(1342-C) Microfluidic in vitro systems for neurological disease modeling under electrical stimulation

Abstract: In the recent years, microfluidic technologies have increasingly been used in neurosciences research to the extend the experimental capabilities. Microfluidic systems are already being developed into models that recapitulate aspects of neurological diseases to better understand the pathological mechanisms and improve drug discovery
In this study, a chip with a fluidic design that allows neuronal cell culture and axon growth monitoring was developed by roll-to-roll (R2R) manufacturing process. This design consists of two separated chambers in which cells are seeded and allows the monitoring of axons outgrowth through the microchannels using fluorescence microscopy. The design was screened in vitro with different neuronal cells and using several substrates that can be used for R2R production.
The design is also compatible with a custom-made electrical stimulus generator. This device can operate in two modes: constant or pulsed current and voltage-controlled stimulation. Output current values range from 0.001 mA to 10 mA, supporting pulse frequencies from 10 Hz to 400 Hz with minimal pulse width of 50 μs.
Among the various substrates investigated, the selection for this study was focused on an Extrusion Coating COC microstructured layer, bonded to COP screen-printed electrodes. In these chips, primary neuronal cells were seeded, in particular Schwann cells and Dorsal Root Ganglion cells (DRGs). Our experiments demonstrate that following DRGs electro-stimulation, a significant augmentation occurred in both axonal growth and complexity. Furthermore, the release of neurotrophins, was quantified in both cell types, revealing a stimulation-dependent increase translating to a cellular activation. Our findings lead to the conclusion that this microchip represents a robust tool for investigating particular neurological disorders