THE DESIGN, CONSTRUCTION, AND VALIDATION OF NOVEL ROTATING WALL VESSEL BIOREACTORS

Abstract

The rotating wall vessel (RWV) bioreactor is a well-established cell culture device for the simulation of microgravity for suspension cells and the generation of spheroids and organoids. The key to the success of these systems is the generation of a delicately maintained fluid dynamics system which induces a solid body rotation capable of suspending cells and other particles in a gentle, low-shear environment. Despite the unique capabilities of these systems, the inherently delicate nature of their fluid dynamics makes the RWV prone to multiple failure modes. One of the most frequently occurring, difficult to avoid, and deleterious modes of failure is the formation of bubbles. The appearance of even a small bubble in an RWV disrupts the crucial laminar flow shells present in the RWV, inducing a high-shear environment incapable of maintaining microgravity or producing true spheroids. The difficulty of eliminating bubbles from the RWV substantially increases the learning curve and subsequent barrier-to-entry for the use of this technology. The objective of this study is to create a novel RWV design capable of eliminating the bubble formation failure mode and to demonstrate the design’s efficacy. The tested hypothesis is: “The addition of a channel capable of segregating bubbles from the fluid body of the RWV will protect its crucial fluid dynamics system while enabling the growth of consistently sized and properly formed cell spheroids, improving ease of use of the RWV and decreasing experimental failure.”