Use of Orbital Shaken Disposable Bioreactors for Mammalian Cell Cultures from the Milliliter-Scale to the 1,000-Liter Scale

Abstract

Driven by the commercial success of recombinant biopharmaceuticals, there is an increasing demand for novel mammalian cell culture bioreactor systems for the rapid production of biologicals that require mammalian protein processing. Recently, orbitally shaken bioreactors at scales from 50 mL to 1,000 L have been explored for the cultivation of mammalian cells and are considered to be attractive alternatives to conventional stirred-tank bioreactors because of increased flexibility and reduced costs. Adequate oxygen transfer capacity was maintained during the scale-up, and strategies to increase further oxygen transfer rates (OTR) were explored, while maintaining favorable mixing parameters and low-stress conditions for sensitive lipid membrane-enclosed cells. Investigations from process development to the engineering properties of shaken bioreactors are underway, but the feasibility of establishing a robust, standardized, and transferable technical platform for mammalian cell culture based on orbital shaking and disposable materials has been established with further optimizations and studies ongoing.

Cultivation of Marine Microorganisms in Single-Use Systems

“…Several studies have proven the suitability of TubeSpin Ò bioreactors for the cultivation of mammalian [16,[91][92][93] and insect cells [94,95] up to a scale of 50 mL. De Jesus et al showed the advantages offered by TubeSpin bioreactors 50 for process development with CHO cell cultures [91].…”

“…No oxygen limitations were observed, and CO 2 was stripped because of the large interface in the headspace. Zhang et al [16] demonstrated that it was possible to conduct parallel cultivations in TubeSpin bioreactors 50 and measured k L a values of up to 45 h -1 . Strnad et al [92] applied a D-optimal design approach in order to optimize process parameters for the cultivation of CHO cells in a TubeSpin bioreactor 50.…”

“…Zhang et al [16] claimed that the highly dynamic interface generated in the TubeSpin system leads to a large surface area of the culture broth, which increases the k L a values. Werner et al [96] complement this hypothesis with the theory that the adjacent gas layer is accelerated by the high velocity of the media, which increases the gas transfer rate in the head space and therefore also the gas transfer rate in the medium.…”

“…A method for the consistent scale-up from small to large volumes was developed in TubeSpin bioreactors up to the m 3 scale for an orbital shaking bioreactor system [16]. The TubeSpin design on a small scale and on a large scale in the SB200-X bioreactor both offer a cylindrical shape without any additional moving parts, which is an advantage common to orbital shaken systems [98].…”

Numerical simulation of orbitally shaken viscous fluids with free surface

“…Thus, we can model them using the Navier-Stokes equations: r u l D 0 in liquid (4) where u a and u l represent the velocity of the gas and the liquid, p a and p l their pressure, a and l their density and a and l their viscosity. T.u, pI / D .ru C ru T / pI is the Cauchy stress tensor and f a and f l represent the forces acting on the gas and the liquid.…”