# Sub-1 um particles for nanoLCMS of intact proteins

> **NIH NIH R01** · PURDUE UNIVERSITY · 2020 · $290,837

## Abstract

Project summary
We propose to advance both the resolution and sensitivity of intact protein separations for nanospray
and microbore liquid chromatography-mass spectrometry. These are urgently needed to advance the
tool of top-down-proteomics, which is an emerging technology that is vital for applications where
multiple post-translational modifications on a single protein matter to the understanding of human
health. Higher resolution is proposed through two primary innovations: the use of use of submicrometer
and the design of polymer bonded phases tailored for protein separations. The proposed higher
resolution of the chromatography will take some of the burden off the mass spectrometer, allowing
wider use of top-down proteomics with sometimes less expensive mass spectrometers. The
chromatographic separations will be developed in the context of an exciting and significant area of
research in human health: epigenetics, where histone variants and post-translation modifications need
to be characterized for a wide variety of diseases. The proposal outlines in the first aim how a 10X higher
sensitivity has already been attained through our use of 0.5 µm particles in reversed phase nanoLCMS,
and describes how at least a three-fold higher resolution can be attained for difficult proteins, such as
the highly cationic histones, without lowering the sensitivity. Capillaries for higher resolution in weak
cation exchange chromatography and for hydrophobic interaction chromatography will be developed in
the second aim for providing a second, orthogonal dimension to the separation. These will be evaluated
in 2D LCMS in the third aim. Success of the proposed work will broadly impact top-down proteomics and
specifically advance the field of epigenetics.

## Key facts

- **NIH application ID:** 10003317
- **Project number:** 5R01GM121910-04
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** CHRISTINE A HRYCYNA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $290,837
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003317

## Citation

> US National Institutes of Health, RePORTER application 10003317, Sub-1 um particles for nanoLCMS of intact proteins (5R01GM121910-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10003317. Licensed CC0.

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