The future of UHPLC: Towards higher pressure and/or smaller particles?

Simple expressions for kinetic gain factor were established to predict the potential gain in separation speed, efficiency or resolution and peak capacity when moving from a given separation condition (pressure, particle type and size) to optimized conditions. The equations show that the possible gain by moving from 1200-bar to 2400-bar instruments would at most lead to a 40% increase in efficiency and only 20% in resolution or peak capacity, while analysis time would halve. These optimal systems would have to operate with short columns packed with very small particles (0.6-1 µm for N = 10,000-25,000), yielding peaks with unprecedentedly small volumes. It would therefore never be possible to realize the full theoretical gain of new investment in pressure due to the instrument contributions. We therefore require radical new designs of chromatographic systems (getting rid of the current need for long connection tubing) to advance the limits of separation power.