Skip to main content
SpringerLink
Log in

A novel electrochemical immunosensor for sensitive detection of depression marker Apo-A4 based on bipyridine-functionalized covalent organic frameworks

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract

A novel electrochemical immunosensor for detecting potential depression biomarker Apolipoprotein A4 (Apo-A4) was developed using a multi-signal amplification approach. Firstly, the sensor utilized a modified electrode material, NG-PEI-COF, combining bipyridine-functionalized covalent organic framework (COF) and polyethyleneimine-functionalized nitrogen-doped graphene (NG-PEI), providing high surface area and excellent electron transfer capability for the first-stage amplification in electrical signal conduction. Subsequently, gold nanoparticles (AuNPs) were further electrodeposited onto the electrode, providing good biocompatibility and abundant binding sites for immobilizing the target antigen, thus achieving the second-stage amplification in target recognition and binding. To address the lack of redox properties of the antigen, a tracer probe was formed by loading AuNPs, anti-Apo-A4, and toluidine blue (TB) successively onto COF, leading to the third-stage amplification in signal conversion. The constructed electrochemical immunosensor TB/Ab/AuNPs/COF-Apo-A4/AuNPs/NG-PEI-COF/GCE exhibited excellent detection performance against Apo-A4 with a linear range of 0.01 to 300 ng mL−1 and had a low detection limit of 2.16 pg mL−1 (S/N = 3). In addition, the biosensor had good reproducibility (RSD = 2.31%), stability, and significant anti-interference performance toward other depression biomarkers. The sensor has been successfully used for the quantitative detection of Apo-A4 in serum, providing potential applications for detecting Apo-A4 in the clinic and serving as a reference for constructing sensing methods based on COF.

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
Fig. 7

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry 62:593–602. https://doi.org/10.1001/archpsyc.62.6.593

    Article  PubMed  Google Scholar 

  2. Shorey S, Ng ED, Wong CHJ (2022) Global prevalence of depression and elevated depressive symptoms among adolescents: a systematic review and meta-analysis. Br J Clin Psychol 61(2):287–305. https://doi.org/10.1111/bjc.12333

    Article  PubMed  Google Scholar 

  3. USPST Force, Mangione CM, Barry MJ, Nicholson WK, Cabana M, Chelmow D, Coker TR, Davidson KW, Davis EM, Donahue KE, Jaen CR, Kubik M, Li L, Ogedegbe G, Pbert L, Ruiz JM, Silverstein M, Stevermer J, Wong JB (2022) Screening for depression and suicide risk in children and adolescents: US preventive services task force recommendation statement. JAMA 328(15):1534–1542. https://doi.org/10.1001/jama.2022.16946

    Article  Google Scholar 

  4. Harsanyi S, Kupcova I, Danisovic L, Klein M (2022) Selected biomarkers of depression: what are the effects of cytokines and inflammation? Int J Mol Sci 24(1). https://doi.org/10.3390/ijms24010578

  5. Sadeghi M, Roohafza H, Afshar H, Rajabi F, Ramzani M, Shemirani H, Sarafzadeghan N (2011) Relationship between depression and apolipoproteins A and B: a case-control study. Clinics 66(1):113–117. https://doi.org/10.1590/S1807-59322011000100020

    Article  PubMed  PubMed Central  Google Scholar 

  6. Guo QW, Si YJ, Shen YL, Chen X, Yang M, Fang DZ, Lin J (2021) Depression augments plasma APOA4 without changes of plasma lipids and glucose in female adolescents carrying G Allele of APOA4 rs5104. J Mol Neurosci 71(10):2060–2070. https://doi.org/10.1007/s12031-020-01766-7

    Article  CAS  PubMed  Google Scholar 

  7. Kato A, Naitou H, Namioka M, Akimoto M, Ishii T, Sakakibara H, Shimoi K, Nakayama T, Ohashi N (2010) Proteomic identification of serum proteins associated with stress-induced gastric ulcers in fasted rats. Biosci Biotechnol Biochem. 74(4):812–8. https://doi.org/10.1271/bbb.90897

    Article  CAS  PubMed  Google Scholar 

  8. Cheng CW, Chang CC, Chen HW, Lin CY, Chen JS (2018) Serum ApoA4 levels predicted the progression of renal impairment in T2DM. Eur J Clin Invest 48(6):e12937. https://doi.org/10.1111/eci.12937

    Article  CAS  PubMed  Google Scholar 

  9. Jeong DH, Kim HK, Prince AE, Lee DS, Kim YN, Han J, Kim KT (2008) Plasma proteomic analysis of patients with squamous cell carcinoma of the uterine cervix. J Gynecol Oncol 19(3):173–180. https://doi.org/10.3802/jgo.2008.19.3.173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Liao X, Zhang C, Qiu S, Qiu Z, Tang Q, Wu S, Xu J, Wu B, Liu Z, Gao F (2022) Proximity hybridization induced rolling circle amplification for label-free SERS detection of the depression marker human apolipoprotein A4. Talanta 244:123402. https://doi.org/10.1016/j.talanta.2022.123402

    Article  CAS  PubMed  Google Scholar 

  11. Wang Y, Sun B, Wei H, Li Y, Hu F, Du X, Chen J (2022) Investigating immunosensor for determination of depression marker-Apo-A4 based on patterning AuNPs and N-Gr nanomaterials onto ITO-PET flexible electrodes with amplifying signal. Anal Chim Acta 1224:340217. https://doi.org/10.1016/j.aca.2022.340217

    Article  CAS  PubMed  Google Scholar 

  12. Liao X, Zhang C, Liu Z, Gao F (2021) Label-free electrochemical homogeneous detection of the depression marker human apolipoprotein A4 based on proximity hybridization triggered rolling circle amplification. Int J Biol Macromol 183:2305–2313. https://doi.org/10.1016/j.ijbiomac.2021.06.027

    Article  CAS  PubMed  Google Scholar 

  13. Molina A, González J (2016) Pulse voltammetry in physical electrochemistry and electroanalysis. Switzerland: Springer International. https://doi.org/10.1007/978-3-319-21251-7

  14. Bard AJ, Faulkner LR (2001) Electrochemical methods fundamentals and applications. New York: John Wiley & Sons, Inc.

  15. Challhua R, Akashi L, Zuniga J, Beatriz de Carvalho Ruthner Batista H, Moratelli R, Champi A (2023) Portable reduced graphene oxide biosensor for detection of rabies virus in bats using nasopharyngeal swab samples. Biosens Bioelectron 232 115291. https://doi.org/10.1016/j.bios.2023.115291

  16. Yang M, Wang H, Liu P, Cheng J (2021) A 3D electrochemical biosensor based on super-aligned carbon nanotube array for point-of-care uric acid monitoring. Biosens Bioelectron 179:113082. https://doi.org/10.1016/j.bios.2021.113082

    Article  CAS  PubMed  Google Scholar 

  17. Yan X, Su D, Li H, Zhao X, Liu X, Liu F, Sun P, Lu G (2023) Ultrasensitive plasmonic immunosensor based on hierarchically porous metal–organic framework‐engineered enzyme catalysts. Adv Funct Mater 33(21). https://doi.org/10.1002/adfm.202215192

  18. Cote AP, Benin AI, Ockwig NW, O’Keeffe M, Matzger AJ, Yaghi OM (2005) Porous, crystalline, covalent organic frameworks. Science 310(5751):1166–1170. https://doi.org/10.1126/science.1120411

    Article  CAS  PubMed  Google Scholar 

  19. Sun F, Bai L, Li M, Yu C, Liu H, Qiao X, Yan H (2022) Fabrication of edge-curled petals-like covalent organic frameworks and their properties for extracting indole alkaloids from complex biological samples. J Pharm Anal 12(1):96–103. https://doi.org/10.1016/j.jpha.2020.12.006

    Article  PubMed  Google Scholar 

  20. Ding S-Y, Gao J, Wang Q, Zhang Y, Song W-G, Su C-Y, Wang W (2011) Construction of covalent organic framework for catalysis: Pd/COF-LZU1 in Suzuki-Miyaura coupling reaction. J Am Chem Soc 133(49):19816–19822. https://doi.org/10.1021/ja206846p

    Article  CAS  PubMed  Google Scholar 

  21. Fu Y, Wu Y, Chen S, Zhang W, Zhang Y, Yan T, Yang B, Ma H (2021) Zwitterionic covalent organic frameworks: attractive porous host for gas separation and anhydrous proton conduction. ACS Nano 15(12):19743–19755. https://doi.org/10.1021/acsnano.1c07178

    Article  CAS  PubMed  Google Scholar 

  22. Dong H, Lu M, Wang Y, Tang H-L, Wu D, Sun X, Zhang F-M (2022) Covalently anchoring covalent organic framework on carbon nanotubes for highly efficient electrocatalytic CO2 reduction. Appl Catal B 303. https://doi.org/10.1016/j.apcatb.2021.120897

  23. Zheng J, Zhao H, Ning G, Sun W, Wang L, Liang H, Xu H, He C, Zhao H, Li CP (2021) A novel affinity peptide-antibody sandwich electrochemical biosensor for PSA based on the signal amplification of MnO(2)-functionalized covalent organic framework. Talanta 233:122520. https://doi.org/10.1016/j.talanta.2021.122520

    Article  CAS  PubMed  Google Scholar 

  24. Hosokawa T, Tsuji M, Tsuchida K, Iwase K, Harada T, Nakanishi S, Kamiya K (2021) Metal-doped bipyridine linked covalent organic framework films as a platform for photoelectrocatalysts. J Mater Chem A 9(17):11073–11080. https://doi.org/10.1039/d1ta00396h

    Article  CAS  Google Scholar 

  25. Xu X, Zhao R, Ai W, Chen B, Du H, Wu L, Zhang H, Huang W, Yu T (2018) Controllable design of MoS2 nanosheets anchored on nitrogen-doped graphene: toward fast sodium storage by tunable pseudocapacitance. Adv Mater 30(27):1800658. https://doi.org/10.1002/adma.201800658

    Article  CAS  Google Scholar 

  26. Wang L, Sun M, Zhu S, Zhang M, Ma Y, Xie D, Li S, Mominou N, Jing C (2021) Cu-Ni bimetallic single atoms supported on TiO2@NG core-shell material for the removal of dibenzothiophene under visible light. Sep Purif Technol 279:119646. https://doi.org/10.1016/j.seppur.2021.119646

    Article  CAS  Google Scholar 

  27. Sun B, Li D, Hou X, Li W, Gou Y, Hu F, Li W, Shi X (2020) A novel electrochemical immunosensor for the highly sensitive and selective detection of the depression marker human apolipoprotein A4. Bioelectrochemistry 135:107542. https://doi.org/10.1016/j.bioelechem.2020.107542

    Article  CAS  PubMed  Google Scholar 

  28. Shang Z, Su T, Jin D, Xu Q, Hu X, Shu Y (2023) An integrated and flexible PDMS/Au film-based electrochemical immunosensor via Fe-Co MOF as a signal amplifier for alpha fetoprotein detection. Biosens Bioelectron 230:115245. https://doi.org/10.1016/j.bios.2023.115245

    Article  CAS  PubMed  Google Scholar 

  29. Xiang Z, Jiang C, Yang J, Huang L, Jiang B, Wang X, Gao C, Li M, Meng Y, Tong L, Ling B, Wang Y, Wu J, Chinese consortium for the study of hepatitis (2023) Serum extracellular vesicle-derived ASS1 is a promising predictor for the occurrence of HEV-ALF. J Med Virol 95(1):e28425. https://doi.org/10.1002/jmv.28425

    Article  CAS  PubMed  Google Scholar 

  30. Pei R, Ye L, Jing C (2023) Enzyme-based electrochemical biosensor for antimonite detection in water. Biosens Bioelectron 229:115244. https://doi.org/10.1016/j.bios.2023.115244

    Article  CAS  PubMed  Google Scholar 

  31. Peng X, Zhu J, Wu Z, Wen W, Zhang X, Chen M-M, Wang S (2023) High-efficient Pt@COF nanospheres-based electrochemical-chemical-chemical redox cycling for ultrasensitive microRNAs biosensing. Sens Actuators B Chem 392. https://doi.org/10.1016/j.snb.2023.134074

  32. Zhao H, Zheng J, Liang H, Liu H-F, Liu F, Zhang Y-P, Li C-P (2023) Electrochemical/colorimetric dual-mode sensing strategy for cardiac troponin I detection based on zirconium nitride functionalized covalent organic frameworks. Sens Actuators B Chem 391. https://doi.org/10.1016/j.snb.2023.134026

  33. Guo L, Mu Z, Yan B, Wang J, Zhou J, Bai L (2022) A novel electrochemical biosensor for sensitive detection of non-small cell lung cancer ctDNA using NG-PEI-COFTAPB-TFPB as sensing platform and Fe-MOF for signal enhancement. Sens Actuators B Chem 350. https://doi.org/10.1016/j.snb.2021.130874

  34. Ranjeesh KC, Illathvalappil R, Veer SD, Peter J, Wakchaure VC, Goudappagouda KV, Raj S, Kurungot S.S. Babu (2019) Imidazole-linked crystalline two-dimensional polymer with ultrahigh proton-conductivity. J. Am. Chem. Soc. 141(38):14950–14954. https://doi.org/10.1021/jacs.9b06080

    Article  CAS  PubMed  Google Scholar 

  35. Ma TQ, Kapustin EA, Yin SX, Liang L, Zhou ZY, Niu J, Li LH, Wang YY, Su J, Li J, Wang XG, Wang WD, Wang W, Sun JL, Yaghi OM (2018) Single-crystal x-ray diffraction structures of covalent organic frameworks. Science 361(6397):48–52. https://doi.org/10.1126/science.aat7679

    Article  CAS  PubMed  Google Scholar 

  36. Wei W, Zhou S, Ma DD, Li Q, Ran M, Li X, Wu XT, Zhu QL (2023) Ultrathin conductive bithiazole-based covalent organic framework nanosheets for highly efficient electrochemical biosensing. Adv Funct Mater. https://doi.org/10.1002/adfm.202302917

    Article  Google Scholar 

  37. Zhou D, Kang Z, Liu X, Yan W, Cai H, Xu J, Zhang D (2023) High sensitivity ammonia QCM sensor based on ZnO nanoflower assisted cellulose acetate-polyaniline composite nanofibers. Sens Actuators B Chem 392. https://doi.org/10.1016/j.snb.2023.134072

  38. Ren Y, Rao R, Bhusal S, Varshney V, Kedziora G, Wheeler R, Kang Y, Roy A, Nepal D (2020) Hierarchical assembly of gold nanoparticles on graphene nanoplatelets by spontaneous reduction: implications for smart composites and biosensing. ACS Applied Nano Materials 3(9):8753–8762. https://doi.org/10.1021/acsanm.0c01555

    Article  CAS  Google Scholar 

  39. Xu L, Wang F, Ge X, Liu R, Xu M, Yang J (2019) Covalent organic frameworks on reduced graphene oxide with enhanced electrochemical performance. Microporous Mesoporous Mater 287:65–70. https://doi.org/10.1016/j.micromeso.2019.05.054

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (81972018), the major science and technology project of Gansu Province (21ZD4FA013), the Gansu Province People's Livelihood Science and Technology Special Project – Rural Revitalization Special Project (22CX2NK004), the Central Government Guiding Local Science and Technology Development Fund Project (22ZY1QA012), the Special Project of Science and Technology Commissioner of Gansu Province (22CX8GA009), and the Talent Innovation and Entrepreneurship Project of Lanzhou (2017-RC-115, 2020-RC-41).

Author information

Authors and Affiliations

  1. School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, Codonopsis Radix Industrial Technology Engineering Research Center, Lanzhou University, Lanzhou, 730000, Gansu Province, China

    Yan Chen, Min Guo, Zixia Wang, Xiaohui Mo & Fangdi Hu

  2. College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China

    Yongling Du

Authors
  1. Yan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zixia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaohui Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fangdi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yongling Du
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Fangdi Hu or Yongling Du.

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.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, Y., Guo, M., Wang, Z. et al. A novel electrochemical immunosensor for sensitive detection of depression marker Apo-A4 based on bipyridine-functionalized covalent organic frameworks. Microchim Acta 191, 179 (2024). https://doi.org/10.1007/s00604-024-06260-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-024-06260-0

Keywords

Search

Navigation