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Acoustic manipulation is a non-contact process that applies acoustic waves to immobilize particles into a specific region for a variety of potential applications. This provides an alternative way to address air ventilation requirements where building systems are becoming smarter and more efficient. Development of such a process within confined spaces can incorporate microscopic interactions to filter aerosol-based particulate matter (PM). In real-engineering conditions, it is hard to filter sub-micron particles (0.25–1.0 μm) than super-micron particles (> 2.5 μm) by using low-grade filters. The objectives of this work are twofold. First, we propose a new acoustic-driven pre-filtering device (i.e., a U-shaped resonant acoustic chamber) that can improve the working efficiency of low-grade filters for capturing such particles. Second, the device can optimize spatial homogeneity to enhance the removal efficiency of airborne particles under lower sound intensity requirements. The U-shaped acoustic-driven device in the form of a resonant chamber allows PM to reside at the pressure node of a standing wave. Experimental studies are conducted to verify the present design. The results show that an overall filtration efficiency of up to 89% for 1.0-μm airborne particles can be achieved when the acoustic-driven device is coupled together with a low-grade MERV-6 coarse filter. As a standalone device, the acoustic effect works well for the sub-micron particles with a filtration efficiency of up to 61% under a lower sound pressure level (116 dB) than as previously reported in the literature. In the analysis, we also discuss the performance dependence on frequency, sound pressure level and flow rate in terms of particle size distribution. The relevance of this research is a major step towards engineering an acoustic-based pre-filtering technique for developing future innovative ventilation solutions.