Contact Free Monitoring of Cell Density in a Bioreactor with Magnetic Resonance Relaxometry

Abstract

Frequent, low-latency measurements of bioreactor culture growth are critical for achieving maximum culture efficiency and productivity. Typical cell density and viability measurements are made by removing a sample from the culture, but this approach is both slow and unsuitable for small culture volumes that cannot support frequent destructive sampling. In this work, magnetic resonance relaxometry measurements taken through the walls of the bioreactor tubing are used to monitor the cell density in near real-time. Using intracellular iron as the marker, the system detects variations in cell density in minutes, enabling rapid intervention to save the culture that would be impossible with the once-daily measurements taken by a traditional sampling-based culture analysis system. Given the biochemical importance of intracellular iron, these measurements have the potential to provide phenotypic information on cells without disrupting the bioreactor culture.