Improving Throughput and Automation of Capillary Liquid Chromatography

Liquid chromatography is one of the most widely employed analytical techniques in the world, with its use only expected to increase in the coming years. To meet this increasing demand, the speed of chromatographic separations can be increased, enabling their use in high throughput screening applications. However, the higher flow rates required to perform these separations with analytical scale columns can cause challenges with waste generation and limit compatibility with mass spectrometry. In this work, several advancements towards capillary scale high throughput separations are demonstrated. These include an isocratic separation with a 4 second cycle time, resulting in an analysis time of 6.4 minutes for a 96 well plate. Additionally, several systems were operated in parallel with a 5 second separation, leading to a 96 well plate being analyzed in 2 minutes. Gradient separations were also performed with 15 second gradients being able resolve several compounds in a 20 second cycle time. With these advancements, the use of high throughput capillary LC for multidimensional analysis will also be discussed.

Although the separations demonstrated can be completed in under 10 seconds, typical injection sequences are often longer (> 15s). To avoid this bottleneck, droplet-based sampling techniques have been developed to provide single second injection times. Previously, these droplet-based setups required user activation of the valve when sample was ready to be injected. Progress towards the automation of these injections to further improve the technique will be detailed.