Chip-based high-performance liquid chromatography for high-speed enantioseparations.

In this work, the first high-performance chiral liquid chromatography in packed microfluidic chips is presented. The chromatographic separation was performed on a column integrated into the microfluidic glass chip and packed with the particulate chiral stationary phase. Cellulose tris(3,5-dimethylphenylcarbamate) coated on 5-µm fully porous silica was used as chiral stationary phase material. Several racemic analytes including pharmaceutical products were baseline separated into their corresponding enantiomers under reversed-phase, polar organic and normal-phase conditions, demonstrating the versatility of the glass chip in the field of chiral separations. Van Deemter plots revealed a reduced plate height of 2.2 and a trend to enhanced mass transfer processes for solutes under low retention conditions. The utilization of very short column lengths of down to 12 mm led to ultrafast separations of enantiomers within 5 s.

High-performance liquid chromatography on glass chips using precisely defined porous polymer monoliths as particle retaining elements.

A stable and permanent integration of miniature packed bed separation columns into microfluidic systems is a major issue in nano liquid chromatography. Various approaches like differently shaped retaining elements or the use of key stone effect have been investigated. We show a flexible integration of miniature packed bed separation columns into microfluidic chips utilising common HPLC material achieved by laser-assisted generation of narrow, photopolymerised frits. The generated retaining elements serve as an in- and outlet frits for the columns. An optimised pre-polymeric solution, consisting of butyl acrylates and a porogen, allows a precise fabrication of frit-type structures with lengths of less than 100 m and the capability to withstand common slurry packing pressures of more than 250 bar. The separation of seven polycyclic aromatic hydrocarbons by pressure-driven, reversed-phase chromatography proves the high quality of the created chromatographic column inside a glass chip. Plate heights down to 2.9 were achieved and extremely fast separations with sub-second peak widths were performed in isocratic and gradient elution modes on very short columns (≤ 25 mm).