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Gold-nanorod-enhanced Raman spectroscopy encoded micro-quartz pieces for the multiplex detection of biomolecules

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Abstract

The rapid analysis and detection of biomolecules has become increasingly important in biological research. Hence, here we propose a novel suspension array method that is based on gold nanorod (AuNR)-enhanced Raman spectroscopy and uses micro-quartz pieces (MQPs) as microcarriers. AuNRs and Raman reporter molecules are coupled together by Au–S bonds to obtain surface-enhanced Raman scattering labels (SERS labels). The SERS labels are then assembled on the surfaces of the MQPs via electrostatic interactions, yielding encoded MQPs. Experimental results showed that the encoded MQPs could be decoded using a Raman spectrometer. A multiplex immunoassay experiment demonstrated the validity and specificity of these encoded MQPs when they were used for bioanalysis. In concentration gradient experiments, the proposed method was found to give a linear concentration response to the target biomolecule at target concentrations of 0.46875–30 nM, and the detection limit was calculated to be 1.78 nM. The proposed method utilizes MQPs as carriers rather than conventional microbeads, which allows the interference caused by the background fluorescence of microbeads to be eliminated. The fluorescence of the encoded MQPs can be simply, rapidly, and inexpensively quantified using fluorescence microscopy. By dividing the quantitative and qualitative detection of biomolecules into two independent channels, crosstalk between the encoded signal and the labeled signal is averted and high decoding accuracy and detection sensitivity are guaranteed.

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References

  1. Pittner A, Wendt S, Zopf D, Dathe A, Grosse N, Csáki A, et al. Fabrication of micro-patterned substrates for plasmonic sensing by piezo-dispensing of colloidal nanoparticles. Anal Bioanal Chem. 2019;411(8):1537–47. https://doi.org/10.1007/s00216-019-01587-7.

    Article  CAS  PubMed  Google Scholar 

  2. Schlücker S. SERS microscopy: nanoparticle probes and biomedical applications. Chemphyschem. 2009;10(9-10):1344–54. https://doi.org/10.1002/cphc.200900119.

    Article  CAS  PubMed  Google Scholar 

  3. Ng P, Tan JJ, Ooi HS, Lee YL, Chiu KP, Fullwood MJ, et al. Multiplex sequencing of paired-end ditags (MS-PET): a strategy for the ultra-high-throughput analysis of transcriptomes and genomes. Nucleic Acids Res. 2006;34(12):e84. https://doi.org/10.1093/nar/gkl444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chen L, Wang Y, Fu X, Chen L. Surface-enhanced Raman scattering nanoprobes. In: Chen L, Wang Y, Fu X, Chen L, editors. Novel optical nanoprobes for chemical and biological analysis. Berlin: Springer; 2014. p. 75–95. https://doi.org/10.1007/978-3-662-43624-0_4.

  5. Xie J, Zhang Q, Lee JY, Wang DIC. The synthesis of SERS-active gold nanoflower tags for in vivo applications. ACS Nano. 2008;2(12):2473–80. https://doi.org/10.1021/nn800442q.

    Article  CAS  PubMed  Google Scholar 

  6. Rennard SI, Berg R, Martin GR, Foidart JM, Robey PG. Enzyme-linked immunoassay (ELISA) for connective tissue components. Anal Biochem. 1980;104(1):205–14. https://doi.org/10.1016/0003-2697(80)90300-0.

    Article  CAS  PubMed  Google Scholar 

  7. Engvall E, Perlmann P. Enzyme-linked immunosorbent assay (ELISA) quantitative assay of immunoglobulin G. Immunochemistry. 1971;8(9):871–4. https://doi.org/10.1016/0019-2791(71)90454-X.

    Article  CAS  PubMed  Google Scholar 

  8. Bowie AR, Sanders MG, Worsfold PJ. Analytical applications of liquid phase chemiluminescence reactions—a review. J Biolumin Chemilumin. 1996;11(2):61–90. https://doi.org/10.1002/(sici)1099-1271(199603)11:2<61::aid-bio406>3.0.co;2-o.

  9. Fähnrich KA, Pravda M, Guilbault GG. Recent applications of electrogenerated chemiluminescence in chemical analysis. Talanta. 2001;54(4):531–59. https://doi.org/10.1016/S0039-9140(01)00312-5.

    Article  PubMed  Google Scholar 

  10. Zhang Z, Long Y, Pan J, Yan X. Preparation of fluorescence-encoded microspheres in a core–shell structure for suspension arrays. J Mater Chem. 2010;20(6):1179–85. https://doi.org/10.1039/B919955A.

    Article  CAS  Google Scholar 

  11. Wilson R, Cossins AR, Spiller DG. Encoded microcarriers for high-throughput multiplexed detection. Angew Chem Int Ed Engl. 2006;45(37):6104–17. https://doi.org/10.1002/anie.200600288.

    Article  CAS  PubMed  Google Scholar 

  12. Long Y, Zhang Z, Yan X, Xing J, Zhang K, Huang J, et al. Multiplex immunodetection of tumor markers with a suspension array built upon core–shell structured functional fluorescence-encoded microspheres. Anal Chim Acta. 2010;665(1):63–8. https://doi.org/10.1016/j.aca.2010.03.009.

    Article  CAS  PubMed  Google Scholar 

  13. He Q, Guan T, He Y, Lu B, Li D, Chen X, et al. Digital encoding based molecular imprinting suspension array for multiplexed label-free sensing of phenol derivatives. Sens Actuators B: Chem. 2018;271:367–73. https://doi.org/10.1016/j.snb.2018.05.101.

    Article  CAS  Google Scholar 

  14. Gao Y, Stanford WL, Chan WCW. Quantum-dot-encoded microbeads for multiplexed genetic detection of non-amplified DNA samples. Small. 2010;7(1):137–46. https://doi.org/10.1002/smll.201000909.

    Article  CAS  Google Scholar 

  15. Mattheakis LC, Dias JM, Choi Y-J, Gong J, Bruchez MP, Liu J, et al. Optical coding of mammalian cells using semiconductor quantum dots. Anal Biochem. 2004;327(2):200–8. https://doi.org/10.1016/j.ab.2004.01.031.

    Article  CAS  PubMed  Google Scholar 

  16. Zhao Y, Shum HC, Chen H, Adams LLA, Gu Z, Weitz DA. Microfluidic generation of multifunctional quantum dot barcode particles. J Am Chem Soc. 2011;133(23):8790–3. https://doi.org/10.1021/ja200729w.

    Article  CAS  PubMed  Google Scholar 

  17. Cao YC, Jin R, Mirkin CA. Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science (New York, NY). 2002;297(5586):1536–40. https://doi.org/10.1126/science.297.5586.1536.

    Article  CAS  Google Scholar 

  18. Cho H, Lee B, Liu GL, Agarwal A, Lee LP. Label-free and highly sensitive biomolecular detection using SERS and electrokinetic preconcentration. Lab Chip. 2009;9(23):3360–3. https://doi.org/10.1039/b912076a.

    Article  CAS  PubMed  Google Scholar 

  19. Lee S, Joo S, Park S, Kim S, Kim HC, Chung TD. SERS decoding of micro gold shells moving in microfluidic systems. Electrophoresis. 2010;31(10):1623–9. https://doi.org/10.1002/elps.200900743.

    Article  CAS  PubMed  Google Scholar 

  20. Kneipp K, Wang Y, Kneipp H, Perelman LT, Itzkan I, Dasari RR, et al. Single molecule detection using surface-enhanced Raman scattering (SERS). Phys Rev Lett. 1997;78(9):1667–70. https://doi.org/10.1103/PhysRevLett.78.1667.

    Article  CAS  Google Scholar 

  21. Schlücker S. Surface-enhanced Raman spectroscopy: concepts and chemical applications. Angew Chem Int Ed Engl. 2014;53(19):4756–95. https://doi.org/10.1002/anie.201205748.

    Article  CAS  PubMed  Google Scholar 

  22. Liu B, Zhao X, Jiang W, Fu D, Gu Z. Multiplex bioassays encoded by photonic crystal beads and SERS nanotags. Nanoscale. 2016;8(40):17465–71. https://doi.org/10.1039/c6nr05588e.

    Article  CAS  PubMed  Google Scholar 

  23. Dasary SSR, Singh AK, Senapati D, Yu H, Ray PC. Gold nanoparticle based label-free SERS probe for ultrasensitive and selective detection of trinitrotoluene. J Am Chem Soc. 2009;131(38):13806–12. https://doi.org/10.1021/ja905134d.

    Article  CAS  PubMed  Google Scholar 

  24. Yap LW, Chen H, Gao Y, Petkovic K, Liang Y, Si KJ, et al. Bifunctional plasmonic-magnetic particles for an enhanced microfluidic SERS immunoassay. Nanoscale. 2017;9(23):7822–9. https://doi.org/10.1039/c7nr01511a.

    Article  CAS  PubMed  Google Scholar 

  25. Orendorff CJ, Gole A, Sau TK, Murphy CJ. Surface-enhanced Raman spectroscopy of self-assembled monolayers: sandwich architecture and nanoparticle shape dependence. Anal Chem. 2005;77(10):3261–6. https://doi.org/10.1021/ac048176x.

  26. Nikoobakht B, El-Sayed MA. Surface-enhanced Raman scattering studies on aggregated gold nanorods. J Phys Chem A. 2003;107(18):3372–8. https://doi.org/10.1021/jp026770+.

  27. Duan J, Park K, MacCuspie RI, Vaia RA, Pachter R. Optical properties of rodlike metallic nanostructures: insight from theory and experiment. J Phys Chem C. 2009;113(35):15524–32. https://doi.org/10.1021/jp902448f.

  28. Li G, Zhu L, Wu Z, He Y, Tan H, Sun S. Digital concentration readout of DNA by absolute quantification of optically countable gold nanorods. Anal Chem. 2016;88(22):10994–1000. https://doi.org/10.1021/acs.analchem.6b02712.

  29. Jiang L, Qian J, Cai F, He S. Raman reporter-coated gold nanorods and their applications in multimodal optical imaging of cancer cells. Anal Bioanal Chem. 2011;400(9):2793. https://doi.org/10.1007/s00216-011-4894-6.

    Article  CAS  PubMed  Google Scholar 

  30. Wu L, Wang Z, Zong S, Huang Z, Zhang P, Cui Y. A SERS-based immunoassay with highly increased sensitivity using gold/silver core-shell nanorods. Biosens Bioelectron. 2012;38(1):94–9. https://doi.org/10.1016/j.bios.2012.05.005.

    Article  CAS  PubMed  Google Scholar 

  31. Tsukruk VV, Bliznyuk VN, Visser D, Campbell AL, Bunning TJ, Adams WW. Electrostatic deposition of polyionic monolayers on charged surfaces. Macromolecules. 1997;30(21):6615–25. https://doi.org/10.1021/ma961897g.

  32. Shen Z, He Y, Zhang G, He Q, Li D, Ji Y. Dual-wavelength digital holographic phase and fluorescence microscopy for an optical thickness encoded suspension array. Opt Lett. 2018;43(4):739–42. https://doi.org/10.1364/ol.43.000739.

    Article  CAS  PubMed  Google Scholar 

  33. He Q, Li D, He Y, Guan T, Zhang Y, Shen Z, et al. Optical demodulation system for digitally encoded suspension array in fluoroimmunoassay. J Biomed Opt. 2017;22(9):1–7. https://doi.org/10.1117/1.jbo.22.9.097003.

    Article  CAS  PubMed  Google Scholar 

  34. Pauliukaite R, Ghica ME, Fatibello-Filho O, Brett CMA. Comparative study of different cross-linking agents for the immobilization of functionalized carbon nanotubes within a chitosan film supported on a graphite−epoxy composite electrode. Anal Chem. 2009;81(13):5364–72. https://doi.org/10.1021/ac900464z.

    Article  CAS  PubMed  Google Scholar 

  35. Sharma R (2015) Glutaraldehyde sandwiched amino functionalised polymer based aptasensor for the determination and quantification of chloramphenicol. RSC Adv. 2015;5:69356–64 https://doi.org/10.1039/c5ra11131e.

  36. Lai Y, Sun S, He T, Schlücker S, Wang Y (2015) Raman-encoded microbeads for spectral multiplexing with SERS detection. RSC Adv. 2015;5:13762–7. https://doi.org/10.1039/C4RA16163G.

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Acknowledgements

Financial support from the Tianjin Applied Basic and Frontier Technology Research Program (16JCZDJC31200), the National Science Foundation of China (NSFC) (61875102, 61675113, 61527808), and the Science and Technology Research Program of Shenzhen City (JCYJ20170412170255060, JCYJ20160324163759208, JCYJ20170412171856582, JCYJ20170816161836562, JCYJ20170817111912585) is acknowledged.

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Authors and Affiliations

  1. School of Precision Instruments & Optoelectronics Engineering, Tianjin University, Tianjin, 300072, China

    Bei Wang

  2. Institute of Optical Imaging and Sensing, Shenzhen Key Laboratory for Minimal Invasive Medical Technologies, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, Guangdong, China

    Tian Guan, Qinghua He, Xuejing Chen, Guangxia Feng, Bangrong Lu, Xuesi Zhou & Yonghong He

  3. Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, Guangdong, China

    Jingying Jiang

  4. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, 100191, China

    Jingying Jiang

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  1. Bei Wang
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Wang, B., Guan, T., Jiang, J. et al. Gold-nanorod-enhanced Raman spectroscopy encoded micro-quartz pieces for the multiplex detection of biomolecules. Anal Bioanal Chem 411, 5509–5518 (2019). https://doi.org/10.1007/s00216-019-01929-5

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