Three-dimensional field effect transistor arrays as a platform technology for intracellular electrophysiology recording.

项目概要 大多数细胞行为和功能依赖于细胞信号传导。检测此事件的直接方法是记录 信号处理过程中与各种离子动力学相关的细胞电位。已经是 研究表明，许多引人注目的疾病，如癫痫、阵发性共济失调、阿尔茨海默病和 帕金森病可能是由电压门控钠、钾和钙通道功能障碍引起的。虽然 这些离子运动的定性知识已经得到了很好的研究，但定量的理解仍然存在 由于缺乏可以对离子运动进行高时空分辨率采样的工具而缺失 细胞内。我的团队致力于开发细胞和组织的软电子接口。这种合成的 电子界面将具有与生物体相似的机械特性，并能与生物体有机融合 目标细胞和组织，这不仅会导致更高的信噪比，而且会导致更长的记录时间 比传统的刚性和笨重的记录系统。这个为期五年的项目旨在开发一个创新的 由高灵敏度三维场效应晶体管 (FET) 阵列组成的蜂窝接口 - 基于可拉伸基板上的传感器。我们使用这种创新的细胞接口来测试以下假设： 离子动力学，包括离子通过细胞膜离子通道的扩散速度、离子漂移驱动 通过离子泵和细胞间信号传播，需要与 产电细胞的疾病，例如神经元、心肌细胞和电兴奋内分泌细胞。 传感器可以同时记录单个细胞或细胞中不同细胞之间的不同位置 网络，从而使我们能够测量和计算离子的时间或速度相关的动力学因素（即 离子移入或移出细胞膜的时间及其速度）。 此外，使用 FET 设计，我们可以直接在目标位置放大记录的信号，实现为 信号放大十倍。此外，我们可以区分特定的离子种类 通过在 FET 传感器表面涂上磷脂，在细胞内外积极发挥作用 具有相应离子通道的双层，允许特定离子渗透细胞膜， 这将导致 FET 传感器记录的电位变化。的 获得的信息将有助于获得细胞通信的新见解，对大脑产生深远的影响 科学、心脏生理学和临床实践。 ！

PROJECT SUMMARY Most cellular behaviors and functions rely on cell signaling. A direct approach to detect this event is to record cellular electrical potentials that are associated with various ionic kinetics during signal processing. It has been shown that a wide range of high profile diseases, such as epilepsy, episodic ataxia, Alzheimer's, and Parkinson's, may result from dysfunction of voltage-gated sodium, potassium, and calcium channels. Although qualitative knowledge of the motions of these ions has been well studied, a quantitative understanding is still missing because of the lack of tools that would allow high-spatiotemporal-resolution sampling of ion motions inside cells. My group is dedicated to developing a soft electronic interface for cells and tissues. This synthetic electronic interface will have similar mechanical properties to the biology, and can organically fuse with the target cells and tissues, which will not only result in higher signal to noise ratio but also longer recording time than conventional rigid and bulky recording systems. This five-year project aims to develop an innovative cellular interface that is composed of an array of highly sensitive three-dimensional field effect transistor (FET)- based sensors on a stretchable substrate. We use this innovative cellular interface to test the hypothesis that ionic kinetics, including the speeds of ionic diffusion through ion channels in the cell membrane, ion drift driven by ion pumps, and inter-cellular signal propagation, entail crucial quantitative information associated with disorders of electrogenic cells, such as neurons, cardiomyocytes, and electrically excitable endocrine cells. The sensors can simultaneously record different positions of a single cell or among different cells in a cellular network, thus enabling us to measure and calculate the time- or speed-related kinetic factors of the ions (i.e., the time at which the ions move in or out of the cell membrane and the speed at which they do, respectively). Also, using an FET design, we can amplify the recorded signal directly at the targeting location, realizing as much as ten-fold signal amplification. Furthermore, we can differentiate the specific ionic species that are actively functioning inside and outside of the cells by coating the surfaces of the FET sensors with phospholipid bilayers that have the corresponding ion channels, allowing the specific ions to permeate the cell membrane, which would result in a change in electrical potential that could be recorded by the FET sensors. The information acquired will help gain new insights in cellular communications, with profound implications for brain sciences, cardiac physiology, and clinical practices. !