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

合作研究：一种微流控-CMOS 横切方法，可实现三模态生物识别，实现高精度病毒诊断

• 批准号: 1711067
• 负责人: Kaushik Sengupta
• 金额: $ 22.5万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1711067&HistoricalAwards=false
• 关键词: Collaborative; Research; Microfluidic; CMOS; Cross

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.

该项目旨在开发一种手指棒的仪器，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，急诊室或其他拥挤的环境中快速筛查，那里传播病毒疾病的可能性很高。病毒病原体的使用点诊断在暴发的响应努力中起着至关重要的作用，但由于患者患者患者患者的异质性和体液中生物标记物的变化，随着时间的流动性变异，众所周知，具有单一的生物分子诊断模式。感染。 在这项工作中，提出了一种微流体-CMOS-CMOS-BIO-BIO化学杂交方法，以启用可移植的，紧凑的使用点的混合设备技术，该技术能够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荷定量，以及病毒载荷定量一个单个样本与答案平台。拟议的三模式诊断平台将使诊断具有最小的假阴性，对诊断至关重要。该项目的横齿方法将跨多个学科参与并培训研究生和本科生。 PI还将与当地学校的高中生互动，并通过其拟议的课程（本科和毕业生）和出版物，研讨会和研讨会来广泛传播知识。拟议的Innovation基于样本，试剂和缓冲处理的小型化，以此为基础。使用低功率的微流体使用硅液体液体中的荧光标记的蛋白质和核酸的多路复用电泵，可重新配置的电渗水泵和多路复用的核酸检测，具有集成的纳米溶质过滤器，以消除复杂的光学扫描剂，镜头，collimators，collimators。该平台设想为通用和重新配置，并且可以将预先功能的墨盒换成不同的传染病。具体而言，拟议的研究旨在通过电子驱动的流体阀和泵来调查和开发多模式检测能力，从而实现芯片免疫测定法，以进行蛋白质检测和芯片核酸纯化，扩增和杂交，以进行病毒载荷测定以及光明测定光明以及光。指导，包装和添加剂制造技术，以实现样品与答案平台。

项目成果

Nano-optical CMOS Systems for Bio-molecular Sensing: In-vitro and In-vivo

用于生物分子传感的纳米光学 CMOS 系统：体外和体内

• DOI: 10.1364/sensors.2020.sm1e.2
• 发表时间: 2020
• 期刊: Optical Sensors and Sensing Congress
• 作者: Sengupta, Kaushik

A Packaged Ingestible Bio-Pill with 15-Pixel Multiplexed Fluorescence Nucleic-Acid Sensor and Bi-Directional Wireless Interface for In-Vivo Bio-Molecular Sensing

具有 15 像素多重荧光核酸传感器和用于体内生物分子传感的双向无线接口的包装可摄入生物药丸

• DOI: 10.1109/vlsicircuits18222.2020.9163060
• 发表时间: 2020
• 期刊: 2020 IEEE Symposium on VLSI Circuits
• 作者: Zhu, Chengjie;Wen, Yuhan;Liu, Tao;Yang, Haw;Sengupta, Kaushik
• 通讯作者: Sengupta, Kaushik

CMOS-Based Electrokinetic Microfluidics With Multi-Modal Cellular and Bio-Molecular Sensing for End-to-End Point-of-Care System

基于 CMOS 的电动微流体，具有多模式细胞和生物分子传感，适用于端到端护理点系统

• DOI: 10.1109/tbcas.2021.3136165
• 发表时间: 2021
• 期刊: IEEE Transactions on Biomedical Circuits and Systems
• 影响因子: 5.1
• 作者: Zhu, Chengjie;Maldonado, Jesus;Sengupta, Kaushik
• 通讯作者: Sengupta, Kaushik

2D Magnetic Sensor Array for Real-time Cell Tracking and Multi-site Detection with Increased Robustness and Flow-rate

用于实时细胞跟踪和多站点检测的 2D 磁性传感器阵列，具有更高的鲁棒性和流速

• DOI: 10.1109/cicc.2019.8780363
• 发表时间: 2019
• 期刊: IEEE Custom Integrated Circuits Conference (CICC
• 作者: Tang H, Venkatesh S

CMOS-Driven Pneumatic-Free Scalable Microfluidics and Fluid Processing with Label-Free Cellular and Bio-Molecular Sensing Capability for an End-to-End Point-of-Care System

CMOS 驱动的无气动可扩展微流体和流体处理，具有无标记细胞和生物分子传感功能，适用于端到端护理点系统

• DOI: 10.1109/isscc42613.2021.9365843
• 发表时间: 2021
• 期刊: IEEE International solid-state circuits conference (ISSCC
• 作者: Zhu, Chengjie;Maldonado, Jesus;Tang, Hao Tang;Venkatesh, Suresh;and Sengupta, Kaushik
• 通讯作者: and Sengupta, Kaushik