Increasing the Throughput of Liquid Chromatography

In this manuscript the ramifications of operating very high pressure chromatographic (VHPLC) instruments at high linear velocities is discussed. Operating at higher inlet pressures causes thermal conditions inside the column to change to an extent that can alter the reproducibility and accuracy of the chromatograms produced. The experiments discussed in this dissertation were focused on the manner in which the mobile phase is eluted through the column; by either constant flow, constant pressure, operator controlled or programmed constant pressure, and conditions which keep the heat loss at the columns wall constant. Additional experiments included other practical considerations in system performance such as void spaces created from improper column connections. The results of these experiments showed that void volumes can be the leading cause of band dispersion. The metric used for all measurements were based on moment analysis, which provides a more rigorous analysis of chromatographic performance than the metrics used by the majority of the community.