Multi-analyte Disease Diagnosis using MEMS Detection

该项目将开发一个原型，便携式医疗诊断平台，用于同时检测多种疾病或健康指标，基于纳米机械悬臂传感器阵列，使用并行光学读出。这将使卫生专业人员有能力在早期干预、时间紧迫的治疗方面产生重大影响（例如在急诊室，由辅助医务人员进行），在资源贫乏的环境中（例如发展中国家）产生重大影响。悬臂梁传感器平台已经在诊断和监测复杂疾病（如癌症）的更广泛领域得到了证明，最近还被用作研究传染病抗生素耐药性的平台。这些传感器还没有被普遍采用，因为严重的困难，在执行一个大的传感器阵列的并行读出，限制在大批量，低成本的悬臂梁传感器的制造，以及在特定的生物标记物结合受体层的阵列中的单个传感器的涂层的困难。我们的联盟拥有针对所有这三个瓶颈的技术解决方案，将首次实现这种诊断技术的全部潜力。实现这一目标的核心是根据STFC以前资助的用于空间应用的低成本聚合物微悬臂梁反射器阵列的工作开发定制传感器。通过用受体层高度特异性地涂覆各个悬臂梁，可以在非常低的样品体积（微升）中以非常高的灵敏度检测目标生物标志物，这是由于在生物标志物附着到受体层时柔性聚合物悬臂梁传感器的诱导弯曲。剑桥最近开发了一种基于干涉测量的光学方法，用于真实的同时阅读任意数量的杠杆的纳米位移，而不需要精确的光学对准。这些技术可以合并以形成手持式诊断设备，该设备具有鲁棒的、高灵敏度的传感器和操作简单的读出技术，具有低成本的电子和光学组件，并且在其对任何数量的分析物的感测响应方面高度灵活。

The project will develop a prototype, portable medical-diagnostic platform for the simultaneous detection of multiple disease or health indicators, based on nano-mechanical cantilever sensor arrays using a parallel optical readout. This will provide health professionals with the capability to have a significant impact in early-intervention, time-critical treatment (e.g. in emergency departments, by paramedics), with a big impact in resource-poor environments (e.g. developing countries). Cantilever-sensor platforms have already been demonstrated in the wider field for the diagnosis and monitoring of complex diseases, such as cancer, and more recently as a platform for studying antibiotic drug resistance of infectious disease. These sensors have not been universally adopted so far because of severe difficulties in performing a parallel readout of large sensor arrays, limitations in the fabrication of high-volume, low-cost cantilever sensors, and difficulties in the coating of individual sensors in arrays with specific biomarker-binding receptor layers. Our consortium has technical solutions for all these three bottlenecks that will allow for the full potential of this diagnostic technology to be realised for the first time. Central to this realisation is the development of customised sensors based on previous STFC-funded work on low-cost polymer-based microcantilever reflector arrays for space applications. Through highly specific coating of individual cantilevers with receptor layers, a target biomarker can be detected in very low sample volume (microlitres) with very high sensitivity due to the induced bending of the flexible polymer cantilever sensors upon attachment of the biomarker to the receptor layers. Cambridge have recently developed an optical method, based on interferometry, for reading out nanometre displacements of an arbitrary number of cantilevers simultaneously and in real time, without the need for precise optical alignment. These technologies can be merged to form a hand-held diagnostic device with robust, highly sensitive sensors and a read-out technique that is simple to operate, has low-cost electronic and optical components, and is highly flexible in its sensing response to any number of analytes.