“Silicon-On-Insulator”-Based Biosensor for the Detection of MicroRNA Markers of Ovarian Cancer

Abstract

Ovarian cancer is a gynecological cancer characterized by a high mortality rate and tumor heterogeneity. Its early detection and primary prophylaxis are difficult to perform. Detecting biomarkers for ovarian cancer plays a pivotal role in therapy effectiveness and affects patients’ survival. This study demonstrates the detection of microRNAs (miRNAs), which were reported to be associated with ovarian cancer tumorigenesis, with a nanowire biosensor based on silicon-on-insulator structures (SOI-NW biosensor). The advantages of the method proposed for miRNA detection using the SOI-NW biosensor are as follows: (1) no need for additional labeling or amplification reaction during sample preparation, and (2) real-time detection of target biomolecules. The detecting component of the biosensor is a chip with an array of 3 µm wide, 10 µm long silicon nanowires on its surface. The SOI-NW chip was fabricated using the “top-down” method, which is compatible with large-scale CMOS technology. Oligonucleotide probes (oDNA probes) carrying sequences complementary to the target miRNAs were covalently immobilized on the nanowire surface to ensure high-sensitivity biospecific sensing of the target biomolecules. The study involved two experimental series. Detection of model DNA oligonucleotides being synthetic analogs of the target miRNAs was carried out to assess the method’s sensitivity. The lowest concentration of the target oligonucleotides detectable in buffer solution was 1.1 × 10−16 M. In the second experimental series, detection of miRNAs (miRNA-21, miRNA-141, and miRNA-200a) isolated from blood plasma samples collected from patients having a verified diagnosis of ovarian cancer was performed. The results of our present study represent a step towards the development of novel highly sensitive diagnostic systems for the early revelation of ovarian cancer in women.

Current strategies for early epithelial ovarian cancer detection using miRNA as a potential tool

“…Biosensors are compact, quick, extremely sensitive, and selective devices. A biosensor has two basic elements: the biorecognition part, which is responsible for recognizing and interacting with the target molecule, and the transducer part, which converts this interaction into readable signals ( Ivanov et al, 2022 ). Extensive research is ongoing to develop miRNA-based sensors for disease detection, including cancers.…”

“…For instance, in a recent work by Ivanov et al, three ovarian cancer-associated plasma miRNA biomarkers, miRNA-21, miRNA-141, and miRNA-200a were detected using silicon nanowire-based biosensors ( Ivanov et al, 2022 ). Here, oligonucleotide probes (oDNA probes) which are complementary to target miRNA, were immobilized on a silicon nanowire-modified sensor surface which detected the miRNAs with a sensitivity of 1.1 × 10 −16 M. In this study, it was stated that being non-amplification-based method, this strategy was less prone to contamination, allowing high specificity in contrast to qPCR, which has sensitivity but is extremely prone to sample contamination.…”

Non-Coding RNAs in Human Health and Diseases

“…This unique methodology was able to discriminate between the plasma of patients and control samples, for increases in previously described autism-associated miRNAs, including miR-106a-5p, miR-106b-5p, and miR-494-5p. There currently is not a blood-based test for autism spectrum disorder diagnosis, but this technology has diagnostic potential for autism [25], as well as some cancers tested by the same group (e.g., [26][27][28]). Three papers in this section take an interesting approach of examining variants in miRNAs that may be associated with two diseases-type 2 diabetes mellitus (T2D), and coronary artery disease.…”