Abstract
The dawn of the new millennium saw a trend towards the dedicated use of microfluidic devices for process intensification in biotechnology. As the last decade went by, it became evident that this pattern was not a short-lived fad, since the deliverables related to this field of research have been consistently piling-up. The application of process intensification in biotechnology is therefore seemingly catching up with the trend already observed in the chemical engineering area, where the use of microfluidic devices has already been upgraded to production scale. The goal of the present work is therefore to provide an updated overview of the developments centered on the use of microfluidic devices for process intensification in biotechnology. Within such scope, particular focus will be given to different designs, configurations and modes of operation of microreactors, but reference to similar features regarding microfluidic devices in downstream processing will not be overlooked. Engineering considerations and fluid dynamics issues, namely related to the characterization of flow in microchannels, promotion of micromixing and predictive tools, will also be addressed, as well as reflection on the analytics required to take full advantage of the possibilities provided by microfluidic devices in process intensification. Strategies developed to ease the implementation of experimental set-ups anchored in the use of microfluidic devices will be briefly tackled. Finally, realistic considerations on the current advantages and limitation on the use of microfluidic devices for process intensification, as well as prospective near future developments in the field, will be presented.
Highlights
Biobased processes have been a mainstay of development for thousands of years, but the current trend towards the use of sustainable production methods has further stressed the role that biotechnology can play in the production of a wide array of products and energy [1,2]
Other designs have been implemented to improve the basic concept, namely [40,63,67]: a) Multi-lamination, where the inlet stream are divided into several sub-streams, in the form of liquid lamellae, usually within few to several tens of micrometers, which are latter recombined into a laminated stream, the process allowing for enhanced mixing by decreasing diffusion path, while enhancing the contact surface between the two fluids [63,66,69]
When microchannel networks are considered two major patterns can be distinguished: (a) a continuous flow microfluidic system, where solutions and solvents are fed by syringe pumps into the continuous-flow microfluidic device through tubing connections, and effluent(s) with the intended product(s) collected at the other end of the device; (b) integrated microfluidics, a more complex system, where a microchannel network is integrated with micromechanical valves and control components
Summary
Biobased processes have been a mainstay of development for thousands of years, but the current trend towards the use of sustainable production methods has further stressed the role that biotechnology can play in the production of a wide array of products and energy [1,2]. With operating volumes under 1 mL, which emulate typical bench-scale reactors, have been thoroughly reviewed recently [17], and will not be considered here Besides their application as reactors, microfluidic devices have been used for downstream steps, namely involving extraction of large biomolecules, as well as for the integration of (bio)conversion and extraction in a single step [16]. The small diffusion path has been considered as the major driving force for bioprocess intensification, albeit other process intensification fields/driving forces, such as electric fields, microwaves or pressure can be used These can be integrated with microreactors for enhancing reaction rates in purely chemical processes, in the case of bioprocesses their integration is more adequate in stages other than the bioconversion/fermentation step [13,28,29,30,31]. The implementation of such process requires a careful evaluation against the current conventional large scale approaches used, both considering the performance of the reactors as well as cost issues
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