# Real-Time Detection of Glutamate using Templated Polymers as Shape-Changing Target Receptors

> **NIH NIH R21** · UNIVERSITY OF NEW HAMPSHIRE · 2021 · $179,571

## Abstract

PROJECT SUMMARY / ABSTRACT
There is a great demand for a new sensing technology that can monitor neurochemicals in brain continuously in
real-time with high temporal resolution. While electrochemical detection of electroactive neurotransmitters (such
as dopamine and serotonin) have been successful using high frequency voltammetric methods (such as fast-
scan cyclic voltammetry), measurement of non-electroactive species (such as glutamate) still remain a great
challenge for achieving real-time monitoring with high time resolution. The goal of this project is to implement a
new electrochemical sensing platform that can monitor glutamate, a well-known non-electroactive
neurotransmitter, with physiologically relevant detection range and high temporal resolution. The proposed
sensing approach can serve as an alternative to enzymatic sensing or microdialysis which have some limitations
with respect to time resolution and stability. Motivated in part by the aptamer-based electrochemical sensors,
the proposed sensing mechanism utilizes a novel synthetic target receptor as both a target recognition unit and
a signal transducer. The glutamate receptor is formed by a single-chain stimuli-responsive templated polymer
that binds specifically to its template molecule, namely, glutamate. Furthermore, upon selective target
recognition, the polymer undergoes conformation change (from linear to folded shape). This change in polymer
morphology can be electrochemically detected through the use of a redox reporter (such as ferrocene) attached
to the polymer. For validation of the proposed sensing approach, the developed sensor will be compared against
two well-established methods, a patch clamp and a microdialysis technique. A patch clamp system is ideal for
measuring fast dynamics (milliseconds) of chemical exchange at the synaptic cleft of the neurons, however,
lacks chemical specificity. A microdialysis in conjunction with liquid chromatography and mass spectrometry
provides exceptional chemical specificity, however, the temporal resolution is poor (on the order of minutes). It
is expected that the developed sensor platform will be able to bridge the gap between these two existing methods
and to provide versatility in sensing performances. The goals of this project will be achieved by pursuing the
following specific aims: (1) optimization of the templated polymer-based glutamate receptor to meet the desired
performance metrics; and (2) validation of the developed glutamate sensor in a physiological environment. The
successful outcome of this project will be the development of a new general platform technology for detection of
neurochemicals in real-time with a time resolution that is sufficient for studying synaptic communications as well
as for monitoring chemicals in the extracellular regions in the brain tissue.

## Key facts

- **NIH application ID:** 10195790
- **Project number:** 1R21EB031433-01
- **Recipient organization:** UNIVERSITY OF NEW HAMPSHIRE
- **Principal Investigator:** Edward Song
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $179,571
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195790

## Citation

> US National Institutes of Health, RePORTER application 10195790, Real-Time Detection of Glutamate using Templated Polymers as Shape-Changing Target Receptors (1R21EB031433-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10195790. Licensed CC0.

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