A microfluidic serial dilutor (MSD): Design optimization and application to tuning of liposome nanoparticle preparation

Dilution of a sample over several orders of magnitude in concentration is a routine procedure in many analytical, bioanalytical, diagnostics, and formulation laboratories. Microfluidics offer the opportunity to automate the dilution procedure with many successful designs to be found in literature, yet fast microfluidic generation of a dilution series over several orders of magnitude remains so far unaddressed. This study realized a microfluidic serial dilutor (MSD) having up to 4 outlets and able to generate fast a serial dilution of a sample up to 4 orders of magnitude. The core design based on a cascade dilution of sample to diluent in a 1:10 volume ratio was fully characterized experimentally and using Computational Fluid Dynamics (CFD). The MSD was interfaced with a new absorbance measuring device based on a laser diode and spectral sensor, which enabled evaluating the dilution performance and confirming the effectiveness of the design. The MSD was applied to the synthesis of liposome nanoparticles by solvent diffusion method, enabling fine-tunning of synthesis of a popular drug and vaccine delivery microcarrier on a wide range of sizes by simply adjusting the flow rate and flow rate ratio. The MSD design showed to be simple, reliable, with operation at reduced pressure drops, and delivery of highly reproducible results.