Developing New Tools for Bioanalysis and Imaging Using Advanced Fluorescent Materials

加拿大和全球保健在今后几年面临许多挑战。科学技术的进步对于找到解决这些挑战的办法至关重要。本研究计划旨在发展荧光材料、方法及技术，以分析与健康及疾病有关的生物标记物。被称为“量子点”和“聚合物点”的纳米粒子材料将用于开发新的即时诊断方法和用于生物医学研究的新型荧光探针。即时诊断是在医生办公室或医院床边进行的低成本和快速的医学检测，而不是在由训练有素的人员操作的拥有精密设备的专业实验室进行。在这种情况下，我们的目标包括开发量子点和聚合物点支持的基于智能手机的平台，用于(i)测量低丰度生物标志物，（ii）通过新型光学条形码检测多种细胞类型，以及（iii）指纹识别与癌症等疾病相关的复杂酶活性。在荧光探针的背景下，我们将使用具有独特能力的基于量子点的“同心FRET”（cFRET）探针来研究和获得对细胞过程的新见解。这些探针代表了新的工具，将有助于推进生物医学研究，以改善疾病的诊断和治疗。我们的目标包括(i)实时、定量地观察与细胞死亡相关的酶级联反应，这种酶级联反应的失调与癌症和神经退行性疾病有关；（ii）测量生长中的肿瘤细胞分泌的生物标志物，以深入了解其生物学和治疗方法；（iii）推动cFRET探针在单分子水平上检测生物标志物。这种基础研究和应用研究的平衡组合将有助于培养下一代科学家，具有未来商业化的潜力，并且通过对未来保健的预期贡献，将帮助加拿大人获得更好的生活质量。

Canadian and global health care faces many challenges in the years ahead. Advances in science and technology will be critical to finding solutions to these challenges. The proposed research program aims to develop fluorescent materials, methods and technologies for the analysis of biological markers that are relevant to health and disease. Nanoparticle materials called “quantum dots” and “polymer dots” will be used to develop new point-of-care diagnostic methods and new fluorescent probes for biomedical research. Point-of-care diagnostics are low-cost and rapid medical tests done at the doctor's office or hospital bedside rather than in a specialized laboratory with sophisticated equipment operated by highly-trained people. In this context, our goals include the development of quantum dot- and polymer dot-enabeled, smartphone-based platforms for (i) measuring low-abundance biomarkers, (ii) the detection of multiple cell types via novel optical barcodes, and (iii) fingerprinting complex enzyme activity relevant to diseases such as cancer. In the context of fluorescent probes, we will use quantum dot-based “concentric FRET” (cFRET) probes with unique capabilities to study and gain new insight into cellular processes. These probes represent novel tools that will help advance biomedical research toward improved diagnosis and treatment of disease. Our goals include (i) real-time, quantitative observation of enzymatic cascades associated with cell death, the misregulation of which is implicated in diseases such as cancers and neurodegeneration; (ii) measuring biomarkers excreted from growing tumour cells to gain insight into their biology and treatment; and (iii) pushing cFRET probes to detect biomarkers at the level of single molecules. This balanced mix of fundamental and applied research will help train the next generation of scientists, has potential for future commercialization, and, through prospective contributions to the future of health care, will help Canadians attain better quality-of-life..