(1219-D) Applications of Open Port Sampling Mass Spectrometry to Increase Throughput
Tuesday, February 6, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: Less than 5% of the human proteome has been targeted successfully for drug discovery. There is a need to create and utilize technologies to enable chemical probe discovery for interrogation of the therapeutic potential of the proteome. High-throughput screening of in-vitro assays for small molecule probe discovery often uses optical detection, which is susceptible to compound-dependent assay interference. However, incorporation of mass spectrometry to in-vitro assay detection allows for direct detection of native substrates and products limiting compound-dependent assay interference. To date, throughput has limited the use of mass spectrometry detection, largely due to use of liquid chromatography to dilute and separate analytes prior to mass spectrometry. Here, we utilize direct open port interface (OPI) sampling to increase throughput and enabling sampling speeds of a few seconds per sample. Applications for OPI sampling include acoustic ejection mass spectrometry, affinity selection mass spectrometry and chemical reaction monitoring. For acoustic ejection mass spectrometry, the vertical orientation for the OPI allows direct droplet mass spectrometry sampling with a sampling speed of two seconds per sample. The dilution to limit ESI signal suppression from co-eluting components enables it to be used for in-vitro assay detection when a full LC separation is not needed. Use of magnetic beads in affinity selection mass spectrometry has increased throughput, but LC separation is often used and slows down throughput. Use of a fixed-tip OPI capable of a ‘dip’ into a sample from a plate and ‘sip’ samples allowed for sampling of 2 seconds/sample from our ‘dip-n-sip’ platform. The OPI allows direct droplet mass spectrometry sampling delivered through an Unchained Labs Junior automated solid/liquid handling platform to demonstrate the automated monitoring of chemical reactions in real-time. Altogether, the OPI allows for incorporation of mass spectrometry detection while maintaining high throughput sampling.