Echo MS is an open-access, high-throughput mass spectrometry platform that eliminates the need for a chromatography step. An acoustic liquid handler (the Labcyte/Beckman Echo) ejects nanoliter droplets directly from a source plate into an open-port sampling interface connected to a mass spectrometer. Without a column to equilibrate, cycle times drop to 1–5 seconds per sample, enabling analysis of a full 384-well plate in ~2 hours, with replicates. This method is best suited for relative quantitation, screening, and titer assays where high throughput matters more than chromatographic resolution. With this protocol, onboard your analyte for future experiments quickly: the MS conditions (spray voltage, curtain gas, ion source settings) and ejection parameters (volume, interval, carrier solvent) are optimized, and a simple sample prep protocol is established — typically a 2–3 day process for a targeted assay on a known compound. Choose to onboard a method for your substrate or product of interest.