Optimized Ratiometric Voltage-Sensitive Dyes for Cardiac Research, Safety Pharmacology

用于心脏研究、安全药理学的优化比例电压敏感染料

基本信息

批准号：
10699121
负责人：
Corey Acker
金额：
$ 95.85万
依托单位：
POTENTIOMETRIC PROBES, LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-08 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10699121
关键词：
Action Potentials Arrhythmia Basic Science Biological Assay Businesses Cardiac Cardiac Electrophysiologic Techniques Cardiac Myocytes Cardiotoxicity Catalogs Cell Line Cell membrane Cells Chemicals Clinical Communities Connecticut Development Drug Screening Drug toxicity Dyes Electrodes Electrophysiology (science)Fluorescence Fluorescent Dyes Future Generations Genetic Predisposition to Disease Goals Growth Heart Heart Research Heart failure Human Image Individual Legal patent Licensing Light Link Maps Marketing Measures Methods Morphologic artifacts Motion Neurosciences Noise Optics Organ Patients Penetration Performance Pharmaceutical Preparations Pharmacology Phase Physiology Preparation Property Proteins Reagent Records Research Research Personnel Resolution Safety Scientist Signal Transduction Small Business Innovation Research Grant Source Speed Stains Technology Testing Thick Time Tissues Toxic effect Toxicology Universities Work calcium indicator chromophore clinical imaging commercialization design drug action drug discovery experimental study heart cell high resolution imaging high throughput screening human stem cells improved in vivo induced pluripotent stem cell derived cardiomyocytes insight invention light intensity novel novel therapeutics optogenetics personalized diagnostics personalized medicine ratiometric rational design research and development screening spatiotemporal tissue/cell culture tool voltage voltage sensitive dye water solubility

项目摘要

Project Summary/Abstract Potentiometric Probes The overall goal of this Phase II SBIR project is to commercialize tools, invented by the founders of Potentiometric Probe, LLC, for high-fidelity optical recording of electrical activity in cardiac cells, tissues, and whole hearts. Potentiometric Probes develops organic voltage-sensitive dyes (VSDs) that convert the changes in voltage across cell membranes to visible changes in fluorescence. Instead of individual electrodes, this technology enables the use of sensitive high-speed cameras, where each pixel can be considered an electrode, for massively parallel high throughput screening, or for high-resolution spatiotemporal maps of electrical signal propagation. Importantly, our VSDs are unique in enabling dual-wavelength ratiometric recording of electrical activity; this is particularly important for cardiac studies because it eliminates contraction-induced motion artifacts, permitting high-fidelity records of the action potential waveform. Human stem cell-derived cardiomyocytes (hiPSC-CMs) and tissues derived from them are increasingly being used for research and development purposes, including screening new drugs for cardiotoxicity, and in the future may be used for “personalized medicine” and the analysis of patient-derived cells. We believe high throughput recording of accurate action potential waveforms from hiPSC-CMs and tissues will be a major market for the proposed technology. Ultimately, the technology may also be applied clinically for high-resolution imaging of action potential propagation in the heart. In this proposal, Potentiometric Probes will synthesize a set of stable, non-toxic ratiometric VSDs with a broad selection of spectral windows, allowing accurate recordings even from beating hearts. The performance of these VSDs will also be fully characterized and validated for their compatibility with sensitive cell lines for both long-term and high-throughput recordings.

项目摘要/摘要电位探针第二阶段 SBIR 项目的总体目标是将由 Potentiometric Probe, LLC 的创始人，用于高保真光学记录电活动心肌细胞、组织和整个心脏发育有机。电压敏感染料 (VSD) 可将细胞膜上的电压变化转换为该技术无需使用单独的电极，即可实现荧光的可见变化。使用灵敏的高速相机，其中每个像素都可以被视为一个电极，大规模并行高通量筛选，或用于高分辨率时空图重要的是，我们的 VSD 在实现双波长方面是独一无二的。电活动的比率记录；这对于心脏研究尤其重要因为它消除了收缩引起的运动伪影，从而允许高保真度记录动作电位波形。人类干细胞衍生的心肌细胞 (hiPSC-CM) 和组织。从它们中提取的物质越来越多地用于研究和开发目的，包括筛选新药的心脏毒性，未来可能用于“个性化” 我们相信高通量记录。 hiPSC-CM 和组织的准确动作电位波形将是该技术的主要市场最终，该技术也可以应用于临床。心脏中动作电位传播的高分辨率成像。电位探针将合成一组稳定、无毒的比率 VSD，具有广泛的用途选择光谱窗口，甚至可以准确记录跳动的心脏。这些 VSD 的性能也将得到全面的表征和兼容性验证具有用于长期和高通量记录的敏感细胞系。