Development of a low cost, label-free, and highly sensitive optical cavity-based biosensor for point-of-care diagnostics

项目摘要 每年，全世界有数百万人遭受癌症、传染病、 和心血管疾病。早期发现和密切监测疾病状况的能力是 对于寻求帮助患病患者的医疗专业人员来说至关重要。疾病的早期发现不仅 帮助患者接受适当的治疗，增加完全康复的机会，但也很重要， 减少由于处理成本和产出损失而造成的经济影响。早期发现的重要性 最近，在我们抗击当前全球爆发的冠状病毒疾病时， （COVID-19）.即时护理（POC）生物传感器可以让患者定期检查他们的健康状况， 床边或附近，而不依赖于中心实验室检测。有效的POC生物传感器将 成本低并且具有无标记操作、高灵敏度、高特异性、多重性（即，能力 同时检测样品流体中的多种分析物）、短周转时间和定量检测。 然而，目前的诊断技术不适合用作POC生物传感器和各种光学传感器。 所开发的生物传感器对于POC的使用仍然具有缺点。 PI的长期目标是开发具有所有所需特性的POC生物传感器。到 为了实现这一目标，PI和他的团队开发了一种基于光腔的生物传感器（OCB）， 差分检测法光学谐振器结构对于生物传感应用具有固有的吸引力 这是由于其无标记操作和谐振特性。OCB的创新之处在于使用低- 通过采用差分检测方法提高了灵敏度。最近，我们能够 以成功展示OCB的低成本、无标签和便携特性。检测限 (LOD)我们能够达到的C-反应蛋白（CRP）分子的浓度为377皮摩尔（pM）。主要 本提案的目的是提高OCB的LOD。我们将研究三种不同的策略， OCB中的LOD。这项研究在医学诊断领域具有重要意义， 它将加强贝勒大学的研究环境，并将为以下方面提供机会： 本科生参与研究项目。在目标1中，我们将尝试通过以下方式改进LOD： 使用改进的光学腔结构和用于差分检测方法的方程。在目标2中， 将研究不同的硅烷化过程中使用气相和溶液相沉积的3- 氨基丙基三乙氧基硅烷（APTES）。最后，在目标3中，我们将开发适当的分配和孵化 皮升流体分配器的过程，以创建更小的感测区域并研究OCB的LOD 具有各种传感区域。最后，我们预计OCB的LOD将达到飞摩尔（fM）范围 这与现有技术的生物传感器的水平相当。

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.