Micro-/nanoparticle separation combining inertial and thermophoretic effects in three-dimensional serpentine-spiral channels

The separation of micro-/nanoparticles on a chip is an important research area with significant applications in biology, biomedical engineering, and materials science. However, conventional single-field separation strategies exhibit certain limitations, such as dependence on particle properties, size selectivity, and a restricted range of separable targets. These limitations can be overcome by combining complementary physical fields, which allows the strengths of each individual field to compensate for the weaknesses of others. In this study, we present a multi-physical field (MPF)-based approach that synergistically combines inertial and thermophoretic effects to achieve continuous, on-chip separation of micro-/nanoparticles. This combined effect allows separation to reach the nanoscale and significantly sharpens the bands of the separated particles. We fabricated a three-dimensional (3D) serpentine-spiral microfluidic device by rolling a thin, flexible microfluidic chip around a cylindrical heating rod, which served as a radial heating source. By independently controlling the flow rate and electrical power, we regulated Dean flow-induced inertial effects and Joule heating-driven thermophoresis, creating a 3D serpentine-spiral and adjustable radial temperature (SART) device. Not only did we numerically simulate the SART device, but we also characterized it to optimize separation parameters for micro-/nanoparticles based on flow rate (inertia) and temperature gradient (thermophoresis). Our results demonstrated that the combined effects of inertia and thermophoresis significantly enhanced separation efficiency for a particle mixture containing microparticles (4.9, 3, and 1 μm) and nanoparticles (500, 380, and 200 nm). Furthermore, we applied the SART device to the separation of live microscale cells from their nanoscale debris, incorporating an in-line thermal cell lysis process. We believe that the 3D SART device can be further developed into a fully automated on-chip bioprocessing system by integrating additional physical fields and advancing microfabrication techniques.