Action potentials of electrogenic cells, such as neurons and cardiomyocytes, are crucial for their physiological functions. Neurons use action potential to transmit signals over long distances, and cardiomyocytes use action potentials to synchronize the contraction of millions of cells during each heartbeat. To understand these important physiological functions, one of the most important tactics is to accurately record the electrical potentials from cells. However, the current two major classes of electrophysiological methods, intracellular and extracellular recording, suffer severe limitations in their applications. Intracellular recording such as patch clamp suffers from extremely low throughput and toxic intracellular dialysis. Extracellular recording such as planar electrode array suffers from poor signal and lack of one-to-one cell-to-electrode coupling. In the last decade, much effort has been focused on developing new generation of electrophysiology tools to achieve high throughput intracellular recording. In particular, nanotechnology-based electrode sensors developed independently in several groups has shown great promise in achieving highly sensitive and high throughput intracellular recording. However, developing these nascent technologies into robust electrophysiological tools would require extensive studies for characterization, validation, and optimization. This proposal aims to develop the nanoelectrode technology into robust electrophysiological tools for biomedical research. When accomplished, this new technology will enable users to (a) perform sensitive, intracellular recording of action potentials from tens to hundreds of individual cells simultaneously; (b) achieve long-term, minimally-invasive recording of the cells for days to weeks; and (c) afford stable culture and recording of the hSC-CMs under optimal environmental conditions.

Public Health Relevance

Accurately recording the tiny fluctuations of membrane potentials is important to understand the functions of brain and heart cells. This study aims to develop nanoscale probes that can address a long-standing technology gap in electrophysiology - parallel and intracellular recording in adherent cells. The proposed technology is expected to provide new capabilities and enables new biomedical research.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM125737-02
Application #
9566246
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Sammak, Paul J
Project Start
2017-09-15
Project End
2021-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
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Santoro, Francesca; Zhao, Wenting; Joubert, Lydia-Marie et al. (2017) Revealing the Cell-Material Interface with Nanometer Resolution by Focused Ion Beam/Scanning Electron Microscopy. ACS Nano 11:8320-8328