Investigating the Acoustic Focusing of Microbubbles for Bioanalytical and Biomedical Applications

Lipid-coated microbubbles are micron-sized spherical structures composed of an inert gas core stabilized by a lipid shell. Due to their unique acoustic properties, these microbubbles have shown great promise for ultrasound applications including imaging and drug delivery. In a related field, micro and nanometer sized particles including biological cells can be focused into distinct flow streams in microfluidic channels under the presence of acoustic forces. The aim of this project is to exploit the unique acoustic properties of microbubbles in an acoustic field in order to find novel applications in bioanalytical and biomedical fields.

The basic principle of standing wave acoustic focusing is that, depending on the particle properties, particles will either focus to the pressure node or to the pressure anti-nodes when acted on by an acoustic standing wave between two reflective walls. For most particles, this focusing occurs at a very specific range of frequencies and voltages. However, we have found that microbubbles display fine-tunable acoustic focusing properties at varying frequencies (0.8 MHz – 5.0 MHz) and voltages (0 V – 40 V) within a microchannel. Experiments were performed using a custom-built square glass capillary microfluidic device with a piezo electric transducer (PZT) attached to the channel. Solutions of microbubbles in buffer solution were pumped through the microfluidic device via liquid ports, at which point they interact with the PZT’s ultrasound signal. The interaction results in a focusing phenomenon unlike solid particles wherein the microbubbles can be focused to controllable positions within the channel.

Since the lipid composition of microbubbles is easily modified, conjugation to target particles such as cells is facile. It then becomes possible to alter or increase the range of frequencies and voltages that the target particle will react to within the microfluidic channel. As a result, the target particles can be displaced and separated in a highly controllable manner from the bulk solution. The initial proof of concept experiment will investigate biotinylated microbubbles attached to avidinated polystyrene microbeads. Once this tunability concept is characterized, experiments will be performed using pathogens and rare cell types such as circulating tumor cells (CTCs).