Diffusion-driven fed-batch fermentation in perforated ring flasks.

PURPOSE: Simultaneous membrane-based feeding and monitoring of the oxygen transfer rate shall be introduced to the newly established perforated ring flask, which consists of a cylindrical glass flask with an additional perforated inner glass ring, for rapid bioprocess development. METHODS: A 3D-printed adapter was constructed to enable monitoring of the oxygen transfer rate in the perforated ring flasks. Escherichia coli experiments in batch were performed to validate the adapter. Fed-batch experiments with different diffusion rates and feed solutions were performed. RESULTS: The adapter and the performed experiments allowed a direct comparison of the perforated ring flasks with Erlenmeyer flasks. In batch cultivations, maximum oxygen transfer capacities of 80 mmol L-1 h-1 were reached with perforated ring flasks, corresponding to a 3.5 times higher capacity than in Erlenmeyer flasks. Fed-batch experiments with a feed reservoir concentration of 500 g glucose L-1 were successfully conducted. Based on the oxygen transfer rate, an ammonium limitation could be observed. By adding 40 g ammonium sulfate L-1 to the feed reservoir, the limitation could be prevented. CONCLUSION: The membrane-based feeding, an online monitoring technique, and the perforated ring flask were successfully combined and offer a new and promising tool for screening and process development in biotechnology.

Novel Optical Position Sensing for Miniaturized Applications and Validation in a Total Artificial Heart.

GOAL: This paper describes the development and testing of various position sensing systems (PSSs) for miniaturized long-term applications with a focus on their validation in a total artificial heart (TAH). After a short description of the TAH's functioning principle, the special requirements for the PSS resulting from the application in a TAH are investigated. METHODS: Three PSS's were designed according to these requirements. A specially designed test method was used to first validate each PSS for general use in a miniaturized application. This test method validated the speed, resolution, and accuracy requirements for the PSS. In a second step, the PSS's were integrated in a TAH to measure its stroke position for the drive control. In this application, further requirements apart from miniaturization were considered. Each PSS's functionality in the TAH was validated in a mock circulation loop, which simulates the human circulatory system. RESULTS: Two of the three designed PSS's showed satisfactory results for all tested requirements inside the pump, whereas the third PSS did not operate properly at full-pump capacity. The best performing PSS was chosen for further use in the TAH. It performed up to a beat rate of 220 b/m. CONCLUSION: The extensive validation resulted in an accurate, miniature PSS for a TAH. SIGNIFICANCE: Besides the use in a TAH, the presented PSS's can be employed in a wide use of miniaturized applications. The introduced testing method allows the validation for general miniaturized applications, e.g., linear motor drives.