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Control over vesicle size during nanoscale liposome synthesis is critical for defining the pharmaceutical properties of liposomal nanomedicines. Microfluidic technologies capable of size-tunable liposome generation have been widely explored, but scaling these microfluidic platforms for high production throughput without sacrificing size control has proven challenging. Here we describe a microfluidic-enabled process in which highly vortical flow is established around an axisymmetric stream of solvated lipids, simultaneously focusing the lipids while inducing rapid convective and diffusive mixing through application of the vortical flow field. By adjusting the individual buffer and lipid flow rates within the system, the microfluidic vortex focusing technique is capable of generating liposomes with precisely controlled size and low size variance, and may be operated up to the laminar flow limit for high throughput vesicle production. The reliable formation of liposomes as small as 27 nm and mass production rates over 20 g/h is demonstrated, offering a path toward production-scale liposome synthesis using a single continuous-flow vortex focusing device.

Hydrocyclones are a simple and powerful particle separation technology, widely used in macroscale industrial processes, with enormous potential for miniaturization. Although recent efforts to shrink hydrocyclones to the centimeter scale have shown great promise for passive and high‐throughput microparticle separations, further miniaturization is constrained by limited understanding of the impact of device size scale and design on separation performance, and challenges in realizing the complex internal structures of hydrocyclones at small size scales using conventional microfabrication techniques. Here, fundamental scaling issues for hydrocyclones with sub‐millimeter critical dimensions are investigated, and the first microscale hydrocyclones with critical feature size as small as 250 µm are demonstrated by taking advantages of 3D printing using stereolithography coupled with digital light processing. The resulting devices are shown to provide high separation efficiency for particles as small as 3.7 µm while operating at high flow rates up to 40 mL min⁻¹, with scaling analysis suggesting that sub‐micrometer particle separations can be achieved with further miniaturization, potentially making the technology suitable for the rapid isolation and concentration of both inorganic and biological nanoparticles.

The use of additive manufacturing to fabricate microfluidic devices capable of high throughout synthesis of nanoscale liposomes with tunable dimensions is demonstrated. Employing a high‐resolution 3D printing process based on stereolithography and digital light projection, microchannel geometries and printing parameters are optimized to enable reliable patterning of channel features with critical dimensions of 200 µm, supporting the production of lipid vesicles below 100 nm in diameter by microfluidic flow focusing. The additive manufacturing approach enables the fabrication of flow focusing microchannels with high aspect ratios, together with seamless fabrication of high‐pressure fluidic ports for world‐to‐chip interfacing, supporting large volumetric flow rates and high‐throughput nanoparticle synthesis, with demonstrated production rates for optimized liposomes as high as 4 mg min⁻¹from a single device.