Microinstrumentation for Brain Organoids.

Brain organoids are three-dimensional aggregates of self-organized differentiated stem cells that mimic the structure and function of human brain regions. Organoids bridge the gaps between conventional drug screening models such as planar mammalian cell culture, animal studies, and clinical trials. They can revolutionize the fields of developmental biology, neuroscience, toxicology, and computer engineering. Conventional microinstrumentation for conventional cellular engineering, such as planar microfluidic chips; microelectrode arrays (MEAs), and optical, magnetic, and acoustic techniques, have limitations when applied to 3D organoids, primarily due to their limits with inherently 2D geometry and interfacing. Hence, there is an urgent need to develop new instrumentation that is compatible with live cell culture techniques and with scalable 3D formats of relevance to organoids. This review discusses conventional planar approaches and emerging 3D microinstrumentation necessary for advanced organoid-machine interfaces. Specifically, the article surveys recently developed microinstrumentation, including 3D printed and curved microfluidics, 3D and fast-scan optical techniques, buckling and self-folding microelectrode arrays, 3D interfaces for electrochemical measurements, and 3D spatially controllable magnetic and acoustic technologies relevant to two-way information transfer with brain organoids. The article highlights key challenges that must be addressed for robust organoid culture and reliable 3D spatiotemporal information transfer. This article is protected by copyright. All rights reserved.