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SERS-based lateral flow immunoassay of troponin I by using gap-enhanced Raman tags

Abstract

The lateral flow immunoassay (LFIA) has emerged as a powerful tool for rapid screening owing to its simplicity and flexibility for detection of various biomarkers. However, conventional LFIA strips have several disadvantages, including limits in quantitative analysis and low sensitivity. Here we developed a novel surface-enhanced Raman scattering LFIA based on nonspherical gap-enhanced Raman tags (GERTs), with Raman molecules (RMs) embedded in a 1-nm gap between Au nanorod core and Au shell. Such tags have a strong and uniform SERS response, an order of magnitude higher than that of other common SERS tags such as Au nanorods, nanostars, Au nanoshells with surface-adsorbed RMs, or spherical GERTs with embedded RMs. The feasibility of the tags was demonstrated by the semiquantitative and sensitive detection of the heart disease biomarker cardiac troponin I (cTnI). GERTs were conjugated with monoclonal antibodies and used for LFIA in the same way as ordinary functionalized colloidal gold. The presence of the target antigen, cTnI, was identified by Raman microscopy mapping of the test zone. With the SERS-based LFIA, the limit of cTnI detection was about 0.1 ng/mL. This value is within the diagnostic range of cTnI in the blood serum of patients with heart infarction and is 30 times lower than that of the colorimetric LFIA test using the same antibodies and either GERTs or colloidal gold as labels.

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References

  1. [1]

    Parolo, C.; Merkoci, A. Paper-based nanobiosensors for diagnostics. Chem. Soc. Rev. 2013, 42, 450–457.

    Article  Google Scholar 

  2. [2]

    Dzantiev, B. B.; Byzova, N. A.; Urusov A. E.; Zherdev, A. V. Immunochromatographic methods in food analysis. TrAC Trends Anal. Chem. 2014, 55, 81–93.

    Article  Google Scholar 

  3. [3]

    Koczula, K. M.; Gallotta, A. Lateral flow assays. Essays Biochem. 2016, 60, 111–120.

    Article  Google Scholar 

  4. [4]

    de Puig, H.; Bosch, I.; Gehrke, L.; Hamad-Schifferli, K. Challenges of the nano–bio interface in lateral flow and dipstick immunoassays. Trends Biotechnol. 2017, 35, 1169–1180.

    Article  Google Scholar 

  5. [5]

    Mak, W. C.; Beni, V.; Turner, A. P. F. Lateral-flow technology: From visual to instrumental. TrAC Trends Anal. Chem. 2016, 79, 297–305.

    Article  Google Scholar 

  6. [6]

    Bahadir, E. B.; Sezgintürk, M. K. Lateral flow assays: Principles, designs and labels. TrAC Trends Anal. Chem. 2016, 82, 286–306.

    Article  Google Scholar 

  7. [7]

    Quesada-González, D.; Merkoçi, A. Nanoparticle-based lateral flow biosensors. Biosens. Bioelectron. 2015; 73, 47–63.

    Article  Google Scholar 

  8. [8]

    Raeisossadat, M. J.; Danesh, N. M.; Borna, F.; Gholamzad, M.; Ramezani, M.; Abnous, K.; Taghdisi, S. M. Lateral flow based immunobiosensors for detection of food contaminants. Biosens. Bioelectron. 2016, 86, 235–2466.

    Article  Google Scholar 

  9. [9]

    Dykman, L.; Khlebtsov, N. Gold nanoparticles in biomedical applications: Recent advances and perspectives. Chem. Soc. Rev. 2012, 41, 2256–2282.

    Article  Google Scholar 

  10. [10]

    Wang, P. L.; Lin, Z. Y.; Su, X. O.; Tang, Z. Y. Application of Au based nanomaterials in analytical science. Nano Today 2017, 12, 64–97.

    Article  Google Scholar 

  11. [11]

    Shan, S.; Lai, W. H.; Xiong, Y. H.; Wei, H.; Xu, H. Y. Novel strategies to enhance lateral flow immunoassay sensitivity for detecting foodborne pathogens. J. Agric. Food Chem. 2015, 63, 745–753.

    Article  Google Scholar 

  12. [12]

    Zherdev, A. V., Dzantiev, B. B. Ways to reach lower detection limits in lateral flow immunoassays. In Rapid Test–Advances in Design, Format and Diagnostic Applications. Anfossi, L., Ed.; InTechOpen: London, 2018, pp 9–43.

    Google Scholar 

  13. [13]

    Brangel, P.; Sobarzo, A.; Parolo, C.; Miller, B. S.; Howes, P. D.; Gelkop, S.; Lutwama, J. J.; Dye, J. M.; McKendry, R. A.; Lobel, L. et al. A serological point-of-care test for the detection of IgG antibodies against Ebola virus in human survivors. ACS Nano 2018, 12, 63–73.

    Article  Google Scholar 

  14. [14]

    Feng, S.; Caire, R.; Cortazar, B.; Turan, M.; Wong, A.; Ozcan, A. Immunochromatographic diagnostic test analysis using Google glass. ACS Nano 2014, 8, 3069–3079.

    Article  Google Scholar 

  15. [15]

    Goryacheva, I. Y.; Lenain, P.; De Saeger, S. Nanosized labels for rapid immunotests. TrAC Trends Anal. Chem. 2013, 46, 30–43.

    Article  Google Scholar 

  16. [16]

    Gong, X. Q.; Cai, J.; Zhang, B.; Zhao, Q.; Piao, J. F.; Peng, W. P.; Gao, W. C.; Zhou, D. M.; Zhao, M.; Chang, J. A review of fluorescent signal-based lateral flow immunochromatographic strips. J. Mater. Chem. B 2017, 5, 5079–5091.

    Article  Google Scholar 

  17. [17]

    Wang, Z. Y.; Zong, S. F.; Wu, L.; Zhu, D.; Cui, Y. P. SERS-activated platforms for immunoassay: Probes, encoding methods, and applications. Chem. Rev. 2017, 117, 7910–7963.

    Article  Google Scholar 

  18. [18]

    Mir-Simon, B.; Reche-Perez, I.; Guerrini, L.; Pazos-Perez, N.; Alvarez- Puebla, R. A. Universal one-pot and scalable synthesis of SERS encoded nanoparticles. Chem. Mater. 2015, 27, 950–958.

    Article  Google Scholar 

  19. [19]

    Samanta, A.; Maiti, K. K.; Soh, K. S.; Liao, X.; Vendrell, M.; Dinish, U. S.; Yun, S. W.; Bhuvaneswari, R.; Kim, H.; Rautela, S. et al. Ultrasensitive near-infrared Raman reporters for SERS-based in vivo cancer detection. Angew. Chem., Int. Ed. 2011, 50, 6089–6092.

    Article  Google Scholar 

  20. [20]

    Khlebtsov, N. G.; Khlebtsov, B. N. Optimal design of gold nanomatryoshkas with embedded Raman reporters. J. Quant. Spectrosc. Radiat. Transfer 2017, 190, 89–102.

    Article  Google Scholar 

  21. [21]

    Wang, Y. Q.; Yan, B.; Chen, L. X. SERS tags: Novel optical nanoprobes for bioanalysis. Chem. Rev. 2013, 113, 1391–1428.

    Article  Google Scholar 

  22. [22]

    Fu, X. L.; Cheng, Z. Y.; Yu, J. M.; Choo, P.; Chen, L. X.; Choo, J. A SERSbased lateral flow assay biosensor for highly sensitive detection of HIV-1 DNA. Biosens. Bioelectron. 2016, 78, 530–537.

    Article  Google Scholar 

  23. [23]

    Wang, X. K.; Choi, N.; Cheng, Z. Y.; Ko, J.; Chen, L. X.; Choo, J. Simultaneous detection of dual nucleic acids using a SERS-based lateral flow assay biosensor. Anal. Chem. 2017, 89, 1163–1169.

    Article  Google Scholar 

  24. [24]

    Choi, S.; Hwang, J.; Lee, S.; Lim, D. W.; Joo, H.; Choo, J. Quantitative analysis of thyroid-stimulating hormone (TSH) using SERS-based lateral flow immunoassay. Sens. Actuat. B Chem. 2017, 240, 358–364.

    Article  Google Scholar 

  25. [25]

    Park, H. J.; Yang, S. C.; Choo J. Early diagnosis of influenza virus A using surface-enhanced Raman scattering-based lateral flow assay. Bull. Korean Chem. Soc. 2016, 37, 2019–2024.

    Article  Google Scholar 

  26. [26]

    Liu, H. B.; Du, X. J.; Zang, Y. X.; Li, P.; Wang, S. A SERS-based lateral flow strip biosensor for simultaneous detection of Listeria monocytogenes and Salmonella enterica serotype enteritidis. J. Agric. Food Chem. 2017, 65, 10290–10299.

    Article  Google Scholar 

  27. [27]

    Wang, J.; Zhang, L.; Huang, Y.; Dandapat, A.; Dai, L.; Zhang, G.; Lu, X.; Zhang, J.; Lai, W.; Chen, T.; Hollow Au-Ag nanoparticles labeled immunochromatography strip for highly sensitive detection of clenbuterol. Sci. Rep. 2017, 7, 41419.

    Article  Google Scholar 

  28. [28]

    Maneeprakorn, W.; Bamrungsap, S.; Apiwat, C.; Wiriyachaiporn, N. Surfaceenhanced Raman scattering based lateral flow immunochromatographic assay for sensitive influenza detection. RSC Adv. 2016, 6, 112079–11208.

    Article  Google Scholar 

  29. [29]

    Hwang, J.; Lee, S.; Choo, J. Application of a SERS-based lateral flow immunoassay strip for the rapid and sensitive detection of staphylococcal enterotoxin B. Nanoscale 2016, 8, 11418–11425.

    Article  Google Scholar 

  30. [30]

    Lim, D. K.; Jeon, K. S.; Hwang, J. H.; Kim, H.; Kwon, S.; Suh Y. D.; Nam J. M. Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap. Nat. Nanotechnol. 2011, 6, 452–460.

    Article  Google Scholar 

  31. [31]

    Gandra, N.; Singamaneni, S. Bilayered Raman-intense gold nanostructures with hidden tags (BRIGHTs) for high-resolution bioimaging. Adv. Mater. 2013, 25, 1022–1027.

    Article  Google Scholar 

  32. [32]

    Gandra, N.; Hendargo, H. C.; Norton, S. J.; Fales, A. M.; Palmer, G. M.; Vo-Dinh, T. Tunable and amplified Raman gold nanoprobes for effective tracking (TARGET): In vivo sensing and imaging. Nanoscale 2016, 8, 8486–8494.

    Article  Google Scholar 

  33. [33]

    Khlebtsov, B.; Khanadeev, V., Khlebtsov, N. Surface-enhanced Raman scattering inside Au@Ag core/shell nanorods. Nano Res. 2016, 9, 2303–2318.

    Article  Google Scholar 

  34. [34]

    Khlebtsov, B. N.; Khlebtsov, N. G. Surface morphology of a gold core controls the formation of hollow or bridged nanogaps in plasmonic nanomatryoshkas and their SERS responses. J. Phys. Chem. C 2016, 120, 15385–15394.

    Article  Google Scholar 

  35. [35]

    Lin, L.; Gu, H. C.; Ye, J. Plasmonic multi-shell nanomatryoshka particles as highly tunable SERS tags with built-in reporters. Chem. Commun. 2015, 51, 17740–17743.

    Article  Google Scholar 

  36. [36]

    Kang, J. W.; So, P. T. C.; Dasari, R. R.; Lim, D. K. High resolution live cell Raman imaging using subcellular organelle-targeting SERS-sensitive gold nanoparticles with highly narrow intra-nanogap. Nano Lett. 2015, 15, 1766–1772.

    Article  Google Scholar 

  37. [37]

    Zhang, Y. Q.; Qiu, Y. Y.; Lin, L.; Gu, H. C.; Xiao, Z. Y.; Ye, J. Ultraphotostable mesoporous silica-coated gap-enhanced Raman tags (GERTs) for highspeed bioimaging. ACS Appl. Mater. Interfaces 2017, 9, 3995–4005.

    Article  Google Scholar 

  38. [38]

    Bao, Z. Z.; Zhang, Y. Q.; Tan, Z. Y.; Yin, X.; Di, W.; Ye, J. Gap-enhanced Raman tags for high-contrast sentinel lymph node imaging. Biomaterials 2018, 163, 105–115.

    Article  Google Scholar 

  39. [39]

    Kim, M.; Ko, S. M.; Kim, J. M.; Son, J.; Lee, C.; Rhim, W. K.; Nam, J. M. Dealloyed intra-nanogap particles with highly robust, quantifiable surfaceenhanced Raman scattering signals for biosensing and bioimaging applications. ACS Cent. Sci. 2018, 4, 277–287.

    Article  Google Scholar 

  40. [40]

    Khlebtsov, B.; Pylaev, T.; Khanadeev, V.; Bratashov, D.; Khlebtsov N. Quantitative and multiplex dot-immunoassay using gap enhanced Raman tags. RSC Adv. 2017, 7, 40834–40841.

    Article  Google Scholar 

  41. [41]

    Zhang, D.; Huang, L.; Liu, B.; Ni, H. B.; Sun, L. D.; Su, E. B.; Chen, H. Y.; Gu, Z. Z.; Zhao, X. W. Quantitative and ultrasensitive detection of multiplex cardiac biomarkers in lateral flow assay with core-shell SERS nanotags. Biosens. Bioelectron. 2018, 106, 204–211.

    Article  Google Scholar 

  42. [42]

    Bruins Slot, M. H. E.; van der Heijde, G. J. M. G.; Stelpstra, S. D.; Hoes, A. W.; Rutten, F. H. Point-of-care tests in suspected acute myocardial infarction: A systematic review. Int. J. Cardiol. 2013, 168, 5355–5362.

    Article  Google Scholar 

  43. [43]

    Soetkamp, D.; Raedschelders, K.; Mastali, M.; Sobhani, K.; Bairey Merz, C. N.; Van Eyk, J. The continuing evolution of cardiac troponin I biomarker analysis: From protein to proteoform. Expert Rev. Proteomics 2007, 14, 973–986.

    Article  Google Scholar 

  44. [44]

    Park, K. C.; Gaze, D. C.; Collinson, P. O.; Marber, M. S. Cardiac troponins: From myocardial infarction to chronic disease. Cardiovasc. Res. 2017, 113, 1708–1718.

    Article  Google Scholar 

  45. [45]

    Han, X.; Li, S. H.; Peng, Z. L.; Othman, A. M.; Leblanc, R. Recent development of cardiac troponin I detection. ACS Sens. 2016, 1, 106–114.

    Article  Google Scholar 

  46. [46]

    Segraves, J. M.; Frishman, W. H. Highly sensitive cardiac troponin assays: A comprehensive review of their clinical utility. Cardiol. Rev. 2015, 23, 282–289.

    Google Scholar 

  47. [47]

    Nikoobakht, B.; El-Sayed, M. A. Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chem. Mater. 2003, 15, 1957–1962.

    Article  Google Scholar 

  48. [48]

    Khlebtsov, B.; Khanadeev, V.; Pylaev, T.; Khlebtsov, N. A new T-matrix solvable model for nanorods: TEM-based ensemble simulations supported by experiments. J. Phys. Chem. C 2011, 115, 6317–6323.

    Article  Google Scholar 

  49. [49]

    Khlebtsov, B.; Panfilova, E.; Khanadeev, V.; Khlebtsov, N. Improved sizetunable synthesis and SERS properties of Au nanostars. J. Nanopart. Res. 2014, 16, 2623.

    Article  Google Scholar 

  50. [50]

    Khanadeev, V. A.; Khlebtsov, B. N.; Khlebtsov N. G. Optical properties of gold nanoshells on monodisperse silica cores: Experiment and simulations. J. Quant. Spectrosc. Radiat. Transfer 2017, 187, 1–9.

    Article  Google Scholar 

  51. [51]

    Byzova, N. A.; Safenkova, I. V.; Chirkov, S. N.; Zherdev, A. V.; Blintsov, A. N.; Dzantiev, B. B.; Atabekov, I. G. Development of immunochromatographic test systems for express detection of plant viruses. Appl. Biochem. Microbiol. 2009, 45, 204–209.

    Article  Google Scholar 

  52. [52]

    Byzova, N. A.; Zherdev, A. V.; Vengerov, Y. Y.; Starovoitova, T. A.; Dzantiev, B. B. A triple immunochromatographic test for simultaneous determination of cardiac troponin I, fatty acid binding protein, and C-reactive protein biomarkers. Microchim. Acta 2017, 184, 463–471.

    Article  Google Scholar 

  53. [53]

    Khlebtsov, B. N.; Khanadeev, V. A.; Burov, A. M.; Khlebtsov, N. G. A new type of SERS tags: Au@Ag core/shell nanorods with embedded aromatic molecules. Nanotechnol. Russia 2017, 12, 495–507.

    Article  Google Scholar 

  54. [54]

    Lin, L.; Zapata, M.; Xiong, M.; Liu, Z. H.; Wang, S. S.; Xu, H.; Borisov, A. G.; Gu, H. C.; Nordlander, P.; Aizpurua, J.; Ye, J. Nanooptics of plasmonic nanomatryoshkas: Shrinking the size of a core-shell junction to subnanometer. Nano Lett. 2015, 15, 6419–6428.

    Article  Google Scholar 

  55. [55]

    Lin, L.; Liu, Z. H.; Li, X. Y.; Gu, H. C.; Ye, J. Quantifying the reflective index of nanometer-thick thiolated molecular layers on nanoparticles. Nanoscale 2017, 9, 2213–2218.

    Article  Google Scholar 

  56. [56]

    Khlebtsov, B. N.; Khanadeev, V. A.; Ye, J.; Sukhorukov, G. B.; Khlebtsov, N. G. Overgrowth of gold nanorods by using a binary surfactant mixture. Langmuir 2014, 30, 1696–1703.

    Article  Google Scholar 

  57. [57]

    Abdelsalam, M. E. Surface enhanced Raman scattering of aromatic thiols adsorbed on nanostructured gold surfaces. Cent. Eur. J. Chem. 2009, 7, 446–453.

    Google Scholar 

  58. [58]

    Le Ru, E. C.; Blackie, E.; Meyer, M.; Etchegoin, P. G. Surface enhanced Raman scattering enhancement factors: A comprehensive study. J. Phys. Chem. C 2007, 111, 13794–13803.

    Article  Google Scholar 

  59. [59]

    Khalid, M.; Sala, F. D.; Ciraci, C. Optical properties of plasmonic core-shell nanomatryoshkas: A quantum hydrodynamic analysis. Opt. Express 2018, 26, 17322–17334.

    Article  Google Scholar 

  60. [60]

    Lerch, S.; Reinhard, B. M. Effect of interstitial palladium on plasmon-driven charge transfer in nanoparticle dimers. Nat. Commun. 2018, 9, 1608.

    Article  Google Scholar 

  61. [61]

    Wang, S. S.; Liu, Z. H.; Bartic, C.; Xu, H.; Ye J. Improving SERS uniformity by isolating hot spots in gold rod-in-shell nanoparticles. J. Nanopart. Res. 2016, 18, 246.

    Article  Google Scholar 

  62. [62]

    Skadtchenko, B. O.; Aroca, R. Surface-enhanced Raman scattering of p-nitrothiophenol: Molecular vibrations of its silver salt and the surface complex formed on silver islands and colloids. Spectrochim. Acta Part A Mol. Biomol. Spectros. 2001, 57, 1009–1016.

    Article  Google Scholar 

  63. [63]

    Futamata, M. Surface-plasmon-polariton-enhanced Raman scattering from self-assembled monolayers of p-nitrothiophenol and p-aminothiophenol on silver. J. Phys. Chem. 1995, 99, 11901–11908.

    Article  Google Scholar 

  64. [64]

    Teguh, J. S.; Liu, F.; Xing, B.; Yeow, E. K. L. Surface-enhanced Raman scattering (SERS) of nitrothiophenol isomers chemisorbed on TiO2. Chem. Asian J. 2012, 7, 975–981.

    Article  Google Scholar 

  65. [65]

    Bai, T. T.; Wang, M.; Cao, M.; Zhang, J.; Zhang, K. Z.; Zhou, P.; Liu, Z. X.; Liu, Y.; Guo, Z. R.; Lu, X. Functionalized Au@Ag-Au nanoparticles as an optical and SERS dual probe for lateral flow sensing. Anal. Bioanal. Chem. 2018, 410, 2291–2303.

    Article  Google Scholar 

  66. [66]

    Serebrennikova, K.; Samsonova, J.; Osipov, A. Hierarchical nanogold labels to improve the sensitivity of lateral flow immunoassay. Nano-Micro Lett. 2018, 10, 24.

    Article  Google Scholar 

  67. [67]

    Juntunen, E.; Arppe, R.; Kalliomaki, L.; Salminen, T.; Talha, S. M.; Myyryläinen, T.; Soukka, T.; Pettersson, K. Effects of blood sample anticoagulants on lateral flow assays using luminescent photon-upconverting and Eu(III) nanoparticle reporters. Anal. Biochem. 2016, 492, 13–20.

    Article  Google Scholar 

  68. [68]

    Cho, J. H.; Kim, M. H.; Mok, R. S.; Jeon, J. W.; Lim, G. S.; Chai, C. Y.; Paek, S. H. Two-dimensional paper chromatography-based fluorescent immunosensor for detecting acute myocardial infarction markers. J. Chromatogr. B 2014, 967, 139–146.

    Article  Google Scholar 

  69. [69]

    Xu, Q. F.; Xu, H.; Gu, H. C.; Li, J. B.; Wang, Y. Y.; Wei, M. Development of lateral flow immunoassay system based on superparamagnetic nanobeads as labels for rapid quantitative detection of cardiac troponin I. Mat. Sci. Eng. C 2009, 29, 702–707.

    Article  Google Scholar 

  70. [70]

    Choi, D. H.; Lee, S. K.; Oh, Y. K.; Bae, B. W.; Lee, S. D.; Kim, S.; Shin, Y. B.; Kim, M. G. A dual gold nanoparticle conjugate-based lateral flow assay (LFA) method for the analysis of troponin I. Biosens. Bioelectron. 2010, 25, 1999–2002.

    Article  Google Scholar 

  71. [71]

    Ryu, Y.; Jin, Z. W.; Kang, M. S.; Kim, H. S. Increase in the detection sensitivity of a lateral flow assay for a cardiac marker by oriented immobilization of antibody. BioChip J. 2011, 5, 193–198.

    Article  Google Scholar 

  72. [72]

    Zhu, J. M.; Zou, N. L.; Zhu, D. N.; Wang, J.; Jin, Q. H.; Zhao, J. L.; Mao, H. J. Simultaneous detection of high-sensitivity cardiac troponin I and myoglobin by modified sandwich lateral flow immunoassay: Proof of principle. Clin. Chem. 2011, 57, 1732–1738.

    Article  Google Scholar 

  73. [73]

    Cai, Y. X.; Kang, K. R.; Li, Q. R.; Wang, Y.; He, X. W. Rapid and sensitive detection of cardiac troponin I for point-of-care tests based on red fluorescent microspheres. Molecules 2018, 23, 1102.

    Article  Google Scholar 

  74. [74]

    Akanda, M. R.; Joung, H. A.; Tamilavan, V.; Park, S.; Kim, S.; Hyun, M. H.; Kim, M. G.; Yang, H. An interference-free and rapid electrochemical lateral-flow immunoassay for one-step ultrasensitive detection with serum. Analyst 2014, 139, 1420–1425.

    Article  Google Scholar 

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Acknowledgements

The work on the synthesis and characterization of GERTs and on the development of SERS-based LFIA was supported by the Russian Scientific Foundation (No. 18-14-00016). Synthesis of labeled antibodies and studies of immune interactions in LFIA systems were supported by the Russian Foundation for Basic Research (No. 18-08-01397). BNK was supported by program No. 32 of the Presidium of the Russian Academy of Sciences (“Nanostructures: physics, chemistry, biology and basic techniques”). We thank D. N. Tychinin for his help in the preparation of the manuscript.

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Correspondence to Boris N. Khlebtsov or Nikolai G. Khlebtsov.

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Khlebtsov, B.N., Bratashov, D.N., Byzova, N.A. et al. SERS-based lateral flow immunoassay of troponin I by using gap-enhanced Raman tags. Nano Res. 12, 413–420 (2019). https://doi.org/10.1007/s12274-018-2232-4

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Keywords

  • surface-enhanced Raman scattering (SERS)
  • lateral flow immunoassay
  • Au core/shell nanorods
  • gap-enhanced Raman tags
  • cardiac Troponin I