An Integrated Flexible Implantable Micro-Probe for Sensing Neurotransmitters

Abstract

In this work, we have developed an integrated flexible implantable probe on a polyimide-film substrate for sensing neurotransmitters. The flexibility of the probe helps to prevent scar forming in tissues aiming for long-term in vivo monitoring. A micro Ag/AgCl reference electrode was integrated in the same probe with the Au/Cr or Pt/Cr working electrodes providing measurements without the need of a separate reference probe. Several electrode configurations have been considered and designed for implantation at various locations in the central nervous system. The prototype device for proof of principle was an enzyme-based electrochemical L-glutamate sensor using L-glutamate oxidase. A comparison between Au and Pt thin films was conducted by cyclic voltammetry to evaluate their performance as working electrodes. The L-glutamate oxidase was deposited on the working electrodes followed by a meta-Phenylenediamine electropolymerization process to improve the selectivity. The self-referencing technique was also utilized to enhance both the limit of detection and selectivity. The assembled sensors were calibrated and tested at various concentrations of L-glutamate with and without the presence of interfering molecules. The results showed good sensitivity and selectivity. In vivo animal tests were conducted to show the capability of detecting changes of electrochemical signals responding to graded peripheral somatosensory stimuli.