Table 1.

Comparison of the attributes of different approaches to fast HPLC

Characteristics	Small Particles	High Pressure	Non-Porous Particles	Core-Shell Particles	High Temperature	Chemometric Curve Deconvolution
Overall Impact on Speed	++	++	+	++	+++	++
Primary Effect on Speed	Lower plate heights, shorter column lengths, and higher optimum eluent velocities	Drives fluid faster. Used in conjunction with smaller particles and narrower columns (≤ 2.1 mm i.d.)	Improved interphase mass transfer and eddy dispersion	Lower reduced plate height through improved eddy dispersion, improved interphase mass transfer.	Reduces viscosity and thus pressure; allows fluid to move faster at same pressure. Improves interphase mass transfer. Can be combined with use of smaller particles	Decreases resolution needed for analytical purposes and thus can speed up analysis considerably
Requirements	Needs high pressure instrument; requires dramatic decrease in extra-column broadening	Needs high pressure instrument; requires dramatic decrease in extra-column broadening when used with small particles	Generally needs high pressure to drive liquid through particles around 1 micron; ultra low dispersion equipment	Requires low extra-column dispersion; almost as important as with sub-two micron porous particles	Does not require high pressure instruments but does require specialized solvent pre-heater and column temperature controller. Generally requires narrow column (≤ 2.1 mm) to minimize thermal mismatch. No PEEK in columns when used above 100 °C	No changes in hardware. But some approaches require extreme repeatability in peak shape and retention time.
Equipment Cost	High	High	High	Medium	Low	N/A
Primary Advantages	Can improve speed significantly. Has minimal effect on selectivity and thus simplifies method transfer from bigger particles of same manufacture.	Can improve speed significantly; The use of narrower columns can lower solvent consumption.	High efficiency for separations of large molecules, especially proteins.	Can be done with conventional HPLC equipment.	Can be done with conventional HPLC equipment.	No real change in instrument.
Primary Disadvantages	Requires mechanically very stable particles; frictional heating.	Generally requires narrow column (≤2.1 mm i.d.) to minimize frictional heating.	Very low sample load capacity and much less retention. Very small particles are hard to pack.	Slightly decreased sample load capacity and retention.	Requires thermally stable stationary phase and stable analytes.	Mathematically complex. Must have very precise retention if deconvolution methods are used.
Effect on relative retention	None provided the substrate and stationary phase chemistry are the same as for larger particles (excluding pressure effects, see right).	Small but real, and analyte dependent.	Minimal	Minimal under isocratic elution, larger under gradient elution.	Considerable	N/A
Sample Capacity	Good	Good	Much less	Somewhat less	Good	N/A
Available	Quite a few and	Quite a few and	Very limited	Few but growing.	Quite a few	N/A