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. !

Public Health Relevance

Conventional intracellular electrical signaling tools are not designed for sensing cellular activities either at different positions of a single cell or among different cells in a cellular network, which is essential for deciphering the propagative and communicative behaviors of electrogenic cells' (e.g., neurons) signals and determining the mechanism and treatment of progressive neurological disorders, such as Parkinson's disease. To overcome these challenges, we propose a 3D array of intracellular sensors featuring a field effect transistor configuration that is highly sensitive, accurate, and scalable to record both intra- and inter-cellular electrophysiological events in a cellular network. !

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Unknown (R35)
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Special Emphasis Panel (ZRG1)
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Nie, Zhongzhen
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University of California, San Diego
Engineering (All Types)
Schools of Arts and Sciences
La Jolla
United States
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