Acoustic Tweezers for Manipulation and Analysis of Cells

操纵细胞的能力在许多生物学应用中都是至关重要的，无论是分选、表型鉴定还是培养。由于细胞通常太小，不能用传统的机械方法处理，因此已经开发了各种操作技术，包括光学镊子、电磁镊子和声学镊子[1]。作为一种精确的、非接触的、无标记的、生物相容的操作方法，声波镊子与其他微操作技术相比具有一些独特的优势。虽然类似于光学镊子，但声波镊子可以施加更大的力，使它们能够操纵细胞、有机物，甚至整个微生物。这导致了声波镊子的一系列生物医学应用，包括细胞聚焦、分类和构图[2]。尽管最近引起了极大的关注，但声波镊子的一些方面要么知之甚少，要么还没有被充分挖掘出来。该项目旨在结合数学建模和实验创新，以声波镊子的原理和应用为基础，属于EPSRC工程和数学科学研究领域。特别是，它将集中在细胞的特征，微泳者，以及在声波捕获过程中涉及的流体流动。通过探索规定的声学作用力和颗粒之间的流体动力相互作用的组合，我希望能够深入了解细胞或有机体的属性，以及更好地理解鞭毛跳动或纤毛运动等力学。这有可能在声能合成微泳者或生物混合设计的创造中继续下去，甚至在计算和自动选择机制方面也是如此。除了声学设备的物理研究外，本博士学位还旨在通过使用快速成型工艺来降低微流控设备制造的门槛。大多数微流控设备是使用平版印刷技术制造的，这通常需要广泛的培训和洁净室。同样，许多声学谐振器设备是由硅或玻璃的湿法蚀刻制成的，这是另一种需要洁净室设施的昂贵工艺。通过在整个博士学位期间采用3D打印和激光切割等快速成型方法，我的目标是改进工艺，以廉价而快速地制造声流控设备。这将大大提高声钳作为临床点诊断工具的适用性。因此，本项目寻求对声学设备的理解和应用方面的创新和提高。[1]A.Martinez-Rivas，G.K.González-Quijano，S.Proa-Coronado，C.Séverac和E.Dague，《用于生物医学应用的微图案化和细胞操纵的微型机器方法》，DOI：10.3390/mi8120347.[2]B.W.Drinkwater，《声学镊子-装置、力和生物医学应用的视角》，《应用物理通讯》，第117卷，第18期，2020年11月，180501页。DOI：10.1063/5.0028443。

The ability to manipulate cells is vital in many biological applications, be it sorting, phenotyping, or culturing. As cells are typically too small to handle with conventional mechanical means, a variety of manipulation techniques have been developed including optical tweezers, electromagnetic tweezers, and acoustic tweezers [1]. As a precise, non-contact, label-free and biocompatible manipulation method, acoustic tweezers possess some unique advantages over other micromanipulation techniques. While similar to optical tweezers, the increased force that can be exerted by acoustic tweezers allows them to manipulate cells, organoids, and even whole microorganisms. This has led to an array of biomedical applications for acoustic tweezers including cell focussing, sorting and patterning [2].Despite a great amount of recent attention, there are still aspects of acoustic tweezers that are either poorly understood or have not yet been explored to their fullest potential. This project aims to build on the principles and applications of acoustic tweezers with a combination of mathematical modelling and experimental innovation and falls within the EPSRC engineering and mathematical sciences research areas. In particular, it will focus on the characterisation of cells, microswimmers, and the fluid flow involved in the acoustic trapping process. By exploring the combination of prescribed acoustic forces and hydrodynamic interactions between particles, I hope to gain insight into cell or organism properties as well as better understand mechanics such as flagellar beating or cilia movement. This has the potential to follow on to the creation of acoustically powered synthetic microswimmers or biohybrid designs, and even to computation and automated selection mechanisms. Investigating the hydrodynamic interactions of particles undergoing acoustic trapping also has the ability to enable novel methods for calibration of acoustofluidic devices and achieve a better understanding of some of the less well understood aspects of the acoustic radiation force.Alongside research into the physics of acoustic devices, this PhD also aims to lower the barrier to entry into the making of microfluidic devices through the use of rapid prototyping processes. The majority of microfluidic devices are manufactured using lithographic techniques that often require extensive training and a clean room. Similarly, many acoustic resonator devices are constructed from wet etching of silicon or glass, another expensive process requiring clean room facilities. By employing rapid prototyping methods such as 3D printing and laser cutting throughout the PhD, I aim to refine processes for cheap and rapid manufacturing of acoustofluidic devices. This would greatly increase the suitability for acoustic tweezers as a tool point-of-care diagnostics.Therefore, this project seeks to innovate and improve on the understanding and application of acoustic devices. Through new approaches to manufacturing, analytical, and experimental techniques, I aim to leverage the exciting technology of acoustic tweezers to new biomedical applications.[1] A. Martinez-Rivas, G. K. González-Quijano, S. Proa-Coronado, C. Séverac, and E. Dague, "micromachines Methods of Micropatterning and Manipulation of Cells for Biomedical Applications", doi: 10.3390/mi8120347.[2] B. W. Drinkwater, "A Perspective on acoustical tweezers-devices, forces, and biomedical applications," Applied Physics Letters, vol. 117, no. 18, p. 180501, Nov. 2020, doi: 10.1063/5.0028443.