A wireless, implantable optoelectrochemical probe for optogenetic stimulation and dopamine detection

Abstract

Physical and chemical technologies have been continuously progressing advances in neuroscience research. The development of research tools for closed-loop control and monitoring neural activities in behaving animals is highly desirable. In this paper, we introduce a wirelessly operated, miniaturized microprobe system for optical interrogation and neurochemical sensing in the deep brain. Via epitaxial liftoff and transfer printing, microscale light-emitting diodes (micro-LEDs) as light sources and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)-coated diamond films as electrochemical sensors are vertically assembled to form implantable optoelectrochemical probes for real-time optogenetic stimulation and dopamine detection capabilities. A customized, lightweight circuit module is employed for untethered, remote signal control, and data acquisition. After the probe is injected into the ventral tegmental area (VTA) of freely behaving mice, in vivo experiments clearly demonstrate the utilities of the multifunctional optoelectrochemical microprobe system for optogenetic interference of place preferences and detection of dopamine release. The presented options for material and device integrations provide a practical route to simultaneous optical control and electrochemical sensing of complex nervous systems.

Soft subdermal implant capable of wireless battery charging and programmable controls for applications in optogenetics

“…Adoption of this material for the device encapsulation can improve the lifetime of the device to several decades as demonstrated in the previous studies 43 . In addition, development and integration of multifunctional flexible probes 17 , 19 , 45 – 47 with high-density, high-rate neural recording interfaces 48 , 49 , and long-life flexible lithium battery 50 , 51 will open innovative opportunities for chronic, closed-loop neuromodulation by enabling continuous monitoring and precise analyses of convoluted neural activities as well as feedback-based optogenetic stimulations using a programmed algorithm.…”

Recent Advances in In Vivo Neurochemical Monitoring

“…Additionally, new wireless data transmission systems are allowing animals to move untethered, potentially improving the quality of behavioral correlations with neurochemical measurements. Miniaturized electronics for wireless, untethered neurochemical sensing from untethered animals have been developed to detect oxygen and DA [ 23 , 256 , 257 ]. Wireless neurochemical sensing has also been employed in humans [ 258 , 259 ].…”

“…Many neurochemicals of interest are present in the brain at pM levels or less and can have huge dynamic changes because of stimuli, behaviors, or disease states. For example, basal levels of DA in the brain range from 1–200 nM and can increase to several µM in a L-DOPA treated Parkinson’s patient or during stimulated release events [ 22 , 23 , 24 , 25 ]. Therefore, an ideal neurochemical sensor must be endowed with a low limit of detection and a wide measurement range.…”

Tonic and Phasic Amperometric Monitoring of Dopamine Using Microelectrode Arrays in Rat Striatum

“…The present study used S2 (Side-by-Side 2nd generation, Figure 1A) and Double-Sided-Pair-Row-8 pairs, conformal DSPR8 ( Figure 1B) ceramic-based MEAs which were obtained from the Center for Microelectrode Technology cost center (University of Kentucky, Lexington, KY, USA). S2 MEAs, have previously been characterized [25]. These comprised n = 4 platinum recording sites (15 × 333 µm each) geometrically arranged as two side-by-side pairs (30 µm between sites within a pair, 100 µm separation between pairs) [30].…”

“…Importantly, smaller sized electrochemical electrodes produce less tissue responsiveness and damage post-implantation in the brain [20,21]. Although advances in electrochemical approaches have opened up new avenues in the area of in vivo neurotransmitter monitoring including 3D printed carbon electrodes, submicron sized cavity carbon-nanopipette electrodes, sub-millisecond resolution measuring DA over months, and optogenetic stimulation, the most significant shortcoming of these approaches for measures of extracellular DA continues to be the inability to resolve resting neurotransmitter levels [14,[22][23][24][25].…”