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Abstract:
The monitoring and research of biotechnology processes demands sample taking and analysis. The sampling system is the sterile interface between bioreactor and analyzer. Our investigation is based on an influenza vaccine process with mammalian cells on microcarriers in a 5 liter reactor. The data obtained from this process are used for mathematical modeling and optimization. At present complete samples are manually taken into 100 mL flasks. A representative sample has a volume of about 50 mL and which results in a maximum sampling rate of 1 to 2 samples per hour due to necessary sterilization times. Depending on the ratio of reactor volume, sample volume and the process time of 7 days samples are taken only twice per day. A separation step is necessary for further analysis. The results of a sterility test is not shown before 1 or 2 weeks. The aim of our development is to reduce the sample volume, the sampling time and to simplify the handling. Here, we describe the design and test of a new sampling system based on a filtration membrane which allows to take almost any sample volume. Now it is possible to increase the sample number within the same time. Additionally the integrity of the filtration membrane can be test prior and after sampling, thus validating each sampling cycle. Because of the cellfree sampling a separation step is not necessary. The design of the system gives the opportunity of automated mode and implementation in a process control. An online analysis is possible with a connected detector useful for the closed-loop control of a bioreactor.
