# Nanoelectrochemistry and Single Cell Metabolomics

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $371,771

## Abstract

Project Summary:
A detailed understanding of human disease at the single cell level constitutes an important
frontier of biomedical science. Cell-to-cell heterogeneities exist within tissues, and
understanding the nature of these differences in terms of metabolite profile has vast implications
regardless the type of disease. Beautiful experiments using fluorescent sensors have been
developed to quantify small molecule metabolites within cells; however, the act of shining light
on a cell has been shown to have deleterious effects. Further, these sensors are not easily
generalizable. We endeavor to make the most accurate measurements of cellular metabolites
with minimal perturbation to cellular homeostasis using nanoelectrochemical measurements.
These measurements have the potential to open the door to unrealized sensitivity in sub-cellular
metabolite quantification. Electrochemistry at nanoelectrodes has been used to interrogate
cellular processes and quantify reactive species within cells. However, the time it takes for a
nanoelectrode to deliver enough charge to convert a cell's contents during amperometric and
voltammetric experiments is on the order of 100 ms. Therefore, novel techniques must be
developed to minimize the perturbation to cellular homeostasis to ensure accurate
measurements of natural cellular processes. Our group has recently investigated open circuit
potentiometry, which was chosen because the measurement is carried out with negligible
current. We have discovered that this technique is independent of electrode size. This finding
indicates the sensitivity of the measurement will not change with time appreciably, and
longitudinal experiments within single cells can be carried out. We propose to develop
metabolite-specific nanoelectrodes that operate under open circuit conditions. We will draw from
our experience fabricating nanoelectrodes and studying oxygen content within single cells and
experience developing sensors to create a generalized platform for single cell metabolomics
measurements. Specificity is gained via oxidoreductase enzymes that are trapped on top of an
electrode surface by a hydrogel. Metabolite concentration is obtained by the enzymatic turnover
rate, which is dependent on substrate concentration. Methodology developed through this grant
period has the potential to forge a foundation for generalized metabolomics studies with
nanoelectrode sensors, where the library of metabolite of interest depends only on the
availability of an associated oxidoreductase enzyme.

## Key facts

- **NIH application ID:** 10029094
- **Project number:** 1R35GM138133-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jeffrey E Dick
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,771
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029094

## Citation

> US National Institutes of Health, RePORTER application 10029094, Nanoelectrochemistry and Single Cell Metabolomics (1R35GM138133-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10029094. Licensed CC0.

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