Abstract: The sensitive detection of molecules is of critical importance in separation technology. As analytical separation methods grow smaller to accommodate the increasing need for higher resolution and speed, the amount of detectable material decreases as well. This trend fuels the demand for detection schemes that can detect trace amounts of analytes within ever decreasing probe volumes. Spectrophotometric techniques are attractive since many molecules possess some affinity for light absorption within the visible ultraviolet spectrum and optical absorption is generally non-destructive to the analyte leaving it intact for further uses. Degenerate Four Wave Mixing is an optical absorption based method that has many desirable characteristics including picoliter scale probe volumes making it an ideal match for micro separation setups.