I have a quick question regarding agarose bead size in affinity chromatography, specifically nickel-coated beads for purification of his-tagged proteins. I'm using small columns (1 ml) on an FPLC. If I have a selection of the same column size with the same binding affinity, only differing in bead size (i.e. 34 µm or 165 µm), what is the advantage of smaller beads? I know that larger beads give me a higher possible flow-rate (less back-pressure) which is generally a good thing, as it saves time. OK. But the smaller beads? Binding capacity is the same (as stated by the manufacturer), resolution should not matter either, right? As this isn't a "dumb" elution by time (as in size exclusion chromatography) but an elution with Imidazole in which I can determine the exact amount to add to specifically elute my protein of interest empirically, so the resolution should be the same no matter the bead size.
So, anyone using columns with small beads on purpose - if so, why?