Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids

Xiao Yang; Csaba Forró; Thomas L Li; Yuki Miura; Tomasz J Zaluska; Ching-Ting Tsai; Sabina Kanton; James P McQueen; Xiaoyu Chen; Valentina Mollo; Francesca Santoro; Sergiu P Pașca; Bianxiao Cui

doi:10.1038/s41587-023-02081-3

Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids

Nat Biotechnol. 2024 Jan 22. doi: 10.1038/s41587-023-02081-3. Online ahead of print.

Authors

Xiao Yang^#^{1

2

3}, Csaba Forró^#^{1

4

5}, Thomas L Li^{1

2

3}, Yuki Miura^{2

3}, Tomasz J Zaluska¹, Ching-Ting Tsai¹, Sabina Kanton^{2

3}, James P McQueen^{2

3}, Xiaoyu Chen^{2

3}, Valentina Mollo⁴, Francesca Santoro^{4

5

6}, Sergiu P Pașca^{7

8}, Bianxiao Cui^{9

10}

Affiliations

¹ Department of Chemistry, Stanford University, Stanford, CA, USA.
² Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
³ Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA.
⁴ Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia, Naples, Italy.
⁵ Institute for Biological I nformation Processing-Bioelectronics, IBI-3, Forschungszentrum Jülich, Jülich, Germany.
⁶ Neuroelectronic Interfaces, RWTH Aachen, Aachen, Germany.
⁷ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. spasca@stanford.edu.
⁸ Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA. spasca@stanford.edu.
⁹ Department of Chemistry, Stanford University, Stanford, CA, USA. bcui@stanford.edu.
¹⁰ Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA. bcui@stanford.edu.

^# Contributed equally.

PMID: 38253880
DOI: 10.1038/s41587-023-02081-3

Abstract

Realizing the full potential of organoids and assembloids to model neural development and disease will require improved methods for long-term, minimally invasive recording of electrical activity. Current technologies, such as patch clamp, penetrating microelectrodes, planar electrode arrays and substrate-attached flexible electrodes, do not allow chronic recording of organoids in suspension, which is necessary to preserve architecture. Inspired by kirigami art, we developed flexible electronics that transition from a two-dimensional to a three-dimensional basket-like configuration with either spiral or honeycomb patterns to accommodate the long-term culture of organoids in suspension. Here we show that this platform, named kirigami electronics (KiriE), integrates with and enables chronic recording of cortical organoids for up to 120 days while preserving their morphology, cytoarchitecture and cell composition. We demonstrate integration of KiriE with optogenetic and pharmacological manipulation and modeling phenotypes related to a genetic disease. Moreover, KiriE can capture corticostriatal connectivity in assembloids following optogenetic stimulation. Thus, KiriE will enable investigation of disease and activity patterns underlying nervous system assembly.