# Development of Next Generation Mass Spectrometric Instrumentation for Proteomics

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $709,118

## Abstract

Project Summary/Abstract
Currently, most mass spectrometric (MS) analyses for proteomics are performed in sequential
mode, wherein various species in a sample are selected and interrogated one after another. As
a consequence of the finite time needed to examine each species in turn, sequential mode MS
suffers from inescapable limitations in sensitivity, speed and ability to analyze all ions, especially
when the composition of the ion beam is complex and rapidly changing. These limitations have
kept vast tracts of biology and biomedicine, including, for example, deep single cell proteome
analysis, out of reach of the current MS technology. In the present proposal, we posit that
sensitivity, speed and dynamic range can be vastly improved by performing MS in parallel (by
analogy to Next Generation DNA Sequencing), thus overcoming the technical barriers inherent to
current commercial mass spectrometers that operate largely in sequential mode.
Here, we propose to develop new MS instrumentation to execute MS in a massively parallel
manner, with two major objectives in mind:
Objective 1. Increase the sensitivity, speed and depth of proteome analyses by up to and
ultimately beyond 1000-fold. The current sequential MS approaches can be likened to sampling
the Niagara Falls with a bucket, where the majority of the sample is wasted. Our proposed parallel
MS technology is designed to eliminate this immense waste.
Objective 2. Filter noise in real time to eliminate unwanted ion background prior to MS analysis,
thereby maximizing the MS utilization of the sample ions of interest and the resulting signal-to-
noise ratios, as well as providing increased dynamic range to measure very low abundance
components in the presence of highly abundant components.
Successful attainment of these objectives will allow deep, comprehensive, high throughput
analyses of proteomes in cases where sample availability is limiting, where the components of
interest elude detection due to their low abundance, or when single cell analysis is needed to
address the biological or biomedical question at hand. Success in this endeavor will propel
forward many areas of basic and applied biomedical research that require proteomic analyses in
a manner analogous to the immense progress that has been made through development of Next
Generation DNA Sequencing.

## Key facts

- **NIH application ID:** 10240528
- **Project number:** 5R01GM136654-03
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Brian T Chait
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $709,118
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240528

## Citation

> US National Institutes of Health, RePORTER application 10240528, Development of Next Generation Mass Spectrometric Instrumentation for Proteomics (5R01GM136654-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240528. Licensed CC0.

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