Size-Based Separation of Ultrasonic Contrast Agent Microbubbles Using a Deterministic Lateral Displacement System

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Abstract Microbubbles, gas-filled, shell-like capsules, are widely used in medical ultrasound imaging and drug delivery. Utilized as ultrasonic contrast agents (UCAs), they enable real-time diagnostics and high-contrast imaging due to their distinct acoustic properties. However, current production methods often yield microbubbles with broad size distributions, limiting efficiency and application. Existing methods for size-based purification are inadequate, making the production of homogeneous, stable microbubbles challenging. This study investigates the applicability of the passive microfluidic method, Deterministic Lateral Displacement (DLD), for size-based purification of microbubbles. The DLD system is designed with the delicate, deformable nature of microbubbles in mind, and finite-element method (FEM) simulations are performed. Results show that microbubbles larger than the critical diameter follow displacement trajectories, while smaller microbubbles move in zigzag mode. The study demonstrates that DLD is a practical approach for size-based microbubble separation. This method could improve purification efficiency and facilitate on-demand production in practice.