(1389-B) Ultra-High Throughput Sample Quality control enabled by Sciex Acoustic Ejection Mass Spectrometry (AE-HRMS) Technology
Monday, February 5, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: High throughput screens (HTS) play a vital role in drug discovery by providing speed, evidence, and cost-effective methods to identify potential hits in a sample library. Confidence in the results generated in HTS screens relies heavily on the quality of samples within a library. Pfizer's internal sample quality control (sQC) has traditionally relied on robust LCMS methods that provide purity and mass confirmation data. However, generating QC data in this manner requires extensive time (~90 seconds per sample) and resources that can delay a screen or lead to samples being screened without current QC data. Acoustic Ejection High-Resolution Mass Spectrometry is a method that has been introduced in recent years to Pfizer's internal QC to enable QC in a timely fashion on large compound libraries. Ultra-high-throughput sample QC accomplished by AE-HRMS methodologies have been validated against traditional LC-sQC workflows in Pfizer's internal system. It provides a 90+% method agreement in a fraction of the time it would take to analyze a sample (~2 seconds per sample). In addition to its speed, AE-HRMS requires only nanoliters of samples and works with Echo 384 and 1536 platting formats commonly used to reformat samples for HTS. Furthermore, samples can be ejected from various liquid classes, including DMSO, aqueous, and organic compositions, which allows AE-HRMS QC screening to be done directly from an assay plate. A variety of tools have been developed to meet the speed of AE-HRMS sample acquisition and enable SQC workflows: 1) HRMS target analysis that scores targets based on a targets mass error and isotopic ratios, 2) mass spectral purity analysis that automatically detect background signals and scores a targets purity based on additional masses found within a sample, and 3) library comparisons software that can be used to assess the quality of a sample library across conditions, such as time or storage practices. Additional techniques are being developed to use AE-HRMS technologies for identifying sample wells that contain trace metals from reactions before being delivered to assays. These tools, paired with high-resolution mass spectral data, allow a more thorough analysis and understanding of the quality of samples within a library.