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Thinking outside the MS box G
raham Cooks wants to bring MS to the masses. “There will be a time when people individually have access to chemical information about themselves and their environment,” says Cooks. Already, he and his colleagues at Purdue University have developed small mass spectrometers (Anal. Chem. 2003, 75, 250 A). But recently, he and his group took another step toward making MS accessible: They moved the ionization process out of the mass spectrometer (Science 2004, 306, 471–473). The new process, called desorption electrospray ionization (DESI), combines desorption ionization and ESI. But, unlike traditional ionization processes that take place in a vacuum within a mass spectrometer, the entire DESI process occurs in ambient air. Charged solvent droplets are sprayed onto a surface containing a sample. Sample molecules are ionized, desorbed, and transferred through a tube into a mass spectrometer. MS researchers are very excited about DESI. John Fenn at Virginia Commonwealth University says, “I think this latest development from Graham’s lab is a tremendous advance.” Fred McLafferty at Cornell University says that DESI is a simple, clever, and fun approach. Ionizing in air is a big advantage, he says. “In all my years as an analytical mass spectrometrist, probably the most common complaint from potential [users] has been the sampling problem caused by our high-vacuum introduction system,” explains McLafferty. “Some years ago, we marveled when atmospheric-pressure chemical ionization could introduce ionized gas samples directly into the mass spectrometer; now DESI does this for solid samples.” Freed from the constraint of a vacuum, researchers can now analyze a myriad of objects and analytes that previously were inaccessible to MS. “You can do live sam© 2005 AMERICAN CHEMICAL SOCIETY
DESI can ionize molecules on the surface of human skin. (Adapted with permission. Copyright 2004 American Association for the Advancement of Science.)
ples,” explains Cooks, who points out that even molecules on human skin can be ionized by the new process. “You find all sorts of interesting things when you turn [DESI] on yourself,” he adds. In fact, an antihistamine was detected by DESI-MS from the finger of Zoltán Takáts, a postdoctoral fellow in Cooks’s lab, who had swallowed a tablet 40 min earlier. Using DESI, the researchers also examined many plant-based compounds. To demonstrate DESI’s utility in the realm of forensics, Cooks’s group ionized an explosive chemical from a leather surface and a simulated chemical warfare agent from a nitrile glove. Many different types of analytes, such as amino acids, peptides, proteins, drug molecules, alkaloids, terpenoids, and steroids, can be ionized by DESI. (A blank can be used to distinguish true positive signals from contaminants in the air.) Other researchers are already pondering new applications for DESI. Gary Siuzdak at the Scripps Research Institute is excited about its potential for drug pharmacokinetic studies. He says that these analyses could be performed in a high-throughput manner, simply
by rapidly moving the surface and sampling the reaction products. Even more intriguing is the prospect of spatially imaging drugs or endogenous metabolites directly from a tissue. Cooks and his colleagues typically use water, methanol, ethanol, or a combination of water and alcohol as the solvent, which can be tailored for a variety of applications. “If we want to look at things which have some specific acid or base property or for some subclass of compounds, then we can very easily spray with a solution that has an appropriate reagent mixed in,” says Cooks. The reaction of a chemical in the solvent with the sample analyte generates products that can confirm an identification. For example, m/z peaks that were characteristic of a particular enzyme–substrate complex were detected when the substrate was sprayed onto an enzyme sample. A potential limitation of DESI, however, may be its sensitivity. “Will this technique be able to obtain the sensitivity accomplished with ESI on a broad range of molecules?” Siuzdak asks. “It’s an important question for the analysis of endogenous biomolecules, yet [DESI’s] application as it is now is still intriguing.” Although DESI’s sensitivity already compared favorably with that of a commercial MALDI source for lysozyme analysis, Cooks says that sensitivity could be increased with future improvements. According to Cooks, DESI development progressed smoothly, thanks in part to a lab environment that encourages instrument development. All the bits and pieces scattered throughout the workspace enable the researchers to test their creative ideas very easily, he says, and it seems to be working. Perhaps it won’t be too long before personal mass spectrometers show up in your local electronics store. a —Katie Cottingham
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