Microinstrumentation for Brain Organoids

Abstract

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

Brain organoid as a model to study the role of mitochondria in neurodevelopmental disorders: achievements and weaknesses

“…Although innovations such as vascularization, genome editing, omics-techniques, high-content imaging (HCI), machine-learning-based and automated systems are already a reality in organoids, protocols need to continue evolving to improve tissue communication, cell patterning signals, body axis simulation and spatial-temporal control of differentiation ( Lokai et al, 2023 ). Engineering and instrumentalization advances to reconstitute brain-mimetic microenvironments will improve the development of efficient and reliable platforms to model and drug discovery of human brain diseases ( Patel et al, 2024 ). Organoid on-chips are microfluidic chamber devices that provide a periodic flow and mimic the cerebrospinal and interstitial spaces.…”