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

Chung, Yong-Ho; Nguyen, Huu Hung; Lin, Derrick T.; Bhatti, Mehwish Saba; Jones-Tinsley, Carolyn E.; An, Hongyu; Frostig, Ron D.; Nenadic, Zoran; Xu, Xiangmin; Lim, Miranda M.; Cao, Hung

doi:10.1016/j.bios.2022.114941

Cited by 16 publications

(5 citation statements)

References 29 publications

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“…This is made possible by the ultraflexibility of the thin film polymer substrate of the MEA that can accommodate the tissue displacement caused by the physical impact. Flexible GLU sensors have previously been used to reduce tissue inflammation due to brain micromotion, ,, and we have previously shown that motion artifacts in sensing data are dramatically reduced in flexible probes compared to traditional stiff probes of similar dimensions …”

Section: Resultsmentioning

confidence: 99%

Improving Sensitivity and Longevity of In Vivo Glutamate Sensors with Electrodeposited NanoPt

Robbins,

Wong,

Pwint

et al. 2024

ACS Appl. Mater. Interfaces

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In vivo glutamate sensing has provided valuable insight into the physiology and pathology of the brain. Electrochemical glutamate biosensors, constructed by cross-linking glutamate oxidase onto an electrode and oxidizing H 2 O 2 as a proxy for glutamate, are the gold standard for in vivo glutamate measurements for many applications. While glutamate sensors have been employed ubiquitously for acute measurements, there are almost no reports of long-term, chronic glutamate sensing in vivo, despite demonstrations of glutamate sensors lasting for weeks in vitro. To address this, we utilized a platinum electrode with nanometer-scale roughness (nanoPt) to improve the glutamate sensors' sensitivity and longevity. NanoPt improved the GLU sensitivity by 67.4% and the sensors were stable in vitro for 3 weeks. In vivo, nanoPt glutamate sensors had a measurable signal above a control electrode on the same array for 7 days. We demonstrate the utility of the nanoPt sensors by studying the effect of traumatic brain injury on glutamate in the rat striatum with a flexible electrode array and report measurements of glutamate taken during the injury itself. We also show the flexibility of the nanoPt platform to be applied to other oxidase enzyme-based biosensors by measuring γ-aminobutyric acid in the porcine spinal cord. NanoPt is a simple, effective way to build high sensitivity, robust biosensors harnessing enzymes to detect neurotransmitters in vivo.

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Section: Resultsmentioning

confidence: 99%

Improving Sensitivity and Longevity of In Vivo Glutamate Sensors with Electrodeposited NanoPt

Robbins,

Wong,

Pwint

et al. 2024

ACS Appl. Mater. Interfaces

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“…For multiple neurotransmitters detection, Cao group fabricated a flexible dual L ‐glutamate and gamma‐aminobutyric acid (GABA) probe and successfully monitored the changes of GABA and glutamate in the primary barrel cortex after K + stimulation. [ 166 ] This provides a powerful tool for investigating the mechanism of early life sleep disruption associated with the imbalance between glutamate and GABA. Recently, an eminent work reported by Bao group presented a soft and stretchable graphene‐based biosensing neural electrode, termed "NeuralString" (Figure 11C, I and II).…”

Section: In Vivo Monitoringmentioning

confidence: 99%

Flexible and Stretchable Electrodes for In Vivo Electrophysiological and Electrochemical Monitoring^†

Sheng,

Lu,

Fan

et al. 2024

Chin. J. Chem.

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Comprehensive SummaryIn vivo monitoring of bioelectrical and biochemical signals with implanted electrodes has received great interest over the past decades. However, this faces huge challenges because of the severe mechanical mismatch between conventional rigid electrodes and soft biological tissues. In recent years, the emergence of flexible and stretchable electrodes offers seamless and conformable biological‐electronic interfaces and has demonstrated significant advantages for in vivo electrochemical and electrophysiological monitoring. This review first summarizes the strategies for electrode fabrication from the point of substrate and conductive materials. Next, recent progress in electrode functionalization for improved performance is presented. Then, the advances of flexible and stretchable electrodes in exploring bioelectrical and biochemical signals are introduced. Finally, we present some challenges and perspectives ranging from electrode fabrication to application.Key ScientistsIn 2001, a seminal work by Kipke et al. first showed flexible polyimide‐based intracortical electrode arrays.[1] This electrode was further expanded to 252‐channel using microelectromechanical systems technology by Stieglitz et al. in 2009 and achieved large‐scale cortical recordings.[2] Later, Lieber et al. created mesh electronics that allow for seamless and minimally invasive three‐dimensional interpenetration with nerve tissues, opening up unique applications for flexible electronics.[3] Subsequently, Rogers et al. described bioresorbable electronics for transient electrical activity recordings in 2016.[4] And Frank et al. proposed polymer electrode arrays capable of resolving single neurons in 2019.[5] It wasn't until 2020 that a significant breakthrough in biochemical signals monitoring by Peng et al. demonstrated functionalized carbon nanotube fibre bundles for multiple disease biomarkers monitoring.[6] Later on, Mooney et al. established the first fully viscoelastic electrode arrays for neural recordings from the brain and heart in 2021.[7] Recently, Bao et al. presented tissue‐mimicking, stretchable neurotransmitter interfaces for monitoring the brain and gut.[8]

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“…To better understand the neural mechanisms underlying neurological disorders, it is crucial to accurately monitor the levels of both excitatory and inhibitory neurotransmitters, such as L-glutamate and GABA, which are key players in the cortical excitation/inhibition balance. In their study, Chu et al [158] presents a flexible electrochemical microsensor that allows for simultaneous real-time detection of both L-glutamate and GABA levels (Figure 10). A flexible polyimide substrate was used to minimize brain damage during implantation and enhanced with Pt-black nanostructures to improve sensitivity.…”

Section: Application Of Enzyme-based Nts Biosensors: In Vivo Monitoringmentioning

confidence: 99%

Enzymatic Electrochemical Biosensors for Neurotransmitters Detection: Recent Achievements and Trends

et al. 2023

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Neurotransmitters (NTs) play a crucial role in regulating the behavioral and physiological functions of the nervous system. Imbalances in the concentrations of NT have been directly linked to various neurological diseases (e.g., Parkinson’s, Huntington’s, and Alzheimer’s disease), in addition to multiple psychotic disorders such as schizophrenia, depression, dementia, and other neurodegenerative disorders. Hence, the rapid and real-time monitoring of the NTs is of utmost importance in comprehending neurological functions and identifying disorders. Among different sensing techniques, electrochemical biosensors have garnered significant interest due to their ability to deliver fast results, compatibility for miniaturization and portability, high sensitivity, and good controllability. Furthermore, the utilization of enzymes as recognition elements in biosensing design has garnered renewed attention due to their unique advantages of catalytic biorecognition coupled with simultaneous signal amplification. This review paper primarily focuses on covering the recent advances in enzymatic electrochemical biosensors for the detection of NTs, encompassing the importance of electrochemical sensors, electrode materials, and electroanalytical techniques. Moreover, we shed light on the applications of enzyme-based biosensors for NTs detection in complex matrices and in vivo monitoring. Despite the numerous advantages of enzymatic biosensors, there are still challenges that need to be addressed, which are thoroughly discussed in this paper. Finally, this review also presents an outlook on future perspectives and opportunities for the development of enzyme-based electrochemical biosensors for NTs detection.

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

Cited by 16 publications

References 29 publications

Improving Sensitivity and Longevity of In Vivo Glutamate Sensors with Electrodeposited NanoPt

Improving Sensitivity and Longevity of In Vivo Glutamate Sensors with Electrodeposited NanoPt

Flexible and Stretchable Electrodes for In Vivo Electrophysiological and Electrochemical Monitoring^†

Enzymatic Electrochemical Biosensors for Neurotransmitters Detection: Recent Achievements and Trends

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

Cited by 16 publications

References 29 publications

Improving Sensitivity and Longevity of In Vivo Glutamate Sensors with Electrodeposited NanoPt

Improving Sensitivity and Longevity of In Vivo Glutamate Sensors with Electrodeposited NanoPt

Flexible and Stretchable Electrodes for In Vivo Electrophysiological and Electrochemical Monitoring†

Enzymatic Electrochemical Biosensors for Neurotransmitters Detection: Recent Achievements and Trends

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Product

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Flexible and Stretchable Electrodes for In Vivo Electrophysiological and Electrochemical Monitoring^†