Abstract
Kinetic studies of biological macromolecules increasingly use microfluidic mixers to initiate and monitor reaction progress. A motivation for using microfluidic mixers is to reduce sample consumption and decrease mixing time to microseconds. Some applications, such as small-angle x-ray scattering, also require large (>10 micron) sampling areas to ensure high signal-to-noise ratios and to minimize parasitic scattering. Chaotic to marginally turbulent mixers are well suited for these applications because this class of mixers provides a good middle ground between existing laminar and turbulent mixers. In this study, we model various chaotic to marginally turbulent mixing concepts such as flow turning, flow splitting, and vortex generation using computational fluid dynamics for optimization of mixing efficiency and observation volume. Design iterations show flow turning to be the best candidate for chaotic/marginally turbulent mixing. A qualitative experimental test is performed on the finalized design with mixing of 10 M urea and water to validate the flow turning unsteady mixing concept as a viable option for RNA and protein folding studies. A comparison of direct numerical simulations (DNS) and turbulence models suggests that the applicability of turbulence models to these flow regimes may be limited.
Highlights
The advent of microfluidics has popularized hydrodynamic focusing [1] to initiate the folding or unfolding process of biological macromolecules such as proteins and RNA via laminar diffusion into a dilution buffer solution
Incorporating more fluid physics such as chaos, turbulence, and cavitation into the mixing process requires the use of computers to design mixers in a rapid fashion to reduce the number of physical iterations and thereby the cost of mixer development
The need to add higher order fluid physics is to increase the disorder in the dilution fluid thereby reducing the mixing times and possibly reducing the bias the dilution fluid induces on the biological macromolecule
Summary
The advent of microfluidics has popularized hydrodynamic focusing [1] to initiate the folding or unfolding process of biological macromolecules such as proteins and RNA via laminar diffusion into a dilution buffer solution. The approach achieves microsecond mixing times with sample consumption of as little as femtomoles [2]. Chaotic mixers improve the performance of laminar mixers by using geometry [3] to add stretching and folding [4,5] of the solutions being mixed (e.g., an unfolded protein solution diluted with refolding buffer), resulting in an increase of the surface area and reduction of the diffusion length to enable faster mixing under certain conditions [3]. Chaotic mixers have larger channels because mixing occurs all throughout the channel instead of just in the focused region as in laminar mixers.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
