Scalable Manufacturing of Nanobubbles via Ultrasonic Shearing for Biomedicine

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高度敏感，暴露在声波中时可以释放其内容物。尽管这些超声响应型纳米气泡有望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，以开发一种名为超声波剪切的新方法，以创建尺寸均匀的纳米气泡，该气泡可以根据需要的大小和化学成分进行调整。该方法利用叶轮将超声作用和剪切作用结合在一起，获得了单分散的纳米气泡。这一进展可能导致纳米气泡的大规模制造，并将其应用于生物医学，如治疗骨质疏松症等疾病的基因和药物输送。此外，这项技术还可以通过改进氧转移和气浮等工艺来增强废水处理系统，从而减少污染。该项目还包括教育努力，以增加对可伸缩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利益以及熟练劳动力的发展做出贡献。各种纳米气泡尺寸表现出不同的行为，但由于缺乏允许精确控制尺寸和尺寸分布的有效制造方法，对其合成的了解仍然有限。此外，对纳米气泡的工艺参数和声学特性之间的关系缺乏基本知识。本研究通过研究超声剪切机理，采用计算模拟和实验相结合的方法，发展了纳米气泡的制备方法。通过对超声剪切能和纳米气泡表面能的计算，模拟了加工过程中的固有能量动态。通过对乳状液内部温度变化的经验评估，建立了液滴汽化与超声剪切能量之间的关系。将该模型与超声剪切方法相结合，能够开发出能够根据超声剪切的函数来定制纳米气泡大小的系统，该系统结合了诸如超声强度、剪切速率和过程持续时间等变量。这项技术可以产生具有受控货物释放机制的可编程纳米气泡。此外，这项研究的目的是利用医学成像应用中的组织模拟材料来识别对超声波具有增强响应性的纳米气泡亚群。最后，该项目探索超声波剪切、治疗性包裹的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NSF的法定使命，并通过使用基金会的智力优势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.