TRAPPING, DETECTION AND REACTION OF VERY LARGE SINGLE MOLECULAR-IONS BY MASS-SPECTROMETRY

RECENT developments have made electrospray-ionization (ESI) mass spectrometry(1-3) an important technique for measuring molecular weights and studying the structures of large molecules of relative molecular masses approaching 200,000 (M(r) 200K). Analysis of still larger molecules is difficult, however: to obtain a mass/charge ratio within the detectable limits, the ions must bear several charges, but a collection of ions of differing multiple charges presents a Spectrum that is hard to interpret. This problem would be avoided if sufficient sensitivity can be achieved to detect individual molecules. Here we describe a technique that realizes this sensitivity for molecules of M(r) to similar to 7 x 10(6), and which has the potential to be extended to M(r) approximate to 10(9). We use ESI and Fourier-transform ion cyclotron resonance mass spectrometry(4) to obtain repeated measurements of the mass-to-charge ratio of single, highly charged molecular ions. We are able to observe stepwise changes in the charge of an isolated ion owing to its reaction with small molecules introduced into the detection cell. This technique should have wide applications for characterization of polymers and large biomolecules.