Collaborative Research: A Microfluidic-CMOS Cross-cut Approach enabling Tri-Modal Biorecognition for Highly Accurate Viral Diagnostics

该项目旨在开发一种手指棒大小的仪器，其目的是快速诊断血液中的病毒感染。提议的使用点设备可用于在机场、急诊室或其他病毒疾病传播可能性高的拥挤环境中快速筛查受试者。病毒性病原体的使用点诊断在应对疫情方面发挥着关键作用，但由于患者之间的异质性和体液中生物标志物随感染时间的变化，单一模式的生物分子诊断是出了名的不可靠。在这项工作中，提出了一种微流体- cmos -生化横切方法，以实现便携式，紧凑的使用点混合设备技术，实现多模态检测能力，包括抗体检测，病毒蛋白检测以及单个样本到答案平台上的病毒载量定量。提出的三模式诊断平台将使诊断具有最小的假阴性，这对诊断至关重要。这个项目的横切方法将吸引和培养跨学科的研究生和本科生。这些项目还将吸引当地学校的高中高年级学生参与，并通过他们建议的课程（本科和研究生）以及出版物、研讨会和讲习班广泛传播知识。提出的创新是基于微流体中样品、试剂和缓冲处理的小型化，使用低功率电子驱动微阀、可重构电渗透泵，以及硅ICS中荧光标记蛋白质和核酸的多路检测，集成纳米等离子体滤波器，消除了复杂光学扫描仪、透镜、准直器的必要性。该平台被设想为通用的和可重构的，预功能化的药盒可以替换为不同的传染病。具体来说，该研究旨在通过电子驱动的流体阀和泵来研究和开发多模态检测能力，从而实现芯片上的免疫分析，用于蛋白质检测，芯片上的核酸纯化、扩增和杂交，用于病毒载量测定，以及光导、包装和增材制造技术，以实现样品到答案的平台。

This project seeks to develop a finger-stick sized instrument whose purpose is to rapidly diagnose viral infections in blood. The proposed point-of-use device can be utilized for rapidly screening subjects at airports, emergency rooms, or other crowded environments where the potential to spread viral disease is high. Point-of-use diagnosis of viral pathogens plays a critical role in response efforts to outbreaks, but is notoriously unreliable with a single mode of bio-molecular diagnostics due to patient-patient heterogeneity and variation of the biomarkers in the body fluid with time of infection. In this work, a microfluidics-CMOS-bio-chemistry crosscut approach is proposed to enable portable, compact point-of-use hybrid device technology that enables multi-modal detection capability including antibody detection, viral protein detection as well as viral load quantification in a single sample-to-answer platform. The proposed tri-modal diagnostic platform will enable diagnosis with minimal false-negatives, critically important for diagnosis. The crosscut approach towards this project will engage and train both graduate and undergraduate students across multiple disciplines. The PIs will also engage high-school seniors from local schools and broadly disseminate the knowledge through their proposed courses (undergraduate and graduate) and through publications, seminars and workshops.The proposed innovation is based on miniaturization of sample, reagent, and buffer handling in microfluidics using low power electronically actuated micro-valves, reconfigurable electroosmotic pumps, and multiplexed detection of fluorescence-labeled proteins and nucleic acids in silicon ICS with integrated nanoplasmonic filters that remove the necessity of complex optical scanners, lenses, collimators. The platform is envisioned to be generic and reconfigurable and the pre-functionalized cartridges can be swapped out for different infectious diseases. Specifically, the proposed research aims to investigate and develop multi-modal detection capability through electronically actuated fluidic valves and pumps enabling on-chip immunoassays for protein detection and on-chip nucleic acid purification, amplification, and hybridization for viral load determination as well as light guiding, packaging and additive manufacturing techniques for enabling a sample-to-answer platform.