Development of an optical-based rapid antimicrobial susceptibility test for clinical applications.

博士项目是跨学科努力的一部分，旨在开发一种快速抗菌素敏感性测试，以减少抗菌素耐药性的影响。具体来说，该项目将研究使用倏逝场照明检测细胞内波动的替代方法。众所周知，这些波动与细胞代谢活动有关，它们可用于在接触抗微生物药物后立即评估细胞活力。我们实验室最近开发的仪器首次在不需要荧光标记的情况下检测到这些细胞内波动，但该装置不适合临床环境，需要更紧凑和用户友好的替代方案。该项目将要求熟悉细胞表征的标准生物物理方法。它将包括共聚焦显微镜和活细菌细胞原子力显微镜的培训，以及开发新的化学功能化方案和微图案沉积，以简化细胞捕获步骤。光学模拟软件（如Lumerical）的使用将支持该方法的替代实现的开发和测试。该项目的最终目标是开发一种可以快速评估细菌样本对抗菌药物敏感性的设备的工作原型。在此过程中，该项目应刺激创造新的检测方法，细菌细胞和倏逝场之间的光相互作用。这些新方法的影响可能远远超出抗菌敏感性，并在细胞生物学和癌症研究中找到更广泛的用途。该项目属于EPSRC医疗保健技术主题。

The PhD project is part of an interdisciplinary effort to develop a rapid antimicrobial susceptibility test to reduce the impact of antimicrobial resistance. Specifically, the project will study alternative ways of detecting intracellular fluctuations using an evanescent field illumination. It is known that these fluctuations are related to cellular metabolic activity, and they can be used to assess cellular viability immediately after exposure to an antimicrobial. The instrument recently developed in our laboratory has detected for the first time these intracellular fluctuations without the need for fluorescence tagging, but the setup is not suitable for a clinical setting, and a more compact and user-friendly alternative is needed. The project will require becoming familiar with standard biophysical methods for cellular characterisation. It will include training in confocal microscopy and atomic force microscopy of living bacterial cell, as well as the development of new chemical functionalisation protocols and micropatterning deposition to simplify the cell capturing step. The use of optical simulation software like Lumerical will support the development and testing of alternative implementations of the method. The final aim of the project is to develop a working prototype of a device that can rapidly assess the susceptibility of a bacterial sample to an antimicrobial. In the process, the project should stimulate the creation of new detection methods of the optical interaction between bacterial cells and evanescent fields. These new methods could have repercussions far beyond antimicrobial susceptibility and find more general uses in cell biology and cancer research. The project falls within the EPSRC Healthcare technologies theme.