Precise and programmable manipulation of microbubbles by two-dimensional standing surface acoustic waves

Lipid-coated microbubbles represent a new class of agents with both diagnostic and therapeutic applications. Microbubbles have low density. Stabilization of microbubbles by lipid coatings creates low-density particles with unusual properties for diagnostic imaging and drug delivery. Perfluorocarbon (PFC) gases entrapped within lipid coatings make microbubbles that are sufficiently stable for circulation in the vasculature as blood pool agents. Microbubbles can be cavitated with ultrasound energy for site-specific local delivery of bioactive materials and for treatment of vascular thrombosis. The blood-brain barrier (BBB) can be reversibly opened without damaging the neurons using ultrasound applied across the intact skull to cavitate microbubbles within the cerebral microvasculature for delivery of both low and high molecular weight therapeutic compounds to the brain. The first lipid-coated PFC microbubble product is currently marketed for diagnostic ultrasound imaging. Clinical trials are currently in process for treatment of vascular thrombosis with ultrasound and lipid-coated PFC microbubbles (SonoLysis Therapy). Targeted microbubbles and acoustically active PFC nanoemulsions with specific ligands can be developed for detecting disease at the molecular level and targeted drug and gene delivery. Bioactive compounds can be incorporated into these carriers for site-specific delivery. Our aim is to cover the therapeutic applications of lipid-coated microbubbles and PFC emulsions in this review.

Surface acoustic waves are used to actuate and process smallest amounts of fluids on the planar surface of a piezoelectric chip. Chemical modification of the chip surface is employed to create virtual wells and tubes to confine the liquids. Lithographically modulated wetting properties of the surface define a fluidic network, in analogy to the wiring of an electronic circuit. Acoustic radiation pressure exerted by the surface wave leads to internal streaming in the fluid and eventually to actuation of small droplets along predetermined trajectories. This way, in analogy to microelectronic circuitry, programmable biochips for a variety of assays on a chip have been realized.