Electrochemical and Photoelectrochemical Immunosensors for the Detection of Ovarian Cancer Biomarkers

Abstract

Photoelectrochemical (PEC) sensing is an emerging technological innovation for monitoring small substances/molecules in biological or non-biological systems. In particular, there has been a surge of interest in developing PEC devices for determining molecules of clinical significance. This is especially the case for molecules that are markers for serious and deadly medical conditions. The increased interest in PEC sensors to monitor such biomarkers can be attributed to the many apparent advantages of the PEC system, including an enhanced measurable signal, high potential for miniaturization, rapid testing, and low cost, amongst others. The growing number of published research reports on the subject calls for a comprehensive review of the various findings. This article is a review of studies on electrochemical (EC) and PEC sensors for ovarian cancer biomarkers in the last seven years (2016-2022). EC sensors were included because PEC is an improved EC; and a comparison of both systems has, expectedly, been carried out in many studies. Specific attention was given to the different markers of ovarian cancer and the EC/PEC sensing platforms developed for their detection/quantification. Relevant articles were sourced from the following databases: Scopus, PubMed Central, Web of Science, Science Direct, Academic Search Complete, EBSCO, CORE, Directory of open Access Journals (DOAJ), Public Library of Science (PLOS), BioMed Central (BMC), Semantic Scholar, Research Gate, SciELO, Wiley Online Library, Elsevier and SpringerLink.

Keywords: cancer biomarkers; electrochemical sensing; ovarian cancer; photoelectrochemical immunosensors.

Figure 1

Basic components of a typical EC immunosensor.

Figure 2

Construction steps of AuNPs/CNOs/SWCTNs/CS/anti–CEA biosensor. SWCNTs: single–walled carbon nanotubes; CNOs: carbon nano–onions; CS: chitosan; BSA: Bovine serum albumin. Reprinted with permission from [42], published by Elsevier, 2018.

Figure 3

Schematic illustration of the fabrication procedure for CEA immunosensor. GA: glutaraldehyde; Ab: antibody; BSA: bovine serum albumin. Reprinted with permission from [43], published by The Royal Society of Chemistry, 2020.

Figure 4

Electrospinning of core–shell honey nanofibers (HNF) onto the surface of a carbon–paste electrode (CPE) and preparation procedure of MWCNTs/GNPs/HNF/CPE based biosensor. MWCNTs: multi wall carbon nanotubes; GNPs: gold nanoparticles. Reprinted with permission from [46], published by Elsevier, 2020.

Figure 5

Schematic illustration of the fabrication process of CS–MWCNT–Fe₃O₄ based immunosensor for electrochemical detection of CA19–9 antigen. CS: chitosan; MWCNT: multiwalled– carbon nanotube; Fe₃O₄: magnetite nanoparticles; Ab: antibody; Ag: antigen. Reprinted with permission from [55], published by Elsevier, 2021.

Figure 6

Fabrication process of electrochemical immunosensor for CA 19–9 detection. CHIT: chitosan; GA: glutaraldehyde; BSA: bovine serum albumin; Zn-Co-S@ G: binary transition metal sulfide (Zn-Co-S) doped with graphene (G) [53].

Figure 7

The schematic representation of chitosan and carbon black composite based electrochemical immunosensor. Step 1: modification of electrode with glutaraldehyde; step 2: immobilization of antibody; step 3: blocking with BSA; step 4: antigen capturing. Reprinted with permission from [69], published by Elsevier, 2018.

Figure 8

Steps in the fabrication of EC immunosensor. PGE: Pencil graphite electrode; Ab: antibody. Reprinted with permission from [75], published by Elsevier, 2021.

Figure 9

Step–by–step fabrication of electrochemical immunosensor. Reprinted with permission from [89], published by Elsevier, 2016.

Figure 10

SPGE/poly(3–HPA)/anti–CA 125 Immunosensor construction process. Reprinted with permission from [90], published by Elsevier, 2020.

Figure 11

Procedure for developing BSA/anti–HER–2/APTES/MoO₃@RGO/ITO immunosensor. RGO: reduced graphene oxide; APTES: (3–aminopropyl) triethoxysilane; BSA: Bovine serum albumin; ITO: indium tin oxide electrode; MoO₃@RGO: graphene oxide doped with molybdenum trioxide. Reprinted with permission from [94], published by American Chemical Society, 2019.

Figure 12

Schematic illustration of the construction process of an immunosensor. Reprinted with permission from [95], published by Elsevier, 2020.

Figure 13

The schematic illustration of the fabrication procedure for CEA immunosensor.GO- NH₂: amine–doped graphene oxide; Ab1: primary antibody; Ab2: secondary antibody; Fc: feroccene; Ox: oxidation; Re: reduction [108].

Figure 14

Illustrative fabrication process of carcinoembryonic antigen (CEA) sandwich immunosensor. Ab₁: capture antibody; Ab₂: secondary antibody; 3DPt/HGO: 3D porous graphene–oxide–supported platinum metal nanoparticles; GCE: glass carbon electrode [113].

Figure 15

The preparation process of Au@Pt DNs/NG/Cu²⁺–Ab2 and schematic illustration of the sandwich–type EC immunosensor. (A): Probe preparation process; (B): Electrode modification process for the capturing of antigen and probe. Au@PDA: polydopamine doped Au nanoparticles; Au@PtDNs: cubic Au doped with Pt dendritic nanomaterials; NG: nitrogen–doped graphene. Reprinted with permission from [114], published by Elsevier, 2018.

Figure 16

Schematic representation of the fabrication process for Ab2 label and sandwich–type electrochemical immunosensor for AFP detection. (A): Probe preparation process; (B): Electrode modification process for the capturing of antigen and probe. PDA–PR–MCS: polydopamine–decorated phenolic resin microporous carbon spheres; PR–MCS: phenolic resin microporous carbon spheres. Reprinted with permission from [118], published by Elsevier, 2018.

Figure 17

Electrochemical immunosensing process for detecting p53. PEDOT: PSS: poly (3, 4–ethylenedioxythiophene): polystyrenesulfonate; DAP: 2, 3–diaminophenazine; ZIF–8: Zeolitic Imidazolate framework-8; Ab1: primary antibody; Ab2: secondary antibody. Reprinted with permission from [119], published by Elsevier, 2020.

Figure 18

Illustration of the preparation of the electrochemical sandwich–type immunosensor using HRP enzyme for CA15–3 detection. (a): preparation process of Au nanoparticles and reduced graphene oxide (Au−rGO) nanocomposite through electrochemical reduction; (b): fabrication of the sensor; (b1): reduction of H₂O₂ by horseradish peroxidase (HRP), using hydroquinone (HQ) as electron mediator: (b2): redox process. Reprinted with permission from [120], published by Springer–Verlag GmbH Austria, 2021.

Figure 19

Fabrication scheme for a sandwich–type EC immunosensor and a DPV chart showing the level of attached electrochemical tracer (Cd²⁺) on the AuNPs (GNPs). Reprinted with permission from [122], published by Springer–Verlag GmbH Germany, 2018.

Figure 20

The construction steps in P5FIn/erGO based PEC immunosensor. GO: graphene oxide; Ab: antibody; P5Fln: poly (5–formylindole); 5Fln: 5–formylindole. Reprinted with permission from [135], published by Elsevier, 2018.

Figure 21

Schematic diagram of the fabrication procedure of a PEC immunosensor and possible charge transfer mechanism at WO₃/Au/CdS interface in the presence of ascorbic acid (AA) as electron donor. e: electron; h: hole; PRET: Plasmon resonance energy transfer. Reprinted with permission from [136], published by Elsevier, 2018.

Figure 22

Schematic Illustration for the Detection Mechanism of CdS/PdPt–Based PEC biosensor and band structure of the PEC system under illumination. e: electron; h: hole: VB: valence band; CB: conduction band: Eg: energy gap. Reprinted with permission from [140], published by American Chemical Society, 2021.

Figure 23

Schematic processes involved in the photoelectrochemical immunoassay of CEA. (A): Fabrication process of the biosensor and photocurrent response; (B): Photoelectric conversion of C₃N₄–BiOCl; (C): mechanism of Cu²⁺ -quenched photocurrent of C₃N₄–BiOCl in the presence of L-cys. Reprinted with permission from [27], published by Springer–Verlag GmbH Austria, 2019.

Figure 24

Schematic illustration and electron transfer mechanism of the PEC immunosensor. e: electron; h: hole: AA: ascorbic acid; AAP: ascorbic acid 2–phosphate; Ag: antigen; Ab1: primary antibody; Ab2: Secondary antibody. Reprinted with permission from [28], published by Elsevier, 2019.

Figure 25

Schematic development process of the immunosensor (A) and photocurrent activity of ZnO/Ag2S nanocomposites (B). VB: valence band; CB: conduction band; e: electron [149].

Figure 26

Construction process of the photoelectrochemical immunoassay for CA19–9 detection and photogenerated electron–hole transfer mechanism of the immunosensor for target antigen (Ag) detection. AA: ascorbic acid; e: electron; Ab₁: primary antibody; Ab₂: secondary antibody. Reprinted with permission from [154], published by Elsevier, 2015.

Figure 27

Procedure for the fabrication of Photocathode–Based Immunosensor ITO/Bi_2+xWO₆/Ab/BSA/HE4. CE: counter electrode; RE: reference electrode; WE: working electrode; Ab: antibody; Ag: antigen. Reprinted with permission from [156], published by American Chemical Society, 2020.

Figure 28

Preparation procedure of Cu–CP–anti–CEA, Pb–CP–anti–CA199, Cd–CP–anti–CA125 and Zn–CP–anti–CA242 immunosensing probes (A) and the fabrication steps involved in the sandwich–type immunosensor (B). CP: chitosan–poly (acrylic acid) nanospheres; Cu-CP: Cu doped with chitosan–poly (acrylic acid) nanospheres; Pb-CP: Pb doped with chitosan–poly (acrylic acid) nanospheres; Cd-CP: Cd doped with chitosan–poly (acrylic acid) nanospheres; GA: glutaraldehyde; chit-Au: chitosan–decorated AuNPs; SWV: square wave voltammetry. Reprinted with permission from [165], published by Elsevier, 2016.