Quantum Dots.pdf

2,244 views 51 slides Mar 24, 2023
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About This Presentation

Qdots


Slide Content

Quantum Dots

NANOPARTICLES

•Nanoparticlesareparticlesthathavedimensionof100
nmorlessinsize.
•Thepropertiesofmanyconventionalmaterialschange
whenformedfromnanoparticles.
•Thisistypicallybecausenanoparticleshaveagreater
surfaceareaperweightthanlargerparticles;thiscauses
themtobemorereactivetocertainothermolecules.

•Iron nanoparticles
are used to clean up carbon tetrachloride
pollution in ground water.
•Designed by Oregon Health & Science
University's OGI School of Science &
Engineering, in collaboration with Pacific
Northwest National Laboratory (PNNL)
and the University of Minnesota.

•Carbon tetrachloride is a manufactured toxic
chemical used mainly in cleaning fluids and
degreasing agents.
•Spillage infiltrates the soil and creates very large
areas of contaminated groundwater and soil in
few areas causing cancer in animals.
•A commercially available product of iron oxide
with a magnetite shell high in sulfur, quickly and
effectively degraded carbon tetrachloride to a
mixture of relatively harmless products.

•ResearchersatMITandHarvardMedicalSchool
havebuilttargetednanoparticlesthatcanclingtoartery
wallsandslowlyreleasemedicine,anadvancethat
potentiallyprovidesanalternativetodrug-releasing
stentsinsomepatientswithcardiovasculardisease.

•Theparticles,dubbed“nanoburrs”,arecoatedwith
tinyproteinfragmentsthatallowthemtosticktotarget
proteins.
•Theyaredesignedtoreleasetheirdrugpayloadover
severaldaysandareoneofthefirstsuchtargeted
particlesthatcanpreciselyhomeinondamagedvascular
tissue.

QUANTUM DOTS

INTRODUCTION
•Quantum dotsaretinyparticles,or
“nanoparticles”,ofasemiconductormaterial,
traditionallychalcogenides(selenidesor
sulfides)ofmetalslikecadmiumorzinc(CdSeor
ZnS),whichrangefrom2to10nanometersin
diameter(aboutthewidthof50atoms).

•Theyarethesmallestobjectsthatcanbesynthesizedon
thenanoscale.
•Likethenamesuggests,itsstructureismuchlikeasmall
dot.Commonshapesincludepyramids,cylinders,lens
shapes,andspheres.
•Differentsynthesisroutescreatedifferentkindsof
quantumdots.

•Quantum dots are so important because they confine
electrons in three dimensions.
•The reason 'quantum' prefixes the name is because the
dots exhibit quantum confinement properties in all three
dimensions i.e. electrons within a dot can't freely move
around in any direction.

•Theabilitytopreciselycontrolthesizeofaquantum
dotenablesthemanufacturertodeterminethe
wavelengthoftheemission,whichinturndetermines
thecolouroflightthehumaneyeperceives.
•Quantumdotsexhibitquantizedenergylevelslikean
atom.Foragiveninputenergy,forinstance,aquantum
dotwillonlyemitspecificspectraoflight.
•Withdecreasingdiametersofquantumdots,thereisa
correspondingincreaseinenergyofemittedlight.

•Quantumdotscanthereforebe“tuned”during
productiontoemitanycolouroflightdesired.Theability
tocontrol,or“tune”theemissionfromthequantumdot
bychangingitscoresizeiscalledthe“sizequantisation
effect”.
•Duetoexcellentconfinementpropertiesnotseenin
nanowiresorquantumwells(inallmodernlasers),
quantumdotsareextremelyefficientatemittinglight.

HISTORY
•In the 1970s the first low dimensional structures QW (Quantum
Wells) were developed.
•1D ( Quantum Wires) and 0D (Quantum Dots) were subsequently
developed.

PROPERTIES OF QUANTUM DOTS
•Beingsmallerthanthewavelengthofthevisiblelight,
theycannotbeseenundernormalconditions.
•QuantumDotsluminesceunderultravioletlight,with
thesizeofthedotscontrollingitscolour.
•Aquantumdotcanhaveanythingfromasingleelectron
toacollectionofseveralthousandselectrons.
•QuantumDotsfluoresceorstaylitmuchlongerthen
dyesconventionallyusedfortaggingcells.
•Theycanbetaggedtoproteinsandtheirglowenables
theidentificationofspecificproteinsorDNAmakingit
possibletodiagnosevariousdiseases.

Theelectronsinquantumdotsareconfinedinasmallspace(quantumbox),
andwhentheradiiofthesemiconductornanocrystalissmallerthanthe
excitonBohrradius(excitonBohrradiusistheaveragedistancebetweentheelectroninthe
conductionbandandtheholeitleavesbehindinthevalenceband),thereisquantizationof
theenergylevelsaccordingtoPauli’sexclusionprinciple.
Thediscrete,quantizedenergylevelsofquantumdotsrelatethemmore
closelytoatomsthanbulkmaterialsandhaveresultedinquantumdots
beingnicknamed'artificialatoms'.
Asthesizeofthecrystaldecreases,thedifferenceinenergybetweenthe
highestvalencebandandthelowestconductionbandincreases.Moreenergy
isthenneededtoexcitethedot,andmoreenergyisreleasedwhenthecrystal
returnstoitsgroundstate,resultinginacolorshiftfromredtoblueinthe
emittedlight.Asaresultofthisphenomenon,quantumdotscanemitany
coloroflightfromthesamematerialsimplybychangingthedotsize.
Additionally,becauseofthehighlevelofcontrolpossibleoverthesizeofthe
nanocrystalsproduced,quantumdotscanbetunedduringmanufacturingto
emitanycoloroflight.
Quantum dots have a unique electronic structure

Quantumdotscanbeclassifiedintodifferenttypesbasedontheircomposition
andstructure.
Core-TypeQuantumDots
Quantumdotscanbesinglecomponentmaterialswithuniforminternal
compositions,suchaschalcogenides(selenidesorsulfides)ofmetalslike
cadmiumorzinc,example,CdSe.Thephoto-andelectroluminescence
propertiesofcore-typenanocrystalscanbefine-tunedbysimplychangingthe
crystallitesize.
Core-ShellQuantumDots
Theluminescentpropertiesofquantumdotsarisefromrecombinationof
electron-holepairs(excitondecay)throughradiativepathways.However,the
excitondecaycanalsooccurthroughnonradiativemethods,reducingthe
fluorescencequantumyield.Toimproveefficiencyandbrightnessof
semiconductornanocrystalsanewmethodisgrowingshellsofanotherhigher
bandgapsemiconductingmaterialaroundthem.Thesequantumdotswith
smallregionsofonematerialembeddedinanotherwithawiderbandgapare
knownascore-shellquantumdots(CSQDs)orcore-shellsemiconducting
nanocrystals(CSSNCs).

Forexample,quantumdotswithCdSeinthecoreandZnSintheshellexhibit
greaterthan80%quantumyield.Coatingquantumdotswithshellsimproves
quantumyieldbypassivizingnonradiativerecombinationsitesandalso
makesthemmorerobusttoprocessingconditionsforvariousapplications.
Thismethodhasbeenwidelyexploredasawaytoadjustthephotophysical
propertiesofquantumdots.
AlloyedQuantumDots
Tuningthepropertiesbychangingcrystallitesizecouldcauseproblemsin
manyapplicationswithsizerestrictions.Multicomponentquantumdotsisan
alternativemethodtotunepropertieswithoutchangingcrystallitesize.
Alloyedsemiconductorquantumdotswithbothhomogeneousandgradient
internalstructuresallowtuningofopticalandelectronicpropertiesbymerely
changingthecompositionandinternalstructurewithoutchangingthe
crystallitesize.Forexample,alloyedquantumdotsofthecompositions
CdS
xSe
1-x/ZnSof6nmdiameteremitslightofdifferentwavelengthsbyjust
changingthecomposition.Alloyedsemiconductorquantumdotsformedby
alloyingtogethertwosemiconductorswithdifferentbandgapenergies
exhibitedinterestingpropertiesdistinctnotonlyfromthepropertiesoftheir
bulkcounterpartsbutalsofromthoseoftheirparentsemiconductors.Thus,
alloyednanocrystalspossessnovelandadditionalcomposition-tunable
propertiesasidefrompropertiesduetoquantumconfinementeffects.

Visible spectrum
•5 nm dots: red
•1.5 nm dots: violet

Quantum dots change color with size because additional
energy is required to “confine” the semiconductor excitation
To a smaller volume
Ordinary light excites all color quantum dots.
(Any light source “bluer” than the dot of interest works.)

COLLOIDALSYNTHESIS
•Colloidalsemiconductornanocrystals-
synthesizedfromprecursorcompounds
dissolvedinsolutions,muchliketraditional
chemicalprocesses.
•Thesynthesisofcolloidalquantumdotsisbased
onathree-componentsystemcomposedof:
precursors,organicsurfactants,andsolvents.

•Theprecursorstransformintomonomerson
heatingtoasuitabletemperature.
•Oncethemonomersreachahighenough
supersaturationlevel,thenanocrystalgrowth
startswithanucleationprocess.
•Thetemperatureduringthegrowthprocess
mustbehighenoughtoallowforrearrangement
andannealingofatomsduringthesynthesis
processwhilebeinglowenoughtopromote
crystalgrowth.

FABRICATION
•Self-assembledquantumdotsaretypicallybetween5and50nmin
size,definedbylithographicallypatternedgateelectrodes,orby
etchingontwo-dimensionalelectrongasesinsemiconductor
heterostructures.
•Somequantumdotsaresmallregionsofonematerialburiedin
anotherwithalargerbandgap.Thesecanbecore-shellstructures,
e.g.,withCdSeinthecoreandZnSintheshellorfromspecialforms
ofsilicacalledormosil.
•Quantumdotssometimesoccurspontaneouslyinquantumwell
structuresduetomonolayerfluctuationsinthewell'sthickness.
•Thisfabricationmethodhaspotentialforapplicationsinquantum
computation.
•Themainlimitationsofthismethodarethecostoffabricationand
thelackofcontroloverpositioningofindividualdots.

VIRAL ASSEMBLY
•Leeetal.(2002)reportedusinggeneticallyengineeredM13
bacteriophagevirusestocreatequantumdotbiocomposite
structures.
•Geneticallyengineeredvirusescanrecognizespecific
semiconductorsurfaces.
•Itisalsoknownthatliquidcrystallinestructuresofwild-
typeviruses(Fd,M13,andTMV)areadjustableby
controllingthesolutionconcentrations,ionicstrength,and
theexternalmagneticfieldappliedtothesolutions.Thus,
thespecificrecognitionpropertiesoftheviruscanbeused
toorganizeinorganicnanocrystals,formingorderedarrays
overthelengthscaledefinedbyliquidcrystalformation.

•Usingthisinformation,Leeetal.(2000)were
abletocreateself-assembled,highlyoriented,
self-supportingfilmsfromaphageandZnS
precursorsolution.Thissystemallowedthemto
varyboththelengthofbacteriophageandthe
typeofinorganicmaterialthroughgenetic
modificationandselection.

ELECTROCHEMICAL ASSEMBLY
•Highlyorderedarraysofquantumdotsmayalsobeself-
assembledbyelectrochemicaltechniques.
•Atemplateiscreatedbycausinganionicreactionatan
electrolyte-metalinterfacewhichresultsinthespontaneous
assemblyofnanostructures,includingquantumdots,ontothe
metalwhichisthenusedasamaskformesa-etchingthese
nanostructuresonachosensubstrate.

BULK MANUFACTURING
•Conventional,small-scalequantumdotmanufacturingreliesona
processcalled“hightemperaturedualinjection”whichis
impracticalformostcommercialapplicationsthatrequirelarge
quantitiesofquantumdots.
•Areproduciblemethodforcreatinglargerquantitiesofconsistent,
high-qualityquantumdotsinvolvesproducingnanoparticles
fromchemicalprecursorsinthepresenceofamolecular
clustercompoundunderconditionswherebytheintegrityofthe
molecularclusterismaintainedandactsasaprefabricatedseed
template.
•Individualmoleculesofaclustercompoundactasaseedor
nucleationpointuponwhichnanoparticlegrowthcanbeinitiated.
Inthisway,ahightemperaturenucleationstepisnotnecessaryto
initiatenanoparticlegrowthbecausesuitablenucleationsitesare
alreadyprovidedinthesystembythemolecularclusters.
•Asignificantadvantageofthismethodisthatitishighlyscalable.

CADMIUM FREE QUANTUM DOTS
•Forcommercialviability,arangeofrestricted,heavymetal-freequantum
dotshasbeendevelopedshowingbrightemissionsinthevisibleandnear
infra-redregionofthespectrumandhavesimilaropticalpropertiestothose
ofCdSequantumdots.
•AnewtypeofCFQDcanbemadefromrareearth(RE)dopedoxide
colloidalphosphornanoparticles.Unlikesemiconductornanoparticles,
excitationwasduetoUVabsorptionofhostmaterial,whichissamefor
differentREdopedmaterialsusingsamehost.
•Multiplexingapplicationscanbethusrealized.Theemissiondependson
thetypeofRE,whichenablesverylargestokesshiftandisnarrowerthan
CdSeQDs.Thesynthesisisaqueousbased,whicheliminatedissuesofwater
solubilityforbiologicalapplications.

31
Applications
•Photovoltaicdevices: solarcells
•QD Solarpaint
•Biology: biosensors, imaging
•Light emittingdiodes: LEDs
•Quantum computation
•Photodetectors
•Lasers
31

32
SolarCells
•Photovoltaiceffect:
▫p-n junction.
▫Sunlight excites electronsand
createselectron-holepairs.
▫Electrons concentrateon one
sideof the celland holeson the
otherside.
▫Connectingthe 2 sidescreates
electricity.
32

33
DifferentGenerationsof SolarCells
•First generation:
▫Single crystalsiliconwafer.
▫Advantages: highcarrier mobility.
▫Disadvantages: mostof photon energyis
wastedas heat, expensive.
•Second generation:
▫Thin-film technology.
▫Advantages: lessexpensive.
▫Disadvantages: efficiencylower
comparedwithsiliconsolarcells.
•Thirdgeneration:
▫Nanocrystalsolarcells.
▫Enhanceelectricalperformances of the
second generationwhilemaintaininglow
production costs.

34
•Thequantumdotbandgapistunableandcanbeusedto
createintermediatebandgaps.Themaximumtheoretical
efficiencyofthesolarcellisashighas63.2%withthis
method.
How Can Quantum Dots Improvethe
Efficiency?

Cheap quantum dot solar paint
•“SunBelievablesolarpaint,”consistsofayelloworbrownpastemade
ofquantumdots.
•Thescientistsexperimentedwiththreetypesofquantumdots:CdS,
CdSe,andTiO
2,allofwhicharepowder-like,withwaterandtert
butanolasthesolvent.
•Insteadofaddingdyetogivethepaintadesiredcolor,theyadded
coloredsemiconductornanocrystalstothesolarpainttoachievethe
desiredopticalandelectronicproperties.

Quantum Dot LEDs
•Used to produce inexpensive,
industrial quality white light.
•Marked improvement over
traditional LED-phosphor
integration by dot’s ability to
absorb and emit at any desired
wavelength.
•Produce white light by
intermixing red, green and blue
emitting dots homogenously
within the phosphor difficult to
accomplish with the traditional
LED-phosphor set up.

Biolabelling
•Multicolor labeling of cells is a powerful technique for visualizing many
structures simultaneously, such as cytoskeletalproteins or organelles, and
to elucidate intracellular processes.
•QDs have been used to label cellular structures both within and external to
the cell membrane. They are delivered inside cells via receptor-mediated
pathways where specific ligandswere attached to QDs to induce cellular
uptake, as well as nonspecific endocytosis(ie, pinocytosis) where cells were
incubated with a concentrated QD solution.

Bioimaging
•Non invasive, real-time in vivofluorescence imaging requires exciting
fluorophoresand detecting their emission through tissue which is
invariably hindered by scattering and absorption of both the excitation and
emission wavelengths.
•Using a filtered halogen source and an IR camera, the collection of QDs
within tissue was monitored in real-time to identify a region for surgical
resection.

PHOTODETECTORS
•Photodetectorsbased on single quantum dots are expected to find uses in
opto-electrical interfaces in future quantum computers, where single
photons will carry information over long distances and single electrons will
be used for computation.

Futuristic applications
•Anti counterfeiting applications: inject dots into liquid mixtures,
fabrics, polymer matrices, etc. Ability to specifically control absorption and
emission spectra to produce unique validation signatures. Almost
impossible to mimic with traditional semi-conductors.
•Counter-espionage/Defense applications:Integrate quantum dots
into dust that tracks enemies. Protection against friendly-fire events.
•New research provides evidence for significant differences between new and
old red blood cells used for transfusions and could provide a cheap, rapid
and effective way to monitor the quality of blood .
•Scientists have discover nanoparticlesthat can disrupt intracellular
transport pathways.

Imagingisanimportantclinicalmodalityusedindeterminingappropriate
cancertherapy.
x-ray,computedtomography,ultrasound,radionuclideimagingandMRI,:
usedwidelyforcancerscreeningandstaging,determiningtheefficacyof
cancertherapyandmonitoringrecurrence.
2majorlimitations
1.donothavesufficientsensitivitytodetectsmallnumbersofmalignant
cellsintheprimaryormetastaticsites.
2.Theimagingtechniqueshavenotbeendevelopedtodetectspecificcancer
cell-surfacemarkers.
Inmanyinstances,thesecell-surfacemarkersmightbetargetsforcancer
therapyandmightassistinthediagnosisandstagingofcancer.
Quantumdot(QD)imagingprobes,althoughstillintheearlydevelopment
stage,providethepotentialtofulfilltheserequirementsforinvivocancer
imaging.
QDs In Cancer Therapy

QDs vsOrganic Fluorescent dyes
QDs offer great advantages over traditional organic fluorescent dyes and
present a number of beneficial characteristics for spectroscopy, such as
1. high fluorescence intensity (brightness)
2. long lifetime
3. good resistance to photobleaching.
4. have broad excitation and narrow and symmetric emission spectra, which
make it feasible to perform 'multiplexing' (simultaneous detection of multiple
signals) imaging using a single excitation source
5. high sensitivity for simultaneous cancer molecular imaging and targeted
therapy.
the sensitivity of QD-based molecular imaging can be two to three orders
larger than that of routine fluorescent dyes.
Furthermore, the fluorescence in near infrared of NIR-QDs can be detected in
deep tissues, making them suitable forin vivoimaging with high signal-to-
background ratio

Biocompatibility of QDs
QDsarehighlyhydrophobicand,therefore,onlysolubleinorganicsolvents.
Thusoftenencapsulatedbyamphiphilicmolecules.
Thehydrophobicsegmentofthesemoleculesinteractswiththehydrophobic
moleculesontheQDsurface,whereasthehydrophilicsegmentinteractswiththe
aqueousmedium,solublizingtheQDs.
Severaltypesofamphiphilicpolymers,includingpolyethyleneglycol(PEG)-derived
phospholipids,triblockcopolymers,octylamine-modifiedpolyacrylicacid,
oligomericphosphineandcopolymersofalkylmonomersandanhydrides,can
servethisencapsulationfunction.
Afterencapsulation,thehydrodynamicradiusofQDsincreasesto10-20nm.
TofunctionalizeQDswithbiomolecules,amphiphilicpolymersareengineeredto
carryreactivegroups,suchasaminesandcarboxylicacids.Biomolecules,suchas
peptides,antibodies,DNAorsiRNA,canreactwiththesefunctionalgroupstoform
covalentlinkagesmediatedbyvariouscouplingreagents.

Inaddition,biomoleculescanbeconjugatedwithQDsthroughnoncovalentaffinity
binding,suchastheinteractionsofbiotin/avidin,ornickelnitrilotriaceticacid(Ni-
NTA)/histidine-taggedpeptides.
Controllingratioofreactivegroupsandreactiontime,theaveragenumberof
biomoleculesconjugatedtoeachQDcanbecontrolledaverageoftwoorafew
biomoleculesaretypicallyconjugatedtooneQD.
EncapsulationandbioconjugationdonotusuallyaltertheopticalpropertyofQDs
significantly.
Recently,QDsbasedonsiliconhavedrawnmuchattentionbecauseoftheirpotential
lowertoxicitythanheavymetalQDs,suchasCd/Sedots.SiliconQDsaretypically2-8
nminsize.ThesurfaceofQDscanbepassivatedwithorganicligands,suchas
octadeceneanddodecene,resultinginQDsthataremorestableduringstoragewith
dramaticallyincreasedquantumyieldandsolubilityinorganicsolvents.
SomesiliconQDsemitfluorescenceatredandinfraredrange,whichisidealforin
vivoimaging.However,theirexcitationwavelengthnormallyliesintheultraviolet
region,whichpenetratespoorlyintotissuesandmightbedamagingtocells.

Detectionofprimarytumorinvitro
BiocompatibleQDswereintroducedforimagingofcancercellsinvitroin1998.
ResearchershavesynthesizedQD-basedprobesconjugatedwithcancerspecific
ligands,antibodies,orpeptidesforcancerimaginganddiagnosisinvitro.
Comparedwithtraditionalimmunohistochemistry,QD-IHCismoreaccurateand
preciseatlowproteinexpressionlevelsandcanachievequantitativedetectionwhich
willprovidemuchmoreinformationforpersonalizedtreatment.
Prostatecancer
Gaoetal.labeledhumanprostatecancercellsbasedontheconjugateofQDswithan
antibodyforprostatespecificmembraneantigen(PSMA).QD-basedimmunolabelling
hasmorestablephoto-intensitycomparedwithconventionalfluorescent
immunolabelling.
SuperiorqualityofQD-IHCcomparedwithconventionalIHChasbeendemonstrated
alongwithsimultaneousdetectionofandrogenreceptorandPSAinprostatecancer
cellsbasedonmultiplexingQDs.ThedetectionsensitivityofQD-basedprostatecancer
biomarkerscanbeenhancedbysurfaceplasmon-coupledemissionwhichhasbeen
introducedasanovelbiosensingtechnologyfordetectingbiosensorsandbiochips.

Breast Cancer
Humanepidermalgrowthfactorreceptor2(HER2)isoverexpressedinapproximately
25%to30%BCpatientsandhasimportantfunctionincancerprogression.Recent
studieshavevalidatedthevalueofHER2detectionforBCtreatmentandprognosis.
Comparedwiththegoldenstandardmethodoffluorescenceinsituhybridization(FISH),
theadvantagesofQD-basedIHChavebeenwelldocumented.
Thismethodiseasier,cheaperandlesstime-consuming.Variousstudieshavereported
thesuccessfuldetectionforBCbyQD-HER2conjugates.Thisapproachhasbeen
extendedtoselectivelylabelMCF-7andBT-474BCcellsforHER2,epidermalgrowth
factorreceptor(EGFR),estrogenreceptor(ER),progesteronereceptor(PR),and
mammaliantargetofrapamycin(m-TOR)byvisibleandNIRQDswhichindicatedthat
QD-basednanotechnologyisanefficientapproachtooffermultiplexedcancer
biomarkerimaginginsituonintacttumortissuespecimensfortumorpathologystudyat
thehistologicalandmolecularlevelssimultaneously.BCwassuccessfullydetectedwith
QD-basedprobeswhichdemonstratedthatlowerexpressionofHER2couldbeclearly
detectedbyQD-IHCcomparedwithconventionalIHC.
Thus,QD-basedmultiplexedimagingwillprovidemoreinformationfortheindividual
eventsoftumor,personalizeddiagnosis,prognosis,andtreatment

Ovarian cancer
QDscanalsobeusedtodetecttheovariancarcinomamarkerCA125indifferent
typesofspecimens,suchasfixedcells,tissuesections,andxenograftpiece.
Additionally,thephotostabilityofQDsignalsismorespecificandbrighterthanthat
ofconventionalorganicdye.Liuetal.synthesizedpH-sensitivephotoluminescent
CdSe/ZnSe/ZnSQDsinSKOV-3humanovariancancercellsthatarepH-dependent,
suggestingapplicationsforintracellularpHsensors.

Gastrointestinalcancer
Bosticketal.detectedfivebiomarkersonthesametissueslidebyQD-based
multiplexedimaging.
bothefficientandconvenient,takesonly7htoanalyzefivebiomarkers,which
wasadvantageousforclinicalapplication.
Pancreaticcancer
QD-basedimagingprobescantargetpancreaticcancerataveryearlystagewith
thehelpofproteins/peptidesdirectedagainstover-expressedsurfacereceptorson
cancercells/tissues,suchastransferringreceptor,antigenclaudin-4,and
urokinaseplasminogenactivatorreceptor.
BothCdSe/CdS/ZnSQDsandnon-cadmium-basedQDswithimproved
photoluminescenceefficiencyandstabilityasopticalagentshavebeenusedforthe
imagingofpancreaticcancercellsusingtransferringandanti-Claudin-4.

InvivoTumorimaging
Directlydemonstratetheevolutionmechanismoftumorprogression.
Moreconvincingevidencecouldbeobtainedfrominvivotumorimagingcompared
withinvitromolecularimaging.
Sensitiveandspecificimagingagentsarerequiredforhigh-qualityinvivotumor
imagingandlessbiologicalimpactsontheanimalmodel.
QD-basedimagingagentscanmeetthisdemandby“enhancedpermeabilityand
retention”(EPR)ortargetedmolecularimaging.TheprincipleofEPR-basedtumor
imagingistheleakinessoftumorbloodvessels.Comparedwithnormaltissues,tumor
vasculatureisquantitativelyhigher,butirregular,leaky,dilated,andvascular
endothelialcellsarepoorlyaligned.
Themorphologyresultsinincreasedleakageofmacromoleculesandnanocarriersout
ofthecirculatorysystemintothetumortissue.Thesefinallyaccumulateinthetumor
microenvironmentbecauseofthelackoflymphaticdrainage.Manystudieshave
reportedthatnon-targetedQDscanbeusedforcelltrafficking,vasculatureimaging,
sentinellymphnode(SLN)mapping,andneuralimaging.

SLNdiagnosiscontributestooperationstrategyincancersurgery.Duringlymphnode
metastasis,cancercellsfirstreachtheSLNvialymphflow.Thecancercellscanbe
detectedwithhighsensitivityintheSLNconnectedtothetumorsite.Thesuperiorityof
NIRQDshasbeendemonstratedinSLNmapping,acommonprocedureinBCsurgery,
wherebythelymphnodeclosesttothetargetedorganismonitoredforthepresenceof
locallydisseminatedcancercells.
Recentlyhighlysensitive,real-timeintra-operativeSLNmappingofthegastrointestinal
tractbyNIRQDsallowingimageguidancethroughouttheentireprocedure,virtually
freeofanybackgroundhavebeenreported.
Thesefindingscontributetoourunderstandingofmetastasis,whichremainsa
fundamentalbarriertothedevelopmentofeffectivecancertherapy.Giventhehigh
sensitivityandpenetrationofNIRQDfluorescence,theapplicationofQD-basedSLN
mappingallowsthesurgeontodefinethetumorborderaccuratelyandminimizethe
sizeofthedissection.
QDsneedtobeeffectively,specifically,andreliablydirectedtoaspecificorganor
diseasesitewithoutalterationtomakethemmorebeneficialforbiomedicalapplications.
SpecifictargetingcanbeachievedbyattachingtargetingmoleculestotheQDsurface.

Standardprotocolsforinvivoimagingoflivercancerxenograftanimalmodelshave
beendeveloped.Animalimagingbyinjectinghumanhepatocellularcarcinomacell
lines(HCCLM6)thatoverexpressalpha-fetoprotein(AFP)withantiAFPmonoclonal
antibodyandQD-IgGprobeshasbeenestablished.HCCLM6hasincreasedpotential
forlungmetastasis,thusitallowsconstructionofaplatformfortheearlymonitoring
ofcancermetastasis
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