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Cardiotoxicity Assays on an Integrated Platform of a Heart-on-a-Chip and an Optical Immunosensor

Award Number: R01GM126571
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: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Cardiotoxicity Assays on an Integrated Platform of a Heart-on-a-Chip and an Optical Immunosensor - Abstract Toxicity assays based on human organs-on-a-chip platforms have become increasingly important for drug discovery and development, since they allow testing cytotoxic effects of pharmaceutical compounds on the physiologically relevant human tissue models before moving forward to expensive animal testing or clinical trials. Multiple physiological and biochemical parameters of the organ-on-a-chip models must be continually monitored in order to assess the responses of these models to drug treatments. Although fluorescence detection has been widely adopted for bioassays, it requires the addition of fluorophores to the samples, which may disturb cellular activities and more seriously, it is practically impossible for real-time fluorescence labeling of the biomarkers that are constantly secreted by the organ models during drug toxicity testing. Thus, fluorescence detection is not a viable option here - direct detection, or “label-free” detection, is required for monitoring the dynamic process of drug interactions with organoids to obtain detailed information on transient as well as delayed or cumulative drug effects. The overarching goal of the proposed research is thus to address these challenging issues of drug toxicity assays by using a human organ-on-a- chip model monitored with an automated, label-free, optical biosensor system that allows for real-time, long- term, sensitive, and kinetic analyses of human cardiac tissue models in response to various drugs in their microenvironments. To accomplish this goal, we propose a unique approach that is based on our patented label-free biosensor in conjunction with advanced organ-on-a-chip technologies. The open-microcavity configuration of our biosensor enables synergistic integration of the sensor chip with a heart-on-a-chip model through an automated microfluidic platform, which has the built-in capability to regenerate the sensor surface for continual kinetic studies over extended periods of time. The heart-on-a-chip model will be developed using an innovative 3D bioprinting approach that produces functional biomimetic cardiac organoids using cardiomyocytes derived from human induced pluripotent stem cells (iPSCs). A microfluidic perfusion bioreactor with the built-in capacity for simultaneous electrical and mechanical stimulations will be constructed to maintain long-term functionality of the organoids. On the other hand, the long-term stability of the proposed biosensor system will be significantly enhanced using negative thermal expansion materials for fabrication of the sensor chip. The cardiotoxicity of a panel of drugs will be evaluated in situ via quantification of the biomarkers secreted by the human cardiac model. The technology developed from this project will be highly transformative, which may be applied for other organs and lead to future personalized screening of drug toxicities, efficacy, and pharmacokinetics for precision medicine.


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 = -$566 )
2024	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	21100 ERWIN ST	WOODLAND HILLS	CA	91367	LOS ANGELES	USA	Biomedical Research and Research Training	001	4	6/13/2024	SUPPLEMENT FOR EXPANSION	-$142
2024	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	21100 ERWIN ST	WOODLAND HILLS	CA	91367	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	6/13/2024	NON-COMPETING CONTINUATION	-$424
														Subtotal = -$566

Issue Date FY: 2021 ( Subtotal = $397,619 )
2021	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	003	4	8/23/2021	NON-COMPETING CONTINUATION	$297,818
2021	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	12/22/2020	SUPPLEMENT FOR EXPANSION	$39,921
2021	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	004	4	8/24/2021	SUPPLEMENT FOR EXPANSION	$59,880
2021	2020	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	002	3	3/31/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$113,706
2021	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	2	3/31/2021	NON-COMPETING CONTINUATION	-$113,706
														Subtotal = $397,619

Issue Date FY: 2020 ( Subtotal = $314,505 )
2020	2020	TERASAKI FAMILY FOUNDATION, THE	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	002	3	9/17/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$314,505
2020	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	3/2/2020	NON-COMPETING CONTINUATION	$0
2020	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	001	2	9/17/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $314,505

Issue Date FY: 2019 ( Subtotal = $298,470 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	8/23/2019	NON-COMPETING CONTINUATION	$298,470
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	001	2	9/26/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $298,470

Issue Date FY: 2018 ( Subtotal = $310,273 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	001	1	9/19/2018	NEW	$0
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	8/30/2018	NEW	$310,273
														Subtotal = $310,273

Grand Total All Awards = $1,320,301

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Cardiotoxicity Assays on an Integrated Platform of a Heart-on-a-Chip and an Optical Immunosensor

Award Number: R01GM126571

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: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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