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Real-Time Quantitation of Transport Across Vascular-Tissue Interfaces in Organ-On-Chip Models Using In Situ Mass Spectrometry

Award Number: R41GM145196
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: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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Real-Time Quantitation of Transport Across Vascular-Tissue Interfaces in Organ-On-Chip Models Using In Situ Mass Spectrometry - Abstract Current in vitro platforms are poor predictors of the in vivo safety, efficacy and pharmacokinetics of therapeutics, owing to a significant difference in the test conditions compared to physiological conditions. Therefore, drug toxicity testing is routinely performed using animal models. However, animal testing is expensive and time consuming. In addition, ethical concerns about the use of animals are increasingly calling for reduction/replacement of animal tests. To overcome these challenges, physiologically relevant organ-on-chip assays have been developed. These assays mimic the dynamic interactions encountered during drug delivery and recapitulates physiological flow rates, vascular architecture and the 3D nature of tissue (liver, lung, kidney, etc.), thereby providing improved quantitative and predictive capabilities to guide the development of drugs via accurate toxicity analysis. However, one of the critical components lacking from current organ-on-chip assays is the real-time analysis of drug concentration at specified locations within the assay to determine drug toxicity at defined tissue sites. To address this need, we propose to integrate our microfluidics-based, organ-on-chip systems with on-chip mass spectrometry analysis to measure drug concentrations across a vascularized liver construct. The Phase I effort will focus on integration the microfluidic device with a novel mass spectrometry (MS) assay. This method enables online temporal and spatial chemical characterization of chemical constituents within microfluidic devices by MS for the first time. The ChemSitu approach enables the means to continuously sample and chemically characterize small volumes of liquid directly from a microfluidic device at any point along the construct in near real-time and without negatively altering the state of the microfluidic system. A multi-disciplinary team of scientists and engineers with expertise in microfluidics-based cell assays and instrumentation development has been assembled for successful completion of this project. By providing an accurate, quantitative and predictive model of and quantitation of physiological interactions, the developed platform promises to establish a new paradigm for in vitro assessment of the physiological response to therapeutics.


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 = -$75,719 )
2024	2022	CFD RESEARCH CORPORATION	6820 MOQUIN DR NW	HUNTSVILLE	AL	35806	MADISON	USA	Biomedical Research and Research Training	000	1	6/6/2024	NEW	-$75,719
														Subtotal = -$75,719

Issue Date FY: 2022 ( Subtotal = $314,215 )
2022	2022	CFD RESEARCH CORPORATION	6820 MOQUIN DR NW	HUNTSVILLE	AL	35806	MADISON	USA	Biomedical Research and Research Training	000	1	3/17/2022	NEW	$314,215
														Subtotal = $314,215

Grand Total All Awards = $238,496

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Real-Time Quantitation of Transport Across Vascular-Tissue Interfaces in Organ-On-Chip Models Using In Situ Mass Spectrometry

Award Number: R41GM145196

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: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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