Reduction in delay time of high-dwell volume pumps in LC-MS applications using short-term low-ratio split flow

We present a simple hardware design which reduces run time of gradient-based LC/MS applications and improves system equilibration. Our approach does not sacrifice efficiency of chromatographic separation, and does not affect analyte retention time and therefore does not require revalidation. Our technical design is based on a six-port/two-position switching valve and flow splitter installed prior to the LC column. This design minimizes time delays caused by the high-dwell volume of some LC pumps. Implementation of short-term (40-55 s) low-ratio (1:10) flow splitting reduced delay times by over four-fold in our application. This approach allowed hardware-associated time delays to be minimized. Alternative plumbing suggestions are also discussed.