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Multiplexed IMS/TOFMS: the ion mobility marathon
Intensity (ion counts)
Intensity (ion counts)
As the different groups of The enormous complexity of (a) 400 released ions move through the human proteome creates the IMS drift tube, the a predicament: how can 300 groups overlap. The resulting thousands of different prosignal appears to be noise but teins with varying abun200 is actually a complex pattern dances be detected sensitively of detected ions resulting and rapidly? Time-consuming 100 from multiple open and fractionation techniques to closed events. Smith says, “At isolate proteins with low 0 any one time we’re detecting abundances and the need to 6 0 60 20 100 120 10 40 80 Drift time (ns) a mix of fast and slow ions, analyze hundreds of samples 14 (b) but a little while later we’re to draw meaningful conclu500 12 detecting a different mix. We sions generate a massive 10 take the resulting data and workload. In the March 15 400 8 do a mathematical transform issue of Analytical Chemistry 6 300 4 that allows us to reconstruct (pp 2451–2462), Richard D. 2 the ion mobility separation Smith and colleagues at Pacif200 0 and determine the mobilities ic Northwest National Labo14.75970 14.75975 14.75980 14.75985 14.75990 10 6 of the components.” Smith ratory introduce a multi100 and co-workers used the plexed ion mobility 0 known PRS with a multiplexspectrometry (IMS)/TOFMS 8 14 10 12 16 18 10 6 ing approach similar to the approach that helps to resolve Drift time (ns) Hadamard transform to dethe standoff between sensitivity and throughput. In multiplexed IMS/TOFMS, (a) the raw multiplexed MS signal is decon- convolute the complex pattern of detected ions and Smith built on previous voluted into (b) a reconstructed signal by the multiplex transformation. assign ion mobility separation innovations introduced by times for a mixture of peptides. better sensitivity and really take advanhis lab and others. David Clemmer and Multiplexed IMS/TOFMS provides tage of the speed of IMS.” co-workers first combined IMS with a much better S/N than previous inTo improve ion utilization, Smith TOFMS in a practical manner for prostrumentation did. In a conventional and co-workers developed a multiplexteomics research, increasing the resoluexperiment, the process of releasing a ing approach. Instead of ions being retion and decreasing the analysis time of group of ions and detecting the signal leased into the IMS drift tube once per complex mixtures compared with conmust be repeated up to 100 times, and separation, groups of ions are sequenventional LC/MS approaches (Anal. tially accumulated and released at differ- the signals are summed to obtain accuChem. 1998, 70, 2236–2242). IMS rate results. Smith says, “With the mulent intervals. Smith says, “It’s like a separates peptide ions on the basis of tiplexed approach, you can do the same marathon that starts groups of runners their differing mobilities through a gasnumber of ion releases much faster beoff at 5-minute increments. Instead of filled drift tube in the presence of an cause you’re overlapping them. So in having one big pulse at the beginning, electric field. To decrease ion losses and the same period of time, you can get a you’ve got many pulses. This has the enhance sensitivity, Smith and co-workadvantage of allowing more ‘runners’ to much better signal-to-noise ratio.” Mulers incorporated electrodynamic ion tiplexed IMS/TOFMS utilizes ~50% of participate.” The timing of ion releases funnels at the interfaces between ESI the ions created by the ion source, comIMS and IMS/MS (Anal. Chem. 2005, is encoded by a pseudorandom separed with ~1%. quence (PRS), a computationally de77, 3330–3339). “Even with these imSmith says, “This paper is mostly rived series of “gate open” and “gate provements, IMS/MS was still fundamodeling and simple experimental vericlosed” events. Smith explains, “At the mentally limited by the efficiency of ion fication, but we’re aiming in the not-soend of the ion funnel between the ESI utilization,” Smith says. “We were distant future at the initial proteomics and the IMS, we have a voltage-conthrowing away more than 95% of the trolled gate that’s either open or closed. applications.” Those include proteomic ions due to charge-capacity limits for profiling of microbial communities and It may be open for one time increment, the ion trap. We realized that if we cancer-related biomarker discovery. a then closed for three, then open for could use more of the ions created by —Laura Tomky Cassiday five, closed for four.” the ion source, we could achieve much A P R I L 1 , 2 0 0 7 / A N A LY T I C A L C H E M I S T R Y
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