Modern Emerging Biosensing Methodologies for the Early Diagnosis and Screening of Ovarian Cancer

Abstract

Ovarian cancer (OC) is one of the leading causes of gynecological cancer-related death worldwide. Late diagnosis at advanced stages of OC is the reason for a higher mortality rate. Earlier diagnosis and proper treatment are important for improving the prognosis of OC patients. Biosensors offer accurate, low-cost, rapid, and user-friendly devices that can be employed for the detection of OC-specific biomarkers in the early stage. Therefore, it is important to consider the potential biomarkers in the biological fluids to confirm the OC prognosis. Out of many biomarkers, the most commonly tested clinically is cancer antigen 125 (CA-125). However, CA-125 is considered to be a poor biomarker for OC diagnosis. Several biosensing methods were developed for the sensitive and quantitative detection of each biomarker. In abnormal expression in OC patients, nucleic acids, enzymes, cells, and exosomes are used as target biomarkers for the construction of biosensors. This review focuses on the development for the detection of various biomarkers using multiple biosensing methods. Here, we describe the origin and the significance of OC-associated biomarkers, the working principle of biosensors, and the classification of biosensors based on their recognition elements and signal transducers. The modes of detection and sensitivity of the sensors are discussed. Finally, the challenges in the fabrication, obstacles in the clinical application, and future prospects are discussed.

Keywords: biosensors; cancer biomarkers; cancer diagnosis; ovarian cancer (OC).

Figure 1

Three main theories regarding the development of ovarian cancer are based on induction of the epithelium of the ovarian surface by hormonal receptors, increased induction of pro-inflammatory agents during continuous ovulation, and cancerous cells originating from the fallopian tube. IL-8, Interleukin-8; CCL2/MCP-1, Monocyte chemoattractant protein-1; CCL5/RANTES, CC Chemokine Ligand-5. The image is adopted from Tazangi et al., 2021, with copyright permission under the terms of the CC BY NC ND 4.0 license [12].

Figure 2

Schematic representation of ovarian cancer biomarkers detection using various recognition elements and sensing materials used for sensor development.

Figure 3

Schematic illustration for preparation of tumor-targeted NIR-II Polymer dots and their application for in vivo metastatic ovarian cancer detection. This image is adapted from the original Zhou et al., 2021, with copyright permission under the terms of the CC-BY-NC-ND 4.0 license [73].

Figure 4

(A) Schematic representation of the two-step synthesis of photoluminescent BSA-AuNCs. (B) The absorption spectra (the inset—BSA-AuNCs under ambient (amb.) and UV illumination); (C) the hydrodynamic size of BSA (red line) and BSA-AuNCs (black line); (D) the photoluminescence; and (E) the HRTEM image of BSA-AuNCs. The image is adapted from Hada et al., 2021, with copyright permission [74].

Figure 5

(A) Schematic illustration of the interaction between DNA-AgNCs-aptas and AuNPs in the absence and in the presence of CEA and CA-125, and the corresponding fluorescence responses. (B,D) Evolution of fluorescence spectra of gDNA1-AgNCs-apta1 and rDNA2-AgNCs-apta2 (in the presence of AuNPs and NaCl) with the increase in target amount, respectively. (C,E) The linear relationships between F/F0 and the concentrations of CEA and CA-125, respectively. F/F0 represents the fluorescence intensity in the presence and absence of targets. The image is adapted from Xu et al., 2020, with copyright permission [83].

Figure 6

(i) Schematic illustration of the proximity hybridization-based multiple-stimuli-responsive immuno-sensing platform. (ii) (A) Photographs and (B) UV–vis absorption spectra of different components in MoS₂ NSs-mediated ABTS-H₂O₂ colorimetric system. (C) Temperature changes in the corresponding reaction solutions (0.2 mL) after irradiating by an 808 nm laser (2.5 W cm⁻²) for 30 s. (D) ECL responses of (a) GCE and (b) GCE/MoS2 NSs without and (c) GCE/MoS2 NSs with 808 nm laser (2.5 W cm⁻²) irradiation for 40 s in 0.1 M PBS4 (0.1 M Na₂HPO₄, 0.1 M NaH₂PO₄, pH 8.0) containing 10⁻⁵ M luminol. a–f in (A,C) correspond with each other. This image was adapted from Zhang et al., 2020, with copyright permission [91].

Figure 7

(i) Fabrication of the hydrogel with the synergistic effect of cell imprinting and boronate affinity (PBA-CIH) for the capture and release of SMMC-7721 cells. (ii) Microscopy images of the SMMC-7721 cells on (a) culture dishes and showing the surface morphology (b) NIH, (c) UCIH, and (d) CIH after removing the cell templates. The insets are zoomed in on the imprinted sites in the microscopy image. Cryo-SEM of the nanostructures inside the microstructures of (e) the UCIH and (f) the CIH. Scale bars (a,d) (a–d 100 µm) (e) represent 340 nm, and scale bar (f) represents 500 nm. The image is adapted from Liu et al., 2020, with copyright permission [147].