On-line solid-phase preconcentration for sensitivity enhancement in capillary electrophoresis

Capillary electrophoresis is attractive for the analysis of biological samples because only a few nanoliters of sample need to be injected. Indeed, optimal resolution is achieved when the injected volume is 1% or less of the total capillary volume. Unfortunately, this advantage leads to severe detection limitations compounded by the fact that many analytes in a biological sample are present at very low concentrations. To overcome the detection sensitivity limitations of CE, nonspecific, on-line preconcentration has been employed in a variety of applications. This technique is based on inserting a small quantity of reversed-phase material (e.g., C18 particles or membrane) near the inlet of the CE capillary for sample enrichment by solid-phase extraction. A detachable cartridge containing the solid phase is relatively simple to construct and permits the injection of large sample volumes (1-100 microL) into the capillary. Elution of adsorbed analyte in less than 100 nL of solvent permits a 100-1000 fold improvement in the effective concentration limit of detection, depending on the hydrophobicity of the compound. Detection of analytes present in complex mixtures at concentrations as low as 20 amol/microL has been reported when using an on-line preconcentration device in conjunction with CE-mass spectrometry. In this review, the potential merits of the technique are described and some examples of direct analysis of biological samples without rigorous off-line pretreatment are given.