Skip to main content

Advertisement

Log in

Surface enhanced Raman spectroscopy and its application to molecular and cellular analysis

  • Review
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

In this paper, we review the state-of-the-art in surface-enhanced Raman scattering (SERS) based optical detection techniques with an application focus on cancer diagnostics. As we describe herein, SERS has several analytical, biological and engineering advantages over other methods including extremely high sensitivity, inherent molecular specificity of unlabeled targets, and narrow spectral bands. We review advances in both in vitro and in vivo applications of SERS and examine how technical issues with the technology are being addressed. A special technology focus is given to emerging optofluidic devices which aim to merge microfluidic and optical detection technologies into simple packages. We conclude with a brief discussion of some of the emerging challenges in the field and some of the approaches that are likely to enhance their application.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Abu-Hatab NA, John JF, Oran JM, Sepaniak MJ (2007) Multiplexed microfluidic surface-enhanced Raman spectroscopy. Appl Spectrosc 61(10):1116–1122

    Article  Google Scholar 

  • Allain LR, Vo-Dinh T (2002) Surface-enhanced Raman scattering detection of the breast cancer susceptibility gene BRCA1 using a silver-coated microarray platform. Anal Chim Acta 469(1):149–154

    Article  Google Scholar 

  • Arlett JL, Maloney JR, Gudlewski B, Muluneh M, Roukes ML (2006) Self-sensing micro- and nanocantilevers with attonewton-scale force resolution. Nano Lett 6(5):1000–1006

    Article  Google Scholar 

  • Breuzard G, Angiboust JF, Jeannesson P, Manfait M, Millot JM (2004) Surface-enhanced Raman scattering reveals adsorption of mitoxantrone on plasma membrane of living cells. Biochem Biophys Res Commun 320(2):615–621

    Article  Google Scholar 

  • Brolo AG, Arctander E, Gordon R, Leathem B, Kavanagh KL (2004) Nanohole-enhanced Raman scattering. Nano Lett 4(10):2015–2018

    Article  Google Scholar 

  • Brus L (2008) Noble metal nanocrystals: plasmon electron transfer photochemistry and single-molecule Raman spectroscopy. Acc Chem Res (in press)

  • Campagnolo C, Meyers KJ, Ryan T, Atkinson RC, Chen YT, Scanlan MJ, Ritter G, Old LJ, Batt CA (2004) Real-time, label-free monitoring of tumor antigen and serum antibody interactions. J Biochem Biophys Methods 61(3):283–298

    Article  Google Scholar 

  • Cao YC, Jin R, Mirkin CA (2002) Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science 297(5586):1536–1540

    Article  Google Scholar 

  • Chen L, Choo J (2008) Recent advances in surface-enhanced Raman scattering detection technology for microfluidic chips. Electrophoresis 29(9):1815–1828

    Article  Google Scholar 

  • Cheng IF, Chang H-C, Hou D, Chang H-C (2007) An integrated dielectrophoretic chip for continuous bioparticle filtering, focusing, sorting, trapping, and detecting. Biomicrofluidics 1(2):021503–021515

    Article  Google Scholar 

  • Chithrani BD, Ghazani AA, Chan WCW (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6(4):662–668

    Article  Google Scholar 

  • Culha M, Stokes D, Allain LR, Vo-Dinh T (2003) Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics. Anal Chem 75(22):6196–6201

    Article  Google Scholar 

  • Demming AL, Festy F, Richards D (2005) Plasmon resonances on metal tips: understanding tip-enhanced Raman scattering. J Chem Phys 122(18):184716

    Article  Google Scholar 

  • Dick LA, McFarland AD, Haynes CL, Van Duyne RP (2002) Metal film over nanosphere (MFON) electrodes for surface-enhanced Raman spectroscopy (SERS): improvements in surface nanostructure stability and suppression of irreversible loss. J Phys Chem B 106(4):853–860

    Article  Google Scholar 

  • Docherty FT, Monaghan PB, Keir R, Graham D, Smith WE, Cooper JM (2004) The first SERRS multiplexing from labelled oligonucleotides in a microfluidics lab-on-a-chip. Chem Commun (1): 118–9

  • Dou X, Yamaguchi Y, Yamamoto H, Doi S, Ozaki Y (1998) NIR SERS detection of immune reaction on gold colloid particles without bound/free antigen separation. J Raman Spectrosc 29(8):739–742

    Article  Google Scholar 

  • Erickson D, Mandal S, Yang AHJ, Cordovez B (2008) Nanobiosensors: optofluidic, electrical and mechanical approaches to biomolecular detection at the nanoscale. Microfluid Nanofluid 4:33–52

    Article  Google Scholar 

  • Fabris L, Dante M, Braun G, Lee SJ, Reich NO, Moskovits M, Nguyen TQ, Bazan GC (2007) A heterogeneous PNA-based SERS method for DNA detection. J Am Chem Soc 129(19):6086–6087

    Article  Google Scholar 

  • Fan XD, White IM, Shopoua SI, Zhu HY, Suter JD, Sun YZ (2008) Sensitive optical biosensors for unlabeled targets: a review. Anal Chim Acta 620(1–2):8–26

    Article  Google Scholar 

  • Faulds K, Jarvis R, Smith WE, Graham D, Goodacre R (2008) Multiplexed detection of six labelled oligonucleotides using surface enhanced resonance Raman scattering (SERRS). Analyst 133(11):1505–1512

    Article  Google Scholar 

  • Felidj N, Truong SL, Aubard J, Levi G, Krenn JR, Hohenau A, Leitner A, Aussenegg FR (2004) Gold particle interaction in regular arrays probed by surface enhanced Raman scattering. J Chem Phys 120(15):7141–7146

    Article  Google Scholar 

  • Grubisha DS, Lipert RJ, Park HY, Driskell J, Porter MD (2003) Femtomolar detection of prostate-specific antigen: an immunoassay based on surface-enhanced Raman scattering and immunogold labels. Anal Chem 75(21):5936–5943

    Article  Google Scholar 

  • Hahn WC, Weinberg RA (2002) Modelling the molecular circuitry of cancer. Nat Rev Cancer 2(5):331–341

    Article  Google Scholar 

  • Hammody Z, Huleihel M, Salman A, Argov S, Moreh R, Katzir A, Mordechai S (2007) Potential of ‘flat’ fibre evanescent wave spectroscopy to discriminate between normal and malignant cells in vitro. J Microsc 228(Pt 2):200–210

    Article  MathSciNet  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    Article  Google Scholar 

  • Haslett TL, Tay L, Moskovits M (2000) Can surface-enhanced Raman scattering serve as a channel for strong optical pumping? J Chem Phys 113(4):1641–1646

    Article  Google Scholar 

  • Hayazawa N, Inouye Y, Sekkat Z, Kawata S (2001) Near-field Raman scattering enhanced by a metallized tip. Chem Phys Lett 335(5–6):369–374

    Article  Google Scholar 

  • Huang L, Reekmans G, Saerens D, Friedt JM, Frederix F, Francis L, Muyldermans S, Campitelli A, Van Hoof C (2005) Prostate-specific antigen immunosensing based on mixed self-assembled monolayers, camel antibodies and colloidal gold enhanced sandwich assays. Biosens Bioelectron 21(3):483–490

    Article  Google Scholar 

  • Huh YS, Chung AJ, Cordovez B, Erickson D (2008) Enhanced on-chip SERS based biomolecular detection using electrokinetically active microwells. Lab Chip (in press)

  • Ilic B, Yang Y, Aubin K, Reichenbach R, Krylov S, Craighead HG (2005) Enumeration of DNA molecules bound to a nanomechanical oscillator. Nano Lett 5(5):925–929

    Article  Google Scholar 

  • Isola NR, Stokes DL, Vo-Dinh T (1998) Surface-enhanced Raman gene probe for HIV detection. Anal Chem 70(7):1352–1356

    Article  Google Scholar 

  • Jackson JB, Westcott SL, Hirsch LR, West JL, Halas NJ (2003) Controlling the surface enhanced Raman effect via the nanoshell geometry. Appl Phys Lett 82(2):257–259

    Article  Google Scholar 

  • Jacobson ML, Rowlen KL (2005) Photo-dynamics on thin silver films. Chem Phys Lett 401(1–3):52–57

    Article  Google Scholar 

  • Jarvis RM, Goodacre R (2008) Characterisation and identification of bacteria using SERS. Chem Soc Rev 37(5):931–936

    Article  Google Scholar 

  • Jun BH, Kim JH, Park H, Kim JS, Yu KN, Lee SM, Choi H, Kwak SY, Kim YK, Jeong DH, Cho MH, Lee YS (2007) Surface-enhanced Raman spectroscopic-encoded beads for multiplex immunoassay. J Comb Chem 9(2):237–244

    Article  Google Scholar 

  • Jung J, Chen L, Lee S, Kim S, Seong GH, Choo J, Lee EK, Oh CH, Lee S (2007) Fast and sensitive DNA analysis using changes in the FRET signals of molecular beacons in a PDMS microfluidic channel. Anal Bioanal Chem 387(8):2609–2615

    Article  Google Scholar 

  • Kambhampati P, Campion A, Song OK (1999) Probing photoinduced charge transfer at atomically smooth metal surfaces using surface enhanced Raman scattering. Phys Status Solidi A 175(1):233–239

    Article  Google Scholar 

  • Kim JH, Kim JS, Choi H, Lee SM, Jun BH, Yu KN, Kuk E, Kim YK, Jeong DH, Cho MH (2006) Nanoparticle probes with surface enhanced Raman spectroscopic tags for cellular cancer targeting. Anal Chem 78(19):6967–6973

    Article  Google Scholar 

  • Kneipp J, Kneipp H, Rice WL, Kneipp K (2005) Optical probes for biological applications based on surface-enhanced Raman scattering from indocyanine green on gold nanoparticles. Anal Chem 77(8):2381–2385

    Article  Google Scholar 

  • Kneipp K, Kneipp H, Deinum G, Itzkan I, Dasari RR, Feld MS (1998a) Single-molecule detection of a cyanine dye in silver colloidal solution using near-infrared surface-enhanced Raman scattering. Appl Spectrosc 52(2):175–178

    Article  Google Scholar 

  • Kneipp K, Kneipp H, Itzkan I, Dasari RR, Feld MS (1999) Ultrasensitive chemical analysis by Raman spectroscopy. Chem Rev 99(10):2957–2976

    Article  Google Scholar 

  • Kneipp K, Kneipp H, Kartha VB, Manoharan R, Deinum G, Itzkan I, Dasari RR, Feld MS (1998b) Detection and identification of a single DNA base molecule using surface-enhanced Raman scattering (SERS). Phys Rev E 57(6):R6281

    Article  Google Scholar 

  • Li T, Guo L, Wang Z (2008) Gold nanoparticle-based surface enhanced Raman scattering spectroscopic assay for the detection of protein–protein interactions. Anal Sci 24(7):907–910

    Article  Google Scholar 

  • Lin C-C, Yang Y-M, Chen Y-F, Yang T-S, Chang H-C (2008) A new protein A assay based on Raman reporter labeled immunogold nanoparticles. Biosens Bioelectron 24(2):178–183

    Article  Google Scholar 

  • Liu YC, Yu CC, Sheu SF (2006) Improved surface-enhanced Raman scattering on optimum electrochemically roughened silver substrates. Anal Chim Acta 577(2):271–275

    Article  Google Scholar 

  • Liu GL, Rosa-Bauza YT, Salisbury CM, Craik C, Ellman JA, Chen FF, Lee LP (2007) Peptide-nanoparticle hybrid SERS probes for optical detection of protease activity. J Nanosci Nanotechnol 7(7):2323–2330

    Article  Google Scholar 

  • Mahajan S, Baumberg JJ, Russell AE, Bartlett PN (2007) Reproducible SERRS from structured gold surfaces. Phys Chem Chem Phys 9(45):6016–6020

    Article  Google Scholar 

  • Michaels AM, Nirmal M, Brus LE (1999) Surface enhanced Raman spectroscopy of individual Rhodamine 6G molecules on large Ag nanocrystals. J Am Chem Soc 121(43):9932–9939

    Article  Google Scholar 

  • Moskovits M, Tay L-L, Yang J, Haslett T (2002) SERS and the single molecule. Optical properties of nanostructured random media: 215–227

  • Ni J, Lipert RJ, Dawson GB, Porter MD (1999) Immunoassay readout method using extrinsic Raman labels adsorbed on immunogold colloids. Anal Chem 71(21):4903–4908

    Article  Google Scholar 

  • Nie S, Emory SR (1997) Probing single molecules and single nanoparticles by surface-enhanced Raman scattering. Science 275(5303):1102–1106

    Article  Google Scholar 

  • Nikoobakht B, El-Sayed MA (2003) Surface-enhanced Raman scattering studies on aggregated gold nanorods. J Phys Chem A 107(18):3372–3378

    Article  Google Scholar 

  • Notingher I, Elfick A (2005) Effect of sample and substrate electric properties on the electric field enhancement at the apex of SPM nanotips. J Phys Chem B 109(33):15699–15706

    Article  Google Scholar 

  • Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500

    Article  Google Scholar 

  • Pal A, Isola NR, Alarie JP, Stokes DL, Vo-Dinh T (2006) Synthesis and characterization of SERS gene probe for BRCA-1 (breast cancer). Faraday Discuss 132:293–301

    Article  Google Scholar 

  • Park T, Lee S, Seong GH, Choo J, Lee EK, Kim YS, Ji WH, Hwang SY, Gweon D-G, Lee S (2005) Highly sensitive signal detection of duplex dye-labelled DNA oligonucleotides in a PDMS microfluidic chip: confocal surface-enhanced Raman spectroscopic study. Lab Chip 5(4):437–442

    Article  Google Scholar 

  • Petrovsky A, Schellenberger E, Josephson L, Weissleder R, Bogdanov A Jr (2003) Near-infrared fluorescent imaging of tumor apoptosis. Cancer Res 63(8):1936–1942

    Google Scholar 

  • Pettinger B, Picardi G, Schuster R, Ertl G (2002) Surface-enhanced and STM-tip-enhanced Raman spectroscopy at metal surfaces. Single Mol 3(5–6):285–294

    Article  Google Scholar 

  • Pettinger B, Ren B, Picardi G, Schuster R, Ertl G (2004) Nanoscale probing of adsorbed species by tip-enhanced Raman spectroscopy. Phys Rev Lett 92(9):96101

    Article  Google Scholar 

  • Qian X, Peng XH, Ansari DO, Yin-Goen Q, Chen GZ, Shin DM, Yang L, Young AN, Wang MD, Nie S (2008) In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat Biotechnol 26(1):83–90

    Article  Google Scholar 

  • Qian XM, Nie SM (2008) Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications. Chem Soc Rev 37(5):912–920

    Article  Google Scholar 

  • Riley MR, Lucas P, Coq DL, Juncker C, Boesewetter DE, Collier JL, DeRosa DM, Katterman ME, Boussard-Plédel C, Bureau B (2006) Lung cell fiber evanescent wave spectroscopic biosensing of inhalation health hazards. Biotech Bioeng 95(4):599–612

    Article  Google Scholar 

  • Schwartzberg AM, Zhang JZ (2008) Novel optical properties and emerging applications of metal nanostructures. J Phys Chem C 112(28):10323–10337

    Article  Google Scholar 

  • Sha MY, Xu H, Penn SG, Cromer R (2007) SERS nanoparticles: a new optical detection modality for cancer diagnosis. Nanomed 2(5):725–734

    Article  Google Scholar 

  • Shafer-Peltier KE, Haka AS, Fitzmaurice M, Crowe J, Myles J, Dasari RR, Feld MS (2002) Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo. J Raman Spectrosc 33(7):552–563

    Article  Google Scholar 

  • Shamsaie A, Jonczyk M, Sturgis J, Robinson JP, Irudayaraj J (2007) Intracellularly grown gold nanoparticles as potential surface-enhanced Raman scattering probes. J Biomed Opt 12(2):020502

    Article  Google Scholar 

  • Shim MG, Song LM, Marcon NE, Wilson BC (2000) In vivo near-infrared Raman spectroscopy: demonstration of feasibility during clinical gastrointestinal endoscopy. Photochem Photobiol 72(1):146–150

    Article  Google Scholar 

  • Strehle KR, Cialla D, Rosch P, Henkel T, Kohler M, Popp J (2007) A reproducible surface-enhanced Raman spectroscopy approach. Online SERS measurements in a segmented microfluidic system. Anal Chem 79(4):1542–1547

    Article  Google Scholar 

  • Sun L, Yu C, Irudayaraj J (2008) Raman multiplexers for alternative gene splicing. Anal Chem 80(9):3342–3349

    Article  Google Scholar 

  • Sun WX, Shen ZX (2003) Apertureless near-field scanning Raman microscopy using reflection scattering geometry. Ultramicroscopy 94(3–4):237–244

    Article  Google Scholar 

  • Tang HW, Yang XB, Kirkham J, Smith DA (2007) Probing intrinsic and extrinsic components in single osteosarcoma cells by near-infrared surface-enhanced Raman scattering. Anal Chem 79(10):3646–3653

    Article  Google Scholar 

  • Tao AR, Yang P (2005) Polarized surface-enhanced Raman spectroscopy on coupled metallic nanowires. J Phys Chem B 109(33):15687–15690

    Article  Google Scholar 

  • Tian Z-Q, Ren B, Li J-F, Yang Z-L (2007) Expanding generality of surface-enhanced Raman spectroscopy with borrowing SERS activity strategy. Chem Commn (34): 3514–3534

  • Utzinger U, Richards-Kortum RR (2003) Fiber optic probes for biomedical optical spectroscopy. J Biomed Opt 8(1):121–147

    Article  Google Scholar 

  • van de Poll SWE, Bakker Schut TC, van der Laarse A, Puppels GJ (2002) In situ investigation of the chemical composition of ceroid in human atherosclerosis by Raman spectroscopy. J Raman Spectrosc 33(7):544–551

    Article  Google Scholar 

  • Verville GJ, Sanderson GA (2000) Early atokan fusulinids from the lower Antler overlap sequence, Lander and Humboldt counties, Nevada. Journal of Paleontology 62(4):520

    Google Scholar 

  • Vo-Dinh T (2008) Nanobiosensing using plasmonic nanoprobes. IEEE J Sel Top Quant 14(1):198

    Article  Google Scholar 

  • Vo-Dinh T, Allain LR, Stokes DL (2002) Cancer gene detection using surface-enhanced Raman scattering (SERS). J Raman Spectrosc 33(7):511–516

    Article  Google Scholar 

  • Wabuyele MB, Vo-Dinh T (2005) Detection of human immunodeficiency virus type 1 DNA sequence using plasmonics nanoprobes. Anal Chem 77(23):7810–7815

    Article  Google Scholar 

  • Wabuyele MB, Yan F, Griffin GD, Vo-Dinh T (2005) Hyperspectral surface-enhanced Raman imaging of labeled silver nanoparticles in single cells. Rev Sci Instrum 76(6):063710–063717

    Article  Google Scholar 

  • Wang H, Levin CS, Halas NJ (2005) Nanosphere arrays with controlled sub-10-nm gaps as surface-enhanced Raman spectroscopy substrates. J Am Chem Soc 127(43):14992–14993

    Article  Google Scholar 

  • Wang M, Jing N, Chou IH, Cote GL, Kameoka J (2007) An optofluidic device for surface enhanced Raman spectroscopy. Lab Chip 7(5):630–632

    Article  Google Scholar 

  • Wen R, Fang Y (2005) An investigation of the surface-enhanced Raman scattering (SERS) effect from a new substrate of silver-modified silver electrode. J Colloid Interface Sci 292(2):469–475

    Article  Google Scholar 

  • Wessel J (1985) Surface-enhanced optical microscopy. J Opt Soc Am B 2(9):1538–1541

    Article  Google Scholar 

  • White IM, Gohring J, Fan X (2007) SERS-based detection in an optofluidic ring resonator platform. Opt Express 15(25):17433–17442

    Article  Google Scholar 

  • Wolfbeis OS (1991) Fiber optic chemical sensors and biosensors. CRC Press, Boca Raton

    Google Scholar 

  • Xu S, Ji X, Xu W, Li X, Wang L, Bai Y, Zhao B, Ozaki Y (2004) Immunoassay using probe-labelling immunogold nanoparticles with silver staining enhancement via surface-enhanced Raman scattering. Analyst 129(1):63–68

    Article  Google Scholar 

  • Xu Y, Wu J, Sun W, Tao D, Yang L, Song Z, Weng S, Xu Z, Soloway RD, Xu D, Xu G (2002) A new mechanism of Raman enhancement and its application. Chemistry 8(23):5323–5331

    Article  Google Scholar 

  • Yakes BJ, Lipert RJ, Bannantine JP, Porter MD (2008) Detection of Mycobacterium avium subsp. paratuberculosis by a sonicate immunoassay based on surface-enhanced Raman scattering. Clin Vaccine Immunol 15(2):227–234

    Article  Google Scholar 

  • Yu KN, Lee SM, Han JY, Park H, Woo MA, Noh MS, Hwang SK, Kwon JT, Jin H, Kim YK, Hergenrother PJ, Jeong DH, Lee YS, Cho MH (2007) Multiplex targeting, tracking, and imaging of apoptosis by fluorescent surface enhanced Raman spectroscopic dots. Bioconj Chem 18(4):1155–1162

    Article  Google Scholar 

  • Zhang CY, Johnson LW (2006) Quantum-dot-based nanosensor for RRE IIB RNA-Rev peptide interaction assay. J Am Chem Soc 128(16):5324–5325

    Article  Google Scholar 

  • Zheng GF, Patolsky F, Cui Y, Wang WU, Lieber CM (2005) Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol 23(10):1294–1301

    Article  Google Scholar 

  • Zou X, Dong S (2006) Surface-enhanced Raman scattering studies on aggregated silver nanoplates in aqueous solution. J Phys Chem B 110(43):21545–21550

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David Erickson.

Additional information

Y. S. Huh and A. J. Chung contributed equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huh, Y.S., Chung, A.J. & Erickson, D. Surface enhanced Raman spectroscopy and its application to molecular and cellular analysis. Microfluid Nanofluid 6, 285–297 (2009). https://doi.org/10.1007/s10404-008-0392-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10404-008-0392-3

Keywords

Navigation