Advanced Diagnostics using Phononics

这项研究将在格拉斯哥大学工程学院进行，将为液体处理奠定一个全新的范例。它涉及控制流体和微制造结构之间的机械相互作用，与声波。尽管它可能对广泛的领域（例如物理和化学）产生影响，但我在该奖学金中的重点将是通过在低成本便携式设备上整合复杂的生物样品处理，在发展中国家和发达国家的偏远地区实现先进的诊断。声波携带的机械能已被成功地用于驱动多种液体功能。特别是，表面声波（SAW）在压电表面上传播，使用电子产品中常见的换能器，可以在液体中折射，导致再循环流动。我开创并改进了一种技术来控制SAW及其与液体和颗粒的相互作用，从而实现更复杂的操作。新平台基于微制造的一次性声子晶格，以频率相关的方式散射或反射声波。这些结构以类似于全息图塑造光的方式塑造声波。当全息图基于折射率时，这种结构依赖于机械对比度。全息图的几何设计提供了不同频率的颜色；在这里，声子晶格几何决定了声音散射的频率。不同频率的超声波与不同的声子结构相互作用，赋予不同的功能，提供不同诊断过程（样品处理，细胞分离，检测）的“工具箱”，当它们组合在一起时，形成一个流体回路，一个完整的诊断分析。与医疗点设备中使用的已建立的微流体系统相反，该系统依赖于通过通道的流动在通道内的不同位置执行不同的功能，我将设计，制造，表征和使用新的声子晶格，在固定样品上结合频域的不同功能。参与这项研究的其他人员包括Miles Padgett教授（物理学院）、Andy Waters教授（分子寄生虫学欢迎中心）、Andrew Winters博士（性健康和艾滋病毒医学顾问，NHS大格拉斯哥和克莱德桑迪福德诊所联合临床主任）和Mhairi Copland博士（Paul O'Gorman白血病研究中心和Beatson癌症研究中心）。我的研究将在诊断和传感方面有三个潜在的结果，即开发新的微系统技术：1。耐药疟疾诊断。我将开发语音几何来进行完整的基于核酸的检测，包括样品制备，扩增和全血检测。这些将用低成本材料（例如玻璃、复合材料）制造，并可能改变发展中国家的疟疾诊断。与英国国家医疗服务体系合作，对一组性传播疾病进行多重检测。执行复杂样品制备的能力有可能在专家系统中集成多路分析，而不是以病原体为中心的诊断测试，该测试具有分析一组症状的能力，这是诊断的决定性转变。白血病细胞侵袭性的分层。我将探索如何将声学探测到的细胞机械信息与细胞膜上的电信息相结合，从而实现对细胞的多维分析。这项研究将有可能创造出在任何地方进行诊断的设备。

The research, which will be carried out in the School of Engineering at the University of Glasgow, will underpin a completely new paradigm in the handling of liquids. It involves the control of the mechanical interactions between fluids and microfabricated structures, with acoustic waves. Notwithstanding its potential impact on a wide range of areas (e.g. physics and chemistry), my focus in this Fellowship will be in enabling advanced diagnostics both in remote areas in developing countries and in the developed world, by integrating complex biological sample processing on low cost portable devices.Acoustic waves carry a mechanical energy that has been successfully used to actuate a wide range of liquid functions. In particular, Surface Acoustic Waves (SAW) propagated on piezoelectric surfaces, using transducers commonly found in electronics, can refract in a liquid, leading to recirculation flows.I have pioneered and enhanced a technique to control SAW and their interactions with the liquid and particles, enabling more complex manipulations. The new platform is based on micromanufactured, disposable phononic lattices, that scatter or reflect the acoustic waves in a frequency dependent manner. These structures shape the acoustic waves, in a manner analogous to that of holograms shaping light.The structures rely on mechanical contrast when holograms are based on refractive index. Geometric aspects of the hologram's design provide colours of different frequencies; here, the phononic lattice geometry determines the frequency at which the sound is scattered. The different frequencies of ultrasound interact with different phononic structures to give different functions, providing a "tool-box" of different diagnostic processes (sample processing, cell separation, detection), which, when combined, form a fluidic circuit, a complete diagnostic assay.Contrary to the established microfluidic systems used in point-of-care devices, which rely on flow through channels to carry out different functions at different positions within the channels, I will design, fabricate, characterise and use new phononic lattices to combine different functions in the frequency domain, on a stationary sample. Others involved in the research include Professor Miles Padgett (School of Physics), Professor Andy Waters (Welcome Centre for Molecular Parasitology), Dr Andrew Winters (Consultant in Sexual Health & HIV Medicine and Joint Clinical Director at The Sandyford Clinic, NHS Greater Glasgow and Clyde) and Dr Mhairi Copland (Paul O'Gorman Leukaemia Research Centre and the Beatson Cancer Research.My research will have three potential outcomes in diagnostics and sensing, namely the development of new Microsystems technologies for:1. Drug resistant malaria diagnostics. I will develop phononic geometries to carry out a complete nucleic acid based test, including sample preparation, amplification, and detection in whole blood. These will be fabricated in low cost materials (e.g. glass, composites) and could transform malaria diagnostics in the Developing World.2. Multiplexed detection of a panel of sexually transmitted diseases, working with the NHS. The ability to perform complex sample preparation has the potential to integrate multiplexed analysis in an expert system, where instead of a diagnostic test centered around a pathogen, the test has the capability to analyse a set of symptoms, a decisive shift in diagnostics.3. Stratification of leukemia cells' aggressiveness. I will explore how the combination of the cells mechanical information probed using acoustics, and coupled with electrical information on cell membranes, could enable a multidimensional analysis of cells.This research will have the potential to create devices to carry out diagnostics anywhere.