Alternative mass analyzers can expand the capability range of plasma source MS.
Denise M. McClenathan Steven J. Ray William C. Wetzel Gary M. Hieftje Indiana University
PLASMA SOURCE TOFMS
E
merging challenges in modern analytical chemistry often drive the development of new instrumentation and, in turn, the enhanced capabilities of these novel instruments foster new and better science. This cycle is evident in plasma source MS (PSMS), where simple bulk determinations of elemental composition have evolved into sophisticated methods that utilize a host of sampling possibilities offering microanalyses and spatially and time-resolved analyses. Today, the need for rapid, sensitive determinations to provide an ever-greater amount of chemical information is driving developments in PSMS. Inductively coupled plasma MS (ICPMS) is the most widely used and popular PSMS technique because of its outstanding capabilities—multielemental determinations, low detection limits (~10–100 fg/mL), a linear dynamic range reaching 108, and applicability to a wide range of sample types and sampling conditions. Alternative plasma sources, such as glow discharges and microwave plasmas, further extend the capabilities of PSMS. In spite of these strengths, PSMS suffers from several serious shortcomings, some of which arise from the inability of most mass spectrometers to simultaneously access all of the elemental and isotopic information produced by the plasma source. Scan-based spectrometers, such as quadrupole mass filters and doublefocusing sector-field instruments, monitor only a single m/z at a time and are scanned sequentially to produce a mass spectrum. As a result, the total analysis time is proportional to the number of m/z monitored, and an inherent tradeoff exists between mass-range coverage and achievable sensitivity and precision. This compromise is particularly evident in transient analyses, where observation time is strictly limited. When the mass analyzer is scanned during the concentration pro-
© 2004 AMERICAN CHEMICAL SOCIETY
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R
G1
Extraction region
FT
Acceleration region
Detector
Field-free region (flight tube)
FIGURE 1. Simplified TOFMS depicting the mass dispersion for three ions of different m/z. R, repeller plate; G1, extraction grid; FT, flight tube entrance grid.
file of a transient signal, various m/z are effectively measured at different sample concentrations. The resulting analysis error, known as spectral skew, adversely affects isotope ratio measurements and internal standardization and can yield erroneous relative abundances. Although mitigated by peak hopping and rapid scanning, spectral skew cannot be entirely eliminated by such methods. Many researchers have explored the use of alternative mass analyzers to overcome these limitations. For example, plasma sources coupled with quadrupole ion trap (1) or FT-ion cyclotron resonance (2) mass spectrometers can accumulate and store ions for selected lengths of time. These trapped ions can be subsequently fragmented by collision-induced dissociation or can undergo ion–molecule reactions to eliminate many isobaric interferences (3). Alternatively, a double-focusing mass spectrograph can be fitted with a focal-plane camera, thereby creating the MS-equivalent of CCD cameras. These devices can monitor the entire mass range of interest continuously and simultaneously (4). TOFMS has also been explored as a method for overcoming some of the limitations of PSMS and is gaining popularity for multielemental and multiisotopic analysis of fast transient signals (5–8).
TOFMS with plasma sources Mass separation in TOFMS is based on the familiar relationship between kinetic energy (KE), mass m, and velocity v, which is KE = 1/2mv2. In TOFMS, ions fill an extraction region defined by a repeller R and an extraction grid G1 (Figure 1). Ions are extracted for mass analysis when a voltage pulse is applied to the repeller. The resulting linear field injects ions into the acceleration region, between G1 and the entrance to the flight tube, where the ions gain their final TOF energy. The ions are then dispersed according to their m/z-dependent velocities in the field-free region, so the time required for an ion to traverse the flight tube is quadratically related to its m/z, as shown in the KE equation. A detector positioned at the exit of this region records the arrival time of the ions, and the time-dependent output of the detector yields a complete mass spectrum. Because all m/z are extracted at the same instant, TOFMS realizes many of the benefits attributable to simultaneous detection and thus possesses a multichannel advantage over sequentially scanned systems. A complete mass spectrum is produced with each repeller event; therefore, multielemental and multi-isotopic analysis is accomplished with the same resolution, sensitivity, and 160 A
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precision regardless of the number of m/z observed. In essence, the population of ions within the extraction region is a compositional snapshot of the plasma at a given moment in time. Hence, simultaneous extraction of these ions can compensate for multiplicative noise sources and improve measurement precision with strategies such as internal standardization and isotope ratioing. TOFMS offers a virtually unlimited mass range—one reason for its popularity in bioanalytical MS. Of course, the time required to record a single mass spectrum is governed by the flight time of the highest m/z, so there is an unavoidable tradeoff between speed and mass range. Because the mass range investigated in PSMS is relatively restricted (1–238 amu), reasonable acceleration voltages (2 kV) and flight-tube lengths (1 m) permit the generation of 20,000–30,000 complete mass spectra each second. This speed ensures that a great number of mass spectra can be recorded across even the most short-lived transient signal, free of spectral skew. Furthermore, the high-mass capability of TOFMS makes it attractive for speciation analyses and metallomics, which is the characterization of metal-containing proteins, where a larger mass range may be necessary. Design considerations for PS-TOFMS are not unlike those for TOFMS instruments tailored to electrospray ionization (ESI) or MALDI. In all types of TOFMS, mass resolution is dependent on the temporal width of the isomass ion packets that strike the detector, and therefore reflects the initial spatial and energy distributions of the ions within the extraction region. The impact of the finite spatial width of the extracted ion packets on resolution is minimized by space-focusing strategies, where the initial spatial distribution of ions is reduced by the application of the appropriate fields (9). Upon extraction, ions nearer the repeller electrode gain energy that is proportionally greater than that imparted to ions closer to the extraction grid (G1 in Figure 1). Hence, lagging ions achieve greater energy and overtake the slower-moving ones at some point in the flight tube. At this “space-focus plane”, the spatial distribution is thereby minimized. Fortunately, the location of the space-focus plane is m/z-independent, and the tight spatial bunching of the ion packets at this position affords the opportunity to selectively remove undesired m/z from the beam. The high concentrations of plasma and matrix ions (Ar+) present in PSMS can cause detector damage, so this sort of deflection is an experimental necessity. Similarly, the detrimental effects produced by differences in initial ion energies are often compensated for by an ion mirror or
Detector Reflectron
“reflectron” (10). In this device, more energetic ions penetrate farther into a reflecting field and therefore follow a longer R G1 FT path than ions with lower initial energy. The longer flight path thereby compensates for the higher energies and velocities. Further, the reflectron serves to image the space-focus plane onto the detector surface, thereby increasing the flight length and improving resolution. The nature of plasma sources and the Vfinal need to efficiently marry an inherently Vy pulsed spectrometer with what are often continuous ion sources have yielded two Incoming ion beam Vx common TOFMS designs (11)—orthogonal acceleration (oa) and axial acceleration (aa), where each appellation indicates FIGURE 2. Simplified diagram of a spontaneous-drift oa-TOFMS instrument. the relative orientation of the incoming The green and blue areas of the extraction region indicate the position from which ions of ion beam and TOF axis. In both metha particular m/z (energy) are sampled. Vy, initial velocity of the ions; Vx, velocity component of ions received from the extraction process; Vfinal, final velocity of ions after extraction; , ods, ions are injected into the extraction angle from the TOF axis that the ions follow into the flight tube. zone before they undergo acceleration, an arrangement that improves the duty factor considerably. In oa-TOFMS, ions are extracted into the flight tube at a right angle from the direction of their initial motion. In this configuration, the vec- sequence of this equation is that a population of monoenergetic tor of the ions’ greatest initial velocity spread lies perpendicular ions will follow the same trajectory in the flight tube. However, to the flight axis and therefore does not influence the observed in instances where Ey within the primary ion beam is a function of flight times or resolution. Further improvement in resolution mass, is dependent on m/z, resulting in an m/z-dependent offcan be obtained without sacrificing sensitivity by restricting the set of ions along the detector surface. Unfortunately, the sampling initial spatial width of the ion packet along the flight axis by ion- of ions from an atmospheric-pressure source, such as an ICP, into optical elements that focus the beam into the shape of a plane the vacuum stage of a mass spectrometer yields a partially isokiperpendicular to the flight tube (12). When coupled to contin- netic ion beam (i.e., the ions have the same velocity). The ions foluous ionization sources, the efficiency with which ions are uti- low an m/z-dependent trajectory in the flight tube, resulting in lized by the mass spectrometer, known as the duty cycle, can be the undesirable mass-dependent instrument response. This artifairly high. Because the velocity of the ions within the primary fact reduces transmission efficiency, causes severe angular diverbeam is low compared with the energy these ions gain upon ac- gence, and necessitates the use of either sizable extraction zones celeration, ions from the primary beam slowly refill the extrac- or detectors with large active surfaces. tion region while mass analysis of the previous packet is under This difficulty is commonly minimized by using ion-steering way. Although this approach is comparatively efficient, it typi- electrodes to compensate for Ey (12). Unfortunately, these corcally results in utilizing only 10% of the ions presented to the rective voltages are m/z-dependent, and such electrodes affect mass analyzer. Another benefit is that the natural modulation of spectrometer resolution adversely. A different approach, called the incoming ion beam in oa-TOFMS limits the number of neu- “spontaneous drift”, uses no steering electrodes (13). As the trals and ions allowed to enter the flight tube and contribute to name suggests, ions follow trajectories prescribed by their origcontinuum background noise. inal motion within the primary ion beam. This strategy has Unfortunately, the oa design also suffers from several inherent been modified to permit efficient sampling of polyenergetic ion limitations. Upon extraction into the flight region, ions follow a beams (14). To strike a specific point on the detector surface, trajectory that is the vector sum of their initial motion and the ions of different energy Ey must be sampled from different ymotion imposed by the perpendicular extraction field. Conse- positions within the extraction region (Figure 2). Those ions quently, the extracted ion packets will follow an angular trajecto- having lower velocities along the y-axis (ions of smaller m/z in ry from the optical axis of the flight tube that is calculated as an isokinetic ion beam) must start their journey from a position closer to the detector (at the top of the extraction zone). ConEy versely, ions of greater m/z must be extracted from positions tan = Ex farther away from the detector along the y-axis (at the bottom in which Ey is the initial energy of the ion and Ex is the energy im- of the extraction zone), which results in the extraction region parted by the extraction and acceleration processes. A simple con- being much larger than the width of the detector. In essence,
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ber of non-extracted ions that enter the flight tube. Modulation is achieved by placing an ion gate before the repeller (Mod in Figure 3). By pulsing the potential on this electrode, the continuous ion beam is parsed to form an ion packet, which moves to the extraction region for mass analysis by means of the ions’ original motion. In aa, the fraction of ions sampled for mass analysis is directly related to the length of the extraction region (distance between R and G1 in Figure 3). However, longer extraction zones increase the demand on space focusing and thus come at the expense of resolution. Additionally, the axis of greatest ion velocity now lies in the direction of the flight tube and thus can contribute directly to measured flight times. For this reason, energyfocusing devices such as the reDetector flectron are critical. ConvenientReflectron ly, atomic MS does not require high resolution, and resolving powers exhibited by aa are better than those typically available from quadrupole mass filters. Furthermore, alignment of the Mod R G1 FT main velocity of the ions with the direction of the flight tube in aa-TOFMS eliminates turnaround-time errors. Despite the apparent advantages and limitations of these competitive geometries, the exFIGURE 3. Simplified diagram of an aa-TOFMS instrument that uses pre-extraction perimental performance of both modulation of the ion beam. designs is similar and comparable Mod, modulation ion gate. with the figures of merit from other ICPMS platforms (16–20). Commonly, ICP-TOFMS systems achieve elemental sensitivithat have a velocity component oriented away from the flight ties of 106–107 cps/ppm/isotope and detection limits of 0.1–10 tube must first be decelerated, then turned around before being ppt for all elements and isotopes of interest, measured concurinjected into the acceleration region. Unfortunately, the time rently. Linearity extends over 7 orders of magnitude at resolvdelay experienced by these ions adversely affects resolution, a ing powers of 1500–2300 (fwhm). The simultaneous sampling problem not easily corrected. of ions by TOFMS has permitted isotope ratios to be measured An aa design devised to circumvent the problems in oa is with high precision (0.006–0.2% RSD) at levels often limited based on the extraction of ions along a flight axis that is co-lin- by ion-counting statistics. This performance has spurred the inear with the incoming beam (15; Figure 3). Because ions are troduction of commercial systems, such as the Renaissance by extracted along the axis of their original motion, their initial ve- Leco and the Optimass 8000 by GBC Scientific, and Analytik locity contributes only a small fraction to the overall energy in Jena expects to market an instrument in the near future. that direction. Consequently, all m/z follow essentially identical flight paths to the detector surface, minimizing angular di- Speciation vergence. The aa-TOFMS geometry also has a potential ad- The chemical form of an element critically affects its toxicity, vantage in transmission efficiency because the dimensions of bioavailability, and metabolism. Hence, determining the chemthe ion beam are dictated by the sampling of the ions into the ical speciation of an element (its oxidation state, associated ligvacuum stage of the mass spectrometer. Thus the beam is nar- and, etc.) can be as important as measuring its total concentrarow (~1 cm diam) and easily focused, which allows the use of tion. Because such information is destroyed by conventional small and circularly symmetrical ion optics. However, unlike oa, plasma sources, elemental speciation is typically performed by where the extraction event inherently modulates the ion beam, coupling a separation technique with sensitive element-specific pre-extraction modulation is often useful in aa to limit the num- detectors. The multielemental speciation of metal– cyanide comthe width of the extraction region defines an envelope of ion energies that will be accurately sampled from the incoming ion beam. When the relative dimensions of the TOFMS are chosen so that ion energies representative of all m/z of interest are included, mass-independent response is achieved. Because this modified spontaneous-drift geometry eliminates the problems of mass-dependent ion trajectories and angular divergence of the extracted ion packets, it should result in greater ion transmission efficiency and more uniform response across the mass range of interest. Like other oa-TOFMS strategies, however, this design suffers from turn-around-time errors. Ions
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Co(II)
Signal (counts; 250-ms intervals)
Ni(II)
Cr(VI)
plexes by CE/ICP-TOFMS is an example 800 of this approach (21; Figure 4). Although As(III) As(V) only selected m/z are displayed here, the Co(III) Cu(II) V(V) multichannel advantage of TOFMS allows the entire atomic mass range to be DMAs monitored throughout a separation and 400 prevents the loss of information about unknown or unexpected species. Furthermore, the element-specific detection of 12 0 PSMS coupled with the high temporal res80 olution of TOFMS allows faster separaM igr tions; resolution can be intentionally ati 0 40 on sacrificed to increase sample throughput, 70 tim e( 60 0 without compromising the final result. s) m/z 50 We used GC/ICP-TOFMS to speciate organotin and organolead compounds with separations that lasted 200–300 s and FIGURE 4. CE/ICP-TOFMS separation and multielemental detection of VV, CrVI, CoII, III II II V III contained peaks with single-second, baseCo , Ni , Cu , As , As , and dimethylarsenic (DMA) cyanide complexes. Injection line-to-baseline widths (22). Isotope-ratio contained 100 pg of each metal analyte per compound (400 pg of metal per armeasurements on the eluting compounds senic species). (Adapted with permission from Ref. 21.) yielded 118Sn/120Sn values with an accuracy of 0.28% and a precision of 2.88% RSD (limited by counting statistics). Additionally, the signal could be ratioed to an In the earlier examples, information about the chemical na“empty” m/z window for a 5-fold improvement in S/N; reported detection limits for the organometallic compounds were ~10–20 fg ture of a species is lost during atomization. A more straightforas the metal. Unlike the ICP, a microwave-induced plasma (MIP) ward approach might use ion sources that provide speciation can be used to directly determine halogens. During the speciation information directly. For example, ESI can produce oxidationof halogenated hydrocarbons by GC/MIP-TOFMS, calculated state information without chromatographic separations. Alter35 + 12 + Cl / C ratios enabled the determination of empirical formu- natively, element-specific detection and direct speciation can be accomplished by ionization sources that generate both atomic las, information useful for definitive peak identifications (23). GC separations on a more rapid timescale have been achieved and molecular mass spectra in an alternating fashion. Atomic mode by using multicapillary columns that consist of several hundred produces simple spectra with high sensitivity and lessened macapillaries bundled in an array. Higher sample loadings are pos- trix effects. Molecular mode produces qualitative mass spectra sible, although column lengths >1 m do not improve separa- that often closely resemble 70-eV electron impact (EI) spectra, tion efficiency. Thus, rapid separations with improved detection which allows EI libraries to be used for identification. Switching limits are realized when only a modest number of theoretical between these modes on a chromatographic timescale (>10 Hz) plates are required. When multicapillary GC/ICP-TOFMS was eliminates retention-time matching and allows definitive idenused to speciate organolead compounds, analysis time was sig- tification of unknown or unexpected components in mixtures. nificantly decreased to
