Skip to main content
Log in

Label-free detection of ssDNA base insertion and deletion mutations by surface-enhanced Raman spectroscopy

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

Abstract

Surface-enhanced Raman spectroscopy (SERS), as a label-free, highly sensitive analytical method, has become an important tool for providing substance fingerprints. In this study, silver nanoparticles containing thiosulfate ions and calcium ions (Ag@SCNPs) have been used as an enhanced substrate to eliminate the interference of impurities on DNA signals. Intrinsic structural information on single-strand DNA (ssDNA) was directly obtained through SERS. The improved enhancement system was used to explore the base-stacking rules of ssDNA in a solution environment. For the first time, single-base insertion mutations and deletion mutations, as well as their exact mutation sites, were identified, and Raman spectra with high stability, repeatability, and high signal-to-noise ratio were obtained. The method is simple, fast, and accurate, and the detection process is nondestructive. It has potential to be applied in the fields of medical diagnosis and genetics research.

Graphical abstract

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

Access this article

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

References

  1. Martínez-Jiménez F, Muios F, Sentís I, Deu-Pons J, Lopez-Bigas N. A compendium of mutational cancer driver genes. Nat Rev Cancer. 2020;20:555–72.

  2. Malapelle U, Bellevicine C, Zeppa P, Palombini L, Troncone G. Cytology-based gene mutation tests to predict response to anti-epidermal growth factor receptor therapy: a review. Diagn Cytopathol. 2011;39(9):703–10.

    Article  Google Scholar 

  3. Lee S, Son JH, Lee LP. Rapid detection of methicillin-resistant Staphylococcus aureus using bubble-free microfluidic PCR. Biophys J. 2014;106(2):417a-a.

    Article  Google Scholar 

  4. You M, Cao L, Xu F. Plasmon-driven ultrafast photonic PCR. Trends Biochem Sci. 2019;45:174–5.

    Article  Google Scholar 

  5. Zhang H, Li H, Zhu H, Pekárek J, Neuil P. Revealing the secrets of PCR. Sens Actuators B. 2019;298:126924.

    Article  CAS  Google Scholar 

  6. Idrees MT, Ulbright TM, Epstein JI. Fluorescent in situ hybridization analysis for 12p alterations in sarcomatoid yolk sac tumors. Am J Surg Patho. 2019;43:1566–73.

    Article  Google Scholar 

  7. Alán L, Zelenka J, JežEk J, JežEk P. Fluorescent in situ hybridization of mitochondrial DNA and RNA. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 2010;1797(supp-S):403–8.

    Google Scholar 

  8. Trcek T, Chao JA, Larson DR, Park HY, Zenklusen D, Shenoy SM, et al. Single-mRNA counting using fluorescent in situ hybridization in budding yeast. Nat Protoc. 2012;7(2):408–19.

    Article  CAS  Google Scholar 

  9. Li D, Yao D, Li C, Luo Y, Jiang Z. Nanosol SERS quantitative analytical method: a review. TrAC Trends Anal Chem. 2020;127:115885.

    Article  CAS  Google Scholar 

  10. Lu Y, Zhong J, Yao G, Huang Q. A label-free SERS approach to quantitative and selective detection of mercury (II) based on DNA aptamer-modified SiO2@Au core/shell nanoparticles. Sens Actuators B. 2018;258(APR):365–72.

    Article  CAS  Google Scholar 

  11. Papadopoulou E, Bell SEJ. Label-free detection of single-base mismatches in DNA by surface-enhanced Raman spectroscopy. Angew Chem. 2011;123(39):9224–7.

    Article  Google Scholar 

  12. Morla-Folc J, Gisbert-Quili P, Masett M, Garcia-Rico E, Alvarez-Puebl RA, Guerrin L. Conformational SERS classification of K-Ras point mutations for cancer diagnostics. Angew Chem Int Ed. 2017;56:2381–5.

    Article  Google Scholar 

  13. Zeng J, Dong M, Zhu B, Chen D, Li Y. Label-free detection of C-T mutations by surface-enhanced Raman spectroscopy using thiosulfate-modified nanoparticles. Anal Chem. 2021;93:1951–6.

    Article  CAS  Google Scholar 

  14. Liu BJ, Lin K, Shu H, Xiang W, Ren B. Extraction of absorption and scattering contribution of metallic nanoparticles toward rational synthesis and application. Anal Chem. 2015;87(2):1058–65.

    Article  CAS  Google Scholar 

  15. Xie L, Lu JL, Chen GY, Liu T, Tian ZQ. Key role of direct adsorption on SERS sensitivity: synergistic effect among target, aggregating agent, and surface with Au or Ag colloid as SERS substrate. J Phys Chem Lett. 2020;11:1022–9.

    Article  CAS  Google Scholar 

  16. Albanese A, Tang PS, Chan WCW. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng. 2012;14(1):1–16.

    Article  CAS  Google Scholar 

  17. Cho EC, Xie J, Wurm PA, Xia Y. Understanding the role of surface charges in cellular adsorption versus internalization by selectively removing gold nanoparticles on the cell surface with a I2/KI etchant. Nano Lett. 2009;9(3):1080–4.

    Article  CAS  Google Scholar 

  18. Zong C, Xu M, Xu LJ, Wei T, Ma X, Zheng XS, et al. Surface-enhanced Raman spectroscopy for bioanalysis: reliability and challenges. Chem Rev. 2018;118:4946–80.

    Article  CAS  Google Scholar 

  19. Cozzi F, Cinquini M, Annuziata R, et al. Dominance of polar/.pi. over charge-transfer effects in stacked phenyl interactions. J Am Chem Soc. 1993;115:5530–1.

    Article  Google Scholar 

  20. Gu J, Wang J, Leszczynski J. Electron attachment to the cytosine-centered DNA single strands: does base stacking matter? J Phys Chem B. 2012;116(4):1458–66.

    Article  CAS  Google Scholar 

  21. Guckian KM, Schweitzer BA, Ren XF, Sheils CJ, Paris PL, Tahmassebi DC, et al. Experimental measurement of aromatic stacking affinities in the context of duplex DNA. J Am Chem Soc. 1996;118(34):8182–3.

    Article  CAS  Google Scholar 

  22. Guckian KM, Schweitzer BA, Ren XF, Sheils CJ, Kool ET. Factors contributing to aromatic stacking in water: evaluation in the context of DNA. J Am Chem Soc. 2000;122(10):2213–22.

    Article  CAS  Google Scholar 

  23. Li Y, Gao T, Xu G, Xiang X, Guo X. The base pair contents and sequences of DNA double helixes differentiated by surface-enhanced Raman spectroscopy. J Phys Chem Lett. 2019;10(11):3013–8.

    Article  CAS  Google Scholar 

  24. Guerrini L, Alvarez-Puebla RA. Structural recognition of triple-stranded DNA by surface-enhanced RAMAN spectroscopy. Nanomaterials. 2021;11(2):326.

    Article  CAS  Google Scholar 

  25. Li D, Xia L, Zhou Q, Wang L, Chen D, Gao X, Li Y. Ultra-small fluorescent metal nanoclusters: synthesis and biological applications. Anal Chem. 2020;92:12769–73.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (21961007), and the Science and Technology Support Project of Guizhou Province ([2020] 4Y218).

Author information

Authors and Affiliations

Authors

Contributions

Yufeng Zhang, Jiayu Zeng, Chao Huang, Bixue Zhu, Qianjun Zhang, and Dongmei Chen are acknowledged for contributing results to this study.

Corresponding author

Correspondence to Dongmei Chen.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 3317 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Zeng, J., Huang, C. et al. Label-free detection of ssDNA base insertion and deletion mutations by surface-enhanced Raman spectroscopy. Anal Bioanal Chem 414, 1461–1468 (2022). https://doi.org/10.1007/s00216-021-03799-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-021-03799-2

Keywords

Navigation