Smaller Particle Fused-Core Silicas for Higher Performance Separations

描述(申请人提供)：生命科学研究和其他关键的生物分析应用将大大受益于更快和更高分辨率的小分子和大分子(如蛋白质、多肽、糖肽和多糖)的高效液相色谱(HPLC)分离。许多具有生物医学意义的高效液相色谱分离，如蛋白质组或糖链分析，需要数小时或数天的时间来解析单个样品。由于生物样品的复杂性，目前的研究文献中有许多例子结合了多维的高效液相色谱分离，通常与在线质谱学(MS)相结合。虽然非常耗时，但这种方法已经产生了关于蛋白质表达和翻译后修饰、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的影响的有用信息。在各种复杂的生物分析工作流程中，高效的LC分离是分析系统的基础，而实现复杂生物样品的高分辨率分离的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核二氧化硅平台技术扩展到更小的颗粒，提供显著更快和更高分辨率的分离来提高高效液相分离效率的方法。我们的目标是创造直径2.3微米和1.8微米的表面多孔熔核二氧化硅颗粒，并将这些材料高效地加载到高效液相色谱柱格式中。拟议工作的目标将产生非常高性能的色谱产品，比目前可用的产品更多，广泛应用于复杂生物样品的分析、制药和生物制药应用，事实上，在任何使用高效液相方法的当前应用中。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。 与公众健康相关：高压液相色谱是分离分子混合物的最广泛使用的分析方法，允许测量混合物中物质的数量和特性。这种方法被广泛应用于生物医学研究，以及治疗干预措施的创建、制造和控制。目前的建议是利用材料科学和化学的新知识，通过液相色谱实现更快、更高效的分离，节省时间和金钱，并使该方法能够新的用途来了解生物分子的结构和功能。

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.