Investigation of the purification properties of ultrasonic contrast agent microbubbles based on size using the deterministic lateral displacement method

Microbubbles, encapsulated shells filled with gas, are widely used in medical ultrasonic imaging and drug delivery systems. As ultrasonic contrast agents (UCAs), microbubbles enable real-time diagnosis and high-contrast imaging due to their acoustic properties differing from tissues. However, existing production methods generally result in microbubbles with a wide size distribution, which limits their efficiency and range of applications. Additionally, the inadequacy of current methods for size-based purification of UCAs hinders the production of homogeneous and stable microbubbles. In this study, the feasibility of using an innovative microfluidic method, Deterministic Lateral Displacement (DLD), for the size-based purification of microbubbles was investigated. DLD is a passive method that separates particles based on their size without requiring any external energy source. In this work, the DLD system was designed with consideration for the delicate and deformable structure of microbubbles, and computational finite-element method simulations were performed. Simulation results demonstrated that microbubbles larger than the critical diameter followed the displacement mode, whereas smaller microbubbles progressed in the zigzag mode. This study theoretically demonstrates, for the first time, that the DLD system is an effective method for the size-based separation of microbubbles. This method offers the potential to enhance purification efficiency and represents a significant contribution to the literature. Supporting these theoretical findings with experimental studies could expand the practical applications of this approach.