hiPSC Cardiomyocyte HTS Electrophysiology System for Detecting Drug Induced Fatal Cardiac Arrhythmias

NIH RePORTER · NIH · R44 · $586,897 · view on reporter.nih.gov ↗

Abstract

CARTOX SBIR Proposal Abstract CARTOX will use SBIR funds to develop a reliable, cost-effective high throughput electrophysiology screening assay system for assessing the impact of compounds on human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) function. The new technology will address the growing need for a human cardiac system assay to accurately and precisely determine the cardiac safety liability of any drug in development. Phase I studies established the feasibility of CARTOX’s proprietary 96 well plates that promote the maturation of hiPSC-CMs for high throughput screening assays to accurately determine proarrhythmia effects of compounds used for validation of the Comprehensive In Vitro ProArrhythmia Assay (CiPA). CARTOX’s assay relies on the use of voltage and calcium sensitive dyes and offer many advantages over currently utilized multi electrode array assays. Phase II studies will further miniaturize the assay to 1) utilize 384-well format plates, and 2) create a machine for automated electrophysiology assays using hiPSC-CM monolayers and voltage or calcium sensitive dyes, and 3) develop a novel human stem cell derived extracellular matrix for use in the MATURA96 assay. Expected products from this SBIR proposal include a) 384 and 96-well plates of functionally mature hiPSC-CM monolayers, b) an optical mapping system that includes a plate reader, high speed camera and multi-parameter quantification applications, and c) consumables including multi well plates containing novel human stem cell derived ECM and reagents, media.

Key facts

NIH application ID
9906226
Project number
5R44ES027703-03
Recipient
CARTOX, LLC
Principal Investigator
TODD Joseph HERRON
Activity code
R44
Funding institute
NIH
Fiscal year
2020
Award amount
$586,897
Award type
5
Project period
2017-09-01 → 2021-03-31