Abstract:
High grade serous ovarian cancer (HGSOC) histologic subtypes make up the majority of epithelial ovarian cancer and 85% of cases are diagnosed at advanced stages, in which the 5-year relative survival could be as low as 20%. Unfortunately, only 20% of patients are diagnosed at stages ? and ? when treatment of the disease is more effective. Moreover, there are no mass screening techniques that are cost-effective and reliable.
Our research involves the development of both a low-cost general screening test for early detection of OC as well as a multiplexed precise medical device that can be used for point-of-care testing (POCT) at the bedside to monitor the progress of the disease during treatment. The former detects the lysophosphatidic acid (LPA), a highly promising biomarker, which was found to be elevated in 90% of stage ? OC and gradually increases as the disease progresses to later stages. And the latter detects LPA together with the known cancer antigen-125 (CA125) biomarker to use as a POCT device. We are employing electrochemical techniques, which are highly sensitive and rapid, to develop the proposed devices. Electrochemical devices can be easily miniaturized, which will reduce the cost of the fabrication.
Such devices that can accurately detect early-stage OC as well as monitor the progress of the disease is highly desired for i) mass screening that reduces fatality rates; ii) avoiding false negatives or false positives that can lead to higher health-care costs and undesired stress to the patient iii) monitoring the progress of the disease during and after the treatment or surgery; and iv) screening drug candidates that accelerating the clinical trials.
Our research includes a novel and unique strategy to avoid fouling of devices surfaces by components of biological fluids. This involves silane-based interfacial chemistry for the mitigation of non-specific adsorption. We are tailoring this strategy by designing novel trichlorosilane molecules using molecular dynamic (MD) computer simulations to provide a scaffold for developing the biorecognition surfaces. Using this scaffold, we are developing electrochemical biosensors for LPA and CA125 detection by following affinity-based and aptamer-based approaches, respectively. We will combine the above biosensors in a miniaturized setup using a microfluidic system to fabricate a POCT device capable of detecting LAP and CA125, which is simple, easy to use, and cost-effective.