# A Research Resource for Ultra-sensitive High Throughput Proteomics

> **NIH NIH P41** · BATTELLE PACIFIC NORTHWEST LABORATORIES · 2022 · $1,593,314

## Abstract

Project Summary – Overall
Advances in high-throughput phenotyping and molecular characterization technologies have had profound
impacts on biological research. However, it is frequently difficult, for example, to study the functional
consequences of genetic changes because of the lack of suitable analytical technologies to define the functional
cellular state. Mass spectrometry (MS) is presently the most powerful approach for quantifying the molecular
changes that arises from altered gene expression, but limitations have prevented it from being a routine and
broadly available tool. Specifically, the sensitivity, throughput and precision of proteomics measurements are
significantly less than other high-throughput technologies that are driving major advances in modern biology
(e.g. sequencing and high-content imaging). In this renewal the Proteomics Resource has the goal of broadly
impacting biomedical research by providing the abilities to: obtain high quality data from at least 10- to 100-
fold smaller samples, produce much more comprehensive quantitative measurements, improve coverage of low
abundance components such as problematic peptide isomers and post translational modifications, and enable
the analysis of far larger sample sets than presently practical by providing large increases in measurement
throughput. We will address the key deficiencies of proteomics using new Structures for Lossless Ion
Manipulations (SLIM) ion mobility (IM)-MS based technologies that will vastly increase proteomic sample
throughput as well as provide improved reproducibility, sensitivity, accuracy of quantification and coverage of
proteomics measurements. These advances will be complemented by innovative approaches for rapid nanoliter
scale robotic processing of much smaller samples than presently feasible, and include analyses of important
functional `sub-proteomes' (e.g. phosphoproteomics and activity-based proteomics samples). The robotic
sample processing will provide throughput matching the speed of the SLIM IM-MS platform. These advances
will occur in conjunction with algorithmic and software developments needed to handle the SLIM IM-MS
platform data flow and bioinformatics for obtaining biological insights from these data. In combination, our
work will lead to the rapid implementation of the new capabilities through their application to a set of
challenging biomedical projects. The developments will be disseminated to the broader community by both
conventional (e.g. workshops and training activities) and direct approaches that include working directly to
`seed' the new technology in a number of outside research laboratories with expertise in developing and
implementing biomedical technologies, and also helping to facilitate commercial implementations from a
number of vendors spanning multiple MS platform types. Our project will result in broad and impactful initial
applications of advanced proteomics capabilities, and effective dissemination of these techno...

## Key facts

- **NIH application ID:** 10461816
- **Project number:** 5P41GM103493-20
- **Recipient organization:** BATTELLE PACIFIC NORTHWEST LABORATORIES
- **Principal Investigator:** RICHARD D SMITH
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,593,314
- **Award type:** 5
- **Project period:** 2003-09-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10461816

## Citation

> US National Institutes of Health, RePORTER application 10461816, A Research Resource for Ultra-sensitive High Throughput Proteomics (5P41GM103493-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10461816. Licensed CC0.

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