Computational fluid dynamics of DNA origami folding in microfluidics

DNA origami science is a promising field to arrange materials with high precision on a nanometer scale. The field has attracted much attention due to the robust self-assembly, with applications emerging in pharmaceuticals, nano-engineering, and single molecule recognition. In this research, a computational fluid dynamics (CFD) study was performed on various microfluidic reactor designs, including single-phase laminar flow, gas-liquid segmented flow, and single-phase Dean flow reactors. A new DNA origami folding kinetic model was developed, which enables the prediction of the transition of DNA origami crystal structures as well as their distribution throughout each reactor. Folding of the DNA origami is thermodynamically controlled at a higher temperature of 329 K while the kinetics control the folding at a lower temperature of 325 K, with 327 K corresponding to the optimal temperature for rapid constant temperature folding. The influence of the staple strand concentration was also considered for the first time. The liquid slug length (0.5 mm) and the Dean number (De = 100) were optimized to better understand the appropriate microfluidics. Batch PCR vials and microfluidic gas-liquid multiphase flow provide >90% yields of DNA origami faster than other designs and with less polydispersity, which makes the latter attractive for manufacturing scenarios. However, the microfluidic single-phase laminar flow forms DNA origami faster at the cost of polydispersity, which makes it attractive for high-throughput screening of the kinetics and/or in situ characterization studies. Microfluidics has tremendous potential to impact the field of DNA origami science.