Segmented flow generation by chip reactors for highly parallelized cell cultivation

Micro system technology offers convenient tools for the production of handling devices for small liquid volumes which can be used in cell cultivation. Here, a modular system for the rapid generation of cell suspension aliquotes is presented. The system is used to produce and analyze high numbers of strongly separated cultural volumes. Selected clones may be retrieved from the system. Therefore, the principle of segmented flow is applies. Portions of aqueous culture medium containing one cell or very small cell ensembles are separated from each other by a nonmiscible liquid like dodecane or mineral oil. In addition, the oil separates the cultivation droplets from the innerside of the walls of chip channels and capillaries. This way, compatibility problems between cell wall surfaces and the chemical character of technical walls are excluded. The separated cultivation droplets are guided by micro flow transportation in different channel and chamber topologies. The whole system has the character of a serially working cell processing system. The aliquot generation can be speeded up to frequencies of about 30 Hz in each micro channel. That means, that about 105 individual cultural volumes can be produced per hour or about 2 million per day.