Shell microelectrode arrays (MEAs) for brain organoids

Qi Huang; Bohao Tang; July Carolina Romero; Yuqian Yang; Saifeldeen Khalil Elsayed; Gayatri Pahapale; Tien-Jung Lee; Itzy E Morales Pantoja; Fang Han; Cynthia Berlinicke; Terry Xiang; Mallory Solazzo; Thomas Hartung; Zhao Qin; Brian S Caffo; Lena Smirnova; David H Gracias

doi:10.1126/sciadv.abq5031

Shell microelectrode arrays (MEAs) for brain organoids

Sci Adv. 2022 Aug 19;8(33):eabq5031. doi: 10.1126/sciadv.abq5031. Epub 2022 Aug 17.

Authors

Qi Huang¹, Bohao Tang², July Carolina Romero³, Yuqian Yang¹, Saifeldeen Khalil Elsayed⁴, Gayatri Pahapale¹, Tien-Jung Lee¹, Itzy E Morales Pantoja³, Fang Han⁵, Cynthia Berlinicke⁶, Terry Xiang¹, Mallory Solazzo¹, Thomas Hartung^{3

7

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9}, Zhao Qin⁴, Brian S Caffo², Lena Smirnova^{3

8}, David H Gracias^{1

10

11

12

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14}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
² Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA.
³ Center for Alternatives to Animal Testing, Department of Environmental Health and Engineering, Bloomberg School of Public Health and Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
⁴ Department of Civil and Environmental Engineering, Syracuse University, Syracuse, NY 13244, USA.
⁵ Department of Statistics, University of Washington, Seattle, WA 98195, USA.
⁶ Department of Ophthalmology, Johns Hopkins University School of Medicine, Wilmer Eye Institute, Baltimore, MD 21287, USA.
⁷ CAAT-Europe, University of Konstanz, 78464 Konstanz, Germany.
⁸ Environmental Metrology & Policy Program, Georgetown University, Washington, DC, 20057, USA.
⁹ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
¹⁰ Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
¹¹ Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.
¹² Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
¹³ Laboratory for Computational Sensing and Robotics (LCSR), Johns Hopkins University, Baltimore, MD 21218, USA.
¹⁴ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Brain organoids are important models for mimicking some three-dimensional (3D) cytoarchitectural and functional aspects of the brain. Multielectrode arrays (MEAs) that enable recording and stimulation of activity from electrogenic cells offer notable potential for interrogating brain organoids. However, conventional MEAs, initially designed for monolayer cultures, offer limited recording contact area restricted to the bottom of the 3D organoids. Inspired by the shape of electroencephalography caps, we developed miniaturized wafer-integrated MEA caps for organoids. The optically transparent shells are composed of self-folding polymer leaflets with conductive polymer-coated metal electrodes. Tunable folding of the minicaps' polymer leaflets guided by mechanics simulations enables versatile recording from organoids of different sizes, and we validate the feasibility of electrophysiology recording from 400- to 600-μm-sized organoids for up to 4 weeks and in response to glutamate stimulation. Our studies suggest that 3D shell MEAs offer great potential for high signal-to-noise ratio and 3D spatiotemporal brain organoid recording.

Abstract

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