The preparation of DNA origami has attracted considerable attention for its relatively robust self-assembly kinetics, ability to arrange molecular configuration on nanoscale with extreme resolution, and unique features as a platform where biomolecules and nanoparticles together form programmable materials.1â3
In practice, a long (around 7kbp) single strand of DNA, which is often referred as a scaffold strand, is folded into well-designed two- or three- dimensional structures with the presence of hundreds of short DNA oligonucleotides, also known as staples, through hybridization reaction.4
The potential applications of DNA nanostructure continue to expand with the construction of increasingly complex DNA origami structures. Achieving more advanced DNA origami designs and effective functionalization by other biomolecules and nanoparticles requires a deeper understanding of the thermodynamic properties and behavior of the DNA origami. In this research we study the influence of different reactor designs on DNA origami folding reaction through CFD (computational fluid dynamics) simulations. Batch PCR vials, single-phase laminar micro-flow, gas-liquid segmented micro-flow, and single-phase Dean flow reactors were investigated. Coupled with a DNA origami folding kinetics model, the heat and mass transfer behaviors of each reaction system are used to predict the transition of DNA origami crystal structures as well as their distribution throughout each reactor. The results of this research provide us with a better understanding of the DNA origami folding reaction, and it prescribes guidelines for choosing the proper reactor for either batch or continuous DNA origami synthesis. Our recommendation of the appropriate laboratory-scale reactor, based on chemical engineering fundamentals, will be presented and discussed.
1. Rajendran, A., Endo, M. & Sugiyama, H. Single-Molecule Analysis Using DNA Origami Angewandte. 874â890 (2012). doi:10.1002/anie.201102113
2. Andersen, E. S. et al. DNA origami design of dolphin-shaped structures with flexible tails. ACS Nano 2, 1213â1218 (2008).
3. SaccÃ , B. & Niemeyer, C. M. DNA origami: The art of folding DNA. Angew. Chemie - Int. Ed. 51, 58â66 (2012).
4. Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297â302 (2006).