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

Award Number: R21EB031433
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY SYSTEM OF NEW HAMPSHIRE	51 COLLEGE RD	DURHAM	NH	03824	STRAFFORD	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	5/6/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $219,209 )
2023	2023	UNIVERSITY SYSTEM OF NEW HAMPSHIRE	51 COLLEGE RD SERVICE BLDG 107	DURHAM	NH	03824	STRAFFORD	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	8/24/2023	NON-COMPETING CONTINUATION	$0
2023	2023	UNIVERSITY SYSTEM OF NEW HAMPSHIRE	51 COLLEGE RD SERVICE BLDG 107	DURHAM	NH	03824	STRAFFORD	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	1/24/2023	NON-COMPETING CONTINUATION	$219,209
														Subtotal = $219,209

Issue Date FY: 2022 ( Subtotal = $180,141 )
2022	2022	UNIVERSITY SYSTEM OF NEW HAMPSHIRE	51 COLLEGE RD SERVICE BLDG 107	DURHAM	NH	03824	STRAFFORD	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	11/30/2021	NON-COMPETING CONTINUATION	$162,126
2022	2022	UNIVERSITY SYSTEM OF NEW HAMPSHIRE	51 COLLEGE RD SERVICE BLDG 107	DURHAM	NH	03824	STRAFFORD	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	8/3/2022	NON-COMPETING CONTINUATION	$18,015
														Subtotal = $180,141

Issue Date FY: 2021 ( Subtotal = $179,571 )
2021	2021	UNIVERSITY SYSTEM OF NEW HAMPSHIRE	51 COLLEGE RD SERVICE BLDG 107	DURHAM	NH	03824	STRAFFORD	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	1	5/28/2021	NEW	$0
2021	2021	UNIVERSITY SYSTEM OF NEW HAMPSHIRE	51 COLLEGE RD SERVICE BLDG 107	DURHAM	NH	03824	STRAFFORD	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	3/18/2021	NEW	$179,571
														Subtotal = $179,571

Grand Total All Awards = $578,921

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

Award Number: R21EB031433

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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