The Ambr250 is one of the most widely used single-use bioreactor systems for mammalian process development. It enables high-throughput process screening, but production-scale bioreactors behave very differently. They mix more slowly, which exposes cells to concentration gradients that are largely absent at small scale.
In our experiment, the small-scale bioreactor mixed in about 4 seconds under the given operating conditions. With one of our off-the-shelf pDS inserts, the mixing time increased to more than 30 seconds, approximating the mixing behavior of a 2000 L production bioreactor.
The mixing time comes from a simple experiment. A pH indicator is added to the reactor, followed by acid or base to cause a pH shift. Digital analysis of the resulting color change then gives the experimental mixing time.
Ambr250 DoEs identify an optimal operating window under very well-mixed conditions. With the pDS insert, selected experiments can be repeated under slower mixing conditions that are relevant for production scale. This needs no additional hardware and no change to the process control strategy, just a different hydrodynamic environment. Repeating only a few experiments under realistic mixing conditions can give valuable insight into how robust a process is to scale-up.
Our standard pDS inserts for the Ambr250 are available off the shelf and offer different mixing times to match your scale-down strategy. Interested in evaluating your process under more representative mixing conditions? Get in touch.
