Acoustic Trapping of Small Biological Particles

描述（由申请人提供）：拟议的项目旨在开发一种用于操纵包括细胞在内的小生物颗粒的新型超声方法，称为声镊。提出了声镊力标定方法，介绍了粘滞阻力法和功率谱法两种声镊力标定方法，并对两种方法的标定结果进行了比较，以检验两种方法的准确性。为了找到更多样化的应用，定义各种捕获模式是至关重要的，通常，瑞利政权和固体弹性颗粒。基于我们对这两种模式的实验研究结果，将通过考虑弹性材料中的瑞利散射以及剪切波的产生来进行理论分析。为了操纵声阱中的细胞水平颗粒，将设计和制造超高频聚焦换能器（>100 MHz）。通过溅射压电元件，例如，在弯曲衬底上的ZnO，或使用薄/厚PZT膜的材料。结合上述结果，将寻求声镊的生物医学体外应用，包括红细胞、白色血细胞-内皮细胞和载药脂球-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小生物粒子提供一种新的替代方案，这种方法产生的力比光镊更强，而且在控制活细胞时更安全，不会造成任何物理损伤。 公共卫生相关性：该项目的目标是开发一种新型的超声方法来操纵包括细胞在内的小生物颗粒，称为声镊。之所以如此命名，是因为所涉及的物理原理与光镊相同。由R21资助的理论分析和实验的初步结果表明，脂质颗粒的横向捕获是可能的。在当前的R 01应用中，提出了四个具体目标来进一步开发该方法。他们将针对声学镊子现象进行彻底的基本调查，并与知名的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）声镊的力校准，（2）其他声捕获模式的定义，（3）超高频声镊（>100 MHz）的开发，以及（4）体外细胞研究的生物医学应用的探索。如果要使用声学镊子进行定量测量，则必须执行第1和第2个特定目标。第三和第四个具体目标将允许声学镊子用于研究小到红细胞的生物颗粒，并与这些领域的研究人员合作，在红细胞-红细胞相互作用和白色细胞-内皮细胞相互作用的定量体外测量中应用。 该项目的成功完成将意味着一种新的工具的可用性，用于操纵小的生物粒子，产生比光镊更高的捕获力。当可能存在光损伤的危险时，它将补充光学镊子，因为产生类似大小的力所需的声学镊子的能级小于光学镊子。

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.