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SIMS and MALDI: better together
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ANALYTICAL CHEMISTRY /
DECEMBER 1, 2008
tical. “The secondary ions come off the surface of the sample with their own energies,” says Winograd. “But by the time they collide with the nitrogen and get through the quadrupole, the secondary ions look the same, regardless of how they were created.” The combination of MALDI and SIMS in a single mass spectrometer allowed the researchers to switch quickly back and forth between the extraction methods in the same sample. The investigators demonstrated the complementarity of the methods in the analysis of digitonin and gramicidin S and in the imaging of gramicidin S overlaid with a copper grid. The introduction of MS/MS and a continuous primary ion beam to the SIMS method is expected to greatly extend current chemical imaging capabilities. “The ability to do MS/MS imagingOto be able to image one of the fragmentation products of a known ionOreally cleans up the image,” says Winograd. “And with the continuous primary ion beam, you can obtain enough secondary ion counts for good imaging in far less time than in a pulsed-beam system. One of our images took on the order of 7 hours, whereas in a typical pulsed-beam system, it would have taken 2.5 years to deliver the same number of primary ions.” Winograd and Carado’s research team is now working on a second-generation instrument with higher spatial resolution and enhanced imaging performance. Winograd also notes that the SIMS imaging field will be further advanced by the introduction of another SIMS instrument with a continuous C60 ion beam and MS/MS capability. In another AC paper (2008, DOI 10.1021/ac8015278), John Vickerman, John Fletcher, and colleagues at the University of Manchester and Ionoptika (both in the U.K.) describe this new instrument. The paper from the Winograd and Carado research teams appears in the November 1, 2008, issue of AC. —Laura Cassiday
ANTHONY CARADO
MS imaging promises unprecedented opportunities to visualize the chemical makeup of a cell. The most commonly used ion extraction techniques for MS imaging experiments are MALDI and secondary ion MS (SIMS). However, each method has drawbacks that limit the ability to obtain a detailed chemical snapshot. That’s why Anthony Carado, Nicholas Winograd, and colleagues at Pennsylvania State University and Applied Biosystems/MDS Analytical The C60 hybrid quadrupole orthogonal TOF mass specTechnologies united the two techtrometer enables high-resolution chemical imaging in the niques in a single mass spectrometer, absence of matrix. In fragment ion imaging (illustrated which will offer expanded capabilities to above), all ejected ions are funneled into the first quadruprobe the chemical compositions of pole rod. The parent ion of interest is selected and fragcomplex samples. They report their mented in the second and third quadrupole rods, respecresults in a new AC paper (2008, DOI tively. The fragments then enter the TOF detector for 10.1021/ac801712s). mass analysis, and from those data, an image is created. To generate a chemical image with MALDI or SIMS, researchers raster scan across the sample surface and acquire According to Carado, the biggest challenge thousands of mass spectra at different locawas minimizing the fragmentation of the tions. Regions with particular chemical com- C60 cluster ions in the high-pressure (8 positions are identified and color-coded to mTorr) region above the sample. He says, produce an image. In MALDI, the sample is “We needed high gas pressure to increase treated with a thin coating of matrix before the throughput of the secondary ions, but desorption with an ionizing laser beam. In we had to make some alterations to prevent C60 SIMS, the sample (which does not rethe high pressure from negatively affecting quire a matrix) is bombarded with a beam of the C60 primary ion beam.” To minimize C60 cluster primary ions, or buckyballs, that C60 fragmentation, the investigators fitted a dislodge secondary ions for mass spectronose cone to the end of the C60 gun column metric detection. and positioned the tip in close proximity to According to Winograd, the two ionizathe sample surface (⬃3 mm away). tion methods are highly complementary. The new configuration offers several ad“MALDI gives fantastic sensitivity and betvantages over traditional C60 SIMS. For ter detection of peptides and higher-mass example, the hybrid quadrupole orthogonal molecules but suffers from relatively low TOF mass spectrometer uses a continuous lateral resolution [20⫺50 m],” he says. rather than pulsed primary ion beam, which increases the number of available primary “The SIMS method gives the possibility of ions by up to 4 orders of magnitude comhigher [nanometer-scale] lateral resolution pared with conventional TOF SIMS. The because you can focus the ion beam better than you can focus the laser beam. Also, you implementation of ion trapping in the new instrument also improves the transmission have less chemical noise in the lower-mass efficiency of secondary ions. region, where you might be interested in Unlike most commercially available drugs or lipid molecules.” SIMS instruments, the new mass spectromTo develop a mass spectrometer that eter has MS/MS capability, which is crucial offers MALDI, SIMS, and ESI capabilities, for the analysis of complex biological Carado, Winograd, and co-workers added a samples. The MS/MS spectra of secondary C60 cluster-ion source to a hybrid quadruions created by MALDI and SIMS are idenpole orthogonal TOF mass spectrometer.
10.1021/AC8021828 2008 AMERICAN CHEMICAL SOCIETY
Published on Web 11/06/2008
