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。建议的使用点设备可用于机场、急诊室或其他可能传播病毒疾病的拥挤环境中的受试者的快速筛查。病毒病原体的使用点诊断在应对疫情的努力中发挥着关键作用，但众所周知，由于患者-患者之间的异质性和体液中生物标记物随感染时间的变化，使用单一生物分子诊断模式是不可靠的。在这项工作中，提出了一种微流控-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，该技术能够在单个样本到答案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量化。拟议的三模式诊断平台将使诊断能够将假阴性降至最低，这对诊断至关重要。这一项目的横切方法将吸引和培训跨多个学科的研究生和本科生。PIS还将吸引当地学校的高三学生，并通过他们拟议的课程(本科和研究生)以及出版物、研讨会和研讨会广泛传播知识。拟议的创新基于微流体中样品、试剂和缓冲处理的微型化，使用低功率电子驱动微阀、可重新配置的电渗泵，以及使用集成纳米等离子过滤器对硅IC中荧光标记的蛋白质和核酸进行多路检测，从而消除了对复杂光学扫描器、透镜和准直器的需求。该平台被设想为通用和可重新配置的，并且可以为不同的传染病更换预先功能化的墨盒。具体地说，拟议的研究旨在通过电子驱动的流体阀和泵来研究和开发多模式检测能力，从而实现蛋白质检测的芯片免疫分析和用于病毒载量测定的芯片核酸纯化、扩增和杂交，以及用于实现样本到答案平台的光引导、包装和添加剂制造技术。

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.