Acoustic and atomic force microscopy characterization of microbubbles with varying shell chemistry

Abstract

Applications of microbubbles (MBs) in diagnostic and therapeutic interventions critically depend on their stability and scattering properties. The shell chemistry of MBs defines these properties. We investigated the effects of shell chemistry on the size, abundance, acoustic response, and mechanical properties of MBs by varying the poly(ethylene glycol) (PEG) molar ratio (0 to 100%) in a two-lipid (DPPC and DPPE-PEG2000) component shell formulation. Increasing PEG concentration from 0% to 10% resulted in an increase in the number of MBs by at least 10-fold, with adverse effects upon further increases. Microbubbles made with 5–10% PEG generated the strongest fundamental as well as nonlinear (subharmonic and second harmonic) components at the excitation frequency of 2.25 MHz. We used interfacial rheological models to determine the mechanical properties of MB shells as functions of PEG concentration using experimentally measured attenuation values. We also employed atomic force microscopy (AFM) to perform thin planar film characterization of the shells. The correlation between the AFM measurements of film properties and the acoustic responses of the corresponding coated MBs will be discussed.