The Leibniz Institute for Analytical Sciences - ISAS e.V. plans to procure high-resolution liquid chromatography - hybrid mass spectrometry systems (LC-MS/MS) to analyze clinical samples with very high molecular coverage and optimal sensitivity. This is particularly required for very small sample volumes, such as heart biopsies, isolated single immune cells after sterile inflammation, or micrometastases. At the same time, the translation of the measurement methods into preclinical applications should be accelerated. Therefore, a combination of two systems is planned that technically complement each other and enable both the identification of biomarker candidates 'Discovery Platform' and the validation of biomarker candidates 'Validation Platform'. The planned sample materials consist of blood (blood plasma, blood cells) and tissue samples from patients. These include, for example: heart biopsies, isolated single immune cells after sterile inflammation, or micrometastases from various tissues. To analyze these samples as effectively as possible, an instrument platform is required that can structurally examine as many analytes as possible in a short time while maintaining very good sensitivity. The device combination to be used should also incorporate modern methods such as 'data-independent acquisition' (DIA). At the same time, focus will be placed on the development of quantitative assays to directly validate the findings in suitable patient cohorts. Based on the experiences at ISAS, the size of such cohorts is in the range of 100-400 patients, in which - depending on the question - about 1000 - 8000 peptides need to be detected to validate the results.

PAR-0001
High-Resolution Liquid Chromatography - Hybrid Mass Spectrometry Systems.
In summary, the following requirements arise: Discovery Platform: - As high mass resolution as possible > 200,000 in overview scan - Ability to couple micro/analytical LC and joint control of the systems - Quick separation of peptides and other biomolecules - Implementation of various fragmentation techniques, e.g. HCD, DDA, all ions parallel (AIF) - Implementation of various techniques for rapid fragmentation (> 15 Hz) of peptides to elucidate their structure. - Low follow-up costs of the LC-MS system - Mass range greater than 6000 m/z for characterizing molecules with high mass and low charge state (e.g. therapeutic antibodies in the blood) Validation Platform: - Adoption of acquisition parameters from the Discovery Platform - High number (> 8000) of analyses that can be targeted detected per hour to achieve sufficient sample throughput for validation cohorts. - Option for MS2 and MS3 fragmentation to reliably distinguish similar analytes - Ability to couple micro/analytical LC and joint control of the systems - Low follow-up costs of the LC-MS system