Disruptive Analytical Technologies for Biomedical Sciences

我的研究项目主要涉及生物医学科学的破坏性分析技术的发展。现代生物医学科学需要精确的工具来研究生物分子相互作用和细胞过程的分子标记。它们还需要有效的工具来产生针对蛋白质靶标的亲和配体。当前的技术范式限制了基于它们的工具的准确性和有效性。我们的使命是建立新的范式，并在此基础上开发改变游戏规则的技术。 我们目前专注于改变三种模式。首先，我们的目标是使基于溶液的方法在生物分子相互作用的动力学表征和亲和配体的选择中占主导地位。第二，我们的工作是在表征单个细胞中的催化过程时，用非任意的（反应速率常数）来取代反应的任意特征。第三，我们的目标是在连续流化学中用分子流分离来增强液-液萃取。在过去的6年中，我们在此基础上开发了许多高性能的分析工具：（i）通过瞬时不完全分离获得精确常数，用于蛋白质-小分子复合物的Kd测量（Angew Chem Int艾德2019，58，6635），（ii）用于适体单轮选择的理想过滤毛细管电泳（Angew Chem Int艾德2019，58，2739），（iii）用于研究跨膜转运的反应速率常数的细胞计数（Anal Chem 2019，91，4186），（iv）复杂生物基质中多种microRNA的高灵敏度定量检测（Anal Chem 2020，92，14251），和（v）用于与连续流有机合成组合的非水连续流电泳（Lab Chip 2019，19，2156）。40名受训人员接受了培训，他们的工作成果发表在60篇论文中，被引用1200次。在接下来的5年里，我们将继续基于我们的三种范式构建新技术。我们还计划继续我们的好奇心驱动的探索/发现研究。这种研究的一个方向是生物分析技术中的人工智能和机器学习。我们的NSERC发现研究将保持高度跨学科，从化学到生物学，从物理学到数学。许多项目将与其他学术实验室和研发公司合作开展。10名研究生在3个程序（化学，生物和物理）和2个PDF将在持续的基础上进行培训。我们期望我们的基础研究成果将在分析化学，物理化学，分子生物学和其他研究领域创造新的知识。我们还希望，我们的应用驱动研究将为生物医学和制药公司提供新的研发工具，以创建新的快速和灵敏的诊断方法，并为癌症等复杂疾病提供更有效的治疗方法。

My research program is mainly concerned with the development of disruptive analytical technologies for biomedical sciences. Modern biomedical sciences require accurate tools for studying biomolecular interactions and molecular markers of cellular processes. They also require effective tools for generation of affinity ligands for protein targets. Current technological paradigms limit accuracy and effectiveness of tools that are based upon them. Our mission is to establish new paradigms and develop game-changing technologies upon them. We currently focus on shifting three paradigms. First, we aim to make the solution-based approach dominate over the surface-based approach in kinetic characterization of biomolecular interactions and selection of affinity ligands. Second, we work towards replacing arbitrary characteristics of reactions with non-arbitrary ones (reaction rate constants) when characterizing catalytic processes in individual cells. Third, we aim to augment liquid-liquid extraction with molecular stream separation in continuous-flow chemistry. Over the past 6 years, we have developed a number of highly-enabling analytical tools based on this foundation: (i) accurate constant via transient incomplete separation for Kd measurements of protein-small molecule complexes (Angew Chem Int Ed 2019, 58, 6635), (ii) ideal-filter capillary electrophoresis for single-round selection of aptamers (Angew Chem Int Ed 2019, 58, 2739), (iii) cytometry of reaction rate constant for studying cross-membrane transport (Anal Chem 2019, 91, 4186), (iv) highly-sensitive quantitative detection of multiple microRNAs in complex biological matrices (Anal Chem 2020, 92, 14251), and (v) non-aqueous continuous-flow electrophoresis for combination with continuous-flow organic synthesis (Lab Chip 2019, 19, 2156). Forty trainees have been trained, and the results of their work were published in 60 papers cited 1200 times. In the next 5 years, we will continue building novel technologies based on our three paradigms. We also plan to continue our curiosity driven exploratory/discovery research. One direction for such research is artificial intelligence and machine learning in bioanalytical technologies. Our NSERC Discovery research will remain highly interdisciplinary ranging from chemistry to biology and from physics to mathematics. Many projects will be carried out in collaboration with other academic laboratories and R&D companies. Ten graduate students in 3 programs (chemistry, biology, and physics) and 2 PDFs will be trained on a continuing basis. We anticipate that the results of our basic research will create new knowledge in analytical chemistry, physical chemistry, molecular biology, and other fields of study. We also expect that our application-driven research will provide biomedical and pharmaceutical companies with new R&D tools required for creation of new rapid and sensitive diagnostics and more effective treatments for complex diseases, such as cancer.