Central laboratory facilities, large-scale biomarker identification studies, and drug discovery campaigns, all rely on high-throughput experimentation, either in terms of organic synthesis or on the analysis of complex biological samples. Traditionally the use of mass spectrometry (MS) in these applications has heavily relied on sample preparation and purification approaches prior to analysis. This, although effective at dealing with complex matrices, drastically limits the inherent throughput of MS analysis and generates multiple challenges when dealing with large-scale sample cohorts. Here we describe the operation and several applications of an automated robotic platform, available now as a Discovery Park Facility, based on desorption electrospray ionization (DESI) MS for the rapid and direct (i.e. no sample workup needed) analysis of high-density (6,144 samples per plate) arrays of samples with throughputs better than 1 sample per second, including relevant examples in biomarker studies, drug functionalization, and bioactivity assessment for drug discovery.