A Scalable Microfluidic Platform for Nanoparticle Formulation: For Exploratory- and Industrial-Level Scales

Area of Science:

• Biotechnology
• Materials Science
• Chemical Engineering

Background:

• Microfluidic platforms offer superior control and reproducibility for nanoparticle (NP) synthesis compared to bulk methods.
• Existing microfluidic NP synthesis platforms are limited by narrow operational flow rate ranges, hindering scalability for research and industrial applications.

Purpose of the Study:

• To develop a universal microfluidic platform for nanoparticle synthesis.
• To enable NP production across a broad spectrum of flow rates (0.1-75 mL/min) for both exploratory research and industrial-scale synthesis.
• To maintain high mixing efficiency and control over physicochemical properties regardless of flow rate.

Main Methods:

• A microfluidic chip utilizing a coaxial flow design with a triangular microstructure was employed.
• This design generates a vortex, ensuring efficient mixing across diverse flow regimes (Reynolds numbers).
• The platform was used for synthesizing various nanoparticles, including polyplexes, lipid nanoparticles (LNPs), and solid polymer nanoparticles, through self-assembly and precipitation.

Main Results:

• The platform demonstrated successful nanoparticle synthesis over an unprecedented flow rate range of 0.1-75 mL/min.
• Nanoparticles synthesized included polyplexes, lipid nanoparticles, and solid polymer nanoparticles.
• The synthesized nanoparticles were effective in delivering GFP plasmid DNA into human T cells, leading to successful gene expression.

Conclusions:

• The developed universal microfluidic platform overcomes flow rate limitations in nanoparticle synthesis.
• It facilitates scalable production of nanoparticles with controlled properties for diverse applications, including gene and protein delivery.
• The platform's versatility supports both small-scale research and large-scale industrial manufacturing of nanoparticles.