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

Award Number: R41GM146269
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/14/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	FORCYTE BIOTECHNOLOGIES, INC.	570 WESTWOOD PLZ BLDG 114	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	8/6/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $350,000 )
2021	2021	FORCYTE BIOTECHNOLOGIES, INC.	1100 GLENDON AVE FL 17	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	9/14/2021	NEW	$350,000
														Subtotal = $350,000

Grand Total All Awards = $350,000

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

Award Number: R41GM146269

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/14/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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