Research progress of nanobiosensor in tumor marker detection_West China Medical Journal

Authors：

OUYANG Jinling , XU Yixin ,  JIAO Lin ,  YING Binwu

Department of Laboratory Medicine, West China Hospital, Sichuan University; Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University; Sichuan Clinical Research Center for Laboratory Medicine; Institution of Medical and Engineering Integration for Molecular Diagnosis, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

JIAO Lin, Email: Jiaolin@scu.edu.cn; YING Binwu, Email: yingbinwu@scu.edu.cn

Keywords：

Nanobiosensor; tumor biomarker; point-of-care testing; clinical translation; multimodal sensing

DOI：

10.7507/1002-0179.202509144

Video：

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Tumor marker detection plays a critical role in early cancer screening, therapeutic evaluation, and recurrence prediction. However, conventional detection methods are constrained by inadequate sensitivity and specificity, limiting their utility in precision diagnosis. The emergence of nanobiosensors offers a promising alternative. This review systematically summarizes recent advances in nanobiosensors for tumor marker detection, with a focus on functionalized nanoprobe design and signal transduction technologies. On this basis, the key bottlenecks hindering clinical translation, including biofouling in complex biological matrices, batch-to-batch reproducibility, and the lack of standardized validation protocols are critically analyzed. Potential solutions are discussed, such as anti-fouling nanointerfaces, artificial intelligence-assisted multi-target analysis, and wearable monitoring. This review aims to provide a reference for the iterative advancement of precision diagnostic technologies for cancer.

Citation： OUYANG Jinling, XU Yixin, JIAO Lin, YING Binwu. Research progress of nanobiosensor in tumor marker detection. West China Medical Journal, 2026, 41(8): 1229-1234. doi: 10.7507/1002-0179.202509144 Copy

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18.	Yan Y, Liu Z, Pang W, et al. Integrated biosensor array for multiplex biomarkers cancer diagnosis via in-situ self-assembly carbon nanotubes with an ordered inverse-opal structure[J]. Biosens Bioelectron, 2024, 262: 116528.
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22.	Ran Y, Dai R, Zhang X, et al. Preparation and application of EpCAM electrochemiluminescent aptamer sensor based on porous UiO-66(Ce) loading CdTe/CdS quantum dots[J]. Sensor Actuat B-Chem, 2025, 436: 137708.
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25.	Chen H, Yuan X, Zhu J, et al. Boosting ultra-sensitivity in surface plasmon resonance sensors with MXene[J]. Laser Photonics Rev, 2026, 20(10): e02348.
26.	Huang S, Chen Q, Li Y, et al. Functionalized metal-organic frameworks integrated with plasmonic nanoparticles: from synthesis to applications[J]. Biosensors (Basel), 2026, 16(1): 53.
27.	Le N, Kim K. Current advances in the biomedical applications of quantum dots: promises and challenges[J]. Int J Mol Sci, 2023, 24(16): 12682.
28.	Li R, Fan H, Zhou H, et al. Nanozyme-catalyzed metasurface plasmon sensor-based portable ultrasensitive optical quantification platform for cancer biomarker screening[J]. Adv Sci (Weinh), 2023, 10(24): e2301658.
29.	Jahani Y, Arvelo ER, Yesilkoy F, et al. Imaging-based spectrometer-less optofluidic biosensors based on dielectric metasurfaces for detecting extracellular vesicles[J]. Nat Commun, 2021, 12(1): 3246.
30.	Shin H, Choi BH, Shim O, et al. Single test-based diagnosis of multiple cancer types using exosome-SERS-AI for early stage cancers[J]. Nat Commun, 2023, 14(1): 1644.
31.	Bizzotto D, Burgess IJ, Doneux T, et al. Beyond simple cartoons: challenges in characterizing electrochemical biosensor interfaces[J]. ACS Sens, 2018, 3(1): 5-12.
32.	Bia?as K, Moschou D, Marken F, et al. Electrochemical sensors based on metal nanoparticles with biocatalytic activity[J]. Mikrochim Acta, 2022, 189(4): 172.
33.	Hao LP, Hanan A, Walvekar R, et al. Synergistic integration of MXene and metal-organic frameworks for enhanced electrocatalytic hydrogen evolution in an alkaline environment[J]. Catalysts, 2023, 13(5): 802.
34.	Kumar S, Ahlawat W, Kumar R, et al. Graphene, carbon nanotubes, zinc oxide and gold as elite nanomaterials for fabrication of biosensors for healthcare[J]. Biosens Bioelectron, 2015, 70: 498-503.
35.	Lin T, Lv X, Hu Z, et al. Semiconductor metal oxides as chemoresistive sensors for detecting volatile organic compounds[J]. Sensors (Basel), 2019, 19(2): 233.
36.	Hauke A, Kumar LSS, Kim MY, et al. Superwetting and aptamer functionalized shrink-induced high surface area electrochemical sensors[J]. Biosens Bioelectron, 2017, 94: 438-442.
37.	Wang C, Cheng G, Li G, et al. Dual metal-organic-frameworks mediated resonance energy transfer for ultrasensitive electrochemiluminescence immunosensing[J]. Mikrochim Acta, 2024, 191(11): 707.
38.	Ngaosri P, Karuwan C, Wanram S, et al. A selective dual-signal electrochemical paper-based device using imprinted sensors for voltammetric and impedance analysis of 4-NQO and carcinoembryonic antigen (CEA)[J]. Anal Chim Acta, 2024, 1330: 343273.
39.	Watari M, Galbraith J, Lang HP, et al. Investigating the molecular mechanisms of in-plane mechanochemistry on cantilever arrays[J]. J Am Chem Soc, 2007, 129(3): 601-609.
40.	Rao D, Mei K, Yan T, et al. Nanomechanical sensor for rapid and ultrasensitive detection of tumor markers in serum using nanobody[J]. Nano Res, 2022, 15(2): 1003-1012.

1. Sawyers CL. The cancer biomarker problem[J]. Nature, 2008, 452(7187): 548-552.
2. Han Q, Wang R, Xing B, et al. Label-free photoelectrochemical immunoassay for CEA detection based on CdS sensitized WO3@BiOI heterostructure nanocomposite[J]. Biosens Bioelectron, 2018, 99: 493-499.
3. Pi?ero F, Dirchwolf M, Pess?a MG. Biomarkers in hepatocellular carcinoma: diagnosis, prognosis and treatment response assessment[J]. Cells. 2020, 9(6): 1370.
4. Djavan B, Moul JW, Zlotta A, et al. PSA progression following radical prostatectomy and radiation therapy: new standards in the new millennium[J]. Eur Urol, 2003, 43(1): 12-27.
5. Mack PC, Banks KC, Espenschied CR, et al. Spectrum of driver mutations and clinical impact of circulating tumor DNA analysis in non-small cell lung cancer: analysis of over 8000 cases[J]. Cancer, 2020, 126(14): 3219-3228.
6. Allard WJ, Matera J, Miller MC, et al. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases[J]. Clin Cancer Res, 2004, 10(20): 6897-6904.
7. 王天義, 胡冰冰. 酶聯免疫吸附檢測法臨床應用進展[J]. 中國療養醫學, 2022, 31(4): 368-370.
8. 吳建偉. 化學發光免疫分析技術的臨床應用及研究進展[J]. 中國實用醫藥, 2010, 5(34): 258-259.
9. Fu Y, An J Y, Zhang M, et al. Nanomaterial-based electrochemical biosensors as tools for detecting the tumor biomarker miR-21[J]. Talanta, 2025, 283: 127183.
10. Kim M, Hong S, Khan R, et al. Recent advances in nanomaterial-based biosignal sensors[J]. Small, 2025, 21(3): e2405301.
11. Daniel MC, Astruc D. Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology[J]. Chem Rev, 2004, 104(1): 293-346.
12. Pothipor C, Bamrungsap S, Jakmunee J, et al. A gold nanoparticle-dye/poly(3-aminobenzylamine)/two dimensional MoSe2/graphene oxide electrode towards label-free electrochemical biosensor for simultaneous dual-mode detection of cancer antigen 15-3 and microRNA-21[J]. Colloids Surf B Biointerfaces, 2022, 210: 112260.
13. Mohammadniaei M, Koyappayil A, Sun Y, et al. Gold nanoparticle/MXene for multiple and sensitive detection of oncomiRs based on synergetic signal amplification[J]. Biosens Bioelectron, 2020, 159: 112208.
14. Akbari Nakhjavani S, Afsharan H, Khalilzadeh B, et al. Gold and silver bio/nano-hybrids-based electrochemical immunosensor for ultrasensitive detection of carcinoembryonic antigen[J]. Biosens Bioelectron, 2019, 141: 111439.
15. Yaiwong P, Jakmunee J, Pimalai D, et al. An electrochemical/SERS dual-mode immunosensor using TMB/Au nanotag and Au@2D-MoS2 modified screen-printed electrode for sensitive detection of prostate cancer biomarker[J]. Colloids Surf B Biointerfaces, 2024, 243: 114124.
16. Saleh Ahammad AJ, Lee JJ, Rahman MA. Electrochemical sensors based on carbon nanotubes[J]. Sensors (Basel), 2009, 9(4): 2289-2319.
17. Meskher H, Ragdi T, Thakur AK, et al. A review on CNTs-based electrochemical sensors and biosensors: unique properties and potential applications[J]. Crit Rev Anal Chem, 2024, 54(7): 2398-2421.
18. Yan Y, Liu Z, Pang W, et al. Integrated biosensor array for multiplex biomarkers cancer diagnosis via in-situ self-assembly carbon nanotubes with an ordered inverse-opal structure[J]. Biosens Bioelectron, 2024, 262: 116528.
19. Wu J, Zeng X, Wang L, et al. Embedding carbon nanotubes in artificial cells enhances probe transfer[J]. Adv Mater, 2025, 37(10): e2418271.
20. Kirkwood N, Monchen JOV, Crisp RW, et al. Finding and fixing traps in II-VI and III-V colloidal quantum dots: the importance of Z-type ligand passivation[J]. J Am Chem Soc, 2018, 140(46): 15712-15723.
21. Freeman R, Willner I. Optical molecular sensing with semiconductor quantum dots (QDs)[J]. Chem Soc Rev, 2012, 41(10): 4067-4085.
22. Ran Y, Dai R, Zhang X, et al. Preparation and application of EpCAM electrochemiluminescent aptamer sensor based on porous UiO-66(Ce) loading CdTe/CdS quantum dots[J]. Sensor Actuat B-Chem, 2025, 436: 137708.
23. Zhang Q, Gao X, Ho YP, et al. Controllable assembly of a quantum dot-based aptasensor guided by CRISPR/Cas12a for direct measurement of circulating tumor cells in human blood[J]. Nano Lett, 2024, 24(7): 2360-2368.
24. Holzinger M, Le Goff A, Cosnier S. Nanomaterials for biosensing applications: a review[J]. Front Chem, 2014, 2: 63.
25. Chen H, Yuan X, Zhu J, et al. Boosting ultra-sensitivity in surface plasmon resonance sensors with MXene[J]. Laser Photonics Rev, 2026, 20(10): e02348.
26. Huang S, Chen Q, Li Y, et al. Functionalized metal-organic frameworks integrated with plasmonic nanoparticles: from synthesis to applications[J]. Biosensors (Basel), 2026, 16(1): 53.
27. Le N, Kim K. Current advances in the biomedical applications of quantum dots: promises and challenges[J]. Int J Mol Sci, 2023, 24(16): 12682.
28. Li R, Fan H, Zhou H, et al. Nanozyme-catalyzed metasurface plasmon sensor-based portable ultrasensitive optical quantification platform for cancer biomarker screening[J]. Adv Sci (Weinh), 2023, 10(24): e2301658.
29. Jahani Y, Arvelo ER, Yesilkoy F, et al. Imaging-based spectrometer-less optofluidic biosensors based on dielectric metasurfaces for detecting extracellular vesicles[J]. Nat Commun, 2021, 12(1): 3246.
30. Shin H, Choi BH, Shim O, et al. Single test-based diagnosis of multiple cancer types using exosome-SERS-AI for early stage cancers[J]. Nat Commun, 2023, 14(1): 1644.
31. Bizzotto D, Burgess IJ, Doneux T, et al. Beyond simple cartoons: challenges in characterizing electrochemical biosensor interfaces[J]. ACS Sens, 2018, 3(1): 5-12.
32. Bia?as K, Moschou D, Marken F, et al. Electrochemical sensors based on metal nanoparticles with biocatalytic activity[J]. Mikrochim Acta, 2022, 189(4): 172.
33. Hao LP, Hanan A, Walvekar R, et al. Synergistic integration of MXene and metal-organic frameworks for enhanced electrocatalytic hydrogen evolution in an alkaline environment[J]. Catalysts, 2023, 13(5): 802.
34. Kumar S, Ahlawat W, Kumar R, et al. Graphene, carbon nanotubes, zinc oxide and gold as elite nanomaterials for fabrication of biosensors for healthcare[J]. Biosens Bioelectron, 2015, 70: 498-503.
35. Lin T, Lv X, Hu Z, et al. Semiconductor metal oxides as chemoresistive sensors for detecting volatile organic compounds[J]. Sensors (Basel), 2019, 19(2): 233.
36. Hauke A, Kumar LSS, Kim MY, et al. Superwetting and aptamer functionalized shrink-induced high surface area electrochemical sensors[J]. Biosens Bioelectron, 2017, 94: 438-442.
37. Wang C, Cheng G, Li G, et al. Dual metal-organic-frameworks mediated resonance energy transfer for ultrasensitive electrochemiluminescence immunosensing[J]. Mikrochim Acta, 2024, 191(11): 707.
38. Ngaosri P, Karuwan C, Wanram S, et al. A selective dual-signal electrochemical paper-based device using imprinted sensors for voltammetric and impedance analysis of 4-NQO and carcinoembryonic antigen (CEA)[J]. Anal Chim Acta, 2024, 1330: 343273.
39. Watari M, Galbraith J, Lang HP, et al. Investigating the molecular mechanisms of in-plane mechanochemistry on cantilever arrays[J]. J Am Chem Soc, 2007, 129(3): 601-609.
40. Rao D, Mei K, Yan T, et al. Nanomechanical sensor for rapid and ultrasensitive detection of tumor markers in serum using nanobody[J]. Nano Res, 2022, 15(2): 1003-1012.

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