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High-throughput cell spheroid production and assembly analysis by microfluidics and deep learning

View ORCID ProfileMartin Trossbach, View ORCID ProfileEmma Åkerlund, Krzysztof Langer, View ORCID ProfileBrinton Seashore-Ludlow, View ORCID ProfileHaakan N. Joensson
doi: https://doi.org/10.1101/2022.10.02.510497
Martin Trossbach
1KTH Royal Institute of Technology and Science for Life Laboratory, Tomtebodavägen 23, 171 65 Solna, Sweden
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  • For correspondence: martin.schappert@scilifelab.se
Emma Åkerlund
2Karolinska Institutet and Science for Life Laboratory, Tomtebodavägen 23, 171 65 Solna, Sweden
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Krzysztof Langer
1KTH Royal Institute of Technology and Science for Life Laboratory, Tomtebodavägen 23, 171 65 Solna, Sweden
3Department of Bioengineering and Therapeutic Sciences, University of California San Francisco
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Brinton Seashore-Ludlow
2Karolinska Institutet and Science for Life Laboratory, Tomtebodavägen 23, 171 65 Solna, Sweden
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Haakan N. Joensson
1KTH Royal Institute of Technology and Science for Life Laboratory, Tomtebodavägen 23, 171 65 Solna, Sweden
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Abstract

3D cell culture models are an important tool in translational research but have been out of reach for high-throughput screening due to complexity, requirement of large cell numbers and inadequate standardization. Here, we present a high-throughput workflow to produce and characterize the formation of miniaturized spheroids using deep learning. We train a convolutional neural network (CNN) for cell ensemble morphology classification, benchmark it against more conventional image analysis, and characterize spheroid assembly determining optimal surfactant concentrations and incubation times for spheroid production for three cell lines with different spheroid formation properties. Notably, this format is compatible with large-scale spheroid production and screening. The presented workflow and CNN offer a template for large scale minispheroid production and analysis and can be extended and re-trained to characterize morphological responses in spheroids to additives, culture conditions and large drug libraries.

Competing Interest Statement

The authors have declared no competing interest.

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Posted October 05, 2022.
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High-throughput cell spheroid production and assembly analysis by microfluidics and deep learning
Martin Trossbach, Emma Åkerlund, Krzysztof Langer, Brinton Seashore-Ludlow, Haakan N. Joensson
bioRxiv 2022.10.02.510497; doi: https://doi.org/10.1101/2022.10.02.510497
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High-throughput cell spheroid production and assembly analysis by microfluidics and deep learning
Martin Trossbach, Emma Åkerlund, Krzysztof Langer, Brinton Seashore-Ludlow, Haakan N. Joensson
bioRxiv 2022.10.02.510497; doi: https://doi.org/10.1101/2022.10.02.510497

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