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Signaling Kinetics of DNA and Aptamer Biosensors Revealing Graphene Oxide Surface Heterogeneity

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Abstract

Adsorption of fluorescently labeled DNA and aptamer probes to graphene oxide (GO) has been one of the most popular methods for developing biosensors. In the presence of target analytes, the quenched fluorescence would recover. In this work, we followed the kinetics of the reactions and found that the fluorescence would eventually drop after an initial increase, and this was attributed to the re-adsorption of the desorbed probe DNA molecules. Both a DNA probe and an aptamer for adenosine were used. This re-adsorption was attributed to the surface heterogeneity of GO, and the DNA probes desorbed from relatively weaker binding sites were re-adsorbed on the stronger binding sites. This re-adsorption can be avoided by extensive washing the samples, and also by blocking the GO surface or by heating. This fundamental understanding is important for achieving a stable signal of such biosensors.

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References

  1. Lu CH, Yang HH, Zhu CL, Chen X, Chen GN. A graphene platform for sensing biomolecules. Angew Chem Int Ed. 2009;48:4785–7.

    Article  CAS  Google Scholar 

  2. Lopez A, Liu J. Covalent and noncovalent functionalization of graphene oxide with DNA for smart sensing. Adv Intell Syst. 2020;2:2000123.

    Article  Google Scholar 

  3. Liu B, Liu J. Sensors and biosensors based on metal oxide nanomaterials. TrAC Trends Anal Chem. 2019;121:115690.

    Article  CAS  Google Scholar 

  4. Wu M, Kempaiah R, Huang P-JJ, Maheshwari V, Liu J. Adsorption and desorption of DNA on graphene oxide studied by fluorescently labeled oligonucleotides. Langmuir. 2011;27:2731–8.

    Article  CAS  PubMed  Google Scholar 

  5. Shi XX, Xu H, Wu YN, Zhao YM, Meng HM, Li ZH, Qu LB. Two-dimension (2D) Cu-MOFs/aptamer nanoprobe for in situ atp imaging in living cells. J Anal Test. 2021;5:165–73.

    Article  Google Scholar 

  6. Schlenoff JB. Zwitteration: coating surfaces with zwitterionic functionality to reduce nonspecific adsorption. Langmuir. 2014;30:9625–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Liu B, Liu J. Interface driven hybrid materials based on DNA-functionalized gold nanoparticles. Matter. 2019;1:825–47.

    Article  Google Scholar 

  8. Zandieh M, Hagar BM, Liu J. Interfacing DNA and polydopamine nanoparticles and its applications. Part Part Syst Charact. 2020;37:2000208.

    Article  CAS  Google Scholar 

  9. Vandeventer PE, Mejia J, Nadim A, Johal MS, Niemz A. DNA adsorption to and elution from silica surfaces: Influence of amino acid buffers. J Phys Chem B. 2013;117:10742–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tang LH, Wang Y, Li JH. The graphene/nucleic acid nanobiointerface. Chem Soc Rev. 2015;44:6954–80.

    Article  CAS  PubMed  Google Scholar 

  11. Liu B, Salgado S, Maheshwari V, Liu J. DNA adsorbed on graphene and graphene oxide: fundamental interactions, desorption and applications. Curr Opin Colloid Interface Sci. 2016;26:41–9.

    Article  CAS  Google Scholar 

  12. Peña-Bahamonde J, Nguyen HN, Fanourakis SK, Rodrigues DF. Recent advances in graphene-based biosensor technology with applications in life sciences. J Nanobiotechnol. 2018;16:75.

    Article  Google Scholar 

  13. Tabunag JS, Guo YJ, Yu HZ. Interactions between hemin-binding DNA aptamers and hemin-graphene nanosheets: reduced affinity but unperturbed catalytic activity. J Anal Test. 2019;3:107–16.

    Article  Google Scholar 

  14. Su S, Sun Q, Gu XD, Xu YQ, Shen JL, Zhu D, Chao J, Fan CH, Wang LH. Two-dimensional nanomaterials for biosensing applications. TrAC Trends Anal Chem. 2019;119:115610.

    Article  CAS  Google Scholar 

  15. Lerf A, He H, Forster M, Klinowski J. Structure of graphite oxide revisited. J Phys Chem B. 1998;102:4477–82.

    Article  CAS  Google Scholar 

  16. Gomez-Navarro C, Meyer JC, Sundaram RS, Chuvilin A, Kurasch S, Burghard M, Kern K, Kaiser U. Atomic structure of reduced graphene oxide. Nano Lett. 2010;10:1144–8.

    Article  CAS  PubMed  Google Scholar 

  17. Liu B, Zhao Y, Jia Y, Liu J. Heating drives DNA to hydrophobic regions while freezing to hydrophilic regions of graphene oxide for highly robust biosensors. J Am Chem Soc. 2020;142:14702–9.

    Article  CAS  PubMed  Google Scholar 

  18. Kushalkar MP, Liu B, Liu J. Promoting DNA adsorption by acids and polyvalent cations: beyond charge screening. Langmuir. 2020;36:11183–95.

    Article  CAS  PubMed  Google Scholar 

  19. Becheru DF, Vlăsceanu GM, Banciu A, Vasile E, Ioniţă M, Burns JS. Optical graphene-based biosensor for nucleic acid detection; influence of graphene functionalization and ionic strength. Int J Mol Sci. 2018;19:3230.

    Article  PubMed Central  Google Scholar 

  20. Lopez A, Zhao Y, Huang ZC, Guo YF, Guan SK, Jia Y, Liu JW. Poly-cytosine deoxyribonucleic acid strongly anchoring on graphene oxide due to flexible backbone phosphate interactions. Adv Mater Interfaces. 2021;8:2001798.

    Article  CAS  Google Scholar 

  21. Huang ZC, Zhao Y, Liu BW, Guan SK, Liu JW. Stronger adsorption of phosphorothioate DNA oligonucleotides on graphene oxide by van der Waals forces. Langmuir. 2020;36:13708–15.

    Article  CAS  PubMed  Google Scholar 

  22. Lee J, Yim Y, Kim S, Choi M-H, Choi B-S, Lee Y, Min D-H. In-depth investigation of the interaction between DNA and nano-sized graphene oxide. Carbon. 2016;97:92–8.

    Article  CAS  Google Scholar 

  23. Lopez A, Liu J. Nanomaterial and aptamer-based sensing: target binding versus target adsorption illustrated by the detection of adenosine and ATP on metal oxides and graphene oxide. Anal Chem. 2021;93:3018–25.

    Article  CAS  PubMed  Google Scholar 

  24. He SJ, Song B, Li D, Zhu CF, Qi WP, Wen YQ, Wang LH, Song SP, Fang HP, Fan CH. A graphene nanoprobe for rapid, sensitive, and multicolor fluorescent DNA analysis. Adv Funct Mater. 2010;20:453–9.

    Article  CAS  Google Scholar 

  25. Wen YQ, Xing FF, He SJ, Song SP, Wang LH, Long YT, Li D, Fan CH. A graphene-based fluorescent nanoprobe for silver(I) ions detection by using graphene oxide and a silver-specific oligonucleotide. Chem Commun. 2010;46:2596–8.

    Article  CAS  Google Scholar 

  26. Dong HF, Gao WC, Yan F, Ji HX, Ju HX. Fluorescence resonance energy transfer between quantum dots and graphene oxide for sensing biomolecules. Anal Chem. 2010;82:5511–7.

    Article  CAS  PubMed  Google Scholar 

  27. Li F, Huang Y, Yang Q, Zhong ZT, Li D, Wang LH, Song SP, Fan CH. A graphene-enhanced molecular beacon for homogeneous DNA detection. Nanoscale. 2010;2:1021–6.

    Article  CAS  PubMed  Google Scholar 

  28. Liu F, Choi JY, Seo TS. Graphene oxide arrays for detecting specific DNA hybridization by fluorescence resonance energy transfer. Biosens Bioelectron. 2010;25:2361–5.

    Article  CAS  PubMed  Google Scholar 

  29. Lu CH, Li J, Liu JJ, Yang HH, Chen X, Chen GN. Increasing the sensitivity and single-base mismatch selectivity of the molecular beacon using graphene oxide as the “nanoquencher.” Chem Eur J. 2010;16:4889–94.

    Article  CAS  PubMed  Google Scholar 

  30. Chang HX, Tang LH, Wang Y, Jiang JH, Li JH. Graphene fluorescence resonance energy transfer aptasensor for the thrombin detection. Anal Chem. 2010;82:2341–6.

    Article  CAS  PubMed  Google Scholar 

  31. Jang H, Kim YK, Kwon HM, Yeo WS, Kim DE, Min DH. A graphene-based platform for the assay by helicase. Angew Chem Int Ed. 2010;49:5703–7.

    Article  CAS  Google Scholar 

  32. Jung JH, Cheon DS, Liu F, Lee KB, Seo TS. A graphene oxide based immuno-biosensor for pathogen detection. Angew Chem Int Ed. 2010;49:5708–11.

    Article  CAS  Google Scholar 

  33. Song YJ, Qu KG, Zhao C, Ren JS, Qu XG. Graphene oxide: Intrinsic peroxidase catalytic activity and its application to glucose detection. Adv Mater. 2010;22:2206–10.

    Article  CAS  PubMed  Google Scholar 

  34. Wang Y, Li ZH, Hu DH, Lin CT, Li JH, Lin YH. Aptamer/graphene oxide nanocomplex for in situ molecular probing in living cells. J Am Chem Soc. 2010;132:9274–6.

    Article  CAS  PubMed  Google Scholar 

  35. Lu C-H, Li J, Lin M-H, Wang Y-W, Yang H-H, Chen X, Chen G-N. Amplified aptamer-based assay through catalytic recycling of the analyte. Angew Chem Int Ed. 2010;49:8454–7.

    Article  CAS  Google Scholar 

  36. Xu S, Zhan J, Man B, Jiang S, Yue W, Gao S, Guo C, Liu H, Li Z, Wang J, Zhou Y. Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor. Nat Commun. 2017;8:14902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Huizenga DE, Szostak JW. A DNA aptamer that binds adenosine and ATP. Biochemistry. 1995;34:656–65.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang F, Liu J. Label-free colorimetric biosensors based on aptamers and gold nanoparticles: a critical review. Anal Sens. 2021;1:30–43.

    Google Scholar 

  39. Zhang F, Huang P-JJ, Liu J. Sensing adenosine and ATP by aptamers and gold nanoparticles: opposite trends of color change from domination of target adsorption instead of aptamer binding. ACS Sens. 2020;5:2885–93.

    Article  CAS  PubMed  Google Scholar 

  40. Zong C, Liu J. The arsenic-binding aptamer cannot bind arsenic: critical evaluation of aptamer selection and binding. Anal Chem. 2019;91:10887–93.

    Article  CAS  PubMed  Google Scholar 

  41. Varghese N, Mogera U, Govindaraj A, Das A, Maiti PK, Sood AK, Rao CNR. Binding of DNA nucleobases and nucleosides with graphene. ChemPhysChem. 2009;10:206–10.

    Article  CAS  PubMed  Google Scholar 

  42. Antony J, Grimme S. Structures and interaction energies of stacked graphene-nucleobase complexes. Phys Chem Chem Phys. 2008;10:2722–9.

    Article  CAS  PubMed  Google Scholar 

  43. Gowtham S, Scheicher RH, Ahuja R, Pandey R, Karna SP. Physisorption of nucleobases on graphene: density-functional calculations. Phys Rev B. 2007;76:033401.

    Article  Google Scholar 

  44. Lu C, Huang P-JJ, Liu B, Ying Y, Liu J. Comparison of graphene oxide and reduced graphene oxide for DNA adsorption and sensing. Langmuir. 2016;32:10776–83.

    Article  CAS  PubMed  Google Scholar 

  45. Lu CH, Zhu CL, Li J, Liu JJ, Chen X, Yang HH. Using graphene to protect DNA from cleavage during cellular delivery. Chem Commun. 2010;46:3116–8.

    Article  CAS  Google Scholar 

  46. Tang ZW, Wu H, Cort JR, Buchko GW, Zhang YY, Shao YY, Aksay IA, Liu J, Lin YH. Constraint of DNA on functionalized graphene improves its biostability and specificity. Small. 2010;6:1205–9.

    Article  CAS  PubMed  Google Scholar 

  47. Liu B, Huang P-JJ, Kelly EY, Liu J. Graphene oxide surface blocking agents can increase the DNA biosensor sensitivity. Biotechnol J. 2016;11:780–7.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Funding for this work was from the Natural Sciences and Engineering Research Council of Canada (NSERC).

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Authors and Affiliations

  1. Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, N2L 3G1, Canada

    Po-Jung Jimmy Huang & Juewen Liu

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  1. Po-Jung Jimmy Huang
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  2. Juewen Liu
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Correspondence to Juewen Liu.

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Huang, PJ.J., Liu, J. Signaling Kinetics of DNA and Aptamer Biosensors Revealing Graphene Oxide Surface Heterogeneity. J. Anal. Test. 6, 20–27 (2022). https://doi.org/10.1007/s41664-021-00201-z

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  • DOI: https://doi.org/10.1007/s41664-021-00201-z

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