Standing surface acoustic waves (SSAWs) have been widely utilized in microfluidic devices to manipulate various cells and micro/nano-objects. Despite widespread application, a time-/cost-efficient versatile 3D model that predicts particle behavior in such platforms is still lacking. Herein, a fully-coupled 3D numerical simulation of boundary-driven acoustic streaming in the acoustofluidic devices utilizing SSAWs has been conducted based on the limiting velocity finite element method. Through this efficient computational method, the underlying physical interplay from the electromechanical fields of the piezoelectric substrate to different acoustofluidic effects (acoustic radiation force and streaming-induced drag force), fluid–solid interactions, the 3D influence of novel on-chip configuration like tilted-angle SSAW (taSSAW) based devices, required boundary conditions, meshing technique, and demanding computational cost, are discussed. As an experimental validation, a taSSAW platform fabricated on YX 128 $$^\circ $$ ∘ LiNbO3 substrate for separating polystyrene beads is simulated, which demonstrates acceptable agreement with reported experimental observations. Subsequently, as an application of the presented 3D model, a novel sheathless taSSAW cell/particle separator is conceptualized and designed. The presented 3D fully-coupled model could be considered a powerful tool in further designing and optimizing SSAW microfluidics due to the more time-/cost-efficient performance than precedented 3D models, the capability to model complex on-chip configurations, and overcome shortcomings and limitations of 2D simulations.

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