Miniaturized Supercritical Fluid Chromatography Coupled with Ion Mobility Spectrometry: A Chip-Based Platform for Rapid Chiral and Complex Mixture Analysis

This study presents the first coupling of miniaturized chip-based supercritical fluid chromatography (SFC) with ion mobility spectrometry (IMS) enabling rapid two-dimensional analysis of moderately polar compounds. For the first time, ionization and analyte transfer at the SFC-IMS interface are achieved solely through eluent decompression in conjunction with a shifted electric IMS inlet potential. This straightforward approach significantly reduces instrumentation complexity and size, promoting system compactness and robustness. The integration of chip-based SFC with IMS enables high-speed separations of complex samples, drastically reducing analysis time while utilizing a detector capable of delivering structural information at a rapid acquisition rate and low cost. Evaluation of the SFC-IMS system as demonstrated through the chiral separation of Tröger’s base revealed exceptional repeatability and sensitivity. Short columns and high flow rates resulted in record-speed SFC-IMS analysis in just six seconds. The system was successfully used to analyze a complex mixture containing five isomers, including naloxone and 6-monoacetylmorphine, in just 30 s.