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Chemical mass shifts in ion traps Quadrupole ion traps have been important to MS since the early 1980s, when the mass-selective instability operating mode was first developed. The technique, which was initially limited to the detection of ions with m/z < 1000, was soon augmented by resonant ion ejection, extending ion trap ranges to m/z ~70,000. Regardless of the ejection mode, early devices suffered from errors in apparent m/z ratios for many ion species. Although chemical mass shift, as the phenomenon is generally known, is corrected in commercial systems by adjusting ion trap geometry, studies have shown that small shifts may persist for some ion species. Other than the attempt to eliminate the problem, chemical mass shifts have received relatively little attention from academia and industry. In this issue of Analytical Chemistry (pp 2677–2683), R. Graham Cooks and co-workers at Purdue University take a closer look at chemical mass shifts, hoping to develop a deeper understanding of the effect and potentially use it to their advantage. According to a model Cooks’s group developed, chemical mass shifts arise from defects in ion trap fields. Apertures in the trap electrodes, which provide egress for ejected ions, are the primary source of the defects. The field errors can delay ion ejection by hundreds of microseconds. In itself, the delay is not detrimental and leads only to an easily corrected calibration error.
However, when ions interact with buffer gases, which are introduced to enhance spectral resolution and trapping efficiency, the ejection delay may be modified through collisions between ions and gas molecules. Because scattering and fragmentation
Collisions During Ejection No Collisions
With Collisions
Mass Shift
Buffer gas molecules improve ion trap resolution and induce compound-dependent shifts in mass measurements.
cross sections are functions of ion chemistry, interactions between ions and buffer gas molecules result in chemically dependent delays and relative changes in the apparent m/z for different ions, despite identical masses and charges. The Purdue model suggests several ways to control chemical mass shift in ion traps. Modifying ion trap geometry, explains Cooks, leads to
Universal on-chip RI detection Despite the broad array of microscale detection strategies, the need still exists for a universal chip-based detector. Refractive index (RI) approaches are simple and universal and have the potential to fill that void. In this issue of Analyti-
higher-order fields that compensate for the aperture effects and rapidly propel ions from the trap, reducing delays and the associated interactions with buffer gas molecules. Alternatively, Cooks’s group has accomplished similar feats by judiciously selecting the resonance ejection working point. Still another alternative is to reverse the conventional scan direction so that high-mass ions are ejected before low-mass ions. Although it’s likely that Cooks’s work will lead to new routes for reducing mass shift artifacts and enhancing MS resolution, the work may provide other, more profound benefits. Cooks explains that most MS approaches involve detecting ionic species solely on the basis of m/z, and, therefore, they cannot distinguish between various isomeric ions. “What we’ve done,” says Cooks, “is demonstrate that you can, in fact, have characteristics of an ion, other than the m/z ratio, show up in the mass spectrum.” Cooks suspects that, in coming years, ion trap MS systems may offer analysts a choice of operating modes: conventional m/z analysis with chemical mass shifts thoroughly suppressed, chemical mass shift analyses, or other resolution-enhancing scan modes that arise from research at Purdue and elsewhere. Cooke says “I don’t think it’s likely that it’ll be done the way that we’ve done it [by varying physical ion trap dimensions], but methods of controlling fields and optimizing them for new kinds of uses, like chemical mass shifts, are probable.” James R. Riordon
cal Chemistry (pp 2690–2695), Darryl J. Bornhop and coworkers at Texas Tech University show that RI measurements based on backscatter interferometry are surprisingly well suited for chip-scale devices. A simple optical train, consisting of a laser source, mirror, and photodetector, is used in the on-chip detection
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system. The setup is similar to their previous microinterIn that respect, it has potential for use as a flow sensor for ferometric backscatter detector (Anal. Chem. 1999, 71, on-chip, picoliter volume, time-resolved enthalpy measure369 A), but instead of whole capillaries, the new detector ments, he says. has etched channels, which have the shape of a half capilThe sensitivity of the detector has already been improved lary or hemisphere, on fused-silica or by switching from a slit/photodiode glass chips. to an avalanche photodiode detector “We didn’t think that if we were to (APD), says Bornhop. “When we cut a capillary in half, put a plate on went to an APD, we got a better sigtop of it, and shine a light on it, we nal output for the same photon flux,” would get good interference pathe explains. They also found that terns,” says Bornhop. But they did. changing from a He–Ne to a diode “Not only do we get high-contrast laser source reduced the noise in the fringes, but the fringes shift spatially system. A correction feedback loop in a way that is very sensitive to the that keeps the intensity of diode lasers optical pathlength changes of the stable is responsible for this drop in fluid in the channel.” In other words, noise, says Bornhop. He–Ne lasers if the detector is configured properly, don’t have such a correction and it can sense RI changes. therefore often have large intensity In its current configuration, the fluctuations. on-chip RI detector can measure mi“Ultimately, the way to do this exBackscatter interference pattern produced cromolar levels of solutes in picoliter periment is with a position sensor,” from the interaction of an unconditioned volumes, but efforts to improve its says Bornhop. “Because what you relaser beam with an etched channel. Shifts in sensitivity are under way. “To really ally want to do is measure the position fringe patterns indicate changes in the reapply it to the kinds of things we’d of the fringe as a function of time and fractive index of the solution. like to, we are probably a factor of 5 not necessarily its intensity.” Those away,” says Bornhop. He envisions experiments are currently under way. the detector being used for applicaUsing an optical model, they are tions such as quantitative protein sequencing and with CE also examining what effect the ratio of the cover slide to for high-throughput screening. “You could multiplex the substrate thickness has on fringe spacing and shift. “The device and have multiple separations analyzed simultaneous- hangup right now is trying to get the chips made in the ly,” he adds. In addition to RI changes, the on-chip detec- appropriate dimensions, to confirm that the predicted imtor is capable of sensing millidegree temperature changes. provement is what we get empirically.” Britt Erickson
GOVERNMENT AND SOCIETY Clinical diagnostics in need of standards In vitro diagnostic (IVD) medical devices in the European Union (EU) market were allowed to begin displaying a stamp of approval or CE mark on June 7, which indicates compliance with European Directive 98/79/EC. The first use of this new label marks a major milestone in a 5-year transition period, which began with the publication of the directive in December 1998. Worldwide, the IVD market is estimated at $20 billion (excluding home test kits), with about $5.6 billion of that coming from Europe. Although
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laboratory supplies, such as reagents and calibrators, make up the majority of the IVD market, analytical instruments comprise about 13% of it. IVD products are used in many applications, from diagnosing diseases to determining the effectiveness of medical treatments to identifying microorganisms in food and drugs. The directive is intended to eliminate trade barriers within Europe and ensure better measurements for health care decision making by creating a single mark of approval for all IVD products on the EU market. Over 60% of the EU’s IVD market, however, is imported from the United States, which,
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as many U.S. IVD manufacturers fear, currently does not have the necessary resources to meet the requirements of the directive. By December 2003, all new IVD products on the EU market must have the CE mark. Existing IVD products without the CE mark can only remain on the market until December 2005. If U.S. manufacturers are unable to get the CE mark on their IVD products in time, they will lose the ability to sell their products in Europe. According to Willie May, chief of the Analytical Chemistry Division at the U.S. National Institute of Standards and Technology (NIST), one of
