Single-cell dispensing and 'real-time' cell classification using convolutional neural networks for higher efficiency in single-cell cloning

Single-cell dispensing for automated cell isolation of individual cells has gained increased attention in the biopharmaceutical industry, mainly for production of clonal cell lines. Here, machine learning for classification of cell images is applied for 'real-time' cell viability sorting on a single-cell printer. We show that an extremely shallow convolutional neural network (CNN) for classification of low-complexity cell images outperforms more complex architectures. Datasets with hundreds of cell images from four different samples were used for training and validation of the CNNs. The clone recovery, i.e. the fraction of single-cells that grow to clonal colonies, is predicted to increase for all the samples investigated. Finally, a trained CNN was deployed on a c.sight single-cell printer for 'real-time' sorting of a CHO-K1 cells. On a sample with artificially damaged cells the clone recovery could be increased from 27% to 73%, thereby resulting in a significantly faster and more efficient cloning. Depending on the classification threshold, the frequency at which viable cells are dispensed could be increased by up to 65%. This technology for image-based cell sorting is highly versatile and can be expected to enable cell sorting by computer vision with respect to different criteria in the future.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Scientific reports - 10(2020), 1 vom: 27. Jan., Seite 1193

Sprache:

Englisch

Beteiligte Personen:

Riba, Julian [VerfasserIn]
Schoendube, Jonas [VerfasserIn]
Zimmermann, Stefan [VerfasserIn]
Koltay, Peter [VerfasserIn]
Zengerle, Roland [VerfasserIn]

Links:

Volltext

Themen:

Antibodies, Monoclonal
Journal Article
Recombinant Proteins

Anmerkungen:

Date Completed 27.05.2020

Date Revised 26.01.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-020-57900-3

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM305845497