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Accelerator MS (AMS) better watch its back because intracavity optogalvanic spectroscopy has now landed on its turf. Daniel Murnick and colleagues at Rutgers University describe the new technique, which can detect attomoles of 14CO produced from submicrogram 2 samples, in their recent AC paper (DOI 10.1021/ac800751y). The method has applications in areas such as monitoring of atmospheric CO2 and microdosing analyses in drug development. Normally, AMS is the technique of choice for measuring vanishingly small numbers of 14C atoms in bioanalytical tracer studies. But its problems include its size (the instrumentation takes up a whole room), technical complexity, and cost. Also, because AMS requires elemental carbon for detection, carboncontaining molecules need to be quantitatively reduced before analysis. So Murnick and his colleagues developed intracavity optogalvanic spectroscopy. The spectrometer is a benchtop instrument that measures CO2 directly. The method has the same sensitivity as AMS, but it’s easier and faster to perform. The investigators had initially established the laser-assisted ratio analyzer (LAR A) technique to measure the natural 1% abundance of 13C. Whenever Murnick presented LAR A, he was always asked if he and his colleagues could detect 14C, which is present at even lower levels—~1 ppt. “Our improvements with 13C were such that, a few years ago, I felt it was possible,” he says. LAR A’s sensitivity depended on the optogalvanic effect, a phenomenon in which an optical input causes an electric change in a weak gas discharge. The optical input resonantly interacts with specific species in the discharge and alters the conductivity of the discharge. To analyze 14C, Murnick and colleagues took advantage of the optogalvanic effect again, but this time combined it with intracavity spectroscopy, which is widely used in molecular spec-
(a)
LAWRENCE LIVERMORE NATIONAL LABORATORY
analysis gets faster and easier DANIEL MURNICK
14C
(b)
14 C
analysis by (a) the benchtop intracavity optogalvanic spectrometer is easier and faster than by (b) AMS. The facility at the Lawrence Livermore National Laboratory is pictured here (https://bioams.llnl.gov).
troscopy, plasma diagnostics, and chemical reaction kinetics. They purchased a stable 14C laser that would be precisely in resonance with molecules of 14CO2 and changed the experimental setup so the sample cell sat inside the laser. At that point, a few kinks still needed to be worked out. For example, “there was background from 12C and 13C. That was a major experimental hurdle that we had to overcome,” says Murnick. The researchers eventually figured out a way to calibrate the spectrum to eliminate the background. The researchers were now ready to test the sensitivity of the instrument. And when they did, they were taken aback. “The first time we did the experiment, we couldn’t believe the sensitivity we got. It really was a ‘Eureka!’ moment,” says Murnick. “We then thought, ‘It can’t be this good’, and it took, as in all science, many months to understand what was going on.” The investigators now think their attomole sensitivity to 14C can be attributed to interactions between the small numbers of 14CO2 molecules in the sample cell with the discharge’s many resonant photons. The optogalvanic effect allows the interactions to be measured. “It’s like a form of calorimetry when you’re looking at tiny energy changes,” explains Murnick, but he adds that in this case, they are measur-
ing electric current instead of heat. The technique is adaptable and can be easily coupled to LC. As fractions come off the LC column, they can be oxidized into CO2 and run into the spectrometer for analysis. And the scope of applications is wide—pharmaceutical analyses, carbon dating, and environmental monitoring. For instance, pharmaceutical companies rely on microdosing analyses to get pharmacokinetic information on new drugs; for such analyses, nontherapeutic trace doses of labeled drugs need to be measured. Because the spectrometer can deal with a continuous flow of CO2, environmental air monitoring also becomes possible. Fossil fuels lack 14CO2 because they are so old (the half-life of 14C is 5730 years); CO2 released from modern-day plants has the normal trace-level abundance of 14C. “If you monitor the radiocarbon in the atmosphere, you get the best measure of how much of the CO2 comes from fossil fuels,” says Murnick. He explains that in this case, the AMS technique can be difficult: “You have to collect . . . a lot of air, extract CO2, and reduce it to a block of carbon.” Although a lot of data have been collected by AMS, it’s very hard to do, he says. But with the new technique, he adds, “we can do real-time continuous monitoring.” a —Rajendrani Mukhopadhyay J u ly 1 , 2 0 0 8 / A n a ly t i c a l C h e m i s t r y
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