Skip to main content

Advertisement

SpringerLink
Log in

MutS protein-based fiber optic particle plasmon resonance biosensor for detecting single nucleotide polymorphisms

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

A Publisher Correction to this article was published on 04 May 2021

This article has been updated

Abstract

A new biosensing method is presented to detect gene mutation by integrating the MutS protein from bacteria with a fiber optic particle plasmon resonance (FOPPR) sensing system. In this method, the MutS protein is conjugated with gold nanoparticles (AuNPs) deposited on an optical fiber core surface. The target double-stranded DNA containing an A and C mismatched base pair in a sample can be captured by the MutS protein, causing increased absorption of green light launching into the fiber and hence a decrease in transmitted light intensity through the fiber. As the signal change is enhanced through consecutive total internal reflections along the fiber, the limit of detection for an AC mismatch heteroduplex DNA can be as low as 0.49 nM. Because a microfluidic chip is used to contain the optical fiber, the narrow channel width allows an analysis time as short as 15 min. Furthermore, the label-free and real-time nature of the FOPPR sensing system enables determination of binding affinity and kinetics between MutS and single-base mismatched DNA. The method has been validated using a heterozygous PCR sample from a patient to determine the allelic fraction. The obtained allelic fraction of 0.474 reasonably agrees with the expected allelic fraction of 0.5. Therefore, the MutS-functionalized FOPPR sensor may potentially provide a convenient quantitative tool to detect single nucleotide polymorphisms in biological samples with a short analysis time at the point-of-care sites.

Graphical abstract

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
Scheme 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

All data generated and analyses during this study are included in this published article and its supplementary material file.

Change history

References

  1. Andrew AS, Gui J, Sanderson AC, Mason RA, Morlock EV, Schned AR, et al. Bladder cancer SNP panel predicts susceptibility and survival. Hum Genet. 2009;125:527–39. https://doi.org/10.1007/s00439-009-0645-6.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Yu L, Yin B, Qu K, Li J, Jin Q, Liu L, et al. Screening for susceptibility genes in hereditary non-polyposis colorectal cancer. Oncol Lett. 2018;15:9413–9. https://doi.org/10.3892/ol.2018.8504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Fertrin KY, Costa FF. Genomic polymorphisms in sickle cell disease: implications for clinical diversity and treatment. Expert Rev Hematol. 2010;3:443–58. https://doi.org/10.1586/ehm.10.44.

    Article  CAS  PubMed  Google Scholar 

  4. Bare LA, Morrison AC, Rowland CM, Shiffman D, Luke MM, Iakoubova OA, et al. Five common gene variants identify elevated genetic risk for coronary heart disease. Gen Med. 2007;9:682–9. https://doi.org/10.1097/GIM.0b013e318156fb62.

    Article  CAS  Google Scholar 

  5. Jonkers IH, Wijmenga C. Context-specific effects of genetic variants associated with autoimmune disease. Hum Mol Genet. 2017;26(R2):R185–92. https://doi.org/10.1093/hmg/ddx254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genom Hum Genet. 2008;9:387–402. https://doi.org/10.1146/annurev.genom.9.081307.164359.

    Article  CAS  Google Scholar 

  7. Shendure J, Balasubramanian S, Church GM, Gilbert W, Rogers J, Schloss JA, et al. DNA sequencing at 40: past, present and future. Nature. 2017;550:345–53. https://doi.org/10.1038/nature24286.

    Article  CAS  PubMed  Google Scholar 

  8. Samura O. Update on noninvasive prenatal testing: a review based on current worldwide research. J Obstet Gynaecol Res. 2020;46:1246–54. https://doi.org/10.1111/jog.14268.

    Article  PubMed  Google Scholar 

  9. Zhang J, Li J, Saucier JB, Feng Y, Jiang Y, Sinson J, et al. Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA. Nat Med. 2019;25:439–47. https://doi.org/10.1038/s41591-018-0334-x.

    Article  CAS  PubMed  Google Scholar 

  10. Fahy E, Nazarbaghi R, Zomorrodi M, Herrnstadt C, Parker WD, Davis RE, et al. Multiplex fluorescence-based primer extension method for quantitative mutation analysis of mitochondrial DNA and its diagnostic application for Alzheimer’s disease. Nucleic Acids Res. 1997;25:3102–9. https://doi.org/10.1093/nar/25.15.3102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen YT, Hsu CL, Hou SY. Detection of single-nucleotide polymorphisms using gold nanoparticles and single-strand-specific nucleases. Anal Biochem. 2008;375:299–305. https://doi.org/10.1016/j.ab.2007.12.036.

    Article  CAS  PubMed  Google Scholar 

  12. Xu W, Xue X, Li T, Zeng H, Liu X. Ultrasensitive and selective colorimetric DNA detection by nicking endonuclease assisted nanoparticle amplification. Angew Chem Int Ed. 2009;48:6849–52. https://doi.org/10.1002/anie.200901772.

    Article  CAS  Google Scholar 

  13. Deng M, Zhang D, Zhou Y, Zhou X. Highly effective colorimetric and visual detection of nucleic acids using an asymmetrically split peroxidase DNAzyme. J Am Chem Soc. 2008;130:13095–102. https://doi.org/10.1021/ja803507d.

    Article  CAS  PubMed  Google Scholar 

  14. Lapitan LDS Jr, Xu Y, Guo Y, Zhou D. Combining magnetic nanoparticle capture and poly-enzyme nanobead amplification for ultrasensitive detection and discrimination of DNA single nucleotide polymorphisms. Nanoscale. 2019;11:1195–204. https://doi.org/10.1039/C8NR07641C.

    Article  CAS  PubMed  Google Scholar 

  15. Gotoh M, Hasebe M, Ohira T, Hasegawa Y, Shinohara Y, Sota H, et al. Rapid method for detection of point mutations using mismatch binding protein (MutS) and an optical biosensor. Gen Anal Biomol Eng. 1997;14:47–50. https://doi.org/10.1016/S1050-3862(97)00009-0.

    Article  CAS  Google Scholar 

  16. Ma X, Truong PL, Ahn NH, Sim SJ. Single gold nanoplasmonic sensor for clinical cancer diagnosis based on specific interaction between nucleic acids and protein. Biosens Bioelectron. 2015;67:59–65. https://doi.org/10.1016/j.bios.2014.06.038.

    Article  CAS  PubMed  Google Scholar 

  17. Lishanski A, Ostrander EA, Rine J. Mutation detection by mismatch binding protein, MutS, in amplified DNA: application to the cystic fibrosis gene. Proc Natl Acad Sci U S A. 1994;91:2674–8. https://doi.org/10.1073/pnas.91.7.2674.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wagner R, Debble P, Radman M. Mutation detection using immobilized mismatch binding protein (MutS). Nucleic Acids Res. 1995;23:3944–8. https://doi.org/10.1093/nar/23.19.3944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Su SS, Lahue RS, Au KG, Modrich P. Mispair specificity of methyl-directed DNA mismatch correction in vitro. J Biol Chem. 1988;263:6829–35. https://doi.org/10.1016/S0021-9258(18)68718-6.

    Article  CAS  PubMed  Google Scholar 

  20. Wang H, Yang Y, Schofield MJ, Du C, Fridman Y, Lee SD, et al. DNA bending and unbending by MutS govern mismatch recognition and specificity. Proc Natl Acad Sci U S A. 2003;100:14822–7. https://doi.org/10.1073/pnas.2433654100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Stanislawska-Sachadyn A, Sachadyn P. MutS as a tool for mutation detection. Acta Biochim Polon. 2005;52:575–83. https://doi.org/10.18388/abp.2005_3417.

    Article  CAS  PubMed  Google Scholar 

  22. Brown J, Brown T, Fox KR. Affinity of mismatch-binding protein MutS for heteroduplexes containing different mismatches. Biochem J. 2001;354:627–33. https://doi.org/10.1042/0264-6021:3540627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Behrensdorf HA, Pignot M, Windhab N, Kappel A. Rapid parallel mutation scanning of gene fragments using a microelectronic protein-DNA chip format. Nucleic Acids Res. 2002;30:e64. https://doi.org/10.1093/nar/gnf063.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Palecek E, Masarík M, Kizek R, Kuhlmeier D, Hassmann J, Schulein J. Sensitive electrochemical determination of unlabeled MutS protein and detection of point mutations in DNA. Anal Chem. 2004;76:5930–6. https://doi.org/10.1021/ac049474x.

    Article  CAS  PubMed  Google Scholar 

  25. Han A, Takarada T, Shibata T, Nakayama M, Maeda M. A MutS protein-immobilized Au electrode for detecting single-base mismatch of DNA. Anal Sci. 2006;22:663–6. https://doi.org/10.2116/analsci.22.663.

    Article  CAS  PubMed  Google Scholar 

  26. Chen H, Liu XJ, Liu YL, Jiang JH, Shen GL, Yu RQ. Electrochemical scanning of DNA point mutations via MutS protein-mediated mismatch recognition. Biosens Bioelectron. 2009;24:1955–61. https://doi.org/10.1016/j.bios.2008.09.029.

    Article  CAS  PubMed  Google Scholar 

  27. Li CZ, Long YT, Lee JS, Kraatz HB. Protein-DNA interaction: impedance study of MutS binding to a DNA mismatch. Chem Commun. 2004:574–5. https://doi.org/10.1039/B314642A.

  28. Gong H, Zhong T, Gao L, Li X, Bi L, Kraatz HB. Unlabeled hairpin DNA probe for electrochemical detection of single-nucleotide mismatches based on MutS−DNA interactions. Anal Chem. 2009;81:8639–43. https://doi.org/10.1021/ac901371n.

    Article  CAS  PubMed  Google Scholar 

  29. Cho M, Lee S, Han SY, Park JY, Rahman MA, Shim YB, et al. Electrochemical detection of mismatched DNA using a MutS probe. Nucleic Acids Res. 2006;34:e75. https://doi.org/10.1093/nar/gkl364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kim S, Kim TG, Byon HR, Shin HJ, Ban C, Choi HC. Recognition of single mismatched DNA using MutS-immobilized carbon nanotube field effect transistor devices. J Phys Chem B. 2009;113:12164–8. https://doi.org/10.1021/jp9063559.

    Article  CAS  PubMed  Google Scholar 

  31. Su X, Robelek R, Wu Y, Wang G, Knoll W. Detection of point mutation and insertion mutations in DNA using a quartz crystal microbalance and MutS, a mismatch binding protein. Anal Chem. 2004;76:489–94. https://doi.org/10.1021/ac035175g.

    Article  CAS  PubMed  Google Scholar 

  32. Wilson PK, Jiang T, Minunni ME, Turner AFP, Mascini M. A novel optical biosensor format for the detection of clinically relevant TP53 mutations. Biosens Bioelectron. 2005;20:2310–3. https://doi.org/10.1016/j.bios.2004.11.020.

    Article  CAS  PubMed  Google Scholar 

  33. Ma X, Song S, Kim S, Kwon MS, Lee H, Park W, et al. Single gold-bridged nanoprobes for identification of single point DNA mutations. Nat Commun. 2019;10:836. https://doi.org/10.1038/s41467-019-08769-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cheng SF, Chau LK. Colloidal gold-modified optical fiber for chemical and biochemical sensing. Anal Chem. 2003;75:16–21. https://doi.org/10.1021/ac020310v.

    Article  CAS  PubMed  Google Scholar 

  35. Chiang CY, Hsieh ML, Huang KW, Chau LK, Chang CM, Lyu SR. Fiber optic particle plasmon resonance sensor for detection of interleukin-1β in synovial fluids. Biosens Bioelectron. 2010;26:1036–42. https://doi.org/10.1016/j.bios.2010.08.047.

    Article  CAS  PubMed  Google Scholar 

  36. Wu CW, Chiang CY, Chen CH, Chiang CS, Wang CT, Chau LK. Self-referencing fiber optic particle plasmon resonance sensing system for real-time biological monitoring. Talanta. 2016;146:291–8. https://doi.org/10.1016/j.talanta.2015.08.047.

    Article  CAS  PubMed  Google Scholar 

  37. Wu WT, Chen CH, Chiang CY, Chau LK. Effect of surface coverage of gold nanoparticles on the refractive index sensitivity in fiber-optic nanoplasmonic sensing. Sensors. 2018;18:1759. https://doi.org/10.3390/s18061759.

    Article  CAS  PubMed Central  Google Scholar 

  38. Chau LK, Lin YF, Cheng SF, Lin TJ. Fiber-optic chemical and biochemical probes based on localized surface plasmon resonance. Sens Actuat B. 2006;113:100–5. https://doi.org/10.1016/j.snb.2005.02.034.

    Article  CAS  Google Scholar 

  39. Origa R. β-Thalassemia. Genet Med. 2017;19:609–19. https://doi.org/10.1038/gim.2016.173.

    Article  CAS  PubMed  Google Scholar 

  40. Wang HC, Hsieh LL, Liu YC, Hsiao HH, Lin SK, Tsai WC, et al. The epidemiologic transition of thalassemia and associated hemoglobinopathies in southern Taiwan. Ann Hematol. 2017;96:183–8. https://doi.org/10.1007/s00277-016-2868-7.

    Article  CAS  PubMed  Google Scholar 

  41. Babic I, Andrew SE, Jirik FR. MutS interaction with mismatch and alkylated base containing DNA molecules detected by optical biosensor. Mutat Res. 1996;372:87–96. https://doi.org/10.1016/S0027-5107(96)00170-4.

    Article  CAS  PubMed  Google Scholar 

  42. Tseng YT, Li WY, Yu YW, Chiang CY, Liu SQ, Chau LK, et al. Fiber optic particle plasmon resonance biosensor for label-free detection of nucleic acids and its application to HLA-B27 mRNA detection in patients with ankylosing spondylitis. Sensors. 2020;20:3137. https://doi.org/10.3390/s20113137.

    Article  CAS  PubMed Central  Google Scholar 

  43. Chaudhari PP, Chau LK, Tseng YT, Huang CJ, Chen YL. A fiber optic nanoplasmonic biosensor for the sensitive detection of ampicillin and its analogs. Microchim Acta. 2020;187:396. https://doi.org/10.1007/s00604-020-04381-w.

    Article  CAS  Google Scholar 

  44. Chang TC, Wu CC, Wang SC, Chau LK, Hsieh WH. Using a fiber optic particle plasmon resonance biosensor to determine kinetic constants of antigen-antibody binding reaction. Anal Chem. 2013;85:245–50. https://doi.org/10.1021/ac302590n.

    Article  CAS  PubMed  Google Scholar 

  45. Yu SN, Tsai TH, Chau LK. Optical biosensing system and method thereof. US Patent Appl Pub: US 2021/0011011 A1.

  46. Hsu WT, Hsieh WH, Cheng SF, Jen CP, Wu CC, Li CH, et al. Integration of fiber optic-particle plasmon resonance biosensor with microfluidic chip. Anal Chim Acta. 2011;697:75–82. https://doi.org/10.1016/j.aca.2011.04.023.

    Article  CAS  PubMed  Google Scholar 

  47. Chiang CY, Huang TT, Wang CH, Huang CJ, Tsai TH, Yu SN, et al. Fiber optic nanogold-linked immunosorbent assay for rapid detection of procalcitonin at femtomolar concentration level. Biosens Bioelectron. 2020;151:111871. https://doi.org/10.1016/j.bios.2019.111871.

    Article  CAS  PubMed  Google Scholar 

  48. Sharma A, Doucette C, Biro FN, Hingorani MM. Slow conformational changes in MutS and DNA direct ordered transitions between mismatch search, recognition and signaling of DNA repair. J Mol Biol. 2013;425:4192–205. https://doi.org/10.1016/j.jmb.2013.08.011.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Ministry of Science and Technology of Taiwan (Grants MOST 105-2113-M-194-009-MY3 and MOST 107-2119-M-194-001) and Center for Nano Bio-Detection from the Featured Research Areas College Development Plan of National Chung Cheng University.

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry and Center for Nano Bio-Detection, National Chung Cheng University, Chiayi, 62102, Taiwan

    Loan Thi Ngo, Yen-Ta Tseng, Ting-Chou Chang & Lai-Kwan Chau

  2. Department of Dentistry, Institute of Oral Medicine, Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan

    Wei-Kai Wang & Tze-Ta Huang

  3. Department of Obstetrics Gynecology, National Cheng Kung University Hospital, College of Medicine and Hospital, National Cheng Kung University, Tainan, 70101, Taiwan

    Pao-Lin Kuo

Authors
  1. Loan Thi Ngo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei-Kai Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yen-Ta Tseng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ting-Chou Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pao-Lin Kuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lai-Kwan Chau
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tze-Ta Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: Lai-Kwan Chau, Tze-Ta Huang. Methodology: Lai-Kwan Chau, Tze-Ta Huang. Resources: Pao-Lin Kuo. Investigation: Loan Thi Ngo, Wei-Kai Wang. Formal analysis: Loan Thi Ngo, Yen-Ta Tseng, Ting-Chou Chang. Writing-original draft: Loan Thi Ngo, Yen-Ta Tseng. Writing-review and editing: Lai-Kwan Chau, Tze-Ta Huang. Funding acquisition: Lai-Kwan Chau.

Corresponding authors

Correspondence to Lai-Kwan Chau or Tze-Ta Huang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

This study was reviewed and approved by the Institutional Review Board (IRB) of National Cheng Kung University Hospital. The patients/participants provided their written informed consent to participate in this study.

Source of biological material

National Cheng Kung University Hospital.

Additional information

Publisher’s note

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

The original online version of this article was revised: Unfortunately, during production the typesetter mistakenly uploaded the wrong file as the graphical abstract figure with black unreadable background color.

Supplementary information

ESM 1

(PDF 336 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ngo, L.T., Wang, WK., Tseng, YT. et al. MutS protein-based fiber optic particle plasmon resonance biosensor for detecting single nucleotide polymorphisms. Anal Bioanal Chem 413, 3329–3337 (2021). https://doi.org/10.1007/s00216-021-03271-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-021-03271-1

Keywords

Search

Navigation