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Development of high-throughput, high-sensitivity EPR sample handling capabilities for biomedical research

Award Number: R01GM140385
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Electron paramagnetic resonance (EPR) spectroscopy is a critically important technique in biomedical research with a unique ability to detect naturally occurring or engineered unpaired electrons in complex biological environments. EPR has wide-ranging applicability to structural biology, metalloprotein research, redox biology, rational drug design, and clinical diagnostics. Groundbreaking advancements in sample volume requirements for biomedical EPR spectroscopy applications were made nearly four decades ago with the development of the loop-gap resonator (LGR), which represented breakthrough benefits such as 10-fold lower sample volume requirements and higher resonator efficiencies to increase signals over the commonly used cavity resonator. To accommodate the biomedical needs of even further increased signal intensity and to provide the broader scientific community with accessible technology, we propose to capitalize on our recent development of the dielectric LGR (dLGR) concept and optimize this resonator technology to increase sensitivity beyond that achieved upon introduction of the LGR. A dLGR is effectively a small dielectric resonator placed inside the inner loop of an LGR where the return flux of the dielectric flows through the outer loops of the LGR. Analytic theory and our high-frequency structure simulations indicate that the dLGR enables an order-of-magnitude improvement in sensitivity over the LGR. To take full advantage of the extremely low volume requirements for the dLGR, we propose to develop efficient sample handling technologies that couple the dLGR to high- throughput sample handling instrumentation. We aim to develop two transformative technologies for biomedical EPR applications: i) a nano-dLGR with a 10-fold increase in sensitivity for ~0.2 µL sample volumes integrated with a customized autosampler and ii) a micro-dLGR for a dramatic increase in sensitivity for ~2 µL sample volumes with an optimized stopped-flow system for millisecond time scale kinetics measurements. These transformative and innovative prototypes with outstanding sensitivity will be easy to use and ultimately widely available to the scientific community. Where the LGR was a transformative advance compared with cavity resonators, the dLGR is expected to be another transformative leap from an LGR.


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 = $334,678 )
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	000	4	11/13/2023	NON-COMPETING CONTINUATION	$334,678
														Subtotal = $334,678

Issue Date FY: 2023 ( Subtotal = $621,864 )
2023	2023	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	001	3	2/21/2023	NON-COMPETING CONTINUATION	$37,186
2023	2023	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	000	3	11/18/2022	NON-COMPETING CONTINUATION	$334,678
2023	2023	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	002	3	8/30/2023	SUPPLEMENT FOR EXPANSION	$250,000
														Subtotal = $621,864

Issue Date FY: 2022 ( Subtotal = $371,894 )
2022	2022	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	001	2	6/30/2022	NON-COMPETING CONTINUATION	$37,189
2022	2022	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	000	2	11/19/2021	NON-COMPETING CONTINUATION	$334,705
														Subtotal = $371,894

Issue Date FY: 2021 ( Subtotal = $483,900 )
2021	2021	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Biomedical Research and Research Training	000	1	12/31/2020	NEW	$483,900
														Subtotal = $483,900

Grand Total All Awards = $1,812,336

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Development of high-throughput, high-sensitivity EPR sample handling capabilities for biomedical research

Award Number: R01GM140385

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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