Application of microbioreactors in fermentation process development: a review

Abstract

Biotechnology process development involves strain testing and improvement steps aimed at increasing yields and productivity. This necessitates the high-throughput screening of many potential strain candidates, a task currently mainly performed in shake flasks or microtiter plates. However, these methods have some drawbacks, such as the low data density (usually only end-point measurements) and the lack of control over cultivation conditions in standard shake flasks. Microbioreactors can offer the flexibility and controllability of bench-scale reactors and thus deliver results that are more comparable to large-scale fermentations, but with the additional advantages of small size, availability of online cultivation data and the potential for automation. Current microbioreactor technology is analyzed in this review paper, focusing on its industrial applicability, and directions for future research are presented.

Assessment of AMBR<sup>TM</sup> as a model for high-throughput cell culture process development strategy

“…One of the HTP strategies utilized in upstream process development is the use of disposable microbioreactors for cell culture process development These disposable micro-bioreactors are expected to perform in a high-throughput manner under controlled bioreactor operation conditions similar to those at bench and largescale, but without extensive bioreactor set-up and cleanup procedures. These systems may replace the use of shake flasks for early stage of cell culture process development and optimization studies [2][3][4][5].…”

Automated, Miniaturized, and Integrated Quality Control-on-Chip (QC-on-a-Chip) for Cell-Based Cancer Therapy Applications

“…Among cell analysis methods, fluorescence spectroscopy is still the most widely used optical technique for on chip cell detection, due to its superior selectivity and sensitivity and the availability of a broad range of optical labels Hata et al, 2003). Recently, a variety of integrated optical oxygen sensors (Schapper et al, 2009) (Stich et al, 2009;Wang and Meier, 2010;Larsen et al, 2011;Feng et al, 2012;Meier and Fischer, 2013) to combine low-cost and easily available imaging equipment with high-resolution imaging for oxygen sensing in microfluidic systems (Figures 3A,B). A CCD camera measuring the intensity at two different wavelengths of the sensors emitted light by using the different color channels of the camera one channel providing the oxygen sensitive intensity image, the other providing a so called reference image, from which ratiometric calculations were conducted to accurately detect respiratory activities.…”

Implementation of Synchronous Micromotor in Developing Integrated Microfluidic Systems

“…Homogenization of cell suspension can be improved with an integrated microstirrer, similar to commonly used bioreactors on the macroscale. These reactor systems have been scaled down by different research groups [23]. However, microtechnological processes were exclusively employed for the microfluidic structures, whereas commercially available miniature stirrers were subsequently assembled and externally actuated via commercial magnets or coils.…”