Single bead and hard tag decoding using accurate isotopic difference target analysis-encoded combinatorial libraries

A single fully automated generic microbore liquid chromatography electrospray time‐of‐flight protocol has been developed for the analysis of single beads, single beads with analytical constructs, and isotopically labelled dialkylamine hard tags. The protocol relies upon the incorporation of an isotopic signature into the linker and/or derivatising molecule to give a specific isotopic ratio together with an accurate isotopic difference. These properties facilitate highly specific and sensitive analysis of beads and hard tags using accurate isotopic difference analysis (AIDA) without prior knowledge of the molecular weight. Three open access methods with automated processing have been developed around a core generic approach. Copyright © 2000 John Wiley & Sons, Ltd.