Biominiaturization of Bioreactors

Bioprocess development largely parallels the drug discovery process. Screening a large number of experimental conditions in the early stages, is required. As scales increase through the pilot to the manufacturing stage, process conditions get more stringent in terms of variation. Ideally, one would like the same quality of process information, independent of scale. Traditionally, early stage experiments to optimize growth media and cultivation parameters have been carried out in flasks and liter-scale bioreactors. This has often resulted in slow development timelines due to a lack of information in the former and the low-throughput nature of the latter. To circumvent these drawbacks in traditional technologies, much effort has been directed toward developing small-scale culturing platforms with monitoring and control capabilities that would mimic production conditions. Such systems would enable more experiments to be carried out simultaneously without compromising the quality of information obtained. In this review, traditional as well as novel systems with monitoring and control capabilities are discussed. We have focused on their application in culture and, in many cases, comparison to larger scale systems. Many small-scale systems have performances comparable to lab-scale bioreactors. These advances should allow for much more efficient process development as well as impact other areas such as bioprospecting, where hitherto “uncultivable” species may now be grown by screening samples for growth under matrices of conditions that were previously impractical. Another area of impact will be to allow industry to more readily incorporate process analytical technologies. Keywords: bioreactor; small scale; optical sensor; high throughput bioprocessing