Scalable Manufacturing of Nanobubbles via Ultrasonic Shearing for Biomedicine

由该奖项资助的研究旨在更好地理解和控制被称为纳米气泡的微小气泡的形成。这些纳米气泡对压力变化非常敏感，当暴露在声波中时可以释放出它们的内容物。尽管这些超声响应的纳米气泡有望用于输送药物或辅助医学成像，但它们的纳米尺寸和均匀尺寸分布的生产一直具有挑战性。该奖项支持基础研究，以开发一种称为超声波剪切的新方法，以产生均匀大小的纳米气泡，可以根据需要调整大小和化学性质。该方法将超声和剪切结合在一起，利用叶轮实现单分散的纳米气泡。这一进展可能导致纳米气泡的大规模制造，并应用于生物医学，例如骨质疏松症等疾病的基因和药物输送。此外，这项技术可以通过改善氧气转移和空气浮选等过程来改善废水处理系统，从而减少污染。该项目还包括教育工作，以增加对可扩展纳米气泡制造及其生物医学应用的理解，特别是在妇女和代表性不足的少数群体中，旨在为科学进步和社会效益以及熟练劳动力的发展做出贡献。不同尺寸的纳米气泡表现出不同的行为，但由于缺乏有效的制造方法来精确控制尺寸和尺寸分布，对其合成的理解仍然有限。此外，对于纳米气泡的加工参数与声学特性之间的关系，目前还缺乏基本的认识。本研究通过研究超声剪切机理，采用计算建模和实验相结合的方法来推进纳米气泡的制造方法。通过计算超声剪切能和纳米气泡表面能，模拟了纳米气泡在制造过程中的内在能量动力学。通过对乳化液内部温度变化的经验评估，建立了液滴汽化与超声剪切产生的能量之间的相关性。将该模型与超声剪切方法相结合，可以开发出能够根据超声剪切来调整纳米气泡尺寸的系统，其中包括超声强度、剪切速率和过程持续时间等变量。该技术可以产生可编程的纳米气泡，并具有受控的货物释放机制。此外，该研究旨在利用组织模拟材料识别对超声反应增强的纳米气泡亚群，用于医学成像应用。最后，该项目探讨了超声剪切、治疗封装纳米气泡和细胞动力学之间的相互作用，特别是在骨质疏松症中，以发现潜在的治疗方法。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.