Numerical Prediction of Microbubble Attachment in Biological Flows

Biofilm infections pose a major threat to human health and are difficult to detect. Microbubbles provide an effective and inexpensive method of detection for biofilm-based infections and other diseases such as cancer. The approach studied here examines the potential of targeted microbubbles, with specific antibodies covalently linked to their surfaces for use as ultrasound contrast agents and drug delivery vehicle. This work presents a novel numerical model for estimating the forces on microbubble conjugates in the vascular system. A full computational fluid dynamics simulation of biological fluid flow and the resulting forces on attached microbubbles is presented as well as comparisons with simplified analytical models. Both the computational and analytical predictions are compared with experimental measurements from Takalkar et al. and Schmidt et al., and these comparisons indicate stable microbubble attachment can be anticipated when the total hydrodynamic force on the microbubble is less than 100 pN. Through the examination of typical biological flows, microbubble attachment can be expected up to an average fluid velocity of 0.025 cm/s near the microbubble (i.e., a particle Reynolds number on the order of .001). The Stokes drag law was shown to predict the drag force (the dominant force) on the microbubble within an order of magnitude of the force predicted by the numerical model. Finally, it was found that the lift force on a microbubble was small relative to the drag force, and that the Saffman equation prediction differed from the numerical model by more than an order of magnitude for the biological flows examined. KEYWORDS: Microbubble Attachment; Ultrasound Contrast Agent; Hydrodynamic Force; Computational Fluid Dynamics