Development of a fast-sampling device for the automatic rapid transfer of exact volumes of fluids from a bioreactor

Intracellular metabolite analysis is a key technology to identify biomarkers and metabolic bottlenecks in cellular systems for pharmaceutical and biotechnological applications. The determination of unbiased metabolite levels requires the transfer of a known amount of cells from the bioreactor without altering the cellular state. Afterwards the cellular metabolism must be stopped as fast as possible. Unfortunately, currently no instrument
is commercially available which fulfills these requirements. In this context two approaches (volumetric cell and mass measurement) were pursued to sample a known volume. Independent of the approaches the device consists of a sampling tube, a 5-valve module and a vacuum pump. Using a volumetric cell of a defined volume resulted in sample volume of 1.2ml ±2% and 57% sample-to-sample carryover. This could be improved by using a mass measurement and a sampling tube made of fluorinated ethylene propylene instead of steel. This reduced carry over to under 5%. The obtained prototype is capable of aseptically transferring 0.5-100 ml of cell broth at a flow rate of approximately 2ml/s.