Deposition chamber technology as building blocks for a standardized brain-on-chip framework

Abstract

In vitro modeling of human brain connectomes is key to explore the structure-function relationship of the central nervous system. The comprehension of this intricate relationship will serve to better study the pathological mechanisms of neurodegeneration, and hence to perform improved drug screenings for complex neurological disorders, such as Alzheimers and Parkinsons diseases. However, currently used in vitro modeling technologies lack potential to mimic physiologically relevant neural structures, because they are unable to represent the concurrent interconnectivity between myriad subtypes of neurons across multiple brain regions. Here, we present an innovative microfluidic design that allows the controlled and uniform deposition of various specialized neuronal populations within unique plating chambers of variable size and shape. By applying our design, we offer novel neuro-engineered microfluidic platforms, so called neurofluidic devices, which can be strategically used as organ-on-a-chip platforms for neuroscience research. Through the fine tuning of the hydrodynamic resistance and the cell deposition rate, the number of neurons seeded in each plating chamber can be tailored from a thousand up to a million, creating multi-nodal circuits that represent connectomes existing within the intact brain. These advances provide essential enhancements to in vitro platforms in the quest accurately model the brain for the investigation of human neurodegenerative diseases.

Modeling Neurodegenerative Diseases Using In Vitro Compartmentalized Microfluidic Devices

“…Both channels were linked by asymmetric microchannel of various length allowing the accurate monitoring of neurite growth kinetics in a neuronal culture. Maisonneuve et al (2021b) have also developed a new microfluidic technology, called deposition chamber, that allows to control both the homogeneity and the density of cell seeded while avoiding excessive shear stresses. They fabricated a single compartment design (Table 1, 1 node), where no microchannels are included and can be used to study functional aspects using electrophysiological recording, optogenetics or calcium imaging.…”

“…Moreover, they used deposition chambers linked with classical microchannels, to create a model of a CNS network affected in NDD: the direct way of basal ganglia (BG) loop, which is known to be involved in PD and HD. This model is composed of five compartments interconnected with microchannels, representing each anatomical region involved in BG loop and respecting the cell number ratios between these brain regions (Table 1, 4+ nodes) (Maisonneuve et al, 2021b).…”

“…Two recent studies (Kamudzandu et al, 2019;Maisonneuve et al, 2021b) have used microfluidic technology to develop a BG loop model deeply involved in Parkinson's disease. Kamudzandu et al (2019) developed a complex in vitro brain circuitry as "organ-on-chip" devices modelling BG.…”

“…In another study, Maisonneuve et al (2021a) used neurofluidic technology to create a model of the direct way of BG loop of the brain, involved in Parkinson disease and Huntington disease, composed of five interconnected compartments. Each nodes represented an anatomical region involved in BG loop and were aligned on the device with respect to the cell number ratios between the various brain regions, linked with microchannel (Table 1) (Maisonneuve et al, 2021b).…”