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Robotic Search for Optimal Cell Culture in Regenerative Medicine

Genki N. Kanda, Taku Tsuzuki, Motoki Terada, Noriko Sakai, Naohiro Motozawa, Tomohiro Masuda, Mitsuhiro Nishida, Chihaya T. Watanabe, Tatsuki Higashi, Shuhei A. Horiguchi, Taku Kudo, Motohisa Kamei, Genshiro A. Sunagawa, Kenji Matsukuma, Takeshi Sakurada, Yosuke Ozawa, Masayo Takahashi, Koichi Takahashi, Tohru Natsume
doi: https://doi.org/10.1101/2020.11.25.392936
Genki N. Kanda
1Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research
2Laboratory for Biologically Inspired Computing, RIKEN Center for Biosystems Dynamics Research
3Robotic Biology Institute Inc
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Taku Tsuzuki
4Epistra Inc
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Motoki Terada
1Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research
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Noriko Sakai
1Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research
6Vision Care Inc
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Naohiro Motozawa
1Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research
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Tomohiro Masuda
1Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research
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Mitsuhiro Nishida
1Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research
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Chihaya T. Watanabe
4Epistra Inc
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Tatsuki Higashi
4Epistra Inc
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Shuhei A. Horiguchi
4Epistra Inc
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Taku Kudo
3Robotic Biology Institute Inc
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Motohisa Kamei
3Robotic Biology Institute Inc
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Genshiro A. Sunagawa
1Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research
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Kenji Matsukuma
3Robotic Biology Institute Inc
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Takeshi Sakurada
4Epistra Inc
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Yosuke Ozawa
4Epistra Inc
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Masayo Takahashi
1Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research
6Vision Care Inc
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Koichi Takahashi
2Laboratory for Biologically Inspired Computing, RIKEN Center for Biosystems Dynamics Research
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Tohru Natsume
3Robotic Biology Institute Inc
5Department of Life Science and Biotechnology, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology
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  • For correspondence: t-natsume@aist.go.jp
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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. The system performed 216 forty-day cell culture experiments, with a total experimentation time of 8,640 days. 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 by the pre-optimized culture in terms of pigmented 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.

Competing Interest Statement

G.N.K., T.K., M.K., K.M., and T.N. are employees, executives, or stakeholders of Robotic Biology Institute Inc., which may benefit financially from the increased scientific use of LabDroid Maholo. T.T., C.T.W., T.H., S.H., T.S., Y.O., and K.T. are employees, shareholders, or stakeholders of Epistra Inc., which may benefit financially from the increased scientific use of developed software. All other authors declare no competing interests.

Footnotes

  • ↵✉ Contact authors

  • ↵# Lead contact: Tohru Natsume, Ph.D. (t-natsume{at}aist.go.jp)

  • Supplemental files updated.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 09, 2022.
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Robotic Search for Optimal Cell Culture in Regenerative Medicine
Genki N. Kanda, Taku Tsuzuki, Motoki Terada, Noriko Sakai, Naohiro Motozawa, Tomohiro Masuda, Mitsuhiro Nishida, Chihaya T. Watanabe, Tatsuki Higashi, Shuhei A. Horiguchi, Taku Kudo, Motohisa Kamei, Genshiro A. Sunagawa, Kenji Matsukuma, Takeshi Sakurada, Yosuke Ozawa, Masayo Takahashi, Koichi Takahashi, Tohru Natsume
bioRxiv 2020.11.25.392936; doi: https://doi.org/10.1101/2020.11.25.392936
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Robotic Search for Optimal Cell Culture in Regenerative Medicine
Genki N. Kanda, Taku Tsuzuki, Motoki Terada, Noriko Sakai, Naohiro Motozawa, Tomohiro Masuda, Mitsuhiro Nishida, Chihaya T. Watanabe, Tatsuki Higashi, Shuhei A. Horiguchi, Taku Kudo, Motohisa Kamei, Genshiro A. Sunagawa, Kenji Matsukuma, Takeshi Sakurada, Yosuke Ozawa, Masayo Takahashi, Koichi Takahashi, Tohru Natsume
bioRxiv 2020.11.25.392936; doi: https://doi.org/10.1101/2020.11.25.392936

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