A Transformative Technology Platform for Interrogating Airborne Adaptation of Respiratory Pathogens

气溶胶在大气中无处不在，其大小从汽车产生的纳米级微粒到云中直径与人的头发丝相似的较大水滴不等。污染颗粒不仅会导致发病率和死亡率的增加，而且还可以作为细菌和病毒的传播手段，促进疾病的传播。事实上，传染病是通过人体产生的气溶胶飞沫通过空气传播的，这些飞沫通过咳嗽和打喷嚏排出。这些事件造成了一些最致命的传染病，包括肺结核、严重急性呼吸系统综合症（萨斯）和细菌性脑膜炎，所有这些都对我们的社会产生重大影响。尽管病原体的空气传播带来了重大的健康和经济负担，但研究气溶胶中的细菌和病毒仍然具有挑战性，因为几乎没有测量技术可以探索空气传播过程中可能发生的活力和感染性的变化。在拟议的研究中，我们将开发一种新的仪器，用于探索影响细菌在空气中存活的过程。特别是，我们将建造和测试一种仪器，该仪器将允许悬浮和操纵含有已知数量细菌的空气中的气溶胶颗粒。例如，我们将开发一种方法来产生模拟我们咳嗽和打喷嚏的单个液滴，每个液滴包含已知数量的细菌。通过巧妙地操纵每个液滴，我们将能够在电场中捕获并悬浮它们任何时间。然后，我们将以受控的方式将液滴存款到含有合适条件的培养皿中，以允许任何存在的细菌生长。在空气中，我们将能够改变液滴所经历的环境的温度和湿度。我们还将它们暴露在光线（类似于阳光）和典型的大气化学物质（如臭氧）下。结合起来，这些能力将使我们能够模拟细菌在人与人之间移动时所经历的过程。因此，我们将能够测量不同的环境条件如何影响在不同时间点有多少细菌存活。一旦仪器已经建成并进行了测试，我们将研究一种细菌（脑膜炎奈瑟氏菌，也称为脑膜炎球菌），它会引起血液和大脑感染，但可以通过咳嗽和打喷嚏在人与人之间传播。我们将测量脑膜炎球菌在不同时间、温度和湿度下的空气传播存活率，条件代表冷湿或冷干环境，以模拟英国典型的冬季条件或非洲干旱季节典型的干热条件。这些情况代表了这两个地区发病率最高的季节。最后，我们将把联合收割机液滴捕获与一种令人兴奋的新仪器纳米线结合起来，纳米线可以测量细菌如何以某种方式变化，从而使它们或多或少地能够引起疾病。总之，测量细菌存活时间以及它们在我们体外如何变化的能力将有助于我们利用数学更好地模拟疾病传播的风险，并确定预防气溶胶（空气传播）传播的人与人之间感染的新方法。

Aerosols are everywhere in the atmosphere, ranging in size from the very small nanometre-sized particles produced by cars through to larger water droplets in clouds with diameters similar to that of a human hair. Not only can pollution particles lead to increased rates of morbidity and mortality, but they can also act as a means of transporting bacteria and viruses, facilitating disease transmission. Indeed, infectious diseases are spread by the airborne route through aerosol droplets produced by the human body and expelled through coughing and sneezing. Such events account for some of the deadliest infectious diseases, including tuberculosis (TB), severe acute respiratory syndrome (SARS) and bacterial meningitis, all of which have a major impact on our society. Despite the significant health and financial burdens that arise from the airborne transmission of pathogens, studying bacteria and viruses in the aerosol phase remains challenging as few measurement techniques exist to explore the changes in viability and infectivity that may occur during airborne transport. In the proposed research, we will develop a novel instrument for exploring the processes that affect how well bacteria survive when in airborne droplets. In particular, we will build and test an instrument that will allow the suspension and manipulation of aerosol particles in air containing a known number of bacteria. For example, we will develop an approach to generate individual droplets that mimic our coughs and sneezes, each containing a known number of bacteria. By subtly manipulating each droplet, we will be able to catch and levitate them in an electric field for any amount of time. We will then, in a controlled way, deposit the droplets into a dish containing suitable conditions to allow any bacteria present to grow. Whilst airborne, we will be able to change the temperature and humidity of the environment experienced by the droplets. We will also expose them to light (similar to sunlight) and also to typical atmospheric chemicals like ozone. Combined, these capabilities will allow us to simulate the processes the bacteria experience whilst moving from person-to-person. Thus, we will be able to measure how different environmental conditions influence how many bacteria remain alive at different time points. Once the instrument has been built and tested, we will study a bacterium (Neisseria meningitidis also known as meningococci) which causes blood and brain infections but can be spread from person to person by coughing and sneezing. We will measure the airborne survival of meningococci at different times, temperatures and humidities, with conditions representative of cold-wet or cold-dry environments to simulate winter day conditions typical of the UK, or hot-dry conditions typical of the Africa dry season. These conditions represent seasons when the disease rates are highest in both regions. Finally, we will combine droplet capture with an exciting new instrument, the NanoString, which can measure how bacteria change in ways which could make them more or less able to cause disease. Together, the capabilities to measure not only how long bacteria survive but how they change outside of our bodies will help us to use mathematics to better model risks of disease spread, and also to identify novel better means of preventing person-to-person infection by aerosol (airborne) transmission.