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: 10673096
• 负责人: Sheng Xu
• 金额: $ 30.57万
• 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/10673096
• 关键词: 3-Dimensional; Alzheimer' s Disease; Behavior; Biology; Brain; Calcium Channel; Cardiac; Cardiac Myocytes; Cell membrane; Cell physiology; Cells; Communication; Dedications; Diffusion; Disease; Electronics; Electrophysiology (science); Endocrine; Epilepsy; Episodic ataxia; Event; Functional disorder; Glycocalyx; 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; System; Testing; Time; Tissues; Transistors; cell behavior; clinical practice; design; electrical potential; innovation; insight; mechanical properties; nervous system disorder; sensor; signal processing; spatiotemporal; surface coating; technology platform; 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. !

项目摘要 大多数细胞行为和功能都取决于细胞信号传导。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势。它一直 表明，各种各样的知名疾病，例如癫痫，情节性共济失调，阿尔茨海默氏症和 帕金森氏症可能是由于电压门控钠，钾和钙通道功能障碍引起的。虽然 对这些离子运动动作的定性知识已经进行了充分的研究，定量理解仍然是 由于缺乏工具而缺少，这些工具会允许对离子运动进行高型颞分辨率采样 内部单元格。我的小组致力于开发用于细胞和组织的软电子界面。这个合成 电子界面将具有与生物学相似的机械性能，并且可以与 目标细胞和组织，这不仅会导致较高的信号与噪声比，还会导致更长的记录时间 比传统的刚性和笨重的记录系统。这个五年的项目旨在发展创新 由一系列高度敏感的三维场效应晶体管（FET） - 组成的细胞界面 基于可拉伸基板的传感器。我们使用这种创新的蜂窝界面来检验以下假设。 离子动力学，包括通过细胞膜中离子通道的离子扩散速度，离子漂移驱动的 通过离子泵和细胞间信号传播，需要与之相关的关键定量信息 电源细胞的疾病，例如神经元，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的不同位置或细胞中不同细胞中的不同位置 网络，从而使我们能够测量和计算离子的时间或速度相关动力学因子（即 离子进出细胞膜及其所做速度的时间）。 另外，使用FET设计，我们可以直接在目标位置扩增录制的信号，以实现为 高达十倍的信号扩增。此外，我们可以区分特定的离子物种 通过用磷脂覆盖FET传感器的表面，在细胞内部和外部积极发挥作用 具有相应离子通道的双层，使特定离子渗透到细胞膜， 这将导致电势的变化，而FET传感器可以记录。这 获得的信息将有助于获得蜂窝通信的新见解，对大脑产生深远的影响 科学，心脏生理和临床实践。 呢

项目成果

Three-dimensional transistor arrays for intra- and inter-cellular recording.

• DOI: 10.1038/s41565-021-01040-w
• 发表时间: 2022-03
• 期刊: Nature nanotechnology
• 影响因子: 38.3
• 作者: Gu Y;Wang C;Kim N;Zhang J;Wang TM;Stowe J;Nasiri R;Li J;Zhang D;Yang A;Hsu LH;Dai X;Mu J;Liu Z;Lin M;Li W;Wang C;Gong H;Chen Y;Lei Y;Hu H;Li Y;Zhang L;Huang Z;Zhang X;Ahadian S;Banik P;Zhang L;Jiang X;Burke PJ;Khademhosseini A;McCulloch AD;Xu S
• 通讯作者: Xu S