(596a) Engineering Considerations for Dissolved Oxygen Sensor Response Across Silicone Membranes in 3-L Single Use Bioreactors

Single use bioreactors are becoming standard in biopharmaceutical development and manufacturing because they reduce capital expenditure, eliminate cleaning complications, and decrease down time between batches. Several successful bioreactor designs are available, but sensor integration poses different challenges between scales. For example, large-scale cultivations require a high degree of sensor fidelity, typically using costly disposable adaptors to sterilize and connect traditional reusable probes. In contrast, high throughput bioprocessing values cheaper sensor technology, often trading off robustness. With bench-scale bioreactors, a gap exists because their use in process characterization and scale-down studies still demands accuracy, precision, and longevity, but at a broad experimental scope that doesn’t allow for high unit cost per run.

If industry leaders want the advantages of single-use vessels as well as the proven reliability of reusable sensors for 3L bioreactors, operators need to sterilize probes separately for aseptic insertion in a hood. To avoid the need for manipulation of dissolved oxygen (DO) sensors, we use a thin silicone membrane as a gas-permeable sterile-barrier. In doing so, we retain the measurement integrity in addition to the economic advantages of reusable probes.

This presentation discusses engineering considerations for DO sensor response when impeded by a secondary membrane. We applied first principles to separate the additional delay from overall probe response, quantified maximum lag times, and demonstrated a robust design window for acceptable performance of mammalian cell culture. We are demonstrating the long-term functionality of this solution by implementing across our routine process development cultivations.