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CHAPTE R
Nanobiotechnolog y
Introductio n
Visualizationa tth eNanoscale
Scannin gTunnelingMicroscopy
AtomicForc eMicroscopy
VirusDetectionvi aAF M
WeighingSingl eBacteriaan dVirusParticles
Nanoparticlesan dTheirUse s
Nanoparticlesfo rLabeling
QuantumSiz eEffec tan dNanocrystalColors
Nanoparticlesfo rDeliveryo fDrugs,DNA ,o rRN A
Nanoparticlesi nCancerTherapy
Assembl yo fNanocrystalsb yMicroorganisms
Nanotubes
AntibacterialNanocarpets
Detectiono fVirusesb yNanowires
IonChannelNanosensors
Nanoengineeringo fDN A
DN AMechanicalNanodevices
ControlledDenaturationo fDN Ab yGoldNanoparticles
ControlledChang eo fProteinShap eb yDN A
BiomolecularMotors
Nanobiotechnolog y
INTRODUCTIO N
I n1959 ,RichardFeynma nwasth efirstscientis tt osugges ttha tdevice san dmaterialscoul d
someda yb efabricate dt oatomi cspecifications :"Th eprinciple so fphysics ,a sfara sIca nsee,
d ono tspea kagains tth epossibilit yo fmaneuveringthing sato mb yatom. "
Molecularbiolog yoriginate dlargel yfro mth estud yo fmicroorganisms.On emicrometer
i son emilliont ho fameter,an dcell so fEscherichiacoli,th egeneticist'sfavorit ebacterium ,
areroughl y1micrometer( ="micron" )i nlength .Ananomete ri son ethousandt ho fa
micrometer=10~
9
meters(Fig .7.1) .Th eterm smicro-an dnano-arebot hfro mGreek.
Mikrosmean s"small. "Moreimaginativ ei snanos,alittl eol dma no rdwarf.Pico-come sfro m
Spanis hwherei tmeansasmal lquantity,o rbeak(fro mLatinbeccus,"beak, "ultimatel yo f
Celti corigin) .Prefixesfo reve nsmalle rquantitie sareshow ni nTabl e7.1 .Asfara slengt hi s
concerned ,thes eareapplicabl eonl yt osubatomi cdimensions .Nevertheless,whe ndealin g
wit hmassesan dvolume so nth enanoscal ew ema yfin dfemtogram san dzeptoliters .
Recently,scienc eha sadvance dint oth eareao fnanotechnology.A sth enam eindicates ,th e
impetu sha scom efro mpursuin gpracticalapplications ,especiall yi nth efield so felectronic s
an dmaterialsscience ,rathe rtha naques tfo rtheoretica lknowledge .Nanotechnolog y
involve sth eindividua lmanipulatio no fsingl emoleculeso reve natoms .Buildin g
component satom-by-ato mo rmolecule-by-moleculei nordert ocreatematerialswit hnove l
o rvastlyimprove dpropertieswasperhap sth eorigina lgoa lo fnanotechnologists .However,
th efiel dha sexpande di narathe rill-define dwayan dtend st oinclud ean ystructuress o
tin ytha tthei rstud yo rmanipulatio nwasimpossibl eo rimpractica lunti lrecently .Atth e
nanoscale ,quantu meffectsemerg ean dmaterialsofte nbehav estrangely,compare dt othei r
bul kproperties.
Th einterna lcomponent so fbiologica lcell sareo nth esam escal ea sthos estudie db y
nanotechnology .Asaconsequence ,nanotechnologist shav elooke dt ocel lbiolog yfo r
usefu lstructures,processes,an dinformation .Cellula rorganelle ssuc ha sribosome sma yb e
regarde da sprogrammabl e"nanomachines "o r"nano-assemblers. "Thu snanotechnolog y
i sspillin gove rint omolecularbiology .Muc ho f"nanobiotechnology "i si nfac tmolecular
biolog yviewe dfro mth eperspectiveo fmaterialsscienc ean ddescribe di nnove lterminology .
Al lchemica lreaction soperat ea tamolecularlevel .Whatdistinguishe stru enanotechnolog y
i stha tsingl emoleculeso rnanostructure sareassemble dfollowin gspecifi cinstructions .
Aribosom edoe sno tmerelypolymeriz eamin oacid sint oachain .I ttake sspecifie damin o
acids ,on ea tatime ,accordin gt oinformatio nprovided ,an dlink sthe mi naspecifi corder.
Thu sth ecriticalpropertieso fananoassemble rinclud eth eabilit yno tonl yt oassembl e
structuresa tth emolecularleve lbu tt od os oi naspecifi can dcontrolle dmanner.
1pm1 0pm10 0pm1nm1 0nm10 0nm1Dm1 0Dm10 0Dm1mm1cm0.1m1m
IIIIIIIIIII II
Electron
microscope
Light
ft
ft
microscope
Unaidedeye
ElectronHydrogenCarbonProteinT2
atomatomphage
FIGUR E7.1SizeComparisons
Theobjectsrang einsizefrom1meterto1picometer.
BacteriaEukaryoticSmall
cellinsect
SmallLarge
insectdog
CHAPTER 7
Table7.1Prefixesan dSizes
Lengt hUnit  Meters  Example s
5.9terameter s  meandistancefro msunt oPluto
Terameter  10
1 2
150gigameters  distancet oth esu n
Gigameter  10
9
38 0megameters  distancet oth emoon
6.3megameters  radiu softh eearth
3.2megameters  lengt hofGreatWallofChina
Megameter  10
6
Kilometer  10
3
3 0meters  bluewhale
Meter  1  larg edo g
Millimeter  10"
3
smallinsec t
Micrometer  10"
6
bacterialcell
500nanometers  wavelengthofvisibleligh t
100nanometers  sizeoftypica lvirus
3.4nanometers  onetur nofDNAdoubl ehelix
Nanometer  10"
9
molecules
35 0picometers  moleculardiameterofwater
26 0picometers  atomi cspacin gi nsoli dcoppe r
7 7picometers  atomi cradiu sofcarbo n( =resolutio nlimi tof
atomi cforc emicroscopea sof2004)
3 2picometers  atomi cradiu sofhydrogen
Angstrom  =100picometers=10"
1 0
meter
2.4picometers  wavelengthofelectron
Picometer  10"
1 2
Femtometer  10"
1 5
radiu sofatomi cnucleus
Attometer
-10-18
radiu sofproton
Zeptomete r  10"
2 1
Yoctometer  10"
2 4
radiu sofneutrino
Th emai npracticalobjectiveso fnanobiotechnolog yareusin gbiologica lcomponent st o
achiev enanoscal etasks .Som eo fthes etask sarenonbiologica lan dhav eapplication si nsuc h
areasa selectronic san dcomputing ,whereasother sareapplicabl et obiolog yo rmedicine.
Th epurpos eo fthi schapte ri st oshow ,b yselecte dexamples ,ho wbiologica lapproache sca n
contribut et onanoscience .
Manyinternalcomponentsofbiologicalcellsareinthenanoscalerange.Asnanotechnologyadvancesitis
developingmanylinkswithbiotechnologyandgeneticengineering.
Nanobiotechnolog y
VISUALIZATIO NA TTH ENANOSCAL E
I norde rt omanipulatemattero na natomi cscale ,w enee dt ose eindividua latom s
an dmolecules.Althoug hindividua lmoleculeshav ebee nvisualize dwithth eelectro n
microscope,i twasth edevelopmen to fscannin gprob emicroscopestha topene du pth efiel d
o fnanotechnology .Thes einstrument sal l
Scanrel yo naminiatureprob etha tscan sacros s
th esurfac eunde rinvestigation .
Al lscannin gprob emicroscopeswork
b ymeasuringsom eproperty,suc h
a selectrica lresistance ,magnetism,
temperature ,o rligh tabsorption ,wit h
ati ppositione dextremel yclos et oth e
sample .Th emicroscoperaster-scans
th eprob eoverth esampl e(Fig .7.2)
whil emeasuringth epropert yo finterest .
Th edat aaredisplaye da saraste rimag e
simila rt otha to natelevisio nscreen .
Unlik etraditiona lmicroscopes,scanned prob esystem sd ono tus elenses ,s oth e
siz eo fth eprob erathe rtha ndiffractio n
limit sthei rresolution .Som eo fthes e
instrument sca nb euse dt oaltersample s
a swella svisualiz ethem .
FIGUR E7.2
PrincipleofRaster
Scanning
I nrasterscanning,the
probemovest oand
froacrossthetarget
region.Theprobescans
onlywhilemovingi n
onedirection("scan") .
Whentheprobetravels
i ntherevers edirection,
i tmovesmorerapidly
withoutmakingcontact
("flyback") .
Th efirsto fthes einstrument swasth escanningtunnelin gmicroscope(STM),whic hwas
develope db yGer dBinni gan dHeinrichRohrera tIB M(se efollowin gsection) .The yreceive d
th eNobe lPrizei n1986 .Th eST Msend selectrons ,tha tis ,a nelectriccurrent,throug hth e
sampl ean ds omeasureselectrica lresistance .Th eatomicforcemicroscope(AFM)i s
especiall yusefu li nbiolog yan dmeasuresth eforc ebetwee nth eprob eti pan dth esample .
Visualizationofindividualmoleculesorevenatomsispossibleusingscanningprobemicroscopes.
SCANNIN GTUNNELIN GMICROSCOPY
Whe nametalti pcome sclos et oaconductin gsurface,electron sca ntunne lfro mon et oth e
other,i neithe rdirection .Th eprobabilit yo ftunnelin gdepend sexponentiall yo nth edistanc e
apart.Surfacecontour sca nb emappe db ykeepin gth ecurrentconstan tan dmeasuringth e
heigh to fth eti pabov eth esurface.Thi sallow sresolutio no findividua latom so nth esurfac e
bein gstudied .Thi si sth eprincipl eo fth escannin gtunnelin gmicroscope(Fig .7.3).
Atom smayals ob emovedusin gth eSTM .I n1989,i nperhapsth emostfamou sexperimen ti n
nanotechnology ,D .M .Eigleran dE .K .Schweize rfabricate dth eIB Mlog ob yarrangin g
3 5xeno natom so nanicke lsurface.The ychos enicke lbecaus eth evalley sbetwee nrow so f
nicke latom saredee penoug ht ohol dxeno natom si nplace,ye tsmal lenoug ht oallo wth e
xeno natom st ob epulle doverth esurface.T omovexeno natoms ,th eST Mti pwasplace dabov e
axeno natom ,usin gimagin gmode .Next,scannin gmod ewasturne dof fan dth e
ti plowere dunti lth etunnelin gcurren tincrease dseveralfol d("fabricatio nmode") .Th e
xeno nato mwasattractedt oth eST Mti pan dwasdragge db ymovin gth eti phorizontally .
Th eato mwasdeposite da titsne wlocatio nb yreducin gth etunnelin gcurrent.Sinc ethe nseveral
diagram shav ebee nmadei nth esam eway.Carbo nmonoxidema ni sshow ni nFig.7.4.
Fro mabiologica lperspective,th eweaknesso fST Mi stha ti trequire saconductin gsurface,
i npracticegenerall yametallaye ro fsom esort.Th eatomi cforc emicroscope(se efollowin g
CHAPTER 7
I
TJ1SIMAY
©
Tipatoms
Sampleatoms.
Finepositioning
control
Coarsepositioning
control
VIBRATIONISOLATION
FIGUR E7.3
Principleof
ScanningTunneling
Microscope
Theprobetipandsurface
atomsofthesampleare
showni ntheinset.
section )ha sth eadvantag eo fno tneedin gconductiv ematerialan dha stherefor ebee nmore
widelyapplie di nbiology .
Thescanningtunnelingmicroscopecanbeusedtodetectormoveindividualatomsonaconductingsurface.
ATOMI CFORCEMICROSCOPY
Visualizationa tth enanoscal ei softe nperforme dusin gatomi cforc emicroscopy.Asth e
nam eindicates ,thi soperatesb ymeasuringforce ,no tb yusin gastrea mo fparticlessuc ha s
photon s(a si nligh tmicroscopy)o relectron s(a si nelectro nmicroscopy).
Physicistssometime scompar eth eoperatio no fa nAF Mt oa nold-fashione drecor dplayer,
whic husesaneedl et oscrap eth esurfaceo farecord .Perhapst oabiologist ,th edifference
betwee naligh tmicroscopean dAF Mi slik eth edifferencebetwee nreadin gtex twithth eeyes
an dfeelin gBraille.
Nanobiotechnolog y
FIGUR E7. 4Carbon
MonoxideManb y
Zeppenfeld
Theatomswerearranged
bySTM.Themedium
i scarbonmonoxideon
platinum.Courtesyof
Internationa lBusiness
MachinesCorporation.
©1995,IBM .
FIGUR E7.5Th e
AtomicForce
Microscope(AFM )
Thedeflectionofthetipof
theprobebythesurface
i smonitoredbyalaser .
Laserbeam
Th eatomi cforc emicroscopewasinvente di n198 5b yGer dBinnig,Calvi n
Quate,an dChristo fGerber.Th eAF Musesashar pprob etha tmoves
overth esurfac eo fth esampl ean dwhic hbend si nrespons et oth eforc e
betwee nth eti pan dth esample .Th emovemen to fth eprob eperform sa
rastersca nan dth eresultin gtopographica limag ei sdisplaye donscreen .
Durin gscanning ,th emovemento fth eti po rsampl ei sperforme db y
a nextremel yprecisepositionin gdevic ean di smad efro mpiezoelectric
ceramics.(Thes earematerialstha tchang eshap ei nrespons et oa n
applie dvoltage. )I tusuall ytake sth efor mo fatub escanne rtha ti scapabl e
o fsub-Angstro mresolutio ni nal lthre edirections.
Th eAF Mprob ei sati po nth een do facantilever.A sth ecantileve rbend s
becaus eo fth eforc eo nth etip ,itsdisplacemen ti smonitoredb yalaser,
a sshow ni nFig.7.5.Th ebea mfro mth elase ri sreflecte dont oaspli t
photodiode .Th edifferencebetwee nth eAan dBsignal smeasuresth e
change si nth ebendin go fth ecantilever.Forsmal ldisplacements ,
th edisplacemen ti sproportiona lt oth eforc eapplied .Henc eth eforc e
betwee nth eti pan dth esampl eca nb ederived.
Th edistanc ebetwee nti pan dsampl ei sadjuste ds otha ti tlie si nth erepulsiv eregio no fth e
intermolecula rforc ecurve;tha tis ,th eAF Mprob ei srepelle db yit smolecularinteractio n
withth esurface.Th erepulsio ngivesameasureo fsurfac etopography ,an dthi si swhati s
generall ydisplayed ,withcolo rcodin gindicatin grelativ eheight .I ti spossibl et osca na
surfacefo rtopograph yan dthe nrais eth eAF Mprob ean dresca nt odetectelectrostatico r
magneticforces .Theseca nthe nb eplotte dfo rcompariso nwithth etopography .
A swithSTM ,i ti spossibl et ous eAF Mt omov esingl eatoms ,althoug hthi swasonl yachieve d
i n2003 .Researchersa tOsak aUniversityi nJapa nremove dasingl esilico nato mfro ma
surfacean dthe nreplace dit.
Usin gAFM ,i ti spossibl et ovisualiz epolymeri cbiologica lmoleculessuc ha sDN Ao r
cellulos ean deve nt oseeth eindividua lmonomer sand ,a thig hresolution ,eve nth eatom s
o fwhic hthe yarecomposed .
Theatomicforcemicroscopecandetectatomsormoleculesbyscanningasurfaceforshapeorelectromagneticproperties.
VIRU SDETECTIONVI AAF M
Th eAF Mca nb euse dt omonitorfo rth epresenceo f
virusparticles,usin gadeviceknow na sa"ViriChip. "
Asilico nchi pi scoate dwithantibodie sspecifi cfo r
th eviruso finterest.I npractice,severaldifferent
antibodie sareapplie dt oseparateregion so fth e
chip ,thu sallowin gmultiplevirusest ob emonitored
simultaneously .Asingl emicrolitero fliqui dfro m
th esampl et ob eanalyze di sapplie dt oth echip ,an d
an yvirusestha tarerecognize db yth eantibodie sare
boun dt oth echip .Th echi psurfacei sthe nscanne d
b yAF Mt odetectth epresenceo fvirusparticles,which
areidentifie db ythei rlocatio no nth echi p(Fig.7.6).
Th edevic eha sbee nsuccessfull yteste dwitha
varietyo fviruses,includin ghuma npathogens ,bu t
i spresentlystil lunde rdevelopment .I nprinciple ,i t
Probetip
CHAPTER 7
4
shoul db epossibl et omonito rfo rthousand so fdifferentviruseso nasingl echip .Eventually
patient sma yb eteste dfo rmultiplevirusesusin gasingl edro po fblood .
Atomicforcemicroscopycandetectandidentifyindividualviruses.
WEIGHINGSINGL EBACTERI AAN DVIRU SPARTICLE S
I tha sbee nknow nfo rman yyearstha tbacteri aareo nth eorde ro f1000nanometer si n
siz ean d1picogra mi nweight.However,i nadditio nt odetectin gmicroorganismsvi a
nanotechnolog yi ti sno wpossibl et oweighthe mindividually .
Th eoscillatio nfrequenc yo fadivin gboar ddepend so nth emassapplied .Scalin gdown ,i ti s
possibl et oconstruc tacantileve ro fmicrometerdimension s(approximatel y6micronslon g
b y0.5micronwid ewitha nen dplatfor mabou t1micronsquare) .Th eoscillatio nfrequenc y
ca nb emeasuredb yusin galase ran dobservin gth ealteredligh treflection .Additio no fsingl e
bacterialcell so reve nviru sparticleschange sth eoscillatio nfrequenc yo fth ecantilever.Th e
masso fsingl ecell so rviru sparticlesha sbee nmeasuredthi swayi nth elaborator yo fHarol d
Craighea da tCornel lUniversity(Fig .7.7) .
T ohol dth ebacteri ao rvirusesi nplace ,th ecantileve ri scoate dwitha nantibod ytha t
recognize sth emicroorganismt ob eweighed.Asingl ecel lo fEscherichiacoliwas
143 0x73 0nanometer si nsiz ean dweighed66 5femtogram s(66 5x10~
15
grams) .
Viruses(weighin garoun d1femtogram )ca nb edetecte db yreducin gth esiz eo fth e
cantileve ran denclosin gi ti navacuum .B ymid-2005,thi stechniqu eha dbee nrefine d
t oweig hasingl emacromolecule—adouble-strande dDN Ao fapproximatel y150 0bas e
pairs(roughl yth esiz eo fatypica lcodin gsequence) .Futuredevelopment sshoul dallo w
measurementso fsmal lprotein san dothe rmoleculesi nth ezeptogra mrang e(10~
21
grams) .
FIGUR E7. 6
Principleofth e
ViriChip
(Leftpanel)Anoptical
micrographoftheViriChip
platform.Theinse tshows
thearrangementof
antibodyspotsi neach
thre ebytE narray( 3x
3shown).(Rightpanel)
Higherresolutio nimage s
oftwoantibodyspots
(anti-fdandanti-CPV)
obtainedbybrightfield
(top),AFM(middle,
Z=15nm),and
fluorescenc e(bottom)
methods.Thefluorescenc e
stainingusedmouse
anti-CPVandrabbitanti-fd
followe dbyanti-mouse
Ig G(labele dwithAlexa
594—red)andanti-rabbit
Ig G(labele dwith
Cy2—green).Eac himag e
fieldi s60micrometers
square.From:Nettikadan
era/.(2003).Virusparticle
detectionbysolidphase
immunocaptur eand
atomicforc emicroscopy.
BiochemBiophys Res
Commun311,540-545.
Reprintedwithpermission.
Lasermonitoringoftheoscillationofananoscalecantileverallowssinglebacteriaorvirusestobeindividually
weighed.
Nanobiotechnolog y
B)
FIGUR E7.7WeighingaSingleBacterium
(A )Scanningelectronmicrographofcantileveroscillatorwithlengt h6microns,width0.5microns,anda1micronby1micronpaddle.Scalebar
correspondsto2microns.Hie ,B.,etal.,"Virusdetectionusingnanoelectromechanicaldevices,"Appl.Phys.Lett.(2004),Vol.95,pgs.2604-2607.
Copyright2004.ReprintedwithpermissionfromtheAmericanInstituteofPhysics.(B )ScanningEMofasingle£colicellattachedtothecantilever
byantibody.CourtesyofCraigheadgroup,CornellUniversity.Hie ,B.,etal,"Singlecelldetectionwithmicromechanicaloscillators,"J.Vac.Sci.
Technol.B(2001),Vol.19,pgs.2825-2828.Copyright2001.ReprintedwithpermissionfromtheAmericanInstitut eofPhysics.
NANOPARTICLE SAN DTHEI RUSES
Nanotechnolog ybega nwit hadvance si nviewin gan dmeasuringth eincredibl ysmall .
I tthe nmove do nt obuildin gstructure sa tth enanoscale .Simpl enanostructure sare
no wbein guse dfo ravariet yo fanalytica lpurposes ,an dasecon dgeneratio ni sbein g
develope dfo rclinica luse .
Attachedmolecules
Tether
Hydrophiliclayer
Protectivelayer
Physicallyactiveinternallayers
Asthei rnam eindicates ,nanoparticlesare
particleso fsubmicro nscale—i npractice,
fro m100n mdow nt o5n mi nsize .The y
areusuall yspherical ,bu trods ,plates,an d
othe rshape saresometime sused .The y
ma yb esoli do rhollo wan darecompose d
o favarietyo fmaterials,ofte ni nseveral
discretelayer swithseparat efunctions .
Typically,ther ei sacentralfunctiona l
layer,aprotectivelayer,an da noute rlaye r
allowin ginteractio nwithth ebiologica l
world.
FIGUR E7. 8Typical
LayeredStructureof
Nanoparticles
Severallayer ssurround
thephysicallyactivecore.
Chemicalgroupsare
oftenaddedtotheexterior
toallowattachmentof
biologicalmolecules.
Th ecentra lfunctiona llaye rusuall y
display ssom eusefu loptica lo r
magneti cbehavior .Mos tpopula ri s
fluorescence .Th eprotectiv elaye r
shield sth efunctiona llaye rfro m
chemica ldamag eb yair,water,o rcel lcomponent san dconversel yshield sth ecel lfro m
an ytoxi cpropertie so fth echemical scomposin gth efunctiona llayer .Th eoute rlayer(s )
allo wnanoparticle st ob e"biocompatible. "Thi sgenerall yinvolve stw oaspects ,water
solubilit yan dspecifi crecognition .Fo rbiologica luse ,nanoparticle sar eofte nmad e
watersolubl eb yaddin gahydrophili coute rlayer .I naddition ,chemica lgroup smust
b epresen to nth eexterio rt oallo wspecifi cattachmen tt oothe rmolecule so rstructure s
(Fig .7.8) .
CHAPTER 7
Nanoparticleshav eavarietyo fuse si nth ebiologica larena :
(a )Fluorescentlabelin gan doptica lcodin g
(b)Detectiono fpathogeni cmicroorganismsand/o rspecifi cprotein s
(c )Purificationan dmanipulationo fbiologica lcomponent s
(d )Deliveryo fpharmaceutical sand/o rgene s
(e )Tumo rdestructio nb ychemica lo rtherma lmeans
tf)Contrastenhancemen ti nmagneticresonanc eimagin g(MRI )
Nanoparticlesarenowwidelyusedinarangeofbiologicalprocedures.Theseincludebothanalyticaland
clinicalapplications.
NANOPARTICLE SFO RLABELIN G
Conside rluminescen tCdS enanorod sa sa nexampl eo fnanoparticle suse dfo rlabelin g
(Fig .7.9) .Thes enanorod sca nb euse da sfluorescen tlabel sfo rmolecularbiolog ybecaus e
the yabsor bligh tfro mth eU Vt oaroun d55 0n man demi tstrongl ya t59 0nm .The ywere
made—appropriatelyenough—i nth ela bo fThoma sNann ,i nFreiberg,Germany.
Thes enanorod smeasureapproximatel y3n mi nwidt hb y1 0t o2 0n mi nlength .Acor eo f
luminou scadmiu mselenid e(CdSe )i ssurrounde db yashel lo fZn S(zin csulfide ,wurtzite)
t oprotectth ecor eagains toxidation .Outsid ethi si salaye ro fsilica ,whic hallow scouplin g
o fphosphonate so ramine st oth eexterioro fth enanorod .Thes ehydrophili cgroup smak e
th enanorod swatersoluble .Thes eoute rchemica lgroup sals oallo wattachmen to fth e
nanorod st oproteins .
Th escaffol dinsid eeukaryoti ccell si sbuil tfro mcylindrica lprotei nstructuresknow n
a smicrotubules.Thes eareofte ndisassemble dint omonomer s(know na stubulin )an d
10-2 0n m
Silica
Cadmiumselenitic
Zin csulfid e
II
Phosphorat ePhosphorat e
Hydrophili cgroup sattache dt osurfac e
3n m
FIGUR E7. 9CdS e
Nanorods
LuminescentCdS e
nanorodsareencased
i nprotectivelayer sof
zincsulfideandofsilica.
Hydrophilicchemical
groupsontheoutside
allowproteinsorother
biologicalmoleculestobe
attached.
Bo x7. 1Trend yTerminolog y
Nanoparticlesarereferredtobyavarietyofnanoterms,depending
ontheirshapeandstructure.Themeaningsofnanorod,nanocrystal,nanoshell,nanotube,nanowire,andsoforth,shouldbeobvious
enough.And,despitewhatyoumightthink,quantumdotsarenota
newbrandoffrozensnackbutanalternativenameforfluorescent
nanocrystals,smallenoughtoshowquantumconfinementandused
inbiologicallabeling.
Nanobiotechnolog y
reassemble di ndifferentlocations .Nanorod sca nb euse dt ofollo wthi sremodelin gb y
attachin gthe mt oth etubuli nmonomers .O nadditio no fguanosin etriphosphat e(GTP) ,
assembl yo fmicrotubulesi sstimulate dan dth efluorescen tnanorod sca nb esee naggregatin g
int olinea rstructures.
Wh yus eacomple xmultilayerednanostructur einstea do fasimpl efluorescen tdye?
(a )Althoug hnanocrystal shav enarro wemissio npeaks ,the yhav ebroa dabsorptio n
peak s(rathe rtha nnarro wone slik etypica ldyes) .Consequenti ythe yd ono tbleac h
durin gexcitatio nan dca ntherefor eb euse dfo rcontinuou slong-ter mirradiatio nan d
monitoring.
tb)Nanocrystalshav ehig hbrightness—th eproduc to fmola rabsorptivit yan dquantu m
yield .(Molarabsorptivityi sth eabsorbanc eo faon emola rsolutio no fpur esolut e
a tagive nwavelength;th ehighe ri tis ,th emor eligh ti sabsorbed .Th equantumyield
i sth erati oo fphoton sabsorbe dt ophoton semitte ddurin gfluorescence. )
te)Th eemissio nmaximu mo fananocrysta ldepend so nth esiz ean ds oca nb esett oan y
desiredwavelengthb ymakin gcrystalso fth eappropriat esiz e(se elate rdiscussion) .
Nanoparticlesca nals ob etargete dt ospecifi ctissues ,suc ha scance rcells ,b yaddin g
appropriat eantibodie so rrecepto rprotein st oth enanoparticl esurface.Fluorescent
nanoparticle sareofte nknow na squantu mdot san dareno wcommerciall yavailabl efo ra
wid erang eo fbiologica llabeling .Althoug hfluorescen tdye sca nb eattache dt oothe r
molecules,nanoparticle saremor eversatilei nthi sregard .Quantu mdot sca nb euse dt o
labe lDN Amoleculesa swella sproteins .Thu slabelin go fPC Rprimer swit hquantu mdot s
result si nfluorescend ylabele dPC Rproducts— avarian treferredt oa squantum dotPCR.
Avarietyo fmaterialshav ebee nuse dt ogivebettercontrastenhancemen ti nMRI .Nanoparticles
containin gavarietyo fmaterialsarebeginnin gt oseeincreasin gus ei nthi sarea.Forexample ,
superparamagneti ciro noxid e(SPIO )nanoparticlesacta sgoo dMR Icontrastagents.Their
magneticpropertiesvarywithparticlesize.Largerparticles,o fgreatertha n30 0nm ,areuse d
fo rbowel ,liver,an dspleen .Smalle rparticles,o f2 0t o4 0nm ,hav eshow nhighe rdiagnosti c
accuracyfo rdetectingearlytumor si nlymp hnode stha nconventiona lmaterials.
Fluorescentnanoparticlesarewidelyusedinbiologicallabeling.Theylastlongerthantraditionalfluorescent
dyesandareoftenbrighter.
QUANTU MSIZ EEFFECTAN DNANOCRYSTA LCOLORS
Whe nmaterialsaresubdivide dint osufficiend ysmal lfragments ,quantu meffectsbegi nt o
influenc ethei rphysica lproperties.Th efluorescen tnanoparticle sdiscusse dearlierarei nfac t
semiconductorstha taresmal lenoug ht osho wsuc hquantu meffects.
Semiconductor saresubstance stha tconduc telectricit yunde rsom econdition sbu tno t
others .I nN-typesemiconductor s(a si nnorma lelectri cwires)th ecurren tconsist so f
negativel ycharge delectrons .I nP-typesemiconductor sth ecurren tconsist so fholes.
Ahol ei sth eabsenc eo fa nelectro nfro ma natom .Althoug hno tphysica lparticles ,hole s
ca nmov efro mato mt oatom .Electronsan dhole sma ycombin ean dcance lout ,aproces s
tha trelease senergy.Conversely,energ yabsorbe db ycertai nsemiconductor sma ygenerat e
a nelectron-hol epai rwhos etw ocomponent sma ythe nmov eof fi ndifferentdirections .
Nanoparticlelabel sca nb emadewithdifferentemissio nwavelengths,coverin gth eUV ,
visibl espectrum ,an dnearinfrared .Emissio nwavelengthsobviousl yvarydependin go nth e
semiconducto rmaterial.However,i naddition ,th equantu msiz eeffect(Fig .7.10)allow sth e
sam esemiconducto rt oemi ta tdifferentwavelengths,dependin go nth esiz eo fth enanoparticle.
Th esmalle rth enanoparticl eth eshorterth ewavelength(i.e.,th ehighe rth eenergy) .
CHAPTER 7
Fluorescentnanoparticle sma yb eregarde d
a sminiaturizedlight-emittin gdiode s
(LEDs) .Thesearesemiconductor stha t
workb yabsorbin generg y(eithe relectrical
o rlight )an dcreatingelectron-hol epairs.
Whe nth eelectronsan dhole srecombine ,
ligh ti semitted .Forbul kmaterial,th e
energy,an dhenc eth ewavelength,o fth e
emitte dligh tdepend so nth echemica l
compositio no fth esemiconductor .
However,a tnanoscal edimensions ,
quantu meffectsbecom esignificant .
I fth ephysica lsiz eo fth esemiconducto r
i ssmalle rtha nth enaturalradiu s
(th eBohrradius)o fth eelectron-hol e
pair,extraenergyi sneede dt oconfin eth e
electron-hol epair.Thi si sreferredt oa s
quantumconfinementan doccurswith
nanocrystalso faroun d2 0n mo rless .
Th esmalle rth esemiconducto rcrystal,th e
moreenergyi sneede dan dth emoreenergetic
(shorte ri nwavelength)i sth eligh treleased .
il l
^^^^

nirr
Theemissionwavelengthofafluorescentnanoparticledependsonitssizeandmaythereforebeeasily
modifiedbytheexperimenter.
NANOPARTICLE SFO RDELIVER YO FDRUGS,DNA ,O RRN A
Becausenanoparticle sca nb etargete dt ospecifi ctissues ,the yca nb euse dt odeliveravariety
o fbiologicall yactivemolecules,includin gbot hpharmaceutical san dgeneti cengineerin g
constructs .
Largepolymeri cmoleculessuc ha sDN Ama ythemselve sb ecompacte dt ofor m
nanoparticle so faroun d5 0t o20 0n mi nsize .Thi sinvolve sadditio no fpositivel ycharge d
molecules(e.g.,cationi clipids ,polylysine )t oneutraliz eth enegativ echarg eo fth ephosphat e
group so fth enuclei caci dbackbone .Othe rmoleculesma yb eadde dt opromot eselectivit y
fo rcertai ncell so rtissues .
Alternatively,hollo wnanoparticle s(nanoshells)ma yobviousl yb euse dt ocarryother,
smalle rmolecules.Suc hnanoshell smustb emad efro mbiocompatibl ematerialssuc h
a spolyethyleneimin e(PEI )o rchitosan .Th elatte ralternativ eseem spopula ra tpresent,
becaus ei ti sbot hnaturall yderivedan dbiodegradable .Chiti ni sabeta-l,4-linke dpolyme r
o fN-acetyl-D -glucosamine .I ti sfoun di nth ecel lwallso finsect san dfung ian damon g
biopolymer si ssecon donl yi nnatura labundanc et ocellulose .Chitosa ni sderive dfro m
chiti nb yremovin gmosto fth eacetylgroup sb yalkal itreatment .
A ninterestin gapproac htha tcombine stw otrend ytechnologie si susin gnanoshell st ocarry
siRN A(shor tinterferin gRNA) .Deliveryo fsiRN Atrigger sRN Ainterference ,whic hresult si n
th edestructio no ftarge tmRN A(se eChapte r5) .Th esiRN Ama yb etargete dagains tmRN A
fro mgene sexpresse dpreferentiallyi ncance rcell so rgene scharacteristico fcertai nviruses.
FIGUR E7.10
QuantumSizeEffect
Nanocrystalsofdifferent
sizesabsorbUVlightand
re-emittheenergy.The
wavelengthofemission
dependsonthesizeofthe
nanocrystal.Thesmaller
thecrystalthemore
energetictheemission.
From:Riegler,Nann
(2004).Applicationof
luminescen tnanocrystals
aslabel sforbiological
molecules.AnalBioanal
Chem379(7-8),
913-919.Withkind
permissionfromSpringer
ScienceandBusiness
Media.
HollownanoparticlesmaybeusedtodeliverDNA,RNA,orproteins.
Nanobiotechnolog y
NANOPARTICLE SI NCANCERTHERAP Y
I ti spossibl et odestroytumo rcellsb yavarietyo ftoxi cchemical so rlocalize dheating .
I nbot hcasesamajorissu ei sdeliveringth efata lreagen tt oth ecance rcellsan davoidin g
nearb yhealth ytissue .Whe nusin gtoxi cchemica lreagents ,th ereagen tmustb eno tonl y
deliveredspecificall yt oth etarge t
FRE T
t ophotosensitize r  3
o
9
Organicallymodified
silic ananoparticl e
Excite d
dy eaggregate s
MEMBRAN E
DESTRUCTIO N
cellsbu tals opreventedfro m
diffusingou to fth ecance rcells.Bot h
relate dobjectivesma yb eachieve db y
usin ghollo wnanoparticle st ocarry
th ereagent .Nanoparticlesma yb e
targete dt otumor sb yaddin gspecifi c
receptor so rreactiv egroup st oth e
outsid eo fth enanoparticles .These
arechose nt orecogniz eprotein stha t
aresolel yo rpredominand ydisplaye d
o nth esurfaceo fcance rcells.I ti s
hope dtha tsuc hnanoparticle swillb e
safet ogiv eb ymouth .
FIGURE7.i l
Nanoparticlefo r
SingletOxygen
Release
Thenear-infraredlase r
excitesthedyesattached
tothenanoparticle.
Energytransferto
"photosensitizersb yFRE T
(fluorescen tresonanc e
energytransfer)results
i nconversionofnormal
(triplet)oxygentosinglet
oxygen.
Diffusioni smoredifficultt odea lwith,bu tma yb elimite dt osom eexten tb ydesignin g
nanoparticle sfo rslo wreleas eo fth ereagent .Acleveralternativ ei st oproduc eth etoxi c
agen tinsid eth enanoparticl eafteri tha sentere dth ecance rcell .Photodynami ccance r
therap yinvolve sgeneratin gsingle toxyge nb yusin galase rt oirradiat eaphotosensitiv edye.
Th esingle toxyge ni shighl yreactiv ean di nparticulardestroysbiologica lmembranesvi a
oxidatio no flipids .Afterdiffusin gou to fth enanoparticle ,th etoxi coxyge nreact ss ofasttha t
i tneverleave sth ecance rcel l(Fig .7.11).
Nanoparticlesma yals ob euse dt okil lcance rcell sb ylocalize dheating .I non eapproac h
nanoparticle swit hamagneticcor eareused .Analternatin gmagneticfiel di suse dt o
suppl yenerg yan dheat sth enanoparticl et oatemperatur eletha lt omammalia ncells .
Anothe rapproac huse smetalnanoshells .Thes econsis to facore ,ofte nsilica ,surrounde d
b yathi nmetallayer ,suc ha sgold .Varyingth esiz eo fth ecor ean dthicknes so fth emetal
laye rallow ssuc hnanoparticle st ob etune dt oabsor bfro man yregio no fth espectru m
fro mU Vthroug hth evisibl et oth eIR .Becauselivin gtissu eabsorb sleas ti nth enea r
infrared ,th enanoparticle saredesigne dt oabsor bradian tenerg yi nthi sregio no fth e
spectrum .Thi sresult si nexterna lnea rinfrare dbein gspecificall yabsorbe dan dheatin gth e
surroundin gtissue .
Nanoparticlesmaybeusedtokillcancercellsbylocalizedheatingorlocalgenerationofatoxicproduct.
Bo x7. 2Th eNanobacteria—Nanotechnolog yMeet sNanomytholog y
Cryptozoologyisthestudyof"undiscovered"creaturessuchasthe
LochNessmonsterorBigfoot.However,studentsofmicrobiology
nolongerneedtofeelleftout.Thenewfieldofnanocryptobiology
ishere.Itisperhapsnotsurprisingthatsomeinvestigatorsclaimed
tohavediscovered"nanobacteria."Theseweresupposedly100-fold
smallerthantypicalbacteria,yetcapableofgrowthandreplication.
Theywereproposedascausativeagentsintheformationofkidney
stonesandthenlinkedtoheartdiseaseandcancer.Unfortunately,
"nanobacteria"aretoosmalltocontainribosomesorchromosomes,
andithasbecomeclearthattheyaremineralartifacts.Theirsupposedreplicationwasduetothefactthatcertainmineralscanactas
nucleiforfurthercrystallization.Itscarcelyneedsaddingthat"fossilizednanobacteria"havealsobeenseeninmeteoritesfromMars
andhavebeenclaimedasevidenceforlifeonMars.However,simila rmineralstructureshavebeenfoundinbothlunarmeteoritesand
terrestrialrocks.
CHAPTER 7
ASSEMBL YO FNANOCRYSTAL SB YMICROORGANISM S
I tha sbee nknow nfo rman yyearstha tbacteriamayaccumulat eavarietyo fmetallicelement s
an dmaymodifythe mchemically,usuall yb yoxidatio no rreduction .Forexample ,man ybacteria
accumulat eanion so fseleniu mo rtelluriu man dreduc e
the mt oelementa lseleniu mo rtellurium ,whic hi sthe n
depositeda saprecipitateeitheronth ecellsurfaceor
internally .Certainspecieso fth ebacteriu mPseudomonas
tha tliv ei nmetal-contaminatedareasan dth efungu s
Verticilliumca nbot hgeneratesilvernanocrystals.
ProteinVIII
displaying
SLTPLTTSHLRS
Recently,i tha sbee nfoun dtha twhe nEscherichiacoliProteinvin
i sexpose dt ocadmiu mchlorid ean dsodiu msulfide ,
i tprecipitatescadmiu msulfid ea sparticlesi nth e
2 -t o5-n msiz erange .I nothe rwords,bacteri aca n
"biosynthesize "semiconducto rnanocrystals .
Rathermoresophisticate di sth eus eo fphag edispla y
t oselectpeptidescapabl eo forganizin gsemiconducto r
nanowires .Asdescribedi nChapte r9 ,phag edispla yi sa
techniqu etha tallow sth eselectio no fpeptide stha tbin d
an ychose ntarge tmolecule.I nbrief,stretcheso fDN A
encodin galibrar yo fpeptid esequence sareengineere d
int oth egen efo rabacteriophag ecoa tprotein.Th eextra
sequence sareattache da teitherth eCterminu sor
Nterminus ,wherethe yd ono tdisruptnorma l
functionin go fth ecoa tprotein.Whe nth ehybri dprotei n
i sassemble dint oth ephag ecapsid ,th einserte dpeptides
aredisplayedo nth eoutsid eo fth ephag eparticle.
Th elibrar yo fphage si sthe nscreene dagainstatarge t
molecule.Thos ephage stha tbin dth etarge tarekept.
Phag edisplaylibrarie shav ebee nscreenedt ofin dpeptidescapabl eo fbindin gZn So rCd S
nanocrystals.ProteinVIIIo fbacteriophageM1 3wasuse dfo rpeptid einsertion .Forexample ,Zn S
wasboun db yth epeptid eVISNHAGSSRR Lan dCd So nth epeptid eSLTPLTTSHLRS .Because
th ebacteriophagecapsi dcontain sman ycopie so fth ecoa tprotein,th edisplayedpeptidei s
als opresenti nman ycopies.Consequentlya narrayo fnanocrystalsform so nth ephag esurface.
BecauseM1 3i safilamentou sphage,th eresulti sasemiconducto rnanowir e(Fig.7.12).
Nanocrystalsandnanowiresmaybeassembledusingunmodifiedbacteriaorsophisticatedphagedisplay
techniques.
NANOTUBE S
Carbo nnanotubesarecylinder smad eo fpur ecarbo nwit hdiameter so f1t o5 0nanometers .
However,the yma yb eu pt oapproximatel y1 0micrometerslong .Pureelementa lcarbo n
existsa sdiamon do rgraphite .I ndiamond ,eac hcarbo ni scovalentl ylinke dt ofou rother s
formin ga3- Dtetrahedra llattic etha ti sextremel ystrong .I ncontrast,graphit econsist so ffla t
sheet so fcarbo natom stha tfor mahexagona lpattern.I nth esheet so fgraphite,eac hcarbo n
ato mi scovalentl ybonde dt othre eneighbor san dth esheet sca nslid esideway sovereac h
other,becaus ether earen ocovalen tlinkage sbetwee natom si ndifferentsheets .
Tofor mananotube ,asingl eshee to fgraphit ei srolle dint oacylinder .Th esheet sma y
b erolle du pstraigh to ra ta nangl et oth ecarbo nlattic ean dma yb eo fvariou sdiameters .
Dependin go nth ediamete ran dth etorsion ,th enanotub ema yacta sametallicconducto r
o rasemiconductor .No tsurprisingly ,nanotube sareno wfindin gman yuse si nelectronics ,a
topi cbeyon dth escop eo fthi sbook .
Screenphagedisplayfor
CdSbindingpeptide
FIGUR E7.12
NanowireAssembl y
o nBacteriophage
Phagedisplayyielded
engineeredversionsof
theM13coatprotein
(protei nVIII )withinserte d
peptides.Someofthese
arecapableofbinding
CdS.I nthepresenceof
Cd Scrystalsananowire
formsalongthesurfaceof
thebacteriophage.
Nanobiotechnolog y
I nbiotechnology ,nanotube sarejus tbeginnin gt ofin dapplications .Th ecriticalissu ei sattaching
otherbiomolecules ,suc ha senzymes ,hormon ereceptors,o rantibodies,t oth enanotub esurface.
On eide ai st obuil dbiosensorswhereinteractio nof,say,a nantibod ywithitstargetantige nwill
chang eth eelectricalbehavio ro fth enanotub eHencei tshoul dbecom epossiblet ogeneratea n
electricalsigna lo ndetectinghormones ,pathogens,pollutants,an ds oforth.
Amajorproble mi nattachin gprotein si stha tth esurfaceo fcarbo nnanotube si shydrophobic .
On ewayt oattac hbiomolecule si st ofirs tmodifyth esurfaceb yaddin gnonioni cdetergents,
suc ha sTritonX100 .Th ehydrophobi cportio no fth edetergentbind st oth enanotub esurface
an dth ehydrophili cregio nca nb euse dfo rbindin go fproteins.Alternatively,chemica l
reagent sma yb euse dtha treactwithth ecarbo nsurfaceo fth enanotub ean dgeneratesid e
chain scarryingreactiv efunctiona lgroups .Proteinsca nthe nb elinke dcovalend yb yreactio n
withthes e(Fig .7.13) .Creationo fdevicesb ycombinin gbiologica lmoleculeswithnanotube s
i sstilli nitsinfancy ,bu tprogressi nthi sareai slikel yt ob erapid .
Hollownanotubesmaybefabricatedtocarryavarietyofbiologicallyusefulsidechains.
Bo x7. 3Magnetosomes :Natura lBacteria lMagneti cNanoparticle s
Naturallyoccurringmagneticnanoparticlesaremadebymagnetotacticbacteria,suchasMagnetospirillum.Thesemicroorganismscan
detectmagneticfieldsandorientthemselvesinresponse.Theycontainmagnetosomes,consistingofnanosizedcrystalsofmagnetic
ironoxide(magnetite,Fe30)or,les soften,ironsulfide(greigite,FegSJ
insideanenvelopeofprotein.Themagnetosomesarealignedin
chainsalongthecellaxis.Synthesisoftheproteinshellandmineralizationofthemagneticcoreareundergeneticcontrol.Atleastinsome
cases,thegenesresponsibleforthemagnetosomeareclusteredon
thebacterialchromosome.
Itispossibletoattachothermoleculestotheoutsideofmagnetosomesbygeneticallymodifyingproteinsofthemagnetosomeenvelope
(Fig .A).ThegenefortheMms16proteinofMagnetospirillum magneticum
hasbeenfusedtothegenesforluciferas eandthedopaminereceptorin
thela bofDr .TadashiMatsunagaoftheTokyoUniversityofAgriculture
andTechnology.Thefusedproteinsaredisplayedonthesurfaceofthe
magnetosomes.Afterdisruptingthebacterialcells,themagnetosomes
carryingtheattachedproteinscanbepurifiedbymagneticseparation.
Thisshouldalloweasieranalysisofmembrane-boundreceptors,suchas
thosefromthehumannervoussystem,inasimplifiedsystem.
FIGUR EAProteinDisplayo nMagnetosomeMembrane
(A )DisplayofhydrophilicproteinusingMagAasananchor.(B )DisplayoftransmembraneproteinusingMms16asananchor.FromMatsunagaand
Okamura(2003).Genesandproteinsinvolve dinbacterialmagneticparticleformation.TrendsMicrobiol11,536-542.Reprintedwithpermission.
CHAPTER 7
HOOC
JiOO C
HOOC
o
o
H
°I
ANTIBACTERIA LNANOCARPET S
Nanocarpetsareforme db ystackin galarg enumbe ro fnanotube stogether ,withthei r
cylindrica laxesaligne dvertically.Nanocarpetscapabl eo fchangin gcolo ran do fkillin g
bacteri ahav ebee nassemble dfro mspeciall ydesigne dlipid stha tspontaneousl yassembl e
int oavarietyo fnanostructure s
dependin go nth econditions .I nHOOC
water,nanotube sareformed .Partial
Q %
rehydratio no fdrie dnanotube s
generatesaside-by-sid earray—the
nanocarpet .
Th elipi dconsist so falon g
hydrocarbo nchai n(2 5carbons )
withadiacetyleni cgrou pi nth e
middl eo fth echain .Th eindividua l
nanotube sareabou t100n mi n
diamete rb y1000n mi nlength .Th e
wallso fth enanotube sconsis to f
fiv ebilayerso fth elipid .Bot hth e
separat elipi dmoleculesan dth e
assemble dnanocarpe tkil lbacteria.
Lik eothe rlong-chai namin o
compounds ,the yacta sdetergentmoleculesan ddisrup tth ecel lmembrane.Consequently,
th enanocarpe tprovide sasurfac eletha lt obacteria.Thi spropert ycoul db everyusefu li f
nanocarpet sareuse di nbiomedica lapplications .
Diacetyleniccompound shav eth einterestin gabilit yt ochang ecolor .Th enanocarpe tstarts
ou twhite,bu ti fexpose dt oultraviole tlight ,i tturn sdee pblue .LTVirradiatio ncause s
crosslink st ofor mb yreactio nbetwee nacetyleni cgroup so nneighborin gmolecules.
Thi spolymerizatio nstabilize sth enanocarpet .Blu enanocarpet schang ecolo ro nexposur et o
avarietyo freagents .Detergentsan dacid schang ethe mfro mblu et ore do ryellow ,an dth e
presenc eo fbacteria,suc ha sE.coli,givesre dan dpin kshades .Eventuallysuc hmaterialsma y
b euse dbot ha sbiosensor san dfo rprotectio nagains tbacterialcontamination .
Nanotubesmaybeassembledtocreatesurfaces(nanocarpets)thatareantibacterialoractasbiosensors.
DETECTIONO FVIRUSE SB YNANOWIRE S
Nanowiresarewha tthei rnam esuggests .The yhav enanoscal ediameter sbu tma yb eseveral
micronslong .The yma yb emetallican dacta selectricalconductor so rthe yma yb emad e
fro msemiconducto rmaterials.
Biosensorsca nb emad eusin gsilico nsemiconducto rnanowires .Thesema yb ecoate dwith
antibodie stha tbin dt oaspecifi cvirus.Bindin go fth evirust oth eantibod ytrigger sachang ei n
conductanc eo fth enanowire .Forap-typesilico nnanowire ,th econductanc edecreaseswhe n
th esurfacecharg eo nth evirusparticlei spositiveand ,conversely,increase si fth evirussurface
i snegative.Singl evirusesmayb edetectedb ythi sapproac h(Fig .7.14).I ti sals opossibl et o
attac hsingle-strande dDN At oth enanowire .I nthi scase,conductanc echange saretriggere db y
bindin go fth ecomplementar ysingl estrand .Possiblefutur eapplication sinclud ebot hclinica l
testin gan dsensor sfo rmonitoringfood ,water,an dairfo rpubli chealt hand/o rbiodefense .
HOOC
^TJOOH
po^°^NH 3
+
B)
NH S
+
FIGUR E7.13
AttachingOrganic
FunctionalGroupst o
Nanotubes
(A )Carbonnanotubescan•
betreatedwithacidsto
purifythemandgenerate
carboxylicgroups.
(B )Alternatively,the ymay
reactwithaminoacid
derivativesandaldehydes
t oaddmorecomplex
hydrophilicgroupstothe
externalsurface.From:
Bianco,Kostarelos,and
Prato(2005).Applications
ofcarbonnanotubesi n
drugdelivery.CurrOpin
ChemBiolQ,674-679.
Reprintedwithpermission.
Nanowiresensorsarecapableofdetectingspecificindividualviruses.Bindingofavirusparticlechanges
theconductanceofthenanowire.
Nanobiotechnolog y
Time(sec)
FIGUR E7.14NanowireBiosensors
(A )AsinglevirusparticlebindingtoanddetachingfromthesurfaceofaSiNWnanowirecoatedwithantibodyreceptors.Thecorrespondingchanges
i nconductanceareshownforeachstep.(B )Conductanceandopticaldataonadditionofinfluenz aAvirus.(C )Schematicofmultiplexedsingle
virusdetection.Conductanceversustimeisrecordedsimultaneouslyforthreechannelsspecificfordifferentviruses.NW1respond stoinfluenz a
AandNW3toadenovirus.TheNW2channelwasnotusedhere.Blackarrows1-Acorrespondtoadditionofadenovirus,influenz aA,purebuffer,
anda1: 1mixtureofadenovirusplusinfluenz aA.Re dandbluearrowsindicat econductancechangesduetothediffusionofviralparticlespastthe
nanowirewithoutspecificbindingforinfluenz aandadenovirus,respectively .CourtesyofCharlesM.Lieber,HarvardUniversity,Cambridge,MA.
CHAPTER 7
IO NCHANNE LNANOSENSOR S
Somewha tmorecomple xtha nnanotube san dnanowire sare
nanoscaleio nchannelstha tareassemble dint omembranes.
Thes echannel saredesigne ds otha tthe yca nb econtrolle dt opermi t
th emovemen to fion sunde ronl ycertai nconditions .Th eio n
flo wgeneratesa nelectricalcurrenttha ti sdetected,amplified ,an d
displaye db yappropriat eelectroni capparatus .
Io nchannel sca nb euse da sbiosensor sb yattachin gabindin gsitefo r
th etarge tmoleculea tth eentryt oth echannel .Attachedantibodie s
areofte nuse dfo rth ebindin gsitesa sdescribe di nChapte r2 3(se e
Fig.23.16) .Th esimples tarrangemen tresult si nth echanne lbein g
ope ni nth eabsenc eo fth etarge tmoleculean dshu twhe ni ti s
detected.Adro pi nio nflo wtherefor esignal sdetectio no fth etarge t
molecule.
A tpresent,suc hio nchannel sarebein gdevelope dusin gmodified
biologica lcomponents .Th eio nchanne litsel fca nb emad eusin g
th epeptid eantibioti cgramicidi nA(mad eb yth ebacteriu mBacillus
brevis).Thi stransport smonovalentcations ,especiall yproton san d
sodiu mions .Naturalgramicidi nspan shal fo fastandar dbiologica l
membrane.Ashort-live dchanne li sforme dwhe ntw ogramicidi n
moleculeslin eup ,a sshow ni nFig.7.15 .Permanen tchannel sma yb e
mad eb ycovalentl ylinkin gtw ogramicidi nmoleculestogether .U pt o
10
7
ions/secon dflo wthroug hasingl egramicidi nchannel .Thi sgives
apicoamper ecurrenttha ti seasil ymeasured.Analternativ ei st o
monito rachang ei nth ep Hdu et omovemen to fH
+
ions .Thi sma y
b edon eb yusin ga noptica lsenso ran dafluorescen tp Hindicator .
Th echannel saremad eresponsiv eb yattachin ga nappropriat e
ligan dmoleculet oth efron ten do fth egramicidin ,s otha ti t
projectsoutwar dfro mth emembran esurface.Thi sligan di schose n
t obin dth etarge tmoleculean dma yb ea nantige no rothe rsmal l
moleculetha ti srecognize db ya nantibod yo rprotei nreceptor .I ti s
als opossibl et oattac hasingle-strande dsegmen to fDN Atha twillrecogniz ean dbin dth e
complementar ysequence .Thu sbiosensor sma yb edesigne dt orespon dt oth epresenc eo fa
varietyo fbiologica lmolecules.
Th emembran eitsel fma yb ealipi dbilaye rmad eusin gnatura lmembran elipids .Typica l
phospholipid sspa nhal famembran e(i.e. ,on emonolayer),an dth etw omonolayers
ca ntherefor eslid erelativ et oon eanother .Th emembran ema yb estabilize db y
includin glipid stha tspa nth ewhol emembrane .Thes ema yb efoun dnaturall yi ncertai n
archaebacteri ao rthe yma yb esynthesize dartificially .Lipi dbilayer sarerelativel yfragil e
an di npractic emustb eassemble do nsom esoli dsupport .Buildin galong-lastin gan d
stabl emembran estructur eha ss ofa rprove ndifficult,an dpractica lio nchanne lsensor sare
stil lunde rdevelopment .
Io nchannelsensorsoperatebyopeningorclosingthechannelInresponsetobindingaspecificmolecule.
Theymaybeusedtodetectavarietyoftargetmolecules.
NANOENGINEERIN GO FDN A
I n"classical "geneti cengineering ,th esequenc eo fDN Ai sdeliberatel yaltere di nordert o
generatene wcombination so fgeneti cinformation .Evenwhe nmajorrearrangement sare
FIGUR E7.15
Naturalan dModified
GramicidinIo n
Channels
Gramicidinform sa
transchanne lforNa
+
an dK
+
ions .(A )Natural
gramicidinchannels
ar eforme dwhentw o
gramicidinmoleculesalign
withinamembrane.
(B )Tw ogramicidin
monomersjoine dbya
photosensitivelinke r(C) .
Absorptionofligh tchange s
th econformationofthe
N=Nbond(red )ofme
linke rfromcistotrans
andopen sorclosesth e
channel.(D )Channels
ar eopene dorclosedby
blockinggroups(blu e
circles)attachedby
photosensitivelinker st o
eac hgramicidinmonomer.
Nanobiotechnolog y
A )
II
GCACGAG T
CGTGCTC A
B)
TGATACC G
ACTATGG C
7"
IV
III
x
JL _
Y
FIGUR E7.16
BranchedDN Afro m
FourSingleStrands
(A )AbranchedDN A
moleculewithfourarms.
Fou rdifferentcolor-coded
strandscombineto
producefourarms
(1,11 ,III ,andIV) .The
branchpointofthis
moleculei sfixed.
(B )Formationofatwodimensionallatticefrom
afour-armjunctionwith
stickyends.XandYare
stickyends,andX'and
Y'aretheircomplements.
Fou rmonomersare
complexedi nparallel
orientationtoyield
thelatticestructure.
DN Aligas ecanseal
thenickslef tinthe
lattice.From :Seema n
(1999) .DN Aengineerin g
andit sapplicationto
nanotechnology.Trends
BiotechnolM,437.
Reprintedwithpermission.
made,i nordert ofunctio na sgeneti cinformation ,th eDN A
mustremai na sabase-paireddouble-strande dheli xwith
a noveralllinea rstructure.
I nnanoengineering ,th eobjectiv ei st omak estructures
usin gDN Amerelya sastructura lelement ,rathe rtha n
t omanipulategeneti cinformation .DN Ai sattractive
becaus eth edoubl eheli xi saconvenien tstructura lmodule.
Moreover,itsnatura lbase-pairin gpropertiesca nb euse dt o
lin kseparat eDN Amoleculestogether .However,acritical
requiremen tfo rassemblin g3 Dstructuresi sbranche d
DNA .Althoug hbranche dstructuresd ofor mi nbiologica l
situation s(especiall yth eHollida yjunctio ninvolve d
i ncrossin goverdurin grecombination) ,the yareno t
permanen to rstable .
Cross-shapedDN Aca nb egeneratedb ymixingfou r
carefull ydesigne dsingl estrand swithdifferentsequences .
Eac hstran dbase-pairswithtw oo fth eothe rstrand sover
hal fit slengt h(Fig .7.16) .I fstick yend sareinclude di nth e
initia lstrands ,i ti spossibl et olin kth ecrossestogethe rint o
atwo-dimensiona lmatrix.Th enick sca nb eseale db yDN A
ligas ei fdesired.Th eprinciple suse di nbranchin gca nb e
extende dt othre edimensions ,an di ti spossibl et obuil d
cubica lDN Alattices .
Th eDN Adoubl eheli xi sabou t2n mwid ewit hahelica l
pitc ho fabou t3.5nm .Henc ei tca nb euse dt obuil d
nanoscal eframeworks .Thes eca nb euse dfo rth eassembl y
o fothe rcomponents ,suc ha smetallicnanowire so rnanocircuits .Not etha twhil eDN A
i sflexibl eoverlonge rdistances ,i ti srelativel yrigi dovernanoscal elengths ,u pt oabou t
5 0nm .
Suc hcross-shape dDN Amolecules(an dth e3 Dcounterparts )hav eth edrawbac ktha tth e
junction sareflexibl ean dd ono tmaintai nrigi d90-degre eangles .Rigi dDN Acomponent s
hav ebee nmad eb yusin gdoubl ecrossove r(DX )DN Amolecules.Tw oisomer so f
antiparalle lD XDN Aexist,wit ha nod d(DAO )o reve n(DAE )numbe ro fhalf-turn s
betwee nth ecrossove rpoint s(Fig .7.17) .(Doubl ecrossove rmoleculeswit hparalle lstrand s
als oexist,bu tbehav epoorl yfro mastructura lviewpoint. )DA Eo rDA Ounit sca nb e
assemble dint oarigi darrayb yprovidin gappropriat estick yends .I ti spossibl et oreplac e
th ecentral ,shor tDN Astran do fth eDA Estructur ewit halonge rprotrudin gstran do fDN A
(DAE+J) .Thi sallow sassembl yo fbranche dstructures .
Whati sth epurpos eo fbuildin garraysan d3 Dstructuresfro mDNA ?Perhapsth emost
plausibl eus esuggeste ds ofari st ous eth eDN Aa sth eframewor kfo rassemblin gnanoscal e
electroni ccircuits.S ofar,normal ,unbranche dDN Aha sbee nuse da sascaffol dt ocreate
linea rmetallicnanowires .Variousmetals(gold ,silver,copper ,palladium ,platinum )hav e
bee nuse dt ocoa tth eDNA ,an ddiameter srang efro m100n mdow nt o3nm .Eventually,
i tshoul db epossibl et opu ttogethe rthes etw oapproache san dbuil dcircuitsfro mmetalcovere d3 DDN Astructures.
DNAmaybeviewedsolelyasastructuralmolecule.Three-dimensionalframeworksmaybebuiltfrom
DNAwhosesequenceisdesignedtogeneratebranchedstructures.SuchDNAstructuresmaybeusedas
nanoscalescaffoldsformetallicnanowiresandcircuits.
CHAPTER 7
A )
DAE
B)
DN AMECHANICA LNANODEVICE S
Arathermorefuturisticus efo r3- DDN Astructuresi sa s
framework sfo rmechanicalnanodevices .Th eessential
component saresom esorto fmovingparts.Several
experimenta lprototype"DN Amachines"havebee n
designe do rconstructedtha tillustrat eth econcept .These
allinvolv ereversiblechange si nconformatio no faDN A
structuredrivenb ychange si nbase-pairing.Suc hchange s
mayb ecause deitherb ychangin gth ephysicalcondition s
(heat,salt,etc.)o rb yaddin gsegment so fsingle-strande d
DN A(ssDNA )tha tbase-pairt osom eregio no fth eDN A
machine,a sillustrate di nFig.7.18.I fssDN Ai sused,the n
anothe rsingl estrand,complementar yt oth efirsti sadde dt o
convertth emachinebac kt oitsoriginalconformation .
Th eresulti samechanicalcycletha tcoul di nprinciple
b euse dt operformsom esorto ftask.Th etw ossDN A
moleculesmayb eregarde da s"fuel,"an dth efina lwaste
produc ti sadouble-strandedDN Aconsistin go fth etw o
pairedssDN Afuelelements .(Not etha tthi sschem edoe sno t
involv ebreakin gcovalen tchemica lbonds .I ti sthu sno ta n
enzymati creactio nan di sdistinctfro mth euseo fDN A
a sadeoxyribozym ea sdescribedi nChapter5.)
DNAhasbeenproposedasaframeworkfornanomachines.Proof-of-conceptprototypeshavebeen
constructed.
DAE+J
»j~m
FIGUR E7.17Rigid
DN ANanomodules
Arraysmaybeassembled
fromdouble-crossover(DX )
molecules.(A )DA Eand
DA Oaretw oanti-parallel
DXisomers .DAE+Ji sa
DA Emoleculei nwhichan
extrajunctionreplace sthe
nicki nthegreenstrandof
DAE .(B )Two-dimensional
arrayderivedfromDX
molecules.Complementary
stickyendsaredepicted
bycomplementary
geometricalshapes.Aisa
conventionalDXmolecule
butB*i saDX+Jmolecule
withaverticallyprotruding
DN Ahairpin(blac kcircle).
From:Seeman(1999).
DN Aengineering
anditsapplicationto
nanotechnology.Trends
BiotechnoiW,437.
Reprintedwithpermission.
TT
FIGUR E7.18PrototypeDN AMachine
ADN AnanomotordesignedbyJ.J.LiandW.Tan.SuccessiveadditionofthecomplementaryDN Astrandslabele d
alphaandbetacausesachangei nconformation.TheDN Ananomotoralternatesbetweenafoldedquadruplex
structureandadouble-strandedstructure.Thenanomotorexpandsandcontractsinawormlikemotion.From:It oand
Fukusaki(2004).DN Aasananomaterial.JMolCatalysisB:Enzymatic28,155-166.Reprintedwithpermission.
Nanobiotechnolog y
CONTROLLE DDENATURATIO NO FDN AB Y
GOLDNANOPARTICLE S
DN Ahybridizatio ni swidelyuse dt odetect1
clinica ldiagnosis .Beforehybridizatio nca ni
FIGUR E7.19
ControllingDN A
Denaturationb yGold
Nanoparticles
On estrandofDN Ahas
agoldnanoparticle(Au )
attachedtooneend
andafluorescentdy e
(F )attheotherend.The
complementarystrand
hasabiotintag(B )at
oneend.Thebiotini s
boundbystreptavidin
andthereforebinds
theDN Astrandt oan
agarosebead.Whenthe
goldabsorbsenergy,i t
meltsthetwostrands
ofDNA.TheDN Astrand
withthefluorescent
dyei sreleasedint o
thesupernatantandit s
fluorescencei smonitored.
:targe tsequences ,bot hi nth elaborator yan di n
Loccur,th eDN Adoubl eheli xmustb edenature d
int osingl estrands .Thi si saccomplishe db yth eheatin go fbul kDNA .However,newl y
emergin gnanotechnolog yma yallo w
specifi cindividua lDN Amoleculest ob e
dissociate dwhe nrequired .
Nanoparticleso fabou t1.4nman d
containin gfewertha n100atom so fgol dare
attachedt odouble-strandedDNA .When
th estructurei sexpose dt oradi owaves
(generate db ya nalternatingmagneticfield) ,
th egol dactsa sa nantenna .I tabsorbsenergy
an dheatsth eDN Amoleculet owhichi ti s
attached.Thismeltsth eDN Adoubl eheli x
an dconvertsi tt osingl estrands.Heating
extendsoverazon eo fabou t1 0n ms o
surroundin gmoleculesareunaffected.Th e
heati sdissipatedi nlesstha n5 0picoseconds,
s oth eDN Amayb erapidl yswitche dbetween
th edouble -an dsingle-strandedstatesb y
turnin gth emagneticfiel do nan doff.Th e
proceduremayb eapplie dt odsDN Amadeo f
tw oseparatesingl estrands(Fig.7.19)ort o
stem-and-loo pstructuresforme db yfoldin g
fro masingl estrando fDNA .
Practicalapplication sareseveralyears
away.However,becaus eradi owaves
penetratelivin gtissu everyeffectively,i tma yeventuall yb epossibl et ocontro lth ebehavio r
o findividua lDN Amoleculesfro moutsid ea norganism .Metalantenna so fdifferent
materialso rsize scoul db euse dt otun edifferentDN Amoleculest oradi owaveso fdifferent
frequencies.
AttachmentofametallicantennaallowsDNAtobemeltedintosinglestrandsbyradiowaves.Itmight
eventuallybepossibletocontrolthebehaviorofDNAfromoutsideanorganism.
CONTROLLE DCHANGEO FPROTEI NSHAP EB YDN A
Allostericproteinschang eshap ei nrespons et oth ebindin go fsigna lmolecules(allosteri c
effectors)a taspecifi csite.Th eessenceo fallostericcontro li stha tth eshap echang ei s
transmitte dthroug hth eprotei nan daffectsth econformatio no fdistantregion so fth eprotein.
I nallostericenzymes ,bindin go fa nallostericeffectora tadistantsitealtersth econformatio n
o fth eactivesitean dmaychang eitsaffinityfo rth esubstrate.I nthi sway,som eenzyme sare
switche do nan dof fi nrespons et osigna lmolecules.Forexample ,phosphofructokinas ei s
switche do nb yth ebuildu po fAMP ,whic hsignal stha tenergyi si nshor tsupply .Th erespons e
increase sflo wint oth eglycolyticpathway.Similarly,man yDN Abindin gproteins,suc ha s
repressorsan dactivators,als ochang eshap eo nbindin gsmal lsigna lmolecules.
I ti spossibl et ochang eth eshap eo faprotei nartificiallyb ymechanicalforce .Thi sha sbee n
demonstrate db yattachin gasingle-strande d60-bas esegmen to fDN Abetwee nth etw opole s
o faprotein .Attachingth eDN Arequire schemica l"handles. "Thes eareengineere dint oth e
CHAPTER 7
FIGUR E7.2 0ControllingProteinShapeb yDN A
Protein-ssDNAchimeraforguanylatekinasefromMycobacteriumtuberculosis(PD Bstructure1S4Q).Thepurpleattachmentpointsforthe
molecularspringcorrespondtomutationsThr75->Cy sandArg171->Cys.(A )Unstretched—asinglestrandofDN Aisattachedtotheprotein.
(B )Theproteini sstretchedbyadditionofthecomplementaryDN Astrand(purple) .CourtesyofGiovanniZocchi.
targe tprotei nb yreplacin gamin oacid sa tappropriat eposition swithcysteine.Th ereactiv e
S Hgrou pi sthe nuse dt ochemicall yattac hth eDNA .
Double-helicalDN Ai smuc hmorerigi dtha nssDNA .Consequendy ,th eadditio no f
th ecomplementar ystran dgeneratestensio na si tbind san dcreatesadoubl ehelix .Thi s
approac hha ss ofarbee ndemonstrate di nth elaborator yo fGiovann iZocch ia tUCL Awith
maltosebindin gprotei nan da nenzyme ,guanylat ekinase .Whe nmaltosebindin gprotei n
i sstretched ,it sbindin gsit efo rmaltoseopen swidertha noptimu man dth eaffinityfo rth e
suga rdecreases.Forguanylat ekinas e(Fig .7.20) ,applyin gtensio ndecreasesenzym eactivity
b ylowerin gaffinityfo rsubstrat ebinding .I nthi scasereleasin gth etensio nb yaddin gDNas e
t odigestth eDN Aswitche sth eenzym eo nagain .
Potentia lapplication sarealon gwayi nth efuture .However,i ti spossibl et oimagin e
biosensor stha tdetectDN Asequence sbase do nthi smechanism.I naddition ,i tmightb e
possibl et oexternall ycontro lenzyme so rothe rprotein sb yaddin gappropriat essDN A
(or,o fcourse,RNA) .
Theshapeofaproteinmaybechangedartificiallybyapplyingforce.Thismaybedemonstratedbyattaching
DNAstrandstotheprotein.Whensingle-strandedDNApairswithitscomplementarystrand,thisgenerates
tensionandstretchestheprotein.
BIOMOLECULA RMOTOR S
Amajorai mo fnanotechnolog yi st odevelo pmolecular-scalemachinerytha tca ncarry
ou tth eprogramme dsynthesi s(o rrearrangement )o fsingl emolecules(o reve natoms) ,
o rothe rsimila rnanoscal etasks .Th eter m(nano )assemble rreferst oananomachin e
tha tca nbuil dnanoscal estructures ,molecul eb ymolecul eo rato mb yatom .An dth e
ter m(nano) replicato rreferst oananomachin eabl et obuil dcopie so fitsel fwhe n
provide dwit hra wmaterialsan denergy.This ,o fcourse ,sound sremarkabl ylik ea
livin gcell .Indeed ,th eorganelle so flivin gcell sma yb eregarde da snanomachine s
Nanobiotechnolog y
Microtubule
FIGUR E7.21Kinesin
LinearMotoro n
Microtubules
Kinesinconsistsofligh t
andheav ychains.Theligh t
chainsbindst okinesin
receptor sonvesiclesthat
aret obetransported.The
heav ychainseachinclud e
motordomainsthatus e
AT Pasenergyt omove
kinesinplustheattached
cargoalongthesurfaceof
amicrotubule.
an dhav eprovide dbot h
inspiratio nan dcomponent sfo r
nanotechnologists .
T ooperate,nanomachine s
willnee denergy,whic hwill
b eprovide db y"molecula r
motors."Atpresentsuc hdevices
arestil li ndevelopment .I tha s
bee nsuggeste dtha tbiologica l
structuresmightb euse dfo r
thi spurpose .Example sinclud e
th eAT Psynthase ,th eflagella r
moto ro fbacterialcells,variou s
enzyme stha tmov ealon gDN A
o rRNA ,an dassortedmoto r
protein so feukaryoti ccells .
Severalo fthes esystem sare
presentlybein ginvestigate d
i nth ehop eo fmakin gusabl e
nanodevice stha tca nb e
couple dt onanomachine st o
provid eenerg yand/o rmovin g
parts.
Th eAT Psynthas ei sarotar ymotor
whos enaturalrol ei st ogenerateATP.I ti sembedde di nth emitochondrialmembranean d
usesenerg yfro mth eproto nmotiveforce .Th eATPsynthas etake sthre estepst ocomplet eeac h
rotation ,an da teac hste pi tmakesa nATP.Forus ei nnanotechnology ,th eF lsubuni twoul d
b edetache dfro mth emembranean dru ni nreverse(i.e.,i twoul db egive nATPa sfue land ,
fro mabiologica lperspective,rotat ebackwards) .
Kinesinan ddynei naremoto rprotein stha tus eAT Pa senerg yt omov ealon gth e
microtubuleso feukaryoti ccells .The ytherefor eacta slinea rste pmotors(Fig .7.21).Their
natura lrol ei st otranspor tmaterial.Kinesinmovescarg ofro mth ecente rt oth eperipher yo f
th ecell ,whereasdynei ncarriescarg ofro mth eperipher yt oth ecenter.Kinesintake ssteps
o f8nanometer san dca nmov ea t100step spe rsecon d(approximatel y3mm/hour!) .Eac h
ste pconsume son eAT Pfo renergy.Th emicrotubulesthe yus ea strack sareprotei ncylinder s
witha noutsid ediamete ro f3 0nm .
Bo x7. 4Fro mMerel yMicr ot oTrul yNano :Lab-in-a-Cel l
Microfluidics(sometimesknownas"lab-on-a-chip")refersto
themanipulationofliquidsamplesatthescaleofmicrometers.
Microfluidicdevicesareavailabletodayandareusedtoprocess
largenumbersofsmallsamples.ApplicationsincludeDNAorprotein
analysisofbloodsamples.Thevolumesinvolvedareusuallyinthe
microliterrange,thoughsomemicrofluidicsdevicescanusevolumes
les sthan1microliter,thatis,nanolitervolumes.Youmightthinkthat
thisentitlesthemtoberegardedasnanotechnology,butremember
thatthedimensionsofvolumearethecubesoflinearmeasure.Thus
acubewithsidesof1micrometer(10
- 6
m)hasavolumeof10
_1B
cubic
metersor10~
15
liters(onefemtoliter).Ananoliter(10~
3
liters)isthevolumeofacubewithsidesof100micrometers.Sohandlingnanoliters
isnotnanotechnology!
Futureprospectsarescalingdownliquidsampleprocessingto
truenanoscale—"lab-in-a-cell."Thiswouldinvolveamicrochipplatformthatusesmodifiedsinglecellsasanalyticaldevices.Thisisstillin
theconceptualstage,butgiventherapidprogressinnanotechnology,
itmaynotbesofarinthefuture.
+ نوشته شده در  سه شنبه پنجم فروردین 1393ساعت 21:21  توسط کوروش  | 

موج

  • امواج غیر مکانیکی: این امواج برای انتشار خود به محیط مادی نیاز ندارند و در خلا نیز منتشر می‌شوند. از جمله این امواج می‌توان به امواج الکترومغناطیسی ، امواج رادیو و تلویزیون ، امواج فرابنفش ، امواج نوری ، امواج ماکروویو اشاره کرد.
موج مادی: در مکانیک کوانتومی به هر ذره مادی یک موج نسبت می‌دهند. به عبارت دیگر برای هر ذره ماده دو گونه طبیعت در نظر گرفته می‌شود. طبیعت موجی و طبیعت ذره‌ای. این دو حالت هیچ وقت بطور همزمان در نظر گرفته نمی‌شود. یعنی امکان ندارد در یک پدیده هم حالت موجی و هم حالت ذره‌ای در مورد یک ذره در نظر گرفته شود.
+ نوشته شده در  دوشنبه سیزدهم آبان 1392ساعت 20:23  توسط کوروش  | 

موج

  • امواج غیر مکانیکی: این امواج برای انتشار خود به محیط مادی نیاز ندارند و در خلا نیز منتشر می‌شوند. از جمله این امواج می‌توان به امواج الکترومغناطیسی ، امواج رادیو و تلویزیون ، امواج فرابنفش ، امواج نوری ، امواج ماکروویو اشاره کرد.
موج مادی: در مکانیک کوانتومی به هر ذره مادی یک موج نسبت می‌دهند. به عبارت دیگر برای هر ذره ماده دو گونه طبیعت در نظر گرفته می‌شود. طبیعت موجی و طبیعت ذره‌ای. این دو حالت هیچ وقت بطور همزمان در نظر گرفته نمی‌شود. یعنی امکان ندارد در یک پدیده هم حالت موجی و هم حالت ذره‌ای در مورد یک ذره در نظر گرفته شود.
+ نوشته شده در  دوشنبه سیزدهم آبان 1392ساعت 20:23  توسط کوروش  |