Combination of On-line pH and Oxygen Transfer Rate Measurement in Shake Flasks by Fiber Optical Technique and Respiration Activity MOnitoring System (RAMOS)

Shake flasks are commonly used for process development in biotechnology industry. For this purpose a lot of information is required from the growth conditions during the fermentation experiments. Therefore, Anderlei et al. developed the RAMOS technology [1, 2], which proviedes on-line oxygen and carbondioxide transfer rates in shake flasks. Besides oxygen consumption, the pH in the medium also plays an important role for the successful cultivation of micro-organisms and for process development. For online pH measurement fiber optical methods based on fluorophores are available. Here a combination of the on-line Oxygen Transfer Rate (OTR) measurements in the RAMOS device with an on-line, fiber optical pH measurement is presented. To demonstrate the application of the combined measurement techniques, Escherichia coli cultivations were performed and on-line pH measurements were compared with off-line samples. The combination of on-line OTR and pH measurements gives a lot of information about the cultivation and, therefore, it is a powerful technique for monitoring shake flask experiments as well as for process development.