Scalable Manufacturing of Nanobubbles via Ultrasonic Shearing for Biomedicine

Research funded by this award aims towards a better understanding and control of the formation of tiny bubbles, known as nanobubbles. These nanobubbles are highly sensitive to pressure changes and can release their contents when exposed to sound waves. Although these ultrasound-responsive nanobubbles hold promise for delivering drugs or aiding in medical imaging, their production with nanometer size and uniform size distribution has been challenging. This award supports fundamental research to develop a new method, called ultrasonic shearing, to create uniform-sized nanobubbles that can be tuned for size and chemistry as needed. The method integrates ultrasonication and shearing using an impeller to achieve monodispersed nanobubbles. This advancement could lead to large-scale manufacturing of nanobubbles with applications in biomedicine, such as gene and drug delivery for diseases such as osteoporosis. Additionally, this technology could enhance wastewater treatment systems by improving processes like oxygen transfer and air flotation, thereby reducing pollution. The project also includes educational efforts to increase the understanding of scalable nanobubble manufacturing and their biomedical applications, particularly among women and underrepresented minority groups, aiming to contribute to both scientific progress and societal benefits as well as the development of a skilled workforce. Various nanobubble sizes exhibit distinct behaviors, yet understanding their synthesis remains limited due to the absence of an efficient manufacturing method allowing precise size and size distribution control. Furthermore, there is a lack of fundamental knowledge on the relationship between the processing parameters and the acoustic properties of nanobubbles. This research advances nanobubble manufacturing methods by investigating the ultrasonic shearing mechanism, employing a combination of computational modeling and experimental methodologies. The inherent energy dynamics in the manufacturing process is simulated by calculating ultrasonic shear energy and nanobubble surface energy. Through the empirical assessment of temperature shifts within the emulsion, a correlation is established between the droplet vaporization and energy derived from ultrasonic shearing. Integrating this model with the ultrasonic shearing method enables the development of systems capable of tailoring nanobubble size as a function of ultrasonic shearing, incorporating variables such as ultrasound intensity, shearing rate, and process duration. This technique can generate programmable nanobubbles with controlled cargo release mechanisms. Additionally, the research aims to identify nanobubble subpopulations with enhanced responsiveness to ultrasound using tissue-mimicking materials for medical imaging applications. Finally, the project explores the interplay between ultrasonic shearing, therapeutic-encapsulated nanobubbles, and cellular dynamics, particularly in osteoporosis, to uncover potential therapeutic approaches. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.