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新的超声方法来操纵包括细胞在内的小生物颗粒，称为声镊子。本文提出了声镊的力标定方法，并介绍了粘滞阻力法和功率谱法两种方法的标定结果，比较了两种方法的精度。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，通常是瑞利模式和固体弹性颗粒。基于我们对两种模式的实验结果，我们将考虑弹性材料中的瑞利散射和剪切波的产生，对其进行理论分析。为了在声阱中操纵细胞级粒子，将设计和制造超高频聚焦换能器（>100 MHz）。紧密聚焦可以通过溅射压电元件（例如，在弯曲的衬底上溅射ZnO）或使用薄/厚PZT薄膜材料来实现。然后，结合上述结果，将寻求声镊子的生物医学体外应用，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小生物粒子提供一种新的选择，这种选择产生的力比光镊产生的力更强，而且在控制活细胞时更安全，不会造成任何物理损伤。

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.