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HIGHLY SELECTIVE MACROBIOMOLECULAR ISOLATION, SOFT-LANDING AND CHARACTERIZATION USING STRUCTURES FOR LOSSLESS ION MANIPULATIONS

Award Number: R01CA283818
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT (30 lines) This project aims to address the current gap in technology for rapid and comprehensive (mass, structure) profiling of biomacromolecules. While high resolution ion mobility and mass spectrometry separations techniques have been extensively developed, their application has been largely limited to small molecules (m/z < 2000). The ability to access structure and mass information in a high-throughput fashion for macrobiomolecules is an aspirational goal in mass spectrometry. In pursuance of this goal, we will develop a high-resolution ion mobility chemical analysis device based on Structures for Lossless Ion Manipulations, and in conjunction with mass spectrometry obtain high-throughput high-resolution IMS/MS of biomacromolecules. The study of the significant heterogeneity in large biomolecular systems, i.e., macrobiomolecules, critical to biological research will be enabled by the development of a new high resolution, high throughput analytical system. The SLIM platform, currently enabled for ultra-high resolution ion mobility profiling (up to the point of separating isotopomers and isotopologues) and manipulations of small molecular ions (<3000 Daltons) will be optimized to efficiently confine, transport and separate macrobiomolecules. Initial optimization of the SLIM will be done by coupling with a TOF-MS system. SLIM-TOF will be used to perform high resolution IMS/MS of ensembles of macrobiomolecular species (with an upper mass limit of about 20,000 Da dictated by the TOF). We will use SLIM-based IMS separations and other manipulations to reveal the extensive structural heterogeneity of macrobiomolecules. Further, we will perform size and mass selective soft-landing of macrobiomolecules using the dynamic switching and rerouting (to deposition substrates) of a selective ion mobility distribution in the SLIM. The soft-landed species will be characterized using cryo-EM and complimentary imaging techniques to elucidate the morphologies of macrobiomolecules with selected mobilities or collision-cross-sections. The combination of ion mobility information and imaging will provide a detailed structural characterization of macrobiomolecules.


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 = $450,205 )
2024	2024	BATTELLE MEMORIAL INSTITUTE	902 BATTELLE BLVD	RICHLAND	WA	99354	BENTON	USA	Cancer Biology Research	000	2	7/23/2024	NON-COMPETING CONTINUATION	$450,205
														Subtotal = $450,205

Issue Date FY: 2023 ( Subtotal = $406,640 )
2023	2023	BATTELLE MEMORIAL INSTITUTE	902 BATTELLE BLVD	RICHLAND	WA	99354	BENTON	USA	Cancer Biology Research	000	1	7/28/2023	NEW	$406,640
														Subtotal = $406,640

Grand Total All Awards = $856,845

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HIGHLY SELECTIVE MACROBIOMOLECULAR ISOLATION, SOFT-LANDING AND CHARACTERIZATION USING STRUCTURES FOR LOSSLESS ION MANIPULATIONS

Award Number: R01CA283818

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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