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Critical angle reflection imaging for label-free quantification of molecular interactions

Award Number: R42GM143986
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: 08/15/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Critical angle reflection imaging for label-free quantification of molecular interactions - TITLE: Critical angle reflection imaging (CARi) for label-free quantification of molecular interactions SUMMARY Measuring molecular interactions of proteins are critical for understanding protein functions and cellular processes, for discovery and validating biomarkers, and for developing and screening drugs. In particular, membrane proteins play key roles in many cellular functions and are the largest class of drug targets. Most popular methods for measuring membrane protein interaction kinetics involves extraction and purification of membrane proteins and stabilizing the proteins in an artificial lipid environment, which is not only time consuming and labor intensive, but also may introduce bias due to the loss of the native cellular microenvironment. We proposed to develop critical angle reflection imaging (CARi) as a breakthrough technology for in-situ cell- based studies of membrane protein binding interaction kinetics to advance the field of biomarker discovery and drug development. CARi builds upon surface plasmon resonance imaging (SPRi), acquiring many of its unique advantages, but overcoming many of its limitations. CARi uses an optical configuration similar to SPRi that measures light reflected from below the sensing surface, which is sensitive to molecular bindings induced refractive index changes above the sensing surface. This enables CARi to detect molecular interaction label- free and in real-time. However, unlike SPRi, CARi exhibits several distinct technological advances, including a ~10 times greater sensitivity, ~100 times greater vertical detection range for measuring entire cell surfaces, simultaneous fluorescence compatibility for orthogonal validation, broader wavelength of light selection, convenient use of glass-based surface chemistries, and simple low-cost glass sensor chips. In this fast-track STTR project, Biosensing Instrument Inc. (BI) will work with the inventor of CARi technology at Arizona State University to develop a commercial prototype multi-functional CARi instrument that can perform CARi, SPRi, and fluorescence imaging. We will also collaborate with potential customers in biomedical research and pharmaceutical industries to validate CARi performance and develop key applications. The success of this project will enable ultra-high sensitivity for label-free kinetic quantification of small molecule interactions on membrane proteins with single-cell resolution and permit simultaneous fluorescence imaging for orthogonal validation. This powerful capability of label-free in-situ cell-based kinetic binding analysis is greatly needed for expediting biomarker discovery, disease diagnosis and drug screening.


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: 2025 ( Subtotal = $0 )
2025	2023	BIOSENSING INSTRUMENT INC	947 E REDFIELD RD	TEMPE	AZ	85283	MARICOPA	USA	Biomedical Research and Research Training	000	3	7/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $832,386 )
2023	2023	BIOSENSING INSTRUMENT INC	947 E REDFIELD RD	TEMPE	AZ	85283	MARICOPA	USA	Biomedical Research and Research Training	000	3	4/5/2023	NON-COMPETING CONTINUATION	$832,386
														Subtotal = $832,386

Issue Date FY: 2022 ( Subtotal = $1,108,523 )
2022	2022	BIOSENSING INSTRUMENT INC	947 E REDFIELD RD	TEMPE	AZ	85283	MARICOPA	USA	Biomedical Research and Research Training	000	2	3/24/2022	EXTENSION WITH OR WITHOUT FUNDS	$825,247
2022	2022	BIOSENSING INSTRUMENT INC	947 E REDFIELD RD	TEMPE	AZ	85283	MARICOPA	USA	Biomedical Research and Research Training	002	2	7/25/2022	SUPPLEMENT FOR EXPANSION	$283,276
2022	2021	BIOSENSING INSTRUMENT INC	947 E REDFIELD RD	TEMPE	AZ	85283	MARICOPA	USA	Biomedical Research and Research Training	001	1	3/24/2022	NEW	$0
														Subtotal = $1,108,523

Issue Date FY: 2021 ( Subtotal = $254,738 )
2021	2021	BIOSENSING INSTRUMENT INC	947 E REDFIELD RD	TEMPE	AZ	85283	MARICOPA	USA	Biomedical Research and Research Training	000	1	8/11/2021	NEW	$254,738
														Subtotal = $254,738

Grand Total All Awards = $2,195,647

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Critical angle reflection imaging for label-free quantification of molecular interactions

Award Number: R42GM143986

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: 08/15/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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