LAUSR

We present an acoustic ejection mass spectrometry (AEMS) setup for contactless ESI-MS based sample injection at sampling rate faster than current ESI and MALDI techniques. For the direct transfer of samples out of 384-well plates into a modified ESI source, an open port interface (OPI) was combined with a modified acoustic droplet ejection (ADE) system. AEMS has the potential to elim-inate bottlenecks known from classical MS approaches, such as speed, reproducibility, carryover, ion suppression as well as sample preparation and consumption. This setup provided a drastically reduced transfer distance between OPI and ESI electrode for opti-mum throughput performance and broadens the scope of applications for this emerging technique. To simulate label-free applica-tions of drug metabolism and pharmacokinetics (DMPK) analysis and high-throughput screening (HTS) campaigns, two stress tests were performed regarding ion suppression and system endurance in combination with minor sample preparation. Maximum sam-pling rate was 6 Hz for dextromethorphan and d3-dextrorphan (each 100 nM) for 1152 injections in 63 s at FWHM of 105 ms and %RSD of 7.7%/7.5% without internal standard correction. Enzyme assay buffer and crude dog plasma caused signal suppression of 51%/73% at %RSD of 5.7%/6.7% (n = 120). An HTS endurance buffer was used for >25.000 injections with minor OPI pollution and constant signals (%RSD = 8.5%, FWHM of 177 ms ± 8.5%, n = 10,557). The optimized hardware and method setup resulted in high-throughput performance and enables the further implementation in a fully automated platform for ESI-MS-based high-throughput screening.