High-Throughput Capillary Liquid Chromatography Using a Droplet Injection and Application to Reaction Screening

Area of Science:

• Analytical Chemistry
• Chromatography
• Mass Spectrometry

Background:

• Standard liquid chromatography (LC) systems face throughput limitations due to long autosampler injection sequences (>15 s).
• Large bore columns in conventional LC systems generate significant mobile phase waste and pose challenges for mass spectrometry interfacing.
• Existing LC methods struggle to achieve high-throughput screening due to cycle time constraints.

Purpose of the Study:

• To develop a droplet injector system to overcome the limitations of conventional autosamplers in LC.
• To enable high-throughput analysis and chemical reaction screening using capillary LC.
• To reduce mobile phase and sample consumption in LC separations.

Main Methods:

• A droplet injector system was designed using a four-port, two-position valve with a 20 nL internal loop, interfaced with a syringe pump and a three-axis positioner.
• The system alternately withdraws sample droplets and immiscible fluid from a well plate into a capillary.
• Capillary LC columns (300 μm inner diameter) were employed to minimize solvent and sample usage.

Main Results:

• The droplet injector system achieved a 5-second cycle time, enabling sequential injection of 20 nL sample droplets.
• The system successfully performed 96 separations of 3-component samples in 8.1 minutes.
• Coupling with a mass spectrometer via electrospray ionization facilitated high-throughput chemical reaction screening.

Conclusions:

• The developed droplet injector system significantly improves LC throughput and reduces cycle times.
• This method offers a viable solution for high-throughput screening with reduced mobile phase and sample consumption.
• The system demonstrates effective interfacing with mass spectrometry for advanced analytical applications.