Non-Spherical Particles for HPLC

用于 HPLC 的非球形颗粒

• 批准号: 9321117
• 负责人: Barry E Boyes
• 金额: $ 17.61万
• 依托单位: ADVANCED MATERIALS TECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321117
• 关键词: Architecture; Beds; Biological; Biological Process; Biological Sciences; Biomedical Research; Caliber; Characteristics; Chemistry; Deposition; Development; Dimensions; Drops; Equipment; Glycoproteins; Goals; High Pressure Liquid Chromatography; Industry; Injectable; Knowledge; Laboratories; Liquid Chromatography; Liquid substance; Measurement; Methods; Outcome; Particle Size; Performance; Permeability; Pharmaceutical Preparations; Phase; Polysaccharides; Process; Proteins; Radial; Resolution; Route; Sampling; Savings; Shapes; Silicon Dioxide; Solid; Speed; Structure; System; Technology; Therapeutic Intervention; Thick; Thinness; Time; Variant; analytical method; base; detector; fitness; functional improvement; improved; interest; macromolecule; materials science; metabolomics; novel; particle; pressure; public health relevance; small molecule; success; ultra high pressure

 DESCRIPTION (provided by applicant): Extending liquid chromatographic column technology to even higher performance levels has given rise to ultra-high pressure liquid chromatography (UPLC), core-shell particle technology and instrumental developments such as lower volumes for injector and detector hydraulics. In spite of these advances, there is still room for improvement in speed, selectivity and resolution of the liquid chromatographic process. We propose that another level of improvement can be obtained with a change in particle shape by using ellipsoidal particles. These particles offer a reduced pressure drop, a higher mass fraction per unit volume of particles and the possibility to minimize wall effects that are characteristic o packed beds of spherical particles. Furthermore, the possibility of extending this non-spherical particle technology to smaller particle size is important because smaller spherical particles, while offering reduced zone broadening offer larger pressure drops. At some point, the advantage of superficially-porous particle architecture diminishes as particle size is reduced below ≈1.5 µm. If a route to smaller superficially porous non-spherical particles can be devised which minimizes the deleterious pressure drop of spheres, then performance can be increased before the pressure drop causes insurmountable difficulties. New chromatographic particles will be synthesized with a solid ellipsoidal or spherocylinder-like core and then a porous layer will be deposited around the outside for chromatographic retention. We have demonstrated previously in Phase I that there are advantages to this structure with regards to pressure drop and this can be rationalized by bed structures and performance that resemble a monolithic column without the problems of radial inhomogeneity and wall-effect-laden zone broadening that are present in monolithic column technology. We think of the proposed bed structure as that from a "pourable monolith." The current proposal uses synthesis technology and process-scale technology that were discovered and refined during Phase I efforts where it was shown that improved performance can be obtained for larger spherocylinder-like particles that are comparable with smaller spherical particles. In this comparison both the non-spherical and spherical particles used core-shell technology which AMT has pioneered. Phase II will expand on this effort, with the purpose of delivering further improved materials and methods to a broader range of applications in small molecule separations, such as metabolomics, to large molecules, such as proteins, glycoproteins and glycans. The aim here is to not only increase chromatographic resolution, but to make faster separations possible.

 描述(申请人提供)：将液相色谱柱技术扩展到更高的性能水平，促进了超高压液相色谱(UPLC)、核-壳颗粒技术和仪器的发展，如注射器和检测器液压的更低体积。尽管取得了这些进展，但在液相色谱过程的速度、选择性和分辨率方面仍有改进的空间。我们提出，通过使用椭球粒子改变粒子形状可以获得另一种程度的改进。这些颗粒具有更小的压降、更高的单位体积颗粒质量分数，并有可能最大限度地减少球形颗粒填充床所特有的壁面效应。此外，将这种非球形颗粒技术扩展到更小颗粒尺寸的可能性很重要，因为更小的球形颗粒，同时提供更小的区域加宽，提供更大的压力降。在某种程度上，当颗粒尺寸减小到≈1.5um以下时，表面多孔颗粒结构的优势就会减弱。如果能够设计出一条更小的表面多孔非球形颗粒的路线 这将有害的球体压降降到最低，然后可以在压降造成难以克服的困难之前提高性能。新的层析粒子将由固体椭圆形或球状柱状核心合成，然后将形成多孔层 存放在外面，用于层析保留。我们以前在第一阶段已经证明，这种结构在压降方面有优势，这可以通过类似于整体柱的床层结构和性能来合理化，而不存在整体柱技术中存在的径向不均匀和壁面效应区域加宽的问题。我们认为拟议的床位结构是来自“浇注整体”的结构。目前的提议使用了在第一阶段工作中发现和改进的合成技术和工艺规模技术，其中表明，可获得与较小球形颗粒相当的较大球状内衬颗粒的性能改进。在这种对比中，非球形和球形颗粒都使用了AMT率先采用的核壳技术。第二阶段将扩大这一努力，目的是将进一步改进的材料和方法应用于更广泛的小分子分离，如代谢组学，以及蛋白质、糖蛋白和多糖等大分子的分离。这里的目的不仅是提高色谱分辨率，而且使更快的分离成为可能。