Dispersion-free inertial focusing (DIF) for high-yield polydisperse micro-particle filtration and analysis†

Inertial focusing excels at the precise spatial ordering and separation of microparticles by size within fluid flows. However, this advantage, resulting from its inherent size-dependent dispersion, could turn into a drawback that challenges applications requiring consistent and uniform positioning of polydisperse particles, such as microfiltration and flow cytometry. To overcome this fundamental challenge, we introduce Dispersion-Free Inertial Focusing (DIF). This new method minimizes particle size-dependent dispersion while maintaining the high throughput and precision of standard inertial focusing, even in a highly polydisperse scenario. We demonstrate a rule-of-thumb principle to reinvent an inertial focusing system and achieve an efficient focusing of particles ranging from 6 to 30 μm in diameter onto a single plane with less than 3 μm variance and over 95% focusing efficiency at highly scalable throughput (2.4–30 mL h⁻¹) – a stark contrast to existing technologies that struggle with polydispersity. We demonstrated that DIF could be applied in a broad range of applications, particularly enabling high-yield continuous microparticle filtration and large-scale high-resolution single-cell morphological analysis of heterogeneous cell populations. This new technique is also readily compatible with the existing inertial microfluidic design and thus could unleash more diverse systems and applications.