Simulation Technology Improves Clone Selection and Cell Culture Process Development

Invitrogen (San Diego, CA, www.invitrogen.com) believes that scaledown technologies can significantly improve clone selection and cell culture media development. The company recently acquired a robotic system at its site in Grand Island, NY, which will expand its offerings to its process development customers. The system’s greatest advantage, company sources say, is that the results scale up more accurately than those from traditional media studies.

“We’ve learned that it’s difficult to de-couple the bioreactor from the media,” says Trent Carrier, PhD, director of business development for Invitrogen BioManufacturing Services. “Cells respond and metabolize differently depending on the environmental conditions they’re placed in.” As a result, Carrier says, early process development studies carried out in traditional systems (such as 96-well plates or shake flasks) fall short in one of two ways: either they are limited in their ability to perform high-throughput studies of multiple factors, or they do not accurately reflect bioreactor conditions.

The “SimCell” robotic system that Invitrogen just acquired from BioProcessors Corporation (Woburn, MA, www.bioprocessors.com), is “a happy medium between the two,” Carrier says. It allows hundreds of media compositions to be tested for primary, secondary, and tertiary interactions, in micro-bioreactors with physical dimensions that can replicate shear and maintain key parameters such as pH and dissolved oxygen levels. The system more closely mirrors the conditions of a full-scale bioreactor.

Power, not speed, is the advantage of these studies, Carrier says. “A traditional media project can look at two or three factors, at the most,” says Carrier. In contrast, a typical run on a SimCell system, using 60 microbioreactors, each with a working capacity of less than 1 mL, can use a 7-factor experimental design. “The breadth of the data that you are able to generate is significantly more,” he says.

Because running these studies is expensive, Carrier recommends SimCell be used only after initial media development work has been carried out. “If a partner hasn’t done much media development yet, we would advocate using traditional methods, say to get from 0.5 g/L to 2 g/L,” says Carrier. “You would use SimCell to get to the next level of performance-say to take 2 g/L and go higher.”

“Although any company could buy this technology, so far only Novo Nordisk, Amgen, and our company (Invitrogen) have made the investment,” says Carrier. “So we are really the first place that people can come [to] for third-party services.” Carrier adds that it takes a lot of work to successfully manage an experiment with a technology such as SimCell. “This system can generate hundreds of different samples that need to be prepared and analyzed, so integrating the upstream and the downstream workflows is a significant undertaking,” he says. “Which is why we think a lot of our clients are going to see the value of having us do that work rather than them having to try to set that up, in house, on their own.”

Carrier says the technology will not solely be used to develop proprietary media. “We often do development work for clients who have their own in-house media, and we will use the SimCell technology to help them enhance their own internal platform,” he says.