Performance limits and kinetic optimization of parallel and serially connected multi-column systems spanning a wide...

Using a set of experimentally determined liquid chromatography column performance data, it has been investigated how a range of efficiencies can best be covered when using a multi-column system. Two main variants are considered: a serially-connected variant (realizing different column lengths by connecting a different number of column segments in series) and a parallel-connected variant (realizing different column lengths by simply switching between columns with a different length arranged in parallel). Both variants are compared for their ability to keep the average analysis time along a given range of efficiencies as close as possible to the intrinsic Knox & Saleem-speed limit. It was found that the serial connection mode offers a better compromise between average speed and amount of required silica (total required column length) than the parallel connection mode for all efficiency ranges running from 5000-10,000 plates up to 75,000-150,000 plates. Considering an ultra-high performance liquid chromatography (UHPLC) operation at 1200 bar, the best possible serial connection system can get within about within 15-25% of the Knox & Saleem-speed limit, whereas a three-column parallel system can only get to within 40-50% of the speed limit, while needing 50-100% more total column length. In absolute terms, the serially-connected system with individually optimized segment lengths should be able to cover a range of 5000-75,000 theoretical plates (dynamic range of 25) in an average analysis time of 14.3 min when using a 1200 bar instrument. At 400 bar, this would be 37.9 min, showing that the construction of wide-efficiency range systems would be one of the application areas where the advantages of UHPLC-conditions would be most fully realized.