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

1.标题：CAREER：用于药物筛选和干细胞培养的CMOS多模态细胞接口平台2。项目目标简述：本CAREER项目研究CMOS细胞接口阵列与新型像素化多模态传感器/致动器，并探索其在变革性生物科学中的应用。摘要：a）非技术性摘要：深入了解细胞的生理行为是推进生命科学前沿研究的前提。现有的传感器和执行器大多是单模态的，其只能处理单一类型的物理信号，例如，电化学的，从细胞。然而，细胞是高度复杂的系统，其中许多分子在数百条途径中运行以维持适当的功能和表型。在这种复杂程度下，细胞通常会经历并发的多物理响应，这是单模态平台无法探索的。这种技术约束构成了一个根本性的限制？通信链路？在电子设备和细胞/组织之间。此外，许多传感器和执行器需要特殊的处理步骤，限制了它们的成本，产量和大规模生产的可扩展性。为了应对这些挑战，这个CAREER项目专注于创新传感器/执行器技术，作为具有新颖像素级多模态传感/执行器功能的大规模阵列。这样的微电子接口允许以高时空分辨率通过多物理信号来询问和刺激活细胞/组织。低成本CMOS（Complementary-Metal-Oxide-Semiconductor）工艺广泛应用于CPU和存储器芯片的制造，将确保高集成度、低成本和高成品率，提出的CMOS多模态蜂窝接口平台将产生广泛的社会影响。例如，捕获复杂的细胞反应可以显著增加药物开发中的通量。作为另一个例子，实时监测干细胞和增强所需的细胞分化轨迹可以大大提高大规模干细胞制造的纯度，并实现低成本的干细胞疗法。此外，细胞接口平台可以作为新的科学发现的新的研究工具。这个CAREER项目的跨学科性质使其成为教育和推广活动的绝佳机会。PI提出了一个？垂直团队合作方法？系统地整合从K-12到研究生水平的不同教育内容。这些组件包括指导高中教师，以提高他们的课程，执行远程实验室演示给高中学生在远程学习计划，并丰富本科/研究生的学习和研究。PI还将在格鲁吉亚理工学院建立一个创客电子俱乐部，为当地高中生提供电子培训/创新机会，激发他们追求STEM领域的兴趣。该计划将与现有的美国国家科学基金会资助的外展计划在格鲁吉亚技术。B）技术摘要：该职业生涯项目的目标是研究新的多模态传感器和致动器技术，以与复杂的生物系统，例如，活细胞和组织，并探索这些技术在变革性生物科学和生物技术中的应用。研究活动包括以下主要组成部分。首先，将进行多模态细胞传感器和致动器阵列的建模、设计和原型制作。不同的器件级设计和电路级技术将被研究，以实现高像素密度和低功耗操作的传感器/致动器前端。将采用片上数据转换器以及片上信号处理/调理电路。接下来，将研究低成本、可扩展和生物相容性的封装解决方案，以便CMOS多模态细胞接口芯片可以以与现有细胞测定完全兼容的标准形状因子托管。最后，PI将演示CMOS多模态细胞接口平台在各种细胞测定中的使用。特别是，实验将集中在增强基于细胞的药物/化学品筛选和干细胞培养过程中，在这个CAREER项目的研究活动将探索和建立多模态传感器/执行器作为生物传感器和执行器的新范式。这些技术将使前所未有的并发多物理信号与活细胞/组织，并最终铺平了道路，在未来的混合生物电子系统。

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.