Acoustic Trapping of Small Biological Particles

描述(由申请人提供)：该项目旨在开发一种新的超声波方法，用于处理包括细胞在内的小生物颗粒，称为声波镊子。在该方案中，提出了声镊力的标定方法，并介绍了粘性阻力和功率谱分析两种方法，并将它们的结果进行了比较，以检验这两种方法的准确性。为了找到更广泛的应用，定义各种捕获模式是至关重要的，通常是瑞利体系和固体弹性粒子。基于这两种模式的实验结果，我们将在考虑弹性材料中瑞利散射和剪切波产生的基础上对其进行理论分析。为了在声学捕获器中操纵细胞水平的粒子，将设计和制造超高频聚焦换能器(&gt；100 MHz)。通过溅射压电元件，例如在弯曲的衬底上溅射氧化锌，或者使用薄/厚的PZT薄膜材料，可以实现紧密聚焦。然后，结合上述结果，将寻求声波镊子的体外生物医学应用，包括红细胞、白细胞-内皮细胞和携带药物的脂球-癌细胞的体外细胞相互作用研究。该项目的成功完成将为操纵微小的生物颗粒提供一种新的选择，这种颗粒产生的力量比光学镊子产生的力量更大，而且在不造成任何物理损害的情况下控制活细胞更安全。 与公共卫生相关：拟议项目的目标是开发一种新的超声波方法，用于操作包括细胞在内的小生物颗粒，称为声波镊子。之所以这样命名，是因为涉及到的物理原理与光学镊子完全相同。由R21拨款支持的理论分析和实验的初步结果表明，横向捕获脂质颗粒是可能的。在目前的R01应用中，提出了进一步发展该方法的四个具体目标。他们将致力于对声波镊子现象进行彻底的基础调查，并与知名研究人员合作探索其生物医学应用，这些研究人员要么以前有光学镊子的经验，要么需要利用这项技术。具体目标是：(1)声波镊子的力校准，(2)其他声波捕获模式的定义，(3)超高频声波镊子的开发(&gt；100 MHz)，以及(4)探索体外细胞研究的生物医学应用。如果要使用声学镊子进行定量测量，则必须实现第一个和第二个特定目标。第三个和第四个具体目标将允许声波镊子用于研究小到红细胞的生物颗粒，并与这些领域的知名研究人员合作，在体外定量测量红细胞-红细胞相互作用和白细胞-内皮细胞相互作用方面的潜在应用。该项目的成功完成将意味着可以使用一种新的工具来操纵微小的生物颗粒，这种颗粒产生的捕获力比光学镊子产生的捕获力更大。当可能存在光损伤的危险时，它将补充光学镊子，因为产生类似强度的力所需的声波镊子的能级比光学镊子小。

DESCRIPTION (provided by applicant): The proposed project is aimed to develop a novel ultrasonic approach for manipulating small biological particles including cells, termed acoustic tweezer. In the proposal, the force calibration method of acoustic tweezers is presented and two methods, using such as viscous drag force and power spectrum analysis, are described, and their results will be compared to check the accuracy of both approaches. To find more diverse applications, it is crucial to define various trapping modes, typically, of Rayleigh regime and solid elastic particles. Based on our experimental findings of both modes, its theoretical analysis will be carried out by considering Rayleigh scatterings as well as shear wave generation in elastic materials. In order to manipulate cellular level particles in acoustic traps, ultra-high frequency focused transducers (>100 MHz) will be designed and fabricated. Tight focusing will be achieved by either sputtering piezoelements, e.g., ZnO on a curved substrate, or using materials of thin/thick PZT films. Biomedical in-vitro applications of acoustic tweezers will then be sought, combined with the aforementioned results, and that includes in-vitro cellular interaction study of red blood cells, white blood cell-endothelial cells, and drug-carrying lipospheres-cancer cells. Successful completion of the project would provide a new alternative for manipulating small biological particles that produces stronger forces than those from optical tweezers, and is yet safer to control living cells without causing any physical damage. PUBLIC HEALTH RELEVANCE: The objective of the proposed project is to develop a novel ultrasonic approach for manipulating small biological particles including cells, termed acoustic tweezer. It is so named because the physical principles involved are identical to optical tweezers. Preliminary results from theoretical analyses and experiments supported by a R21 grant have shown that lateral trapping of lipid particles is possible. In the present R01 application, four specific aims are proposed to further develop the approach. They will be directed at a thorough fundamental investigation of the acoustic tweezer phenomenon and at exploring its biomedical applications in collaboration with well-known investigators, who have either previous experience with optical tweezers or a need to utilize this technology. The specific aims are (1) force calibration of acoustic tweezers, (2) definition of other acoustic trapping modes, (3) development of ultra-high frequency acoustic tweezers (>100 MHz), and (4) exploration of biomedical applications for in-vitro cellular study. The 1st and 2nd specific aims must be carried out if the acoustic tweezer is to be utilized for quantitative measurements. The 3rd and 4th specific aim would allow the acoustic tweezer to be used for studying biological particles as small as red blood cells and for potential applications in quantitative in-vitro measurements of red cell-red cell interaction and white cell-endothelial cell interaction in collaboration with established investigators in these areas. Successful completion of the project would mean the availability of a new tool for manipulating small biological particles that yields trapping forces higher than those from optical tweezers. It would complement optical tweezers when there may be the danger of photodamage since the energy level of acoustic tweezers needed to produce similar magnitude of forces is smaller than optical tweezers.