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

Real-time tracking of neurotransmitter levels in vivo has been technically challenging due to the low spatio-temporal 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 neuro-transmitter 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 electro-chemically 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 perfor-mance, 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 mecha-nisms of normal brain function and various neurological disorders.

Automated summary

Real-time tracking of neurotransmitter levels in vivo has been challenging due to the limitations of current methods. This study developed a flexible electrochemical microsensor for simultaneous detection of L-glutamate and GABA, crucial neurotransmitters associated with the balance of cortical excitation/inhibition ratios. The sensor was validated in vitro, ex vivo, and in vivo, and showed promise for accurate, real-time, and long-term monitoring of the E:I balance in neurological disorders.