ABSTRACT
This article describes and demonstrates the performance of a novel disposable culture platform, the rolling tube, which we
have developed, tested, and found superior, in many aspects, compared with current platforms being used in process development
applications such as media screening and clone selection. The rolling-tube platform provides a balance between throughput
and scale or volume (necessary to perform analytical assays); it also is robust, easy to set up, and ergonomic to use, as
well as versatile, saving time and money. Importantly, results obtained with this system are applicable to larger platforms
used in commercial production. This platform is now being implemented in our laboratories in California and Europe.
EDEN BIODESIGN
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Throughput, robustness, and low cost are major system requirements in cell culture process development projects, ranging from
clone selection to media screening. A desirable system also should allow for sufficient sample volumes to perform a comprehensive
analysis for testing metabolites, viable cell growth, product titer, and quality attributes. Ideally, the system would closely
mimic the outcome in production bioreactors and thus provide high confidence in obtaining a beneficial outcome following scale-up
and implementation.
Disposability is now common across a growing spectrum of platform scales.1 Traditionally, 2-L roller bottles on a rolling device placed in a humidified, temperature and CO2-controlled incubator served as a common screening system for the aforementioned applications, toward implementation in perfusion,
batch, and fed-batch bioreactors. They are inexpensive and disposable, provide a low-shear culture environment, and often
demonstrate predictability of culture behavior following scale-up, making them a good choice compared to other small-scale
platforms such as spinner and shake flasks. However, their size, rolling equipment space requirements, and cumbersome handling
are major drawbacks that limit throughput. They also are wasteful because smaller volumes of culture and spent-media usually
are required for titer, potency, and spent-media and metabolite analysis.
The volume of the 2-L roller bottles is not large enough to allow purification and a comprehensive characterization of the
product or impurities. Smaller, low-cost platforms such as T-flasks and plate systems have advantages in throughput, space
use, and ease of use while allowing for sufficient sample volume for analysis and being predictive of performance at large
scale. In previous experiments, we have found that T-flasks performed similarly or even better than the large roller bottles
(not shown). However, both flask and plate systems have drawbacks such as ergonomics and gas transfer and condensation problems
resulting from their design combined with lower volume (especially multi-well plates) that can significantly affect culture
performance. Therefore, we set out to develop a platform that would preserve the advantages of the traditional roller bottle
along with those of the more advanced flask and plate systems. Here, we describe the performance of the roller tube platform
compared to two small-scale platforms: T-flasks and 6-well plates.
