An electrophysiology platform that enables robust, scalable and long-term intracellular recording of cardiomyocytes

一个电生理学平台，能够对心肌细胞进行稳健、可扩展和长期的细胞内记录

基本信息

批准号：
10500961
负责人：
Bianxiao Cui
金额：
$ 47.66万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10500961
关键词：
3-Dimensional Academia Action Potentials Adopted Affect Amplifiers Biomedical Research Cardiac Cardiac Myocytes Cardiotoxicity Cell membrane Cells Chemistry Chronic Communities Coupled Custom Data Detection Development Diagnosis Drug Screening Electrodes Electrophysiology (science)Electroporation Funding Opportunities Goals Heart Heart Atrium Human In Situ Incubators Industrialization Industry Ion Channel Manuals Measurement Mediating Membrane Methods Monitor Nature Neurons Nodal Organoids Patch-Clamp Techniques Performance Pharmaceutical Preparations Pharmacologic Substance Physiologic pulse Physiological Process Relaxation Research Research Personnel Risk System Techniques Technology Time Translating Translations Ventricular design drug mechanism extracellular flexibility frontier heart function human pluripotent stem cell improved industry partner instrument interest miniaturize minimally invasive monolayer nanoelectrode array patch clamp pre-clinical programs screening solid state stem cell technology stem cells three dimensional structure tool usability voltage

项目摘要

PROJECT SUMMARY/ABSTRACT: Action potentials are temporal changes of the electrical voltage across the cell membrane, which are crucial for the physiological function of excitable cells such as neurons and cardiomyocytes. In the human heart, cardiac action potentials coordinate the synchronous contraction and relaxation of billions of cardiomyocytes. The waveforms of intracellular action potentials reflect the coordination of a multitude of ion channels, some of which are affected by pharmaceutical drugs to collectively contribute toward proarrhythmic risks. The waveforms of intracellular action potentials also reflect the subtype such as atrial-, ventricular-, or nodal-like cardiomyocytes, or their maturation status. Measurements of intracellular action potentials are mostly performed by the patch clamp technique, which is accurate but invasive, one cell at a time, laborious, and requires specialized expertise. Due to its low throughput and invasive nature, patch clamp is not suitable for drug screening or functional characterization of human pluripotent stem cell derived cardiomyocytes. In the last decade, vertically-aligned and solid-state nanoelectrode arrays (NEAs) have emerged as promising tools with the potential of achieving parallelizable and minimally invasive cardiac AP recording from monolayers of stem-cell-derived cardiomyocytes. However, despite the significant progress and the strong interest, the NEA technology has largely been confined to research groups that develop the technologies, instead of being broadly adopted by the research community. We identified several critical challenges that have hindered such effort. In this proposal, through the partnership between an academic lab and a startup company, we aim to overcome these challenges and develop a robust electrophysiological tool that enables reliable, scalable, and long-term intracellular recording of cardiomyocytes. The goal of this proposal aims to transition the NEA technology from a demonstration of possibility to a status useful to end-users.

项目摘要/摘要：动作电位是整个细胞膜电压的时间变化，这对于至关重要可激发细胞的生理功能，例如神经元和心肌细胞。在人心中，心脏动作电位协调了数十亿个心肌细胞的同步收缩和放松。这细胞内作用电位的波形反映了许多离子通道的协调，其中一些是受药物的影响，共同促进心律失常的风险。波形细胞内作用电位还反映了亚型，例如心房，心室或淋巴结状的心肌细胞，或他们的成熟状态。细胞内动作电位的测量主要由斑块进行夹具技术是准确但具有侵入性的，一次是一个细胞，费力，需要专业知识。由于其低吞吐量和侵入性性质，斑块夹不适合药物筛查或功能性人多能干细胞衍生的心肌细胞的表征。在过去的十年中，垂直对准和固态纳米电极阵列（NEAS）已成为有前途的具有从单层可行的和微创的心脏AP录制的工具干细胞衍生的心肌细胞。但是，尽管进展很大和浓厚的兴趣，但NEA 技术在很大程度上仅限于开发技术的研究小组，而不是广泛地由研究界通过。我们确定了一些阻碍了这种努力的关键挑战。在通过学术实验室和一家初创公司之间的合作伙伴关系，我们的旨在克服这些挑战并开发出强大的电生理工具，可实现可靠，可扩展和长期心肌细胞的细胞内记录。该提案的目标旨在将NEA技术从证明对最终用户有用的状态的可能性。