Reaction and separation opportunities with microfluidic devices

Microfluidic devices make precisely controlled processing of substances possible on a microliter level. The advantage is that, due to the small sizes, the driving forces for mass and heat transfer are high. The surface to volume ratios are also high, which can benefit many surface oriented processes. In addition, because of their small volumes, microfluidic devices reduce reagent consumption and risk of failure compared to larger counterparts. Furthermore, the parallelization of such devices can increase productivity while maintaining their characteristics. Overall, these advantageous properties give many opportunities for reaction and separation processes. Although researchers have intensively studied microfluidics for analytical and sensory applications, microfluidics for preparative processes is still in its infancy. This thesis research involved exploring these processes for biocatalysis and bio-separations with microfluidic devices. The purpose of this thesis was to yield a better understanding of microfluidics for the preparative processes and larger-scale production. We therefore addressed subjects including microfluidic parallelization, membrane separation, biocatalysis, and design. The presented research is useful for further developing innovative process intensification by means of microfluidic devices. Parallelization of microfluidic devices can facilitate the generation of more data or product in less time. In Chapter 2, we present a proof of concept of such a parallelization for obtaining information on reaction and separation kinetics. We assembled different microfluidic contactors into a single device in order to perform distinct experiments simultaneously. The concept of the parallelization was based on the decoupling of pressure drop from residence time. We demonstrated this by microfluidic membrane separations and determination of membrane properties. The reported device enabled a three times higher throughput compared to devices with a single separation region. Processes such as chromatographic separation and nanofiltration can remove low molecular weight sugars from liquid mixtures of oligosaccharides. In Chapter 3, we present a novel separation process based on the concept of mass diffusion. Differences between diffusivities of the components drive such a separation, while membranes, in particular nanofiltration membranes, can enhance the separation. We demonstrate this by the use of a membrane microfluidic device for the separation of small molecular weight components. Our results show that mass diffusion separation in liquids is a feasible concept. With optimized microchannel and membrane dimensions, the presented separation process might compete with currently available separation technologies. For diffusion-based processes, such as mass diffusion separation shown in Chapter 3, small diffusion distances – and thus thinner membranes – can reduce diffusion times significantly. In Chapter 4, we used a microfluidic contactor to contact liquid streams via such extremely thin membranes. We show that the presented concept can be useful for diffusion-based pre-concentration or downstream processes such as fractionation and enrichment. Our results indicate that also this method can yield a feasible process. Moreover, the technology is generally applicable to any diffusing component – regardless of its absolute diffusivity or concentration. Fast mass transfer and low reagent consumption have made enzyme microreactors popular research tools. In Chapter 5, we used such a microreactor to study the effect of diffusion on enzyme activity. We found that the Michaelis-Menten kinetic parameters were similar at the microscale and bench scale. Our results show that with residence times below a few seconds, diffusion effects limited the reaction rate and therefore reduced the conversion per volume of enzyme microreactor. The critical residence time where this limitation occurred increased quadratically with channel width, increased with enzyme concentration, and decreased with substrate concentration. We concluded that in order to use an enzyme microreactor efficiently, such effects should be taken into account. Many parameters such as the enzyme properties, operating conditions, and dimensions of the microreactor determine to what extent mass transfer restrictions affect the reaction rate and the productivity. The use of microchannels can indeed shorten the characteristic mass transfer time, as shown in Chapter 5, but may also affect the productivity of the microreactor. Chapter 6 provides the correlations between these parameters for coflow enzyme microreactors obeying Michaelis-Menten kinetics. These correlations outline the design space based on reduced mass transfer restrictions and maximum productivity respectively. The methodology that yields the design space provides a generic hands-on approach to optimally design coflow enzyme microreactors. Microfluidics involves the exploitation of the phenomena that manifest themselves on microscale. This thesis shows that microscale applications can indeed offer unprecedented benefits. The discussion in Chapter 7 summarizes and reflects on the previous parts of this thesis. We conclude that it is important to explore and exploit other characteristics of continuous production in microfluidic devices beyond mass transfer effects in order to develop novel processes. In addition, we stress the importance of adoption of microfluidics, and show which determinants are involved in this. Knowledge of these determinants is of utmost importance to reduce skepticism towards and stimulate the adoption of microfluidics by industry.