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

• Published in: TrAC, Trends in analytical chemistry (Regular ed.) Vol. 63; pp. 65 - 75
• Main Authors: Broeckhoven, K., Desmet, G.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2014
• Subjects: Band broadening; Column technology; Impedance; Instrument design; Kinetic plot; Knox and Saleem limit; Particle size; Pressure limitation; Separation power; UHPLC; Particle size; Separation power; Instrument design; Knox and Saleem limit; Column technology; Pressure limitation; UHPLC; Impedance; Band broadening; Kinetic plot
• ISSN: 0165-9936; 1879-3142
• DOI: 10.1016/j.trac.2014.06.022

•We quantify the potential gain of a future doubling of operating pressure.•We establish expressions for kinetic gain factors.•We take into account the effect of extra-column band broadening.•We construct corrected Knox and Saleem limits.•We demonstrate the need to eliminate connection tubing. 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.