"Lab of the Future"-Today: Fully Automated System for HighThroughput Mass Spectrometry Analysis of Biotherapeutics

Here we describea state-of-the-art, integrated, multi-instrumentautomated system designed to execute methods involved in mass spectrometrycharacterization of biotherapeutics. The system includes liquid andmicroplate handling robotics and utilities, integrated LC-MS, alongwith data analysis software, to perform sample purification, preparation,and analysis as a seamless integrated unit. The automated processbegins with tip-based purification of target proteins from expressioncell-line supernatants, which is initiated once the samples are loadedonto the automated system and the metadata are retrieved from ourcorporate data aggregation system. Subsequently, the purified proteinsamples are prepared for MS, including deglycosylation and reductionsteps for intact and reduced mass analysis, and proteolytic digestions,desalting, and buffer exchange via centrifugation for peptide mapanalysis. The prepared samples are then loaded into the LC-MS instrumentationfor data acquisition. The acquired raw data are initially stored ona local area network storage system that is monitored by watcher scriptsthat then upload the raw MS data to a network of cloud-based servers.The raw MS data are processed with the appropriately configured analysisworkflows such as database search for peptide mapping or charge deconvolutionfor undigested proteins. The results are verified and formatted forexpert curation directly in the cloud. Finally, the curated resultsare appended to sample metadata in the corporate data aggregationsystem to accompany the biotherapeutic cell lines in subsequent processes.