Three-dimensional (3D) organoid engineering aims to steer cell aggregates toward physiological mimicking of human tissue and organ systems at the cellular level, essentially serving as tissue and organ proxies that recapitulate biological parameters (e.g., spatial organization of heterogenous tissue-specific cells, cell-cell interactions, etc.). In their amenability to extended cultivation, manipulation and reconstruction in a controlled manner, organoid systems serve to bridge the gap between current animal models of cell behavior and the human body. Indeed, engineered organoid systems may serve as proxies for in vivo tissues and organs and allow for physiologically relevant experiment to be performed that cannot be conducted in animals or people, ultimately toward advancement in basic and translational research and therapeutic interventions. Of particular interest are organ-on-a-chip systems, or miniaturized 3D microfluidic devices that may provide a platform for studying biochemical, genetic, and metabolic processes in more detail under conditions that closely resemble those of in vivo. Compared to conventional macroscale 3D organoid culture systems, microfluidic-based organ-on-a-chip systems allow control and monitoring of features such as cell position, fluid flow, and mechanical cues, helping to dissect their contribution to tissue and organ function. Several miniaturized models of functional biological units, such as the lung, liver, and blood-brain barrier, have already been fabricated on a chip. However, attempts of elucidating a brain-on-a-chip model that mimics the physiological microenvironment and tissue of the brain remains an area of scrutiny. Currently, attempts at generation of brain organoids do not mature beyond the prenatal brain equivalent, the major obstacle being the lack of vascularization in the initial embryoid bodies that ultimately limit the growth and maturation of the organoids. Thus, attention is turned toward generation of a brain-on-a-chip model that can serve as a relevant model of the human brain in its recapitulation of the neuronal circuit. As cellular bio-architecture varies significantly in different regions of the brain, the brain-on-a-chip design process must allow for compartmentalized microenvironments that can represent these varied structures and circuitries.In this study, soft lithography techniques using polydimethylsiloxane (PDMS) elastomers were implemented to fabricate a microfluidic chip. A mold was created using computer aided design (CAD) via SolidWorks and 3D printing. The PDMS polymer, formed with the heterogeneous mixture of a base and curing agent, was poured into the mold for microfluidic chip curing and formation. The material was then bonded onto a glass substrate. Copper microelectrodes were manually inserted into the device to serve as probes for organoid excitation detection. To detect the organoid voltage excitations, an amplifier board was deployed. From this, experiments were conducted to acquire and analyze organoid reaction data under a variety of conditions. These include baseline control tests, spheroids exposed to light, pure media tests, and media exposed to organoids tests.&nbsp;Keywords: organoid engineering; brain-on-a-chip; microfluidics; polydimethylsiloxane

Design, Microfabrication and Testing of Brain-on-a-Chip (BOC) Platform Using Neural Organoids (Spheroids)

Paper Proceedings: https://asmedigitalcollection.asme.org/FEDSM/FEDSM2021/volume/85284

ASME 2021 Fluids Engineering Division Summer Meeting (FEDSM2021)

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