Smaller Particle Fused-Core Silicas for Higher Performance Separations

描述（由申请人提供）：生命科学研究和其他关键的生物分析应用将从更快、更高分辨率的小分子和大分子（如蛋白质、肽、糖肽和聚糖）的液相色谱（HPLC）分离中受益匪浅。许多生物医学领域的高效液相色谱分离，如蛋白质组学或糖谱分析，需要数小时或数天才能解决单个样品。由于生物样品的复杂性，目前的研究文献中有许多将HPLC分离的多个维度结合起来的例子，通常与在线质谱（MS）相结合。虽然非常耗时，但这种方法已经获得了关于蛋白质表达和翻译后修饰的有用信息，蛋白质表达和修饰的生物学过程，以及发育，疾病状态和各种环境和遗传因素对其的影响。在各种复杂的生物分析工作流程中，高效液相色谱分离是分析系统的基本组成部分，而实现复杂生物样品的高分辨率分离时间是一个很大的瓶颈。该提案描述了一种通过将我们专有的熔融核心二氧化硅平台技术扩展到更小的颗粒来提高HPLC分离效率的方法，提供了显着更快和更高分辨率的分离。我们的目标是创建2.3和1.8微米直径的表面多孔硅芯颗粒，并有效地将这些材料装入高效液相色谱柱格式。所提出的工作目标将产生比目前可用的更高性能的色谱产品，广泛应用于复杂生物样品的分析，制药和生物制药应用，实际上在任何当前使用HPLC方法的应用中。所描述的分离技术将直接导致有重大技术和市场需求的有用产品。

DESCRIPTION (provided by applicant): Life sciences research and other critical bioanalytical applications would strongly benefit from faster and higher resolution liquid chromatographic (HPLC) separations for both small molecules and larger molecules such as proteins, peptides, glycopeptides, and glycans. Many HPLC separations of biomedical interest, such as proteomic or glycomic profiling, require hours or days for resolution of a single sample. Due to the complexity of biological samples, there are many examples in the current research literature that combine multiple dimensions of HPLC separations, often with online mass spectroscopy (MS). Although very time consuming, this approach has yielded useful information on protein expression and post-translational modifications, the biological processes underlying protein expression and modifications, and the effects thereon of development, disease state, and various environmental and genetic factors. In various complex bioanalytical workflows, high efficiency LC separations are a fundamental part of the analytical systems, and the time to achieve high resolution separations of complex biological samples is a great bottleneck. This proposal describes an approach to improve the separation efficiency of HPLC by extending our proprietary Fused-Core silica platform technology to smaller particles, providing significantly faster and higher resolution separations. Our objectives are to create 2.3 and 1.8 micron diameter superficially porous Fused-Core silica particles, and to load these materials efficiently into HPLC column formats. The goals of the proposed work would yield very high performance chromatographic products, greater than those currently available, to be applied broadly in analysis of complex biological samples, pharmaceutical and biopharmaceutical applications, in fact in any current application that uses HPLC methods. The separations technology described will directly lead to useful products for which there is a significant technical and market demand. PUBLIC HEALTH RELEVANCE: High pressure liquid chromatography is the most widely used analytical method to separate mixtures of molecules, allowing measurement of quantities and identities of materials in a mixture. This method is broadly used in biomedical research, as well as in the creation, manufacture and control of therapeutic interventions. The current proposal is to use new knowledge in materials science and chemistry to enable faster and more efficient separations by liquid chromatography, saving time and money, as well as enabling new uses of the method to understand the structure and function of biological molecules.