Microinstrumentation for Brain Organoids

Devan Patel; Saniya Shetty; Chris Acha; Itzy E Morales Pantoja; Alice Zhao; Derosh George; David H Gracias

doi:10.1002/adhm.202302456

Microinstrumentation for Brain Organoids

Adv Healthc Mater. 2024 Jan 13:e2302456. doi: 10.1002/adhm.202302456. Online ahead of print.

Authors

Devan Patel¹, Saniya Shetty², Chris Acha¹, Itzy E Morales Pantoja³, Alice Zhao⁴, Derosh George¹, David H Gracias^{1

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Affiliations

¹ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
² Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
³ Center for Alternatives to Animal Testing (CAAT), Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
⁴ Department of Biology, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁵ Department of Chemistry, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁶ Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁷ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
⁸ Laboratory for Computational Sensing and Robotics (LCSR), Johns Hopkins University, Baltimore, MD, 21218, USA.
⁹ Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
¹⁰ Center for MicroPhysiological Systems (MPS), Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.

PMID: 38217546
DOI: 10.1002/adhm.202302456

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, has limitations when applied to three-dimensional (3D) organoids, primarily due to their limits with inherently two-dimensional geometry and interfacing. Hence, there is an urgent need to develop new instrumentation compatible with live cell culture techniques and with scalable 3D formats relevant to organoids. This review discusses conventional planar approaches and emerging 3D microinstrumentation necessary for advanced organoid-machine interfaces. Specifically, this article surveys recently developed microinstrumentation, including 3D printed and curved microfluidics, 3D and fast-scan optical techniques, buckling and self-folding MEAs, 3D interfaces for electrochemical measurements, and 3D spatially controllable magnetic and acoustic technologies relevant to two-way information transfer with brain organoids. This article highlights key challenges that must be addressed for robust organoid culture and reliable 3D spatiotemporal information transfer.

Keywords: microfluidics; microphysiological systems; neuromodulation; neuromorphic computing; organoid intelligence.

Publication types

Review