Binding-Induced DNA Assembly and Novel Applications to Ultrasensitive Detection of Proteins

癌症是加拿大男性和女性发病率和死亡率的主要原因。早期发现癌症虽然仍是局部和可治愈的，但有望不仅降低总体癌症死亡率，而且还能降低发病率和经济负担。开发基于生物标记物(生物状态指标)的癌症筛查工具是在癌症早期阶段识别癌症的最有前途的方法之一。早期癌症检测需要高度敏感和特定的技术，进一步实现对生物标志物的快速、可重复性、成本效益和高通量检测。尽管蛋白质是临床上使用的大多数癌症生物标志物，但几乎没有一种可用的蛋白质检测技术满足所有这些要求。为了满足蛋白质检测用于癌症早期检测的需求，我提议开发一个通用工具箱，包括两种具有互补行为的新型均相分析。第一种类型的分析将被开发成能够检测到少至100个生物标记物分子，这对于检测早期癌症阶段存在的超低水平的生物标记物非常重要。将开发第二种检测方法，以便能够在患者护理地点或附近检测生物标记物，从而能够方便和立即地向患者提供检测。为了发展这些分析，我提出了一个有吸引力的策略，称为结合诱导DNA组装(BINDA)。宾达赋予这些检测方法一些吸引人的特点，包括高灵敏度和特异性，易于操作，以及在单管中进行检测。这项研究计划将有助于癌症早期检测的技术要求和用于均相分析的生物分析化学的基本原理。

Cancer is the leading cause of morbidity and mortality in both Canadian men and women. Early detection of cancer while still localized and curable promises to reduce not only overall cancer mortality but also morbidity and economic burden. Developing tools for cancer screening based on biomarkers (indicators of biological states) represents one of the most promising approaches to identification of cancer at its early stages. Early cancer detection requires highly sensitive and specific technologies that furthermore enable rapid, reproducible, cost-effective, and high-throughput detection of biomarkers. Almost none of the available technologies for protein detection meet all of these requirements, even though proteins account for the majority of cancer biomarkers in clinical use. To fulfill the demands of protein detection for early cancer detection, I propose to develop a versatile toolbox including two types of novel homogeneous assays with complementary behaviors. The first type of assays will be developed to enable detection of as few as a hundred biomarker molecules, which is of great importance for detection of biomarkers present at ultra-low levels at early cancer stages. The second type of assays will be developed to enable detection of biomarkers at or near the site of patient care, which allows for the delivery of testing conveniently and immediately to patients. To develop these assays, I propose an attractive strategy termed binding-induced DNA assembly (BINDA). BINDA bestows some appealing features on these assays, including high sensitivity and specificity, ease of operation, and detection in a single tube. This research program will contribute to technological requirements for early cancer detection and to the basic principles of bioanalytical chemistry for homogeneous analysis.