface states or traps, tends to have a quenching eect and to therefore decrease the uorescence yield [123]. The presence of organic functional groups from surfactants or capping agents on the surface can passivate such surface structural defects, and cause a strong increases in uorescence yield and PL intensity. Coating quantum dots with another material possessing a wider band gap has likewise been shown in many system to enhance their quantum yield. In particular, the eects of silica coatings on the physical and photoluminescence properties of ZnS:Mn quantum dots have been extensively studied [23, 52], and include a further increase in uorescence yield due to passivation of surface electron traps and an enhanced thermal stability due to the reduced mobility of surface atoms.
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2.6.2.2
Eect of annealing
Benedikt Steitz et al. [100, 101] found that thermal annealing of silica coated ZnS:Mn nanoparticles in dierent atmospheres results in changes in the uorescence emission spectra of these quantum dots. The emission intensity of the ZnS:Mn2+ @SiO2 passes through a minimum when annealed at 600 C due to the sphaerulite to wurtzite phase transformation of ZnS through a non emissive transition phase. Upon annealing at higher temperatures (>800 C) ZnS:Mn2+ @SiO2 yields dierent high intensity emissions in dierent atmospheres. In air, green emissions (530 nm) due to the formation of a new manganese doped zinc silicate phase called willemite (Zn2 SiO4 :Mn2+ ) is obtained, probably due to the oxidation of sulphur into gaseous sulphur dioxide gas. In formier gas, an emission peak is found again at 590 nm (orange) due to the conservation at higher temperatures of ZnS:Mn quantum dots in their wurtzite phase.
2.6.3
ZnS:Mn nanoparticles were precipitated from a solution of zinc sulphate upon addition of sodium sulphide in the presence of L-cysteine as surfactant. Silica coating was carried out in a second stage by condensation of tetramethoxy orthosilicate (TMOS) on the quantum dots in aqueous environment. This suspension was then freeze dried to produce a ne white powder (see [101] for details). Oven annealing was carried out in a thermo-gravimetric analysis (TGA) machine (Mettler). The ZnS:Mn2+ @SiO2 powder samples were placed into alumina 70 l TGA crucible, and heated up at 20 C/min to temperatures between 400 C and 1200 C, in a ow of air or formier gas. Immediately upon reaching the desired annealing temperature, the samples were left to cool down to room temperature in the gas ow. 96 wells microplate: a layer of alumina powder (-Al2 O3 , AT-DS) was rst compressed in each well to about half height to act as a support layer. A layer of ZnS:Mn2+ @SiO2 powder was then compressed on top of it (see g 2.31A). The well plates were placed in a chamber under a Nd:YAG (=1064
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Figure 2.31: Dierent sample preparation methods for laser annealing. A and B: 96 well microplate; C: quartz glass plates sandwich structure; D: pressed pellet;
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2.6 Laser annealing of silica coated ZnS:Mn2+ nanoparticles nm) laser (Quantronix Condor100) in Q-switched mode. The laser was programmed to re inside the wells. This setup allowed to re the laser with a wide sweep of parameters (dwell time, power and laser frequency) directly arranged in an array. It also allowed the characterisation of uorescence directly in a microplate reader. Quarz glass plates: the setup consists in a sandwich structure between two quartz glass plates separated by a PTFE spacer. The spacer has a window in which ZnS:Mn2+ @SiO2 powder is deposited (gure 2.31C). This method was designed to provide as awritingsurface for the laser, and was characterised by photographs under UV light. Pressed pellet: 2 to 5 g of ZnS:Mn2+ @SiO2 powder were pressed into pellets in a 2 cm diameter matrix placed in a uniaxial press at a pressure of 20 MPa. The pellets thus formed are quite fragile and consume a large amount of powder for a relatively limited writing surface when compared to the quartz glass sandwich structure. Laser annealing was attempted with the following lasers: 1. Nd:YAG infared laser (1064 nm, Q-switched mode.) Quantronix Condor100 . 2. Argon continuous laser Innova 300 (514 nm, 5 W). 3. UV pulsed excimer KrFNe-lled laser (248 nm) Lambda Physik LPX-100 laser. 4. Nd:YAG infared laser (1064 nm) SLAB LASAG. All laser annealing attempts were done in air. Fluorescence spectra were acquired on a Tecan Saphire2 microplate reader in top mode with zero lag time and 40 s integration time. The photographs of uorescent samples were taken under a shortwave UV lamp (Waldmann Lichttechnik GmbH). X-ray diraction was realised on a Philips Xpert diractometer with a Cu K -radiation.
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Cathodoluminescence images and spectra were realised on a Cambridge S-360 CL system tted with a LaB6 lament producing a 1 to 40 keV beam with currents from a few pA to 1 A. The emitted light is collected by a semi-elliptical mirror into a monochromator and detected by an InGaAs photodiode. The sample investigated was a pressed pellet exposed to a Nd:YAG (=1064 nm) laser 570 J). (Quantronix Condor100 ) in Q-switched mode (19 A, 2.2 kHz for 15 seconds ;
2.6.4
2.6.4.1

Oven annealing
Samples annealed in air at 600 C did not show any emission immediately after annealing, in accordance with previous observations, but started to develop a strong blue emission within 48 h (see 2.33). This eect was not previously reported and is due to the gradual oxidation of ZnS:Mn2+ into zinc oxide, as demonstrated by XRD spectra. This new property is of interest as it allows the production of a third color, blue, in addition to the original orange emission, and the green emission of the manganese doped zinc silicate with one starting material.
Figure 2.32: Colours obtained after annealing of ZnS:Mn2+ @SiO2 at dierent temperatures and in dierent atmospheres.
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Figure 2.32 shows a summary of the dierent colors obtained during the different annealing processes. The maximal intensities of the dierent spectra were set as 1 so as to allow comparison between them, although the intensity of the blue emission is more intense than the green one. Human vision is however not linear and sees green and orange better than blue [30], which is why the apparent brightness of the dierent colors seems to be in the same order of magnitude on gure 2.32.
Figure 2.33: Emission spectra of annealed ZnS:Mn2+ @SiO2 samples. The maximal emission intensity was set as 1 for all spectra. Excitation at ex = 301 nm for pristine material and 1100 C in formier gas, 370 nm for 600 C in air and 250 nm for 1100 C in air.
These colors could potentially act as primary colors for the development of RGB (red, or rather orange, green and blue) static multicolor uorescent images. 2.6.4.2 Laser annealing
Laser induced emission colour change can be achieved using both infrared lasers (SLAB LASAG and Quantronics Condor100 ).
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The two other lasers (green and ultraviolet) do not achieve sucient heating to create the willemite phase, and only result in a loss of uorescence at the impact points. This can be caused either by a moderate heating of the material below 500 C (see gure 2.32), or to bleaching of the quantum dots. Upon intensive irradiation, light induced lattice defects in the quantum dot, sometimes partially reversible, create extra non radiative recombination pathways and cause a signicant loss of signal [107]. The relatively short wavelengths used in both cases (514 nm and 248 nm respectively) are susceptible of being absorbed by the QDs and to cause photobleaching. No change in agglomeration or appearance of the powder (as seen under optical microscope) at the impact site can be detected, indicating that the temperature probably did not exceed 500 C. No blue emission is detected at the impact site at any time after the experiment, which means that the zinc sulphide is not oxidised to zinc oxide, as is observed in the oven-annealed samples heated at 600 C after 24 hours. IR lasers used. The rst attempts were conducted on the Quantronics laser in well plates, testing a wide range of lamp currents, pulse durations and irradiation times in order to nd appropriate conditions. The thermal change occurs only after a certain threshold of illumination time (up to tens of seconds), before which no eect can be detected, and then progresses extremely rapidly. In all the wells where an eect can be seen, the diameter of the thermally aected zone (1 to 2 mm) is substantially larger than the beam diameter (10 m). The response is thus strongly non-linear with respect to nominal total power and irradiation time. This eect can be explained by the fact that silica is quite transparent to IR radiations, and that with a xed pulse duration of only 130 ns, the heat generated by each pulse is dissipated before the next pulse arrives. In this case, the temperature increase remains moderate and no thermally induced phase change is observed at rst. The continuous illumination of the same spot for tens of seconds can however cause optical breakdown of the material. The laser creates coloured centres in the material which increases the absorbance locally, making it more liable to create other coloured centres, resulting in a feedback eect that Laser induced thermal annealing can however be achieved with both pulsed
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leads to a sudden, non linear increase in temperature, and the formation of a plasma [81]. This is how a thermal annealing eect is nally obtained with this laser, proving that the concept is valid, but showing the necessity of optimising the laser parameters in order to decrease the diameter of the thermally aected zone and shorten the irradiation time. On the SLAB LASAG infrared laser, contrary to the Quantronix , the pulse
duration can be chosen. The experiments in this case was performed on quartz glass sandwich samples, and the powder was exposed to single, long laser pulses. The pulse duration was varied between 0.75 and 3 ms, which is three to four orders of magnitudes greater than the duration of the pulse on the other IR laser. The thermal eect in this case is probably also due to the creation of a cascade of coloured centres, but the process is better controlled and occurs over a single pulse. The eect is therefore more local, the thermally aected zone is in the order of the beam diameter (200 m), which allows the creation of patterns. In order to have an eect visible by eye, square shaped arrays of laser impacts of 2x2 mm2 were created. The impacts are spaced by 170 m in one direction and 200 m in the other.
Figure 2.34: Array of laser impact points. Optical microscopy.
The eect of thermal treatment by laser in air is comparable to that of the traditional oven treatment and yields a strong emission in the green. The total pulse energy is an important factor, and seems to yield similar results with dierent parameters. Squares 15 and 13 have the same energy but dierent pulse lengths
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Square number Pulse duration [ms] Voltage Energy [J] 1 3 250 2.4 2 3 250 2.4 3 3 350 3.4 4 2 250 1.6 5 1.5 250 0.97 6 1.5 250 0.92 7 1.25 250 0.75 8 1 250 0.55 9 0.75 250 0.36 10 0.75 250 0.36 11 0.5 250 0.16 12 2 235 0.92 13 2 210 0.55 14 3 197 0.53 15 0.75 271 0.55
Table 2.8: List of conditions tested. The numbers correspond to the squares on gure 2.35.
Figure 2.35: Laser annealing of ZnS:Mn2+ @SiO2 powder in dierent conditions. A: photograph under white light. B: photograph under UV light.
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and voltages. They however look similar in their colour and intensity. Squares with the highest powers look more green (> 1 J), those with intermediate powers (> 0.5 J) look more blue, and those with the lowest powers are hardly aected at all and remain orange. It is interesting to note that no photobleaching eect is visible on these squares although they have been exposed to strong IR radiations. This characterisation method is qualitative and does not give exact emission spectra, due to the diculty in measuring uorescence intensities on an arbitrary surface. Cathodoluminescence could not be attempted on these samples due to the quartz glass plate covering the powder, which could not be removed without modifying the sample too much. It should be noted that a non emissive zone can be seem at the edge of the laser treated zone, which appears as a darker rim around the squares. The powder undergoes partial sintering during the laser treatment and the treated zones appear more dense and whiter. There is some shrinkage of the powder linked to sintering and a relative depletion of powder at the border zones occurs, creating this dark rim eect. As a proof of concept, the laser was programmed to draw the EPFL logo on a quartz glass sandwich sample. The result is encouraging although the letters remain rather ill-dened due to the size of the pixels (laser impacts) available with respect to the size of the writing surface.
Figure 2.36: EPFL logo drawn by IR laser on a bed of ZnS:Mn2+ @SiO2 . A: photograph under white light. B: photograph under UV light.
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2.6.4.3
Cathodoluminescence
The lasers thermally aected zone was characterised by cathodoluminescence. Cathodoluminescence is a technique which consists in using an electron beam to excite the uorescence of samples, and to collect and analyse these light emissions using a semi-elliptical mirror coupled to a monochromator. It was particularly adapted in our case as a space resolved-spectrum of the impact zone could thus be acquired.
Figure 2.37: Emission spectra of the laser treated and non treated zones by cathodoluminescence.
The emission peak in the thermally aected zone is situated around 550 nm, similarly to the emission peak of the sample annealed at 1200 C in air (gure 2.33). The non aected zone has a the usual orange-red emission peak (around 600 nm) of the pristine powder. The results correspond to those obtained with photoluminescence. Two secondary peaks are present at 450 nm and 650 nm on both spectra. The former is most likely the emission peak of undoped ZnS, quite visible in the non-treated spectum, and much less so in the thermally treated one. The latter could however not be attributed to any event in particular.
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Figure 2.38: Cathodoluminescence of ZnS:Mn2+ @SiO2 before and after laser treatment. A: luminescence in pristine region; B: SE image of laser impacted region; C: luminescence at 450 nm of zone shown in B; D: luminescence at 550 nm of zone shown in B.
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The morphology of the compressed powder becomes smooth and porous during laser treatment, with spherical pores that could point to some gas formation (bubbles, probably SO2 ) in the melted silica (gure 2.38B). The luminescence is generated homogeneously over the whole surface of the pristine sample (2.38A). In the laser treated region however, the light seems to be more intense coming from the pores (2.38C and D). This is probably due to the greater penetration depth of electron compared to visible light. Only light generated near the surface can be detected, the rest being absorbed before reaching the surface and the detector. Pores appear brighter because they constitute pathways through which light can emerge from within the material. EDX mapping of the pristine powder surface show inhomogeneous concentrations of zinc and sulphur, indicating that the quantum dots are present as agglomerates inside the silica. In the laser treated zone on the contrary, these elements are homogeneously distributed and seem to have diused throughout the material.
2.6.5
Conclusion and outlook
The applicability of ZnS:Mn2+ @SiO2 powder for the production of multicolour uorescent images by laser annealing was proven. A two colour picture (the EPFL logo) was realised thanks to a rst optimisation of the laser treatment parameters, which made it possible to diminish considerably the size of the thermally aected zone and the irradiation time. It was seen that blue or green hues could be obtained by adapting the total energy of the laser pulse. The system remains however quite experimental and a great deal of optimisation and further characterisation is necessary to progress towards a possible application. Firstly, laser annealing could be attempted in dierent atmospheres, such as argon of formier gas in order to achieve dierent colours, or even non emissive powder. A moderate oven pre-annealing in formier gas at 400 C could for example extinguish all luminescence in the sample, yielding a dark background. Subsequent laser annealing in the same atmosphere would rekindle a orange-red emission at desired sites only. One could then attempt to create real multicolour
72
pictures using the three primary colours available (red, green and blue) as laser annealed colour pixels. The laser treatment also leaves room for improvement, in diminishing the diameter of the thermally aected zone for example, to gain in resolution. The mounting of the samples and the size distribution and properties of the powder also have to be re-thought. Finally, the excitation by UV light could be replaced by a more convenient electroluminescence setup, by placing the powder in a strong electric eld.
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Figure 2.39: SE image of compacted ZnS:Mn2+ @SiO2 surface and chemical mapping of the surface.
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Figure 2.40: SE image of laser treated ZnS:Mn2+ @SiO2 surface and chemical mapping of the surface.
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76
3 Titanium surface structuring
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3. TITANIUM SURFACE STRUCTURING
3.1
3.1.1
Introduction
Titanium
Titanium is a transition metal found in various naturally occurring ores such as rutile or ilemite. Despite its abundance in the earths crust, it is one of the most recently discovered structural metals. Its mechanical resistance is similar to that of steel while its density is twice as low, making it a particularly essential material for the aerospace industry. It is also widely employed in the automotive industry, in the chemical industry as a catalyst, as a structural material in sporting items as well as for dental and orthopedic applications [7]. Beyond its excellent mechanical properties, its biocompatibility, its resistance to corrosion as well as its availability make it an important material for many current and future applications. Titanium is mostly used either as a pure metal (grades 1 to 4), or as alloys containing for example aluminium and vanadium (grade 5). The pure metal has a hexagonal close packed structure (-phase) at room temperature. Above 882 C, an allotropic transformation occurs from hexagonal close packed to body centered cubic structure ( ). The Ti-6Al-4V alloy (Grade 5) has a duplex microstructure with both and phase at room temperature thanks to the stabilising eect of aluminium on the high temperature phase. These alloys have excellent mechanical properties, good workability thanks to the ductile phase, and are widely used in orthopedic implants.
3.1.2
3.1.2.1
Electrochemical properties
Passivity
Titanium is a passive metal that has a thin oxide layer on its surface, called passive lm, which separates it from its environment. This tenacious oxide is stable over a broad range of pH and potential conditions as can be seen from the Pourbaix diagram of titanium (gure 3.1). The typical thickness of such passive lms is in the order of 1 to 3 nm.
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3.1 Introduction
Figure 3.1: Pourbaix diagram for titanium in aqueous environment. According to [113].
The dissolution rate of a passivated metal (or passive dissolution) is very low and constant over a large potential range. This explains its extreme chemical resistance in all sorts of aggressive environments. 3.1.2.2 Anodic oxide lm growth
Anodic oxide growth involves ion transfer reactions at the metal-oxide interface and at the oxide electrolyte interface. It also involves ion transport inside the oxide layer from one interface to the other. These phenomena occur under the inuence of a strong electric eld (typically 108 V/m) in the lm. The reaction at the metal-oxide interface consists in the creation of titanium ions from the bulk metal, which take up cationic sites in the oxide, according to the following equation [54]: Ti Ti4+ + 4e (ox.) (3.1)
There are two possible charge transfer reactions at the oxide-electrolyte interfaces: dissolution of the metal ions, or the deposition of O2 ions. (ox.) Ti4+ Ti4+ (ox.) (aq.) (3.2)
79
O2 + 2H+ H2 O (ox.) (aq.)
(3.3)
The transport mechanism inside the oxide lm is governed by high eld conduction. In the absence of an electric eld, the transport of ions in the oxide is governed by diusion in the form of thermally activated jumps between sites in the lattice, without preferential directions. In the presence of an electric eld, the potential barrier for the jumps in the direction of the eld is reduced and the one for the reverse direction is increased. A net ionic current ows which is an exponential function of the electric eld. The thickness, structure and quality of the lm thus formed depend mostly on the applied potential prole (potentiostatic, potentiodynamic, galvanostatic etc. ) and on the composition of the electrolyte. In the standard conditions used throughout this study (potentiostatic mode, 0 to 100 V in 0.5 sulphiric acid), the lm thickness t depends linearly on the maximal applied voltage V following a simple rule t = 2.5V [6]1 . The structure of the oxide layer is mostly amorphous at anodisation voltages below 20 V, a mix of amorphous oxide and anathase between 20 and 50 V and fully crystallised anathase between 50 and 100 V. At higher anodisation voltages, lm destruction due to dielectric breakdown starts to appear in the form of crater-like pores, mostly identied as polycrystalline anathase [115]. The mechanism for this breakdown is not clear, but the inuence of temperature elevation and internal stresses on the crystallinity of the lm is pointed out. The crytallinity of the layer could increase its conductance, or cause an embrittlement leading to cracks.
3.2
Structuring of titanium surface
The objective of the current chapter is to create a general technology platform to achieve nanometer-scale structuring of anodisable metals using particle lithography, and to attempt to understand the mechanisms at play in such systems. The two main directions in the surface structuring of titanium are anodic structuration by anodisation in specic electrolytes, and top-down lithography methods.
1
Reference from the thesis of P.-F. Chauvy [16].
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3.2 Structuring of titanium surface
These methods are often used in combination as they do not necessarily produce features at the same length scale. Kim et al. [50] have formed various nanostructures by anodising titanium in dierent mixtures of phosphoric acid and hydrouoric acid. Titania nanotubes with a mean diameter under 100 nm are grown out of the surface. The structures obtained are quite homogeneous, but direct morphological control of the features produced is dicult with such methods. Another method, named local anodic oxidation (LAO) consists in performing a local anodisation of the titanium surface using an AFM tip as an electrode, by applying a voltage between the tip and the surface. In ambient air, the titanium surface is covered by a thin water lm which dissociates under the inuence of the electric eld, allowing the adsorption of OH ions and the growth of an anodic oxide layer [31]. The molar volume increase due to the anodisation process results in topographic structures. This method was briey considered for this work as a potential complementary study to the e-beam experiment, as it could have made it possible to locally measure anodisation currents around surface defects such as masks of adsorbed particles. This could however not be realised for technical reasons, but remains an interesting option for further studies The other strategy comprises various lithography techniques, including classical lithography [128], laser lithography [16, 17, 42] and electron beam lithography [48, 49, 55]. These methods all rely on a system of masks, either deposited or constituted of titanium oxide grown from the surface itself. Electrochemical treatments, either anodic oxidation or electrolytic dissolution of the material are then performed selectively and in a space resolved way. These techniques are often grouped under the term electrochemical micromachining (EMM). The typical length scale of such structurations is in the micrometer range upwards. Chauvy et al. [17] have shown that the patterning of anodised titanium can be directly achieved laser irradiation, without the need for a photo-resist. The oxide layer can be locally sensitised towards dissolution by a single long UV laser pulse. Through-mask dissolution is then performed to create cavities in the surface. Through-mask anodisation of e-beam lithography samples was performed by Kern et al. using 50 nm diameter circular SU-8 masks and anodising up to 150
81
V without delamination or dielectric breakdown of the mask. The structures produced are characterised by SEM but no specic attention was paid to the topography of the sample after through-mask anodisation. The main focus of the work remains through-mask dissolution anodisation. Chu et al. [19] have created well organised titania rod-like structures using a combined anodisation approach. A layer of aluminium is sputtered on titanium and then anodised. The well characterised hexagonal planar pore structure of anodised aluminium is then used as a mask through which the anodisation of the underlying titanium is performed. Titania grows inside the pores, which leaves an hexagonal array of vertical titania rods (60 nm height, 30 nm diameter) after the removal of the alumina mask. This method represents an interesting mixture between anodic structuration (of the alumina mask) and though-mask electrochemical machining. No mention could be found in literature of the use of particle lithography techniques for the structuring of titanium surface by anodisation, either at the nanometer or at the micron scale.
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3.3 Electrochemical polishing of titanium
3.3
3.3.1
Electrochemical polishing of titanium

Introduction
In order to better understand the eect of particles on the topography of anodised titanium, very at, smooth titanium surfaces were a prerequisite for this work and had to be produced in sucient numbers. The samples must be smooth enough to allow the detection of the defects caused by the particles. If the original roughness of the surface is of the same order of magnitude as the pits or bumps caused by the particles, they cannot not be detected. The samples must therefore be polished to sub-nanometer roughness. The surface should furthermore be macroscopically homogeneous and regular to serve as model surface for the ordered deposition of particles by dip coating and other methods. Too great a variance in the quality of the samples would render the investigation of the deposition mechanisms very dicult by causing meniscus jumps during dip coating and inhomogeneity in wetting ability. The number of samples produced also had to be large enough to allow the study of deposition processes. Electrochemical polishing was chosen for this study as it allows the production of very smooth surfaces and presents several advantages with respect to mechanical polishing:
No residual stress in the supercial layers No impurities or inclusions Time gains Better results in the micro-roughness range (<1 m).
The electropolishing process was adapted from a method developed at EPFL by Olivier Piotrowski [85]. Two directions were developed in parallel: an increase in the quality of the polishing in order to meet the requirements mentioned above, and an increase in the number of samples that could be produced. As a rst approach towards increasing the quality of the polishing, a systematic experimental optimization method was applied, starting from Piotrowskis experimental setup. New setups were also imagined to increase productivity and polish several samples at once.
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3.3.2
Theory
It is not our purpose here to go in depth into theory, as electrochemical polishing is a complex subject on which much research has been done. A few basic concepts ought however to be introduced in order to understand the problems encountered and how they were solved. The principle of electrochemical polishing is the dissolution of a metal in an electrolyte by a combination of a chemical potential and an electrical (anodic) potential. In the case of titanium, the native inert oxide layer present on its surface necessitates the use of high anodic potentials and concentrated acidic electrolytes. The polishing eect is generally explained by the fact that the rate of dissolution is limited by the speed of material transport at the surface. The diusion rate of ionic species involved in the dissolution process is the rate limiting step in the reaction. If the initial roughness is in the order of magnitude of the diusion layer, ions dissolving from peaks have comparatively a shorter diusion path to tread than from valleys (see gure 3.15). As a result of their greater accessibility, peaks dissolve faster than valley and a levelling eect occurs.
Figure 3.2: Levelling eect. Scheme of a sinusoidal surface of period and amplitude . The solid line represents Nernsts diusion layer (thickness ). Picture adapted from [85].
Several conicting theories exist as to exactly which diusion phenomenon limits the process. According to some, it is the diusion of metallic ions produced at the anode, for others, it is the diusion of acceptor compounds, or complexing ions from the solution to the anode. The results obtained by O. Piotrowski point
84
to the diusion of tetravalent titanium ions as the limiting phenomenon in our case. Another similar phenomenon called brightening occurs at the surface, but at a scale of the order of a few nanometers. It is also a mass transport limitation, and is due to the existence at the surface of a thin layer called brightening layer or Hoar layer. An explanation for this phenomenon is the formation of a contaminated oxide layer permeable to metallic ions. The eect of this layer, also called adsorbate layer or anhydrous layer, is to annihilate the eect of crystallographic orientation and grain boundaries on the dissolution rate and thus avoid crystallographic etching [37]. This is an advantage in our case as it allows the production of very smooth homogeneous surfaces from a polycrystalline material. Polishing and brightening occur only with a limitation in mass transport, which is not obtained for all metals and in all situations. Achieving this condition depends in our case on the experimental setup. Under mass transport limitation, the current density at the anode is independent from the potential applied. It goes through a plateau over a wide range of anodic potentials. Above this range, sparking, heating and gas evolution appear and no polishing occurs. Below this range, the current is limited mainly by the Ohmic resistance of the electrolyte. As for all valve metals, the anodic dissolution of titanium takes place after the dissolution of its native passive titanium dioxide layer. With increasing anodic polarisation, the formation of pits in this passive layer occurs randomly across the surface, as determined by local conditions (eg. defects, impurities). Polarisation curves (current intensity measured as a function of increasing voltage) by Piotrowski for titanium in methanol-sulphuric acid electrolyte show that current intensities measured are very irreproducible and that the surfaces thus treated are not polished, but inhomogeneously pitted, and that dissolution only take place in these pits. On the other hand, inverse polarisation curves, starting at high potentials and going down to zero, show good reproducibility, and the samples treated are smooth. When starting at high anodic potential, pitting very quickly occurs all over the surface so that it can be considered as homogeneously activated. This activated surface can then dissolve homogeneously and does not form pits. This
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depassivation treatment avoids the random character of the pitting process and was applied in our polishing process. Under polishing conditions, the current density strongly depends on the speed of the electrolyte ow on the anode. A high electrolyte ow speed on the titanium surface will increase the value of the current density plateau and therefore the dissolution rate. The best results are obtained with a homogeneous laminar ow of electrolyte across the surface. To achieve this, a relative movement between the sample and the electrolyte is needed, either by stirring the electrolyte or by moving the sample in the electrolyte. Both types of approach were attempted, namely rotating anodes, and stirred electrolyte.
3.3.3
3.3.3.1
Materials and Methods

Electrolyte
Figure 3.3: Titanium sample before polishing.
The electrolyte used for the electrochemical polishing of titanium is 3 M sulphuric acid (sigma 95-97%) in methanol (puriss, H2 O<0.2%). Sulphuric acid is added dropwise to methanol in a calibrated ask under magnetic stirring. The magnetic stirrer is then removed and the ask is lled up to the mark with methanol. Special care is taken to avoid excessive heating of the mixture, as the mixing and the reaction between methanol and sulphuric acid is strongly exothermic. The electrolyte is used freshly prepared.
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3.3.3.2
Sample preparation
The samples are machined at a high level of nish out of a grade 2 titanium plate of 0.5 mm thickness (cold laminated and annealed according to ASTM B 265 Gr. 2, Bibus Metalle AG) into rectangular strips of dimensions 40 x 7 mm2 , or alternatively into discs of 15 mm diameter. They are cleaned for 5 minutes in an ultrasonic baths in D.I. water, acetone and isopropanol successively. The samples were then masked as shown on gure 3.3, leaving an area of 0.7 cm2 on one end to be polished and an uncovered segment at the other end for electrical contact (see gure 3.3). Masking was done using painters adhesive tape, which has excellent chemical resistance to the polishing electrolyte. 3.3.3.3 Rotating disc electrode
This setup is composed of a Pine Modulated Speed Rotator (MSR, see gure 3.4) tted with a disc rotating electrode, using the 15 mm titanium discs. The electrolyte is cooled to a temperature of 15 C in a double wall 1 l glass container tted to a cryostat circulator. The circulator is lled with a cooling uid composed of 40 %vol ethanol in water. The counter electrode is composed of a tubular stainless steel grid covering the inside of the glass container. 3.3.3.4 Multisample rotating electrode
The multisample rotating electrode was constructed to increase the productivity of rectangular samples. Rectangular samples were preferred to discs for their potential application in dip coating. It is composed of a central cylindrical aluminium piece, on which up to six titanium strips can be xed (see gure 3.4B). This electrode is mounted on a shaft compatible with the Pine setup is otherwise identical to the rotating disc electrode. 3.3.3.5 Electrochemical cell
MSR. The end
of the strips are immersed in the electrolyte and rotated at variable speeds. The
The setup is based on a magnetically stirred double walled glass electrochemistry cell with ve necks. A homemade sample holder xes the rectangular sample
87
Figure 3.4: Rotating electrode setups. A: Pine Modulated Speed Rotator with disc electrode; B: Multisample rotating electrode with up to six samples.
88
vertically, the end dipping in the electrolyte. Two platinum counter-electrodes of 1 cm2 each are xed at the other side of the cell. 250 ml of electrolyte are poured into the cell and cooled to 15 C under vigorous magnetic stirring. The sample is oriented to a 30 angle with respect to the ow to ensure homogeneous laminar ow across its surface. 3.3.3.6 Multisample electrochemical cell
This setup is built around a stainless steel refrigerated cathode (also connected to the cryostat circulator) placed in a magnetically stirred bath containing 600 ml of electrolyte. The bath is hermetically covered with a lid equipped with an O-ring and maintained with plastic clamps (see gure 3.5). The lid is perforated to t four independent sample holders, each capable of maintaining one rectangular sample in position. The samples are connected electrically by crocodile clamps, and the cathode is connected by a standard connector through the lid. Polymeric foam is placed around the bath for thermal insulation, and to minimize frost formation on the setup.
Figure 3.5: Multisample electrochemistry cell. Complete setup with four sample holders (A); Refrigerated cathode and lid (B).
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3.3.3.7
Roughness measurements
Larger roughness scales measurements were done using a UBM laser prolometer with a 1 m diameter laser and a vertical resolution of 10 nm. The scanning length was 2000 mm with a resolution of 2000 points/mm. 5 proles were measured for each sample. Small scale roughness measurements were done by atomic force microscopy (AFM) using a Veeco CPII microscope in non-contact mode on 20x20
m2 or 25x25 m2 surfaces with a resolution of 256x256 points.
3.3.3.8
Roughness parameter
For each prole, an ideal baseline can be plotted where all the total area above the line is equal to the total area below. Dierent roughness parameters can then be calculated with respect to this baseline. Ra is the most generally used and is calculated by taking the arithmetic average of the dierence between each prole point and the baseline over the whole prole length. 1 Ra = n
n
|zi |
i=1
Where n is the number of points in the prole, zi is the height dierence between the prole and the baseline. Ra was the only roughness parameter used for all measurements. Roughness values are strongly dependant on the scale at which one performs the topographic measurement. For example, mechanical polishing yields very at surfaces when measured on the millimetre scale and quite rough surfaces on the micrometre scale, whereas the opposite is observed for electrochemical polishing. Our topographic proles were therefore analysed using a multi-scale roughness analysis program called Scale Crawler developed by P.F. Chauvy at EPFL [18]. This program breaks down topographic proles into baseline segments of variable lengths (scales) and measures the corresponding average roughness for each scale. It thus makes it possible to plot the roughness of the sample against the scale and gives a complete overview of the topography.
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3.3.4
3.3.4.1
Experimental optimisation of polishing

Experiment plan
The rotating disc electrode was used to perform a rst study of the polishing process. The factors chosen were the rotation speed of the electrode, the duration of the polishing process and the applied anodic potential. It should be noted here that all potentials given are measured between the counter electrode (cathode) and the working electrode (anode), and that no standard reference electrode was used. A 2x3x3 complete experiment plan was designed; the dierent factors and levels can be seen in table 3.1. Factor Denition A B C Levels 1 2 Rotation speed [rpm] 500 750 Time [min] 5 6 Anodic potential [V] 10 15
3 7 20
Table 3.1: Structure of the experiment plan.
The samples were characterised by laser prolometer, and the value of roughness Ra at a scale of 200 m was taken as the measured response. The 18 experiments were conducted in random order so as to minimise systematic errors. All samples were rst treated at 30 V for 30 seconds, so as to activate the entire surface. The voltage was then decreased to the nominal values indicated in table 3.2. 3.3.4.2 Results and discussion
The results obtained from this experimental optimisation plan are summarised in gure 3.6. The list of signicant eects and interactions, as well as the magnitude of these eects on the roughness parameter is shown in gure 3.7. As can seen on gure 3.7, factor C, the applied potential, does not have an inuence on the roughness of the sample. This is not unexpected as polishing
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Figure 3.6: Results: Experimental values and values predicted by the statistical model (Adjusted values) for all the dierent treatments.
Figure 3.7: Eect of the factors. Only four factors have an inuence on the roughness.
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Treatment Exp. n Rotation [rpm] Time [min] Potential [V] 111 1 500 5 10 211 2 750 5 10 121 3 500 6 10 221 4 750 6 10 131 5 500 7 10 231 6 750 7 10 112 7 500 5 15 212 8 750 5 15 122 9 500 6 15 222 10 750 6 15 132 11 500 7 15 232 12 750 7 15 113 13 500 5 20 213 14 750 5 20 123 15 500 6 20 223 16 750 6 20 133 17 500 7 20 233 18 750 7 20
Table 3.2: List of experiments.
occurs under mass transport limitation, and therefore independently of potential. Both rotation speed and time have a strong inuence on the roughness. The eect of factors spread on three levels is interpreted as the sum of two orthogonal polynomials that can be determined independently, one linear polynomial multiplied by a factor (B1) and a parabolic polynomial multiplied by a second factor (B2). In this instance, the eect of B is signicant for both these components. The four factors shown in gure 3.7 account for 90.16 % of the experimental variability, the remainder being considered as experimental error. Experiment plans aim to describe a local response surface for a given system. The physical interpretation of each signicant eect is not always possible, nor is it the purpose of the method. For simple eects, such as the eect of A, the rotation speed, we can say that faster electrolyte ow on the surface improves
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the quality of polishing. Conversely, the eect of AB2, the interaction of factor A with the quadratic component of factor B does not necessarily lead to meaningful conclusions on the mechanisms at play. The best approach is therefore to plot the response surface, as is done on gure 3.8, and choose the appropriate factor levels to minimize Ra .
Figure 3.8: Response surface at 20 V. Roughness parameter Ra as a function of polishing time and rotation speed.
In this case, one would choose long polishing times and fast electrolyte ow rates.
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3.3.5
3.3.5.1
Other factors aecting polishing.

Eect of water.
The surface roughness of the samples produced was very variable, and although good quality surfaces could sometimes be obtained, the method lacked reproducibility. The whole process was therefore investigated and as a result, the reproducibility and the roughness of the surfaces produced were signicantly improved. The reproducibility of the method can be impaired by two main factors which had to be well understood and controlled. The rst of these factors was the inuence of water in the polishing electrolyte. The electrolyte must be water free as the presence of water causes re-passivation of the titanium and results in pitting. Characteristic polishing defects are caused by very small water concentrations. The eect of large quantities of water on this electrochemical polishing process was investigated by Olivier Piotrowski, who found that with more than 5 % water content, the titanium surface is passivated. Once formed, the oxide lm tends to prevent surface dissolution. He also found that polishing could be obtained with electrolytes containing up to 5 % water provided the voltage condition chosen ensured that a saline dissolution lm had a chance to form in the rst place. It should however be noted here that a major dierence exists between roughness characterisation methods implemented by O. Piotrowski and those used here. Piotrowski used laser prolometry as a main characterisation method, which gives very good results in the micron size range, but cannot detect topographic features in the nanometric scale. Given the objectives of this project, and the typical length scale of the structurations created, AFM was used as topographical survey tool throughout this study. As a result, many surfaces deemed mirror polished by laser prolometry were in fact quite rough on the nanoscale, and typical polishing defects caused by the presence of very small water contents were not detected. They however represented a real quality and reproducibility problem for our application. A typical example of such water-caused polishing defects can be seen on gure 3.9. The topographic features are only a few nanometers in height, but they are in the range of our nanostructurations. The exact mechanism for this phenomenon
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Figure 3.9: AFM-Typical polishing defects caused by small amounts of water in the electrolyte. The electrolyte was contaminated though condensation from ambient air.
is not known, but it could be due to a local breakdown of the brightening layer (or anhydrous layer) due to the presence of water. 3.3.5.2 Sources of water contamination.
Assuming the use of anhydrous starting chemicals, there are three main sources of water contamination. The rst one is the fact that these chemicals (methanol, puriss. and sulphuric acid 95-97%) are very hygroscopic and that their exposure to moist air will in time deteriorate the quality of the electrolyte. The second, and perhaps major source of contamination is the condensation of water from the atmosphere onto the surface of the electrolyte which is cooled at 15 C. Surfaces at such temperatures tend to condense water very eciently, even more so when the ambient relative humidity is high. This eect was rst suspected when looking at the quality of polished samples produced over a period of one year. It was noticed that samples produced during spring and summer presented more polishing defects than those produced during winter. The ambient relative humidity during summer can be as high as 80 %, whereas it usually drops to 20 % during the winter. To avoid this seasonal
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variance, the dierent polishing setups were placed in a glove box under a ow of dry compressed air. The relative humidity could thus be lowered to values well below 20 %, which was the lower measuring limit of the hygrometers used. The preparation of the electrolyte and the handling of water sensitive chemicals were also done in the glove box. The third source of water contamination comes from the electrolyte itself. Methanol and sulphuric acid react together according to [85]: MeOH + H2 SO4 MeOH+ + HSO MeOSO3 H + H2 O 4 2 (3.4)
The rst reaction produces persulphate ions and protonated methanol, and is necessary for the dissolution reaction of titanium. The second reaction produces methyl sulfonate and water and is therefore detrimental to the eciency of the electrolyte. It is furthermore dangerous for the health as methyl sulfonate is poisonous. The second reaction is slow at room temperature, but can proceed faster in an excess of sulphuric acid, or in case the electrolyte heats up too much. This can happen during the preparation of the electrolyte, which is a strongly exothermic process. To avoid this problem, the electrolyte must be prepared fresh and prevented from heating up above 60 C. 3.3.5.3 Non-anodic current limitations.
The second problem encountered can be summarised as non-anodic current limitations. The current in the electrochemical cell is limited during polishing by mass transport at the anode, which is mainly determined by the speed of the electrolyte ux on the anode surface, as well as by the surface area of the anode. Indirectly therefore, increasing the ux (faster stirring), or polishing large surfaces increase the demand in electrical current. As long as the electrical source can provide it, the polishing process goes on. As soon as some other factor becomes limiting, the roughness increases dramatically, particularly on the parts of the sample where the ux is highest. The non-anodic current limiting factors are the cathodic reaction and the maximal power of the electrical source. In the latter case, not much can be done apart from decreasing the size of the sample. In the former case however, the
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surface area of the cathode can be increased. This explains why when polishing in the exact same conditions two samples of slightly dierent sizes, the results could be extremely dierent. The cathodic reaction can also be hindered by surface contaminants (mainly titanium), which is easily remedied by inversing the polarity of the polishing cell for a few seconds to dissolves them o the platinum cathode.
3.3.6
3.3.6.1
Assessment of the dierent polishing setups.

Rotating electrode setups
The rotating disc electrode was a useful setup for the optimization of the polishing parameters. It had however certain drawbacks, such as the fact that the electrolyte bath was not conned hermetically, letting substantial water condensation take place and by that limiting the quality of the samples. Furthermore, the sample shape was not adapted to the envisaged dip coating process. The multisample rotating electrode did not have this problem, as it was built for rectangular samples, but the results obtained were disappointing. First of all it also suers from water condensation, and secondly, an inadequacy in the design cause turbulent ow to appear already at low rotation speeds. Furthermore, the demand in current for six samples was greater than what could be provided by the power source. This option was therefore not pursued any further. 3.3.6.2 Fixed electrode setups
The conclusions from the experiment plan, in combination with the considerations detailed in section 3.3.5.1 were implemented to the single sample electrochemical cell setup with success. The parameters chosen in this case were a duration time of 10 minutes and the maximal stirring speed attainable with the magnetic stirrer, approximately 900 rpm. It is with this setup that the best results were obtained. Figure 3.10 shows the plot of the roughness parameter Ra against the scale before and after optimization as measured by AFM. The roughnesses obtained before optimisation are similar to Piotrowskis results at the same scale. The best samples produced in controlled atmosphere with the single sample electrochemical cell do not exceed Ra values of 1.75 nm at 20
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Figure 3.10: Multiscale roughness measurement from AFM proles for samples polished before and after optimisation.
m segment length. An example of such a surface can be seen on gure 3.11. A
slight crystallographic etching is visible, with level dierences between grains of the order of 1 nm. The multisample electrochemical cell worked well in principle and was used to produce samples for the particle deposition studies. The results obtained were similar to those for the single sample cell. For practical reasons however, the single sample cell was preferred when the accent had to be put on quality rather than quantity. It was furthermore never placed in controlled atmosphere, which would certainly have improved its performance.
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Figure 3.11: AFM-Polished titanium surface.
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3.4 Particle-substrate contact
3.4
3.4.1
Particle-substrate contact
Introduction
To understand and control the masking eect of particles on the titanium surface, the dimension and nature of the contact between the polymeric beads and the titanium surface was measured, modeled and eventually modied. In that perspective, the eect of heat treatments and acetone vapour on the particlesubstrate contact radius was investigated.
3.4.2
Commercially available polystyrene (PS) particle suspensions in water were used for all experiment. They were purchased (estapor w/w suspension in water. Electropolished titanium substrates were treated for 5 minutes in air plasma to enhance their wettability. 10 l drops of 0.01 %vol suspension of 500 nm or 200 nm diameter PS particles in D.I. water were deposited on the surface. The suspension was allowed to dry in a climatic chamber at 80% RH and 20 C. The heated samples were placed in a stove at 150 C for dierent times. They were then taken out and either dipped in D.I. water at room temperature, or left to cool in air. Samples treated with acetone vapour were placed in a sealed chamber containing a petri dish lled with acetone. They are taken out after certain times and dried in a ux of compressed air. The particle-substrate contact diameter was measured on a high resolution scanning electron microscope with an in lens secondary electron detector, at a tilt angle of 85 so as to be able to image the contact site. The measurements were done using imageJ image analysis program. Ten measurements were made of each type of particle.
, France) in two dierent
nominal diameters, 200 and 500 nm (ref. K020 and K050 respectively) as 10%
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3.4.3
3.4.3.1

Pristine particles
The results of the measurements can be seen in table 3.4. Figure 3.12 shows views of the particles at 85 tilt angle. The contact diameter is visible and can be measured with around 5 % error on ten measurements.
Figure 3.12: Contact diameter measurement. 500 nm diameter particles.
A classical model to describe adhesive contact between deformable surfaces is the one developped by Johnson, Kendal and Roberts (JKR) in 1971 [43]. It is a simple extension of the Hertz theory of elastic contact that takes into account deformations and stresses caused by adhesion phenomena at the contact site [56, 67] and is valid under the following assumptions [95]:
Deformations are assumed to be purely linear elastic Materials are elastically isotropic Youngs modulus and Poissons ratio do not change under pressure
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The contact radius is small compared to the radius of the particle.
The contact radius a0 between an adhesive deformable sphere of radius R and a sti surface can be described by equation 3.5. a0 =
3
9R2 (1 )/E
(3.5)
Where is the interfacial energy between the polystyrene and the titanium, E and are Youngs modulus and Poissons ratio for polystyrene. Youngs Modulus (at RT) 2.2 GPa Youngs Modulus (at 150 C) 1 MPa Poissons ratio 0.34 H Hardness 27 MPa Glass temperature 110 C Melting Point 270 C Surface energy 0.034 J/m2 [88] [98] [98] [88] [98] [98] [97]
Table 3.3: Properties of polystyrene. From literature.
The contact areas predicted by this model for polystyrene particles on titanium can be seen in table 3.4. R [nm] a0 JRK [nm] a0 measured [nm] 100 23.2 38 250 42.8 70
Table 3.4: Contact radii predicted by the JKR model vs. measured contact radii.
The contact radii predicted by the JKR model are in a reasonable order of magnitude, although signicantly lower than those measured. This indicates that the assumptions made above are not all true and that the JKR model cannot be applied directly. It is likely, as reported by Rimai et al. [89], that some plastic deformation occurs at the contact site.
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The Maugis-Pollock model [68] is an extension of the JKR model taking into account plastic deformations at the contact zone. It predicts a square root dependency between the contact radius and the particle radius according to equation 3.6. Ha2 = 2RwA 0 (3.6)
where wA is the work of adhesion, H is the hardness of the polystyrene. wA is related to the surface energies of the material and their interfacial energy by wA = T i + P S T iP S (3.7)
Rimai et al. [88] have studied the adhesion of polystyrene spheres on silicium wafers in quite a lot of detail. They have found the Maugis-Pollock model to be suitable and were able to deduce a reasonable value for the work of adhesion. Although the substrate is dierent, the surface energy of silicium (0.75 J/m2 ) is in the same order of magnitude that of anathase (0.74 J/m2 [59]), the low temperature polymorph of titanium dioxide. It is thus arguable that the works of adhesion would be comparable. The radii measured in our case were therefore directly plotted alongside theirs to assess the applicability of their model to our situation. The particles they used were larger than ours and ranged from 0.81
m to 5.9 m, as can be seen in gure 3.13.
The results follow the trend predicted by the Maugis-Pollock model, our points being very close to the linear regression curve established by Rimai et al. For our situation, wA was therefore taken as equal to the one measured by them, namely 0.72 J/m2 . 3.4.3.2 Eect of heat
The main eect of heating above Tg is to decrease the Youngs modulus of the particles by several orders of magnitude. The minimal temperature to obtain this eect is around 150 C, which is higher than the literature value of 110 C for Tg of polystyrene (table 3.3). This could be explained by the small dimensions of the particles, which can cause shift in the glass temperature of the particles with respect to the bulk material due
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Figure 3.13: Linear plot of the contact radius a0 against the square root of the particle radius. The results of Rimai et al. (diamonds) and our results (triangles) follow the Maugis-Pollock model.
Figure 3.14: Eect of heat on the contact diameter. 500 nm diameter particles heated at 150 C for 20 seconds.
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to entropic eects [69] as we approach a particles sizes similar to the radius of gyration of the polymer chains. It could also be due to the level of cross-linking of the particles surface. The heating time did not have a noticable eect on the morphology of the deformed particles as for all times between 10 second and 5 minutes, the contact radius did not change signicantly. The JKR model cannot be applied to the case of the heated particles as the contact radius is no longer small compared to the particle radius. Another model developed by Lau et al. [56] describes the spreading of soft latex particles on a substrate. The latex particles they use are styrene butadiene copolymer with dierent degrees of cross-linking. These polymers have a glass transition temperatures below room temperature and are therefore used in the rubbery state. At temperatures above Tg, Youngs modulus for polystyrene decreases by two to three orders of magnitude. As in the previous models, the nal shape of the deformed particle at equilibrium is determined by the minimization between the mechanical energy required to deform the particle, and the work of adhesion. Due to the diculty of a formal computation of the elastic energy for such high deformations, this model computes the elastic energy over large deformations by resorting of a scaling picture (see gure 3.15), assuming a spherical cap geometry of the deformed particle and volume conservation.
Figure 3.15: Geometry of a deformed elastic sphere. a0 is the contact radius, h the height of the spherical cap, R the radius of the sphere, uz () is the deformation.
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The surface Energy Us is given by: Us = A wa = a2 wa 0 (3.8)
Where A is the contact area, a0 is the contact radius and wa is the work of adhesion. Assuming a constant total volume, we can calculate the radius R of the deformed truncated sphere. R = 1 3 4R3 + h3 h2 (3.9)
The contact radius a can then be calculated to be: a= R 2 (R h)2 (3.10)
Using the value for the work of adhesion wa found by Rimai et al. [88], see section 3.4.3.1 we can calculate the surface energy for all deformations h/2R. The elastic energy as a function of h is thus calculated according to equation 3.11 8 Uel = KR3 (h/2R) 3 scaling function given as: 4 4 x1 x2 (1 x)2 (1 x)(x1 x2 ) + (x1 x2 ) 9 45 (3.11)
where K is a stiness parameter dened as K = E/(1 2 ), and (x) is a
(x) =
(3.12)
Minimizing the total energy Utot = Uel + Us , and knowing the exact material constants of the polymer, we can predict the equilibrium contact radius (see gure 3.16). The main unknown parameter in this case is the exact value of Youngs modulus for the particles at 150 C, this temperature being in the zone of transition around Tg . Using the literature value of Youngs modulus for bulk polystyrene above Tg (see table 3.3) does not give credible results.
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Youngs modulus was therefore varied in order to t the model to the experimental data. The conclusion is that if this model is correct, the 500 and 200 nm particles do not have the same mechanical properties. The 200 nm particles seem to be stier than the 500 nm particles.
Figure 3.16: Elastic, surface and total energies for the spreading of 200 nm and 500 nm PS particles at 150 C. The energy minima are at h/2R = 0.57 and 0.65 respectively.
R [nm] h measured [nm] Calculated Youngs modulus [MPa] 100 116 5 7.8 250 353 14 3.3
Table 3.5: Calculated Youngs modulus according to the Lau et al. model.
This phenomenon of size dependent stiness for latex microspheres has been reported in literature, particularly for cross-linked particles above Tg [36]. During synthesis, the surface of the particles is cross-linked in order to obtain the desired mechanical and surface properties. As a result, a core-shell eect is observed, where the supercial layer around the particles is stier than the inside. The absolute thickness of this layer is constant for all particle sizes, and this shell eect is thus more dominant on the mechanical properties of smaller particles. This could explain why the smaller particles are stier.
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Figure 3.17: 500 and 200 nm deformed particles (150 C for 5 minutes). The two particles seem to have dierent stinesses.
The calculated moduli (table 3.5) are in the correct order of magnitude, the literature value for the bulk being around 1 MPa (see table 3.3). 3.4.3.3 Eect of acetone
Another approach to modify the particle-substrate contact area was to make use of the capillary condensation eect which occurs at the particle-substrate interface. The interface region is a very narrow gap which tends to condense vapours from the ambient atmosphere, as schematized on gure 3.18.
Figure 3.18: Capillary condensation around a spherical particle in presence of a vapour. Picture taken from [44].
Samples were placed in a saturated acetone atmosphere for 10 minutes before they were taken out. The eect of this treatment was observed by SEM and can be seen on gure 3.19.
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Figure 3.19: Eect of acetone capillary condensation. solvent for PS and softens the particles.
Acetone acts as a
This eect is interesting to modify the particle-surface contact. Heating was however preferred for all structuring experiments as it is easier to control.
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3.5 Particle deposition
3.5
3.5.1
Particle deposition
Introduction
Self assembled monolayers (SAM) are 2 dimensional periodic lattices formed of monodisperse spherical colloidal particles. Self assembly of colloidal particle can be achieved by making use of attractive capillary forces due to solvent evaporation (see gure 3.20).
Figure 3.20: Schematic illustration of the phenomenon of particle diusion toward the meniscus encountered in processes such as dip coating and drop-drying. Figure adapted from [44].
Evaporation causes a solvent ow towards the meniscus which carries the particles along with it. They accumulate at the meniscus without agglomerating and begin to arrange themselves in a close-packed conformation. They are then forced
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into adhesive contact with each other and with the surface by the interstitial capillary forces encountered during drying and form a hexagonal close packed array of one or more layers. To achieve colloidal self assembly of particles on a surface, a good colloidal stability of the particles against agglomeration is essential. The particles must have strong repulsive interactions, due to electrostatic charges at the surface for example, even at relatively short ranges (5 to 10 nm). They must moreover have a strong repulsive interaction with the surface. In our case, the latex particles used are negatively charged in water at neutral pH, with a zeta potential of -50 to -70 mV. The titania surface is also negatively charged, which provides adequate conditions of particle monolayer deposition. The particle size distribution is also an important factor for the quality of the SAMs produced. Inhomogeneity in the size of the particles has a detrimental eect on the ordering of the colloidal crystal produced. The particles used in our case are monodisperse, with less than 5% dispersion in particle diameter and can thus form high quality SAMs. One of the original objectives of this study was to optimise the particle deposition process in order to be able to coat large surfaces (several tens of cm2 ), such as the surface of implants, with dense self assembled monolayer from colloidal particles. The experimental diculties encountered with the polishing process, as well as those linked to the actual structuring of surfaces by anodisation, reduced the urgency of optimising this aspect of the method. Deposition methods were however found that allow the production of dense homogeneous SAMs over hundreds of microns, up to a few mm2 , which was quite sucient for the requirements of this research.
3.5.2
Polystyrene particle suspensions (estapor experiment.
, France) in water were used for all
Dip coating was realised on a dip-coater at various speeds using rectangular polished titanium samples. The samples were pre-treated 5 minutes in air plasma, dipped at various speeds in dierent particle suspensions (concentrations between 0.1 and 10 % w/w) and then dried in ambient air.
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Drop drying was performed on rectangular polished samples after 5 minutes of air plasma treatment. A 10 l drop of particles suspension at various concentration was pipetted at the center of the polished area. The drop was then allowed to dry in a climatic chamber at 20 C and either 10 or 80 % relative humidity. The samples were characterised by scanning electron microscopy.
3.5.3
Dip coating
No dense SAMs could be achieved by dip coating. The deposits produced were generally quite inhomogeneous, with substancial de-wetting of the sample and many meniscus jumps, and great local variations in particle coverage densities. Figure 3.21 shows some of the dierent structures observed for a range of dip conditions. For these reasons, and because of the quality and reproducibility of drop drying, dip coating was abandoned as a deposition method. In certain conditions, however, some order due to long-range electrostatic repulsion between the particle was observed, as can be seen on gure 3.21B. This ordering eect was used for the rst structuring attempts (section 3.7.3.1). Blttler et al. [12] have successfully deposited PS particle monolayers on glass a slides or silicium wafers by using very low retraction speed (from 1 to 10 m/s) in a strictly controlled atmosphere with 50 5 % RH and 22 1 C. These very low speeds are not attainable with our setup which furthermore cannot be placed in a controlled atmosphere.
3.5.4
Drop drying
Drop drying is easier to control and more reproducible than dip coating. The relative humidity level and the temperature determine the evaporation rate. Figure 3.22 shows the results obtained for the drying of 10 l drops of 0.1 % suspension of 200 (K020) and 500 (K050) nm particles at 10 and 80 % relative humidity. Samples dried at 80 % RH give better long range order than those dried at 10 %. Slower drying leaves more time for the migration and arrangement of the particles, which can thus from larger ordered domains. Figures 3.22 A and B show dense SAMs spreading over several microns.
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Figure 3.21: Dierent deposits obtained by dip coating of 200 nm particle. A: 10% 10 mm/min.; B: 0.25 %, 1000 mm/min; C: 1%, 600 mm/min; D: 1%, 300 mm/min.
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Figure 3.22: Self assembled monolayers by drop drying. A: K050, 80% RH; B: K050, 80 % RH; C and D: K050, 10% RH.
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3.6
3.6.1
Air plasma treatments

Air plasma for particle deposition
An important use of air plasma in this study is to increase the surface energy of the polished titanium substrates. All deposition processes being based on aqueous particle suspensions, the relative hydrophobicity of the titanium after polishing is a problem as unwetting of the surface, as well as meniscus jumps are detrimental to the desired homogeneity and ordering of the coating. After a ve minute treatment in air plasma, the surface is wet perfectly by water, without the need for additional surfactants. This eect lasts for approximately one hour, depending on the ambient humidity conditions, and so deposition processes were performed within a few minutes after the end of the plasma treatment.
3.6.2
Air plasma for SAM preparation
The preparation of dense particle monolayers with high particle-substrate contact radii cannot be realised directly as adjacent particles submitted to a heat treatment above Tg tend to coalesce, as can be seen on gure 3.14. Such a heat treatment, whilst increasing the particle-surface contact radius, causes the particles in a self assembled monolayer to coalesce into a lm, which is not a desired eect of the treatment. Oxygen plasma oxidises the polystyrene particles and causes an erosion of the material surface and a more or less uniform decrease in radius [12]. Applied to dense particle monolayers, a short treatment causes the particle-particle contacts, which are necessary to the ordering of the layer, to be eroded away, leaving isolated particles in an ordered hexagonal array (see gure 3.23). The thermal treatment (150 C for 30 seconds in a stove, followed by tempering in water at RT) can then be applied, increasing the particle-substrate contact radii without signicant coalescence of the particles. The appropriate time for such plasma treatments depends on the original size of the particles. 200 nm diameter particles subjected to an identical 2 minutes treatment do not retain their order but are partially destroyed.
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3.6 Air plasma treatments
Figure 3.23: Dense monolayer of 500 nm particles before (A) and after (B) 2 minutes oxygen plasma treatment. The particles retain their order but do not touch each other.
Figure 3.24: Ordered array of hemispherical PS particles. Obtained from a particle monolayer by plasma and thermal treatments.
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Figure 3.25: 200 nm diameter particles after 2 minutes plasma treatment.
3.6.3
Air plasma for cleaning
After anodisation, the particles are removed using a combination of ultrasound bath in acetone and oxygen plasma. A study of the eect of plasma treatment was realised to assess its eciency as a cleaning method. A sample was anodised in the presence of deformed PS particles. The sample was treated with oxygen plasma for one minute and then imaged by SEM under 85 tilt. The same operation was repeated 4 times, each time imaging the exact same locations on the sample. The particles could thus be almost completely removed by plasma cleaning, although some small polymer deposits could remain even after prolonged treatment. Blttler et al. report large star-shaped PS residues (> 200nm) that a cannot be removed by plasma cleaning. Such large residues were not seen in our study, which could be due to the use of particles from a dierent supplier, with possibly a smaller degree of cross-linking.
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3.6 Air plasma treatments
Figure 3.26: Deformed particle after dierent plasma treatment times. A: 1 min.; B: 2 min.; C: 3 min.; D: 4 min.
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Figure 3.27: Deformed particle array after dierent plasma treatment times. A: 1 min.; B: 2 min.; C: 3 min.; D: 4 min.
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3.7 Surface structuring with polystyrene particles
3.7
Surface structuring with polystyrene particles
3.7.1
Introduction
A rst step was the characterisation of the eect of isolated particles on the topography of the surface using atomic force microscopy. Determining whether there is a bump or a cavity in the oxide layer underneath the particle was to give us indications on the mechanism at work. A second step was to investigate the eect of a self assembled monolayer of particles on the topography. Finally, structuring attempts were made with heat deformed particles, both as individual particles and SAMs. To detect structures caused by particles, it is important that the anodisation process itself does not create too many topographic feature. Most studies were therefore realised at an anodisation voltage of 40 V because it is an appropriate voltage for the growth of a smooth, amorphous oxide layer with few anodisation defects and a layer thickness of 100 nm which is enough to start observing eects on the topography. The inuence of the particle-surface contact radius, the eect of deposition in SAMs as well as the eect of anodisation conditions (anodisation voltage and voltage-time proles) were investigated.
3.7.2
PS microspheres of 200 nm or 500 nm diameter are used (estapor
K020 and
K050) for all experiments. Several dilutions between 10 and 0.05 % vol were prepared in DI water and used either in dip-coating or drop drying as described previously. Sparse coverages were obtained by dip-coating in 0.25% vol particle suspension at 1000 mm/min. and drying in ambient air. Self-assembled monolayers were obtained by depositing a 10 l drop of 0.2 % vol of particles on a surface previously treated in air plasma for 5 minutes, followed by slow drying in a climatic chamber at 20 C and 80 % RH.
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Anodisation was performed using a computer driven Agilent
6030 A source
at dierent voltages in 500 ml of 0.5 M sulphuric acid against a cathode made of a 30 x 10 cm2 stainless steel grid lining the walls of a 1 l glass beaker. The samples were dipped approximately 1 cm into the electrolyte. The particles were removed from the substrates after anodisation either by 20 minutes ultrasound treatment in D.I. water followed by 5 minutes in air plasma in the case of the pristine particles, or by a 15 minute treatment in air plasma in the case of the deformed particles. The samples were observed in a SEM (Phillips XLF30) without further preparation after dip coating, after anodisation and after cleaning. AFM was performed using a Veeco Instruments CPII setup with MPP11123-10 tips in non-contact mode.
3.7.3
3.7.3.1

Inuence of the contact radius
A diculty in investigating the eect of a single particle on the topography of the anodised surface is to be sure that any feature detected by AFM is indeed caused by the presence of the particle during anodisation. To do so, the best way would be to take a SEM picture of a certain area of the sample after dip coating, perform the anodisation, remove the particles and then make an AFM picture of the exact same spot.
Figure 3.28: Structuring with particles. The reality look more like this than like gure 1.1.
This is however practically very hard to do, as moving the tip of the AFM to a predened location is not possible in our setup. The best option then was to have a particle coating that was homogeneous on the majority of the surface, and presented recognisable features (interparticle spacing, general appearance),
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so that the features then detected by AFM, if they showed the same type of properties, could be without doubt attributed to the inuence of the particles.
Figure 3.29: Sample coated with 200 nm particles. Dip-coating at 1000 mm/min in 0.25 %vol suspension.
The samples chosen to perform the topographical study present an homogeneous distribution of particles that is quite recognisable, as can be seen from gure 3.29. Due to strong repulsion forces between them, the particles are spread out to a large majority as single particles, with a few pairs and triplets. The particles retain this type of order after anodisation, indicating that they remain still during the process. The topography of the particle covered sample (gure 3.30) presents many protrusions between 10 and 15 nm in height and around 80 nm in radius, spread evenly across the surface. The right picture gives an idea of what the sample would have looked like before the particles were removed, under the assumption that the detected features were indeed caused by them. If one compares it to gure 3.29, one sees that the general appearance of the two pictures is very similar. One can see that pairs and triplets are at the correct distance from each other ( 200 nm), indicating beyond doubt that the detected topographical features are the eect of the particles. Figure 3.31 shows a plot of the prole across two of these defects, and allows us to measure their dimensions.
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Figure 3.30: AFM image of anodised samples. All pictures are 5x5 m2 . The picture on the right gives an idea of what the sample looked like before the particles were removed (200 nm circles represent the particles).
Figure 3.31: Topography prole across protrusions. The peaks measure 10 to 15 nm in height and around 80 nm radius.
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These protrusions are very small and dicult to detect even with atomic force microscopy. They were also dicult to reproduce. No structuration was observed in the case of self-assembled monolayers of both 200 nm and 500 nm particles. Heat deformed particles on the other hand have a signicant eect on the topography.
Figure 3.32: Eect of heat deformed particles on the topography.
Figure 3.33: Surface structuring with deformed particles. AFM, 500 nm particles, anodised at 40 V.
As seen on gure 3.14, 500 nm diameter particles have contact radius after heat treatment of the order of 700 nm. This large contact radius causes a much more visible eect on the topography than in the case of the pristine particles. As can be seen on gure 3.34, these structures are typically composed of a protruding rim on the outside, immediately followed by a depression, or pit,
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Figure 3.34: Prole across the imprint of a deformed particle. The rim is well visible on either side of the prole.
approximately 6 to 7 nm in depth and a radius corresponding to the particlesurface contact radius. At 40 V anodisation voltage, the oxide layer is approximately 100 nm thick, and the height dierence between anodised and non-anodised titanium is around 50 nm. This means that although the particles have an eect on the growth of the oxide lm, they do not hinder it completely: anodisation occurs underneath the particles. This is perhaps more surprising than for the case of the pristine particles, where the particle-substrate contact area is a hundred times smaller, and the contact radius is in the size range of the oxide layer thickness. In the case of the deformed particles however, with contact diameters almost reaching micron sizes, it poses the question of the growth mechanism of the oxide layer underneath the mask. In the z direction, the electric conductivity of the oxide layer is the limiting factor for the propagation of the oxidation process. As seen before, and for our anodisation conditions, it virtually comes to a standstill after reaching a thickness of 100 nm. One can thus argue that in the presence of a mask, the same limitation should apply to the the horizontal propagation of the oxidation process as well, assuming it occurs using the same transport mechanisms (i.e. ionic conduction in high elds). Anodisation should thus not be able to progress further horizontally than about 100 nm from the edge inwards. It however evidently does, which points to a dierent transport mechanism than high eld ionic conduction.
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3.7.3.2
Eect of particle deposition
Figure 3.35: Surface structuring with self-assembled monolayers of deformed particles. SEM, 500 nm particles, anodised at 40 V.
The eect is enhanced when the particles form SAMs. The average height of the structurations in SAMs anodised at 40 V is around 12 nm, that is to say twice the height of the structurations for isolated particles (gure 3.39). The phenomenon causing the protrusion of the rims thus appears to be additive. Some SAMs obtained through optimised heat and plasma treatment do not coalesce, and can form regular honeycomb structures over surfaces up to several hundreds of m2 (gures 3.36 and 3.37A). Straight wall-like segments form between particles separated by narrow gaps (< 200 nm), as are found in such non-coalesced SAMs, which outline a well dened hexagonal array. These structures, which could be named narrow gap structures, are 30 to 50 nm in height. This is an enhancement of the rim eect of approximately ve to six times that of single isolated particles, and by that a promising feature for surface structuring. In other cases, the particles are still in contact in some points, and limited coalescence occurs, yielding somewhat dierent structures (gure 3.37B).
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Figure 3.36: Regular honeycomb structurations caused by SAMs of deformed particles. Anodisation at 40V.
Figure 3.37: Details of structurations by SAMs. A: non-coalesced (regular) monolayer; B: partially coalesced monolayer.
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3.7.3.3
Inuence of the anodisation voltage
Dierent anodisation voltages were applied between 10 and 100 V on 500 nm diameter heat deformed particles.
Figure 3.38: Imprint of deformed particles after anodisation at dierent voltages. 20 V (A), 40V (B), 80V (C) and 100 V (D).
The eect of anodisation voltage on the height of the structuration produced was characterised by two measurements realised on AFM proles, as can be seen on gure 3.39. The rst (Rim) was the height of the top of the rim with respect to the rest of the surface, while the second (Max) was the total amplitude of the structuration, between the highest and the lowest point (see gure 3.34).
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Figure 3.39: Height of topographic features as a function of anodisation voltage. Rim: height dierence between the rim and the rest of the surface; Max: total amplitude of the structuration, between the highest and the lowest point.
These height dierences evolve similarly with the anodisation voltage. The height of the rim represents for approximately 30 % of the total height of the structuration, irrespective of the anodisation voltage. The eect of particles on topography does not increase linearly with layer thickness, but is enhanced at higher anodisation voltages. Another notable inuence of the anodisation voltage is the morphology of the oxide layer formed under the masks. Figure 3.38 shows details of the oxide layers underneath particles at dierent voltages, and while a more or less homogeneous surface is found at 20 and 40 V, radial dendritic-like structures can be seen on samples at 80 and 100V. The oxide layer on these samples is visibly less dense underneath the mask. A network of canals are formed between the edge and the centre of the imprints (see gure 3.40). This canal network constitutes a possible alternative pathway to high eld ionic conduction for the transport of matter underneath the mask. A model to explain this phenomenon could be the competition between the oxidation reaction and the dissolution of titanium ions during anodisation. Under normal anodisation conditions with unlimited spacial access to the
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Figure 3.40: Structure of the oxide layer underneath the particles. Anodisation at 100 V.
electrolyte, only approximately 20% of the titanium ions arriving at the oxideelectrolyte interface go into solution instead being oxidised [26]. It is possible that this ratio is dierent underneath the mask, as the access to the electrolyte is limited and the sites in the vicinity of the edges cannot provide sucient adsorbed oxygen to oxidate all the titanium ions. As a result, a large proportion of the titanium starts to dissolve, creating cavities and canals in the underlying material. These could then constitute pathway for the inltration of the electrolyte underneath the mask, allowing the propagation of the oxidation process further than would have been possible with a classic high eld conduction model. Such a combination of dissolution and oxidation (growth) could explain how the anodic oxidation of titanium can progress underneath masks. Another interesting feature on gure 3.40A are the well visible narrow gap structures. The growth of the titanium oxide dendrites (for lack of a better word) seem to originate preferentially from these structures. The masking eect is probably increased by the proximity of the other particles which could enhance the dissolution-growth eect. 3.7.3.4 Inuence of the anodisation prole
Anodisation was performed in the majority of cases in potentiostatic mode, with a voltage step function (A, see gure 3.41). To study the eect of the voltage prole
131
on the structuration, some samples were anodised in potentiodynamic mode. Two voltage increase rates were applied, 20 V/s (B) and 400 V/s (C).
Figure 3.41: Scheme of the dierent anodisation treatments. A: Potentiostatic mode; B: Potentiodynamic mode at 400 V/s (not to scale); C: Potentiodynamic mode at 20 V/s.
Samples anodised in potentiodynamic mode at either sweep rates did not present any structurations at the voltage applied (40V), and no imprints of the particles could be found. The rapid increase in voltage in the case of the potentiostatic anodisation is limited only by the power of the electrical source, and corresponds to a high initial growth rate of the oxide. This seems to be a determining factor in the formation of the topographic features.
3.7.4
Conclusion
The eect of adsorbed particles on the topography of the anodic layer was studied in detail. It was found that anodisation was not prevented by the presence of the particles, whether deformed of not, and that the anodisation voltage, as well as the anodisation voltage prole had a strong inuence on the topography. Topography eects are also enhanced when the particles are separated by narrow gaps, which results in larger structures in particle monolayers.
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3.8 Model experiment using e-beam lithography
3.8
Model experiment using e-beam lithography
3.8.1
Aim of the experiment
The following observations were during preliminary studies on the eect of polystyrene particles on the topography of anodised titanium: 1. Particles do not prevent anodisation of titanium at the contact zone. 2. They nonetheless have an eect on topography. 3. They tend to leave protrusions rather than pits. 4. This eect is small and dicult to detect. 5. The particle-substrate contact area is small. These observations prompted the posing of the following questions: 1. How large must a particle or mask be to prevent anodisation? 2. Are there specic conditions at the edges that locally cause the occurrence of protrusions or pits? 3. Where are these topographic features situated with respect to the edge? 4. What is the eect of the masks size on the topography? 5. What is the structure of the oxide layer grown underneath the mask? To answer these questions, a model experiment was designed. The idea consists in creating an array of circular masks of dierent diameters on the titanium surface, starting from the diameter of the particles and increasingly larger (100nm, 200 nm, 400 nm, 800nm, 2 m, 4 m and so on up to 100 m). The titanium is then anodised, the masks are removed by cleaning, and the topography of the ensuing oxide layer is measured by atomic force microscopy. The process ow diagram, along with a scheme of the pattern created can be seen on gure 3.42.
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Figure 3.42: Process ow and pattern for e-beam lithography. 1: Spin coating of e-beam resist; 2: Exposure; 3: Development; 4: Anodisation; 5: AFM characterisation.
Having such broad range of mask sizes on a single sample allows the covering of several length scales at once, while the array design makes it easy to locate with precision where each mask was situated, even after it was removed. The smallest features (100 and 200 nm diameter masks) were too small to be produced by conventional lithography technique. Electron beam lithography was however perfectly adapted to our requirements, as it allows the fabrication of both the smallest and the largest masks with good writing precision. The principle of electron beam lithography is to expose a resin-coated surface to an electron beam according to specic patterns. The beam trigger a chemical reaction in the resin (e-beam resist) and causes it either to polymerise (positive resist) or to degrade (negative resist). The resin is then developed, and the unwanted areas are removed, leaving the desired pattern. For positive resists, as was used in our case, only the exposed areas remain after the development step, whereas the opposite is true for negative resists. The main advantage of ebeam lithography is its capacity to go beyond the diraction limit of light, which typically limits the applicability of traditional lithography to the fabrication of
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structures in the sub-micron range. The use of this technique in our case was however not straightforward, and several experimental diculties had to be solved. Existing e-beam systems are made to operate on standard silicium wafers, and the shape and dimensions of our samples were not necessarily adapted to the processes used in microtechnique. Furthermore, most available e-beam resists were silica based and had to be removed with hydrouoric acid. This was not an option in this case as there was a good chance that the HF would interact with the amorphous titanium oxide layer. A new polymeric resin was therefore tried, which despite wide use in lithography had not been thoroughly tested for e-beam.
3.8.2
Polished rectangular titanium samples were taken to a clean room under yellow light, cleaned in an ultrasonic bath for ve minutes in acetone and isopropanol and then dried under a clean nitrogen ux. They were then taped to a silicium wafer with Capton adhesive tape, placing the polished area at the center of the wafer. The wafer was then xed on a spin coater and the samples were spin coated at 2000 rpm for 1 minute with 3 ml of nLOF resist in PGMEA at a dilution of 1/3. The samples were removed from the wafer and heated on a hot plate at 110 C for 1 minute 45 seconds to bake the resin. They were then placed in the electron beam lithography setup, and exposed to the pattern chosen. For technical reasons the design was separated into two parts. The arrays of smaller masks were written with a ne resolution. The larger masks were then written with a coarser resolution so as reduce the writing time. The pattern was written twelve times at increasing electron dosages in order to nd optimal conditions, starting a 200 C/cm2 , and increasing by a factor 1.2 at each iteration up to 1486 C/cm2 . The sample were then post-baked at 110 C on a hot plate for 1 minute, and dipped in AZ 726 developer containing 2.38 % tetramethyl ammonium hydroxide for 30 seconds under gentle swirling. They were then rinsed for 30 seconds in D.I. water. The patterns were visible by eye at that stage.
135
Anodisation was performed in potentiostatic mode at 40 or 55 V in 1 M or 0.5 M H2 SO4 for 2 seconds. The resin was removed by 20 min ultrasound bath in acetone followed by 5 minutes in air plasma. The topographies were characterised by SEM and AFM as described before. Focused ion beam (FIB) cross sections were performed using a NVision 40 CrossBeam (Zeiss) with the help of Dr. Marco Cantoni (CIME, EPFL).
3.8.3
3.8.3.1

E-beam lithography
Figure 3.43 shows a general top view of the twelve repetitions of the design with increasing dosages the top right to the bottom left corner, row by row. The process yielded well dened structures for the weakest exposition dosage (200 C/cm2 ). Larger dosages cause charging and decreases the resolution of the patterns drastically.
Figure 3.43: Overview of the e-beam patterns for dierent electron dosages. Leak currents and charging cause blurring of the features at higher dosages.
At 200 C/cm2 the ne features are well fabricated, although due to resolution problems, the circularity of the smallest masks is not perfect as can be seen on gure 3.44. This is a limitation of the technique and cannot easily be remedied. The thickness of the masks was measured by SEM by imaging at a wide tilt angle of 85 . This imaging technique is very sensitive to topographical features,
136
Figure 3.44: Arrays of masks by e-beam lithography.
the grazing incident electron beam giving excellent contrast, which combined to the large eld depth of scanning electron microscopy makes it an indispensable characterisation tool. The thickness of the masks is approximately 200 nm and is homogeneous throughout the sample (gure 3.45).
Figure 3.45: Tilt view of the 4 m, 800 nm, 400 nm and 100 nm masks.
137
3.8.3.2
Eect of the masks on topography
The samples were imaged by SEM at each stage, before and after anodisation and after removal of the masks.
Figure 3.46: 2 m mask at dierent stages of the process.
Figure 3.46 shows the surface (2 m mask) at these dierent stages. A certain amount of delamination (mask peel-o) takes place during the process. It occurs probably after the main topographical features (outermost rims) have been formed, as they are well visible underneath the peeled o mask. As can be seen on gure 3.49, the small masks are too small to prevent anodisation, and the oxide layer is formed underneath. For the larger masks however (4
m diameter), a relatively deep hole (45 nm deep) is visible in the centre, corre-
sponding to the level dierence between anodised and non-anodised titanium. For this voltage and in these conditions, anodisation stops abruptly approximately 1
m away from the edge of the masks. Figure 3.51 shows the height proles across
the dierent masks. The step between the anodised and the non anodised metal is visible on the 4000 nm proles anodised at 40 V.
138
Figure 3.47: SEM image of the e-beam sample after anodisation and removal of the masks.
Figure 3.48: Tilt SEM image of the e-beam sample after anodisation and removal of the masks.
139
Figure 3.49: AFM topography of the e-beam sample after anodisation and cleaning. Anodisation at 40 V in 0.5M sulphuric acid.
Figure 3.50: AFM topography of the e-beam sample after anodisation and cleaning. Details of the 100 and 200 nm masks.
140
Figure 3.51: Height proles across the dierent masks. Anodisation at 40 V in 0.5 M sulphuric acid.
There are rims around all the masks of about 10 nm in height, except for the smallest 100 nm masks which did not leave any detectable topographical features. Concentric height minima and maxima are visible on the edges of the masks. The eect of mask diameter on the amplitude of the topographic structurations at the edges is shown in gure 3.52. The measurement displayed here is identical to Max on gure 3.39, namely the height dierence between the rst maximum (top of the rim) and the minimum point of the oxide layer (see gure 3.51). There is no signicant eect of mask diameter at 40 V anodisation voltage. At 55 V, the eect of mask diameter is more pronounced but does not seem to evolve linearly. 3.8.3.3 Eect of anodisation parameters
There are notable dierences in topography between the sample anodised at 55 V and the ones anodised at 40 V. As can be seen on gure 3.53, the oxide layer at 55 V could form on the whole sample surface, including underneath the masks. The titanium was completely anodised, even under the largest 100 m masks. The reason for this dierence probably lies in the fact that the electric eld
141
Figure 3.52: Eect of mask diameter on the edge structure.
Figure 3.53: Eect of the anodisation parameters. Topography left by the 400 nm (A) and 800 nm (B) masks for dierent anodisation conditions.
142
trough the masks was strong enough to cause sparking across it, damaging it and making it permeable to the electrolyte. The damage is visible on gure 3.55.
Figure 3.54: Proles across the dierent masks for dierent anodisation conditions.
The sparking results in a very rough surface, presenting needle-like structures, some of which are visible sticking out through the mask on gure 3.55. The topography at the rim is similar for all samples and all mask sizes, although the height dierence between the rst maximum and the rst minimum is larger for the 55 V samples than for the 40V samples: 20 nm instead of 10 on average. This can be explained by the higher thickness of the oxide layer formed at 55 V (approximately 140 nm). The electrolyte concentration does no seem to have a very notable eect on the topography, except that the transition between anodised and non-anodised titanium seems to be smoother. Another noteworthy dierence is that neither the 55V-0.5M sample nor the 40V-1M samples had visible topographic eects underneath the 200 nm masks, whereas the 40V-0.5M samples clearly did (gure 3.50). This could either be an eect of the anodisation conditions themselves,
143
Figure 3.55: Damage through a 100 m mask after anodisation at 55 V.
or to some batch eect, these two samples having been prepared and anodised at a later date. The production of such samples is very time consuming and requires trained sta in a clean room; statically signicant numbers could not be produced, and so it is dicult to assess the reproducibility of the process. The samples do however look identical in the SEM. The 800 nm 55V-0.5M sample (gure 3.53) has radial structures that could be an indication of the way the oxide layer grew underneath the mask. These structure are similar to the ones observed on the substrates structured with particles at 80 V and 100 V (see gure 3.40). 3.8.3.4 Cross-sections by focused ion beam
The focused ion beam technique was very helpful in investigating the structure and morphology of the oxide layer underneath the masks. The principle of the technique is to use a focused beam of gallium ions to mill away materials in a very controlled and precise way. It is coupled to a scanning electron microscope, which makes it possible to realise cross sections, TEM samples and other nanoand micrometer scale machining tasks. In our case, the technique was employed to image cross sections of the oxide layer, especially underneath the masks. A conducive carbon layer is rst deposited on the site to avoid charging of the sample, starting from a gaseous precursor injected into the microscope chamber and which decomposes into amorphous carbon under the action of the ion beam. A trench is then milled away so as to give access to the desired cross section (gure 3.56). The information sought in doing this experiment was chiey concerning the situation of the metal-oxide interface, of which nothing could be learned from
144
Figure 3.56: Dierent steps of the FIB technique. A: original surface; B: carbon layer deposition; C: milling; D: detail of the cross section.
145
atomic force microscopy or the other techniques used so far. The second point of interest was to image the oxide layer itself and try to see if any morphological dierences could be found between regular areas and under-mask zones. Figure 3.57 shows the dierent cross sections on the e-beam sample anodised at 40 V in 0.5 M sulphuric acid. A shows the 4 m masks imprint. The oxide layer is visible on either sides of the imprint and gradually becomes thinner in the center where it disappears. The original titanium surface is situated approximately in the middle of the oxide layer, indicating that it grows in both directions equally. The layer is about 100 nm thick, which agrees with the 2.5 nm/V rule applied to potentiostatic anodisation of titanium between 0 and 100 V [6]. The rim protrusions are visible on the cross section and are marked by arrow heads. The metal oxide interface presents uctuations much like the oxide electrolyte interface. When looking closely at the oxide layer underneath the masks, one can see that its colour is slighly darker than for the rest of the layer, and that small pores are present. These images were taken using the backscattered electron detector, and a darker colour in that case indicates a lower density of the material. The eroded titanium underneath the masks presents so-called waterfall or curtain eect, visible as a series of vertical lines. This eect is seen when the ion beam encounters a material with density variations, which cause it to be slightly deected, resulting in these lines. 3.8.3.5 Conclusion
The observations made on the e-beam samples support the ones made on the particle structurations in section 3.7: the growth mechanism underneath the masks imply the formation of pores in the layer. In the case of low anodisation voltages, i.e. slower lm growth rates, the pores are not easily visible on the layer in top views, but appear in cross sections. They are smaller and less oriented, and seem to be dispersed randomly in the layer. For higher anodisation voltages (> 50 V), the growth rate is higher, the pore are larger, further apart and more oriented. Not only do the pores orient radially, they also tend to align in concentric circles, as can be seen from the topography proles on gure 3.51. Although
146
the exact correlation between concentric rings and pores is not clear and would require a slice by slice FIB tomography of the entire imprint, it is reasonable to assume that they are indeed correlated. The e-beam experiment allowed a thorough characterisation of the eects of the masks diameter, and provided a complete picture of the typical edge defects caused by masks during anodisation.
147
C
Figure 3.57: FIB cross-section across the dierent e-beam imprint. A: 4 m imprint (the top images are AFM 3D reconstructions of the edge of the imprint.); B: 2 m and 800 nm imprints; C: 200 nm imprint. Arrow heads mark the edges of the masks, arrows mark the edges of the oxide layer.
148
3.9 Finite element modeling
3.9
3.9.1
Finite element modeling

Introduction
Finite element modeling was used to gain insight into the mechanisms behind the observed topographic structuring eect. A commercial program called COMSOL
Multiphysics was used. This program makes it possible to create 2D or
3D models and to apply several types of physical calculations at once. These different physics, as they are called, can be coupled together in order to take into account their interactions. A classical example of this is the electrical conduction through a resistance. The electric current density is inuenced by the conductivity of the material, which is a temperature dependent parameter. The electric current produces heat (Joule eect), increasing the temperature and modifying the conductivity. The two parameters are thus intimately coupled and can be calculated by two dierent sets of partial dierential equations using COMSOL multiphysics.
3.9.2
Single physic model
First, a simple model was created to study the way the electric current at the metal oxide interface behaves around an insulating mask. The DC-conductive media physic was chosen and a 2D model representing the e-beam lithography system was drawn. The system was schematized as shown on gure 3.58, and each domain of the system was given a conductivity value taken from literature, corresponding to titanium, PMMA and the electrolyte, 0.5 M sulphuric acid (table 3.6). The passivation layer was omitted for this rst model. The two vertical external boundaries were set on electrical insulation (normal component of the current density jn = 0), the top external boundary was set as grounded, and the bottom boundary was set to a constant electrical potential of 40 V. The solution can be seen on gure 3.59, with the arrows showing the magnitude and direction of the current, and the surface showing the total current density. The current density at the edge of the masks much higher than else-
149
Domain Material Conductivity [S/m] Substrate Titanium 7.4 x 105 Passivation layer Titanium dioxide 1 x 10 6 Mask PMMA 1 x 1014 Electrolyte 0.5 M H2 SO4 4.3 x 104
Table 3.6: Electrical conductivities.
Figure 3.58: Scheme of the model system. 1: titanium substrate, 2: PMMA mask, 3: Electrolyte.
150
Figure 3.59: Current density around a mask. Arrows show the direction of the current, colour scale shows the current density
where in the layer. The growth rate of the oxide layer, which is inuenced by the local current density, would therefore also be higher at the edge.
3.9.3
Two physics model
To simplify the model and shorten calculation times, only the oxide layer itself was included in this second model. The conductivity of the electrolyte and of the titanium substrate are indeed so much higher than that of the oxide layer, that these interfaces can be considered as conductive boundaries (tangential component of the current jt = 0). The PMMA mask was replaced by a completely insulating external boundary (jn = 0) instead of a continuity condition at an internal boundary with an extremely insulating material. The native layer has normally a thickness ranging between 1nm and 5 nm [94] but due to meshing diculties, such a small layer caused the calculations to stop. As a result, the native layer was drawn proportionally thicker than it actually is, but still less than a tenth of the size of the mask. Ultimately, it is like simulating
151
Boundary type DC-conductive media Moving Mesh Vertical (1, 6) Insulation Free displacement Top (3, 5) Ground Equation 3.14 Bottom (2) Potential (40 V) Equation 3.13 Mask (4) Insulation Free displacement
Table 3.7: Boundary conditions. Edge numbers correspond to gure 3.60
the anodisation at 40 V of sample that would have been pre-anodised at 5 V. According to Faradays law, the amount of product in an electrochemical reaction is proportional to the amount of charge that has passed through the system. This is actually a simplication of the situation in the case of the anodic oxidation of titanium, as a signicant part of the current lost in a series of other reactions. The dissolution reaction of titanium in the electrolyte accounts for example for approximately 20 % of the total current [16]. For simulation purposes however, the growth rate of the oxide layer can be considered proportional to the local current density. In order to simulate the growth of the oxide layer during anodisation, a second physic called moving mesh was introduced and coupled to the Direct current conductive media. A moving mesh system makes it possible modify the geometry of a system by moving single points, boundaries or entire domains as a function of local physical variables. Anodic oxidation was thus simulated by moving the boundaries of the oxide layer as a function of the local current density. The bottom boundary (see gure 3.60) is given the displacement condition:
Figure 3.60: Oxide layer with mask. Boundary conditions can be seen in table 3.7.
vn =
F MTi jn Ti n
(3.13)
152
Where vn is the normal velocity, MTi is the molar mass of titanium, F is Faradays constant, Ti is the density of titanium and n is the valency number of titanium ions. Accordingly, the top boundary is given the condition: vn = F MTiO2 jn F MTi jn TiO2 n Ti n (3.14)
The mask boundary is left to move freely, as are the two vertical boundaries. This means that for each Coulomb going through the oxide layer, the top boundary moves up by a certain distance, and the bottom boundary moves down by another distance . It is worth noting that titanium dioxide has a molar volume of 19.97 cm3 /mol and titanium one of 10.62 cm3 /mol. This means that the velocities of the top and bottom boundaries are in fact almost equal and opposite, as each nanometre of titanium oxidized gives roughly 2 nm of oxide.
3.9.4
Figure 3.61: Oxide layer growth around a mask. The edge of the mask is higher than the rest of the layer.
A second situation was simulated where two masks (of dierent sizes in this case) are separated by a small gap, as would be the case between adjacent particles. The idea is to see if the edge eect is additive, and if the topography at a narrow gap between two masks protrudes more than at the edge of a single mask.
153
Figure 3.62: Detail of the edges at dierent anodisation times.
As can be seen on gure 3.63, the eect is indeed at least partially additive, as the protrusion situated between the masks is clearly higher than the rest of the surface.
Figure 3.63: Oxide growth between two adjacent masks.
3.9.5
Conclusion
This model gives an explanation to the presence of rims around the masks: the increased current density at the rim causes a faster growth of the oxide at that location. It describes reasonably well the situation at the very early stages of anodisation and gives insight into the formation of the topographic features encountered in our study. An enhancement of the eect at narrow gaps is observed, as was the case between adjacent particles in SAM. The model does not however explain the growth of the oxide layer underneath the mask. It is does not take into account mask peel-o, titanium dissolution, sparking, heating or gas evolution. Furthermore, the DC current conductive media physics relies on an Ohmic conductivity behaviour which does not adequately
154
describe high eld ionic conduction. In the real case, the growth rate of the layer decreases exponentially according to [54, p. 251]: dL = A i = A exp dt B L (3.15)
Where A and B are material constants L is the layer thickness and is the potential dierence across the layer. With an Ohmic behaviour, the growth rate of the layer follows
dL dt
const. . L
155
156
4 Conclusion and outlook

The original objectives and concepts underlying this project were partially fullled, and partially found to be unrealistic. Surface structuring by anodisation in the presence of particles was shown to be a valid concept which can produce ordered topographic features in the nanometre range. Mesoporous silica multifunctional particles were found to be inadequate for this application. A gel-emulsion synthesis method was however scaled up and optimised, allowing the production of up to 60 mg of multifunctional particles per synthesis. This synthesis could be further improved by using a continuous emulsication process such as for example a high pressure homogeniser instead of a turbine. The multifunctional particles developed were thoroughly characterised, and although they were not applied to surface structuring, they were investigated for other potential applications such as drug delivery, bio-imaging and display applications. The interactions of the particles with the model drug paclitaxel was studied, leading to a better understanding of the drug loading, transport and release phenomena, and possibly opening the way to their application as magnetic drug delivery vehicles. The biological eect of the drug loaded particles should be investigated in future both in vitro and in vivo, along with the potential enhancement of magnetic resonance imaging due to their magnetic properties. The production of near-IR uorescent nanoparticles without heavy metals was attempted using the chromium doped alumina system. Although interesting results were obtained, and near IR uorescence was observed, this development
157
4. CONCLUSION AND OUTLOOK
was dropped after a point as the subject was though too far thematically from the main focus of this work. The interesting eects of thermal annealing of silica coated ZnS:Mn nanoparticles on their uorescence was exploited to successfully produce multicolour uorescent images by laser thermal annealing. The polishing process was mastered suciently to provide excellent starting surfaces for surface structuring. The eect of particles on the topography was thoroughly characterised, and the e-beam model experiment as well as the numerical models provided some insight on the system. The next step would be to optimise particles deposition and deformation, so as to allow the creation of structured surfaces of the order of mm2 , for example by dip-coating or inkjet printing. This perhaps opens the way for particle lithography in electrochemistry, not only for anodisation, but also for through mask titanium dissolution. A few attempts were conducted during this project, without success, but it could probably be achieved. The advantages of a well controlled bottom up process such as colloidal self assembly could be of interest for some applications compared to complex top-down lithography techniques. Finally, this system could be used to investigate the role of dierent structurations at dierent scales, on the adhesion and proliferation of cells on anodised titanium, for example in the case of titanium bone implants. The creation of structured topographies using particles, and the understanding of the phenomena involved, have been general thematic guidelines of this project. The exploratory nature of the subject however left me the freedom to be creative in the ideas and methods used to move towards this goal. I enjoyed this freedom very much, although it was necessarily accompanied by a relative thematic isolation in my work.
158
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A rthur G anz
Chem in de Fontenay 13 1007 Lausanne 078 737 47 19 arthur.ganz@ ep .ch French (m other tongue) English (C2),Germ an (C1) 29 years old,m arried,one child Swiss and French nationalities
PhD in material science

Independent and interdisciplinary, I aim to apply my expertise in material science and expand my proj management skills in a dynamic research and development team. ect
Education
2010 2005 1998 PhD thesis, Ecole Polytechnique Fdrale de Lausanne. Nanostructured functional particles and surfaces. Engineering diploma in material science, Eidgenssische Technische Hochschule Zrich (ETHZ). International Baccalaureate and Bilingual Diploma (En-Fr), International School of Geneva. Graduated with honours.
W ork experience
O ct. 2006 to present Professor assistant, Laboratoire de technologie des poudres,Ecole s Polytechnique Fdrale de Lausanne. -W riting of m y PhD thesis; -D evelopm ent of innovative technological solutions for the creation of titanium im plant surfaces; -Independent m anagem ent of m ultiple proj ects; -Supervision of the work of 3 students; -Teaching of laboratory courses; -O ral and poster com m unications at national and international conferences; I developed a complete technology platform allowing the nanoscale topographic structuring of surfaces. This was an entirely new eld of research for the laboratory. Research engineer, Centre des M atriaux,Ecole des M ines de Paris. -European proj Nanodiam onds for biom edical applications; ect, -Interactions with European and French research groups; -In charge of coordination and assessm ent of post-graduate training courses; Beyond my research activities, I acted as the students sole representative in the committee in charge of selecting external course providers. Diploma thesis, Institut national pour la sant et la recherche m dicale (INSERM ) unit 706,Paris. -Characterisation of intercellular adhesion forces using deform able substrates; -Interdisciplinary research proj between bio-physics and biology; ect -Training in biological techniques; I conceived a method for coating functional proteins on substrates in a space resolved way. The results obtained were published in Biology of the Cell (cited 28 times).
2005-2006
2004-2005
A pri- y 2003 lJul
I nternship ( m onths) RO LEX SA ,G eneva. 4 , -D evel opm ent proj at the w atch l ect aboratory; -Tri ogi study f the opti i on ofanodi al i um ; bol cal or m sati sed um ni I conducted a extensive statistical experiment plan which lead to a better control of wear phenomena on anodised aluminium. A gent,SO S EVA SA N SA ,G eneva. -Travelers i l nsurance; -O rgani on ofrepatri ons and sani sati ati tary evacuati ons; -A ssi stance to travelers; l -O cer i charge at the em ergency cal centre; n l -Responsi e f consti ng lti on l f the l bl or tuti i gati es or egaldepartm ent; I handled emergency situations ( illnesses,accidents) and provided guidance and , assistance to travellers in di culty abroad. I nternship ( w eeks) Franci ex SA ,Rennes,France. 6 , a -Producti ofhouse cl on osures; -W ork at the producti lne; on i -O pti i on ofi m sati nventory m anagem ent; -Contact w i peopl f th e rom di erent backgrounds; I implemented a more e cient inventory management system for accessory parts using the Kanban method.
M arch- y 1999 Jul and O ct. arch -M 2002-2003
M arch-A pri 2000 l
Com puter and technicalskil s l

M SO ce,O ri n,Latex,A dobe Il gi lustrator I ageJ, CO M SO L m ul physi ,m ti cs.
A tom i f c orce m i croscopy,scanni ng/transm i on el ssi ectron m i croscopy,opti m i cal croscopy,parti e si cl ze m easurem ent,cel cul l ture.
H obbies and interests

Si ng,saii badm i ngi lng, nton,sw i m i sking. A cti m em ber ofa chari organi on. m ng, i ve ty sati
A rthur G anz,m ay 2010.

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Rsum e e

Mots clefs : titane, nano-structuration, topographie, silice mesoporeuses, particules multifonctionnelles.

` A Gabrielle et a Joseph. ` Life, oh life, oh life. . . Desree

LMCH for their help with electrochemistry and their equipment.

experimental methodology and particle size measurements

three and a half years a very pleasant time.

Materials and methods . . . . . . . . . . . . . . . . . . . .

Mesoporous silica spheres as drug delivery vehicles . . . . . . . . . 2.4.1 2.4.2

Results and discussion . . . . . . . . . . . . . . . . . . . .

Chromium doped alumina . . . . . . . . . . . . . . . . . . . . . . 2.5.1 2.5.2 2.5.3

Application to multifunctional particles . . . . . . . . . . . 2.5.4.1 2.5.4.2

Conclusion and outlook . . . . . . . . . . . . . . . . . . . .

Conclusion and outlook . . . . . . . . . . . . . . . . . . . .

Experimental optimisation of polishing . . . . . . . . . . .

Other factors aecting polishing. . . . . . . . . . . . . . .

Assessment of the dierent polishing setups. . . . . . . . .

Air plasma treatments . . . . . . . . . . . . . . . . . . . . . . . . 116 3.6.1 3.6.2 3.6.3

Surface structuring with polystyrene particles . . . . . . . . . . . 121 3.7.1 3.7.2 3.7.3

4 Conclusion and outlook Bibliography

Context of the work

1.2 Objectives of the project

Objectives of the project

These two directions were developed in parallel, on one side attempting to

1.2 Objectives of the project

Structure of the thesis

2 Multifunctional mesoporous silica particles

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

Functional nanoparticles used

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

2.2 Gel emulsion synthesis

Gel emulsion synthesis

Figure 2.1: Scheme of the emulsication process.

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

2.2 Gel emulsion synthesis

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

The AOT-octane-water system

Figure 2.2: Phase diagram for the AOT-octane-water system.

2.2 Gel emulsion synthesis

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

Materials and methods

laser on emulsions without addition of base.

2.2 Gel emulsion synthesis

Results and discussion

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

2.2 Gel emulsion synthesis

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

2.2 Gel emulsion synthesis

Optimisation of emulsion parameters

Table 2.1: Structure of the emulsion experiment plan.

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

2.2 Gel emulsion synthesis

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

2.3 Materials characterisation

Results and discussion

Figure 2.8: SEM micrographs of composite silica-SPION particles.

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

2.3 Materials characterisation

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

2.3 Materials characterisation

2. MULTIFUNCTIONAL MESOPOROUS SILICA PARTICLES

Mesoporous silica spheres as drug delivery vehicles

Figure 2.12: Paclitaxel molecule.

2.4 Mesoporous silica spheres as drug delivery vehicles

Materials and methods