We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Skip to main content
SpringerLink
Log in

Au@Zr-based metal–organic framework composite as an immunosensing platform for determination of hepatitis B virus surface antigen

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

Abstract

An ultrasensitive electrochemical immunosensor has been prepared using an immunofunctionalized zirconium (Zr)-based metal–organic framework (MOF) with gold (Au) decoration Au@UiO-66(NH2) composite-coated glassy carbon electrode (GCE) for the determination of infectious hepatitis B surface antigen (HBsAg). We fabricated GCE with specific composite via immune-functionalization using anti-HBsAg with Au nanoparticles embedded in UiO-66(NH2). The electrochemical sensing performance of the immunofunctionalized Au@UiO-66(NH2)/GCE with HBsAg was characterized by cyclic voltammetry and differential pulse voltammetry. Under optimized conditions, there was a linear dynamic relationship in the buffer system between the electrical signal and HBsAg levels over the range 1.13 fg mL−1–100 ng mL−1 (R2 = 0.999) with a detection limit of 1.13 fg mL−1. The total analysis time was 15 min per sample. Further validations were performed with HBsAg-spiked human serum samples, and similar detection limits as in the buffer system were observed with reduced signal intensities at lower concentrations of HBsAg (1, 10, and 100 fg mL−1) and minimal interference. The HBsAg electrochemical immunosensing assay had good selectivity and excellent reproducibility, thereby indicating its significant potential in the super-fast diagnosis of hepatitis B.

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

Similar content being viewed by others

Abbreviations

AFP:

Alpha-fetoprotein

BSA:

Bovine serum albumin

CEA:

Carcinoembryonic antigen

CRP:

C-reactive protein

ELISA:

Enzyme-linked immunosorbent assay

GCE:

Glass carbon electrode

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B virus antigen

HR-TEM:

High-resolution transmission electron microscopy

LSPR:

Light surface plasmon resonance

MOF:

Metal–organic framework

PSA:

Prostate-specific antigen

RT-PCR:

Real-time polymerase chain reaction

SEM:

Scanning electron microscopy

XRD:

X-ray diffractometry

XPS:

X-ray photoelectron spectroscopy

References

  1. Chowdhury AD, Takemura K, Li T, Suzuki T, Park EY (2019) Electrical pulse-induced electrochemical biosensor for hepatitis E virus detection. Nat Commun 10:e3737. https://doi.org/10.1038/s41467-019-11644-5

    Article  CAS  Google Scholar 

  2. Mokaya J, Maponga TG, McNaughton AL, Schalkwyk MV, Hugo S, Singer JB et al (2020) Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults. J Clin Virol 129:e104548. https://doi.org/10.1101/2020.03.18.20038216

    Article  Google Scholar 

  3. Cruz HM, de Paula VS, Cruz JCM, do Ó KMR, Milagres FAP, Bastos FI et al (2019) Evaluation of accuracy of hepatitis B virus antigen and antibody detection and relationship between epidemiological factors using dried blood spot. J Virol Methods 277:e113798. https://doi.org/10.1016/j.jviromet.2019.113798

    Article  CAS  Google Scholar 

  4. Ding C, Li H, Hu K, Lin JM (2010) Electrochemical immunoassay of hepatitis B surface antigen by the amplification of gold nanoparticles based on the nanoporous gold electrode. Talanta 3:1385–1391. https://doi.org/10.1016/j.talanta.2009.09.040

    Article  CAS  Google Scholar 

  5. Li M, Wang P, Pei F, Yu H, Chen P, Dong Y et al (2018) Highly sensitive immunosensor for Hepatitis B surface antigen detection based on a novel signal amplification system of gold nanorods and mesoporous Au@Pd@Pt core-shell nanospheres. J Electroanal Chem 809:14–21. https://doi.org/10.1016/j.jelechem.2017.12.044

    Article  CAS  Google Scholar 

  6. Zhao F, Bai Y, Cao L, Han G, Fang C, Wei S, Chen Z (2020) New electrochemical DNA sensor based on nanoflowers of Cu3(PO4)2-BSA-GO for hepatitis B virus DNA detection. J Electroanal Chem 867:e114184. https://doi.org/10.1016/j.jelechem.2020.114184

    Article  CAS  Google Scholar 

  7. Gou L, Sheng Y, Peng Q, Ling J, Yue H, Chen F, Tang H (2020) Ternary nanocube-based “off-on” blinking-type electrochemiluminescence towards enzyme-free detection of hepatitis B virus (HBV)-related DNA. Sensor Actuat B Chem 312:e127987. https://doi.org/10.1016/j.snb.2020.127987

    Article  CAS  Google Scholar 

  8. Kaminska A, Witkowska E, Winkler K, Dzięcielewski I, Weyher JL, Waluk J (2015) Detection of hepatitis B virus antigen from human blood: SERS immunoassay in a microfluidic system. Biosens Bioelectron 66:461–467

    Article  CAS  Google Scholar 

  9. Zhou S, Zhang S, Wang M, Cheng A, Zhu D, Chena S et al (2019) Development and evaluation of an indirect ELISA based on recombinant nonstructural protein 3A to detect antibodies to duck hepatitis A virus type 1. J Virol Methods 268:56–61. https://doi.org/10.1016/j.jviromet.2019.03.012

    Article  CAS  PubMed  Google Scholar 

  10. Bahari D, Babamiri B, Salimi A, Hallaj R, Amininasab M (2020) A self-enhanced ECL-RET immunosensor for the detection of CA19-9 antigen based on Ru(bpy)2(phen-NH2)2+ - amine rich nitrogen-doped carbon nanodots as probe and graphene oxide grafted hyperbranched aromatic polyamide as platform. Anal Chim Acta 1132:55–65. https://doi.org/10.1016/j.aca.2020.07.023

    Article  CAS  PubMed  Google Scholar 

  11. Zhang Y, Zhang Z, Yang F (2007) A sensitive immunoassay for determination of hepatitis B surface antigen and antibody in human serum using capillary electrophoresis with chemiluminescence detection. J Chromatogr B 857:100–107. https://doi.org/10.1016/j.jchromb.2007.07.006

    Article  CAS  Google Scholar 

  12. Hong Y, Huh Y, Yoon DS, Yang J (2012) Nanobiosensors based on localized surface plasmon resonance for biomarker detection. J Nanomater 2012:1–13. https://doi.org/10.1155/2012/759830

    Article  CAS  Google Scholar 

  13. Kim J, Oh SY, Shukla S, Hong SB, Heo NS, Bajpai VK et al (2018) Heteroassembled gold nanoparticles with sandwich-immunoassay LSPR chip format for rapid and sensitive detection of hepatitis B virus surface antigen (HBsAg). Biosens Bioelectron 107:118–122. https://doi.org/10.1016/j.bios.2018.02.019

    Article  CAS  PubMed  Google Scholar 

  14. Bollella P, Fusco G, Tortolini C, Sanzo G, Favera G, Gorton L et al (2017) Beyond graphene: Electrochemical sensors and biosensors for biomarker detection. Biosens Bioelectron 89:152–166. https://doi.org/10.1016/j.bios.2016.03.068

    Article  CAS  PubMed  Google Scholar 

  15. Krishnan S, He X, Zhao F, Zhang Y, Liu S, Xing R (2020) Dual labelled mesoporous silica nanospheres based electrochemical immunosensor for ultrasensitive detection of carcinoembryonic antigen. Anal Chim Acta 1133:119–127. https://doi.org/10.1016/j.aca.2020.07.080

    Article  CAS  PubMed  Google Scholar 

  16. de Eguilaza MR, Cumbaa LR, Forster RJ (2020) Electrochemical detection of viruses and antibodies: A mini review. Electrochem Commun 116:e106762. https://doi.org/10.1016/j.elecom.2020.106762

    Article  CAS  Google Scholar 

  17. Roushani M, Valipour A (2016) Using electrochemical oxidation of Rutin in modeling a novel and sensitive immunosensor based on Pt nanoparticle and graphene–ionic liquid–chitosan nanocomposite to detect human chorionic gonadotropin. Sensor Actuat B: Chem 222:1103–1111. https://doi.org/10.1016/j.snb.2015.08.031

    Article  CAS  Google Scholar 

  18. Wu Y, Wu Y, Lv X, Lei W, Ding Y, Chen C et al (2020) A sensitive sensing platform for acetaminophen based on palladium and multi-walled carbon nanotube composites and electrochemical detection mechanism. Mater Chem Phys 239:e121977. https://doi.org/10.1016/j.matchemphys.2019.121977

    Article  CAS  Google Scholar 

  19. Alhans R, Singh A, Singhal C, Narang J, Wadhwa S, Mathur A (2018) Comparative analysis of single-walled and multi-walled carbon nanotubes for electrochemical sensing of glucose on gold printed circuit boards. Mater Sci Eng C 90:273–279. https://doi.org/10.1016/j.msec.2018.04.072

    Article  CAS  Google Scholar 

  20. Ehzari H, Amiri M, Safari M (2020) Enzyme-free sandwich-type electrochemical immunosensor for highly sensitive prostate specific antigen based on conjugation of quantum dots and antibody on surface of modified glassy carbon electrode with core–shell magnetic metal-organic frameworks. Talanta 210:e120641. https://doi.org/10.1016/j.talanta.2019.120641

    Article  CAS  Google Scholar 

  21. Joseph T, Thomas N (2020) A facile electrochemical sensor based on titanium oxide (TiO2)/reduced graphene oxide (RGO) nano composite modified carbon paste electrode for sensitive detection of epinephrine (EP) from ternary mixture. Mater Today-Proc 41:606–609. https://doi.org/10.1016/j.matpr.2020.05.257

    Article  CAS  Google Scholar 

  22. Manjakkal L, Szwagierczak D, Dahiya R (2020) Metal oxides based electrochemical pH sensors: Current progress and future perspectives. Prog Mater Sci 109:e100635. https://doi.org/10.1016/j.pmatsci.2019.100635

    Article  CAS  Google Scholar 

  23. Shahzad F, Iqbal A, Zaidi SA, Hwang S-W, Koo CM (2019) Nafion-stabilized two-dimensional transition metal carbide (Ti3C2Tx MXene) as a high-performance electrochemical sensor for neurotransmitter. J Ind Eng Chem 79:338–344. https://doi.org/10.1016/j.jiec.2019.03.061

    Article  CAS  Google Scholar 

  24. Othong J, Boonmak J, Kielar F, Hadsadee S, Jungsuttiwong S, Youngme S (2020) Self-calibrating sensor with logic gate operation for anthrax biomarker based on nanoscaled bimetallic lanthanoid MOF. Sensor Actuat B: Chem 316:e128156

    Article  Google Scholar 

  25. Oar-Arteta L, Wezendonk T, Sun X, Kapteijn F, Gascon J (2017) Metal organic frameworks as precursors for the manufacture of advanced catalytic materials. Mater Chem Front 2017:1709–1745. https://doi.org/10.1039/C7QM00007C

    Article  Google Scholar 

  26. Li D, Zhang S, Feng X, Yang H, Nie F, Zhang W (2019) A novel peroxidase mimetic Co-MOF enhanced luminol chemiluminescence and its application glucose sending. Sensor Actuat B: Chem 296:e126631

    Article  Google Scholar 

  27. Zhou J, Zhao J, Liu R (2020) Defect engineering of zeolite imidazole framework derived ZnS nanosheets towards enhanced visible light driven photocatalytic hydrogen production. Appl Catal B: Environ 278:e119265. https://doi.org/10.1016/j.apcatb.2020.119265

    Article  CAS  Google Scholar 

  28. Zhuang D, Liu D (2020) Conductive MOFs with photophysical properties: Applications and thin-film fabrication. Nano-Micro Lett 12:e132. https://doi.org/10.1007/s40820-020-00470-w

    Article  CAS  Google Scholar 

  29. Kumar P, Kim KH, Rarotra S, Ge L, Lisak G (2019) The advanced sensing systems for NOx-based on Metal-organic frameworks: Applications and future opportunities. Trends Anal Chem 122:e115730

    Article  Google Scholar 

  30. An J, Li Y, Chen W, Li G, He J, Feng H (2020) Electrochemically-deposited PANI on iron mesh-based metal-organic framework with enhanced visible-light response towards elimination of thiamphenicol and E. coli. Environ Res 191:e110067. https://doi.org/10.1016/j.envres.2020.110067

    Article  CAS  Google Scholar 

  31. Shen L, Liang S, Wu W, Liang R, Wu L (2013) Multifunctional NH2-mediated zirconium metal–organic framework as an efficient visible-light-driven photocatalyst for selective oxidation of alcohols and reduction of aqueous Cr(VI). Dalton Trans 42:e13649. https://doi.org/10.1039/C3DT51479J

    Article  Google Scholar 

  32. Zhang H-T, Zhang J-W, Huang G, Dub Z-Y, Jiang H-L (2014) An amine-functionalized metal–organic framework as a sensing platform for DNA detection. Chem Commun 50:e12069. https://doi.org/10.1039/C4CC05571C

    Article  CAS  Google Scholar 

  33. Hassan KM, Khalifa Z, Elhaddad GM, Abdel Azzem M (2020) The role of electrolytically deposited palladium and platinum metal nanoparticles dispersed onto poly(1,8- diaminonaphthalene) for enhanced glucose electrooxidation in biofuel cells. Electrochim Acta 355:e136781. https://doi.org/10.1016/j.electacta.2020.136781

    Article  CAS  Google Scholar 

  34. Li R, Wu D, Li H, Xu C, Wang H, Zhao Y et al (2011) Label-free amperometric immunosensor for the detection of human serum chorionic gonadotropin based on nanoporous gold and graphene. Anal Biochem 414:196–201. https://doi.org/10.1016/j.ab.2011.03.019

    Article  CAS  PubMed  Google Scholar 

  35. Jiang Y, Cui J, Zhang T, Wang M, Zhu G, Miao P (2019) Electrochemical detection of T4 polynucleotide kinase based on target-assisted ligation reaction coupled with silver nanoparticles. Anal Chim Acta 1085:85–90. https://doi.org/10.1016/j.aca.2019.07.072

    Article  CAS  PubMed  Google Scholar 

  36. Haldorai Y, Hwang SK, Gopalan AI, Huh YS, Han YK, Voit W, SaiAnand G, Lee KP (2016) Direct electrochemistry of cytochrome C immobilized on titanium nitride/multi-walled carbon nanotube composite for amperometric nitrite biosensor. Biosens Bioelectron 79:543–552. https://doi.org/10.1016/j.bios.2015.12.054

    Article  CAS  PubMed  Google Scholar 

  37. Muain MFA, Cheo KH, Omar MN, Hamzah ASA, Lim HN, Salleh AB et al (2018) Gold nanoparticle-decorated reduced-graphene oxide targeting anti hepatitis B virus core antigen. Bioelectrochemistry 122:199–205. https://doi.org/10.1016/j.bioelechem.2018.04.004

    Article  CAS  Google Scholar 

  38. Cabral DGA, Lima ECS, Moura P, Dutra RF (2016) A label-free electrochemical immunosensor for hepatitis B based on hyaluronic acid–carbon nanotube hybrid film. Talanta 148:209–215. https://doi.org/10.1016/j.talanta.2015.10.083

    Article  CAS  PubMed  Google Scholar 

  39. Ma C, Liang M, Wang L, Xiang H, Jiang Y, Li Y et al (2013) MultisHRP-DNA-coated CMWNTs as signal labels for an ultrasensitive hepatitis C virus core antigen electrochemical immunosensor. Biosens Bioelectron 47:467–474

    Article  CAS  Google Scholar 

  40. Chakraborty B, Ghosh S, Das N, Chaudhuri CR (2018) Liquid gated ZnO nanorod FET sensor for ultrasensitive detection of Hepatitis B surface antigen with vertical electrode configuration. Biosens Bioelectron 122:58–67. https://doi.org/10.1016/j.bios.2018.09.019

    Article  CAS  PubMed  Google Scholar 

  41. Mandli J, Attar A, Ennaji M, Amine A (2017) Indirect competitive electrochemical immunosensor for hepatitis A virus antigen detection. J Electroanal Chem 799:213–221. https://doi.org/10.1016/j.jelechem.2017.05.047

    Article  CAS  Google Scholar 

  42. Oliveira DA, Silva JV, Flauzino JMR, Sousa HS, Castro ACH, Moço ACR et al (2019) Carbon nanomaterial as platform for electrochemical genosensor: A system for the diagnosis of the hepatitis C in real sample. J Electroanal Chem 844:6–13. https://doi.org/10.1016/j.jelechem.2019.04.045

    Article  CAS  Google Scholar 

  43. Ghanbari K, Roushani M, Azadbakht A (2017) Ultra-sensitive aptasensor based on a GQD nanocomposite for detection of hepatitis C virus core antigen. Anal Biochem 534:64–69. https://doi.org/10.1016/j.ab.2017.07.016

    Article  CAS  PubMed  Google Scholar 

  44. Ahangar LE, Mehrgardi MA (2017) Amplified detection of hepatitis B virus using an electrochemical DNA biosensor on a nanoporous gold platform. Bioelectrochemistry 117:83–88. https://doi.org/10.1016/j.bioelechem.2017.06.006

    Article  CAS  PubMed  Google Scholar 

  45. Pei F, Wang P, Ma E, Yang Q, Yu H, Gao C et al (2019) A sandwich-type electrochemical immunosensor based on RhPt NDs/NH2-GS and Au NPs/PPy NS for quantitative detection hepatitis B surface antigen. Bioelectrochemistry 126:92–98

    Article  CAS  Google Scholar 

  46. Rezki M, Septiani NLW, Iqbal M, Harimurti S, Sambegoro P, Adhika DR, Yuliarto B (2021) Amine-functionalized Cu-MOF nanospheres towards label-free hepatitis B surface antigen electrochemical immunosensors. J Mater Chem B 9:5711–5721. https://doi.org/10.1039/D1TB00222H

    Article  CAS  PubMed  Google Scholar 

  47. Akkapinyo C, Khownarumit P, Waraho-Zhmayev D, Poo-Arporn RP (2020) Development of a multiplex immunochromatographic strip test and ultrasensitive electrochemical immunosensor for hepatitis B virus screening. Anal Chim Acta 1095:162–171. https://doi.org/10.1016/j.aca.2019.10.016

    Article  CAS  PubMed  Google Scholar 

  48. Tan Z, Dong H, Liu Q, Liu H, Zhao P, Wang P, Dong Y (2019) A label-free immunosensor based on PtPd NCs@ MoS2 nanoenzymes for hepatitis B surface antigen detection. Biosens Bioelectron 142:e111556. https://doi.org/10.1016/j.bios.2019.111556

    Article  CAS  Google Scholar 

  49. Reed GF, Lynn F, Meade BD (2003) Use of coefficient of variation in assessing variability of quantitative assays. Clin Diagn Lab Immunol 10:e1162. https://doi.org/10.1128/CDLI.10.6.1162.2003

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by Researchers Supporting Project number (RSP-2021/144), King Saud University, Riyadh, Saudi Arabia.

Funding

This work was supported by the DBT India Ramalingaswami Research Grant D.O. NO. BT/HRD/35/02/2006), Government of India. This research was funded by the Researchers Supporting Project Number (RSP-2021/144), King Saud University, Riyadh, Saudi Arabia.

Author information

Authors and Affiliations

  1. Department of Energy and Materials Engineering, Dongguk University, 30 Pildong-ro 1-gil, Seoul, 04620, Republic of Korea

    Vivek K. Bajpai & Young-Kyu Han

  2. Department of Nanoscience and Technology, Bharathiar University, Coimbatore, 641046, Tamil Nadu, India

    Yuvraj Haldorai

  3. The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA

    Imran Khan

  4. Department of Biological Sciences and Bioengineering, Nano-Bio High-Tech Materials Research Center, Inha University, Incheon, 22212, Republic of Korea

    Sonam Sonwal & Yun Suk Huh

  5. Department of Immunology, Mayo Clinic, Rochester, MN, 55905, USA

    Mahendra Pal Singh

  6. Department of Civil Engineering, Yeungnam University, Gyeongsan, 38541, Gyeongbuk, Republic of Korea

    Seema Yadav

  7. Department of Zoology, College of Science, King Saud University, PO Box 2455, Riyadh, 11451, Kingdom of Saudi Arabia

    Bilal Ahamad Paray

  8. Department of Clinical Pharmacy, College of Pharmacy, King Saud University, PO Box 2455, Riyadh, 11451, Saudi Arabia

    Basit Latief Jan

  9. Department of Green Chemical Engineering, Sangmyung University, Cheonan, Chungnam, 31066, Republic of Korea

    Sung-Min Kang

  10. TERI-Deakin Nanobiotechnology Centre, The Energy and Resources Institute, Gwal Pahari, Gurugram, Haryana, 122003, India

    Shruti Shukla

Authors
  1. Vivek K. Bajpai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuvraj Haldorai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Imran Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sonam Sonwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mahendra Pal Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seema Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bilal Ahamad Paray
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Basit Latief Jan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sung-Min Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yun Suk Huh
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Young-Kyu Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shruti Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yun Suk Huh, Young-Kyu Han or Shruti Shukla.

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 2519 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bajpai, V.K., Haldorai, Y., Khan, I. et al. Au@Zr-based metal–organic framework composite as an immunosensing platform for determination of hepatitis B virus surface antigen. Microchim Acta 188, 365 (2021). https://doi.org/10.1007/s00604-021-05022-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-021-05022-6

Keywords

Search

Navigation