Non-Spherical Particles for HPLC

 描述（由申请人提供）：将液相色谱柱技术扩展到甚至更高的性能水平已经引起了超高压液相色谱（UPLC）、核-壳颗粒技术和仪器开发，例如用于进样器和检测器液压的更低体积。尽管取得了这些进展，但液相色谱法在速度、选择性和分辨率方面仍有改进的余地。我们建议，另一个层次的改善，可以通过使用椭球形颗粒的颗粒形状的变化。这些颗粒提供了降低的压降、每单位体积颗粒的更高质量分数以及使壁效应最小化的可能性，壁效应是球形颗粒的填充床的特征。此外，将这种非球形颗粒技术扩展到更小粒度的可能性是重要的，因为更小的球形颗粒在提供减小的区域加宽的同时提供更大的压降。在某些情况下，当颗粒尺寸减小到小于1.5 μm时，表面多孔颗粒结构的优势会减弱。如果能设计出一种更小的表面多孔的非球形颗粒 这使球体的有害压降最小化，然后在压降引起不可克服的困难之前，性能可以提高。新的色谱颗粒将被合成为具有固体椭圆形或球柱状核心，然后将多孔层 沉积在外部用于色谱保留。我们先前在阶段I中已经证明，这种结构在压降方面具有优势，并且这可以通过类似于整体柱的床结构和性能来合理化，而没有整体柱技术中存在的径向不均匀性和壁效应负载区加宽的问题。我们认为所提出的床层结构是一个“块体”。“目前的提案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，其中表明可以获得与较小球形颗粒相当的较大球形圆柱体状颗粒的改进性能。在这个比较中，非球形和球形颗粒都使用AMT开创的核-壳技术。第二阶段将扩大这一努力，目的是提供进一步改进的材料和方法，以更广泛地应用于小分子分离，如代谢组学，大分子，如蛋白质，糖蛋白和聚糖。这样做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。

 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.