In a lab in Indianapolis , a student takes a tablet of a common antihistamine. About 40 minutes later, researchers detect the drug in his system simply by directing a spray of alcohol and water onto his finger and instantly analyzing the mixture with a common lab instrument. This is not a scene from CSI or ER but rather a real-life demonstration of a new technique developed by Purdue University analytical chemist R. Graham Cooks and his colleagues. The advance expands the utility of a common laboratory method called mass spectrometry, and it could soon enable doctors and forensic specialists to immediately reveal what substances are present on surfaces such as wood, cloth, and even skin, eliminating the need to send samples off the lab and wait for the results.
This method that they have worked out is a means of providing a new kind of nose on an old dog, says John Fenn, an analytical chemist at Virginia Commonwealth University who won a share of the 2002 Nobel Prize for chemistry for developing the technique on which the new method is based. It’s very exciting.
Mass spectrometry is used to identify unknown samples by precisely determining their molecular weight. But analyzing substances this way requires that the molecules be given an electric charge. This ionization process has entailed the use of cumbersome vacuum chambers or extensive sample preparation, limiting mass spectrometry’s use to the lab. Cooks’s new technique, described in the October 15 issue of the journal Science, demands neither special preparation nor a vacuum. Instead, an electrically charged stream of pressurized liquid such as water or alcohol (or an alcohol-water mixture) is sprayed onto any surface to be analyzed. The droplets act as microscopic projectiles, knocking off invisible bits of the sample and transferring charge to those molecules as well. The droplets, along with whatever sample molecules they are now carrying, are then sucked into a standard mass spectrometer.
Forensics and public safety applications top Cooks’s list of possible uses for the new technique. You could use it to examine a crime scene; you could use it to examine a suspect, he says. Another use Cooks suggests is airport security, where agents could identify explosive residues on baggage or passengers more quickly and specifically than is possible with current techniques. Fenn expands the list: You can look at the surface of soils or automobiles, or anything else, and look for toxic substances, chemical warfare agents, or even biological warfare agents.
Cooks’s new method allows researchers to analyze any ordinary material, such as cloth, leather, or paper, in the air, and to move it around during the process. This would enable them to quickly examine an entire surface in a single experiment, scanning a suitcase for traces of explosives, for instance, instead of having to take samples from different locations. Rather than taking the samples back to the lab, you would get an on-the-spot answer, Cooks says. His team has been able to analyze as many as 20 samples per second in the lab with sensitivity comparable to that of conventional mass spectrometry experiments. For use in the field, Cooks says, the spray system would be coupled to a miniature mass spectrometer, which the team is developing separately. In fact, over the last four to five years, Cooks’s group has produced a complete instrument weighing less than 16 kilograms. You can carry it around like a backpack, Cooks says. He hopes to develop even smaller, handheld systems in cooperation with researchers at Sandia National Labs.
Other experts predict important medical uses. One application that could really be powerful is looking at drug molecules, says Gary Siuzdak, senior director of the Center for Mass Spectrometry at the Scripps Research Institute in La Jolla, CA. Cooks’s spray technique could be used to rapidly analyze multiple blood samples in drug development experiments, such as those that determine what chemicals the body creates as it metabolizes a drug. The new technique, Siuzdak says, could potentially speed up the whole drug discovery process.
The experiment in which the team detected an ingested antihistamine by analyzing the subject’s skin particularly fascinates both Siuzdak and Fenn. That is very impressive, Siuzdak says. Graham has really done something very interesting and innovative here. Fenn says the results suggest the possibility of immediately diagnosing what medications a patient has taken or what foreign substances are in his or her body. The remarkable thing is that you can do this on the skin of a person, he says. It is perfectly painless and harmless. Combined with a portable mass spectrometer, the technique could be used in an emergency room or even by paramedics in the field.
Before any of this can happen, however, the researchers must answer some questions. They must, for instance, determine what types of surfaces can be analyzed, what substances can be reliably detected, and the final sensitivity of the method. We may be missing stuff, Cooks acknowledges. We’ve only had this experiment going for a couple of months. I can’t claim it’s universal. Already, however, Purdue has licensed the technology to Indianapolis-based startup Prosolia for commercial development. Within just a few years, the technique could make real-life medicine and criminal investigation as quick as the Hollywood versions.
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