(1147-B) Sample Preparation for Next-Generation Mass Spectrometry for High-Throughput Screening in Drug Discovery

Abstract: There is a growing demand in biopharmaceutical laboratories for label-free, high-throughput screening using mass spectrometry (MS). In particular, MALDI-TOF (Matrix Assisted Laser Desorption/Ionisation Time-of-Flight) MS is proving valuable for screening small molecules, peptides and proteins for enzyme assays in both high-throughput (HTS - 10,000 compounds/day) and ultra-high-throughput (Ultra-HTS - 100,000 compounds/day) modes. The high-throughput mode of analytical instruments such as the Bruker MALDI Pharma Pulse® MS aims to generate as much and, above all, as high-quality data as possible. This places special demands on sample preparation. In collaboration with Bruker, Analytik Jena is presenting an advanced automated liquid handling system that increases the quality and efficiency of MS sample preparation.

The CyBio Well vario pipetting robot (96-1536 channels) achieves a coefficient of variation (CV) of less than 5% and enables the transfer of small spots down to 100 nL. The desalting technology (on target washing) of spots on the target plate guarantees a consistently high signal quality in the readout process of the mass spectrometer. A high quality of the pipetted spots, which correlates with a high data quality in the analysis process, is only one factor for a stable process in high-throughput screening. Not only a high quality of the individual spot, but a consistently high quality across 1536 parallel pipetted spots requires further innovative technological approaches in the sample preparation process, such as active spot drying. Active drying technology ensures that all spots are dried homogeneously and shortens the cycle time. These unique innovations for sample preparation mean that the full potential of the Bruker MALDI Pharma Pulse® MS can be utilised with a read-out rate of up to 3 wells/sec. This liquid handling automation solution for drug screening can overcome application bottlenecks and lead to a breakthrough in throughput, robustness, and reliability of MALDI-MS sample preparation, enabling ultra-HTS screening with fully integrated Bruker MALDI PharmPulse® MS systems.