SAN FRANCISCO A new method for using mass spectrometry to analyze samples as they exist in nature may have broad applications, including the proteomic analysis of samples in situ, forensic work, homeland security, and pharmaceutical applications.
The method, called Desorption Electrospray Ionization, or DESI, was commercialized by the Indianapolis-based company Prosolia. Graham Cooks, the Purdue University chemistry professor who developed the DESI technology, originally published his work on the new method in Science in October 2004.
"The idea is that you spray an electrospray of solvent onto samples," said Cooks during his talk on DESI at the Seventh International Symposium on Mass Spectrometry in the Health and Life Sciences, held here this week. "There is zero sample prep, and analysis time is extremely short."
Showing a photo of a bunch of red flowers being sprayed by the solvent electrospray, Cooks explained that his new method allows for the analysis of biological samples as they exist in nature. Molecules from the surface of the sprayed sample are ionized and passed into a mass spectrometer for analysis.
"You can do direct tissue analysis," said Cook. "If you're looking at serum, you can take the serum and put it on a suitable surface, for example paper, and then submit the sample for overall compound analysis. Or you can look at, for example, freshly cut chicken heart tissue with absolutely no sample prep."
"This is very exciting for mass spec imaging and other commercial applications, for example for the detection of explosives. But I wouldn't use this for traditional protein work because of the lack of separation. There's only so much space in a mass spectrum. If they took a blood sample and tried to image proteins, they'd see hemoglobin, hemoglobin and a little bit of albumin. You're only ever going to see the most abundant proteins."
While Cooks' new method seemed to have good applications if researchers already know what protein or compound they are looking for, several proteomic researchers said they were skeptical that the technology would work for proteomic discovery of disease biomarkers.
"This is very exciting for mass spec imaging and other commercial applications, for example for the detection of explosives," said Julian Whitelegge, a professor at the David Geffen School of Medicine at the University of California Los Angeles who does top-down proteomics work. "But I wouldn't use this for traditional protein work because of the lack of separation. There's only so much space in a mass spectrum. If they took a blood sample and tried to image proteins, they'd see hemoglobin and a little bit of albumin. You're only ever going to see the most abundant proteins."
John Haley, a senior fellow at OSI Pharmaceuticals, concurred with Whitelegge. "It's good if you're looking for very simple things with a background that's not too complicated," he told ProteoMonitor. "For proteomics, I'm not so sure."
However, Christopher Farnsworth, a staff scientist at Amgen, noted that in Richard Caprioli's laboratory at Vanderbilt University, researchers have successfully analyzed histological samples using MALDI.
"If the Caprioli team can look at whole protein modifications, this new technology could [also] be very valuable," Farnsworth said. "Think about if you could put a drop of blood onto a piece of blotter paper and just stick it in."
Cooks acknowledged that the technology was not best suited for finding low-abundant proteins within complex samples.
"If you take the world's most complex samples, you're going to have to do separations in advance," he said. "But you can get away with less."
If it is not quite suitable for proteomics discovery work, the new DESI technology may have a broad range of other applications, including forensic work, homeland security and pharmaceutical applications.
Cooks said he envisioned his technology being used at airports to analyze clothing and suitcases for trace amounts of explosives.
In forensics, the technology could be used to analyze, for example, blood stains on carpet, other surfaces with dried blood, or to analyze live human skin, for example, on a human finger.
The technology may also be used for drug testing. In his presentation, Cooks showed that in the mass spectrum of an individual's finger 50 minutes after the individual ingested the allergy medication loratadine, also known as Claratin, Loratadine could be detected.
As an example of a pharmaceutical application, Cooks showed the results of a series of multivitamin tablets analyzed directly using DESI-MS. With a single scan, the technology was able to identify the majority of the vitamins contained in the tablet, even those at low concentrations. Cooks proposed that this could lead to applications in pharmaceutical quality control.
"There are a lot of uses for the technology. At this point, it's about how to make it affordable so that it can be used, for example, in all the airports," said Mahbod Hajivandi, a senior research associate at Invitrogen. "For quick trace analysis, for example, if you're testing for biological warfare, it could be really useful."
Tien-Shun Lee ([email protected])