Development of highly sensitive, flexible dual L-glutamate and GABA microsensors for in vivo brain sensing

Sung Sik Chu; Hung Anh Nguyen; Derrick Lin; Mehwish Bhatti; Carolyn E Jones-Tinsley; An Hong Do; Ron D Frostig; Zoran Nenadic; Xiangmin Xu; Miranda M Lim; Hung Cao

doi:10.1016/j.bios.2022.114941

Development of highly sensitive, flexible dual L-glutamate and GABA microsensors for in vivo brain sensing

Biosens Bioelectron. 2023 Feb 15:222:114941. doi: 10.1016/j.bios.2022.114941. Epub 2022 Nov 24.

Authors

Affiliations

¹ Department of Biomedical Engineering, University of California Irvine, CA, 92697, USA.
² Department of Electrical Engineering and Computer Sciences, University of California Irvine, 92697, CA, USA.
³ Department of Neurology, University of California Irvine, CA, 92697, USA.
⁴ Department of Neurobiology and Behavior, University of California, CA, 92697, USA.
⁵ VA Portland Health Care System, Department of Neurology, Oregon Health and Science University, OR, 97239, USA.
⁶ Department of Biomedical Engineering, University of California Irvine, CA, 92697, USA; Department of Neurobiology and Behavior, University of California, CA, 92697, USA.
⁷ Department of Biomedical Engineering, University of California Irvine, CA, 92697, USA; Department of Anatomy and Neurobiology, University of California Irvine, CA, 92697, USA; Center for Neural Circuit Mapping, University of California Irvine, CA, 92697, USA.
⁸ Department of Biomedical Engineering, University of California Irvine, CA, 92697, USA; Department of Electrical Engineering and Computer Sciences, University of California Irvine, 92697, CA, USA; Center for Neural Circuit Mapping, University of California Irvine, CA, 92697, USA; Department of Computer Science, University of California Irvine, CA, 92697, USA. Electronic address: hungcao@uci.edu.

PMID: 36455372
DOI: 10.1016/j.bios.2022.114941

Abstract

Real-time tracking of neurotransmitter levels in vivo has been technically challenging due to the low spatiotemporal resolution of current methods. Since the imbalance of cortical excitation/inhibition (E:I) ratios are associated with a variety of neurological disorders, accurate monitoring of excitatory and inhibitory neurotransmitter levels is crucial for investigating the underlying neural mechanisms of these conditions. Specifically, levels of the excitatory neurotransmitter L-glutamate, and the inhibitory neurotransmitter GABA, are assumed to play critical roles in the E:I balance. Therefore, in this work, a flexible electrochemical microsensor is developed for real-time simultaneous detection of L-glutamate and GABA. The flexible polyimide substrate was used for easier handling during implantation and measurement, along with less brain damage. Further, by electrochemically depositing Pt-black nanostructures on the sensor's surface, the active surface area was enhanced for higher sensitivity. This dual neurotransmitter sensor probe was validated under various settings for its performance, including in vitro, ex vivo tests with glutamatergic neuronal cells and in vivo test with anesthetized rats. Additionally, the sensor's performance has been further investigated in terms of longevity and biocompatibility. Overall, our dual L-glutamate:GABA sensor microprobe has its unique features to enable accurate, real-time, and long-term monitoring of the E:I balance in vivo. Thus, this new tool should aid investigations of neural mechanisms of normal brain function and various neurological disorders.

Keywords: Dual sensing; Electrochemical sensor; GABA; L-glutamate; Microelectrode array; Platinum black.

MeSH terms

Animals
Biosensing Techniques*
Brain
Glutamic Acid*
Neurotransmitter Agents
Rats
gamma-Aminobutyric Acid

Substances

Glutamic Acid
Neurotransmitter Agents
gamma-Aminobutyric Acid