Skip to main content

Advertisement

SpringerLink
Log in

An excellent electrochemical aptasensor for amyloid-β oligomers based on a triple-helix aptamer switch via target-triggered signal transduction DNA displacement events

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

Abstract

An excellent aptasensor for electrochemical detection of amyloid-β oligomers (AβOs) at trace levels was fabricated based on a triple-helix aptamer switch (THAS) via target-triggered signal transduction DNA displacement events. Specifically, a single-stranded anti-AβO aptamer (Apt) carrying two symmetrical arm segments was first attached via Au-S binding to an Au electrode. Gold nanoparticle (GNP)-tagged signal transduction probes (GNP-STPs) were simultaneously hybridized with the two arm segments of the Apt, and a rigid THAS was formed on the Au electrode. Compared to the conventional hybrid, the number of GNPs on the Au electrode increased significantly with the THAS, effectively improving the stability of the Apt to avoid lodging. Trithiocyanuric acid (TA) was utilized to further gather the GNPs and form network-like TA/GNPs. As a result, the differential pulse voltammetry (DPV) response of GNPs was clearly enhanced. When AβOs were present, target-triggered signal transduction DNA displacement events were carried out from THAS via the reaction of the Apt with the AβOs, which caused the GNP-STP to dissociate from the Au electrode, and thus a significant reduction in the DPV response was observed. The assay was able to sensitively detect trace AβOs by monitoring the AβO-controlled DPV response change. It exhibited a wide linear range from 1 fM to 10 pM with a low detection limit of 0.5 fM, and was successfully employed for the determination of AβOs in 20 serum samples, with good recovery. Moreover, the developed assay can provide a sensitive and selective platform for many studies or investigations related to Alzheimer’s disease (AD) monitoring and treatment.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Kaya I, Zetterberg H, Blennow K, Hanrieder J. Shedding light on the molecular pathology of amyloid plaques in transgenic Alzheimer’s disease mice using multimodal MALDI imaging mass spectrometry. ACS Chem Neurosci. 2018;9:1802–17.

    Article  CAS  Google Scholar 

  2. Ryan P, Patel B, Makwana V, Jadhav HR, Kiefel M, Davey A, et al. Peptides, peptidomimetics, and carbohydrate-peptide conjugates as amyloidogenic aggregation inhibitors for Alzheimer’s disease. ACS Chem Neurosci. 2018;9:1530–51.

    Article  CAS  Google Scholar 

  3. Bieschke J, Herbst M, Wiglenda T, Friedrich RP, Boeddrich A, Schiele F, et al. Small-molecule conversion of toxic oligomers to nontoxic beta-sheet-rich amyloid fibrils. Nat Chem Biol. 2012;8:93–101.

    Article  CAS  Google Scholar 

  4. Hamley IW. The amyloid beta peptide: a chemist’s perspective role in Alzheimer’s and fibrillization. Chem Rev. 2012;112:5147–92.

    Article  CAS  Google Scholar 

  5. Rabbito A, Dulewicz M, Kulczynska-Przybik A, Mroczko B. Biochemical markers in Alzheimer’s disease. Int J Mol Sci. 2020;21:1989.

    Article  CAS  Google Scholar 

  6. Jamerlan A, An SSA, Hulme J. Advances in amyloid beta oligomer detection applications in Alzheimer’s disease. TrAC Trends Anal Chem. 2020;129:115919.

    Article  CAS  Google Scholar 

  7. Zhang XL, Tian YL, Zhang C, Tian XY, Ross AW, Moir RD, et al. Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease. Proc Natl Acad Sci. 2015;112:9734–9.

    Article  CAS  Google Scholar 

  8. Raymond SB, Treat LH, Dewey JD, McDannold NJ, Hynynen K, Bacskai BJ. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer’s disease mouse models. PLoS One. 2008;3:e2175.

    Article  Google Scholar 

  9. Smith SV. Molecular imaging with copper-64. J Inorg Biochem. 2004;98:1874–901.

    Article  CAS  Google Scholar 

  10. Bruggink KA, Jongbloed W, Biemans EALM, Veerhuis R, Claassen JAHR, Kuiperij HB, et al. Amyloid-β oligomer detection by ELISA in cerebrospinal fluid and brain tissue. 2013. Anal Biochem. 2013;433:112–20.

    Article  CAS  Google Scholar 

  11. Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat Rev Mol Cell Biol. 2007;8:101.

    Article  CAS  Google Scholar 

  12. Cernescu M, Stark T, Kalden E, Kurz C, Leuner K, Deller T, et al. Laser-induced liquid bead ion desorption mass spectrometry: an approach to precisely monitor the oligomerization of the β-amyloid peptide. Anal Chem. 2012;8:5276–84.

    Article  Google Scholar 

  13. Jin XF, Liu CH, Xu TL, Su L, Zhang XJ. Artificial intelligence biosensors: challenges and prospects. Biosens Bioelectron. 2020;165:112412.

    Article  CAS  Google Scholar 

  14. Veloso AJ, Chow AM, Ganesh HVS, Li N, Dhar D, Wu DCH, et al. Electrochemical immunosensors for effective evaluation of amyloid-beta modulators on oligomeric and fibrillare aggregation processes. Anal Chem. 2014;86:4901–9.

    Article  CAS  Google Scholar 

  15. Sun L, Zhong Y, Gui J, Wang X, Zhuang X, Weng J. A hydrogel biosensor for high selective and sensitive detection of amyloid-beta oligomers. Int J Nanomedicine. 2018;13:843–56.

    Article  CAS  Google Scholar 

  16. Zhu LL, Zhang JY, Wang FY, Wang Y, Lu LL, Feng CC, et al. Selective amyloid β oligomer assay based on abasic site-containing molecular beacon and enzyme-free amplification. Biosens Bioelectron. 2016;78:206–12.

    Article  CAS  Google Scholar 

  17. Qin J, Jo DG, Cho M, Lee Y. Monitoring of early diagnosis of Alzheimer’s disease using the cellular prion protein and poly(pyrrole-2-carboxylic acid) modified electrode. Biosens Bioelectron. 2018;113:82–7.

    Article  CAS  Google Scholar 

  18. Li H, Xie HN, Cao Y, Ding XR, Yin YM, Li GX. A general way to assay protein by coupling peptide with signal reporter via supermolecule formation. Anal Chem. 2013;85:1047–52.

    Article  CAS  Google Scholar 

  19. Zhou J, Meng LC, Ye WR, Wang QL, Geng SZ, Sun C. A sensitive detection assay based on signal amplification technology for Alzheimer’s disease’s early biomarker in exosome. Anal Chim Acta. 2018;1022:124–30.

    Article  CAS  Google Scholar 

  20. Deng CY, Liu H, Zhang MM, Deng HH, Lei CY, Shen L, et al. Light-up nonthiolated aptasensor for low-mass, soluble amyloid-β 40 oligomers at high salt concentrations. Anal Chem. 2018;90:1710–7.

    Article  CAS  Google Scholar 

  21. Zhou YL, Zhang HQ, Liu LT, Li CM, Chang Z, Zhu X, et al. Fabrication of an antibody-aptamer sandwich assay for electrochemical evaluation of levels of β-amyloid oligomers. Sci Rep. 2016;6:35186.

    Article  CAS  Google Scholar 

  22. Ke H, Sha HF, Wang YF, Guo WW, Zhang X, Wang ZM, et al. Electrochemiluminescence resonance energy transfer system between GNRs and Ru(bpy)32+: application in magnetic aptasensor for β-amyloid. Biosens Bioelectron. 2018;100:266–73.

    Article  CAS  Google Scholar 

  23. Zhang YT, Figueroa-Miranda G, Lyu ZZ, Zafiu C, Willbold D, Offenhausser AD, et al. Monitoring amyloid-beta proteins aggregation based on label-free aptasensor. Sensor Actuat B-Chem. 2019;288:535–42.

    Article  CAS  Google Scholar 

  24. Zhou Y, Wang HJ, Zhuo Y, Chai YQ, Yuan R. Highly efficient electrochemiluminescent silver nanoclusters/titanium oxide nanomaterials as a signal probe for ferrocene-driven light switch bioanalysis. Anal Chem. 2017;89:3732–8.

    Article  CAS  Google Scholar 

  25. Wang YF, Zhang Y, Sha HF, Xiong X, Jia NQ. Design and biosensing of a ratiometric electrochemiluminescence resonance energy transfer aptasensor between a g-C3N4 Nanosheet and Ru@MOF for amyloid-β protein. ACS Appl Mater Interfaces. 2019;11:36299–306.

    Article  CAS  Google Scholar 

  26. You M, Yang S, An Y, Zhang F, He PG. A novel electrochemical biosensor with molecularly imprinted polymers and aptamer-based sandwich assay for determining amyloid-β oligomer. J Electroanal Chem. 2020;862:114017.

    Article  CAS  Google Scholar 

  27. Nie GM, Bai ZM, Yu WY, Chen J. Electrochemiluminescence biosensor based on conducting poly(5-formylindole) for sensitive detection of ramos cells. Biomacromolecules. 2013;14:834–40.

    Article  CAS  Google Scholar 

  28. Bagheri E, Abnous K, Alibolandi M, Ramezani M, Taghdisi SM. Triple-helix molecular switch-based aptasensors and DNA sensors. Biosens Bioelectron. 2018;111:1–9.

    Article  CAS  Google Scholar 

  29. Xiao Y, Piorek BD, Plaxco KW, Heeger AJ. A reagentless signal-on architecture for electronic, aptamer-based sensors via target-induced strand displacement. J Am Chem Soc. 2005;127:17990–1.

    Article  CAS  Google Scholar 

  30. Shamsipur M, Farzin L, Tabrizi MA. Ultrasensitive aptamer-based on-off assay for lysozyme using a glassy carbon electrode modified with gold nanoparticles and electrochemically reduced graphene oxide. Microchim Acta. 2016;183:2733–43.

    Article  CAS  Google Scholar 

  31. Zhang ZP, Tao CC, Yin JG, Wang YH, Li YS. Enhancing the response rate of strand displacement-based electrochemical aptamer sensors using bivalent binding aptamer-cDNA probes. Biosens Bioelectron. 2018;103:39–44.

    Article  CAS  Google Scholar 

  32. Doluca O, Withers JM, Filichev VV. Molecular engineering of guanine-rich sequences: Z-DNA, DNA triplexes, and G-quadruplexes. Chem Rev. 2013;113:3044–83.

    Article  CAS  Google Scholar 

  33. Wang XZ, Jiang AW, Hou T, Li F. A versatile label-free and signal-on electrochemical biosensing platform based on triplex-forming oligonucleotide probe. Anal Chim Acta. 2015;890:91–7.

    Article  CAS  Google Scholar 

  34. Abnous K, Danesh NM, Ramezani M, Alibolandi M, Hassanabad KY, Emrani AS, et al. A triple-helix molecular switch-based electrochemical aptasensor for interferon-gamma using a gold electrode and methylene blue as a redox probe. Microchim Acta. 2017;184:4151–7.

    Article  CAS  Google Scholar 

  35. Liu QQ, Liu JQ, He DG, Qing TP, He XX, Wang KM, et al. Triple-helix molecular switch-induced hybridization chain reaction amplification for developing a universal and sensitive electrochemical aptasensor. RSC Adv. 2016;6:90310–7.

    Article  CAS  Google Scholar 

  36. Mao YF, Liu JQ, He DG, He XX, Wang KM, Shi H, et al. Aptamer/target binding-induced triple helix forming for signal-on electrochemical biosensing. Talanta. 2015;143:381–7.

    Article  CAS  Google Scholar 

  37. Stine WB, Dahlgren KN, Krafft GA, LaDu MJ. In vitro characterization of conditions for amyloid-beta peptide oligomerization and fibrillogenesis. J Biol Chem. 2003;278:11612–22.

    Article  CAS  Google Scholar 

  38. Saha K, Agasti SS, Kim C, Li XN, Rotello VM. Gold nanoparticles in chemical and biological sensing. Chem Rev. 2012;112:2739–79.

    Article  CAS  Google Scholar 

  39. Song YJ, Feng LY, Ren JS, Qu XG. Stabilization of unstable CGC(+) triplex DNA by single-walled carbon nanotubes under physiological conditions. Nucleic Acids Res. 2011;39:6835–43.

    Article  CAS  Google Scholar 

  40. Huang CC, Huang YF, Cao ZH, Tan WH, Chang HT. Aptamer-modified gold nanoparticles for colorimetric determination of platelet-derived growth factors and their receptors. Anal Chem. 2005;77:5735–41.

    Article  CAS  Google Scholar 

Download references

Funding

The work was supported by the Qinglan Project funded by universities in Jiangsu and the Fundamental Research Funds for the Central Universities (No.2242020 K40191).

Author information

Authors and Affiliations

  1. Key Laboratory of the Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China

    Xiaoying Wang, Xuan Gu, Linyu Li, Bingjia Yu, Liangrui Lv, Qingqing Chen & Mingming Xu

Authors
  1. Xiaoying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xuan Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Linyu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bingjia Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Liangrui Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qingqing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mingming Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaoying Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The collections and experiments on the human biological samples were approved by the Ethics Committee of Zhongda Hospital affiliated with Southeast University.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, X., Gu, X., Li, L. et al. An excellent electrochemical aptasensor for amyloid-β oligomers based on a triple-helix aptamer switch via target-triggered signal transduction DNA displacement events. Anal Bioanal Chem 413, 3707–3716 (2021). https://doi.org/10.1007/s00216-021-03319-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-021-03319-2

Keywords

Search

Navigation