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

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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.