Acoustic Tweezers for Manipulation and Analysis of Cells

操纵细胞的能力在许多生物学应用中至关重要，无论是分选、表型分析还是培养。由于细胞通常太小而不能用常规机械手段处理，因此已经开发了各种操纵技术，包括光学镊子、电磁镊子和声学镊子[1]。声镊作为一种精确、非接触、无标记、生物相容性好的微操作技术，具有其他微操作技术所不能比拟的优点。虽然类似于光学镊子，但声学镊子可以施加更大的力，使它们能够操纵细胞、类器官甚至整个微生物。这导致了声镊的一系列生物医学应用，包括细胞聚焦，分选和图案化[2]。尽管最近受到了大量的关注，但仍然有一些方面的声镊要么知之甚少，要么尚未被充分发掘其潜力。该项目旨在建立在声学镊子的原理和应用的基础上，结合数学建模和实验创新，并属于EPSRC工程和数学科学研究领域的福尔斯。特别是，它将集中在表征细胞，microswimmer，并在声学捕获过程中涉及的流体流动。通过探索规定的声学力和粒子之间的流体动力学相互作用的组合，我希望能够深入了解细胞或生物体的特性，并更好地理解鞭毛跳动或纤毛运动等力学。这有可能继续创造声学动力合成微型游泳者或生物混合设计，甚至计算和自动选择机制。研究经历声捕获的颗粒的流体动力学相互作用也能够实现用于校准声流体装置的新方法，并更好地理解声辐射力的一些不太好理解的方面。除了研究声学装置的物理学，这个博士学位也旨在通过使用快速原型制作工艺来降低微流体装置的制造门槛。大多数微流体设备是使用光刻技术制造的，这通常需要大量的培训和洁净室。类似地，许多声谐振器装置由硅或玻璃的湿法蚀刻构造，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快速原型制作方法，如3D打印和激光切割，我的目标是改进声学流体设备的廉价快速制造工艺。这将大大增加声学镊子作为床旁诊断工具的适用性。因此，本项目旨在创新和提高对声学设备的理解和应用。通过新的方法来制造，分析和实验技术，我的目标是利用令人兴奋的技术声镊新的生物医学应用。[1]A.马丁内斯-里瓦斯湾K. González-Quijano，S.普罗阿-科罗纳多角Séverac和E. Dague，“微加工方法的微图案化和操纵细胞的生物医学应用”，doi：10.3390/mi 8120347。[2]B。W. Drinkwater，“声学镊子-设备，力和生物医学应用的观点”，应用物理快报，第117卷，第18号，第180501页，2020年11月，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.