Arhitectura Nanorobot pentru asigurarile n domeniul

medicinii
Platforma integrat i arhitectura hardware-ului pentru aplicaiile cu
nanoroboi ar facilita n timp real pronosticul n ceea ce privete
infeciile cu agenii biologici.
1. Introducere

Dezvoltarea nanoroboilor este o descoperire tehnologic care poate

facilita prognozarea n timp real a diferitor probleme biomedicinale.
Deosebit de interesant este faptul c nanoroboii medicali ofer un
instrument efectiv de aprare contra conataminrii cu ageni biologici.
n mod normal, pentru zonele cu risc de calamiti sau cele de conflict,
lipsa apei potabile, substanelor lichide, electricitii i lipsa turnurilor
pentru reelele de comunicare, inclusiv a telefoniei prin cablu sau
wireless, sunt predominante. n asemenea situaii, infrastructura nu
permite funcioanrea laboratoarelor de analize exate i rapide. Pentru
astfel de aspecte, nanoroboii echipai cu nanobiosensori pot facilita
transmiterea n timp real a informiei, folosind telefoanele mobile
pentru transmisiuni wireless prin intermediul sateliilor artificiali. De
fapt, nanoroboii nsemana dispozitive medicale puternice care ofer
monitorizare biomedical exact, att pentru militari ct i pentru civili.
Arhitectura hardware are scopul de a folosi nanoroboii medicali ca o
platform integrat pentru a ine sub control bolile epidemice
contagioase.
Astfel, prezentul model servete pentru a facilita monitorizarea bolilor
contagioase, care ar avea scopul de a proteja personalul unei grzi
aflate n conflict sau n cadrul unei misiuni umanitare.
Mai mult dect att, un aspect important i interesant al arhitecturii
respective este faptul c aceeai tehnic poate fi folosit i n alte

situaii, cum ar fi catastrofele natuarale sau posibilele contaminri cu

ageni biologici. Acesta ajut mpotriva izbucnirii bolilor pandemice,
atunci cand timpul reprezint soluia primordiala pentru a monitoriza
sntatea oamenilor.
n scopul crerii unei imperesii asupra tehnologiei respective,
nanoroboii sunt programai pentru a depista gripa n interiorul corpului
pe baza unei mostre de snge i a semnalelor proteice.
Pentru activarea sensorilor digitalo-analogici, nanobiosenzorii au la baz
proprieti electrochimice.
2. Dezvoltarea nanoroboilor n scopul auto-aparrarii

Industria auto-aprrii are avea un beneficiu n mod remarcabil

datorit orientrii i realizrii sistemelor integrate a
nanobiotehnologiilor.
2.1. Nanoroboii Medicali

Cercetarea i dezvoltarea nanoroboilor cu nanobiosenzori ncastrai i

mecanisme care genereaz aciuni automate, sunt considerai ca fiind o
posibilitate real pentru aprovizionarea doctorilor cu noi mijloace i
procedee n vederea tratamentului.
Utilizarea microdispozitivelor n chirurgie i tratamente medicale a
condus la mbuntirea procedurilor clinice n ultimii ani. Un exemplu
destul de relevant ar fi ca pe lng instrumentele biomedicinale folosite,
caterizarea se bucur de un real succes ca metodologie pentru
interveniile chirurgicale intercraniene i cardiace.
Apariia tiinei biomoleculare i a noilor tehnici de producie permite
progresul de la miniaturizare la nanolectronice.
Senzorii pentru aplicaiile biomedicale avanseaz din punct de vedere
tehnologic n domeniul chirurgiei i a medicinii n general. Aceeai
tehnic formeaza practic baza industriei biomoleculare.
Aparatele moleculare complexe, sau nanoroboii, care au ataate
dispozitive nanoscopice, reprezint noi instrumente pentru procedurile

medicale.
Motivare

Infectiile si bolile microbice raspanadite in intreaga lume

constituie aproximativ 40% din totalul de 50 mln de decese care
se produc anual. Avand in vedere proprietatile contagioase ale
agentilor biologici periculosi, acestea constituie o amenintare ce
paote afecta intreaga populatie, in special cea din zonele
metropolitae, unde contaminarea se poate raspandi extrem de
rapid.
Din momentul infectarii, uinnele boili contagioase pot arata
primele simptome dupa cateva ore , o saptamana sau o
perioada indelungata, precum ani sau zeci de ani. Aceasata
inseamnaca ca de exemplu atunci cand autoritatile publice au
observat infectia la o persoana contaminata care a manifestat
simptome evidente, virsul a avut destul timp sa se raspandeasca
intr-un cerc de prieteni si colegi de srviciu ai victimei infectate.
INtre timp acei colegi transmiteau virusl mai departe, astfel
incepand-use un lat vicios catastrofal. utilizarea nanorobotilor cu
echipament atasat pentru controlul epidemic in timp real poate
fi util in vederea evitarii unei contaminari serioase care ar putea
lua proportii. De fapt acesta poate salva o mare parte din
populatie in termeni de evacuare rapida si luarea in carantina a
pacientilor. Astfel, aceasta ar trebui sa permita actiunimi mai
eficinete impotriva agentilor biologici daunatori.
Itmeans,forexample,thatwhenthe
publicauthoritiesnoticedtheinfectionfromacontaminatedperson,showingexternalsymptoms,a
virushadenoughtimetospreaditselfthroughacircleoffriendsandworkmatesoftheinfectedvictim.
Meantime,thosemateswereadverselydrivingthevirusforward,andhadstartedacatastrophicchain
circle[13].Theuseofnanorobotswithembeddednanodevicesforrealtimeepidemiccontrol,aslabon
achip,canbeusefultoavoidseriouscontaminationwithlargeproportions.nfact,itcanhelpsavea
largepartofapopulationntermsoffastevacuationandeffectivepatientsquarantine.Thus,itshould
enableamoreeffectiveactionagainstbiohazardmaterials.

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ns
ors
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Weimplementedasystemsimulationandarchitectureofnanorobotsforsensingthebloodstream,
targetingbiochemicalchangesagainstpathologicalsignals.Actualadvancesnwirelesstechnologies,
nanoelectronicsdevices,andtheirusentheimplementationofnanorobotsappliedtoepidemiccontrol,
illustratewhatupcomingtechnologiescanenablentermsofrealtimehealthmonitoring.
Theapproachfor n vivomonitoringchemicalconcentrationsshouldalsoapplytootherbiomedical
problems,andlikewisebeusefulforprognosisofcomplexdiseasesandphamacokineticscontrol.
Furthermore,ntheproposedplatformarchitecture,differentprogramsandcommandscanbesentand
informationretrievedfrominsidebodythroughwirelesscommunication,providingimportantaspects
oninterfaceandmedicalinstrumentationofnanorobots.
2.3. Prevention and Control
TheWorldHealthOrganization(WHO)hasstartedn1948theinitiativetoimplementaworldwide
identificationofnewinfluenzaviruses[14].Currentlydemandforvaccinesandeffectivewaysto
quicklymanageandfightapandemicoutbreakareenormous,whichalsomotivatedWHOtodevelop
theGlobalOutbreakAlertandResponseNetwork,enhancingtheworldscollaborationncontainment
ofinfectiousdiseases[47].
Somehighlycontagiousgerms,suchasSARS(severeacuterespiratorysyndrome)[15],smallpox
[11]andinfluenza[17],canbringdeadlyconsequences,andspreadeasilyacrossbordersandamong
populationsfromdifferentcountries.nfaceofinternationalsecuritydemandfordefenseagainstnew
threatsdrivenbypossiblybiohazardoutbreaks,thecurrent$13billionglobalvaccinebusinessshould
grow18%ayearto$30billionby2011[48].Theconcerntoavoidpersonnellosseshasalsomotivated
theimplementationofperiodicalcrewimmunizationofUSNavyagainstinfluenzaandotherplagues
assurveillancesafetyaction[2,3].Theconcernnthismatter,nordertosaveandprotectlives,helpus
tounderstandhowimportantistoimprovepopulationwidediseaseoutbreakdetection[49],preventing
anypandemiconset.nfact,apandemicinfluenzaoutbreakwouldlikelycausethemostseverevaccine
shortagestodatewithglobalconsequences[50].
Notwithstandingthatimproveddrugsandvaccineshaveevolvedalot,antimicrobialsareoflimited
usefulnessduetothefollowingaspects:antimicrobialresistancetodrugsandantibiotics,thelarge
numberofpossiblemicrobesthatcanbeusedforweapons,andlimitationsntechnicalfeasibilityfor
developingvaccinesandeffectiveantibacterialsagainstcertaingerms[3,4].Therefore,nrecentyears
acrescentconcernandinteresthasemergedformethodstoefficientlyprotectpeoplelivesnotonly
throughimmunization,butalsoandevenmoreaccuratelythroughadvancedrealtimebiomolecular in
vivovirusdetection[51].
Anefficientbioharzarddefensesystemshouldaddressfrequentcollectionofdata,fastinformation
transfer,earlysignatureoftheoutbreak,immediateanalysisofincomingdata,andimmediateoutput
[10].Onsuchaspects,thecurrenttrendsonnewnanobiosensors,andminiaturizationofmicroto
nanoelectronics,opennewpossibilitieswiththedevelopmentofmedicalnanoroboticsforthe
implementationofefficientbiohazarddefensesystems.

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Figure 1.Thebloodstreamflowsthroughthevesselnthe3Dmodel.Thevessel
endothelialcellsdenotenbrowncolortheinfluenzavirusbeginningtospreadfromone
celltoanother.

3. Influenza Characteristics
Timeforincubationofpandemicsyndromesmayvaryfromonecontagiousplaguetoanother,and
firstsymptomscanbepredictedgivenclinicalinformationandprevioushistoricoccurrences,using
statisticalmodels.Thesizeofanoutbreakisdirectlycorrelatedandinfluencedbythedelayfor
recognitionaboutthecontaminatedarea.Theincubationperiodofdiseaseisthetimefromexposureto
theinfectiousagenttotheonsetofdisease,anddependingontheinfectiondoseofinfluenza,itcan
varyabout2to5days[13].Forinfluenza,thecontaminationcanhappensthroughinhalation,
ingestion,ordirectcontactthroughhandshakingandconversation.Influenzacanlivenducks,
chickens,wildbirds,horses,pigsandhumans.
Theinfluenzavirusinvadescell(Fig.1),andafterthecellinvasion,itmakesuseofenzymesto
decreaseintracellularpH,slightlyincreasing~1 oCintracellulartemperature,whichisusedtoaccelerate
viruscellfusionactivity[5254].Beforeapersonshowssymptomaticreactions,shortafterbeing
infectedbyinfluenza,thebloodstreambeginstoreceiveahigherconcentrationofalphaN
acetylgalactosaminidase(alphaNAGA),whichissecretedfromtheinvadedcells[16].Theprotein
hemagglutininservesasvirusenvelopeforinfluenza,promotingalphaNAGAsignals.AlphaNAGA
isaproteinidentifiedthroughthegenomemapping,whichbelongstochromosome22[55].Thelack
ofmacrophage,incurredfromthealphaNAGAenzymesecretedthroughtheinfectedcells,leadsto
immunosuppressionandhelpsthevirustospreadeasilythroughthebody.

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Thus,thischangeofchemicalconcentration,withoverexpressionofalphaNAGAnthe
bloodstream,isusedtotriggerthenanorobotprognosticbehavior,whichsendselectromagnetic
backpropagatedsignalstothemobilephonecarriedwiththeperson.Asanintegratedbiohazard

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defensesystem,oncethenanorobotactivatedthecellphone,thisinformationisretransmittedforthe
satellitesutilizedasfeasibletelecommunicationsystem.Wheneverthecentralisalarmedaboutthe
case zero,theadministrationtakesthenecessaryaction,automaticallysendingSMS(shortmessage
service)fortheneartroopmembers,insideanareawitharadiusofapproximately20KMs,informing
identificationandthecurrentpositionofthepersonwhoiscontaminated.Technically,the case zerois
thefirstoccurrenceofsomeonecontaminatedbytheinfluenzancertainarea,whichmeansthata
pandemicisrunninganywhereelseclosetothatlocation.
4. Nanobioelectronics
Currentdevelopmentsnnanoelectronics[56]andnanobiotechnology[57]areprovidingfeasible
developmentpathwaystoenablemolecularmachinemanufacturing,includingembeddedand
integrateddevices,whichcancomprisethemainsensing,actuation,datatransmission,remotecontrol
uploading,andcouplingpowersupplysubsystems,addressingthebasicsforoperationofmedical
nanorobots.
Arecentactuatorwithbiologicallybasedcomponentshasbeenproposed[58].Thisactuatorhasa
mobilememberthatmovessubstantiallylinearlyasaresultofabiomolecularinteractionbetween
biologicallybasedcomponentswithintheactuator.Suchactuatorscanbeutilizednnanoscale
mechanicaldevicestopumpfluids,openandclosevalves,ortoprovidetranslationalmovement.
Tohelpcontrolnanorobotposition,asystemfortrackinganobjectnspacecancomprisea
transponderdeviceconnectabletotheobject.Thetransponderdevicehasoneorseveraltransponder
antennasthroughwhichatranspondercircuitreceivesanRF(radiofrequency)signal.Thetransponder
deviceaddsaknowndelaytotheRFsignal,therebyproducingRFresponsefortransmittingthrough
thetransponderantenna[59].Aseriesofseveraltransmittersandantennasallowapositioncalculator,
associatedwiththetransmittersandreceivers,tocalculatethepositionoftheobjectasafunctionofthe
knowndelay,andthetimeperiodbetweentheemissionoftheRFsignalandthereceptionoftheRF
responsefromthefirst,secondandthirdantennas.
Nanotechnologyismovingfasttowardsnanoelectronicsfabrication.Chemicallyassembled
electronicnanotechnologyprovidesanalternativetousingcomplementarymetaloxidesemiconductor
(CMOS)forconstructingcircuitswithfeaturesizesnthetensofnanometers[60].ACMOS
componentcanbeconfigurednasemiconductorsubstrateaspartofthecircuitassembly[24].An
insulatinglayerisconfiguredonthesemiconductorsubstrate,whichcoverstheCMOScomponent.A
nanoelectroniccomponentcanbeconfiguredaboveaninsulatinglayer.Ifseveralnanoelectronic
componentsareprovided,theyarepreferablygroupednnanocircuitblocks[24].
Biosensorsarecurrentlyusedtoincorporatelivingcomponents,includingtissuesorcellswhichare
electricallyexcitableorarecapableofdifferentiatingintoelectricallyexcitablecells,andwhichcanbe
usedtomonitorthepresenceorlevelofamoleculenaphysiologicalfluid[61].CNTs(carbon
nanotubes)andDNA(deoxyribonucleicacid)arerecentcandidatesfornewformsofnanoelectronics
[62].Thesearecombinedtocreatenewgeneticallyprogrammedselfassemblingmaterialsfor

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facilitatingtheselectiveplacementofCNTsonasubstratebyfunctionalizingCNTswithDNA.
ThroughrecombinantDNAtechnology,targetslabeledwithdistinctdetectablebiomarkerscanbe
defined,suchasfluorescentlabels,enzymelabels,orradioactivepatterns,andemployedassuitable
proteintransducers[63].

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5. Integrated System Platform

Theproposedmodeluseselectromagneticradiowavestocommandanddetectthecurrentstatusof
nanorobotsinsidethebody.Therefore,thecellphoneisappliedformedicalnanoroboticsplatform
[7,64,65].ThisoccursasthecellphoneemitsamagneticsignaturetothepassiveCMOSsensors
embeddednthenanorobot,whichenablessendingandreceivingdatathroughelectromagneticfields
[66].Fromthelastsetofeventsrecordednpatternarrays,informationcanbereflectedbackbywave
resonance[64].
ThenanorobotmodelincludesembeddedIC(integratedcircuit)nanoelectronics[67],andthe
architectureinvolvestheuseofsatellitesandmobilephonesfordatatransmissionandcouplingenergy
[68,69].ThenanorobotisprogrammedforsensingandtodetectconcentrationofalphaNAGAnthe
bloodstream[7,16,70].ThenanorobotarchitectureusesanRFID(radiofrequencyidentification
device)CMOStranspondersystemfor n vivopositioning[70],adoptingwellestablished
communicationprotocols,whichallowtrackinformationaboutthenanorobotposition[5,7].
Theabilitytomanufacturenanorobotsshouldresultfromcurrenttrendsandnewmethodologiesin
fabrication,computation,transducersandnanomanipulation.Dependingonthecase,different
gradientsontemperature,concentrationofchemicalsnthebloodstream,andelectromagneticsignature
aresomeofrelevantaspectswhenmonitoring n vivobiochemicalparameters.CMOSVLSI(very
largescaleintegration)designusingdeepultravioletlithographyprovideshighprecisionanda
commercialwayformanufacturingearlynanodevicesandnanoelectronicssystems.Innovative
CMOSFET(complementarymetaloxidesemiconductorfieldeffecttransistor)andsomehybrid
techniquesshouldsuccessfullydrivethepathwayfortheassemblyprocessesneededtomanufacture
nanorobots,wherethejointuseofnanophotonicsandCNTscanevenacceleratefurthertheactual
levelsofresolutionrangingfrom248nmto157nmdevices[71].Tovalidatedesignsandtoachievea
successfulimplementation,theuseofVHDL(veryhighspeedintegratedcircuithardwaredescription
language)hasbecomethemostcommonmethodologyutilizedntheintegratedcircuitmanufacturing
industry[72].
6. Nanorobot Architecture
Themedicalnanorobotforbiohazarddefenseshouldcompriseasetofintegratedcircuitblockasan
ASIC(applicationspecificintegratedcircuit).Thearchitecturehastoaddressfunctionalityfor
commonmedicalapplications[18],providingasynchronousinterfaceforantenna,sensor,andalogic
nanoprocessor,whichisabletodeliberateactuatorandultrasoundcommunicationactivationwhen
appropriate(Fig.2).Themainparametersusedforthenanorobotarchitectureanditscontrolactivation,
aswellastherequiredtechnologybackgroundthatcanadvancemanufacturinghardwareformolecular

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Figure 2.Integratedcircuitblockdiagram.

machines,aredescribednext.Asapracticalrule,thenumberofnanodevicestointegrateananorobot
shouldkeepthehardwaresizesnregardtoinsidebodyoperationapplicability.

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6.1. Chemical Sensor

Manufacturingsiliconbasedchemicalandmotionsensorarraysusingatwolevelsystem
architecturehierarchyhasbeensuccessfullyconductednthelast15years.Applicationsrangefrom
automotiveandchemicalindustry,withdetectionofairtowaterelementpatternrecognition,through
embeddedsoftwareprogramming,andbiomedicalanalysis.Throughtheuseofnanowires,existing
significantcostsofenergydemandfordatatransferandcircuitoperationcanbedecreasedbyupto
60%[67].CMOSbasedsensorsusingnanowiresasmaterialforcircuitassemblycanachievemaximal
efficiencyforapplicationsregardingchemicalchanges,enablingnewmedicalapplications[21,73,74].
Sensorswithsuspendedarraysofnanowiresassembledintosiliconcircuits,decreasedrastically

selfheatingandthermalcouplingforCMOSfunctionality[75].Factorslikelowenergyconsumption
andhighsensitivityareamongsomeoftheadvantagesofnanosensors[76].Nanosensormanufacturing
arrayprocessescanuseelectrofluidicalignmenttoachieveintegratedCMOScircuitassemblyasmulti
elementsystems[67].Passiveandburiedelectrodescanbeusedtoenablecrosssectiondrive
transistorsforsignalprocessingcircuitryreadout.Thepassiveandburiedalignedelectrodesmustbe
electricallyisolatedtoavoidlossofprocessedsignals.Forthenanorobotarchitecture,theantibody
antidigoxigeninisincludedformodellingtheICbiosensor;theantibodyservestoidentifyhigher
concentrationsofproteinsthatcouplealphaNAGAisoformstointracellularbloodstreamsignaling
[45].Thenanobiosensorprovidesanefficientintegratedwayfornanorobotsidentifyingthelocations
withoccurrencesofalphaNAGA.EnzymesecretionfromcellhostageproducesalphaNAGA
overexpression,whichisdenotedbychangesofgradientsnthebloodstream.Therefore,anefficient
prognosticcanbeachieved,evenbeforesymptomaticreactions,helpingtofightavirusoutbreak.
CarbonnanotubesserveasidealmaterialsforthebasisofaCMOSICnanobiosensor[67,77,78].
SomelimitationstoimprovingBiCMOS(bipolarCMOS),CMOSandMOSFETmethodologies
includequantummechanicaltunnelingforoperationofthinoxidegates,andsubthresholdslope.
However,thesemiconductorbranchhasmovedforwardtokeepcircuitcapabilitiesadvancing.Smaller
channellengthandlowervoltagecircuitryforhigherperformancearebeingachievedwithbiomaterials
aimedtoattendthegrowingdemandforhighcomplexVLSIs.Newmaterialssuchasstrainedchannel
withrelaxedSiGe(silicongermanium)layercanreduceselfheatingandimproveperformance[79].
Recentdevelopmentsnthreedimensional(3D)circuitsandFinFETsdoublegateshaveachieved
astonishingresultsandaccordingtothesemiconductorroadmapshouldimproveevenmore.Tofurther
advancemanufacturingtechniques,silicononinsulator(SOI)technologyhasbeenusedtoassemble
highperformancelogicsub90nmcircuits[80].Circuitdesignapproachestosolveproblemswith
bipolareffectandhystereticvariations,basedonSOIstructures,havebeendemonstratedsuccessfully
[79].Thus,while10nmcircuitsarecurrentlyunderdevelopment,alreadyfeasible45nmNanoCMOS
ICsrepresentbreakthroughtechnologydevicesthatarecurrentlybeingutilizednproducts.
6.2. Actuator
Therearedifferentkindsofactuators,suchaselectromagnetic,piezoelectric,electrostatic,and
electrothermal.Whichcanbeutilized,dependingtheaimandtheworkspaceswhereitwillbeapplied
[81].Flagellamotorhasbeenquotedquitefrequentlyasanexampleforakindofbiologicallyinspired

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actuatorformolecularmachinepropulsion[82].Adenosinetriphosphate,alsoknowforshortasATP,
isequallyusedasanalternativefornanomotors[83].DNAandRNA(ribonucleicacid)prototypes
werealsoproposedfordesigningdifferenttypesofdevices.
Asetoffullerenestructureswerepresentedfornanoactuators[84].TheuseofCNTsasconductive
structurespermitselectrostaticallydrivenmotionsprovidingforcesnecessaryfornanomanipulation.
CNTscanbeusedasmaterialsforcommercialapplicationsonbuildingdevicesandnanoelectronics
suchasnanotweezersandmemorysystems.SOItechnologyhasbeenusedfortransistorswithhigh
performance,lowheatingandlowenergyconsumptionforVLSIdevices.CNTselfassemblyandSOI
propertiescanbecombinedtoaddressingCMOShighperformanceondesignandmanufacturing
nanoelectronicsandnanoactuators[85].OwingtothematurityofsiliconCMOStechnology,aswellas
theuniquepropertiesofCNTs,theintegrationofCNTandtheCMOStechnologycanmakeuseofthe

advantagesofboth[86].
Foramedicalnanorobot,applyingCMOSasanactuatorbasedonbiologicalpatternsandCNTsis
proposedforthenanorobotarchitectureasanaturalchoice.nthesamewayDNAcanbeusedfor
couplingenergytransfer,andproteinsserveasbasisforionicfluxwithelectricaldischargerangesfrom
5070mVdcvoltagegradientsncellmembrane[87],anarrayformatbasedonCNTsandCMOS
techniquescouldbeusedtoachievenanomanipulatorsasanembeddedsystemforintegrating
nanodevicesofmolecularmachines[56].Ionchannelscaninterfaceelectrochemicalsignalsusing
sodiumfortheenergygenerationwhichisnecessaryformechanicalactuatorsoperation[87].
Embeddedactuatorsareprogrammedtoperformdifferentmanipulations,enablingthenanorobota
directactiveinteractionwiththebloodstreampatternsandmolecularparametersinsidethebody.
6.3. Power Supply
TheuseofCMOSforactivetelemetryandpowersupplyisthemosteffectiveandsecurewayto
ensureenergyaslongasnecessarytokeepthenanorobotnoperation.Thesametechniqueisalso
appropriateforotherpurposeslikedigitalbitencodeddatatransferfrominsideahumanbody[88].
Thus,nanocircuitswithresonantelectricpropertiescanoperateasachip,providingelectromagnetic
energysupplying1.7mAat3.3Vforpower,whichallowstheoperationofmanytaskswithfeworno
significantlossesduringtransmission[65].RFbasedtelemetryprocedureshavedemonstratedgood
resultsnpatientmonitoringandpowertransmissionthroughinductivecoupling[66],usingwell
establishedtechniquesalreadywidelyusedncommercialapplicationsofRFID.Theenergyreceived
canalsobesavednrangesof~1Wwhilethenanorobotstaysninactivemodes,justbecomingactive
whensignalpatternsrequireittodoso.Sometypicalnanorobotictasksmayrequirethedeviceonlyto
spendlowpoweramounts,onceithasbeenstrategicallyactivated.Forcommunication,sendingRF
signals~1mWisrequired.Alliedwiththepowersourcedevices,thenanorobotsneedtoperform
preciselydefinedactionsntheworkspace,usingavailableenergyresourcesasefficientlyaspossible.
Apracticalwaytoachieveeasyimplementationofthisarchitectureshouldobtainbothenergyand
datatransfercapabilitiesfornanorobotsbyemployingcellphonesnsuchprocess[7].Themobile
phonecanbeuploadedwiththecontrolsoftwarethatincludesthecommunicationandenergytransfer
protocols.

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6.4. Data Transmission

Theapplicationofdevicesandsensorsimplantedinsidethehumanbodytotransmitdatafora
personhealthcarecanenablegreatadvantagesncontinuousmedicalmonitoring[89].Itcanalso
providesaninnovativetoolforaccurateandntimeprognosisofcontagiousdiseases.Mostrecently,
theuseofRFIDfor n vivodatacollectingandtransmissionwassuccessfullytestedfor
electroencephalograms[65].Forcommunicationnliquidworkspaces,dependingontheapplication,
acoustic,light,RF,andchemicalsignalsmaybeconsideredaspossiblechoicesforcommunicationand
datatransmission.Chemicalsensingandsignalingcanbequiteusefulfornearbyorientationand
communicationpurposesamongnanorobots[1,90].Acousticcommunicationismoreappropriatefor
longerdistancecommunicationanddetectionwithlowenergyconsumptionascomparedtolight
communicationapproaches[5,91].Althoughopticalcommunicationpermitsfasterratesofdata
transmission,itsenergydemandmakesitnotidealformedicalnanorobotics[92].

WorkswithRFIDhavebeendevelopedasanintegratedcircuitdeviceformedicine[70].Using
integratedsensorsfordatatransferisthebetteranswertoreadandwritedatanimplanteddevices.
Thus,thenanorobotshouldbeequippedwithsinglechipRFIDCMOSbasedsensors[65,93].CMOS
withsubmicronSoCdesignaddressesextremelylowpowerconsumptionfornanorobots
communicatingcollectivelyatlongerdistancesthroughacousticsensors.Forcommunication,aswell
asfornavigationalpurposes,theuseofnanoacousticsfornanorobotinteractionscaneffectively
achieveresolutionsof700nm[94].Fordatarecognition,theacousticphononsscatteredfromtheorigin
shouldbepropagatedatsufficientdistances,andtheacousticwavefieldshouldbemeasuredby
diffractionpropagation.Forthenanorobotactivesonarcommunication,frequenciescanreachupto
20W@8Hzatresonancerateswith3Vsupply[91].
MorewidelyacceptedandusualthananRFCMOStransponder,mobilephonescanbeextremely
practicalandusefulassensorsforacquiringwirelessdatatransmissionfrommedicalnanorobots
implantedinsidethepatientsbody.Cellphonescanbeagoodchoiceformonitoringpredefined
patternsnvariousbiomedicalapplications,suchashelpingnubiquitoushealthcareforrealtime
influenzadetection.Toaccomplishthat,chemicalnanobiosensorsshouldbeembeddednthe
nanorobottomonitoralphaNAGAlevels.Thenanorobotemitssignalstosendanalarm,ncaseof
detectionofanyalphaNAGAproteinoverexpression,denotingwhenapersonwascontaminatedwith
influenza.Fornanorobotpassivedatatransferring~4.5kHzfrequencywithapproximate22sdelays
arepossiblerangesfordatacommunication.
Inourmolecularmachinearchitecture,tosuccessfullysetanembeddedantennawith200nmsizefor
thenanorobotRFcommunication,asmallloopplanardeviceisadoptedasanelectromagneticpickup
havingagoodmatchingonlownoiseamplifier(LNA);itisbasedongoldnanocrystalwith1.4nm 3,
CMOSandnanoelectroniccircuittechnologies[65,95].Frequenciesrangingfrom1to20MHzcanbe
successfullyusedforbiomedicalapplicationswithoutanydamage[65].

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Figure 3.Infectedcellsnbrowncolorrepresentedasearlystageofviruscellinvasion.

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7. System Implementation
ThenanorobotmodelprototypingusesataskbasedapproachwithdetectionofproteinalphaNAGA
higherconcentrations.Thesimulationandanalysisconsistofadoptingamultiscaleviewofthe
scenariowithbloodstreamsimulation.Itincorporatesthephysicalmorphologyofthebiological
environmentalongwithphysiologicalfluidflowpatterns,andthisisalliedwiththenanorobotsystems
fororientation,drivemechanisms,sensingandcontrol.Therealtime3Dsimulationisusedtoachieve
highfidelityoncontrolmodellingandequipmentprototyping.Hence,theNCD(NanorobotControl
Design)softwarewasimplementedandisusedfornanorobotsensingandactuation.Thecomputational
modelisappliedasapracticaltoolforcontrolandmanufacturingdesignanalyses.Realtime3Ddesign
andsimulationareimportantforthefastdevelopmentofnanotechnology,helpingalsontheresearch
anddevelopmentofmedicalnanorobots[96,97].Suchtoolshavesignificantlysupportedthe
semiconductorindustrytoachievefasterVLSIimplementation[98].Ithassimilarlydirectimpacton
nanomanufacturingandalsonanoelectronicsprogress[24].Simulationcananticipateperformance,
helpnnewdeviceprototypingandmanufacturing,nanomechatronicscontroldesignandhardware
implementation[1,80].
Thenanorobotexteriorshapebeingcomprisedofcarbonmetalnanocomposites[99],towhich
shouldbeattachedanartificialglycocalyxsurface[100],isusedtominimizefibrinogenandother
bloodproteinsadsorptionorbioactivity,ensuringsufficientbiocompatibilitytoavoidimmunesystem
attack[63,92].Differentmoleculetypesaredistinguishedbyaseriesofchemotacticsensorswhose
bindingsiteshaveadifferentaffinityforeachkindofmolecule[42,101].Thesesensorscanalsodetect
obstacleswhichmightrequirenewtrajectoryplanning[102].Thenanorobotsensorycapabilitiesare

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simulated,allowingittodetectandidentifythenearbypossibleobstaclesnitsenvironment,aswellas
alphaNAGAproteinoverexpressionforcontinuousrealtime n vivoprognosispurpose.Forchemical
detectionavarietyofsensorsispossible,enablingidentificationofvarioustypesofcells[42,61,67,75].
Asetofdifferentviewsfromthe3Denvironmentcanbeobserved(Figs.3and4).Amultiplicityof
nanorobotsallowsprecisedetectionofalphaNAGAninitialstagesofinfluenzainfection.
8. Physical Parameters
Themicroenvironmentsofthecirculatorysystemvaryconsiderablynsize,flowrates,andother
physicalproperties.Chemicalsnthebloodcanpresentdistinctdiffusioncoefficients,andlikenany
othersurgical,prognosis,orintegratedpharmacokineticsystem,thereisarangeofplausibledesigns
forthenanorobotsdependingoncustomizedrequirements[5].ndefiningthenanorobotapplication,
physicalparametersisthekeypointtodeterminingthearchitectureprototype[1],sensorbased
actuation[102],andstrategiestoincreasethemedicalinstrumentationefficiency[18].
Smallvesselshavediametersofuptoseveraltensofmicrons,andlengthsofaboutamillimeter.
Notwithstandingourcontrolactuationcanbesetwithdifferentparameters,suchasadjustingdetection
thresholds,weadoptedtypicalvaluesfortheseproperties.Theworkspaceusednthesimulator
comprisedanenvironmentconsistingofasegmentofthevesselwithlength L =60manddiameter K
=30m.Themodelhasalsoasmallgroupofhostagecells,asthemedicaltargetonthevesselwall
(Fig.5),releasingalphaNAGAproteinsintothefluid.Cellsandnanorobotscontinuallyenteroneend

oftheworkspacealongwiththefluidflow.Wetreatnanorobotsnotrespondingwhilewithinthe
workspaceasiftheydidnotdetectanysignal,sotheyflowwiththefluidasitleavestheworkspace.
Thus,wechoosetheworkspacelengthsufficienttoincludetheregionwherethechemicalfromthe
targetissignificantlyabovethebackgroundlevel.Thecellsoccupyabout1/5thoftheworkspace
volume,atypical hematocritvalueforsmallbloodvessels.
Thenanorobotmorphologyisbasedonmicrobiology,presentingacylindersshapewith2min
lengthand0.5mndiameter,whichallowsfreeoperationinsidethebody[103].Therefore,the
nanorobotscustomizeddesignisusefulforhealthmonitoring,butitalsoenablesthenanorobotto
crossthebloodbrainbarrierforotherbiomedicalapplications,suchasrequiredforintracranial
therapies.Thisprototypingallowsthenanorobottohaveacompletekinematicmotioncontrolnregard
toBrownianmotioneventsinsidemicroenvironmentsatlowReynoldsnumber.
Thesimulatorcomprisesarealtime3Denvironment,includingnanorobotsandchemicalsignal
parameters.Mostofthecellsareredbloodcells,with6mdiameter.Thenumberdensitiesofplatelets
andwhitebloodcellsareabout1/20thand1/1000ththatoftheredcells,respectively.Asspecific
example,weconsideralphaNAGAproteinsignal,producednresponsetotheinfluenza,having
molecularweightof52kDa(kilodaltons),withconcentrationnearthehostagecellsat 30ng/mland
backgroundconcentrationnthebloodstreamabout300timessmaller.Thischoiceprovidesan
interestingnanorobottask,thoughwecouldequallywellstudytasksinvolvingchemicalswithdifferent
concentrationsrelevantforothersimilarbiomedicalproblems,suchasfornewdrugtargettofight
HCV(hepatitisCvirus)orHIV(humanimmunodeficiencyvirus)[1,16,46,90].nourstudy,the
chemicalsignalwastakentobeproduceduniformlythroughoutvesseloncethepersonwasinfectedby
influenzaattherateQ.Thisratechangesnproportiontothediseaseprogression.

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9. Target Identification
Nanorobotsusingchemicalsensorsasembeddednanoelectronicscanbeprogrammedtodetect
differentlevelsofalphaNAGAsignals.Basedonclinicalanalysis,thealphaNAGAproteinsarewell
establishedasmedicaltargetsforearlystagesofinfluenzadevelopment[16].Nanorobotsasmobile
medicaldevicesinjectedthroughthebloodstreamareusednourstudy;themedical3Denvironment
compriseshistoricalclinicaldataofbloodflowpatternsandmorphologicalparametersfrompatients
withinfluenzavirus(Figs.6and7).Thebehaviourusedbyinfluenzatocellinvasionandfusionis
quitesimilarwithtacticsalsousedbyotherviruses,likeSmallpoxorSARS.Theproposedplatform
withnanorobotprototypeasaquiteeffectivearchitectureappliedtoinfluenzaprognosis,canalso
addressabroadrangeofbiohazarddefensepossibilities,thereforeprovidinganewvirusfighting
technology.
Basedonprecisepersonnelhealthmonitoring,thepresentedmodelcansupportthemilitary
commandheadquarterstowardsapervasivesurveillanceintegratedplatformformedicaldefense.The
nanorobotcomputationisperformedthroughasynchronousintegratedcircuitarchitecturewithatask
basedmodularapproach.TheembeddednanobiosensorisusedfordetectionofalphaNAGA
concentrationsnthebloodstream.Duetobackgroundcompounds,somedetectionoccursevenwithout
alphaNAGAconcentrationsspecifiedasinfluenzainfection.Therefore,forthechemicaldiffusiona
capturerate isadoptedforinfluenzaidentification,giventheradius Rforaregionwithconcentration
as:

4DR

(1)

Drepresentsthediffusioncoefficient,and Cisthechemicalconcentration[104].Withindependent
randommotionsforthemolecules,detectionoveratimeinterval tisbasedonaPoissonprocesswith
meanvalue t.Whenobjectsoccupyonlyasmallfractionofthevolume,thevelocityatdistance r
fromthecenterofthevesselisrepresentedby:
w2v(1(r/(d/2))2).

(2)

Thevelocityhasaparabolicflownrelationtothecells.Forafluidmovingatvelocity vnthe

positive xdirection,itpassingaplanecontainingapointofachemicalsourceproducedatarate Q
(moleculespersecond),andadiffusioncoefficient D.Thus,diffusionequationisdefinedas:
(3)

D2C vC/x.

Theboundaryconditionsattainasteadypointsourceattheorigin,havingnonetfluxacrossthe
3

point(x, y, z)by[1]:

Q
ev( r x)/(2 D)
C(x, y,
2Dr
z)

(4)

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Figures 4-9.Screenshotswithnanorobotsandredbloodcellsinsidethevessel.
Therealtime3Dsimulationoptionallyprovidesvisualizationeitherwithor
withouttheredbloodcells.Theinfluenzainfectionwithcellhostagebeginsto
spreadfrominfectedtonearbyuninfectedcells.Thenanorobotsflowwiththe
bloodstreamsensingforproteinoverexpression.

Figure7

Figure4

and risthedistancetothe
source:

Figure8

Figure5

boundaryplaneat y=0;therebythesteadystateconcentrationC(moleculesper m)isdeterminedat

r x2 y2
z2.

Figure9

Figure6

(5)

10. Nanorobot Simulation and Results

Arangeofdifferentpatternsignalsaredirectlycorrelatedtospecificdiseases.Hence,chemical
signalscanserveformedicaltargetidentification,diagnosis,andactuation[1].Fortheproblemofa
pandemicvirus,thenanorobotsareusedforidentifyingandtopredictbloodstreamproteinparameters,
whichcanpreventagainstchemicalreactivityhazards.Asetofproteinsorspecificselfassembled
chemicalcellscanbecharacterizedasatypicalvirus,withprofoundconsequencesforalarge
populationnthecaseofepidemicproliferation.

Sensors 2008, 8
Nanobioelectronics,usingnanowiresasmaterialforembeddedbiosensorsandintegratedcircuit
packaging,canachievemaximalefficiencyforapplicationsregardingchemicalchanges[5].Thus,
usingchemicalsensors,nanorobotscanbeprogrammedtodetectdifferentlevelsofdistinctproteins.
Thenanorobotshouldbeuseful,therefore,tofindavirus,whichmaybeproliferatingintoapersons
Figure 10.Militarystrategicandtacticalrelaysatellitescanuseultrahighfrequencyfor
longdistanceepidemicmonitoringandcontrol,backtrackinginformationfromthe
mobilephone.Communicationinterfaceprovidespersonidentificationandposition,
usingnanorobotswithPDAsmartcellphone.

2947

Figure 11.Nanobiosensoractivation.

160

Nanorobot sensor activation: influenza detection

140
120
100
80
60
40
20
0
-20
time (ms)

bloodstreamthroughcellinvasion.Integratednanobiosensorscanbeutilizedenablingprecisecell
biologyinterfaces,anddetectingdifferentconcentrationsofchemicalsignalsinsidethebody,itshould
providerealtimemedicalmonitoringtofightanepidemicdiseaseninitialstagesofcontamination
[12,105,106].
Thechemicaldetectionnacomplexdynamicenvironmentisanimportantfactortoconsiderfor
nanorobotsnthetaskofinteractingwiththehumanbody.Thenanorobotsneedtotracktheinfluenza
developmentbeforeapandemicoutbreakhappens.Themaincellmorphologicalchanges,given

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influenzainfection,weretakenformodellingbloodstream,whichprovidesthenecessaryenvironment
formedicalnanorobotinteractionanalysisandprototyping(Figs.8and9).
Theapplicationofultrahighfrequencysatellitecommunicationsnetworkcanbesuccessfully
-NAGgSnailTrsduce:().

appliedfornanorobotdatatransmission,usingwirelessphonesforlongdistancecommunication
4l
4
[7,68,69,107].ThecellphonePDA(personaldigitalassistant)systemprovidesalsothepersons
3.5 l

3l
Figure 12.NanorobotsdetectinghigherconcentrationsofalphaNAGAsignalswithin
2.5l
thebloodstream.
2l

30

59

2l

88

117 146 175 204 233

identificationwithrespectivepositionforthemomentthenanorobotdetectedsomevirusprotein
profile(Fig.10).
CarbonnanotubesserveasidealmaterialsforthebasisofaCMOSICbiosensor.nfact,carbon
basedsensorhasbeenusedsuccessfullyfor n vivoproteindetection[108].Consideringtheimportance
ofalphaNAGAagainstneuroaxonaldystrophy[109],smallconcentrationsofthisproteininsidebody
cancausesomefalsepositives.TypicalconcentrationsofalphaNAGAproteinarelessthan1
nmole/min/106cells.NormalconcentrationsofalphaNAGAnthebloodstreamarenaverageless
than2l.Forapersoninfectedwithinfluenza,alphaNAGAconcentrationsfrombloodsample
increases,rangingfrom1.26to4.63nmole/min/106cells[16].Therefore,ifthenanorobots
electrochemicalsensordetectsalphaNAGAnlowquantitiesorinsideexpectedgradients,itgenerates
aweaksignallowerthan50nA.nsuchcasethenanorobotignoresthealphaNAGAconcentration,
assumingitasexpectedlevelsofbloodstreamconcentration.However,ifthealphaNAGAreaches
concentrationhigherthan3l,itproducesacurrentflowthatcorrespondstotherateofantigen
enzymaticreaction,whichgeneratesacurrenthigherthan80nA(Fig.11),henceactivatingthe
nanorobot.Everytimeithappens(Fig.12),thenanorobotemitsanelectromagneticsignalback

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propagatedforthemonitoringintegratedplatform,whichrecordsthecellphonePDAassociatedwith
thepersonidentification[107].Thisapproachcanenabletheheadquarterstoautomaticallyidentifythe
personinfectedwithinfluenza,andsendanurgentSMStomultiplerecipients.Therefore,themembers
ofasamegroupcantakethenecessaryactiontoimmediatelyassistwhowasinfected,avoidingany
possiblepandemicoutbreak.
Figure 13.NanorobotsactivationinsidevesselwithrespectiveYXpositions.
Inside vessel: nanorobot positions
25400

25000

fiftyth
first

24600

24200

hundredth
23800

10000

20000

30000

40000

50000

60000

Detected positions: first, mid and last nanorobot

Figure 14.Electromagneticbackpropagatedsignalsgeneratedfromnanorobotsactivation.

Inside vessel: -NAGA detection

30000
25000
20000
15000
10000
5000
0

10000

20000

30000

40000

50000

60000

Detected positions: hundred nanorobot signals

Asathresholdtoavoidnoisedistortionsandachieveahigherresolution,atleastatotalof100
nanorobotsmustemitahigherproteomicsignaltransductionforasameperson(Fig.13).nsuchcase,
Vesl:Y-axinm(zo )

thesystemconsidersastrongevidenceofinfluenzacontamination.Thus,themedicalnanorobotcanbe
extremelyusefultoidentifyapatientwithearlydevelopmentofinfluenza(Fig.14).

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11. Molecular Machine Manufacturing

Developmentsonnanobioelectronicsandproteomicsshouldenablefullyoperationalnanorobots,
integratedasmolecularmachines,forusencommonmedicalapplications[42,110112].nthepresent
approach,theproposedarchitectureassemblesasananoelectronicbiochipintegrationprocess[5,113
116].Progressntechnologyhashistoricallyshownthattechnicalchallengescanbeconvertedto
opportunities[117].Thus,althoughimportantbreakthroughsaredemandedforthefully
implementationofhardwaretoenablenanorobots,themainbarrierscouldbesuccessfullyovercomeby
researchandcontinuousdevelopment.Forexample,lithographyhassuccessfullyenabled
esVl:Y-axnmi

manufacturingofcompactcomponentscomprisingseveralnanowirelayerstointegratenanoelectronics
[118120].CMOShasenhancedminiaturizationandindustrialmanufacturingtechniques
[119,121,122],whichhaveprovidedwaystoachievecommercializedproductsasnanoelectronics
integrateddevices.NanosensorsusingDNAandCNTasinnovativematerialsweresuccessfully
demonstratedforproteindetection[112,120,123,124].TherecentimplementationofhighK/metalgate
inthe45nmsilicontechnologynodeshouldresultnpositiveimpactontheprogressofhighK
researchforInSb(indiumantimonide)andInGaAs(indiumgalliumarsenide)[119],enablingnew
waystoachievesmallernanoICpackaging.nthesametime,blockcopolymercanbeviewedasa
promisingapproachtoimprovemanufacturingminiaturizationofcurrentnanoelectronics[122,125],
evenenablingcomplex3Dnanodevices,notpreviouslyallowedbytraditionalCMOStechniques.
Thosemethodsandnewmaterialsshouldthereforebeinvestigatedtogethertoenablemorecomplex
nanoelectronicpackaging,suchasnecessaryforintegrationofnanorobots.Toextendfurtherthe
CMOSperformanceimprovementsfoundwithdimensionalscaling,newmaterialsforplanar
MOSFETsandnonclassicalMOSFETstructuresarecurrentlyndevelopment,whichshouldalsobe
consideredtoadvancenanoelectronicsandnewbiosensorsmostlyusefulfornanomedicine[126,127].
12. Conclusions and Outlook

Thisworkuseda3Dapproachtoshowhownanorobotscaneffectivelyimprovehealthcareand
medicaldefense.Nanorobotsshouldenableinnovativerealtimeprotectionagainstpandemic
outbreaks.Theuseofnanomechatronicstechniquesandcomputationalnanotechnologycanhelpnthe
processoftransducersinvestigationandndefiningstrategiestointegratenanorobotcapabilities.A
bettercomprehensionabouttherequirementsananorobotshouldaddress,nordertobesuccessfully
usedfor n vivoinstrumentation,isakeyissueforthefastdevelopmentofmedicalnanorobotics.
Detailsoncurrentadvancesonnanobioelectronicswereusedtohighlightpathwaystoachieve
nanorobotsasanintegratedmolecularmachinefornanomedicine.Moreover,basedonachievements
andtrendsnnanotechnology,newmaterials,photonics,andproteomics,anewinvestigation
methodology,usingclinicaldata,numericalanalysisand3Dsimulation,hasprovidedananorobot
hardwarearchitecturewithrealtimeintegratedplatformforpracticallongdistancemedicalmonitoring.
Thismodelcanenablenanorobotsasinnovativebiohazarddefensetechnology.
Inthe3Dsimulation,thenanorobotswereabletoefficientlydetectalphaNAGAsignalsnthe
bloodstream,withtheintegratedsystemretrievinginformationaboutapersoninfectedwithinfluenza.
Themodelprovideddetailsondesignformanufacturability,majorcontrolinterfacerequirements,and

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insidebodybiomolecularsensingforpracticaldevelopmentandapplicationofnanorobotsnmedical
prognosis.
Theuseofnanorobotsfor n vivomonitoringchemicalparametersshouldsignificantlyincreasefast
strategicdecisions.Thus,nanorobotformedicaldefensemeansaneffectivewaytoavoidanaggressive
pandemicdiseasetospreadintoanoutbreak.Asadirectimpact,itshouldalsohelppublichealth
sectorstosavelivesanddecreasehighmedicalcosts,enablingarealtimequarantineaction.An
importantandinterestingaspectnthecurrentdevelopmentisthefactthat,thesimilararchitecture
presentedntermsofhardwareandplatformintegration,canalsobeusedtodetectmosttypesof
biohazardcontaminants.Theresearchanddevelopmentofnanorobotsforcommonapplicationnfields
suchasmedicineanddefensetechnologyshouldleadusforasaferandhealthierfuture.
Acknowledgements
TheauthorsthankBillNace,DeclanMurphy,LiorRosen,RobertA.FreitasJr.,TadHogg,Toshio
Fukuda,andWarrenW.Wood,forhelpfulcommentsprovidedduringthedevelopmentofthisproject.
ThisprojectwaspartiallysupportedbytheAustralianResearchCouncil(ARC).
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