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Smart, integrated well-plates for ultra-high-throughput screening of excitation-contraction coupling in tissues

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41GM146269-01
Agency Tracking Number: R41GM146269
Amount: $350,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIGMS
Solicitation Number: PA20-265
Timeline
Solicitation Year: 2020
Award Year: 2021
Award Start Date (Proposal Award Date): 2021-09-14
Award End Date (Contract End Date): 2022-08-31
Small Business Information
11957 DARLINGTON AVE, # 202
Los Angeles, CA 90049-5626
United States
DUNS: 080588735
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 IVAN PUSHKARSKY
 (859) 420-4398
 ivan@forcytebio.com
Business Contact
 IVAN PUSHKARSKY
Phone: (859) 420-4398
Email: pushivan9@gmail.com
Research Institution
 UNIVERSITY OF CALIFORNIA-IRVINE
 
160 ALDRICH HALL
IRVINE, CA 92697-0001
United States

 Nonprofit College or University
Abstract

Project Summary
Heart disease remains the leading cause of mortality in the world and, drug-induced cardiotoxicity is a major
cause of drug failure and withdrawal from the clinic or the market, contributing to the poor overall success rate
of drug development programs. In vitro models of cardiac contractility have the potential to generate predictive
data earlier in the pipeline to reduce later-stage failure due to cardiotoxicity, and enable discovery and
development of effective therapeutics more likely to successfully translate in the clinic. Such cardiac contractility
models could serve as valuable high-throughput phenotypic screening tools for target-guided (antagonistic) or
target-agnostic discovery of contraction-modulating agents (e.g. small molecules, biologics, RNAi) that enhance
or rescue the healthy phenotype. Similarly, a high-throughput cardiac contractility assay system could be used
to test possible treatments in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM)
to identify patient specific “precision medicine” treatments. Unfortunately, no single solution address all of the
key needs of the end-user and in existing technologies reporting mechanical endpoints, electrical pacing
capabilities have come at the expense of throughput. This STTR proposal will deliver an integrated product
addressing these needs by combining an optimized version of Forcyte’s FLECS contractility assay with a
proposed novel “Pace-Cap” electrical pacing system designed for the standard well-plate format that will be
embedded directly on the microplate lid. In aim, a 24-well prototype of the in-lid electrical pacing mechanism will
be developed and validated using calcium flux as a preliminary readout. In aim 2, Forcyte’s contractility platform
will be developed into a cardiac micro-tissue evaluation platform and the resulting assay will be used to mechano-
functionally validate the Pace-Cap. If successful, this would represent the first all-in-one cardiac contractility
assay kit that is both high-throughput and has internal pacing capabilities. Phase 2 work will focus on extending
the prototype throughput to 96-wells and developing rapid production strategies.NARRATIVE
Heart disease is the world’s leading killer and drug side-effects on the heart are a big reason why drugs fail. The
main function of the heart is to pump oxygenated blood through the body by beating in response to an electrical
signal, so there is a big need to model this heart function outside of the human body to help discover new
treatments and test existing ones. A major problem with existing heart-on-a-chip technologies that measure
beating in heart cells outside of the body is that systems that can pace heart cells electrically are very slow and
complex. This project aims to build a simpler product that has both a micro well-plate format and an electrical
pacing system built into the lid of the microplate. If successful, the product will be simple enough for any
researcher to use.

* Information listed above is at the time of submission. *

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