A problem faced during cell process development is discerning the real effects of varying conditions from the noise. The use of extremely simple media during feed and supplement optimization, mentioned earlier, is an example of how to assure that real effects stand out.
Human variability is another area that may drown out signs of significant improvement (or problems).
“Cell culture involves a lot of manual processing,” observes Tim Ward, director of strategic marketing at The Automation Partnership (TAP). “Automation eliminates dependence on workers, while completing repetitive processes with a lot less labor and improved efficiency.”
Despite practice, consistency is difficult to achieve with manual manipulations. Small differences in how a task is performed from day to day, between or among individuals, even when they are following the same protocol, can result in cells experiencing different conditions.
The efficiency and consistency of automation, Ward says, “opens up a whole spectrum of ways to employ automated systems to change the way cell culture is done, for everything from producing cells for experimentation through process development and manufacturing.”
Readers are well aware of the value of automation in carrying out repetitive tasks on large numbers of small samples, e.g., in microtiter plates. The same level of automation, consistency, and control are available for cell-culture optimization as well. For example, TAP’s ambr™ cell culture workstation carries out up to 48 bioreactor experiments simultaneously in microreactors that mimic bioreactors in most important physical/mechanical respects.
With 10–15 mL of working volume, ambr microreactors are much larger than microwells. The TAP reactors also employ impeller stirring, constantly monitor pH and dissolved oxygen, and feature independent control of oxygen and carbon dioxide.
“Customers want to do many more early experiments, and the ambr system allows that,” says Shaw, who opines that ambr compliments but does not replace microplates. “You still need two stages. The first should still be a front-end screen, some form of selection pressure or colony picking, which is best done in 96-deep-well plates.”