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Профессиональный Документы
Культура Документы
ISyPeM II
enrico.accastelli@epfl.
ch
enrico.accastelli@epfl.
ch
enrico.accastelli@epfl.
ch
Imatinib exposure
(ng/ml)
IMMUNOSUPPRESSIVE
DRUGS
CANCER TARGETED
THERAPIES
IV ANTIBIOTICS
enrico.accastelli@epfl.
ch
Patient
Only
Qualitative!
Drug
concentration
needs to be
quantified with
Syva RapidTest
15% accuracy
for TDM
Hand-held
CANCER TARGETED
THERAPIES
Accu-Chek product
iSTAT, Abbott lines.
Roche Diagnostics
Top bench
IV ANTIBIOTICS
enrico.accastelli@epfl.
ch
cobas Lab-in-a
tube
Roche
Diagnostics
Clonit
StMicroelectronics
5
Monitoring of treatment
is often needed in
newborn and child care
BIOCHEMICAL/ANALYTICAL CHALLENGES
Compact, affordable
analytical systems
Measurement performed at
the MD
integrated with decision
support software
enrico.accastelli@epfl.
ch
Renaud Lab
J-M Segura
M Geiser
Immunoassays
(FPIA,
CMIA, MIA)
25 cm
20 cm
enrico.accastelli@epfl.
ch
Renaud Lab
J-M Segura
M Geiser
Immunoassays
(FPIA,
CMIA, MIA)
Abbott "Architect ci8200"
ISyPeM II demonstrator
Low-cost
Fully integrated
Based on High sensitive FPIA
Works on capillaries
enrico.accastelli@epfl.
ch
Renaud Lab
http://dbs-system.ch
enrico.accastelli@epfl.
ch
reference system
0.220
Anisotropy
300 m
capillary
0.200
Renaud Lab
0.180
0.160
0.140
0
10
12
Concentration [g/ml]
http://dbs-system.ch
J-M Segura
enrico.accastelli@epfl.
ch
10
TACROLIMUS
IMATINIB
TOBRAMYCIN
enrico.accastelli@epfl.
ch
11
IMATINIB
TOBRAMYCIN
Streptavidin-coated
magnetic beads
Guiducci Lab
- CCTTACCTAGGTGTAG- 5'
5' - GGAATGGATCCACATC-
(A) Loading
Conversion to ssDNA
conjugation beads-aptamers
(B) Selection
exposition of the small
molecule to the aptamers' pool
Binding aptamers - drug
(C) Partitioning
Separation of binding
aptamers from the pool
R2=0.993
LOD=0.15 M
Clin. Pharmac.
DNA aptamers can
be obtained in a
few steps that are
better or equal to
existing RNA
aptamers
Functional in serum
and proved on
patient samples,
meeting the clinical
range
Specificity
demonstrated
Method can be
applied to different
drugs
12
TOBRAMYCIN
Guiducci Lab
Clin. Pharmac.
G. et al. Analytical Chemistry, April 2015 . Contributed by EPFL, CHUV and STMicroelectronics
enrico.accastelli@epfl.
ch
13
TACROLIMUS
Heinis Lab
J-M Segura
First in vitro
selection of
antibodies
against
Tacrolimus ever
performed
Two approached
deployed to
competition
assay
Peptide
macrocyclesbased approach
C. Heinis, Bicyclic peptide phage display, 10th Peptide Therapeutics Symposium,
enrico.accastelli@epfl.
for assays
ch23.10.2015, The Salk Institute, La Jolla, USA
14
DATA INTERPRETATION
AND MANAGEMENT
enrico.accastelli@epfl.
ch
15
Now in use at
CHUV and
connected with
MOLIS database
Largely
outperforming
any existing
support systems
Validation and
Clinical trials in
progress for
certification and
commercializatio
n
16
AMINOGLYCOSIDES EFAVIRENZ
IMATINIB
Consolidation of
population studies for
TDM
Statistical combination
of independent
population studies
enrico.accastelli@epfl.
ch
17
LDB
metadata
Anonymization
Module
RSDB
Query/Ex
change
Data
ch
RSDB
LDB
Initiator
A1
Negotiat
e
Tuple-center
No centralized
system for
data storage
Contributors
can share
their data and
get
anonymized
data from the
enrico.accastelli@epfl.
others
Contributor
P2P Network
Publish/Subscribe
Contributor
RSDB
enrico.accastelli@epfl.
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19
enrico.accastelli@epfl.
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20
enrico.accastelli@epfl.
ch
21
Measurement of drug
concentration
Immunoassays
(FPIA,
CMIA, MIA)
Abbott "Architect ci8200"
Imatinib exposure
(ng/ml)
Blood sampling
Patient
LC-MS/MS
time after dose (hrs)
Courtesy of N. Widmer
Agilent
http://e-sante.futura-sciences.com,
22
Hand-held
Accu-Chek product
iSTAT, Abbott lines.
Roche Diagnostics
Top bench
cobas Lab-in-a
tube
Roche
enrico.accastelli@epfl.
Diagnostics
ch
Clonit
StMicroelectronics
Syva RapidTest
EMIT (Enzyme multiplied
immunoassay technique)
Only Qualitative!
Drug concentration
needs to be quantified
with 15% accuracy for
TDM
23
enrico.accastelli@epfl.
ch
24
enrico.accastelli@epfl.
ch
25
ISyPeM integrated
approach to TDM
Hand-held
Accu-Chek product
iSTAT, Abbott lines.
Roche Diagnostics
Top bench
cobas Lab-in-a
tube
Roche
enrico.accastelli@epfl.
Diagnostics
ch
Clonit
StMicroelectronics
eHealth
standar
ds
Data
security
Cartridge
with stable
reagents
Low sample
volume
Supported
Interpretation
for non
specialists
At the clinic
and outside
26
Our methodology
Develop and demonstrate the feasibility of in vitro selection techniques to identify suitable
probes for drug molecules
Achieve microvolume processing and analysis
Develop novel compact and fully-integrated assays proving their
Stability of molecules in complex matrix and in presence of sample treatment
reagents
Specificity
Accuracy
Equip local clinical institutions and selected cabinets with certified decision support
systems for drug dosage
Largely outperforming existing tools for usability and value of elaboration
approaches employed.
Connected with local databases, secure and connected in a P2P network to enrich
enrico.accastelli@epfl.
pharmacokinetic databases
ch
27
TOBRAMYCIN
Competitive assay
(high sensitivity)
20 cm
25 cm
enrico.accastelli@epfl.
ch
Renaud Lab
Functional on wells,
tested on capillaries
and paper
28
Progress of demonstrator
enrico.accastelli@epfl.
Not integrated
ch
Partially integrated
Integrated
29
BACK UP slides
enrico.accastelli@epfl.
ch
30
enrico.accastelli@epfl.
ch
[Imatinib]
enrico.accastelli@epfl.
ch
Simulatio
ns
and remodeling
P50
P25
P5