Mixing and oxygen transfer characteristics of a microplate bioreactor with surface‐attached microposts

Abstract

Bioprocess optimization for cell-based therapies is a resource heavy activity. To reduce the associated cost and time, process development may be carried out in small volume systems, with the caveat that such systems be predictive for process scale-up.The transport of oxygen from the gas phase into the culture medium, characterized using the volumetric mass transfer coefficient, k L a, has been identified as a critical parameter for predictive process scale-up. Here, we describe the development of a 96-well microplate with integrated Redbud Posts to provide mixing and enhanced k L a.Mixing in the microplate is characterized by observation of dyes and analyzed using the relative mixing index (RMI). The k L a is measured via dynamic gassing out method.Actuating Redbud Posts are shown to increase rate of planar homogeneity (2 min) verse diffusion alone (120 min) and increase oxygenation, with increasing stirrer speed (3500-9000 rpm) and decreasing fill volume (150-350 μL) leading to an increase in k L a (4-88 h −1 ). Significant increase in Chinese Hamster Ovary growth in Redbud Labs vessel (580,000 cells mL -1 ) versus the control (420,000 cells mL -1 ); t(12.814) = 8.3678, p ≤ .001), and CD4 + Naïve cell growth in the microbioreactor indicates the potential for this technology in early stage bioprocess development and optimization.

Self‐Cleaning Surfaces Realized by Biologically Sized Magnetic Artificial Cilia

“…From previous research, we know that the Redbud posts that form our b‐MAC can be actuated at 6000 rpm for days without any loss of function or visible damage. [ 39 ]…”

“…( 1 From previous research, we know that the Redbud posts that form our b-MAC can be actuated at 6000 rpm for days without any loss of function or visible damage. [39] Supporting Information. Note: Since the observed microparticle behavior in the final steady states is similar for all the microparticle sizes, here we only show 40 µm-sized microparticles as an example.…”

“…Note: All cleaning experiments reported in this figure lasted 900 s (15 min). During this time, no loss of the b-MAC function was observed.From previous research, we know that the Redbud posts that form our b-MAC can be actuated at 6000 rpm for days without any loss of function or visible damage [39].…”

A modular microfluidic device that uses magnetically actuatable microposts for enhanced magnetic bead-based workflows

“…The ASAPs provide enhanced mixing by generating chaotic advective flow. 24 Inspired by cilia, moving hair-like structures found in myriad biological systems, biomimetic cilia (such as ASAPs) have previously been shown to produce directed flow, 24 liquid–liquid mixing (homogenization), enhanced transport for cell growth 25 and generate anti-fouling surfaces. 26 In this work BeadPak, a new technology that utilizes ASAPs for microfluidic bead assays, was investigated with regard to how various design parameters impact capture efficiency in a biotin-avidin model system.…”

Lithographically Defined Micropost Arrays for Programmable Actuation and Interfacial Hydrodynamics

“…Cilia-driven fluid transport and mixing phenomena in biological systems have inspired the fabrication of synthetic micropillars for research and industrial fluid manipulation applications. − Pumping, mixing, and particle sorting in low Reynolds number (Re) environments present technical challenges requiring attention to both cutting edge fabrication techniques as well as the latest understanding of fluid physics in the Stokes (low Re) regime. Synthetic micropillar arrays have also been used as a platform for studying cellular structure and forces , and have even been used for light manipulation and synthetic adhesive development .…”