CAREER: A CMOS Multi-Modality Cellular Interfacing Platform for Drug Screening and Stem Cell Culture

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1. Title: CAREER: A CMOS Multi-Modality Cellular Interfacing Platform for Drug Screening and Stem Cell Culture2. Brief Description of Project Goals: This CAREER project investigates CMOS cellular interfacing arrays with novel pixelated multi-modality sensors/actuators and explores their use in transformative bioscience.3. Abstract:a) Nontechnical Abstract: Fully understanding the physiological behaviors of cells is a prerequisite to further advance the frontiers in bioscience. Existing sensors and actuators are mostly of single-modality, which can only process one single type of physical signals, e.g., electrochemical, from the cells. However, cells are highly complex systems with numerous molecules operating in hundreds of pathways to maintain proper functions and phenotypes. At this scale of complexity, cells often undergo concurrent multi-physics responses, which cannot possibly be explored by single-modality platforms. This technology constraint poses a fundamental limit on the ?communication link? between the electronics and cells/tissues. Moreover, many sensors and actuators require exotic processing steps, limiting their cost, yield, and scalability in mass production.To address these challenges, this CAREER project focuses on innovating sensor/actuator technologies as large-scaled arrays with novel pixel-level multi-modality sensing/actuation functionalities. Such microelectronics interfaces allow interrogating and stimulating living cells/tissues via multi-physics signaling at a high spatiotemporal resolution. Low-cost CMOS (Complementary-Metal-Oxide-Semiconductor) processes, widely used for manufacturing CPU and memory chips, will be employed to ensure high-integration, low-cost, and high-yield.The proposed CMOS multi-modality cellular interfacing platform will lead to broad societal impacts. For example, capturing the complex cellular responses may substantially increase the throughput in drug development. As another example, real-time monitoring the stem cell and enhancing the desired cell differentiation trajectories may drastically improve the purity in large-scale stem cell manufacturing and enable low-cost stem cell therapies. In addition, the cellular interfacing platform may serve as a novel research tool for new scientific discoveries.The interdisciplinary nature of this CAREER project makes it an excellent opportunity for education and outreach activities. The PI proposes a ?Vertical Teaming Approach? to systematically integrate different education components from K-12 to graduate levels. These components include mentoring high school teachers to enhance their curricula, performing remote lab demos to high school students in distance learning programs, and enriching undergraduate/graduate learning and research. The PI will also develop a Makers Electronics club at Georgia Tech to provide electronics training/innovation opportunities to local high school students and inspire their interest to pursue STEM fields. This program will be integrated with the existing NSF funded outreach programs at Georgia Tech.b) Technical Abstract: The goal of this CAREER project is to investigate novel multi-modality sensor and actuator technologies to interface with complex biological systems, e.g., living cells and tissues, and explore the use of these technologies in transformative bioscience and biotechnologies.The research activities include the following key components. First, the modeling, design, and prototyping of multi-modality cellular sensor and actuator arrays will be performed. Different device-level designs and circuit-level techniques will be investigated to achieve sensor/actuator front-ends with high pixel density and low power operation. On-chip data convertors as well as on-chip signal processing/conditioning circuitries will be employed. Next, low-cost, scalable, and biocompatible packaging solutions will be studied, so that the CMOS multi-modality cellular interfacing chips can be hosted in a standard form-factor fully compatible with existing cellular assays. Finally, the PI will demonstrate the use of the CMOS multi-modality cellular interfacing platform in various cellular assays. In particular, the experiments will focus on enhancing cell-based drug/chemical screening and stem-cell culture processes.The research activities in this CAREER project will explore and establish multi-modality sensors/actuators as a new paradigm of biosensors and actuators. Such technologies will enable unprecedented concurrent multi-physical signaling with living cells/tissues and will eventually pave the way toward hybrid bioelectronics systems in the future.