# A Nanofluidic/Microfluidic System for Enhanced Low-Input and Single-Cell Proteomics

> **NIH NIH R41** · FLUIDISPEC LLC · 2024 · $350,000

## Abstract

Within living cells, proteins are the primary cellular machinery, performing most biological functions. Aberrant protein
expression or modification often leads to cellular dysfunction that causes illness and disease. Thus, an improved
understanding of how proteins change within cells in response to disease progression is needed. These quantitative
measurements of changes in proteins and their modifications are necessary for improved biological models of cellular
function. More accurate and detailed mechanisms of disease transformation will improve diagnostics and allow rational
design of new treatments. To gain as complete a picture as possible of cellular state, proteomics aims to identify and
characterize all the proteins and their proteoforms in a biological sample. Such proteomic analyses are challenging due to
the large number of proteins expressed, the large dynamic range of protein relative abundance, the dynamic nature of
protein expression, the numerous biologically essential modifications, and the loss of proteins by surface adsorption. The
diverse structures and complexity of cells complicates the initial purification and preparation of proteomic samples.
Currently, there is a movement within the field of proteomics to improve single cell analyses to better understand cellular
heterogeneity, which is critical to understanding the mechanisms of disease and response to treatment. To help overcome
these challenges, a new microfluidic/nanofluidic sample preparation platform is proposed to provide efficient extraction
of proteins from the cellular milieu, removal of contaminants, and protein denaturation. This platform will be integrated
into both top-down and bottom-up workflows and is expected to overcome the longstanding challenge of reliably
providing solubilized proteins with negligible contaminants and ion-suppressing agents for top-down proteomics. For
bottom-up proteomics, an additional advantage of improved protein denaturation is anticipated. Additionally, the
proposed microfluidic/nanofluidic systems are well-suited for the preparation of samples down to the single-cell level.
The Aims include fundamental studies of the protein purification process and measurement of the anticipated
improvement in both top-down and bottom-up proteome analyses. If successful, this application will provide a widely
accessible system for low input and single-cell proteomics sample preparation that will significantly improve the depth of
proteome coverage and speed of single-cell proteomics.

## Key facts

- **NIH application ID:** 11008589
- **Project number:** 1R41GM156144-01
- **Recipient organization:** FLUIDISPEC LLC
- **Principal Investigator:** Aaron T Timperman
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $350,000
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-09-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11008589

## Citation

> US National Institutes of Health, RePORTER application 11008589, A Nanofluidic/Microfluidic System for Enhanced Low-Input and Single-Cell Proteomics (1R41GM156144-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11008589. Licensed CC0.

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