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Research Projects

Novel tandem MS instrumentation for ultrasensitive, rapid & comprehensive characterization of proteins

At present, most tandem mass spectrometry is performed by (i) isolating the precursor ion of interest (often from a complex mixture of ion species), (ii) causing this specific ion of interest to dissociate, and (iii) measuring the resulting fragmentation spectrum. Although this is an enormously enabling strategy, it is inherently extremely wasteful — since, at any given time, all ion species except for the one that is specifically isolated are thrown away. For example, in a typical neutral loss linked-scan experiment (see Fig. below), the maximum possible efficiency is Δm/M, where Δm is the m/z isolation window and M is the m/z scan range. Typical values for Δm = 1 - 4 and M = 2000 — 4000, yielding a maximum efficiency for this type of experiment of ~1/1000.

We are currently investigating a new strategy for overcoming this inefficiency (see Fig. below). Here, we capture ions (generated, e.g., from a proteolytic peptide mixture) in a novel high capacity ion trap (capable of holding ~107 ions), cool these ions in the trap, sequentially eject the trapped ions at increasing m/z ratios, & fragment each of these ejected ions in turn — thereby producing MS/MS information on all the trapped ion species, without the usual scanning losses.