Colum-based SPE (Fig. 2A) is the earliest online format that
has been routinely used. Most of the online SPE columns are
particle-packed columns, which facilitates the utilization of various
absorbents. However, the smaller particles the SPE column is
packed with, the higher pressure the online system has to bear.
Such drawback is disadvantageous to the online coupling, which
limits the application of some novel sorbents with small particle
size, for example nanoscale materials. Another disadvantage of the
column-based SPE format is the easy deterioration of the SPE column
due to analyte carryover, column clogging, malfunctions of the
active entities, or bounding of nonspecific and irreversible matrix
interfering compounds [5].