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Recent Advances in Electrochemical and Optical Biosensors for Cancer Biomarker Detection

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Abstract

Cancer is a universal disease with a high mortality rate and caused by an uncontrolled growth of abnormal cells. Each cancer has its unique molecular change such as up/down-regulations of biological molecules in cancer cells. These biological molecules have been identified as biomarkers and used as a target analyte for cancer diagnosis. Since the level of cancer biomarkers is very insufficient at an early stage cancer, there is a need for technological advances that can be more accurate, ultra-sensitive, trustworthy, and selective to biomarkers. This review summarizes evaluation methods and recent advances in electrochemical and optical (fluorescent and colorimetric) biosensors to detect various cancer biomarkers as molecular targets. Electrochemical methods demonstrate rapid and ultra-sensitive detection of cancer biomarkers. And, fluorescent biosensors present improved target detection sensitivity by signal amplification strategy as well as provide the possibility to sense multiple biomarker targets with multiple fluorescent probes. Colorimetric biosensors easily and quickly detect cancer biomarkers by the naked eye for use as a point-of-care testing (POCT) platform. These biosensors can be further improved by understanding the complication of cancer cells and the molecular alterations in cancer progression for early diagnosis of cancer and patient prognosis.

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Fig. 1
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Copyright 2021, Elsevier. b CV response of BSA/anti-ANXA2/f-MWCNT/ITO immunoelectrode as a function of ANXA2 concentration (0–60 ng/mL). Reprinted with permission from [45]. Copyright 2021, Elsevier. c Fabrication of polymer PThiEpx-modified ITO immunosensor for detection of IL 1α cancer biomarker. Reprinted with permission from [46]. Copyright 2019, Elsevier. d CV response of polymer PThiEpx-modified ITO immunosensor after incubation with different concentrations of IL 1α (0.01–5.5 pg/mL). Reprinted with permission from [46]. Copyright 2019, Elsevier. e Competitive electrochemical immunosensor based on DA/MUC-1/fMWCNTs probe and MUC-1 antibody-modified gelatin working electrode for detection of MUC-1, a breast cancer biomarker. Reprinted with permission from [47]. Copyright 2021, Elsevier. f CV response of competitive electrochemical immunosensor with different concentrations of MUC-1 (0.05–940 U/mL). Reprinted with permission from [47]. Copyright 2021, Elsevier

Fig. 4

Copyright 2022, American Chemical Society. b DPV response of BSA/anti-CD44/GO-IL-AuNPs/GCE working electrode depending on different concentrations of CD44 antigen (100 fg/mL–50 μg/mL). Reprinted with permission from [52]. Copyright 2022, American Chemical Society. c Anti-PSMA antibody (a-PSMA)/Cys-AuNP/SPGE electrochemical immunosensor for detection of PSMA prostate cancer biomarker. Reprinted with permission from [53]. Copyright 2022, Elsevier. d DPV response of a-PSMA/Cys-AuNP/SPGE working electrode as a function of PSMA concentration (0–250 ng/mL). Reprinted with permission from [53]. Copyright 2022, Elsevier. e AuNPs@NIPAm-co-AAc microgel-modified electrodes for detection of miRNA-21 as a breast cancer biomarker. Reprinted with permission from [54]. Copyright 2022, Elsevier. f DPV response of AuNPs@NIPAm-co-AAc microgel electrode for various miRNA-21 contents (0–1 pM). Reprinted with permission from [54]. Copyright 2022, Elsevier

Fig. 5

Copyright 2022, Elsevier. b SWV response of magnetogenosensor with different concentrations of miRNA-203 (0–500 fmol/L). Reprinted with permission from [61]. Copyright 2022, Elsevier. c Electrochemical immunosensor based on gold nanostructured electrode and SWV measurement of a HRP label for blood cancer biomarker (PHB2) detection. Reprinted with permission from [62]. Copyright 2022, Elsevier. d SWV response of HRP-labeled immunosensor as a function of PHB2 (0–50 ng/mL). Reprinted with permission from [62]. Copyright 2022, Elsevier. e SWV electrochemical biosensor (Phage/AuNPs/WS2QDs/GCE) for detection of c-Met, colon cancer biomarker. Reprinted with permission from [63]. Copyright 2022, BioMed Central. f SWV response of Phage-AuNPs-WS2QDs-GCE sensor depending on the concentration of c-Met (1–1000 pg/mL). Reprinted with permission from [63]. Copyright 2022, BioMed Central

Fig. 6

Copyright 2019, ACS Publications. b Impedance response of EIS sensing platform as a function of PCA3 concentration (10–16–10–6 mol/L). Reprinted with permission from [69]. Copyright 2019, ACS Publications. c EIS electrochemical aptasensor ([Fe(CN)6]3−/4−/CEA-A/AuNPs/graphene working electrode) for detection of CEA, lung cancer biomarker. Reprinted with permission from [70]. Copyright 2021, FRONTIERS MEDIA SA. d Impedance response of aptasensor depending on the concentration of CEA (0.2–15.0 ng/mL) Reprinted with permission from [70]. Copyright 2021, FRONTIERS MEDIA SA. e EIS biosensor based on a specific enzyme substrate (F6P) for detection of RmPGI, a protein model of AMF cancer biomarker. Reprinted with permission from [71]. Copyright 2017, Elsevier. f Nyquist plots of EIS sensing system after interaction with various concentrations of RmPGI (10 pM–100 nM). Reprinted with permission from [71]. Copyright 2017, Elsevier

Fig. 7

Copyright 2017, Elsevier. b Detection of ovarian cancer biomarker HE4 using graphene quantum dot (GQD) FRET sensor. Reprinted with permission from [85]. Copyright 2021, Elsevier. c Detection mechanism of two breast cancer biomarkers (miR-593 and miR-155) based on the FRET effect between UCNPs and MoS2 nanosheets. Reprinted with permission from [86]. Copyright 2021, Elsevier. d FRET-based DNA nanoprobe using smartphone RGB camera for detection of nucleic acids encoding anti-apoptotic cancer biomarker survivin. Reprinted with permission from [87]. Copyright 2020, Elsevier

Fig. 8

Copyright 2018, Elsevier. b IFE-based PL sensing system for detection of sarcosine, a biomarker of prostate cancer. Reprinted with permission from [91]. Copyright 2022, Elsevier. c IFE-based CdTe/CdS QD fluorescent probe for detection of ALP as breast, gastric, and prostate cancer biomarkers. Reprinted with permission from [92]. Copyright 2019, Elsevier

Fig. 9

Copyright 2021, Royal Society of Chemistry. b PET-based H2L “turn-on” fluorescence sensor for detection of Zn2+, an early prostate cancer biomarker. Reprinted with permission from [98]. Copyright 2020, Elsevier. c Nanozyme PET sensor array based on aptamer-modified C3N4 nanosheets (Apt/C3N4 NSs) and solvent-mediated signal amplification for detection of cancer-derived exosomes. Reprinted with permission from [99]. Copyright 2020, ACS Publications

Fig. 10

Copyright 2020, Royal Society of Chemistry. b Colorimetric aptasensor based on PDDA-induced aggregation of AuNPs for prostate cancer biomarker (PSA) detection. Reprinted with permission from [107]. Copyright 2020, Elsevier. c AuNPs-based colorimetric aptasensor to diagnose ovarian cancer biomarker (PDGF) under high salt conditions. Reprinted with permission from [108]. Copyright 2022, Elsevier

Fig. 11

Copyright 2020, Elsevier. b Colorimetric detection of breast and prostate cancer biomarker ALP based on pAP-mediated growth of AgNPs. Reprinted with permission from [110]. Copyright 2021, Elsevier. c Colorimetric detection of liver cancer biomarker AFP by Nb-ALP and MnO2 nanoflakes in an enzyme cascade-amplified immunoassay (ECAIA). Reprinted with permission from [112]. Copyright 2021, Elsevier

Fig. 12

Copyright 2020, Elsevier. b Imidazolium group-functionalized PDA colorimetric sensor to detect expression level of phospholipase D as tumor biomarker. Reprinted with permission from [114]. Copyright 2019, Elsevier

Fig. 13

Copyright 2020, Elsevier. b Paper-based Cys-AuNC colorimetric sensor with peroxidase-like activity for detection of citrate as a biomarker of prostate cancer. Reprinted with permission from [119]. Copyright 2019, Elsevier. c Aptamer-based colorimetric LFA for detection of HER2 as a breast cancer biomarker using the adsorption–desorption mechanism. Reprinted with permission from [122]. Copyright 2020, Elsevier

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Acknowledgements

This work was supported by the Technology Innovation Program (20009356) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea). This work was partially supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT, and Future Planning (MSIT) (NRF-2021EG053010113 & 2022R1A2C1009383).

Funding

Ministry of Trade, Industry and Energy (Grant no. 20009356); Ministry of Science, ICT and Future Planning (Grant no. 2021EG053010113, 2022R1A2C1009383).

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  1. Min Hyeong Son, Seok Won Park, and Hee Yeon Sagong have contributed equally to this work.

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  1. Department of Nanoscience and Engineering, Inje University, Gimhae, 50834, Republic of Korea

    Min Hyeong Son, Seok Won Park, Hee Yeon Sagong & Yun Kyung Jung

  2. School of Biomedical Engineering, Inje University, Gimhae, 50834, Republic of Korea

    Yun Kyung Jung

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Son, M.H., Park, S.W., Sagong, H.Y. et al. Recent Advances in Electrochemical and Optical Biosensors for Cancer Biomarker Detection. BioChip J 17, 44–67 (2023). https://doi.org/10.1007/s13206-022-00089-6

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