Development of a low cost, label-free, and highly sensitive optical cavity-based biosensor for point-of-care diagnostics - Project Summary Each year, millions of people around the world suffer and die from diseases such as cancers, infectious diseases, and cardiovascular diseases. Early detection and the ability to closely monitor the status of the disease are critical for medical professionals seeking to help diseased patients. The early detection of diseases not only helps patients to receive proper treatment and increases the chance of full recovery but also is important to reduce the economic impact due to treatment costs and output losses. The importance of early detection has been widely recognized recently as we fight against the current global outbreak of coronavirus disease 19 (COVID-19). Point-of-care (POC) biosensors could allow patients to regularly check their health condition at the bedside or near them without being dependent on the central laboratory testing. Effective POC biosensors would be low cost and would have label-free operation, high sensitivity, high specificity, multiplexability (i.e., ability to detect multiple analytes in a sample fluid simultaneously), a short turnaround time, and quantitative detection. However, current diagnostic technologies are not suitable to be used as POC biosensors and the various optical biosensors developed still have drawbacks for POC use. The long-term goal of the PI is to develop a POC biosensor with all the required characteristics. To achieve this goal, the PI and his team have developed an Optical Cavity-based Biosensor (OCB) with a differential detection method. An optical resonator structure is inherently attractive for the biosensing application due to its label-free operation and resonant characteristics. The innovative aspect of our OCB is the use of low- cost components with enhanced sensitivity by employing a differential detection method. Recently, we were able to successfully demonstrate low-cost, label-free, and portable characteristics of the OCB. The limit of detection (LOD) we were able to achieve was 377 picomolar (pM) for the C-reactive protein (CRP) molecules. The main goal of this proposal is to improve the LOD of the OCB. We will investigate three different strategies for improving the LOD in our OCB. The proposed research could have substantial significance in the medical diagnosis field, it will strengthen the research environment of Baylor University, and it will provide opportunities for undergraduate students to be involved in the research project. In Aim 1, we will attempt to improve the LOD by using an improved optical cavity structure and equation used for the differential detection method. In Aim 2, we will investigate different silanization processes using vapor-phase and solution-phase deposition of 3- aminopropyltriethoxysilane (APTES). Finally, in Aim 3, we will develop proper dispensing and incubation processes for a picoliter fluid dispenser to create a smaller sensing area and investigate the LODs of the OCB with various sensing areas. In the end, we anticipate achieving the LOD of the OCB in the femtomolar (fM) range which is comparable to that of the state-of-the-art biosensors.
