Abstract
Laboratory automation is a key driver in biotechnology and an enabler for powerful new technologies and applications. In particular, in the field of personalized therapies, automation in research and production is a prerequisite for achieving cost efficiency and broad availability of tailored treatments. For this reason, we present the StemCellDiscovery, a fully automated robotic laboratory for the cultivation of human mesenchymal stem cells (hMSCs) in small scale and in parallel. While the system can handle different kinds of adherent cells, here, we focus on the cultivation of adipose-derived hMSCs. The StemCellDiscovery provides an in-line visual quality control for automated confluence estimation, which is realized by combining high-speed microscopy with deep learning-based image processing. We demonstrate the feasibility of the algorithm to detect hMSCs in culture at different densities and calculate confluences based on the resulting image. Furthermore, we show that the StemCellDiscovery is capable of expanding adipose-derived hMSCs in a fully automated manner using the confluence estimation algorithm. In order to estimate the system capacity under high-throughput conditions, we modeled the production environment in a simulation software. The simulations of the production process indicate that the robotic laboratory is capable of handling more than 95 cell culture plates per day.
Highlights
Laboratory automation has received increasing attention from the biotechnology industry over the last two decades
In order to demonstrate the feasibility of automated production including the deep learning-based confluence algorithm, human adipose-derived mesenchymal stem cells from the abdominal fat tissue were cultivated on the StemCellDiscovery
The cultivation process was demonstrated on the StemCellDiscovery using adiposederived human mesenchymal stem cells (hMSCs) from two female donors that were seeded into two six-well plates
Summary
Laboratory automation has received increasing attention from the biotechnology industry over the last two decades. Thereby, planar cultivation methods are most suitable if only small quantities are required, for example, for screening In this context, automation can provide support in terms of standardization, parallelization and the handling of labor-intensive tasks. Examples include the Freedom EVO from Tecan, the Cellhost from Hamilton Robotics or the Biomek Cell Workstation from Beckman Coulter [18] While these systems provide a high flexibility, they are limited in terms of space and number of devices to be integrated. In contrast to other solutions, the StemCellDiscovery integrates an industrial six-axis robotic arm mounted on a linear axis with a custom gripper for manipulation of disposables and complex handling jobs This way, many different devices can be integrated simultaneously, representing a fully automated laboratory environment. The image is cropped to the phase contrast region with a size of [8208 × 8208] px
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