New microscale sample processing approaches for application to proteomics and bioanalysis

加拿大人的健康和福祉不仅依赖于准确的诊断和有效的治疗，而且还依赖于无污染的生活环境。化学分析在实现这些目标的过程中发挥着关键作用，它有助于揭示疾病的原因，或通过跟踪病人的药物治疗反应，或通过测试水、土壤和空气中对植物和动物的毒素。到目前为止，最常用的化学分析方法被归为“分析分离”，包括色谱、电泳和质谱等强大的技术。提交化学分析的样品非常复杂，有时含有一千多种不同的化合物，因此在分析分离之前需要严格的样品制备技术。事实上，随着针对分析的制备技术的发展，上述分析分离方法的选择性和检测灵敏度大大提高。因此，我们的研究项目致力于开发和优化样品制备方法，具体应用于微升尺度的生物分析，并提高最先进的分析分离的能力。

The health and the well-being of Canadians rely not only on accurate diagnosis and effective treatment but also a pollution-free environment in which to live. Chemical analysis plays a key role in such goals by helping uncover the causes of disease, or by following a patient’s drug therapy response, or by testing water, soil and air for toxins to both plants and animals. By far the most common methods for said chemical analyses are grouped under the term “analytical separations”, encompassing the powerful techniques of chromatography, electrophoresis and mass spectrometry. The complexity of samples submitted for chemical analysis, sometimes containing over a thousand different compounds, is such that rigorous sample preparation techniques are required prior to the analytical separation. In fact, the selectivity and detection sensitivity of the above-mentioned analytical separation methods improve greatly with preparation techniques tailored to the analysis. Therefore, our research program is dedicated to developing and optimizing sample preparation methods with specific application to microliter scale bioanalysis and towards enhancing the power of state-of-the-art analytical separations. The identification of proteins and the understanding of their biological interactions is key to developing diagnostic and therapeutic strategies. Therefore, we are designing sample preparation methods that aid in protein determination, including proteins at low abundance because these are the ones suspected to have relevance for disease diagnosis. We are developing fractionation strategies and enzymatic methods that render proteins easier to analyze by mass spectrometry and address the current trend towards miniaturization. Capillary electrophoresis is our main microscale method, which is ideally suited because nanolitre volumes can be injected, it is easily automated and it can be translated into microchip format for additional miniaturization. Our immobilized enzyme microreactor methods are being developed to allow simple construction and rapid protein digestion for better mass spectrometry analysis. Innovative combinations of these microscale techniques and methods applied to minute sample volumes has the long term potential to impact disease diagnosis and monitoring in humans and animals.