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

Abstract

The in vitro modeling of human brain connectomes is key to exploring the structure-function relationship of the central nervous system. Elucidating this intricate relationship will allow better studying of the pathological mechanisms of neurodegeneration and hence result in improved drug screenings for complex neurological disorders, such as Alzheimer’s and Parkinson diseases. However, currently used in vitro modeling technologies lack the potential to mimic physiologically relevant neural structures. Herein, we present an innovative microfluidic design that overcomes one of the current limitations of in vitro brain models: their inability to recapitulate the heterogeneity of brain regions in terms of cellular density and number. This device allows the controlled and uniform deposition of any cellular population within unique plating chambers of variable size and shape. Through the fine tuning of the hydrodynamic resistance and cell deposition rate, the number of neurons seeded in each plating chamber can be tailored from a thousand up to a million. By applying our design to so-called neurofluidic devices, we offer novel neuro-engineered microfluidic platforms that can be strategically used as organ-on-a-chip platforms for neuroscience research. These advances provide essential enhancements to in vitro platforms in the quest to provide structural architectures that support models for investigating human neurodegenerative diseases.