(360e) Electrochemical Dopamine Sensing for Blood-Brain-Barrier Microphysiological System Drug Screening Applications

An implantable, multi-electrode array (MEA) probe modified for electrochemical dopamine biosensing applications has been microfabricated. The quantification of changes in dopamine concentration is of great interest to neuroscientists studying abnormal neural pathways and their associated behaviors, such as Parkinson’s disease, schizophrenia, and opioid addiction. Creation of these probes required the development of a post-fabrication method for the electrochemical deposition of iridium oxide (IrOx), which enabled the integration of an IrOx reference electrode (RE) onto the same MEA as the working electrode. The on-probe IrOx RE is an attractive alternative to commonly used Ag/AgCl wire REs, which can be unstable and can cause inflammatory responses in living tissue. The on-probe IrOx RE was tested in two and three-electrode systems with dopamine biosensors. The biosensors were shown to detect a physiologically relevant range of dopamine concentrations with high sensitivity (85.2 ± 3.1 pA/mM) and low limits of detection (16 nM). Permselective coatings were used to engineer selectivity, as demonstrated by the rejection of the important interfering species, ascorbic acid. By incorporating all electrodes onto a single device, baseline noise was reduced by an average of 61% in vitro. These dopamine biosensors have shown exceptional promise in multi-organ, microphysiological systems (MPSs) based on the use of human induced pluripotent stem cell (iPSC)-derived midbrain-fated dopamine/γ-aminobutyric acid (GABA) neurons. Such systems incorporate blood-brain-barrier and liver metabolism modules to permit the screening of drugs that can combat opioid abuse.