Localized Drug Application and Sub-Second Voltammetric Dopamine Release Measurements in a Brain Slice Perfusion Device

Abstract

The use of fast scan cyclic voltammetry (FSCV) to measure the release and uptake of dopamine (DA) as well as other biogenic molecules in viable brain tissue slices has gained popularity over the last two decades. Brain slices have the advantage of maintaining the functional three-dimensional architecture of neuronal network while also allowing researchers to obtain multiple sets of measurements from a single animal. In this work, we describe a simple, easy-to-fabricate perfusion device designed to focally deliver pharmacological agents to brain slices. The device incorporates a microfluidic channel that runs under the perfusion bath and a microcapillary that supplies fluid from this channel up to the slice. We measured electrically-evoked DA release in brain slices before and after the administration of two dopaminergic stimulants, cocaine and GBR-12909. Measurements were collected at two locations, one directly over and the other 500-µm away from the capillary opening. Using this approach, the controlled delivery of drugs to a confined region of the brain slice, and the application of this chamber to FSCV measurements, were demonstrated. Moreover, the consumption of drugs was reduced to tens of microliters, which is thousands of times less than traditional perfusion methods. We expect that this simply fabricated device will be useful in providing spatially resolved delivery of drugs with minimum consumption for voltammetric and electrophysiological studies of a variety of biological tissues both in vitro and ex vivo.

Transition metal oxide based non‐enzymatic electrochemical sensors: An arising approach for the meticulous detection of neurotransmitter biomarkers

“…Some typical examples include the fabrication of a 4‐channel intracorticol glassy carbon microelectrode array incorporated on a flexible substrate, [ 231 ] a wearable electrochemical recording device for the real‐time detection of neurotransmitters, [ 232 ] and a perfusion device incorporated with a microcapillary for the detection of neurotransmitters released by brain slices. [ 233 ] Metal oxides have also proven as an efficient material for the in vivo analysis of neurotransmitters. As a reference, nanostructured SnO 2 integrated conductive carbon yarns were developed as binder‐free electrodes for the detection of neurotransmitters, which can be further developed as wearable electrochemical sensors.…”

Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

“…Thus, these models allow for the reproduction of synaptic competition [ 105 ], cell line authentication [ 92 , 93 ], study of neuronal migration in embryonic brain explants [ 95 ], axonal guidance during brain development [ 93 ] ( Figure 1 C) and myelination [ 94 ]. The use of brain explants within microfluidic devices also allows for the exposure to multiple compounds at once or in sequence, thus improving the existent models towards an individual medicine approach as a guided therapeutic decision-making [ 100 , 104 , 108 ]. Of great interest is the possibility to exploit microfluidics for high-throughput mapping of brain-wide activity in awake and drug-responsive vertebrates (e.g., zebrafish) [ 101 ].…”

Square‐Wave Voltammetry as Analytical Tool for Real‐Time Study of Controlled Naproxen Releasing from Cellulose Derivative Materials

“…In both cases, the voltammetric protocol provided direct and reliable assessment of the drug releasing kinetics profile. Voltammetric techniques have also been used to study releasing of different species from living cells 13 and dopamine releasing from brain tissue slices 14. In addition, a recent work has described the use of multiple pulse amperometry to directly study the in‐vitro doxorubicin releasing profile from therapeutic nanoparticles 15.…”