Achieving efficient microfluidic mixing with minimal hydraulic cost remains challenging for integrated microfluidic devices. This study presents a compact, topology-optimized passive micromixer that achieves over 90% mixing efficiency while maintaining moderate pressure drop. Unlike conventional designs relying on long channels or repetitive structures, we introduce localized velocity control points, targeted regions where topology optimization induces strategic flow perturbations. A two-stage design of experiments framework systematically evaluates spatial arrangement and velocity configurations of these control points. The optimization, driven by velocitybased objectives within an artificial porous domain, generates solid obstacles that redirect flow and enhance chaotic advection. The optimal compact design achieves MI = 0.901 with Δp = 365.2 Pa at Re = 70, demonstrating 1–3 orders of magnitude lower pressure drop than comparable passive mixers while maintaining high mixing performance. This compact design (L/H0 ≈ 10) offers superior hydraulic efficiency, making it particularly suitable for pressure-sensitive pplications such as Lab-on-a-CD platforms and point-of-care diagnostics.

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