# Spatially and Temporarily Resolved Precision Delivery for Quantitative Biological Studies

> **NIH NIH R35** · UNIVERSITY OF TEXAS AT AUSTIN · 2022 · $383,391

## Abstract

Project Summary
Spatial and temporal heterogeneity in the cellular environment has profound implications in biological processes
related to human health/disease. Many single-cell analytical tools have been developed over the years to reveal
the heterogeneity among cells, e.g., the spatial distribution of chemicals and ions. However, one missing piece
in the single-cell analysis is the ability to reveal quantitatively the spatial and temporal heterogeneity cellular
response to chemical stimulus. This is challenging because controlling the exact concentration of chemicals at
a specific location depends on the interplay between dynamics of mass transport in the complex cellular
environment and the reactivity of the molecules. Indeed, some physiologically important molecules, including
reactive oxygen species (ROS), reactive nitrogen species (RNS), are highly reactive and have short lifetimes. A
tool for precision delivery of molecules, including these reactive ones, are necessary to quantitatively study their
effect at the single-cell level.
 Our research lab will focus on developing nanoscale precision delivery tools to quantitatively control the
delivery of molecules of biological interest, including those highly reactive ones. The strategy is based on a
functionalized nanopipette electrode that is capable of in situ generation of the molecule of interest
electrochemically with spatial and temporal control. This will be demonstrated by the delivery of nitric oxide (NO),
a reactive molecule whose transient concentration is important in neuron transmission, immune response, and
blood coagulation. Spatial and temporally resolved delivery is achieved by combining the electrochemical
chemical delivery system with nanoscale electrochemical imaging techniques. This delivery modality can be
extended to other reactive molecules, including H2S, CO, and ROS. In addition, we will develop a precision
delivery tool called digital delivery, where we will precisely control the number of biomolecules or other non-
biological entities being delivered, including proteins and nanoparticles, by counting their number during the
delivery in a resistive pulse fashion. Lastly, we will quantitatively map the spatially resolved rate of uptake of the
molecules being delivered.
 Ultimately, the precision delivery methods developed in our proposed research will enable quantitative
investigation of many fundamental biological and physiological questions related to the reactive molecules at the
single-cell level. For example, the tools can be used to reveal the spatial and temporal heterogeneity in the
neuron response by precision delivery of neuron transmitters or their vesicles. The modality can also be applied
to quantitatively modulate or stimulate the inflammatory response at the single-cell level.

## Key facts

- **NIH application ID:** 10501883
- **Project number:** 1R35GM147172-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Hang Ren
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $383,391
- **Award type:** 1
- **Project period:** 2022-08-16 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501883

## Citation

> US National Institutes of Health, RePORTER application 10501883, Spatially and Temporarily Resolved Precision Delivery for Quantitative Biological Studies (1R35GM147172-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10501883. Licensed CC0.

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