Attempts to miniaturize columns for liquid chromatography (LC) have be
en reported since the late 70's. A series of advantages were repeatedl
y claimed in the use of microcolumns, whose inner diameters were less
than 1 mm. However, several requirements and limitations have kept mic
rocolumn LC within a very limited area of applications. On the contrar
y, semi-microcolumn LC (inner diameter: 1 similar to 2 mm) has been wi
dely accepted in academia and industry, possessing both advantages sho
wn by microcolumn LC and the reliability of conventional LC. Although
certain modifications, such as miniaturizing dead volumes of component
s, are required in instrumental arrangements, it became possible to ea
sily obtain highly efficient separation with a semi-microcolumn, even
under isocratic conditions. The benefits of semi-microcolumn LC seem m
ost pronouncing when a column-switching system is arranged. A tremendo
us concentrating effect could be earned by first injecting a sample so
lution into a short conventional-bore precolumn, and then transferring
an analyte-containing fraction to a semi-microcolumn connected into a
detector. This analytical format was applied to the analysis of vario
us substances contained in biological liquids at very low concentratio
ns. The later sections of the article discuss some of these applicatio
ns, including forensic analysis and diagnosis in clinical chemistry.