Skip to main content
Log in

Electrochemical α-fetoprotein immunosensor based on Fe3O4NPs@covalent organic framework decorated gold nanoparticles and magnetic nanoparticles including SiO2@TiO2

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

Abstract

The early diagnosis of major diseases such as cancer is typically a major issue for humanity. Human α-fetoprotein (AFP) as a sialylated glycoprotein is of approximately 68 kD molecular weight and is considered to be a key biomarker, and an increase in its level indicates the presence of liver, testicular, or gastric cancer. In this study, an electrochemical AFP immunosensor based on Fe3O4NPs@covalent organic framework decorated gold nanoparticles (Fe3O4 NPs@COF/AuNPs) for the electrode platform and double-coated magnetic nanoparticles (MNPs) based on SiO2@TiO2 (MNPs@SiO2@TiO2) nanocomposites for the signal amplification was fabricated. The immobilization of anti-AFP capture antibody was successfully performed on Fe3O4 NPs@COF/AuNPs modified electrode surface by amino-gold affinity, while the conjugation of anti-AFP secondary antibody on MNPs@SiO2@TiO2 was achieved by the electrostatic/ionic interactions. Transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) analysis, cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS) techniques were used to characterize the nanostructures in terms of physical and electrochemical features. The limit of detection (LOD) was 3.30 fg mL−1. The findings revealed that the proposed electrochemical AFP immunosensor can be effectively used to diagnose cancer.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Srinivas PR, Kramer BS, Srivastava S (2001) Trends in biomarker research for cancer detection. Lancet Oncol 2(11):698–704

    Article  CAS  PubMed  Google Scholar 

  2. Giannetto M, Elviri L, Careri M, Mangia A, Mori G (2011) A voltammetric immunosensor based on nanobiocomposite materials for the determination of alpha-fetoprotein in serum. Biosens Bioelectron 26(5):2232–2236

    Article  CAS  PubMed  Google Scholar 

  3. Zhong XL, Zhang M, Guo LA, Xie YZ, Luo RF, Chen WX, Cheng FL, Wang LS (2021) A dual-signal self-checking photoelectrochemical immunosensor based on the sole composite of MIL-101(Cr) and CdSe quantum dots for the detection of alpha-fetoprotein. Biosens Bioelectron 189:113389

    Article  CAS  PubMed  Google Scholar 

  4. Li N, Ma HM, Cao W, Wu D, Yan T, Du B, Wei Q (2015) Highly sensitive electrochemical immunosensor for the detection of alpha fetoprotein based on PdNi nanoparticles and N-doped graphene nanoribbons. Biosens Bioelectron 74:786–791

    Article  CAS  PubMed  Google Scholar 

  5. Teramura Y, Iwata H (2007) Label-free immunosensing for alpha-fetoprotein in human plasma using surface plasmon resonance. Anal Biochem 365(2):201–207

    Article  CAS  PubMed  Google Scholar 

  6. Zhou F, Li ZY, Bao ZT, Feng K, Zhang Y, Wang T (2015) Highly sensitive, label-free and real-time detection of alpha-fetoprotein using a silicon nanowire biosensor. Scand J Clin Lab Inv 75(7):578–584

    Article  CAS  Google Scholar 

  7. Bader D, Riskin A, Vafsi O, Tamir A, Peskin B, Israel N, Merksamer R, Dar H, David M (2004) Alpha-fetoprotein in the early neonatal period - a large study and review of the literature. Clin Chim Acta 349(1–2):15–23

    Article  CAS  PubMed  Google Scholar 

  8. Wang XW, Xu B (1998) Stimulation of tumor-cell growth by alpha-fetoprotein. Int J Cancer 75(4):596–599

    Article  CAS  PubMed  Google Scholar 

  9. Lin JH, He CY, Zhang LJ, Zhang SS (2009) Sensitive amperometric immunosensor for alpha-fetoprotein based on carbon nanotube/gold nanoparticle doped chitosan film. Anal Biochem 384(1):130–135

    Article  CAS  PubMed  Google Scholar 

  10. Qu ZY, Xu H, Xu P, Chen KM, Mu R, Fu JP, Gu HC (2014) Ultrasensitive ELISA using enzyme-loaded nanospherical brushes as labels. Anal Chem 86(19):9367–9371

    Article  CAS  PubMed  Google Scholar 

  11. Qian J, Zhou ZX, Cao XD, Liu SQ (2010) Electrochemiluminescence immunosensor for ultrasensitive detection of biomarker using Ru(bpy)(3)(2+)-encapsulated silica nanosphere labels. Anal Chim Acta 665(1):32–38

    Article  CAS  PubMed  Google Scholar 

  12. Scarano S, Scuffi C, Mascini M, Minunni M (2010) Surface plasmon resonance imaging (SPRi)-based sensing: a new approach in signal sampling and management. Biosens Bioelectron 26(4):1380–1385

    Article  CAS  PubMed  Google Scholar 

  13. Shafik HM, Ayoub SM, Ebeid NH, Someda HH (2014) New adjuvant design using layered double hydroxide for production of polyclonal antibodies in radioimmunoassay techniques. J Radioanal Nucl Ch 301(1):81–89

    Article  CAS  Google Scholar 

  14. Zhou L, Ji FH, Zhang T, Wang F, Li YC, Yu ZX, Jin XP, Ruan B (2019) An fluorescent aptasensor for sensitive detection of tumor marker based on the FRET of a sandwich structured QDs-AFP-AuNPs. Talanta 197:444–450

    Article  CAS  PubMed  Google Scholar 

  15. Wang GL, Yuan JL, Gong BL, Matsumoto K, Hu ZD (2001) Immunoassay by graphite furnace atomic absorption spectrometry using a metal chelate as a label. Anal Chim Acta 448(1–2):165–172

    Article  CAS  Google Scholar 

  16. Darain F, Park SU, Shim YB (2003) Disposable amperometric immunosensor system for rabbit IgG using a conducting polymer modified screen-printed electrode. Biosens Bioelectron 18(5–6):773–780

    Article  CAS  PubMed  Google Scholar 

  17. Wang JN, Zhang SP, Dai H, Zheng HL, Hong ZS, Lin YY (2019) Dual-readout immunosensor constructed based on brilliant photoelectrochemical and photothermal effect of polymer dots for sensitive detection of sialic acid. Biosens Bioelectron 142:111567

    Article  CAS  PubMed  Google Scholar 

  18. Xie YZ, Zhang M, Bin QY, Xie SL, Guo LA, Cheng FL, Lv WZ (2020) Photoelectrochemical immunosensor based on CdSe@BiVO4 Co-sensitized TiO2 for carcinoembryonic antigen. Biosens Bioelectron 150:111949

    Article  CAS  PubMed  Google Scholar 

  19. Karaman O, Ozcan N, Karaman C, Yola BB, Atar N, Yola ML (2022) Electrochemical cardiac troponin I immunosensor based on nitrogen and boron-doped graphene quantum dots electrode platform and Ce-doped SnO2/SnS2 signal amplification. Mater Today Chem 23:100666

    Article  CAS  Google Scholar 

  20. Karaman C, Yola BB, Karaman O, Atar N, Polat I, Yola ML (2021) Sensitive sandwich-type electrochemical SARS-CoV-2 nucleocapsid protein immunosensor. Microchim Acta 188(12):1–13

    Article  Google Scholar 

  21. Chen Y, Yuan PX, Wang AJ, Luo XL, Xue YD, Zhang L, Feng JJ (2019) A novel electrochemical immunosensor for highly sensitive detection of prostate-specific antigen using 3D open-structured PtCu nanoframes for signal amplification. Biosens Bioelectron 126:187–192

    Article  CAS  PubMed  Google Scholar 

  22. Li H, Wang X, Zhang X, He M, Zhang J, Liu P, Tang X, Li C, Wang Y (2022) Eu-MOF nanorods functionalized with large heterocyclic ionic liquid for photoelectrochemical immunoassay of α-fetoprotein. Anal Chim Acta 7:339459

    Article  Google Scholar 

  23. Tan M, Zhang C, Li Y, Xu Z, Wang S, Liu Q, Li Y (2022) An efficient electrochemical immunosensor for alpha-fetoprotein detection based on the CoFe Prussian blue analog combined PdAg hybrid nanodendrites. Bioelectrochemistry 145:108080

    Article  CAS  PubMed  Google Scholar 

  24. Zhu LP, Ye J, Yan MX, Yu LY, Peng Y, Huang JS, Yang XR (2021) Sensitive and programmable “signal-off” electrochemiluminescence sensing platform based on cascade amplification and multiple quenching mechanisms. Anal Chem 93(4):2644–2651

    Article  CAS  PubMed  Google Scholar 

  25. Kang X, Li YW, Zhu MZ, Jin RC (2020) Atomically precise alloy nanoclusters: syntheses, structures, and properties. Chem Soc Rev 49(17):6443–6514

    Article  PubMed  Google Scholar 

  26. Madhusudan P, Shi R, Xiang SL, Jin MT, Chandrashekar BN, Wang JW, Wang WJ, Peng OW, Amini A, Cheng C (2021) Construction of highly efficient Z-scheme ZnxCd1-xS/Au@g-C3N4 ternary heterojunction composite for visible-light-driven photocatalytic reduction of CO2 to solar fuel. Appl Catal B-Environ 282:119600

    Article  CAS  Google Scholar 

  27. Holm A, Goodman ED, Stenlid JH, Aitbekova A, Zelaya R, Diroll BT, Johnston-Peck AC, Kao KC, Frank CW, Pettersson LGM, Cargnello M (2020) Nanoscale spatial distribution of supported nanoparticles controls activity and stability in powder catalysts for CO oxidation and photocatalytic H-2 evolution. J Am Chem Soc 142(34):14481–14494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhu L, Liang GL, Guo CP, Xu MR, Wang MH, Wang CB, Zhang ZH, Du M (2022) A new strategy for the development of efficient impedimetric tobramycin aptasensors with metallo-covalent organic frameworks (MCOFs). Food Chem 366:130575

    Article  CAS  PubMed  Google Scholar 

  29. Zhang ZH, Lou YF, Guo CP, Jia QJ, Song YP, Tian JY, Zhang S, Wang MH, He LH, Du M (2021) Metal-organic frameworks (MOFs) based chemosensors/biosensors for analysis of food contaminants. Trends Food Sci Tech 118:569–588

    Article  CAS  Google Scholar 

  30. He HM, Zhu QQ, Yan Y, Zhang HW, Han ZY, Sun HM, Chen J, Li CP, Zhang ZH, Du M (2022) Metal-organic framework supported Au nanoparticles with organosilicone coating for high-efficiency electrocatalytic N2 reduction to NH3. Appl Catal B-Environ 302:120840

    Article  CAS  Google Scholar 

  31. Gomez-Pastora J, Dominguez S, Bringas E, Rivero MJ, Ortiz I, Dionysiou DD (2017) Review and perspectives on the use of magnetic nanophotocatalysts (MNPCs) in water treatment. Chem Eng J 310:407–427

    Article  CAS  Google Scholar 

  32. Mohammed L, Gomaa HG, Ragab D, Zhu J (2017) Magnetic nanoparticles for environmental and biomedical applications: a review. Particuology 30:1–14

    Article  CAS  Google Scholar 

  33. Stanicki D, Elst LV, Muller RN, Laurent S (2015) Synthesis and processing of magnetic nanoparticles. Curr Opin Chem Eng 8:7–14

    Article  Google Scholar 

  34. Laurent S, Forge D, Port M, Roch A, Robic C, Elst LV, Muller RN (2008) Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem Rev 108(6):2064–2110

    Article  CAS  PubMed  Google Scholar 

  35. Jeelani PG, Mulay P, Venkat R, Ramalingam C (2020) Multifaceted application of silica nanoparticles. A review Silicon-Neth 12(6):1337–1354

    Article  CAS  Google Scholar 

  36. Stöber W, Fink A, Bohn E (1968) Controlled growth of monodisperse silica spheres in the micron size range. J Colloid Interface Sci 26(1):62–69

    Article  Google Scholar 

  37. Byrne C, Subramanian G, Pillai SC (2018) Recent advances in photocatalysis for environmental applications. J Environ Chem Eng 6(3):3531–3555

    Article  CAS  Google Scholar 

  38. Alvarez PM, Jaramillo J, Lopez-Pinero F, Plucinski PK (2010) Preparation and characterization of magnetic TiO2 nanoparticles and their utilization for the degradation of emerging pollutants in water. Appl Catal B-Environ 100(1–2):338–345

    Article  CAS  Google Scholar 

  39. Katta KV, Dubey RS (2021) Comparative study of doped-TiO2 nanocrystals prepared by sol-gel and solvothermal approaches. Mater Today-Proc 39:1422–1425

    Article  CAS  Google Scholar 

  40. Jahani PM, Beitollahi H, Tajik S, Tashakkorian H (2020) Selective electrochemical determination of bisphenol A via a Fe3O4 NPs derivative-modified graphite screen-printed electrode. Int J Environ an Ch 100(11):1209–1225

    Article  Google Scholar 

  41. Xu YL, Shi XF, Hua R, Zhang R, Yao YJ, Zhao B, Liu T, Zheng JZ, Lu G (2020) Remarkably catalytic activity in reduction of 4-nitrophenol and methylene blue by Fe3O4@COF supported noble metal nanoparticles. Appl Catal B-Environ 260:118142

    Article  CAS  Google Scholar 

  42. Yola ML, Atar N, Qureshi MS, Ustundag Z, Solak AO (2012) Electrochemically grafted etodolac film on glassy carbon for Pb(II) determination. Sensor Actuat B-Chem 171:1207–1215

    Article  Google Scholar 

  43. Zhang L, Wu Z, Chen LW, Zhang LJ, Li XL, Xu HF, Wang HY, Zhu G (2016) Preparation of magnetic Fe3O4/TiO2/Ag composite microspheres with enhanced photocatalytic activity. Solid State Sci 52:42–48

    Article  CAS  Google Scholar 

  44. Wang J, Yang JH, Li XY, Wei B, Wang DD, Song H, Zhai HJ, Li XF (2015) Synthesis of Fe3O4@SiO2@ZnO-Ag core-shell microspheres for the repeated photocatalytic degradation of rhodamine B under UV irradiation. J Mol Catal a-Chem 406:97–105

    Article  CAS  Google Scholar 

  45. Yola ML, Atar N (2021) Novel voltammetric tumor necrosis factor-alpha (TNF-alpha) immunosensor based on gold nanoparticles involved in thiol-functionalized multi-walled carbon nanotubes and bimetallic Ni/Cu-MOFs. Anal Bioanal Chem 413(9):2481–2492

    Article  CAS  PubMed  Google Scholar 

  46. Medetalibeyoglu H, Beytur M, Akyildirim O, Atar N, Yola ML (2020) Validated electrochemical immunosensor for ultra -sensitive procalcitonin detection: Carbon electrode modified with gold nanoparticles functionalized sulfur doped MXene as sensor platform and carboxylated graphitic carbon nitride as signal amplification. Sensor Actuat B-Chem 319:128195

    Article  CAS  Google Scholar 

  47. Yola ML, Atar N (2019) Development of cardiac troponin-I biosensor based on boron nitride quantum dots including molecularly imprinted polymer. Biosens Bioelectron 126:418–424

    Article  CAS  PubMed  Google Scholar 

  48. Li H, Kou BB, Yuan YL, Chai YQ, Yuan R (2022) Porous Fe3O4@COF-Immobilized gold nanoparticles with excellent catalytic performance for sensitive electrochemical detection of ATP. Biosens Bioelectron 197:113758

    Article  CAS  PubMed  Google Scholar 

  49. Xu H, Gao J, Jiang DL (2015) Stable, crystalline, porous, covalent organic frameworks as a platform for chiral organocatalysts. Nat Chem 7(11):905–912

    Article  CAS  PubMed  Google Scholar 

  50. Saeed M, Iqbal MZ, Ren WZ, Xia YZ, Liu C, Khan WS, Wu AG (2018) Controllable synthesis of Fe3O4 nanoflowers: enhanced imaging guided cancer therapy and comparison of photothermal efficiency with black-TiO2. J Mater Chem B 6(22):3800–3810

    Article  CAS  PubMed  Google Scholar 

  51. Hui C, Shen CM, Tian JF, Bao LH, Ding H, Li C, Tian YA, Shi XZ, Gao HJ (2011) Core-shell Fe3O4@SiO2 nanoparticles synthesized with well-dispersed hydrophilic Fe3O4 seeds. Nanoscale 3(2):701–705

    Article  CAS  PubMed  Google Scholar 

  52. Deng Y, Qi D, Deng C, Zhang X, Zhao D (2008) Superparamagnetic high-magnetization microspheres with an Fe3O4@SiO2 core and perpendicularly aligned mesoporous SiO2 shell for removal of microcystins. J Am Chem Soc 130(1):28–29

    Article  CAS  PubMed  Google Scholar 

  53. Fernandes IL, Barbosa DP, de Oliveira SB, da Silva VA, Sousa MH, Montero-Munoz M, Coaquira JAH (2022) Synthesis and characterization of the MNP@SiO2@TiO2 nanocomposite showing strong photocatalytic activity against methylene blue dye. Appl Surf Sci 580:152195

    Article  Google Scholar 

  54. Jardim KV, Palomec-Garfias AF, Andrade BYG, Chaker JA, Bao SN, Marquez-Beltran C, Moya SE, Parize AL, Sousa MH (2018) Novel magneto-responsive nanoplatforms based on MnFe2O4 nanoparticles layer-by-layer functionalized with chitosan and sodium alginate for magnetic controlled release of curcumin. Mat Sci Eng C-Mater 92:184–195

    Article  CAS  Google Scholar 

  55. Arman A, Saglam S, Uzer A, Apak R (2022) Electrochemical determination of nitroaromatic explosives using glassy carbon/multi walled carbon nanotube/polyethyleneimine electrode coated with gold nanoparticles. Talanta 238:122990

    Article  CAS  PubMed  Google Scholar 

  56. Kulpa A, Ryl J, Schroeder G, Koterwa A, Anand JS, Ossowski T, Niedzialkowski P (2020) Simultaneous voltammetric determination of Cd2+, Pb2+, and Cu2+ ions captured by Fe3O4@SiO2 core-shell nanostructures of various outer amino chain length. J Mol Liq 314:113677

    Article  CAS  Google Scholar 

  57. Huang XB, Wang G, Yang M, Guo WC, Gao HY (2011) Synthesis of polyaniline-modified Fe3O4/SiO2/TiO2 composite microspheres and their photocatalytic application. Mater Lett 65(19–20):2887–2890

    Article  CAS  Google Scholar 

  58. Yuan Q, Li N, Geng WC, Chi Y, Li XT (2012) Preparation of magnetically recoverable Fe3O4@SiO2@meso-TiO2 nanocomposites with enhanced photocatalytic ability. Mater Res Bull 47(9):2396–2402

    Article  CAS  Google Scholar 

  59. Karaman C, Karaman O, Yola BB, Ulker I, Atar N, Yola ML (2021) A novel electrochemical aflatoxin B1 immunosensor based on gold nanoparticle-decorated porous graphene nanoribbon and Ag nanocube-incorporated MoS2 nanosheets. New J Chem 45(25):11222–11233

    Article  CAS  Google Scholar 

  60. Er E, Sanchez-Iglesias A, Silvestri A, Arnaiz B, Liz-Marzan LM, Prato M, Criado A (2021) Metal nanoparticles/MoS2 surface-enhanced Raman scattering-based sandwich immunoassay for a-fetoprotein detection. Acs Appl Mater Inter 13(7):8823–8831

    Article  CAS  Google Scholar 

  61. Zhao J, Wu C, Zhai LP, Shi XF, Li X, Weng GJ, Zhu J, Li JJ, Zhao JW (2019) A SERS-based immunoassay for the detection of alpha-fetoprotein using AuNS@Ag@SiO2 core-shell nanostars. J Mater Chem C 7(27):8432–8441

    Article  CAS  Google Scholar 

  62. Liang RP, Yao GH, Fan LX, Qiu JD (2012) Magnetic Fe3O4@Au composite-enhanced surface plasmon resonance for ultrasensitive detection of magnetic nanoparticle-enriched alpha-fetoprotein. Anal Chim Acta 737:22–28

    Article  CAS  PubMed  Google Scholar 

  63. Alizadeh N, Salimi A, Hallaj R (2018) Magnetoimmunosensor for simultaneous electrochemical detection of carcinoembryonic antigen and α-fetoprotein using multifunctionalized Au nanotags. J Electroanal Chem 811:8–15

    Article  CAS  Google Scholar 

  64. Li YJ, Ma MJ, Zhu JJ (2012) Dual-signal amplification strategy for ultrasensitive photoelectrochemical immunosensing of alpha-fetoprotein. Anal Chem 84(23):10492–10499

    Article  CAS  PubMed  Google Scholar 

  65. Zhang LN, Li L, Ma C, Ge SG, Yan M, Bian CR (2015) Detection of alpha-fetoprotein with an ultrasensitive electrochemiluminescence paper device based on green-luminescent nitrogen-doped graphene quantum dots. Sensor Actuat B-Chem 221:799–806

    Article  CAS  Google Scholar 

  66. Li H, Wang X, Zhang X, He M, Zhang J, Liu P, Tang X, Li C, Wang Y (2022) Eu-MOF nanorods functionalized with large heterocyclic ionic liquid for photoelectrochemical immunoassay of alpha-fetoprotein. Anal Chim Acta 1195:339459

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mehmet Lütfi Yola.

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 (DOC 336 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bölükbaşi, Ö.S., Yola, B.B., Karaman, C. et al. Electrochemical α-fetoprotein immunosensor based on Fe3O4NPs@covalent organic framework decorated gold nanoparticles and magnetic nanoparticles including SiO2@TiO2. Microchim Acta 189, 242 (2022). https://doi.org/10.1007/s00604-022-05344-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-022-05344-z

Keywords

Navigation