Precisely separation of multicomponent particle mixtures has great potential to clinical diagnosis. Herein, we propose a novel two-stage separation platform combining deterministic lateral displacement (DLD) with inertia which can achieve high-throughput, sheathless, and precise multi-target particle separation. The first-stage inertial unit, consisting of contraction–expansion arrays, was used for both separating the large particles and prefocusing the remaining particles. The second-stage DLD unit was then used to further separate medium and small particles. In particular, the inertial unit can also replace sheath flow in the DLD unit to prefocus and limit the entry position of the particle flow. Moreover, flow matching of the two-stage connection region has ensured that the input flow of the second stage meets the conditions for effective separation of the DLD unit. The structure parameters and input conditions of each unit were optimized based on the evaluation of separation performance by numerical simulation and particle experiment. The results show that continuous and rapid separation of 5 μm, 10 μm and 20 μm particles can be achieved with high efficiency (96.3 %, 94.7 % and 100 %) and high purity (98.65 %, 92.65 % and 85.5 %) based on the superposition of inertia and DLD units. Our two-stage separation platform is capable of high throughput operation while maintaining separation accuracy, which has strong practical significance in biological, clinical and point-of-care applications.

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