Skip to main content

Advertisement

SpringerLink
Log in

Plasmonic SERS biosensing nanochips for DNA detection

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

The development of rapid, cost-effective DNA detection methods for molecular diagnostics at the point-of-care (POC) has been receiving increasing interest. This article reviews several DNA detection techniques based on plasmonic-active nanochip platforms developed in our laboratory over the last 5 years, including the molecular sentinel-on-chip (MSC), the multiplex MSC, and the inverse molecular sentinel-on-chip (iMS-on-Chip). DNA probes were used as the recognition elements, and surface-enhanced Raman scattering (SERS) was used as the signal detection method. Sensing mechanisms were based on hybridization of target sequences and DNA probes, resulting in a distance change between SERS reporters and the nanochip’s plasmonic-active surface. As the field intensity of the surface plasmon decays exponentially as a function of distance, the distance change in turn affects SERS signal intensity, thus indicating the presence and capture of the target sequences. Our techniques were single-step DNA detection techniques. Target sequences were detected by simple delivery of sample solutions onto DNA probe-functionalized nanochips and measuring the SERS signal after appropriate incubation times. Target sequence labeling or washing to remove unreacted components was not required, making the techniques simple, easy-to-use, and cost-effective. The usefulness of the nanochip platform-based techniques for medical diagnostics was illustrated by the detection of host genetic biomarkers for respiratory viral infection and of the dengue virus gene.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, Dewar RL, Planta A, Liu SY, Metcalf JA, Mellors JW, Coffin JM (2003) New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 41(10):4531–4536

    Article  CAS  Google Scholar 

  2. Niemz A, Ferguson TM, Boyle DS (2011) Point-of-care nucleic acid testing for infectious diseases. Trends Biotechnol 29(5):240–250

    Article  CAS  Google Scholar 

  3. Park S, Zhang Y, Lin S, Wang TH, Yang S (2011) Advances in microfluidic PCR for point-of-care infectious disease diagnostics. Biotechnol Adv 29(6):830–839

    Article  CAS  Google Scholar 

  4. Feuillie C, Merheb MM, Gillet B, Montagnac G, Daniel I, Hanni C (2011) A novel SERRS sandwich-hybridization assay to detect specific DNA target. PLoS One 6(5), e17847

    Article  CAS  Google Scholar 

  5. Longo MC, Berninger MS, Hartley JL (1990) Use of uracil DNA glycosylase to control carry-over contamination in polymerase chain-reactions. Gene 93(1):125–128

    Article  CAS  Google Scholar 

  6. Bessetti J (2007) An introduction to PCR inhibitors. Profiles in DNA 10(1):9–10

  7. Jiang L, Mancuso M, Lu Z, Akar G, Cesarman E, Erickson D (2014) Solar thermal polymerase chain reaction for smartphone-assisted molecular diagnostics. Sci Rep 4:4137

    Google Scholar 

  8. Chin CD, Linder V, Sia SK (2012) Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip 12(12):2118–2134

    Article  CAS  Google Scholar 

  9. Chang CM, Chang WH, Wang CH, Wang JH, Mai JD, Lee GB (2013) Nucleic acid amplification using microfluidic systems. Lab Chip 13(7):1225–1242

    Article  CAS  Google Scholar 

  10. Culbertson CT, Mickleburgh TG, Stewart-James SA, Sellens KA, Pressnall M (2014) Micro total analysis systems: fundamental advances and biological applications. Anal Chem 86(1):95–118

    Article  CAS  Google Scholar 

  11. van Reenen A, de Jong AM, den Toonder JMJ, Prins MWJ (2014) Integrated lab-on-chip biosensing systems based on magnetic particle actuation – a comprehensive review. Lab Chip 14(12):1966–1986

    Article  Google Scholar 

  12. Schlücker S (2014) Surface-enhanced Raman spectroscopy: concepts and chemical applications. Angew Chem Int Ed Engl 53(19):4756–4795

    Article  Google Scholar 

  13. Kneipp K, Wang Y, Kneipp H, Perelman LT, Itzkan I, Dasari R, Feld MS (1997) Single molecule detection using surface-enhanced Raman scattering (SERS). Phys Rev Lett 78(9):1667–1670

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Zrimsek AB, Henry AI, Van Duyne RP (2013) Single molecule surface-enhanced Raman spectroscopy without nanogaps. J Phys Chem Lett 4(19):3206–3210

    Article  CAS  Google Scholar 

  16. Darby BL, Etchegoin PG, Le Ru EC (2014) Single-molecule surface-enhanced Raman spectroscopy with nanowatt excitation. Phys Chem Chem Phys 16(43):23895–23899

    Article  CAS  Google Scholar 

  17. von Maltzahn G, Centrone A, Park JH, Ramanathan R, Sailor MJ, Hatton TA, Bhatia SN (2009) SERS-coded gold nanorods as a multifunctional platform for densely multiplexed near-infrared imaging and photothermal heating. Adv Mater 21(31):3175–3180

    Article  Google Scholar 

  18. Doering WE, Nie S (2003) Spectroscopic tags using dye-embedded nanoparticles and surface-enhanced raman scattering. Anal Chem 75(22):6171–6176

    Article  CAS  Google Scholar 

  19. Faulds K, Barbagallo RP, Keer JT, Smith WE, Graham D (2004) SERRS as a more sensitive technique for the detection of labelled oligonucleotides compared to fluorescence. Analyst 129(7):567–568

    Article  CAS  Google Scholar 

  20. Kneipp K, Haka AS, Kneipp H, Badizadegan K, Yoshizawa N, Boone C, Shafer-Peltier KE, Motz JT, Dasari RR, Feld MS (2002) Surface-enhanced Raman Spectroscopy in single living cells using gold nanoparticles. Appl Spectrosc 56(2):150–154

    Article  CAS  Google Scholar 

  21. Xu H, Sha M, Cromer R, Penn S, Holland E, Chakarova G, Natan M (2012) Portable SERS sensor for sensitive detection of food-borne pathogens. In: Kumar CSR (ed) Raman spectroscopy for nanomaterials characterization. Springer, Berlin Heidelberg, pp 531–551. doi:10.1007/978-3-642-20620-7_19

    Chapter  Google Scholar 

  22. Vo-Dinh T (1998) Surface-enhanced Raman spectroscopy using metallic nanostructures. Trac-Trend Anal Chem 17(8–9):557–582

    Article  CAS  Google Scholar 

  23. Vo-Dinh T, Dhawan A, Norton SJ, Khoury CG, Wang HN, Misra V, Gerhold MD (2010) Plasmonic nanoparticles and nanowires: design, fabrication and application in sensing. J Phys Chem C 114(16):7480–7488

    Article  CAS  Google Scholar 

  24. Vo-Dinh T, Fales AM, Griffin GD, Khoury CG, Liu Y, Ngo H, Norton SJ, Register JK, Wang HN, Yuan H (2013) Plasmonic nanoprobes: from chemical sensing to medical diagnostics and therapy. Nanoscale 5(21):10127–10140

    Article  CAS  Google Scholar 

  25. Vo-Dinh T, Liu Y, Fales AM, Ngo H, Wang HN, Register JK, Yuan H, Norton SJ, Griffin GD (2015) SERS nanosensors and nanoreporters: golden opportunities in biomedical applications. Wiley Interdiscip Rev Nanomed Nanobiotechnol 7(1):17–33

    Article  CAS  Google Scholar 

  26. Vo-Dinh T, Hiromoto MYK, Begun GM, Moody RL (1984) Surface-enhanced Raman spectrometry for trace organic-analysis. Anal Chem 56(9):1667–1670

    Article  CAS  Google Scholar 

  27. Khoury CG, Vo-Dinh T (2012) Plasmonic nanowave substrates for SERS: fabrication and numerical analysis. J Phys Chem C 116(13):7534–7545

    Article  CAS  Google Scholar 

  28. Ngo HT, Wang HN, Fales AM, Vo-Dinh T (2013) Label-free DNA biosensor based on SERS molecular sentinel on nanowave chip. Anal Chem 85(13):6378–6383

    Article  CAS  Google Scholar 

  29. 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  CAS  Google Scholar 

  30. Masson JF, Gibson KF, Provencher-Girard A (2010) Surface-enhanced Raman spectroscopy amplification with film over etched nanospheres. J Phys Chem C 114(51):22406–22412

    Article  CAS  Google Scholar 

  31. Fu CY, Kho KW, Dinish US, Koh ZY, Malini O (2012) Enhancement in SERS intensity with hierarchical nanostructures by bimetallic deposition approach. J Raman Spectrosc 43(8):977–985

    Article  CAS  Google Scholar 

  32. Im H, Bantz KC, Lee SH, Johnson TW, Haynes CL, Oh SH (2013) Self-assembled plasmonic nanoring cavity arrays for SERS and LSPR biosensing. Adv Mater 25(19):2678–2685

    Article  CAS  Google Scholar 

  33. Kim D, Campos AR, Datt A, Gao Z, Rycenga M, Burrows ND, Greeneltch NG, Mirkin CA, Murphy CJ, Van Duyne RP, Haynes CL (2014) Microfluidic-SERS devices for one shot limit-of-detection. Analyst 139(13):3227–3234

    Article  CAS  Google Scholar 

  34. Farcau C, Astilean S (2010) Mapping the SERS efficiency and hot-spots localization on gold film over nanospheres substrates. J Phys Chem C 114(27):11717–11722

    Article  CAS  Google Scholar 

  35. Ma K, Yuen JM, Shah NC, Walsh JT, Glucksberg MR, Van Duyne RP (2011) In vivo, transcutaneous glucose sensing using surface-enhanced spatially offset Raman spectroscopy: multiple rats, improved hypoglycemic accuracy, low incident power, and continuous monitoring for greater than 17 days. Anal Chem 83(23):9146–9152

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  37. Hu J, Zheng PC, Jiang JH, Shen GL, Yu RQ, Liu GK (2010) Sub-attomolar HIV-1 DNA detection using surface-enhanced Raman spectroscopy. Analyst 135(5):1084–1089

    Article  CAS  Google Scholar 

  38. Kang T, Yoo SM, Yoon I, Lee SY, Kim B (2010) Patterned multiplex pathogen DNA detection by Au particle-on-wire SERS sensor. Nano Lett 10(4):1189–1193

    Article  CAS  Google Scholar 

  39. He Y, Su S, Xu TT, Zhong YL, Zapien JA, Li J, Fan CH, Lee ST (2011) Silicon nanowires-based highly-efficient SERS-active platform for ultrasensitive DNA detection. Nano Today 6(2):122–130

    Article  CAS  Google Scholar 

  40. He SJ, Liu KK, Su S, Yan J, Mao XH, Wang DF, He Y, Li LJ, Song SP, Fan CH (2012) Graphene-based high-efficiency surface-enhanced Raman scattering-active platform for sensitive and multiplex DNA detection. Anal Chem 84(10):4622–4627

    Article  CAS  Google Scholar 

  41. Li JM, Wei C, Ma WF, An Q, Guo J, Hu J, Wang CC (2012) Multiplexed SERS detection of DNA targets in a sandwich-hybridization assay using SERS-encoded core-shell nanospheres. J Mater Chem 22(24):12100–12106

    Article  CAS  Google Scholar 

  42. Li M, Cushing SK, Liang HY, Suri S, Ma DL, Wu NQ (2013) Plasmonic nanorice antenna on triangle nanoarray for surface-enhanced Raman scattering detection of hepatitis B virus DNA. Anal Chem 85(4):2072–2078

    Article  CAS  Google Scholar 

  43. Zhang H, Harpster MH, Park HJ, Johnson PA (2011) Surface-enhanced Raman scattering detection of DNA derived from the West Nile virus genome using magnetic capture of Raman-active gold nanoparticles. Anal Chem 83(1):254–260

    Article  CAS  Google Scholar 

  44. Zhang H, Harpster MH, Wilson WC, Johnson PA (2012) Surface-enhanced Raman scattering detection of DNAs Derived from virus genomes using Au-coated paramagnetic nanoparticles. Langmuir 28(8):4030–4037

    Article  CAS  Google Scholar 

  45. Li JM, Ma WF, You LJ, Guo J, Hu J, Wang CC (2013) Highly sensitive detection of target ssDNA based on SERS liquid chip using suspended magnetic nanospheres as capturing substrates. Langmuir 29(20):6147–6155

    Article  CAS  Google Scholar 

  46. Donnelly T, Smith WE, Faulds K, Graham D (2014) Silver and magnetic nanoparticles for sensitive DNA detection by SERS. Chem Commun (Camb) 50(85):12907–12910

    Article  CAS  Google Scholar 

  47. Zhang ZL, Wen YQ, Ma Y, Luo J, Jiang L, Song YL (2011) Mixed DNA-functionalized nanoparticle probes for surface-enhanced Raman scattering-based multiplex DNA detection. Chem Commun 47(26):7407–7409

    Article  CAS  Google Scholar 

  48. van Lierop D, Faulds K, Graham D (2011) Separation free DNA detection using surface enhanced Raman scattering. Anal Chem 83(15):5817–5821

    Article  Google Scholar 

  49. MacAskill A, Crawford D, Graham D, Faulds K (2009) DNA sequence detection using surface-enhanced resonance Raman spectroscopy in a homogeneous multiplexed assay. Anal Chem 81(19):8134–8140

    Article  CAS  Google Scholar 

  50. Yi Z, Li XY, Liu FJ, Jin PY, Chu X, Yu RQ (2013) Design of label-free, homogeneous biosensing platform based on plasmonic coupling and surface-enhanced Raman scattering using unmodified gold nanoparticles. Biosens Bioelectron 43:308–314

    Article  CAS  Google Scholar 

  51. 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  CAS  Google Scholar 

  52. 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  CAS  Google Scholar 

  53. Wang HN, Vo-Dinh T (2009) Multiplex detection of breast cancer biomarkers using plasmonic molecular sentinel nanoprobes. Nanotechnology 20(6):065101

  54. Wang HN, Dhawan A, Du Y, Batchelor D, Leonard DN, Misra V, Vo-Dinh T (2013) Molecular sentinel-on-chip for SERS-based biosensing. Phys Chem Chem Phys 15(16):6008–6015

    Article  CAS  Google Scholar 

  55. Wang HN, Fales AM, Zaas AK, Woods CW, Burke T, Ginsburg GS, Vo-Dinh T (2013) Surface-enhanced Raman scattering molecular sentinel nanoprobes for viral infection diagnostics. Anal Chim Acta 786:153–158

    Article  CAS  Google Scholar 

  56. Ngo H, Wang H-N, Burke T, Ginsburg G, Vo-Dinh T (2014) Multiplex detection of disease biomarkers using SERS molecular sentinel-on-chip. Anal Bioanal Chem 406(14):3335–3344

    Article  CAS  Google Scholar 

  57. Ngo HT, Wang HN, Fales AM, Nicholson BP, Woods CW, Vo-Dinh T (2014) DNA bioassay-on-chip using SERS detection for dengue diagnosis. Analyst 139(22):5655–5659

    Article  CAS  Google Scholar 

  58. Wang HN, Fales AM, Vo-Dinh T (2015) Plasmonics-based SERS nanobiosensor for homogeneous nucleic acid detection. Nanomed 11(4):811–814

    Article  CAS  Google Scholar 

  59. Tyagi S, Kramer FR (1996) Molecular beacons: probes that fluoresce upon hybridization. Nat Biotechnol 14(3):303–308

    Article  CAS  Google Scholar 

  60. Wei XP, Su S, Guo YY, Jiang XX, Zhong YL, Su YY, Fan CH, Lee ST, He Y (2013) A molecular beacon-based signal-off surface-enhanced Raman scattering strategy for highly sensitive, reproducible, and multiplexed DNA detection. Small 9(15):2493–2499

    Article  CAS  Google Scholar 

  61. Pang YF, Wang JF, Xiao R, Wang SQ (2014) SERS molecular sentinel for the RNA genetic marker of PB1-F2 protein in highly pathogenic avian influenza (HPAI) virus. Biosens Bioelectron 61:460–465

    Article  CAS  Google Scholar 

  62. Wang H, Jiang XX, Wang X, Wei XP, Zhu Y, Sun B, Su YY, He SD, He Y (2014) Hairpin DNA-assisted silicon/silver-based surface-enhanced Raman scattering sensing platform for ultrahighly sensitive and specific discrimination of deafness mutations in a real system. Anal Chem 86(15):7368–7376

    Article  CAS  Google Scholar 

  63. Qi J, Zeng J, Zhao F, Lin SH, Raja B, Strych U, Willson RC, Shih WC (2014) Label-free, in situ SERS monitoring of individual DNA hybridization in microfluidics. Nanoscale 6(15):8521–8526

    Article  CAS  Google Scholar 

  64. Stiles PL, Dieringer JA, Shah NC, Van Duyne RP (2008) Surface-enhanced Raman spectroscopy. Annu Rev Anal Chem 1(1):601–626

    Article  CAS  Google Scholar 

  65. Zaas AK, Burke T, Chen M, McClain M, Nicholson B, Veldman T, Tsalik EL, Fowler V, Rivers EP, Otero R, Kingsmore SF, Voora D, Lucas J, Hero AO, Carin L, Woods CW, Ginsburg GS (2013) A host-based RT-PCR gene expression signature to identify acute respiratory viral infection. Sci Transl Med 5(203):203ra126

    Article  Google Scholar 

  66. McNay G, Eustace D, Smith WE, Faulds K, Graham D (2011) Surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS): a review of applications. Appl Spectrosc 65(8):825–837

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was sponsored by the Duke Faculty Exploratory Research Fund, the Defense Advanced Research Projects Agency (HR0011-13-2-0003), the Department of Energy (DE-SC0014077), and the Wallace H. Coulter Foundation Endowment. Hoan Thanh Ngo is supported by Fellowships from the Vietnam Education Foundation and the Fitzpatrick Foundation. The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA

    Hoan T. Ngo, Hsin-Neng Wang, Andrew M. Fales & Tuan Vo-Dinh

  2. Fitzpatrick Institute for Photonics, Duke University, Durham, NC, 27708, USA

    Hoan T. Ngo, Hsin-Neng Wang, Andrew M. Fales & Tuan Vo-Dinh

  3. Department of Chemistry, Duke University, Durham, NC, 27708, USA

    Tuan Vo-Dinh

Authors
  1. Hoan T. Ngo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hsin-Neng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew M. Fales
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tuan Vo-Dinh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tuan Vo-Dinh.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Published in the topical collection Analytical Applications of Biomimetic Recognition Elements with guest editors Maria C. Moreno-Bondi and Elena Benito-Peña.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ngo, H.T., Wang, HN., Fales, A.M. et al. Plasmonic SERS biosensing nanochips for DNA detection. Anal Bioanal Chem 408, 1773–1781 (2016). https://doi.org/10.1007/s00216-015-9121-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-015-9121-4

Keywords

Search

Navigation