The measuring chamber was built according to concurrent sterile construction guidelines to achieve a design which does not compromise the sterility of a cell culture process. A modular design was chosen, thus it is possible to maximize the flexibility and adapt the chamber onto different kind of probe dimensions and measurement principles.
One of the main objectives was to develop a bypass measuring chamber that enabled the use of standard sensors, without the need of reconstructing the probes itself. Larger stainless steel bioreactors, as used in production scale, provide mainly two different ports for mounting analytical probes or other peripheral devices for inline measurements. Those are the Ingold-port, a mostly sideways accessible opening with a diameter of 25 mm and the primarily lid-mounted probes for PG 13.5-Ports, which have 12 mm in diameter.
At one end of every chamber a lock ring clamps onto the outer part of the probe and fixes the position of the chamber. The chamber ring has two opposing openings that are used as an inlet and outlet for the sample. The chamber is sealed against the bottom and top part with one O-ring on each side. The lid, which design depends on the dimensions of the probe and the underlying measuring principle, seals the chamber. Optical probes, e.g. the 2D-fluorescence spectrometer BioView® (DELTA, Hørsholm, Denmark), are measuring light reflection at the end of the probe [1, 2]. Other systems like the BioPAT®Spectro NIR (Sartorius Stedim Biotech BmbH, Göttingen, Germany) or the in house developed insitu microscope (ISM) are measuring through a measuring gap [3–5]. Therefore a possibility to adapt the chamber to the respective analytic principle has to be available. This flexibility was achieved by the two lid-designs, a closed lid for terminal measurements and a seal ring for placing it close to a measurement gap. Figure 1 (top) shows the two versions.
The chamber is attached to the reactor via tubing to a sample taking port. Figure 1 (bottom) depicts a schematic of the setup, with the sample transport through measurement chambers and the possibility for offline sample taking after the bypass measurements. The chamber design allows the operation of different sensors in series. Thereby it is possible to connect more than one sensor into only one sample taking port. This makes it possible to test different analytical sensors during only one process in small scale.