技術論文とプレゼンテーション

Small EVs (100-600 nm), sub-micron lipid-bilayer particles, are promising therapeutic agents for conditions like neurological disorders and cancers, which can cross biological barriers, such as the blood-brain barrier, the gut barrier, and tumor barriers, to aid repair or to be modified for targeted drug delivery [1]. Plasma-derived EVs, readily obtained from blood, serve as minimally invasive biomarkers that reflect whole-body physiology. Conventional isolation techniques, such as ultracentrifugation, risk damaging small EVs, and no high-recovery protocols exist. Inertial microfluidics operate at higher flow rates and offer very high throughput [2]. While inertial separation is effective for larger micro-sized particles, it struggles with nano-sized particles such as EVs due to their small size. Therefore, this challenge remains a significant issue in current research. This work presents a COMSOL Multiphysics-driven design and optimization of a cascaded spiral microfluidic platform capable of sequentially separating particles spanning multiple length scales. The proposed system combines two spiral inertial microfluidic devices in series. The first-stage spiral removes large particles and cellular debris, and the second-stage spiral separates micron-sized particles (~1 µm) from submicron particles (~100-500 nm). This cascade architecture enriches nanoscale particles progressively while maintaining high throughput and label-free operation. COMSOL Multiphysics was used to study inertial lift and Dean drag forces in curved microchannels. Using Laminar Flow and Particle Tracing interfaces, the team modeled velocity fields, Dean vortices, and particle trajectories across various sizes. A two-step workflow was adopted: first, fluid dynamics simulations to analyze velocity and vortex formation; then, particle tracing to assess migration and focusing of particles from 100 nm to 10 µm. Channel walls, particle-wall interactions, and outlet strategies were included to predict separation efficiency. For the first-stage device, COMSOL simulations demonstrated stable focusing of 10 µm particles toward the inner wall, while smaller particles migrated toward the outer outlet. Parametric studies identified an optimal channel cross-section of 250 µm × 50 µm for efficient size-based separation. For the second-stage device, channel dimensions were reduced to enhance Dean drag effects on submicron particles. Various geometries with widths ranging from 30 to 50 µm and a channel height of about 8 µm were optimized. Simulation showed different streamlines for 1 µm and 100 nm particles, allowing separation by adjusting flow conditions controlled by the Dean number. The study indicates that cascading spiral microfluidic devices expand the applications of inertial microfluidics, from micron-sized particle sorting to submicron particle enrichment. Factors such as channel size, curvature, and flow-rate ratios significantly affect particle focusing. This scalable system enables high-throughput, label-free separation of extracellular vesicles, which are valuable for liquid biopsy and diagnostic applications.