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.