Bacterial cytometry for rapid antibiotic susceptibility testing

预计细菌对抗生素的耐药性（抗菌素耐药性- AMR）将成为导致死亡的主要原因，到2050年每年夺去1000万人的生命。目前，在欧洲，抗微生物药物耐药性的负担与流感、结核病和艾滋病毒的综合负担相似。一份英国政府关于抗菌素耐药性的报告（O’neill, 2016）确定了包括快速诊断在内的一些需求。这将促进强制性检测，以便适当地给予抗生素并减少抗菌素耐药性。这一研究项目将解决的挑战是传统检测的速度太慢（100小时），无法实现知情处方。本研究项目将研究暴露于抗生素的单个细菌的表型（可观察到的生物物理特征）反应，有许多不同的抗生素以不同的机制起作用-将开发检测方法来探索不同类别的抗生素和抗生素类别内的测试插值。将开发连续监测系统，以取代固定时间测量系统，研究生长动态和生物物理变化，进一步减少测量时间窗口。传感芯片目前的分析范围有限，因此将开发新的电子设备来增强测量，包括更高的频率来测量新的生物物理特性，包括细胞质和新的电极几何形状来测量形状变化。该项目还将开发样品制备分析，以实现对患者样品的直接测量，并使用基于微流体的方法对单个样品进行多种抗生素的多重暴露。

The resistance of bacteria to antibiotics (antimicrobial resistance - AMR) is predicted to be the primary cause of death and claim 10 million lives per year by 2050. Currently, within Europe the burden of AMR is similar to the combined burden of influenza, tuberculosis, and HIV. A UK Government report into AMR (O'Neill, 2016) identified a number of needs including rapid diagnostics. This would facilitate mandatory testing so that antibiotics can be given appropriately and reduce AMR. The challenge that this research project will address is the speed of conventional tests which are far too slow (>24 hours) to enable informed prescription. This research project will investigate phenotypic (observable biophysical characteristics) response of single bacteria exposed to antibiotics,There are many different antibiotics which act in different mechanisms - assays will be developed to explore different classes of antibiotic and test interpolation within antibiotic classes. A continuous monitoring system will be developed to replace the fixed-time measurement system and investigate the dynamics of growth and biophysical change to further reduce the measurement time window. The sensing chip is currently limited in analysis range, so new electronics will be developed to enhance the measurement including higher frequencies to measure new biophysical properties including the cytoplasm and new electrode geometries to measure shape changes. The project will also develop sample preparation assays to enable direct measurement from patient samples, and for multiplexed exposure of a single sample to multiple antibiotics using microfluidics-based approaches.