Ultra-high throughput HPLC-MS analysis using active flow technology

Abstract

High through-put analysis is increasingly in demand in many aspects of the analytical world. In concert with the need for high throughput, there is the need for higher sensitivity and better resolution. Further, for complex mixtures there is the need often there is a requirement for comprehensive sample characterization. These requirements are the driving forces for continuous developments in instrumentation. High performance liquid chromatography with mass spectrometry detection quickly evolved from predominantly university researcher environments to a tool that is now utilised on an everyday basis for qualitative and quantitative analyses in a wide variety of disciplines. Despite the general superiority of LC-MS as the go-to analytical tool, there are still many challenging issues and limitations, especially in relation to the interface between the LC and the MS detector. The work undertaken in this thesis develops strategies and technology as a solution to the interface problem between LC and MS. In particular this thesis investigates how to undertake LC-MS analyses in modes that are described here as 'ultra-high' throughput, consistent with the paradigm change in the enabled workflow. Indeed, the speed of the LC-MS analyses presented in this thesis rival direct injection protocols, but with the advantage that separation takes place prior to detection. A preliminary investigation was undertaken to assess the applicability of the ultra-high speed LC-MS developed herein as a tool for monitoring live reactions that require frequent sampling for reaction rate determinations. This was achieved employing a new column technology, called Active Flow Technology (AFT), which overcomes the limitations of the interface between HPLC and MS. The two important designs of AFT that are related to this thesis are the Curtain Flow column and the Parallel Segmented Flow column.

Date of Award	2015
Original language	English