Molecularly Imprinted Heavy Metal-free Quantum Dots as Fluorescent Probes for Rapid and Accurate Detection of Viruses

最近，新出现的病毒如SARS-COV-2、寨卡病毒、猴痘和新的流感病毒株使新病毒感染的风险变得明显。需要及早和准确地发现病毒感染，以便进行适当治疗并预防严重的健康并发症。目前的检测，如实时聚合酶链式反应，需要很长的时间(~1-2天)，价格昂贵(对消费者来说是~GB 42)，并且需要高技能的人员。抗原检测(如新冠肺炎侧向血流检测)提供了快速(15-30分钟)和便携的分析；然而，它们的敏感度要低得多，可能不足以满足某些应用。该项目的目的是开发一种足够快速和准确的设备，供卫生专业人员诊断病毒疾病，并在适当的情况下为患者提供最适当的治疗和/或尽快将他们隔离。在这项提议中，将开发由半导体量子点(QD)纳米晶体和分子印迹聚合物(MIP)组成的荧光探针来检测唾液中的病毒样本。我们的目标是通过利用量子点的独特性质来实现这一目标：在溶液中的单分散性，高比表面积与体积比，用于结合测量的稳定的荧光，高的荧光量子产率(90%-100%)，以及与尺寸和形状相关的性质。我们将合成无毒、不含镉的量子点，并对其进行表面修饰，使其具有水溶性、致密性和稳定性。我们将把它们与特定结合病毒颗粒的分子印迹蛋白联系起来。MIPS通常被称为“塑料”抗体，可以与其靶标牢固而稳定地结合。一旦病毒颗粒与量子点-MIP接触，它们将与MIP结合，这将导致量子点通过为检测到的病毒产生独特的荧光信号来翻译结合相互作用。这些量子点将是纸条和横向流动装置等平台的理想选择。我们的目标是将它们用于微流控纸张分析装置的原型。这将涉及在纸张设备上创建微流控通道，并将量子点-MIP探针绑定到纸张表面，以便通过肉眼荧光检测病毒。拟议概念的多功能性和灵活性将确保传感器可以快速进行修改，以应对未来由其他传染性病原体引起的任何潜在突变或新的疫情。

Recently, the risks from new viral infections have been made evident by emerging viruses such as SARS-COV-2, Zika virus, monkeypox and new strains of influenza. Viral infections need to be detected early and accurately to allow appropriate treatment and prevent serious health complications. Current tests such as real-time polymerase chain reaction takes a long time (~1-2 days), are expensive (~£42 to the consumer) and require highly skilled personnel. Antigen tests (such as Covid-19 lateral flow tests) offer rapid (15-30 minutes) and portable analysis; however, they have a much lower level of sensitivity that may not be sufficient for some applications. The aim of this project is to develop a device that is sufficiently rapid and accurate enough for health professionals to diagnose viral diseases and give patients the most appropriate treatment and/or isolate them as quickly as possible if appropriate. In this proposal, fluorescent probes composed of semiconductor quantum dot (QD) nanocrystals with molecularly imprinted polymers (MIP) will be developed to detect viral samples in saliva. We aim to achieve this goal by exploiting the QDs' unique properties: monodispersity in solution, high surface area-to-volume ratio, stable fluorescence for binding measurements, high fluorescence quantum yield (90-100%), and size and shape-dependent properties. We will synthesize non-toxic QDs that are free from cadmium, and modify their surface to make them water-soluble, compact and stable. We will link them to MIPs that bind specifically to the viral particles. MIPs are often referred to as "plastic" antibodies and can bind strongly and stably to their targets. Once the viral particles come into contact with the QDs-MIPs, they will bind to the MIP, which will result in the QDs translating the binding interaction by generating a unique fluorescence signal for the detected virus. These QDs will be ideal for platforms such as paper strips and lateral flow devices. Our aim is to use them in a prototype microfluidic paper analytic device. This will involve creating microfluidic channels on the paper device and binding the QDs-MIP probes onto the paper surface to allow the virus to be detected fluorescently via the naked eye. The versatility and agility of the proposed concept will ensure that the sensor can be modified quickly to address any potential future mutations or new outbreaks caused by other infectious pathogens.