The ability to measure neurotransmitter activity using implanted electrochemical sensors offers researchers a potent technique for analyzing neural activity across specific neural circuitry. We have developed a wirelessly controlled device, WINCS Harmoni, to observe and measure neurotransmitter dynamics at up to four separate sensors, with high temporal and spatial resolution. WINCS Harmoni also incorporates a versatile neurostimulator that can be synchronized with electrochemical recording. The WINCS Harmoni platform is thus optimally suited for probing the neurochemical effects of neurostimulation, and may in turn enable the development of personalized therapies for multiple brain disorders.
Bioelectronic Medicines is an emerging field that capitalizes on minimally-invasive technology to stimulate the autonomic nervous system in order to evoke therapeutic biomolecular changes at the end-organ. The goal of Bioelectronic Medicines is to realize both 'precision and personalized' medicine. 'Precise' stimulation of neural circuitry creates biomolecular changes targeted exactly where needed to maximize therapeutic effects while minimizing off-target changes associated with side-effects. The therapy is then 'personalized' by utilizing implanted sensors to measure the biomolecular concentrations at, or near, the end-organ of interest and continually adjusting therapy to account for patient-specific biological changes throughout the day. To realize the promise of Bioelectronic Medicines, there is a need for minimally invasive, real-time measurement of biomarkers associated with the effects of autonomic nerve stimulation to be used for continuous titration of therapy. In this study we examine the feasibility of using fast scan cyclic voltammetry (FSCV) to measure norepinephrine levels, a neurochemical relevant to end-organ function, directly from blood. FSCV is a well-understood method for measuring electroactive neurochemicals in the central nervous system with high temporal and high spatial resolution that has yet to be adapted to the study of the autonomic nervous system. The results demonstrate that while detecting the electroactive neurochemical norepinephrine in blood is more challenging than obtaining the same FSCV measurements in a buffer solution due to biofouling of the electrode, it is feasible to utilize a minimally invasive FSCV electrode to obtain neurochemical measurements in blood.
Deficiency of the eye-stabilizing vestibulo-ocular reflex (VOR) is a defining feature in multiple diseases of the vestibular labyrinth, which comprises the inner ear's sensors of head rotation, translation and orientation. Diagnosis of these disorders is facilitated by observation and measurement of eye movements during and after head motion. The video head impulse test has recently garnered interest as a clinical diagnostic assessment of vestibular dysfunction. In typical practice, it involves use of video-oculography goggles to measure eye movements while a clinician examiner grasps the subject's head and manually rotates it left or right at sufficient acceleration to cover ~20 deg over ~150 mS, reaching a peak velocity of >120 deg/S midway through the movement. Manual delivery of head impulses incurs significant trial-by-trial, inter-session and inter-operator variability, which lessens the test's reliability, efficiency, safety and standardization across testing facilities. We describe application of a novel, compact and portable automated head impulse test (aHIT™) device that delivers highly repeatable head motion stimuli about axes parallel to those of the vestibular labyrinth's six semicircular canals, with programmable Gaussian and sinusoidal motion profiles at amplitudes, velocities and accelerations sufficient to test VOR function over the spectral range for which the VOR dominates other vision-stabilizing reflexes. We tested the aHIT™ on human subjects and demonstrated its high reproducibility compared to manually delivered head impulses. This device has the potential to be a valuable clinical and research tool for diagnostic evaluation and investigation of the vestibular system.
3D printing technology has been widely used as a rapid prototyping fabrication tool in several fields, including electrochemistry. In this work, we incorporate 3D printing technology with carbon nanotube yarns for electrochemical sensing of dopamine in the presence of ascorbic acid and uric acid. The novel 3D printed electrode provides a circular concavity detection zone with grooves to insert three electrodes. The electrode connections are fully compatible with conventional screen printed electrode workstation setups. The CNT yarn 3D printed electrode showed excellent electrocatalytic activity for the redox reaction of dopamine (DA) in the presence of ascorbic acid (AA) and uric acid (UA). Three well-defined sharp and fully resolved anodic peaks were found with the peak potentials using cyclic voltammetry (CV) at 50 mV, 305 mV, and 545 mV for AA, DA, and UA respectively and using differential pulse voltammetry (DPV) at 91 mV, 389 mV, and 569 mV, respectively. DA detection limit was 0.87 ± 0.09 μM. The CNT yarn 3D printed electrode displayed high reproducibility and stability. The electrode design enables the study of electrode reactions at the sidewall of CNTs, which cannot be performed using electrodes made by conventional fabrication methods. The new fabrication method provides a new platform to prototype new electrode materials for electrochemistry, providing a low-cost, customizable design compatible existing screen printed electrodes technology.