biostudies-literatureEisert JGenome Canada through Ontario Genomics InstituteBundesministerium für Bildung und ForschungStructural Genomics ConsortiumBayer AG, Boehringer Ingelheim, Bristol Myers Squibb, GenentechDeutsche ForschungsgemeinschaftAlexander von Humboldt-StiftungFonds der Chemischen IndustrieInnovative Medicines Initiative 2 Joint UndertakingDeutsche KrebshilfeHessisches Ministerium für Wissenschaft und Kunste2500658https://www.ebi.ac.uk/biostudies/studies/S-EPMC12825326biostudies-literatureUnknown10(2)Native mass spectrometry (MS) is an important technique in structural biology and drug discovery, due to its ability to study non-covalent assemblies in the gas phase. Drawbacks include the incompatibility of electrospray ionization (ESI) with non-volatile salts and the risk of protein signal suppression by small molecules. Overcoming these often requires offline buffer exchange and/or parallel sample preparation to other methods, reducing the adoption and throughput of native MS. Here, we exploit the dynamics of analytes flowing through an open tubular capillary to keep molecules with a small hydrodynamic radius (e.g., salts) inside a Taylor dispersion regime while pushing larger species (e.g., proteins) into a non-Taylor regime. As such, larger species elute earlier, and are effectively Small methodsNative Taylor/Non-Taylor Dispersion-Mass Spectrometry (TNT-MS) Allows Rapid Protein Desalting and Multiplexed, Label-Free Ligand Screening.PMC12825326875510SchwerpunktTACTICLOEWE109773746137242403ZU1109FAForschungsstipendiumOGI-196TRABITA524226614Maciel EVSDederer VBerwanger ALermyte FKnapp SEisert JJensen HĐikic IMathea SEmpting MBailey HJfalseNative Taylor/Non-Taylor Dispersion-Mass Spectrometry (TNT-MS) Allows Rapid Protein Desalting and Multiplexed, Label-Free Ligand Screening.Native mass spectrometry (MS) is an important technique in structural biology and drug discovery, due to its ability to study non-covalent assemblies in the gas phase. Drawbacks include the incompatibility of electrospray ionization (ESI) with non-volatile salts and the risk of protein signal suppression by small molecules. Overcoming these often requires offline buffer exchange and/or parallel sample preparation to other methods, reducing the adoption and throughput of native MS. Here, we exploit the dynamics of analytes flowing through an open tubular capillary to keep molecules with a small hydrodynamic radius (e.g., salts) inside a Taylor dispersion regime while pushing larger species (e.g., proteins) into a non-Taylor regime. As such, larger species elute earlier, and are effectively 2026-01-01T00:00:00Z2026 Jan2026-06-06T20:15:50.741Z2026-06-04T03:14:17.348ZS-EPMC128253264033142710.1002/smtd.202500658