Use of High-Throughput Automated Microbioreactor System for Production of Model IgG1 in CHO Cells

Abstract

Automated microscale bioreactors (15 mL) can be a useful tool for cell culture engineers. They facilitate the simultaneous execution of a wide variety of experimental conditions while minimizing potential process variability. Applications of this approach include: clone screening, temperature and pH shifts, media and supplement optimization. Furthermore, the small reactor volumes are conducive to large Design of Experiments that investigate a wide range of conditions. This allows upstream processes to be significantly optimized before scale-up where experimentation is more limited in scope due to time and economic constraints. Automated microscale bioreactor systems offer various advantages over traditional small scale cell culture units, such as shake flasks or spinner flasks. However, during pilot scale process development significant care must be taken to ensure that these advantages are realized. When run with care, the system can enable high level automation, can be programmed to run DOE's with a higher number of variables and can reduce sampling time when integrated with a nutrient analyzer or cell counter. Integration of the expert-derived heuristics presented here, with current automated microscale bioreactor experiments can minimize common pitfalls that hinder meaningful results. In the extreme, failure to adhere to the principles laid out here can lead to equipment damage that requires expensive repairs. Furthermore, the microbioreactor systems have small culture volumes making characterization of cell culture conditions difficult. The number and amount of samples taken in-process in batch mode culture is limited as operating volumes cannot fall below 10 mL. This method will discuss the benefits and drawbacks of microscale bioreactor systems.

Impacts of intentional mycoplasma contamination on CHO cell bioreactor cultures

“…Media samples were run in triplicate, with error bars indicating standard deviations. Additional information on this method can be found in past work (Velugula‐Yellela, Kohnhorst, et al, ).…”

“…Samples were thawed at room temperature and titer was measured using Protein A dip‐and‐read BLI sensors (FortéBio, 18‐5010) on the Octet RED96 system (FortéBio) as described previously (Velugula‐Yellela, Kohnhorst, et al, ). Cell‐specific IgG1 production rates ( Q p, pg·cell −1 ·day −1 ) for each perfusion day were calculated using the following adapted formula (Clarke et al, ) where …”

Multivariate data analysis of growth medium trends affecting antibody glycosylation

“…28 Briefly, the ambr ® 15 system (Sartorius, Hertfordshire, UK) was run in batch mode while using four culture stations to support running 36 micro bioreactors (only sparged). 28 Briefly, the ambr ® 15 system (Sartorius, Hertfordshire, UK) was run in batch mode while using four culture stations to support running 36 micro bioreactors (only sparged).…”

“…This procedure is demonstrated in Journal of Visualized Experiments. 28 Briefly, the ambr ® 15 system (Sartorius, Hertfordshire, UK) was run in batch mode while using four culture stations to support running 36 micro bioreactors (only sparged). An in-house CHO DG44 cell line was inoculated at a density of 1 × 10 6 cells/ml.…”

Distributed Biological Foundries for Global Health

“…The biomanufacturing and clinical instrumentation sectors have also benefited from IoT. Liquid handling systems such as the Ambr15 and Tecan can do high‐throughput automated media screening, immunoassays, and mass spectrometry, relaying their results at a distance. Bringing bioprocessing to the beside, researchers at Draper Labs have designed a microfluidic system for chimeric antigen receptor T‐cell therapy (CAR‐T) in an end‐to‐end device that will alert a user's phone in case there are any issues with the bioprocessing steps .…”