Microbioreactors for nutrient-controlled microbial cultures: Bridging
the gap between early bioprocess development and industrial scale use
Abstract
It is common practice in the development of bioprocesses to genetically
modify a microorganism and study a large number of resulting mutants in
order to select the ones that perform best for use at the industrial
scale. At industrial scale, strict nutrient-controlled growth conditions
are imposed to control the metabolic activity and growth rate of the
microorganism, thereby enhancing the expression of the product of
interest. Although it is known that microorganisms that perform best
under these strictly controlled conditions are not the same as the ones
that perform best under uncontrolled batch conditions, screening, and
selection is predominantly performed under batch conditions. Tools that
afford high throughput on the one hand and dynamic control over
cultivation conditions on the other hand are not yet available.
Microbioreactors offer the potential to address this problem, resolving
the gap between bioprocess development and industrial scale use. In this
review, we highlight the current state-of-the-art of microbioreactors
that offer the potential to screen microorganisms under dynamically
controlled conditions. We classify them into: (i) microtiter plate-based
platforms, (ii) microfluidic chamber-based platforms, and (iii)
microfluidic droplet-based platforms. We conclude this review by
discussing the opportunities of nutrient-fed microbioreactors in the
field of biotechnology.