Controlled PLGA microparticle production across different microfluidic channel sizes

Precise control of microparticle synthesis is essential for advanced drug delivery systems. Microfluidics offers improved controllability and particle quality, yet challenges remain in scalability and the consistent production of small (<5 μm) particles without extensive post-processing. This study develops a generalized framework for controlling microparticle size and uniformity across different microfluidic device scales. Poly (lactic-co-glycolic acid) (PLGA) microparticles were produced using two geometrically similar flow-focusing microfluidic devices (30 μm and 100 μm). By directly comparing droplet formation dynamics and particle characteristics, we derive transferable insights and dimensionless design rules. Key operational parameters (i.e., surfactant concentration, polymer concentration, flow rate ratio (FRR), fluid velocity, and residence time) were varied to assess their impact on droplet and particle characteristics (i.e., size and polydispersity). Results revealed that increasing surfactant concentration and FRR yields smaller, more monodisperse particles, whereas increasing polymer concentration leads to larger particles and higher polydispersity. The effect of FRR in the 30 μm device was ∼45% greater, producing smaller (2-11 μm) and more uniform particles compared to those in the 100 μm device (9-25 μm). A predictive model for particle size based on Capillary number, Reynolds number, and dimensionless droplet size achieved an average deviation of 6.2%.