instrumentals
Clathrates lead to MS without a matrix A new surface-based MS ionization technique enables the analysis of untreated biological samples.
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Jon V. Apon, Trent Northen, and Gary Siuzdak
f you were lying on a giant honeysurface that yielded smaller pores. utility of being able to analyze biologicomb that was zapped and exploded, The team tried a dozen different cal fluids with minimal or no sample vaporizing the honey underneath you, initiator molecules ranging from 200 preparation. “In clinical diagnostics where would you go? Up. That’s the to 14,000 Da, and the perfluorinated and prognostics, if this new technology principle behind the new MS ionization siloxanes turned out to be the best can be used for very simple analysis of technique developed by Gary Siuzdak initiators for laser NIMS. Control urine and blood and other biofluids, and colleagues at the Scripps then it could be a way to Research Institute, the Unimove closer to the clinic and versity of California Santa screen samples from many Barbara, and the University patients,” says Jensen. “But of Oregon (Nature 2007, again, before that can be GPCho 449, 1033–1063). achieved, the method has m/z 782 Nanostructure-initiator to prove its robustness and MS (NIMS), a laser desorpreproducibility.” Like Jention method, bypasses the sen, Amina Woods at the need for matrix; instead, it National Institute on Drug m/z 100 1500 uses clathrate nanostrucAbuse is impressed with the tures. Wikipedia defines lack of sample preparation in a clathrate as “a chemical MS imaging of glycerophosphatidylcholine (GPCho) localized around NIMS, but she would like to substance consisting of a lata developing vertebra from a mouse embryo section (right). The see more work done on the tice of one type of molecule resulting 300-µm-wide false-color mass intensity image (expanded single cells and proteins, she trapping and containing a view) reveals a higher intensity surrounding the developing vertesays. second type of molecule.” In bra. Order of intensity: red > yellow > cyan > dark blue. Siuzdak and colleagues NIMS, liquid initiator molfind NIMS to be compleecules are trapped within a nanoporous experiments confirmed that the initiator mentary in many ways to MALDI and silicon surface, and the analyte is depos- was not acting as a matrix and that the ESI. For example, NIMS is better for ited on top of this clathrate. When the phenomenon was a unique action of the analyzing metabolites than MALDI and surface is heated by a laser or ion beam, clathrate, not the nanoporous surface or is more tolerant of salt and yields differthe initiator molecules are vaporized, the initiator molecule individually. In ent charge states than ESI. “But with and the analyte molecules go into the addition to a laser beam, the team also metabolomics, we not only get good acgas phase. Siuzdak says, “We’ve been tested the principle with an ion beam; curacy because we’re in a relatively low trying to soften the surface up in order they termed this method ion NIMS. mass range—which gives us some into make the molecules come off in an The group’s second breakthrough formation in itself, like elemental comintact way.” occurred when postdoc Oscar Yanes position—but on top of that, you also Previously, the group had used pocame up with the concept of ablating get MS/MS data . . . a lot of MS/MS rous silicon surfaces with their desorpthe top layers of tissue samples with a data,” Siuzdak says. tion/ionization on silicon (DIOS) tech- higher laser power before performing The researchers are handling the nique. Then, postdoc Trent Northen NIMS analysis of the tissue at the lower mountains of data they’re producing had the idea of trying to remove the laser power. “We think that for NIMS, with their own open-source bioinforsurface from underneath the sample we need a very, very thin layer of mematics software (XCMS) and the online while it was in a vacuum. “We kicked tabolites or peptides just in contact with metabolite database (METLIN) that around ideas of how to do this, and or on top of the initiator,” says Yanes. they developed in collaboration with eventually hit on this idea of making a With this pre-ablation step, good specRuben Abagyan’s group and the Scripps surface very hot, which would vaporize tra could then be obtained from tissue Center for Mass Spectrometry. a viscous, vacuum-compatible liquid,” or blood without any sample pretreatSiuzdak is enthusiastic about the Northen says. In progressing from ment or the need for super-thin tissue potential of NIMS for metabolomics. “I DIOS to NIMS, they switched from slices. think this could open up another winan n-type to a p-type silicon and found Ole Jensen of the University of dow into the metabolomics world.” a a simpler procedure for preparing the Southern Denmark highlighted the —Christine Piggee © 2008 American Chemical Societ y
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