I've done mass balance around the reactor but I'm stuck at the volume bit because volume is not constant.
Reactor volumes per day (RVD) control is probably the most simplistic method by which a perfusion process can be developed and operated. Typically, a flow rate is set per day and increased as the cell concentration increases. This can be achieved using a commercially available CD-CHO type growth media, typically starting at 1 RVD once any lag phase has been passed, and the cells start growing exponentially.
The RVD is increased daily based on the observed growth rate and basic metabolomics data such as bioreactor glucose, lactate, and ammonia concentrations. Depending on the cell line and the final cell density required, the final RVD can increase to between 5 and 10 RVD. The general rule is if the growth rate slows, then the RVD is increased. In this way, depletion of key metabolites and/or build-up of growth inhibiting byproduct can be balanced.
This is a very simple way of starting a perfusion process development. However, the resulting process will likely consume significantly more volume of media (measured as a cell specific perfusion rate pL/cell/day) than a well-developed process. However, once developed, this process is relatively insensitive to small variance on feed/perfusate flow rate, as the media use will generally be excessive, making process control marginally simpler using calibrated peristaltic pumps.
With regard to a fed-batch bioreactor volume, much will depend on the feed rate. Please see the attached document:
Maurice Ekpenyong Thank you so much. I really appreciate the help. The attached document is really helpful.
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