Photoelectrochemical Sensors for the Detection of Disease Biomarkers: Principles and Applications
DOI:
https://doi.org/10.54097/6qa2qw69Keywords:
Photoelectrochemical Biosensors, Disease Biomarkers, Functional Materials, Clinical Diagnostics.Abstract
The rapid and accurate detection of disease biomarkers is crucial for the early diagnosis, prognosis assessment, and therapeutic monitoring of major diseases, including cancer, cardiovascular diseases, inflammatory responses, and infectious diseases. Conventional analytical techniques such as enzyme-linked immunosorbent assay (ELISA), mass spectrometry, and nucleic acid amplification, while reliable, are often constrained by complicated procedures, high cost, and limited applicability in point-of-care settings. In response to the aforementioned challenges, photoelectrochemical (PEC) sensors have garnered significant attention in recent years due to their advantages of low background noise, high sensitivity, and simple instrumentation, emerging as a promising direction in biosensing. This review systematically elucidates the fundamental operating principles of PEC biosensors and summarizes the key functional materials involved in their construction (such as semiconductor optoelectronic materials, photosensitizers, and electron transport aids) and their interfacial regulation strategies. Furthermore, recent progress in the application of PEC sensors for the detection of disease-related biomarkers is critically examined, with representative examples targeting cancer-associated proteins, cardiovascular disease markers, inflammatory mediators, pathogen-derived nucleic acids, and antigens. The performance of different detection strategies is also compared in terms of sensitivity, selectivity, and practical feasibility. Finally, the challenges hindering the broader application of PEC biosensors are discussed. Future perspectives are outlined, highlighting material innovation, interfacial optimization, and device miniaturization as key directions to advance PEC biosensors toward clinical translation and portable diagnostic applications.
Downloads
References
[1] Zhang Guoming, Guo Xuxiao. Combining PCT with CRP is better than separate testing for patients with bacteriuria in the intensive care unit: a retrospective study [J]. European Journal of Medical Research, 2024, 29(1): 441.
[2] Yang Xianggui, Zeng Jun, Yu Xuejing, et al. PCT, IL-6, and IL-10 facilitate early diagnosis and pathogen classifications in bloodstream infection [J]. Annals of Clinical Microbiology and Antimicrobials, 2023, 22(1): 103.
[3] Liu Yuxin, Sun Qihao, Long Houtao, et al. The value of IL-6, PCT, qSOFA, NEWS, and SIRS to predict septic shock after Percutaneous nephrolithotomy [J]. BMC Urology, 2024, 24(1): 116.
[4] Qaraqe Marwa, Elzein Almiqdad, Belhaouari Samir, et al. A novel few shot learning derived architecture for long-term HbA1c prediction [J]. Scientific Reports, 2024, 14(1): 482.
[5] Pei Junyu, Wang Xiaopu, Pei Zeyu, et al. Glycemic control, HbA1c variability, and major cardiovascular adverse outcomes in type 2 diabetes patients with elevated cardiovascular risk: insights from the ACCORD study [J]. Cardiovascular Diabetology, 2023, 22(1): 287.
[6] Bülent Demirelli, Burcu Boztepe, Elif Gülcan Şenol, et al. Non-diabetic nephropathy in diabetic patients: incidence, HbA1c variability and other predictive factors, and implications [J]. International Urology and Nephrology, 2024, 56(9): 3091-3100.
[7] MATSON R S. Interference in ELISA [M]. Springer US, 2023: 91-99.
[8] Alberoni C, Pavan G, Scattolin T, et al. Critical Aspects and Challenges in the Design of Small Molecules for Electrochemiluminescence (ECL) Application [J]. ChemPlusChem, 2024, 89(8): e202400142.
[9] Snigdha Rai, Ashi Ikram, Sonal Sahai, et al. CNT based photoelectrodes for PEC generation of hydrogen: A review [J]. International Journal of Hydrogen Energy, 2017, 42(7): 3994-4006.
[10] Manpreet Kaur, Prashant Kumar, et al. A review on advances in photoelectrochemical (PEC-type) photodetectors: A trending thrust research area [J]. International Journal of Hydrogen Energy, 2024, 49: 1095-1112.
[11] Zhang Ling, Shi Xiaomei, XU Y T, et al. Binding-induced formation of DNAzyme on an Au@Ag nanoparticles/TiO2 nanorods electrode: Stimulating biocatalytic precipitation amplification for plasmonic photoelectrochemical bioanalysis [J]. Biosensors and Bioelectronics, 2019, 134: 103-108.
[12] Du Haotian, Yin Tengyue, Wang Jianru, et al. Multifunctional Photoelectrochemical Biosensor Based on ZnIn2S4/ZnS QDs@Au–Ag-Reversed Photocurrent of Cu-Metal–Organic Framework Coupled with CRISPR/Cas-12a-Shearing for Assay of Dual Targets [J]. Analytical Chemistry, 2023, 95(17): 7053-7061.
[13] Zhang Qinging, Liu Suying, Zheng Hejie, et al. Magnetic photoactive Fe3O4@Sb2S3 nanospheres assisted homogeneous photoelectrochemical–electrochemical biosensing platform integrating with MOFs-derived bifunctional NPC@Thi nanopolyhedra-mediated dual “signal-on” strategy for protein tyrosine kinase activity [J]. Chemical Engineering Journal, 2023, 476: 146592.
[14] Zhang Qi, Gu Mengmeng, Zhang Lan, et al. Metal–to–particle charge transfer invoked photoelectrochemistry on ferroelectric SrTiO3 for split–mode and high–throughput aptasensing [J]. Analytica Chimica Acta, 2024, 1331: 343318.
[15] Liu Ying, Liu Jing, Zhang Qinghua, et al. CuO/Ag2S/CuS Nanohybrids-Integrated Photoelectric and Photothermal Effects for Ultrasensitive Detection of Inorganic Pyrophosphatase [J]. AdvancedFunctional Materials, 2022, 32(5): 2106854.
[16] Wang Ruiming, Wang Shuai, Guo Wangze, et al. Flow injection analysis coupled with photoelectrochemical immunoassay for simultaneous detection of anti-SARS-CoV-2-spike and anti-SARS-CoV-2-nucleocapsid antibodies in serum samples [J]. Analytica Chimica Acta, 2023, 1280: 341857.
[17] Zheng Hejie, Bai Linghe, Du Cuicui, et al. PEC-EC dual-mode biosensing platform for PFOA assay based on competitive binding between HSA and PFOA or hemin [J]. Sensors and Actuators B: Chemical, 2025, 429: 137326.
[18] Zou Huiyu, Wu Wuming, Zhou Jingjing, et al. SILAR Growth of ZnO NSs/CdSQDs on the Optical Fiber-Based Opto-Electrode with Guided In Situ Light and ItsApplication for the “Signal-On” Detection of Inflammatory Cytokine [J]. Analytical Chemistry, 2024, 96(14): 5446-5454.
[19] Li Hao, Lin Zhenfu, Chen Zhencheng, et al. Research advances in chemical sensing of p-Aminophenol: A review [J]. Microchemical Journal, 2025, 208: 112424.
[20] Ghoti Akash N, Patil Ashokrao B, Pardeshi Satish K. Li sensitized CdS/TiO2 nanocomposite photoanode for solar water splitting, hydrogen generation and photoelectrochemical (PEC) performance [J]. International Journal of Hydrogen Energy, 2024, 51: 1586-1597.
[21] Zhong Yu, Xu Zhiwei, Cheng Zhangjian, et al. A Y-shape-structured photoelectrochemical biosensor based on Bi4NbO8Cl/TiO2 heterojunction and enzyme-mediated electrocatalysis for sensitive and selective determination of microRNA in serum [J]. Microchemical Journal, 2025, 214: 113954.
[22] Ahmadi N, Bagherzadeh M, Nemati A. Comparison between electrochemical and photoelectrochemical detection of dopamine based on titania-ceria-graphene quantum dots nanocomposite [J]. Biosensors and Bioelectronics, 2020, 151: 111977.
[23] Ma Fei, Li Chenchen, Zhang Chunyang. Development of quantum dot-based biosensors: principles and applications [J]. Journal of Materials Chemistry B, 2018, 6(39): 6173-6190.
[24] Wang Dannni, Zhao Xiayu, Wei Yunyun, et al. A pH-responsive colorimetric detection of human telomerase RNA based on a three-dimensional DNA amplifier [J]. Analytica Chimica Acta, 2020, 1111: 67-74.
[25] Chu Yanxin, Deng Anping, Wang Weijing, et al. Concatenated Catalytic Hairpin Assembly/Hyperbranched Hybridization Chain Reaction Based Enzyme-Free Signal Amplification for the Sensitive Photoelectrochemical Detection of Human Telomerase RNA [J]. Analytical Chemistry, 2019, 91(5): 3619-3627.
[26] Zhang Xiafei, Cheng Rui, Shi Zhilu, et al. Label-free Fluorescence Assay of Telomerase RNA Based on Strand Displacement Amplification [J]. Chemical Journal of Chinese Universities-chinese, 2016, 37(1): 12.
[27] Yang Xu, Yu Zhouyi, Yin Zhengzhi, et al. A dual-mode sensor based on surface molecularly imprinted Pt nanoclusters for detection of SARS-CoV-2 spike protein [J]. Sensors and Actuators B: Chemical, 2024, 415: 136020.
[28] Liang Chaolan, Liu Bochao, Li Jinfeng, et al. A nanoenzyme linked immunochromatographic sensor for rapid and quantitative detection of SARS-CoV-2 nucleocapsid protein in human blood [J]. Sensors and Actuators B: Chemical, 2021, 349: 130718.
[29] Amouzadeh Tabrizi M, Nazari L, Acedo P. A photo-electrochemical aptasensor for the determination of severe acute respiratory syndrome coronavirus 2 receptor-binding domain by using graphitic carbon nitride-cadmium sulfide quantum dots nanocomposite [J]. Sensors and Actuators B: Chemical, 2021, 345: 130377.
[30] Guo Aijiao, Pei Fubin, Feng Shasha, et al. A photoelectrochemical immunosensor based on magnetic all-solid-state Z-scheme heterojunction for SARS-CoV-2 nucleocapsid protein detection [J]. Sensors and Actuators B: Chemical, 2023, 374: 132800.
[31] Xu Rongwangzhe, Wang Hanyu, Li Yuyang, et al. A sandwich-type photoelectrochemical immunosensor for the detection of SARS-CoV-2 N protein based on CdS:Mn sensitized Bi2MoO6/In2S3 and NaYF4:Yb, Er for signal amplification [J]. Sensors and Actuators B: Chemical, 2025, 427: 137210.
[32] Wang Wenhai, Luo Lun, Li Yanmei, et al. Detection of SARS-CoV-2 using machine learning-enabled paper-assisted ratiometric fluorescent sensors based on target-induced magnetic DNAzyme [J]. Biosensors and Bioelectronics, 2024, 255: 116272.
[33] Zeeshan, Selvam S P, Park J, et al. Electrochemical Detection ofS-RBD Protein for Point-of-Care SARS-CoV-2 Monitoring UsingPlatinum-Black-Based Sensor Array [J]. BioChip Journal, 2024, 18(2): 330-343.
[34] Cho Hana, Shim Suhyun, Cho Wonwoo, et al. Electrochemical Impedance-Based Biosensors for the Label-Free Detection of the Nucleocapsid Protein from SARS-CoV-2 [J]. ACS Sensors, 2022, 7(6): 1676-1684.
[35] Khodaie A, Heidarzadeh H. Evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a high figure-of-merit plasmonic multimode refractive index optical sensor [J]. Scientific Reports, 2024, 14(1): 25499.
[36] Akinrinade George Ayankojo, Roman Boroznjak, Jekaterina Reut, et al. Molecularly imprinted polymer based electrochemical sensor for quantitative detection of SARS-CoV-2 spike protein [J]. Sensors and Actuators B: Chemical, 2022, 353: 131160.
[37] Xu Bing, Li Yan, Xiang Xiaoying, et al. Optical fiber LSPR sensor for SARS-CoV-2 N gene detection based on AuNRs [J]. Optics & Laser Technology, 2025, 180: 111435.
[38] Yang Xingsheng, Cheng Xiaodan, Tu Zhijie, et al. PDA-mediated colorimetric-fluorescence co-enhanced immunochromatography assay for the simultaneous and rapid detection of SARS-CoV-2 and HAdV [J]. Chemical Engineering Journal, 2024, 481: 148756.
[39] CHEN P H, HUANG C C, WU C C, et al. Saliva-based COVID-19 detection: A rapid antigen test of SARS-CoV-2 nucleocapsid protein using an electrical-double-layer gated field-effect transistor-based biosensing system [J]. Sensors and Actuators B: Chemical, 2022, 357: 131415.
[40] CATUNDA L G da S, MARTIMIANO DO PRADO T, DE OLIVEIRA T R, et al. SARS-CoV-2 detection enabled by a portable and label-free photoelectrochemical genosensor using graphitic carbon nitride and gold nanoparticles [J]. Electrochimica Acta, 2023, 451: 142271.
[41] BHATT S, BOSE N, SHUSHAMA K N, et al. Surface Plasmon Resonance Biosensor with High Sensitivity for Detecting SARS-CoV-2 [J]. Plasmonics, 2025, 20(2): 843-853.
[42] TU W, WANG Z, DAI Z. Selective photoelectrochemical architectures for biosensing: Design, mechanism and responsibility [J]. TrAC Trends in Analytical Chemistry, 2018, 105: 470-483.
[43] LI Z, DONG W, DU X, et al. A novel photoelectrochemical sensor based on g-C3N4@CdS QDs for sensitive detection of Hg2+ [J]. Microchemical Journal, 2020, 152: 104259.
[44] ZHAO D, ZHANG Y, JI S, et al. Molecularly imprinted photoelectrochemical sensing based on ZnO/polypyrrole nanocomposites for acrylamide detection [J]. Biosensors and Bioelectronics, 2021, 173: 112816.
[45] DASHTIAN K, HAJATI S, GHAEDI M. Molecular Imprinted Poly(2,5-benzimidazole)-Modified VO2–CuWO4 Homotype Heterojunction for Photoelectrochemical Dopamine Sensing [J]. Analytical Chemistry, 2022, 94(18): 6781-6790.
[46] LIU J, LIU Y, WANG W, et al. Component reconstitution-driven photoelectrochemical sensor for sensitive detection of Cu2+ based on advanced CuS/CdS p-n junction [J]. Science China Chemistry, 2019, 62(12): 1725-1731.
[47] JIAN J, KUMAR R, SUN J. Cu2O/ZnO p-n Junction Decorated with NiOx as a Protective Layer and Cocatalyst for Enhanced Photoelectrochemical Water Splitting [J]. ACS Applied Energy Materials, 2020, 3(11): 10408-10414.
[48] FENG K, DI Y, HAN M, et al. A photoelectrochemical aptasensor based on double Z-scheme α-Fe2O3/MoS2/Bi2S3 ternary heterojunction for sensitive detection of circulating tumor cells [J]. Frontiers in Bioengineering and Biotechnology, 2024, 12.
[49] DONG Q, DING Q, YUAN R, et al. AuNPs/CdS QDs/CeO2 ternary nanocomposite coupled with scrollable three-dimensional DNA walker mediated cycling amplification for sensitive photoelectrochemical miRNA assay [J]. Analytica Chimica Acta, 2022, 1228: 340344.
[50] MA X Q, LIU W, LI Z P, et al. The high-efficiency PEC material prepared by porphyrin grafted with Au nanoparticles embedded in porous carbon for PTK-7 detection [J]. Sensors and Actuators B: Chemical, 2024, 403: 135141.
[51] MENG H, LIU P, MO F, et al. A novel ultrasensitive photoelectrochemical biosensor for detecting microRNA 21 based on cosensitization strategy and p-n heterojunction quenching mode [J]. Sensors and Actuators B: Chemical, 2020, 325: 128782.
[52] HUANG X, LIN Q, LU L, et al. In2O3/CdIn2S4 heterojunction-based photoelectrochemical immunoassay of carcinoembryonic antigen with enzymatic biocatalytic precipitation for signal amplification [J]. Analytica Chimica Acta, 2022, 1228: 340358.
[53] CAO J T, DONG Y X, MA Y, et al. A ternary CdS@Au-g-C3N4 heterojunction-based photoelectrochemical immunosensor for prostate specific antigen detection using graphene oxide-CuS as tags for signal amplification [J]. Analytica Chimica Acta, 2020, 1106: 183-190.
[54] HU X, WANG Y, ZUPING X, et al. Novel Aggregation-Enhanced PEC Photosensitizer Based on Electrostatic Linkage of Ionic Liquid with Protoporphyrin IX for Ultrasensitive Detection of Molt-4 Cells [J]. Analytical Chemistry, 2022, 94(8): 3708-3717.
[55] KIM H, WANG Y, DENISOV N, et al. DC sputter deposited TiO2 layers on FTO: towards a maximum photoelectrochemical response of photoanodes [J]. Journal of Materials Science, 2022, 57(27): 12960-12970.
[56] TAY Y F, ZHANG M, ZHANG S, et al. Charge transfer enhancement at the CZTS photocathode interface using ITO for efficient solar water reduction [J]. Journal of Materials Chemistry A, 2023, 11(48): 26543-26550.
[57] NG W C, CHONG M N. Organic-inorganic p-type PEDOT:PSS/CuO/MoS2 photocathode with in-built antipodal photogenerated holes and electrons transfer pathways for efficient solar-driven photoelectrochemical water splitting [J]. Sustainable Materials and Technologies, 2023, 38.
[58] LEE S, LEE H, PARK Y S, et al. Self-assembled monolayer mediated fast charge transport of Sb 2 (S,Se) 3 photocathode enabling high-performance unbiased water splitting [J]. Nano Energy, 2024, 126.
[59] HU J, YANG L, YANG P, et al. Polydopamine free radical scavengers [J]. Biomaterials Science, 2020, 8(18): 4940-4950.
[60] PARK H K, PARK J H, LEE H, et al. Material-Selective Polydopamine Coating in Dimethyl Sulfoxide [J]. ACS Applied Materials & Interfaces, 2020, 12(43): 49146-49154.
[61] DELPARASTAN P, MALOLLARI K G, LEE H, et al. Direct Evidence for the Polymeric Nature of Polydopamine [J]. Angewandte Chemie-International Edition, 2019, 58(4): 1077-1082.
[62] HU K, ZHOU J, HAN S, et al. Silane coupling agent enhances recycle aggregate/asphalt interfacial properties: An experimental and molecular dynamics study [J]. Materials Today Communications, 2024, 39.
[63] BHUYAN M A H, BUSQUETS R, CAMPOS L C, et al. Separation of microplastics from water using superhydrophobic silane-coupling-agent-modified geopolymer foam [J]. Separation and Purification Technology, 2024, 339.
[64] LI C, LIAO H, GAO H, et al. Enhancing interface compatibility in high-filled coal gangue/polyethylene composites through silane coupling agent-mediated interface modification [J]. Composites Science and Technology, 2024, 251.
[65] PENG Z, YU M, NIU Y, et al. Enhanced mechanical, thermal, water and UV aging resistance properties of bamboo fiber/HDPE composites through silane coupling agent modified nano-SiO2-TiO2 [J]. Industrial Crops and Products, 2024, 222.
[66] LU Y, WANG H, SHI X M, et al. Photoanode-supported cathodic immunosensor for sensitive and specific detection of human chorionic gonadotropin [J]. Analytica Chimica Acta, 2022, 1199: 339560.
[67] YAN T, FENG Y, REN X, et al. Fabrication of CDs hybrid MIL-68(In) derived In2O3In2S3 hollow tubular heterojunction and their exceptional self-powered PEC aptasensing properties for ampicillin detecting [J]. Journal of Materiomics, 2021, 7(4): 721-727.
[68] DENG Y, YAN W, GUO Y, et al. Highly sensitive and selective photoelectrochemical aptasensing of di-2-ethylhexyl phthalate based on graphene quantum dots decorated TiO2 nanotube arrays [J]. Journal of Hazardous Materials, 2022, 426: 128107.
[69] WANG C, WANG Y, ZHANG H, et al. Molecularly imprinted photoelectrochemical sensor for carcinoembryonic antigen based on polymerized ionic liquid hydrogel and hollow gold nanoballs/MoSe2 nanosheets [J]. Analytica Chimica Acta, 2019, 1090: 64-71.
[70] D’ORAZIO P. Biosensors in clinical chemistry [J]. Clinica Chimica Acta, 2003, 334(1-2): 41-69.
[71] MAO C, QIN Y, ZHOU X, et al. Late-model Bi-MOF＆CdS-QDs materials: Excellent properties and performance in PEC sensors for lung cancer markers [J]. Chemical Engineering Journal, 2024, 490: 151560.
[72] XU Z Z, XU B F, TANJUNG A P, et al. Bio-inspired MOF nanozyme-engineered biocatalytic precipitation strategy mediates electron transfer for ultrasensitive photoelectrochemical immunoassay [J]. Sensors and Actuators B-Chemical, 2024, 412.
[73] CHEN X, LIN Q, HONG Y, et al. In-situ generated CuS triggered near-infrared photoelectrochemical/fluorescent dual-modal microsensor for efficiently detecting and in vivo monitoring hydrogen sulfide [J]. Sensors and Actuators B: Chemical, 2025, 444: 138343.
[74] LIU F, CHEN L, ZHU L, et al. Aptamer-Amplified and CRISPR-Cas12a-Assisted Dual-Mode PEC-SERS Biosensor for Ultrasensitive Detection of Inflammatory Bowel Disease Biomarkers [J]. Analytical Chemistry, 2025, 97(27): 14377-14387.
[75] JIANG Z W, ZHAO T T, LI C M, et al. 2D MOF-Based Photoelectrochemical Aptasensor for SARS-CoV-2 Spike Glycoprotein Detection [J]. ACS Applied Materials & Interfaces, 2021, 13(42): 49754-49761.
[76] XU M, CHEN K, ZHU L, et al. MOF@COF Heterostructure Hybrid for Dual-Mode Photoelectrochemical–Electrochemical HIV-1 DNA Sensing [J]. Langmuir, 2021, 37(45): 13479-13492.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Highlights in Science, Engineering and Technology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
