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

Huanhuan Shi, Zhihao Xie, Yu Cao, Yali Zhao, Congxuan Zhang, Zhen Chen, Nuno M. Reis, Zhengchun Liu

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish
Article number118080
JournalChemical Engineering Science
Early online date17 Sept 2022
Publication statusPublished - 14 Dec 2022


  • Absorbance measurement
  • Liposome nanoparticle
  • Micro-mixing
  • Microfluidic dilutor
  • Tunable fabrication

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Industrial and Manufacturing Engineering


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