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

三维场效应晶体管阵列作为细胞内电生理学记录的平台技术。

• 批准号: 10029579
• 负责人: Sheng Xu
• 金额: $ 30.61万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10029579
• 关键词: 3-Dimensional; Alzheimer' s Disease; Behavior; Biology; Brain; Calcium Channel; Cardiac; Cardiac Myocytes; Cell membrane; Cell physiology; Cells; Communication; Diffusion; Disease; Electrophysiology (science); Endocrine; Epilepsy; Episodic ataxia; Event; Functional disorder; Ion Channel; Ion Pumps; Ions; Kinetics; Knowledge; Location; Measures; Motion; Neurons; Noise; Parkinson Disease; Phospholipids; Physiology; Positioning Attribute; Potassium Channel; Resolution; Sampling; Science; Signal Transduction; Sodium Channel; Speed; Stretching; System; Technology; Testing; Time; Tissues; Transistors; base; cell behavior; clinical practice; design; electrical potential; innovation; insight; mechanical properties; nervous system disorder; sensor; signal processing; spatiotemporal; surface coating; tool; voltage

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. !

项目总结 大多数细胞的行为和功能依赖于细胞信号。检测这一事件的直接方法是记录 在信号处理过程中与各种离子动力学有关的细胞电势。一直以来 显示一系列备受瞩目的疾病，如癫痫、发作性共济失调、阿尔茨海默氏症和 帕金森氏症可能是由电压门控钠、钾和钙通道功能障碍引起的。虽然 对这些离子运动的定性知识已经得到了很好的研究，但对定量的理解仍然很少。 失踪是因为缺乏允许对离子运动进行高时空分辨率采样的工具 在牢房里。我的团队致力于为细胞和组织开发一种软电子接口。这种合成物 电子接口将具有与生物相似的机械特性，并可以与 目标细胞和组织，这不仅会导致更高的信噪比，而且记录时间也会更长 而不是传统的刚性和笨重的记录系统。这项为期五年的项目旨在开发一种创新的 由高灵敏度三维场效应晶体管(FET)阵列组成的蜂窝接口 基于可伸缩衬底上的传感器。我们使用这种创新的细胞接口来检验这一假设 离子动力学，包括离子在细胞膜离子通道中的扩散速度，离子漂移驱动 通过离子泵和细胞间信号传播，需要与以下相关的关键定量信息 产生电的细胞的紊乱，如神经元、心肌细胞和电兴奋的内分泌细胞。 传感器可以同时记录单个细胞或细胞内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与时间或速度相关的动力学因子(即， 离子进入或离开细胞膜的时间以及它们移动的速度)。 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，实现如下 相当于十倍的信号放大。此外，我们可以区分出特定的离子物种 通过在FET传感器表面涂上磷脂，在细胞内外发挥积极作用 具有相应离子通道的双层，允许特定离子穿透细胞膜， 这将导致FET传感器可以记录的电势的变化。这个 获得的信息将有助于获得对蜂窝通信的新见解，并对大脑产生深远影响 科学、心脏生理学和临床实践。 好了！