Lab automation in cultivation of adherent cells

This paper introduces the latest technology developments in the field of adherent cell culturing. This highly multidisciplinary field is first matched with its numerous applications, such as the production of therapeutics, drug development, and toxicology. Further, the paper focuses on perfusion cell culturing systems intended for difficult-to-culture cells (such as primary and stem cells) and high-content screening (HCS) purposes. Parts of such advanced adherent cell culturing systems are presented including the open questions related to them. The system constituents are addressed in terms of cells and tissue models, cell culturing media, culturing vessels, actuation instrumentation, measurement instrumentation, and control. Finally, the paper outlines future directions for laboratory automation with regard to cultivation of primary and stem cells. Note to Practitioners-This paper discusses the latest technology developments and open automation challenges in the field of adherent cell culturing. Adherent cells are cells that need a surface to attach in order to grow. Most of the human cells are adherent cells. With the legislation push supported by the cost reductions, researchers are avoiding testing of various new compounds (e.g., drug candidates, environmental toxins) on animals. Instead, human cells are grown outside of the body (i.e., in vitro) for testing purposes. Growing cells in vitro is a challenge. The cells need to be maintained at a correct temperature, pH, oxygen, and humidity levels, and they need to be fed with a proper mixture of nutrients and growth factors. In other words, the cell cultivation system, which keeps the cells alive, must mimic the human body conditions as close as possible. Instruments have been developed to perform the needed functions, and a few robot-based automation systems are available to transfer the cells from an instrument to another with high throughput. Cells traditionally cultured are immortalized cell lines of cancer origin and of one cell type. These are easier to cultivate but are not as good models of human tissues as researchers would wish. Therefore, biologists are developing new models which contain many types of cells taken directly from a patient. These various kinds of primary cell cultures are more dema- nding to cultivate and need sophisticated, preferably integrated instruments and control algorithms to ensure homogenous stable environment for all of the cells. This paper provides an insight in the applications and current research trends of adherent cell cultivation. It also discusses the various subsystems needed and the automation engineering challenges posed by the new tissue models being developed by the biologists.