In medical imaging applications, gas-filled microbubbles stabilized with a surfactant or a polymer coating are routinely used as ultrasound contrast agents due to their ability to significantly enhance the ultrasound backscatter signal from blood. Increasingly, these microbubbles are being used as drug or gene delivery vehicles as they allow for targeted cell therapy and improved cell permeability and hence drug absorption. However, the acoustic response and hence, the clinical utility of these microbubbles is highly dependent on the microbubbles’ physical characteristics and the mechanical properties of its coating layer. In turn, these physical and mechanical properties are dependent upon the manufacturing process of these microbubbles.
In general, microbubbles are fabricated with standard emulsification methods like sonification. This method, however, produces microbubbles which are highly heterogeneous; with different sizes, surface properties, stability or dynamic response and drug loading properties. On the other hand, fabrication with microfluidic devices produces microbubbles with highly uniform sizes. Yet, microfluidic devices suffer from low production rates, short device life time and are lacking in control over the surface properties of these microbubbles. Hence, there is a need for an improved system in controlling the properties of microbubbles during fabrication to maximize their clinical effectiveness.
In this technology, a microfluidic-sonication device is developed which allows for the generation of highly uniform microbubbles. With this device, the properties of the physical environment where microbubble formation occurs can be highly controlled. This ensures reproducible manufacturing of microbubbles of more uniform sizes. At the same time, other properties of these microbubbles such as size, distribution, concentration and physical properties could be fine-tuned for enhanced microbubble stability and acoustic response.
This technology integrates current technology of sonication together with microfluidics to develop a system which address the limitations of current manufacturing techniques such as emulsification and conventional microfluidics. A prototype has been developed and highly stable microbubbles with very narrow size distributions can be fabricated with a high throughput (approximately 1 million microbubbles per second). Furthermore, these microbubbles can be customized for various applications; either via surface functionalization or incorporating nanoparticles for enhanced acoustic response in medical imaging.
This technology allows for the fabrication of highly uniform microbubbles which can be used in various applications:
With its advantages of safety, low cost and easy access compared with conventional medical imaging techniques, ultrasound imaging is one of the most common diagnostic modality in the clinical setting. However, the specificity and sensitivity of this imaging technique is limited by the low contrast differences between human tissue and blood. This limitation can be mitigated with the use of gas-filled targeted microbubbles. In addition to being a superior contrast agent, microbubbles can also be used as gene or drug delivery vehicles for therapeutic applications. With multiple applications not limited to only the medical and pharmaceutical industry, the global market for microbubbles is expected to grow at a CAGR of 25.2% to reach USD 1,584.5 million by 2024.