Nanoparticles can enable the encapsulation of drug- or mRNA molecules in the form of carrier nanoparticles, or provide higher bioavailability in the form of drug nanoparticles. The ultimate goal in microfluidic approaches is to produce nanoparticles with narrow size distributions while avoiding impurities and achieving sufficiently high throughput. To achieve this a novel microfluidic precipitation device was developed and realised by two-photon polymerisation. Mixing elements were designed, so that the fluids undergo a repeated stretch-and-fold transformation, resulting in an enlarged interface and mixing times of less than 10 µs. These elements and an additional 3D flow focussing ensure that no organic phase is exposed to the channel walls and unwanted deposits are avoided. The production of lipid nanoparticles was carried out at different flow rates and mixing ratios. Flow rates of up to 800 μl min-1 resulted in particle sizes ranging from 42 nm to 166 nm with the desired very narrow size distribution. This micromixer produced by using two-photon polymerisation ensures a stable and continuous process, thus enabling scalable production.
Original Article:
Erfle P, Riewe J, Cai S, Bunjes H, Dietzel A. Horseshoe lamination mixer (HLM) sets new standards in the production of monodisperse lipid nanoparticles. Lab on a Chip. 2022;22(16):3025–44. doi:10.1039/d2lc00240j. pubs.rsc.org/en/content/articlehtml/2022/lc/d2lc00240j