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 m. 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.
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 sample. 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.
| Schure, Mark R; Maier, Robert S (2018) Ellipsoidal particles for liquid chromatography: Fluid mechanics, efficiency and wall effects. J Chromatogr A 1580:30-48 |
| Chen, Qile P; Schure, Mark R; Siepmann, J Ilja (2018) Using molecular simulations to probe pore structures and polymer partitioning in size exclusion chromatography. J Chromatogr A 1573:78-86 |
| Schure, Mark R; Moran, Robert E (2017) Size exclusion chromatography with superficially porous particles. J Chromatogr A 1480:11-19 |
| Schure, Mark R; Davis, Joe M (2017) Orthogonality measurements for multidimensional chromatography in three and higher dimensional separations. J Chromatogr A 1523:148-161 |
| Wagner, Brian M; Schuster, Stephanie A; Boyes, Barry E et al. (2017) Superficially porous particles with 1000Å pores for large biomolecule high performance liquid chromatography and polymer size exclusion chromatography. J Chromatogr A 1489:75-85 |
