表面增强拉曼光谱生物成像技术及其应用-周明辉

65201310ChineseOpticsVol．6No．5Oct．20132013-09-122013-10-13No．21006079No．201261011100171674-2915201305-0633-1012113*11．7100692．7100693．710069。、。、。拉曼散射;表面增强拉曼光谱;生物成像;生物医学O657．37Q-334Adoi10．3788/CO．20130605．0633Bioimagingtechnologiesbasedonsurface-enhancedＲamanspectroscopyandtheirapplicationsZHOUMing-hui1LIAOChun-yan2ＲENZhao-yu1FANHai-ming13*BAIJin-tao11．InstituteofPhotonics＆Photon-technologyNorthwestUniversityXi'an710069China2．PhysicsDepartmentNorthwestUniversityXi'an710069China3．SchoolofChemicalEngineeringNorthwestUniversityXi'an710069China*[e-mail]echnologybasedontheSurface-enhancedＲamanSpectroscopySEＲShase-mergedasapotentialalternativeduetoitsnarrowbandwidthweakbackgroundinterferencehighstabilityoflabelagentandspecificity．Ｒamanimagingtechniquecannotonlyanalyzeasinglepointofthesamplebutalsoofferanintegraldescriptionofingredientdistributionandvariationforalargescaleselectedregion．ThispaperintroducestheprincipleofsurfaceenhancedＲamanscatteringanditsenhancementmechanism．ThenitreviewstherecentdevelopmentofSEＲSbasedbioimagingwherebothnon-labeledandlabelledSEＲSima-gingtechniquesareincludedanddescribesitsapplicationstothebiomedicine．FinallyitdiscussessomeproblemsexistedinthecurrenttechnologyandpointsoutthefuturedevelopingtrendsoftheSEＲS-basedbio-imaging．KeywordsＲamanscatteringsurface-enhancedＲamanspectroscopybioimagingbiomedicine1引言ＲamanScattering。C．V．Ｒaman19281。。“”。。。。。、、、、、、。ＲamanImagingＲamanMapping。、、。、。Surface-enhancedＲamanSpectroscopySEＲS。SEＲSSEＲS、。2SEＲS的原理1。。1hν0hν0－Δνhν0+Δν2。1Fig．1SimplifiedenergyleveldiagramofＲamanscat-teringFleischmann1974104～1063。Fleischmann。1977D．L．Jeanmaire4M．G．Albrecht5436610105～106Fleischmann。SEＲSSEＲS。SEＲS31ImageFieldEffect。2LightningＲodEffect“”。“”6。“”SEＲS。3SurfacePlasmaＲesonance。。SEＲS。104～10106。SEＲS。71028。SEＲS。P．S．KumarSEＲS。SEＲSλinλout。SEＲSSEＲS=∫surfaced2sΓλinΓλoutAΓ0λinΓ0λout1AΓλΓ0λ。21＞700nm500nm1089。2Fig．2LeftcalculatedＲamanenhancementinatwo-tipgoldparticleinair．Ｒightscatteringcrosssec-tionofthesameparticle．TheparticleshapeandgeometricalparametersareshownintheinsetsSEＲS“”、。SEＲSSEＲS。3103。SEＲSSEＲSSEＲSSEＲS、、、、5365SEＲSSEＲSSEＲS2。3Fig．3Calculatedelectromagneticfieldintensitiesfordifferentmetalnanoparticleshapesanddimersatlocalizedsurfaceplasmonresonancewave-lengths3SEＲS在生物成像中的应用3．1SEＲS。、。、、。SEＲS。SEＲSSEＲS。SEＲS。SEＲS101411SEＲSSEＲS、SEＲSSEＲS。SEＲS。SEＲS。SEＲS。10－15mol。SEＲS12。4SEＲSFig．4SchematicdiagramoflabeledSEＲSimaging6366SEＲS13。SEＲS4SEＲS、SEＲS。5SEＲSMCF-7SEＲS。ab785nmSEＲS。bSEＲS。5MCF-7SEＲSFig．5MicroscopeandSEＲSimagesofMCF-7breastcancercellSEＲS。、。1s60×60pixel60×60=3600s=1hCCD。SEＲS。5ms。14-19。。。SEＲS、。3．2SEＲS。SEＲS“”SEＲS。SEＲS6SEＲSFig．6SchematicdiagramoftheintegratedmicrofluidicchipoflabelfreeSEＲSimagingandthebiomo-lecularSEＲSimagingsystem736520-21。G．L．Liu22SEＲS。PDMSPDMS6SEＲS。6SEＲS。3．3SEＲS。。。SEＲS、。Manfait1990SEＲS23-24。Efrima、25。C．D．Syme264-4-MBASEＲS。7SEＲS。SEＲS。、。74-MBASEＲSFig．7Time-courseSEＲSmappingofatrappedlivecellcontaining4-MBA-coatednanoparticlestrappedonamicrofluidicdeviceSEＲS、、、。K．V．Kong27SEＲSSEＲS。SEＲS。10－7m。28。3．429。8366。30。SEＲS。SEＲS31-35。SEＲS33'-DTTCiSEＲSXimeiQian341～2cm。DTTCiSEＲS36-37。A．Samanta3880SEＲSSEＲSDTTCi。SEＲSSEＲSSEＲSSEＲS39-40。SEＲS。SEＲS。SEＲS。41。1nm42SEＲS。SEＲS。C．L．ZavaletaSEＲS。10SEＲSSEＲS831。810SEＲSSEＲSFig．8ASEＲSmapingof10differentSEＲSnanotagsinjectedsubcutaneouslyinanudemouseSEＲS、、。K．K．MaitiCyNAMLA-381Cy7LA9SEＲSaCyNAMLA-381523cm－1bCy7LA503cm－1cCy7．5LA586cm－1Fig．9MultiplexSEＲSmappingimagesLeftcolumnfromliversiteandrightcolumnfromtumorsiteamappingcorrespondingtopeak523cm－1forCyNAMLA-381bmappingcorrespondingtopeak503cm－1forCy7LAandcmappingcorrespondingtopeak586cm－1forCy7．5LA9365Cy7．5LASEＲS。CyNAMLA-381Cy7LASEＲSEGFＲCy7．5LASEＲSEGFＲ。3OSCCSEＲS9。CyNAMLA-381Cy7LASEＲSOSCC3SEＲS。SEＲS8。SEＲS43。SEＲS。4结束语SEＲSSEＲS。SEＲS、。SEＲS、、、、、、。SEＲS、SEＲS。SEＲS。［1］ＲAMANCV，KＲISHMANKS．Anewtypeofsecondaryradiation［J］．Nature，1928，121:501-502．［2］段建民．D．2009．DUANJM．StudiesonlocalizedelectromagneticenhancementofmetallicnanoparticlebynumericalsimulationD．DalianDalianUniversityofTechnology2009．inChinese3FLEISHMANNIMHENDＲAJPMCQUILLIANAJ．ＲamanspectraofpyridineadsorbedatasilverelectrodeJ．Chen．Phys．Lett．1974262163-166．4JEANMAIＲEDLVANDUYNEＲP．SurfaceramanspectroelectrochemistryPartⅠ．Heterocyclicaromaticandali-phaticaminesadsorbedontheanodizedsilverelectrodeJ．J．Electroanal．Chem．Inter．Electro．19778411-20．5ALBＲECHTMGCＲEIGHTONJA．AnomalouslyintenseＲamanspectraofpyridineatasilverelectrodeJ．J．Am．Chem．Soc．197799155215-5217．6MOSKOVITSM．Surface-enhancedspectroscopyJ．Ｒev．Mod．Phys．198557783-826．7LIANGEJKIEFEＲW．ChemicaleffectofSEＲSwithnear-infraredexcitationJ．J．ＲamanSpectroscopy199627879-885．8ADＲIANFJ．Chargetransfereffectsinsurface-enhancedＲamanscatteringJ．J．Chem．Phys．198277115302-5315．9KUMAＲPSPASTOＲIZA-SANTOSIＲODＲIGUEZ-GONZALEZBetal．．High-yieldsynthesisandopticalresponseofgoldnanostarsJ．Nanotechnology200819015606．10STOEＲZINGEＲKALINJYODOMTW．NanoparticleSEＲSsubstrateswith3DＲaman-activevolumesJ．Chem．Sci．201121435-1439．11KNEIPPKWANGYKNEIPPHetal．．SinglemoleculedetectionusingSurface-EnhancedＲamanSca