Robotic search for optimal cell culture in regenerative medicine

Author:

Kanda Genki N123ORCID,Tsuzuki Taku4,Terada Motoki15,Sakai Noriko15,Motozawa Naohiro1,Masuda Tomohiro15,Nishida Mitsuhiro15,Watanabe Chihaya T4,Higashi Tatsuki4,Horiguchi Shuhei A4ORCID,Kudo Taku3,Kamei Motohisa3,Sunagawa Genshiro A16,Matsukuma Kenji3,Sakurada Takeshi4,Ozawa Yosuke4,Takahashi Masayo157,Takahashi Koichi289,Natsume Tohru310ORCID

Affiliation:

1. Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research

2. Laboratory for Biologically Inspired Computing, RIKEN Center for Biosystems Dynamics Research

3. Robotic Biology Institute Inc.

4. Epistra Inc.

5. VCCT Inc.

6. Laboratory for Molecular Biology of Aging, RIKEN Center for Biosystems Dynamics Research

7. Vision Care Inc.

8. Graduate School of Media and Governance, Keio University

9. Graduate School of Frontier Biosciences, Osaka University

10. Department of Life Science and Biotechnology, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology

Abstract

Induced differentiation is one of the most experience- and skill-dependent experimental processes in regenerative medicine, and establishing optimal conditions often takes years. We developed a robotic AI system with a batch Bayesian optimization algorithm that autonomously induces the differentiation of induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells. From 200 million possible parameter combinations, the system performed cell culture in 143 different conditions in 111 days, resulting in 88% better iPSC-RPE production than that obtained by the pre-optimized culture in terms of the pigmentation scores. Our work demonstrates that the use of autonomous robotic AI systems drastically accelerates systematic and unbiased exploration of experimental search space, suggesting immense use in medicine and research.

Funder

Japan Agency for Medical Research and Development

New Energy and Industrial Technology Development Organization

Japan Science and Technology Agency

RIKEN

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference38 articles.

1. A mobile robotic chemist;Burger;Nature,2020

2. Bioreactor design for clinical-grade expansion of stem cells;dos Santos;Biotechnology Journal,2013

3. Bayesian Optimization for Materials Design;Frazier,2015

4. A Bayesian experimental autonomous researcher for mechanical design;Gongora;Science Advances,2020

5. Batch Bayesian Optimization via Local Penalization;Gonzalez,2016

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