# Increasing the Selectivity of Hybrid Mass Spectrometry using Multidimensional Ion Mobility Spectrometry

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $288,903

## Abstract

SUMMARY
Current tools for rapidly characterizing the structures, heterogeneity, quality, and similarity of biomolecules do
not provide the level of selectivity needed for many applications, including biotherapeutic development,
production, and regulation. Mass spectrometry (MS) and ion mobility (IM) are particularly appealing for
addressing these unmet needs due to their speed, sensitivity, tolerance for sample heterogeneity, and
scalability. This project will result in a new platform that will enable higher-performance and higher-dimensional
characterization of biomolecules, including intact proteins and multiprotein complexes. The new measurements
enabled by this platform are not possible using existing IM-MS platforms. This platform will use modular
components to separate, select, and trap native-like ions, which will be combined into a large array of modules
(Aim 1) and integrated with complementary probes of ion structure (Aim 2). This platform will enable multiple
dimensions of analysis that probe the shapes, stabilities, internal interactions, and reactivity of the ions. The
orthogonality between these dimensions of analysis will increase the selectivity of measurements, without
compromising the underlying strengths of IM and MS. These aims will be (Aim 3) evaluated using model
proteins, protein-ligand complexes, and protein-protein complexes in order to assess the potential of this
platform to answer challenging problems in biomedical research. More generally, this research will improve the
feasibility of higher-dimensional IM-MS experiments and will improve the understanding of the orthogonality
than can be achieved between each dimensions of analysis. This project benefits greatly from modular
components and rapid prototyping, but with the outcomes of this research, we anticipate that this flexibility of
experimental design and the selectivity of these measurements can be translated to architectures that are
more user friendly (albeit less modular) and thereby have broad impact across the biomedical sciences and
biopharmaceutical industries.

## Key facts

- **NIH application ID:** 10114298
- **Project number:** 5R01GM130708-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Matthew Francis Bush
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $288,903
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114298

## Citation

> US National Institutes of Health, RePORTER application 10114298, Increasing the Selectivity of Hybrid Mass Spectrometry using Multidimensional Ion Mobility Spectrometry (5R01GM130708-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10114298. Licensed CC0.

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