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针刺大小的仪器，其目的是快速诊断血液中的病毒感染。所提出的使用点设备可用于在机场、急诊室或其他病毒性疾病传播可能性高的拥挤环境中快速筛查受试者。病毒病原体的使用点诊断在应对疫情的努力中起着关键作用，但众所周知，由于患者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不可靠的。在这项工作中，提出了一种微流控-CMOS-生物化学横切方法，以实现便携式、紧凑型使用点混合设备技术，该技术能够在单个样品-应答平台中实现多模式检测能力，包括抗体检测、病毒蛋白检测以及病毒载量定量。拟议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。对这个项目的横切方法将从事和培训跨多个学科的研究生和本科生。PI还将吸引当地学校的高中毕业生，并通过其拟议的课程（本科生和研究生）以及出版物、研讨会和讲习班广泛传播知识。所提出的创新是基于使用低功率电子致动微阀、可重新配置的电渗泵以及具有集成纳米等离子体滤波器的硅ICS中的荧光标记的蛋白质和核酸的多重检测的微流体中的样品、试剂和缓冲液处理的小型化，所述集成纳米等离子体滤波器消除了复杂的光学扫描仪、透镜、准直器的必要性。该平台被设想为通用的和可重构的，并且预功能化的盒可以针对不同的传染病进行交换。具体而言，拟议的研究旨在通过电子驱动的流体阀和泵研究和开发多模式检测能力，从而实现用于蛋白质检测的芯片上免疫测定和用于病毒载量测定的芯片上核酸纯化、扩增和杂交，以及用于实现样品应答平台的光导、包装和增材制造技术。

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.