Towards an automatic analysis of CHO-K1 suspension growth in microfluidic single-cell cultivation

Abstract Motivation Innovative microfluidic systems carry the promise to greatly facilitate spatio-temporal analysis of single cells under well-defined environmental conditions, allowing novel insights into population heterogeneity and opening new opportunities for fundamental and applied biotechnology. Microfluidics experiments, however, are accompanied by vast amounts of data, such as time series of microscopic images, for which manual evaluation is infeasible due to the sheer number of samples. While classical image processing technologies do not lead to satisfactory results in this domain, modern deep-learning technologies, such as convolutional networks can be sufficiently versatile for diverse tasks, including automatic cell counting as well as the extraction of critical parameters, such as growth rate. However, for successful training, current supervised deep learning requires label information, such as the number or positions of cells for each image in a series; obtaining these annotations is very costly in this setting. Results We propose a novel machine-learning architecture together with a specialized training procedure, which allows us to infuse a deep neural network with human-powered abstraction on the level of data, leading to a high-performing regression model that requires only a very small amount of labeled data. Specifically, we train a generative model simultaneously on natural and synthetic data, so that it learns a shared representation, from which a target variable, such as the cell count, can be reliably estimated. Availability and implementation The project is cross-platform, open-source and free (MIT licensed) software. We make the source code available at https://github.com/dstallmann/cell_cultivation_analysis; the dataset is available at https://pub.uni-bielefeld.de/record/2945513.