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

癌症是加拿大男女发病和死亡的主要原因。早期发现癌症，同时仍然局限于局部和可治愈的承诺，不仅降低整体癌症死亡率，而且发病率和经济负担。开发基于生物标志物（生物状态指标）的癌症筛查工具是在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异性的技术，这些技术还能够快速、可重复、具有成本效益和高通量地检测生物标志物。几乎没有可用的蛋白质检测技术满足所有这些要求，即使蛋白质占临床使用的大多数癌症生物标志物。为了满足早期癌症检测的蛋白质检测的需求，我建议开发一个多功能的工具箱，包括两种类型的新的同质检测互补的行为。将开发第一种类型的测定法，以能够检测少至100种生物标志物分子，这对于检测在早期癌症阶段以超低水平存在的生物标志物非常重要。将开发第二种类型的检测方法，以便在患者护理现场或附近检测生物标志物，从而方便并立即向患者提供检测。为了开发这些检测方法，我提出了一个有吸引力的策略，称为结合诱导的DNA组装（BINDA）。BINDA为这些检测提供了一些吸引人的功能，包括高灵敏度和特异性，易于操作，以及在单管中检测。该研究计划将有助于早期癌症检测的技术要求和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.