Electrochemical Biosensors in Hepatocellular Carcinoma: Diagnostic Advances and Pharmacological Perspectives

Electrochemical Biosensors in Hepatocellular Carcinoma: Diagnostic Advances and Pharmacological Perspectives Ramaiyan Velmurugan 1Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. https://orcid.org/0000-0002-9399-3579 Yokesh Shanmugam 1Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. https://orcid.org/0009-0009-9102-5548 Patibandla Jahnavi 2Department of Pharmaceutics, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, India https://orcid.org/0009-0004-2501-7375 Rajeshwar Vodeti 3Department of Pharmaceutics, School of Pharmacy, Anurag University, Hyderabad, Telangana, India Elias Joel Mart 4Department of Pharmacology, Vels institute of science, Technology and Advanced studies (VISTAS), PV Vaithiyalingam Rd, Velan Nagar, Krishnapuram, Pallavaram, Chennai, Tamil Nadu, India https://orcid.org/0009-0000-9560-674X Konatham Teja Kumar Reddy 5Department of Pharmaceutical Analysis, Malla Reddy Institute of Pharmaceutical Sciences, Malla Reddy Vishwavidyapeeth (Deemed to be University), Secunderabad, Telangana, India. https://orcid.org/0000-0003-0227-2248 Balaji Pandiyan 6Department of Pharmacology, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies, Pallavaram, Chennai, India. Soniya Rani 7Department of Pharmacology, GITAM School of Pharmacy, GITAM (Deemed to be University), campus Hyderabad, Telangana, India Prem Shankar Gupta 8Department of Pharmaceutics, Teerthankar Mahaveer College of Pharmacy, Teerthankar Mahaveer University, Moradabad (U.P), India. Lokeshvar Ravikumar 1Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. https://orcid.org/0000-0001-6869-3446 Rahul Ambati 1Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. https://orcid.org/0000-0002-8466-7667

Liver cancer, particularly hepatocellular carcinoma (HCC), has a poor prognosis and a high fatality rate, making it a serious global health issue that is primarily caused by late stage finding. Despite the widespread use of alpha-fetoprotein (AFP) and other conventional biomarkers, their low specificity and sensitivity, especially in the initial stages of disease, highlight the urgent need for improved diagnostic methods. In recent years, the development of novel protein (e.g., glypican-3, des-gamma-carboxy prothrombin) and genetic (e.g., microRNAs, circulating tumor DNA, long non-coding RNAs) biomarkers has significantly enhanced the prospects for HCC surveillance and early detection. Because of their great sensitivity, quick reaction time, and potential for point-of-care use, electrochemical biosensors have demonstrated remarkable promise among developing technologies. Significant advances in detection limits, frequently approaching femtogram levels and dynamic ranges, have been made possible by developments in nanomaterials, surface modification methods, and biorecognition components like aptamers and molecularly imprinted polymers. These innovations have enabled multiplexed and label-free sensing approaches that integrate with microfluidic platforms for more efficient, cost-effective diagnostics. Despite considerable progress, challenges such as reproducibility in complex biological matrices, standardization, and clinical validation remain. Future directions include the incorporation of artificial intelligence for signal processing, development of intelligent materials, and scalable fabrication methods for clinical translation. Overall, electrochemical biosensing represents a transformative approach in liver cancer diagnostics, providing fresh approaches to better patient outcomes, individualized care, and early identification.
12 31 2025 12 30 2025 2551 8648 http://creativecommons.org/licenses/by/4.0/ 10.13005/bpj/3276 https://biomedpharmajournal.org/vol18no4/electrochemical-biosensors-in-hepatocellular-carcinoma-diagnostic-advances-and-pharmacological-perspectives/ https://app.ithenticate.com/en_us/dv/20220511?o=116951826&lang=en_us 10.1021/acs.analchem.9b05218 Huang L, Chen J, Yu Z, Tang D. Self-powered temperature sensor with seebeck effect transduction for photothermal–thermoelectric coupled immunoassay. Analytical chemistry. 2020 Jan 15;92(3):2809-14. CrossRef 10.1021/acs.analchem.8b03538 Ren R, Cai G, Yu Z, Zeng Y, Tang D. Metal-polydopamine framework: an innovative signal-generation tag for colorimetric immunoassay. Analytical Chemistry. 2018 Aug 23;90(18):11099-105. CrossRef 10.4018/IJCAC.2022010109 Anil BC, Dayananda P, Nethravathi B, Mahesh SR. Efficient local cloud-based solution for liver cancer detection using deep learning. International Journal of Cloud Applications and Computing (IJCAC). 2022 Jan 1;12(1):1-3. CrossRef 10.1016/j.chemosphere.2022.134826 Ahmadian E, Janas D, Eftekhari A, Zare N. Application of carbon nanotubes in sensing/monitoring of pancreas and liver cancer. 2022 Sep 1;302:134826. CrossRef 10.1016/j.bbe.2020.10.005 Gunasekhar P, Vijayalakshmi S. Optimal biomarker selection using adaptive Social Ski-Driver optimization for liver cancer detection. Biocybernetics and Biomedical Engineering. 2020 Oct 1;40(4):1611-25. CrossRef 10.1021/acsabm.3c00116 Chauhan D, Chandra R, Kumar S. Hemocompatible functionalized hydrogen substituted graphdiyne based highly durable biosensor for liver cancer detection. ACS Applied Bio Materials. 2023 May 17;6(6):2257-65. CrossRef 10.1021/acs.analchem.8b01825 Lv S, Zhang K, Zeng Y, Tang D. Double photosystems-based ‘Z-Scheme’photoelectrochemical sensing mode for ultrasensitive detection of disease biomarker accompanying three-dimensional DNA walker. Analytical Chemistry. 2018 May 18;90(11):7086-93. CrossRef 10.1021/acs.analchem.7b04479 Qiu Z, Shu J, Tang D. Near-infrared-to-ultraviolet light-mediated photoelectrochemical aptasensing platform for cancer biomarker based on core–shell NaYF4: Yb, Tm@ TiO2 upconversion microrods. Analytical chemistry. 2018 Jan 2;90(1):1021-8. CrossRef 10.1039/D0NR00075B Ren Y, He S, Huttad L, Chua MS, So SK, Guo Q, Cheng Z. An NIR-II/MR dual modal nanoprobe for liver cancer imaging. Nanoscale. 2020;12(21):11510-7. CrossRef 10.1016/j.media.2020.101854 Kim YJ, Jang H, Lee K, Park S, Min SG, Hong C, Park JH, Lee K, Kim J, Hong W, Jung H. PAIP 2019: Liver cancer segmentation challenge. Medical image analysis. 2021 Jan 1;67:101854. CrossRef 10.1080/17474124.2018.1512855 Tzartzeva K, Singal AG. Testing for AFP in combination with ultrasound improves early liver cancer detection. Expert review of gastroenterology & hepatology. 2018 Oct 3;12(10):947-9. CrossRef 10.1016/j.cgh.2022.01.047 Tayob N, Kanwal F, Alsarraj A, Hernaez R, El-Serag HB. The performance of AFP, AFP-3, DCP as biomarkers for detection of hepatocellular carcinoma (HCC): a phase 3 biomarker study in the United States. Clinical Gastroenterology and Hepatology. 2023 Feb 1;21(2):415-23. CrossRef 10.1016/S0009-8981(01)00644-1 Li D, Mallory T, Satomura S. AFP-L3: a new generation of tumor marker for hepatocellular carcinoma. Clinica chimica acta. 2001 Nov 1;313(1-2):15-9. CrossRef 10.3389/fonc.2022.1012418 Jiang D, Zhang Y, Wang Y, Xu F, Liang J, Wang W. Diagnostic accuracy and prognostic significance of Glypican-3 in hepatocellular carcinoma: a systematic review and meta-analysis. Frontiers in Oncology. 2022 Sep 23;12:1012418. CrossRef 10.1186/s12951-022-01378-w Deng H, Shang W, Wang K, Guo K, Liu Y, Tian J, Fang C. Targeted-detection and sequential-treatment of small hepatocellular carcinoma in the complex liver environment by GPC-3-targeted nanoparticles. Journal of nanobiotechnology. 2022 Mar 24;20(1):156. CrossRef 10.1016/S1499-3872(13)60028-4 Yao M, Yao DF, Bian YZ, Wu W, Yan XD, Yu DD, Qiu LW, Yang JL, Zhang HJ, Sai WL, Chen J. Values of circulating GPC-3 mRNA and alpha-fetoprotein in detecting patients with hepatocellular carcinoma. Hepatobiliary & Pancreatic Diseases International. 2013 Apr 15;12(2):171-9. CrossRef 10.1021/acs.analchem.2c03606 Zeng R, Qiu M, Wan Q, Huang Z, Liu X, Tang D, Knopp D. Smartphone-based electrochemical immunoassay for point-of-care detection of SARS-CoV-2 nucleocapsid protein. Analytical chemistry. 2022 Oct 17;94(43):15155-61. CrossRef 10.1021/acs.analchem.9b03177 Lv S, Zhang K, Zhu L, Tang D, Niessner R, Knopp D. H2-based electrochemical biosensor with Pd nanowires@ ZIF-67 molecular sieve bilayered sensing interface for immunoassay. Analytical chemistry. 2019 Aug 22;91(18):12055-62. CrossRef 10.1007/s42823-023-00558-4 Zou Y, Gu H, Yang J, Zeng T, Yang J, Zhang Y. A high sensitivity strategy of nitrite detection based on CoFe@ NC nanocubes modified glassy carbon electrode. Carbon Letters. 2023 Dec;33(7):2075-86. CrossRef 10.1016/j.aej.2023.10.045 Yi K, Xu S, Cheng H, Chen S, Jiang S, Tu J. A label-free sensor based on a carbon nanotube-graphene platform for the detection of non-Hodgkin lymphoma genes. Alexandria Engineering Journal. 2023 Dec 1;84:93-9. CrossRef 10.1002/sstr.202400034 Zhu Y, Liu TH, Zhou W, Shi M, Wu M, Shi P, Zhao N, Li X, Zhang Z, Zhang D, Lv Y. An “On‐Site Transformation” strategy for electrochemical formation of TiO2 nanoparticles/Ti3C2Tx Mxene/reduced graphene oxide heterojunction electrode controllably toward ultrasensitive detection of uric acid. Small Structures. 2024 Aug;5(8):2400034. CrossRef 10.1007/s11694-023-02094-1 Su J, Su X. Determination of tartrazine in sports drinks by a disposable electrochemical sensor modified with Co2O3. Journal of Food Measurement and Characterization. 2023 Dec;17(6):5856-63. CrossRef 10.1016/j.bios.2024.116749 Wang X, Wang H, Wan X, Wei Q, Zeng Y, Tang D. Smartphone-based point-of-care photoelectrochemical immunoassay coupling with ascorbic acid-triggered photocurrent-polarity conversion switching. Biosensors and Bioelectronics. 2025 Jan 1;267:116749. CrossRef 10.1021/acs.analchem.2c01373 Zeng R, Gong H, Li Y, Li Y, Lin W, Tang D, Knopp D. CRISPR-Cas12a-derived photoelectrochemical biosensor for point-of-care diagnosis of nucleic acid. Analytical chemistry. 2022 May 12;94(20):7442-8. CrossRef 10.1007/s11694-023-02112-2 Tang M, Guo J, Shen Z. Rapid detection of carbendazim residue in tea by machine learning assisted electrochemical sensor. Journal of Food Measurement and Characterization. 2023 Dec;17(6):6363-9. CrossRef 10.1016/j.snb.2024.136608 Xu F, Ai QY, Wang AJ, Mei LP, Song P, Liu W, Feng JJ, Cheang TY. Pronounced signal enhancement with gourd-shaped hollow PtCoNi bunched nanochains for electrochemical immunosensing of alpha-fetoprotein. Sensors and Actuators B: Chemical. 2025 Jan 1;422:136608. CrossRef 10.1016/j.snb.2019.03.061 Wang AJ, Zhu XY, Chen Y, Yuan PX, Luo X, Feng JJ. A label-free electrochemical immunosensor based on rhombic dodecahedral Cu3Pt nanoframes with advanced oxygen reduction performance for highly sensitive alpha-fetoprotein detection. Sensors and Actuators B: Chemical. 2019 Jun 1;288:721-7. CrossRef 10.1016/j.aej.2023.10.024 Li Z, Liu H. Study on electrochemical properties of lead calcium tin anode for hydrometallurgy. Alexandria Engineering Journal. 2023 Nov 1;82:389-95. CrossRef 10.1021/acs.analchem.8b02421 Luo Z, Zhang L, Zeng R, Su L, Tang D. Near-infrared light-excited core–core–shell UCNP@ Au@ CdS upconversion nanospheres for ultrasensitive photoelectrochemical enzyme immunoassay. Analytical chemistry. 2018 Jun 25;90(15):9568-75. CrossRef 10.1021/acs.analchem.8b05959 Luo Z, Qi Q, Zhang L, Zeng R, Su L, Tang D. Branched polyethylenimine-modified upconversion nanohybrid-mediated photoelectrochemical immunoassay with synergistic effect of dual-purpose copper ions. Analytical chemistry. 2019 Feb 22;91(6):4149-56. CrossRef 10.3389/fchem.2022.883627 Liang Y, Xu Y, Tong Y, Chen Y, Chen X, Wu S. Graphene-based electrochemical sensor for detection of hepatocellular carcinoma markers. Frontiers in Chemistry. 2022 Apr 8;10:883627. CrossRef 10.1002/ange.202420200 Yu Z, Xu Z, Zeng R, Xu M, Zou M, Huang D, Weng Z, Tang D. Tailored metal–organic framework‐based nanozymes for enhanced enzyme‐like catalysis. Angewandte Chemie. 2025 Feb 10;137(7):e202420200. CrossRef 10.1016/j.bios.2017.10.027 Zhou Q, Lin Y, Zhang K, Li M, Tang D. Reduced graphene oxide/BiFeO3 nanohybrids-based signal-on photoelectrochemical sensing system for prostate-specific antigen detection coupling with magnetic microfluidic device. Biosensors and Bioelectronics. 2018 Mar 15;101:146-52. CrossRef 10.1021/acs.analchem.5b04005 Lin Y, Zhou Q, Li J, Shu J, Qiu Z, Lin Y, Tang D. Magnetic graphene nanosheet-based microfluidic device for homogeneous real-time electronic monitoring of pyrophosphatase activity using enzymatic hydrolysate-induced release of copper ion. Analytical Chemistry. 2016 Jan 5;88(1):1030-8. CrossRef 10.1021/acs.analchem.4c00324 Gao Y, Tang J, Zhou Q, Yu Z, Wu D, Tang D. Excited-state intramolecular proton transfer-driven photon-gating for photoelectrochemical sensing of CO-releasing molecule-3. Analytical Chemistry. 2024 Mar 14;96(12):5014-21. CrossRef 10.1021/acs.analchem.3c03573 Lu L, Zeng R, Lin Q, Huang X, Tang D. Cation exchange reaction-mediated photothermal and polarity-switchable photoelectrochemical dual-readout biosensor. Analytical chemistry. 2023 Oct 25;95(44):16335-42. CrossRef 10.1021/acs.analchem.9b04199 Shu J, Tang D. Recent advances in photoelectrochemical sensing: from engineered photoactive materials to sensing devices and detection modes. Analytical chemistry. 2019 Nov 18;92(1):363-77. CrossRef 10.1021/acs.analchem.4c02606 Wang Y, Zeng R, Tian S, Chen S, Bi Z, Tang D, Knopp D. Bimetallic single-atom nanozyme-based electrochemical-photothermal dual-function portable immunoassay with smartphone imaging. Analytical Chemistry. 2024 Aug 10;96(33):13663-71. CrossRef 10.1039/D4AN01109K Yaman D, Jimenez M, Ferreira-Gonzalez S, Corrigan D. Current trends in electrochemical approaches for liver biomarker detection: a mini-review. 2024. CrossRef 10.1371/journal.pone.0228857 Zhang J, Chen G, Zhang P, Zhang J, Li X, Gan DN, Cao X, Han M, Du H, Ye YA. The threshold of alpha-fetoprotein (AFP) for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis. PLoS One. 2020 Feb 13;15(2):e0228857. CrossRef 10.1097/MD.0000000000027673 Zhou JM, Wang T, Zhang KH. AFP-L3 for the diagnosis of early hepatocellular carcinoma: A meta-analysis. Medicine. 2021 Oct 29;100(43):e27673. CrossRef 10.1159/000366308 Zhang YS, Chu JH, Cui SX, Song ZY, Qu XJ. Des-γ-carboxy prothrombin (DCP) as a potential autologous growth factor for the development of hepatocellular carcinoma. Cellular Physiology and Biochemistry. 2014 Aug 21;34(3):903-15. CrossRef 10.1016/j.cca.2016.10.006 Sauzay C, Petit A, Bourgeois AM, Barbare JC, Chauffert B, Galmiche A, Houessinon A. Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma. Clinica chimica acta. 2016 Dec 1;463:39-44. CrossRef 10.2147/JHC.S48517 Ofuji K, Saito K, Yoshikawa T, Nakatsura T. Critical analysis of the potential of targeting GPC3 in hepatocellular carcinoma. Journal of Hepatocellular Carcinoma. 2014 May 21:35-42. CrossRef 10.1016/j.livres.2020.11.003 Shih TC, Wang L, Wang HC, Wan YJ. Glypican-3: a molecular marker for the detection and treatment of hepatocellular carcinoma. Liver research. 2020 Dec 1;4(4):168-72. CrossRef 10.1042/BST20200653 Zhang J, Li D, Zhang R, Gao P, Peng R, Li J. The miR-21 potential of serving as a biomarker for liver diseases in clinical practice. Biochemical Society Transactions. 2020 Oct 30;48(5):2295-305. CrossRef 10.1016/j.jhep.2014.10.004 Bandiera S, Pfeffer S, Baumert TF, Zeisel MB. miR-122–a key factor and therapeutic target in liver disease. Journal of hepatology. 2015 Feb 1;62(2):448-57. CrossRef 10.1038/s12276-018-0153-7 Ye D, Zhang T, Lou G, Liu Y. Role of miR-223 in the pathophysiology of liver diseases. Experimental & molecular medicine. 2018 Sep;50(9):1-2. CrossRef 10.1053/j.seminoncol.2011.08.001 Braconi C, Henry JC, Kogure T, Schmittgen T, Patel T. The role of microRNAs in human liver cancers. In Seminars in oncology 2011 Dec 1 (Vol. 38, No. 6, pp. 752-763). WB Saunders. CrossRef 10.3390/ijms24119342 Kopystecka A, Patryn R, Leśniewska M, Budzyńska J, Kozioł I. The Use of ctDNA in the diagnosis and monitoring of hepatocellular carcinomaliterature review. International Journal of Molecular Sciences. 2023 May 26;24(11):9342. CrossRef 10.1002/cam4.2799 Zhang Z, Chen P, Xie H, Cao P. Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta‐analysis. Cancer medicine. 2020 Feb;9(4):1349-64. CrossRef 10.1016/j.biopha.2020.111158 Xing C, Sun SG, Yue ZQ, Bai F. Role of lncRNA LUCAT1 in cancer. Biomedicine & Pharmacotherapy. 2021 Feb 1;134:111158. CrossRef 10.3390/ijms21082883 Kim YA, Park KK, Lee SJ. LncRNAs act as a link between chronic liver disease and hepatocellular carcinoma. International journal of molecular sciences. 2020 Apr 20;21(8):2883. CrossRef 10.1039/D0CC05709F Li Z, Zhu M. Detection of pollutants in water bodies: electrochemical detection or photo-electrochemical detection?. Chemical Communications. 2020;56(93):14541-52. CrossRef 10.1016/j.bios.2020.112069 Trotter M, Borst N, Thewes R, von Stetten F. Electrochemical DNA sensing–Principles, commercial systems, and applications. Biosensors and Bioelectronics. 2020 Apr 15;154:112069. CrossRef 10.1016/j.aca.2015.05.027 Sun D, Lu J, Chen Z, Yu Y, Mo M. A repeatable assembling and disassembling electrochemical aptamer cytosensor for ultrasensitive and highly selective detection of human liver cancer cells. Analytica Chimica Acta. 2015 Jul 23;885:166-73. CrossRef 10.1007/s00604-019-3354-4 Chikhaliwala P, Rai R, Chandra S. Simultaneous voltammetric immunodetection of alpha-fetoprotein and glypican-3 using a glassy carbon electrode modified with magnetite-conjugated dendrimers. Microchimica Acta. 2019 Apr;186:1-2. CrossRef 10.1016/j.microc.2024.110703 Kamel RM, Abdel-aal FA, Mohamed FA, Abdeltawab A, Abdel-Malek MO, Othman AA, Mohamed AM. Copper@ eggshell nanocomposite/chitosan gelified carbon paste electrode as an electrochemical biosensor for l-tyrosine analysis as a biomarker in the serum of normal and liver disease patients. Microchemical Journal. 2024 Jun 1;201:110703. CrossRef 10.3390/s21093183 Leung WH, Pang CC, Pang SN, Weng SX, Lin YL, Chiou YE, Pang ST, Weng WH. High-sensitivity dual-probe detection of urinary miR-141 in cancer patients via a modified screen-printed carbon electrode-based electrochemical biosensor. Sensors. 2021 May 3;21(9):3183. CrossRef 10.1016/j.talanta.2023.124492 Wu H, Zhang G, Yang X. Electrochemical immunosensor based on Fe3O4/MWCNTs-COOH/AuNPs nanocomposites for trace liver cancer marker alpha-fetoprotein detection. Talanta. 2023 Jul 1;259:124492. CrossRef 10.1016/j.msec.2017.02.132 Sheikhpour M, Golbabaie A, Kasaeian A. Carbon nanotubes: A review of novel strategies for cancer diagnosis and treatment. Materials Science and Engineering: C. 2017 Jul 1;76:1289-304. CrossRef 10.1016/j.bios.2018.07.060 Ruiyi L, Fangchao C, Haiyan Z, Xiulan S, Zaijun L. Electrochemical sensor for detection of cancer cell based on folic acid and octadecylamine-functionalized graphene aerogel microspheres. Biosensors and Bioelectronics. 2018 Nov 15;119:156-62. CrossRef 10.1016/j.jelechem.2021.115213 Fu X, Li X, Han D, Yang W, Liu C, Fan L, Ding S, Ma Y. Ultrasensitive electrochemical biosensor for des-gamma-carboxy prothrombin analysis based on core-shell Pd@ PtCu-alloy loaded on WS2 nanosheet. Journal of Electroanalytical Chemistry. 2021 May 1;888:115213. CrossRef 10.1039/C9CS00174C Masud MK, Na J, Younus M, Hossain MS, Bando Y, Shiddiky MJ, Yamauchi Y. Superparamagnetic nanoarchitectures for disease-specific biomarker detection. Chemical Society Reviews. 2019;48(24):5717-51. CrossRef 10.1016/j.snb.2011.06.070 Giannetto M, Mori L, Mori G, Careri M, Mangia A. New amperometric immunosensor with response enhanced by PAMAM-dendrimers linked via self assembled monolayers for determination of alpha-fetoprotein in human serum. Sensors and Actuators B: Chemical. 2011 Nov 28;159(1):185-92. CrossRef 10.1016/j.sintl.2020.100040 Purohit B, Vernekar PR, Shetti NP, Chandra P. Biosensor nanoengineering: Design, operation, and implementation for biomolecular analysis. Sensors International. 2020 Jan 1;1:100040. CrossRef 10.1016/j.talanta.2021.123146 Taheri N, Khoshsafar H, Ghanei M, Ghazvini A, Bagheri H. Dual-template rectangular nanotube molecularly imprinted polypyrrole for label-free impedimetric sensing of AFP and CEA as lung cancer biomarkers. Talanta. 2022 Mar 1;239:123146. CrossRef 10.1016/j.snb.2017.09.062 Liu S, Ma Y, Cui M, Luo X. Enhanced electrochemical biosensing of alpha-fetoprotein based on three-dimensional macroporous conducting polymer polyaniline. Sensors and Actuators B: Chemical. 2018 Feb 1;255:2568-74. CrossRef 10.1108/SR-02-2020-0030 Al-Shami A, Oweis RJ, Al-Fandi MG. Developing an electrochemical immunosensor for early diagnosis of hepatocellular carcinoma. Sensor Review. 2021 May 17;41(2):125-34. CrossRef 10.1021/acsabm.3c01126 Gangopadhyay B, Roy A, Paul D, Panda S, Das B, Karmakar S, Dutta K, Chattopadhyay S, Chattopadhyay D. 3-polythiophene acetic acid nanosphere anchored few-layer graphene nanocomposites for label-free electrochemical immunosensing of liver cancer biomarker. ACS Applied Bio Materials. 2024 Jan 2;7(1):485-97. CrossRef 10.3389/fbioe.2023.1182880 Yaiwong P, Anuthum S, Sangthong P, Jakmunee J, Bamrungsap S, Ounnunkad K. A new portable toluidine blue/aptamer complex-on-polyethyleneimine-coated gold nanoparticles-based sensor for label-free electrochemical detection of alpha-fetoprotein. Frontiers in Bioengineering and Biotechnology. 2023 May 22;11:1182880. CrossRef 10.2174/0929867329666220222113707 Pusta A, Tertis M, Graur F, Cristea C, Al Hajjar N. Aptamers and new bioreceptors for the electrochemical detection of biomarkers expressed in hepatocellular carcinoma. Current Medicinal Chemistry. 2022 Aug 1;29(25):4363-90. CrossRef 10.1016/j.tibtech.2018.08.009 Ahmad OS, Bedwell TS, Esen C, Garcia-Cruz A, Piletsky SA. Molecularly imprinted polymers in electrochemical and optical sensors. Trends in biotechnology. 2019 Mar 1;37(3):294-309. CrossRef 10.1016/j.microc.2023.108838 Moussa FB. Molecularly imprinted polymers meet electrochemical cancer chemosensors: A critical review from a clinical and economic perspective. Microchemical Journal. 2023 Aug 1;191:108838. CrossRef 10.1016/j.ijoes.2023.100081 Liu C, Liu T. A graphene-assisted electrochemical sensor for detection of alpha-fetoprotein in serum. International Journal of Electrochemical Science. 2023 Apr 1;18(4):100081. CrossRef 10.1149/1945-7111/ab7f20 Forouzanfar S, Alam F, Pala N, Wang C. A review of electrochemical aptasensors for label-free cancer diagnosis. Journal of The Electrochemical Society. 2020 Mar 27;167(6):067511. CrossRef 10.3390/bios13030333 Sanko V, Kuralay F. Label-free electrochemical biosensor platforms for cancer diagnosis: Recent achievements and challenges. Biosensors. 2023 Mar 1;13(3):333. CrossRef 10.1016/j.electacta.2022.140808 Li G, Wang B, Zhao L, Shi X, Wu G, Chen W, Sun L, Liang J, Zhou Z. Label-free detection of glypican-3 using reduced graphene oxide/polyetherimide/gold nanoparticles enhanced aptamer specific sensing interface on light-addressable potentiometric sensor. Electrochimica Acta. 2022 Sep 10;426:140808. CrossRef 10.3390/s18114032 Kim DH, Oh HG, Park WH, Jeon DC, Lim KM, Kim HJ, Jang BK, Song KS. Detection of alpha-fetoprotein in hepatocellular carcinoma patient plasma with graphene field-effect transistor. Sensors. 2018 Nov 19;18(11):4032. CrossRef 10.1016/j.bioelechem.2024.108767 Li G, Wang B, Li S, Li X, Yan R, Tan X, Liang J, Zhou Z. Competitive electrochemical aptasensor for high sensitivity detection of liver cancer marker GP73 based on rGO-Fc-PANi nanocomposites. Bioelectrochemistry. 2024 Dec 1;160:108767. CrossRef 10.1039/D3AY00702B Olorundare FO, Sipuka DS, Sebokolodi TI, Kodama T, Arotiba OA, Nkosi D. An electrochemical immunosensor for an alpha-fetoprotein cancer biomarker on a carbon black/palladium hybrid nanoparticles platform. Analytical Methods. 2023;15(29):3577-85. CrossRef 10.1021/acs.analchem.2c05193 Zhang JH, Liu M, Zhou F, Yan HL, Zhou YG. Homogeneous electrochemical immunoassay using an aggregation–collision strategy for alpha-fetoprotein detection. Analytical Chemistry. 2023 Jan 24;95(5):3045-53. CrossRef 10.20964/2022.10.14 Li J, Xing H, Jin P, Li M, Liu H. Electrochemical immunosensing based on signal amplification strategy for alpha-fetoprotein detection. International Journal of Electrochemical Science. 2022 Oct 1;17(10):22107. CrossRef 10.3390/bios13060628 Zhang T, Yang L, Yan F, Wang K. Vertically-ordered mesoporous silica film based electrochemical aptasensor for highly sensitive detection of alpha-fetoprotein in human serum. Biosensors. 2023 Jun 6;13(6):628. CrossRef 10.1016/j.electacta.2024.144094 Shao H, Liu Z. Epitope imprinted electrochemical sensor for highly sensitive detection of alpha-fetoprotein. Electrochimica Acta. 2024 Apr 20;484:144094. CrossRef 10.1038/s41598-021-93399-y Upan J, Youngvises N, Tuantranont A, Karuwan C, Banet P, Aubert PH, Jakmunee J. A simple label-free electrochemical sensor for sensitive detection of alpha-fetoprotein based on specific aptamer immobilized platinum nanoparticles/carboxylated-graphene oxide. Scientific Reports. 2021 Jul 7;11(1):13969. CrossRef 10.1016/j.bios.2021.113466 Zhao S, Liu N, Wang W, Xu Z, Wu Y, Luo X. An electrochemical biosensor for alpha-fetoprotein detection in human serum based on peptides containing isomer D-Amino acids with enhanced stability and antifouling property. Biosensors and Bioelectronics. 2021 Oct 15;190:113466. CrossRef 10.1016/j.snb.2021.130258 Liao X, Wang X, Li P, Chen S, Zhang M, Mei L, Qi Y, Hong C. Electrochemical immunosensor using artificial enzyme-induced metallization for the ultra-sensitive detection of alpha fetoprotein. Sensors and Actuators B: Chemical. 2021 Oct 1;344:130258. CrossRef 10.1016/j.talanta.2021.122924 Rahmati Z, Roushani M, Hosseini H. Hierarchical nickel hydroxide nanosheets grown on hollow nitrogen doped carbon nanoboxes as a high-performance surface substrate for alpha-fetoprotein cancer biomarkers electrochemical aptasensing. Talanta. 2022 Jan 15;237:122924. CrossRef 10.1016/j.bioelechem.2024.108773 Wu H, Yang X. Biofunctional photoelectrochemical/electrochemical immunosensor based on BiVO4/BiOI-MWCNTs and Au@ PdPt for alpha-fetoprotein detection. Bioelectrochemistry. 2024 Dec 1;160:108773. CrossRef 10.1016/j.snb.2022.132736 Shu Y, Su T, Lu Q, Shang Z, Feng J, Jin D, Zhu A, Xu Q, Hu X. based electrochemical immunosensor device via Ni-Co MOF nanosheet as a peroxidase mimic for the label-free detection of alpha-fetoprotein. Sensors and Actuators B: Chemical. 2022 Dec 15;373:132736. CrossRef 10.1016/j.talanta.2024.126082 Gong L, Wu S, Liu J, Zhang M, Zhuang J, Xu D. Construction of an immunosensor based on Cys/Au@ TiO2 modification for the detection of liver cancer marker PIVKA-II. 2024 Aug 1;275:126082. CrossRef 10.1016/j.bioelechem.2020.107696 Li G, Feng H, Shi X, Chen M, Liang J, Zhou Z. Highly sensitive electrochemical aptasensor for Glypican-3 based on reduced graphene oxide-hemin nanocomposites modified on screen-printed electrode surface. Bioelectrochemistry. 2021 Apr 1;138:107696. CrossRef 10.1016/j.bios.2023.115081 Lu W, Xie X, Lan X, Wu P, Peng H, He J, Zhong L, Liu X, Deng Z, Tan Z, Wu A. An electrochemical immunosensor for the detection of Glypican-3 based on enzymatic ferrocene-tyramine deposition reaction. Biosensors and Bioelectronics. 2023 Apr 1;225:115081. CrossRef 10.1007/s00604-020-04284-w Zhou Z, Zhao L, Li W, Chen M, Feng H, Shi X, Liang J, Li G. Glypican-3 electrochemical aptamer nanobiosensor based on hemin/graphene nanohybrids peroxidase-like catalytic silver deposition. Microchimica Acta. 2020 May;187:1-1. CrossRef 10.1007/s10800-021-01534-4 Shi X, Chen M, Feng H, Zhou Z, Wu R, Li W, Liang J, Chen J, Li G. Glypican-3 electrochemical aptasensor based on reduced graphene oxide‐chitosan‐ferrocene deposition of platinum–palladium bimetallic nanoparticles. Journal of Applied Electrochemistry. 2021 May;51:781-94. CrossRef 10.1007/s00604-024-06419-9 Li G, Guo F, Liang J, Wan B, Liang J, Zhou Z. Sandwich-type supersensitive electrochemical aptasensor of glypican-3 based on PrGO-Hemin-PdNP and AuNP@ PoPD. Microchimica Acta. 2024 Jun;191(6):340. CrossRef 10.1016/j.bioelechem.2024.108709 Li G, Feng H, Li X, Li S, Liang J, Zhou Z. A dual-signal output electrochemical aptasensor for glypican-3 ultrasensitive detection based on reduced graphene oxide-cuprous oxide nanozyme catalytic amplification strategy. Bioelectrochemistry. 2024 Aug 1;158:108709. CrossRef 10.3390/molecules28052271 Li G, Wang B, Li L, Li X, Yan R, Liang J, Zhou X, Li L, Zhou Z. H-rGO-Pd NPs nanozyme enhanced silver deposition strategy for electrochemical detection of glypican-3. 2023 Feb 28;28(5):2271. CrossRef 10.1149/1945-7111/abfc9f Ozer T, Henry CS. Recent advances in sensor arrays for the simultaneous electrochemical detection of multiple analytes. Journal of The Electrochemical Society. 2021 May 7;168(5):057507. CrossRef 10.1016/j.teac.2020.e00106 Kaya SI, Cetinkaya A, Bakirhan NK, Ozkan SA. Trends in sensitive electrochemical sensors for endocrine disruptive compounds. Trends in Environmental Analytical Chemistry. 2020 Dec 1;28:e00106. CrossRef 10.3390/bios12010036 Gunasekaran D, Gerchman Y, Vernick S. Electrochemical detection of waterborne bacteria using bi-functional magnetic nanoparticle conjugates. 2022 Jan 12;12(1):36. CrossRef 10.1016/j.talanta.2021.122108 Mollarasouli F, Zor E, Ozcelikay G, Ozkan SA. Magnetic nanoparticles in developing electrochemical sensors for pharmaceutical and biomedical applications. Talanta. 2021 May 1;226:122108. CrossRef 10.1016/j.microc.2021.106424 Hassanpour S, Hasanzadeh M. Label-free electrochemical-immunoassay of cancer biomarkers: Recent progress and challenges in the efficient diagnosis of cancer employing electroanalysis and based on point of care (POC). Microchemical Journal. 2021 Sep 1;168:106424. CrossRef 10.3390/mi10100662 Mohammadniaei M, Nguyen HV, Tieu MV, Lee MH. 2D materials in development of electrochemical point-of-care cancer screening devices. Micromachines. 2019 Sep 30;10(10):662. CrossRef 10.1016/j.ijoes.2024.100921 Du J, Tao H. Recent advances in electrochemical detection methods for liver cancer biomarkers. Int J Electrochem Sci. 2025;20(1):100921. doi:10.1016/j.ijoes.2024.100921. CrossRef