On-Line Mass Spectrometry: A Faster Route to ... - ACS Publications

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Ind. Eng. Chem. Res. 1999, 38, 1192-1204

On-Line Mass Spectrometry: A Faster Route to Process Monitoring and Control Kelsey D. Cook,* Kevin H. Bennett, and Martin L. Haddix Department of Chemistry, University of Tennessee, Knoxville, Tennessee 37996-1600

A critical review of on-line mass spectrometry is presented, illustrating instrumentation, data treatment, and applications drawn from both control and research environments. Both direct and membrane inlets are included. The discussion of instrumentation focuses on commercially available options, although some research options that offer promise for future process applications are also mentioned briefly. Special considerations attendant upon the high-precision measurements needed for simultaneous analysis and continuous process control are emphasized. Applications illustrate a range of problems benefitting from rapid, simultaneous analysis of volatiles. Introduction In science and engineering, it is important to distinguish between facts and “conventional wisdom”. Process control requires information. That is a fact. In the factory environment, this information can normally take two forms: real-time feedback from monitors at key points in a batch reactor or process stream (including feed, product, and waste streams), and off-line analytical data acquired from “grab samples”. While it may be granted that more information can generally provide better control, it must be kept in mind that the more complex a system, the more chance there is for breakdown and incumbent losses. Because of these concerns, conventional wisdom dictates that process “monitors” be kept to a minimum (usually entailing sensors for temperature, pressure, and flow), while chemical analyzers (capable of providing “analytical” information about composition) are generally relegated to the relative safety and calm of the laboratory. What is lost in optimum plant performance, it is often argued, is more than made up in operational reliability. Although such a philosophy has held sway in a successful industry for decades, changes in both the competitiveness of the market and the sophistication and reliability of chemical instrumentation are stimulating philosophical changes. The use of chemical analyzers in the factory and even on-line, while still far from the norm, is at least becoming far from extraordinary. Potential rewards are fairly obvious, as are the risks. Better and quicker information can indeed afford better control, in turn significantly increasing the overall efficiency, as measured in terms such as yield, product quality, resource utilization, discharge composition, or safety.1 For example, if drifts in product quality toward the bounds of marginal acceptability can be detected online, a quick control adjustment can remedy the problem before production of any material outside specifications.2 The down side comes if a plant reliant on analyzers must be shut down to allow for their maintenance or repair. Despite marked improvements in reliability, downtime tends to correlate with sophistication. Analyzer redundancy is a viable but sometimes expensive remedy. In such a context, conventional wisdom might deem the concept of “process mass spectrometry” (PMS) to be

intrinsically oxymoronic (self-contradictory). To be sure, mass spectrometers (described in a recent Anal. Chem. product review as no longer “prickly stainless steel elephants”3) are more complex than the typical pressure or temperature sensor; most, in fact, incorporate pressure and temperature sensors. However, the analytical power of the instruments (primarily in terms of speed, selectivity, dynamic range, and capacity for multiplexing and multicomponent analysis) combined with the instrumental simplifications and enhanced reliability resulting from increased computer and electronics sophistication has resulted in rapid expansion of PMS applications since the early assessments of feasibility.4-6 The analyzer hardware employed runs the gamut from simple “mass-selective detectors”7-9 to “new-fangled” quadrupole ion traps,10 all of which can now be operated in the process environment with little operator intervention. Interfacing the instrument is more challenging than for photon-based analyzers (e.g., process infrared, Raman or ultraviolet/visible spectrometers; see reference 11 for a detailed comparison), but systems with greater chemical complexity can be monitored. This review is not intended to be exhaustive; there are several excellent and reasonably contemporaneous reviews to which the reader is referred.12-15 Instead, a general overview is offered of the philosophy and instrumentation of PMS, followed by brief descriptions of some recent applications illustrating the breadth of potential. The discussion of instrumentation will also be brief; those seeking more detailed information are directed to excellent contemporary texts on mass spectrometry (MS) like Watson’s.16 Applications will generally fall into two broad categories: on-line reaction monitoring and on-line process monitoring. The distinction may be an artificial one, but it is one based mainly on the nature of the problem addressed. Reaction monitoring may generally be considered to be a research function, aimed at characterizing (once and for all) the detailed chemistry of a particular system. Once that chemistry is understood, the mass spectrometric experiment will have served its purpose (providing useful insight into the dynamics of the reaction, including the identity, abundance, and time dependence of reactants, intermediates, and products). Both qualitative and quantitative information may be derived and may be useful in subsequent modeling and optimization. In

10.1021/ie9707984 CCC: $18.00 © 1999 American Chemical Society Published on Web 02/09/1999

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contrast, true PMS process monitoring entails continuous multicomponent quantitation, usually with the instrument serving as part of a control loop. There are special considerations of instrument precision and data treatment implicit; these will be discussed along with the overview of instrumentation and applications. General “Philosophy” The mass spectrum (a plot of intensity versus massto-charge ratio (m/z) of detected ions) of a compound provides a characteristic “signature” of that material, generated ordinarily by energetic processes which both ionize a molecule and break its most labile bonds.17 For those materials sufficiently volatile to be admitted intact into a spectrometer “ion source”, conventional ionization by interaction with energetic electrons provides particularly representative spectra comprising peaks of characteristic relative intensity at each of several characteristic mass-to-charge ratios. If the pressure in the source is kept sufficiently low to avoid ion/ion and ion/neutral encounters (,1 Torr), mixture mass spectra can be treated as linear combinations of the characteristic spectra of contributing components. Quantitation then becomes a simple linear algebraic exercise in deconvoluting the superimposed spectra. Because the mass spectrum of each constituent usually contains more than one peak, the number of peaks in the mixture mass spectrum often exceeds the number of constituents. In such an “overdetermined” case, linear leastsquares calculations are generally used to determine the set of constituent concentrations best predicting the measured mixture spectrum. That exercise is preceded by sampling, ionization, mass analysis, and detection. There are multiple, sometimes interdependent options available for each of these steps and for the data analysis. These are considered here in turn, with an aim of objectively highlighting some of the strengths and drawbacks of each. Precision in all steps of the analysis is critical; process analysis is often more concerned with detecting and correcting small changes than it is with knowing the absolute “right answer”. Instrument manufacturers typically quote dynamic ranges of 6 orders of magnitude or more, with precision better than 1% [relative standard deviation (RSD)], but these figures of merit will generally be compound- and matrix-dependent. There is, at least at present, no “one size fits all” panacea; no single approach to PMS seems to be “the best” for all applications. Instrumentation Sampling. Process MS, as conventionally defined, generally entails analysis of process streams, implicitly suggesting liquid or gas analysis. In one sense, this is a natural match to the traditional realm of MS; the ultimate requirement for gas-phase analyte ions for MS characterization has led to a natural designation of MS as a volatiles analyzer, like process gas chromatography. There have, however, been remarkable strides in the MS of high-mass materials;18 important and nearly commonplace analytical applications of MS now include synthetic and biopolymers with mass in excess of 104 Da (Da, a unit of molecular weight). One arena for these advances has been electrospray (ES) MS,19 which has the capability for continuous on-line sampling of ionic and nonionic materials dissolved in liquid matrixes. The process capabilities of ES have been discussed (e.g., see

Figure 1. Typical direct capillary inlet.

ref 20) but not yet demonstrated. Thus, ES MS will be described briefly with other ionization techniques below, but only volatiles inlets will be discussed in this section. True “on-line” PMS analysis of volatiles typically employs one of the two sampling inlet types described below: direct and membrane inlets. With either of these, accommodation of volatile liquids generally requires that the full system be heat-traced at temperatures high enough to ensure vaporization without recondensation once the sample enters the system. A sampling valve (see below) is often the temperature-limiting component; units are available that can handle temperatures up to at least 300 °C, so materials with appreciable vapor pressure (a few Torr) at this temperature may be considered to be reasonable candidates for PMS analysis. (a) Direct Inlets. The direct capillary inlet is the most common interface for sampling gases in PMS. It typically consists of a 10-200 µm i.d. silica sampling capillary of length (typically several centimeters) sufficient to limit flow and maintain a vacuum in the spectrometer source.11 The outer surface is generally polymer coated for durability, and the inside is sometimes silanized to prevent or reduce sample interactions with the wall and help avoid memory effects (as, for example, in ref 21). The capillary material is essentially the same as that used in chromatographic applications, so it is commercially available and inexpensive. The sampling capillary passes directly into the low-pressure ion source of the instrument via a ferrule-sealed vacuum feedthrough. It will typically sample a fraction of the gas or vapor removed from a reactor or process stream through a larger “transfer tube”; the balance of the sample stream is directed to a vent. A typical transfer tube may be fabricated from standard 1/16 in. glass-lined stainless steel tubing, often fitted with an in-line filter to prevent plugging of the sampling capillary. The transfer tube may be almost arbitrarily long, but long transfer lines will increase the overall system response time; to avoid this problem, analyzers are often housed in class 1 division 2 enclosures so they can be placed on-site. The interface between the transfer tube and sampling capillary is accomplished via a “T”-type fitting (Figure 1). A multiposition sampling valve can select any one of several (typically 16-64) transfer tubes for connection to the sampling capillary. This important feature enables multiplexing of the PMS analyzer, a critical feature facilitating both calibration and timesharing of the instrument (for analysis of multiple related or independent test points and streams). In normal applications, stream or reactor pressurization provides the flow necessary to carry analyte to the sampling interface. Unselected transfer tubes remain connected to the vent to ensure continuous flow and rapid response to changes in stream composition as soon

1194 Ind. Eng. Chem. Res., Vol. 38, No. 4, 1999 Table 1. Common Membrane Materials Used in MIMS and Their Applications material

application

separation mechanism

ref

polypropylene poly(tetrafluoroethylene) (PTFE, Teflon) cellulose silicone rubber dimethylvinyl silicone polyethylene zeolite

organic solvents volatile organic compounds (VOC’s) VOC’s fermentation monitoring, VOC’s fermentation monitoring VOC’s (isomeric) hydrocarbons

partition size exclusion “affinity” partition partition partition size exclusion, adsorption

10 24 24 24 25 26 27

as a tube is selected. When stream pressure is insufficient to maintain flow, the “exhaust” side of the sampling T may be fitted with a small vacuum pump to draw sample to the instrument; such an arrangement may suffer from relatively low sensitivity because of the reduced pressure differential across the sampling capillary. In some designs, the sampling capillary is replaced by a “molecular leak” (a simple micron-sized pinhole aperture) or a porous frit (sintered glass or metal). The latter choice may reduce plugging, at a cost of increased memory effects. In most cases, these flow-restricting components must be sufficient to maintain low ion source (,1 Torr) and analyzer (e10-5 Torr) pressures. (b) Membrane Inlets.22 In many applications, a liquid solvent constitutes a matrix of little analytical or process interest but containing solutes of critical importance; an example is the analysis of volatile organic compounds (VOCs) in aqueous waste streams. In such cases, using heat tracing to vaporize the entire sample would substantially reduce the (molar) concentration of the materials of interest and may compromise the analysis. Use of a selective preliminary separation (e.g., gas chromatography) may remedy this situation but at a cost of often precious time. It is for such a circumstance that membrane inlet MS (MIMS) was developed. In MIMS, the selective permeance of a membrane is exploited to reduce background contributions and enhance detectability of materials of interest. Full or partial separation can be accomplished, often much more rapidly than with a chromatographic separation step. Limits of detection (LODs) as low as parts per quadrillion have been reported.23 Table 1 lists several types of membranes, the associated separation mechanism(s), and some typical applications for each. An ideal membrane for a given application will have a large permeation rate for the compound(s) of interest and small or zero permeation for all other (background) chemicals. In many cases temperature becomes an important variable that can be used to affect the speed and/or selectivity of separation. Separation mechanisms include simple partition (e.g., enrichment of organics by their solubility in nonpolar rubber membranes); size exclusion (e.g., in microporous membranes); differentiation based on diffusivity (which may result from both geometrical and polarity differences); and combinations of these.24 In “affinity MIMS”, a preconcentration step accumulates analyte in the membrane (e.g., benzaldehyde in a cellulose sheet24) for a fixed period of time. Analyte is then “flushed” from the membrane using a second solvent which also carries it to the mass spectrometer. The method can be extremely sensitive, but quick response is sacrificed for this improved sensitivity. This selectivity/speed tradeoff arises often with membrane inlets; for example, microporous Teflon membranes24,28 are less selective but provide up to 5 times faster response than the more widely used silicone rubber membranes10,29-31 for the analysis of polar compounds

a

b

c

Figure 2. Membrane inlets. (a) Flow-through sheet membrane interface. (b) Membrane probe interface with jet separator. (c) Flow-through tubular membrane interface.

in freshwater and seawater. Despite reduced selectivity, the microporous membranes reportedly provide lower LODs for volatile organic compounds (VOCs) than do silicone membranes.24,28 Common membrane configurations include both sheets (Figure 2a,b) and hollow fibers (Figure 2c). The membrane itself may serve as a flow restrictor sustaining the required source and analyzer vacuum, in which case it may even be positioned inside the evacuated ion source. Alternatively, material passing through the membrane may be swept via a transfer tube to a sampling valve and sampling capillary (as described above) by a carrier gas flowing by the permeate side of the membrane. In either case there is a rough correlation between membrane surface area and sensitivity. Some MIMS systems are sufficiently flexible to support sampling from gas, liquid, and even soil matrixes.32 Fast response time often entails the use of thinner and/or larger membranes, which in turn can increase

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the gas load on the spectrometer. This increase can induce nonlinearities and distorted spectra. A remedy sometimes employed is incorporation of a jet separator interface between the membrane and the MS source (Figure 2b). However, degradation of LODs can result from this expedient, as in the on-line analysis of toxic emissions in air and volatile/semivolatile organic compounds in water.33 Furthermore, fractionation of species in the jet can result in enrichment of heavier components, thus distorting quantitation. In addition to the intrinsic membrane response time, the overall cycle time is an important consideration for on-line process applications of MIMS. Contributions to dead time include memory effects (requiring time to clear samples from the membrane) as well as simple mass transport (the time lag for transport through a long transfer tube; see above). Memory effects are intrinsic to the slow analyte enrichment associated with affinity MIMS but can affect other membrane applications as well. The resulting dead times may negate some advantages of on-line analysis, slowing the time-scale so that it becomes comparable to that of off-line and chromatographic measurements. Ionization. Electron ionization (EI) is by far the most common method of ionization in PMS. Probably the oldest MS ionization technique, EI occurs when gaseous analyte molecules are bombarded by energetic electrons from a hot wire filament in a vacuum. Common filament materials include tungsten and rhenium, but thoriated iridium provides similar electron emission (microamperes) with lower heating current, thus prolonging filament lifetimes (especially in applications sampling oxygen-rich environments, including air). Replacing a burned filament requires instrument downtime, so longevity (which will be application-dependent but will typically exceed 6 months) is an important consideration. Although most sample molecules require only 5-20 eV for ionization, ionizing electrons in EI MS are typically accelerated to 70-100 eV. This represents a compromise among several factors. Near the ionization threshold energy, absolute ion intensities are relatively low and relative intensities are highly sensitive to electron energy. Although spectra are relatively simple (e.g., Figure 3c), spectral reproducibility and quantitation precision suffer because exact control of the electron energy is difficult. Operating well above threshold (Figure 3a,b) provides not only the high precision needed for quantitative work but also mass spectra relatively “rich” in fragment ions. While fragmentation distributes the available material among multiple ions (thereby diminishing the maximum signal, especially for the intact “molecular ion” species), it provides the distinctive spectral signature which enriches the information content of the mass spectrum (relative, for example, to the information derived from gas chromatographic retention times). The net result is a significant enhancement in quantitation capabilities for unresolved mixtures, and even the possibility of using the observed fragmentation signature to identify unexpected species detected in an upset condition (by applying standard spectral interpretation tools17 to the “residual” ion intensities not attributable to expected analytes). If the source pressure becomes too high, ions and neutrals in the source can collide and react. Uncontrolled, this provides a source of variability that can complicate or even prevent quantitation based on EI spectra. For example, in an application monitoring feed

Figure 3. Series of mass spectra of a suspected mixture of compounds. The ionizing potential of electrons diminishes as the series of spectra progresses; note the shift in relative intensities of fragment and molecular-ion peaks as the ionizing energy decreases from 70 eV (top) to 12 eV (bottom). (Reprinted with permission from ref 16. Copyright 1997 Lippincott-Raven Publishers.)

streams and reaction mixtures for an acetone and butanol fermentation reactor, concentrations determined by MIMS were significantly different from those obtained by gas chromatography.25 The differences were traced to the effects of excessive hydrogen and carbon dioxide in the MIMS ion source and were eliminated by lowering the surface area of the membrane. In some instances, the source is purposefully “swamped” with a large excess (up to ∼1 Torr) of a reagent gas, so that ion-molecule reactions involving charge exchange with ions of the reagent gas become the predominant analyte ionization mechanism. Energies involved in these ion-molecule reactions are much lower than those involved in direct EI; much simpler spectra result (ignoring the reagent ions), and sensitivity can be enhanced. This chemical ionization (CI)16 experiment offers an alternative to EI, reducing (by swamping) some variability arising from unintentional ion-molecule reactions. A degree of selectivity can be

1196 Ind. Eng. Chem. Res., Vol. 38, No. 4, 1999 Table 2. Features of Various Analyzer Types quadrupole

magnetic sector

ion trap

ion mobility

ion separation

filtered by an electric field (dc + rf)

dispersed by a magnetic field

low (eV) e10-4

high (keV) e10-5

drift in a dc electric field through a high-pressure gas low (eV) 1 atm

drift in a vacuum

ion energy analyzer pressure (Torr) simultaneous multi-ion detection distinguishing characteristic

trapped then ejected by an electric field (dc + rf) low (eV) e10-3

no

with multiple detectors

following accumulation

following sampling pulse

following sampling pulse

flat-topped peaks

MS/MS

inexpensive

fast (microseconds/ spectrum)

realized by choosing reagent ions that will react with the analyte of interest but not with concomitants. For example, CI by charge exchange with xenon was reported to give selective detection of SO2 and H2S in continuous monitoring of automobile exhaust.34 However, although CI is widely used in analytical MS, it has yet to find wide use in PMS. The same may be said of one of the most dynamic areas of current MS research: ES MS.19 In this technique, a few microliters per minute (up to ∼1 mL/min) of a dilute (micromolar) analyte solution is sprayed through a small metal capillary (10-200 µm i.d.) which is maintained at high voltage (2-5 kV) to promote liquid dispersion into a mist of fine, charged droplets at atmospheric pressure. As the droplets are accelerated through a heated interface toward a differentially pumped MS inlet, the solvent evaporates, eventually releasing free analyte ions that are sampled and detected. Low- and high-mass (>105 Da) species can be analyzed by this approach, with exquisite (attomole) sensitivities in favorable cases. The method provides a versatile and sensitive interface between liquid chromatography and mass spectrometry (LC/MS). While this offers some promise for process applications probing nonvolatile components of liquid streams,20 the methodology has yet to be applied in this arena. A related technique is atmospheric pressure chemical ionization,35 wherein ion-molecule reactions of the type discussed above take place at atmospheric pressure using the solvent as a source of reagent ions (usually produced by an electric discharge near the spray probe). In favorable cases, these reactions can provide selective ionization of target analytes. For example, proton transfer from H3O+ reagent ions (formed from water solvent) can ionize polar organic constituents such as acetonitrile and propanol but not air constituents or other nonpolars.36 The resulting low background can provide an excellent LOD for target compounds. Although useful for LC/MS and reportedly usable in other on-line applications, the methodology must still be considered at best a “developing” technique for process analysis. Finally, there have been a few reported process applications of thermal ionization, wherein species are ionized by impact with a hot surface of low work function.37 Primarily a means of elemental analysis, thermal ionization has been used to continuously monitor airborne radionuclides, even when incorporated into microparticles.38 Selectivity can be gained by pretreating the hot filament, as reported for selective monitoring of I2 in process off-gas using specially treated rhenium filaments for negative ion PMS.39 Analyzers. There are five distinct analyzer types that have been used in process mass spectrometry (Table 2). In each case, the physical operating principles are

time-of-flight

high (keV) e10-5

identical to those employed in corresponding analytical (laboratory) instruments, but the specifications may differ significantly. For example, it is rare for a magnetic process analyzer to exploit the high-resolution capabilities of some magnetic mass spectrometers or for a quadrupole-based process analyzer to meet (or need) the mass range specifications of its analytical “cousins”. The critical figure of merit for virtually all process analyzers is nearly always precision (particularly precision of intensity measurements). For a detailed discussion of the operating principles and performance of various analyzers, the reader is referred once again to a general monograph like reference 16. Only a brief description of principles will be included here. The most widely used is the quadrupole mass analyzer, which consists of four metal rods roughly 1 cm in diameter and 20 cm in length. The rods are arranged in a parallel array at the four corners of a square (viewed end-on). By a superposition of dc and radiofrequency (rf) voltages, these devices filter relatively low-energy (a few electronvolts) ions according to their mass-to-charge ratio (m/z), generally focusing one m/z at a time onto a detector (see below). Ions of the selected m/z follow a complex path roughly parallel to the rods at the center of the array, while other ions either collide with the rods or are accelerated out of the array. These analyzers can scan a defined mass range quickly and reproducibly by varying the dc and rf voltages. For optimum precision in process applications, however, only certain sample ions of selected m/z are usually monitored, the so-called “selected ion monitoring” (SIM) mode.11 In this mode, the analyzer cycles among selected m/z’s; while sampling one m/z (typically for up to a second), ions of all other m/z will be missed. Selection of the ions to monitor (“parametrization”) is an issue of some importance for all analyzers and will be considered separately below. In normal operation, quadrupole analyzers do not have sufficient resolution to distinguish “isobars” (ions of different elemental composition but the same nominal mass; e.g., CO at 27.994 91 Da and N2 at 28.006 14 Da both have nominal mass “28”). As described in more detail below, this is not intrinsically a serious limitation because there are usually other spectral characteristics allowing distinction of species giving rise to isobaric ions. Alternatively, a separation can be invoked if time allows. In a magnetic sector analyzer, ions created in the source and accelerated to high kinetic energies (on the order of kiloelectronvolts) are dispersed through a curved, evacuated flight tube by a magnetic field perpendicular to the direction of ion travel. The radius of curvature of an ion’s flight path depends on its momentum (and therefore its energy and m/z).16 With adequate fields and radii, plus careful control of ion energy, “high-resolution” magnetic instruments can

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often resolve isobars. This capability is widely used in laboratory analysis of environmental contaminants such as dioxins and polychlorinated biphenyls (PCBs) but rarely, if ever, invoked in process applications because it adds to the capital cost and complexity and can actually reduce sensitivity (and therefore precision) in cases where the background is not limiting. Indeed, for process applications magnetic analyzers are generally tuned to obtain “flat-topped” peak shapes (achieved at low resolution with instruments using physical slits to define the shape of the ion beam11). With “flat” peaks, small m/z instabilities minimally affect the measured ion intensity, thereby providing improved precision in intensity measurements. In practice, quadrupole analyzers can also provide essentially flat-topped peaks with careful tuning and/or the use of large quadrupole rods; it is therefore not clear whether there is an intrinsic difference in the precision attainable with these analyzers. However, magnetic instruments do offer the unique possibility of accommodating an array of detectors (see below) on the focal plane where the ions emerge from the magnetic field, thus allowing true simultaneous monitoring of several distinct m/z’s and providing enhanced stability relative to scanning or SIM40 modes. More often, however, instrumental simplicity demands fitting an instrument with a single detector, in which case scanning can be achieved by varying either the magnetic field strength (with an electromagnet; scan rates are limited by magnet hysteresis) or the ion energy. The latter is faster and instrumentally simpler (a permanent magnet can be employed) but may compromise precision due in part to the dependence of sensitivity on ion energy. [For some dectectors (see below), response decreases with decreasing ion energy and with increasing ion mass. With quadrupoles, ion energies are uniformly low. With energy-scanning magnetic sectors, ion energy is inversely proportional to m/z (double the mass, halve the energy), so both factors can contribute to a change in sensitivity when scanning over a wide mass range. Some instruments employ extra acceleration after mass analysis (“postacceleration”) to compensate for this effect.] As with quadrupoles, magnetic instruments fitted with a single detector will generally employ the SIM mode for best precision. It is debatable whether these two most common analyzers differ significantly in the complexity of their electronics; a magnetic instrument needs no rf generator, and a quadrupole requires fewer high-voltage electronics and optics. Finally, it has been reported that magnetic sector analyzers are less susceptible to contamination because they generally operate at lower pressures.11 Of course, there is no requirement for high pressure in quadrupoles; these analyzers merely tolerate elevated pressure (somewhat above roughly 10-5 Torr) better than magnetic instruments do because of the focusing properties of the quadrupole electric field. Overall, then, these two instrument types may be considered close competitors. Both are commercially available at competitive prices. While analytical magnetic instruments are generally larger and more expensive than analytical quadrupoles, corresponding process analyzers are comparable in size (usually limited by an explosion-proof enclosure) and price (typically somewhat over $100K, depending on features and options). Although not yet widely used in process applications, the ion trap mass spectrometer16,41 offers some attractive features relative to either quadrupoles or magnetic

sectors. Like the quadrupole, this instrument employs superimposed dc and rf voltages to select ions of a particular m/z for detection. The device is comprised of a doughnut-shaped “ring” electrode capped above and below with hemispherical “end-cap” electrodes. The device is intrinsically pulsed in its operation, typically with a millisecond time scale. Low-energy ions (a few electronvolts) can be trapped in a potential well within the device during a “gating” pulse, and applied potentials can then be varied to select ions of a particular m/z or range of m/z’s for ejection through a hole in an end cap and toward an external detector. All trapped ions can be detected, but ions arriving between gating pulses are lost. Trapping allows manipulation of gasphase ion-molecule reactions for better selectivity (as in the real-time analysis of styrene and ethylbenzene in stack emissions42). It also enhances tolerance of high pressures; in fact, the instrument performs best with a significant pressure (∼10-3 Torr) of an inert “buffer gas” (e.g., helium) to collisionally cool trapped ions, thus preventing their ejection except when selected by the applied field. Although not a routine mode of operation, high-resolution measurements (sufficient to distinguish isobars) are feasible. The analyzer can be quite small (baseball-sized) and is at least as rugged as the other instruments. High pressures and the resulting potential for space charge effects in the trap may affect the precision of measured intensities; the quantitative capabilities of the ion trap are being investigated.43 For low cost, simplicity, and robustness, ion mobility spectrometry (IMS, sometimes referred to as plasma chromatography) is probably unrivaled among mass analyzers.44 Ions are distinguished by their drift velocities in an electric field applied between a pulsed source and a detector, all in a region near atmospheric pressure. In principle, all ions sampled in a given pulse can be detected, although ions formed between pulses may be missed (as in the ion trap). The millisecond time frame is similar to that of the ion trap, so similar duty cycles can be achieved. Strictly speaking, the IMS is not a “mass analyzer” because drift times depend on molecular cross sections (and therefore molecular geometry) rather than directly on mass. As a rule, however, cross sections correlate reasonably well with mass and are in any case comparably characteristic. Little or no vacuum is required, and ionization is often achieved using a small amount of a radioactive β emitter (for example, 63Ni or 241Am) in place of an electron filament to allow atmospheric pressure operation and to minimize powered electronics components. Apart from radiation licensing considerations, this makes IMS especially attractive for field-portable and even hand-held instrumentation. Photoionization sources have also been tested.45 Sensitivity can be high, and precision can be sufficient for at least some process monitoring applications (for example, the on-line analysis of ethanol during yeast fermentation46). Resolution is rather low and may ultimately limit applicability for complex systems. Nevertheless, process applications of IMS may be expected to increase if precision and reliability prove adequate. At least superficially related to the IMS is the timeof-flight (TOF) mass spectrometer, in which ions are again distinguished on the basis of their velocities. Here, however, ions are formed in a vacuum and accelerated to constant energy, so that their velocity (and hence arrival times at the detector following a sampling or

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ionization pulse) is dependent on m/z. Ideally, no collisions take place within the spectrometer, so there is no dependence on ion cross sections; the TOF is a true mass analyzer. Because of the need for pumping and one or more high-voltage power supplies, instrumental sophistication is intermediate between that of the IMS and those of other true mass analyzers. For typical flight paths (∼1 m) and acceleration voltages (on the order of kilovolts), flight times are on the order of microseconds; analysis can be very rapid, and duty cycles can be high (especially with research instruments that can store ions between sampling pulses). Furthermore, with a fast detector (see below), all ions from a given sampling pulse can be detected; this can offer better sensitivity or precision relative to scanning instruments, where ions of one m/z will be missed if the instrument is focused on some other m/z. (This “multiplex advantage” also applies to IMS and, to a lesser extent, to the ion trap.) These features are attractive for combination with socalled “fast gas chromatography”, where short columns and rapid heating give quick elution and require rapid scanning to avoid missing materials.47,48 Mass resolution sufficient to resolve some isobars can be achieved, but typical TOF instruments use only low or moderate resolution (like the quadrupole, distinguishing ions which differ by one unit of m/z). As for the other uncommon PMS analyzers, the precision and quantitative capabilities of TOF analyzers have not been thoroughly characterized. Detectors. Two ion detectors are dominant in PMS: the Faraday cup and the secondary electron multiplier. The Faraday cup is merely a metallic electrode intercepting the ion beam. It may be shaped to avoid scattering losses (hence, “cup”), but a simple plate geometry can also be effective. The detector is connected through a high-impedance resistor to ground. The neutralization current that develops in response to the impinging ions creates a voltage as it passes through the resistor; this voltage constitutes the signal. The device is characterized by unit gain: one neutralizing charge flows through the resistor for each impinging ionic charge. Thus, the response is independent of the energy, mass, or chemical nature of the ions. Neutralization currents are small, typically on the order of nanoamperes or less, so relatively large amplification is needed to afford a measurable response. This can limit instrument response time; Faraday cups are generally not used when extremely rapid detection is needed.11,16 However, the simplicity, low cost, accuracy, unbiased response, and low noise of the Faraday cup make it the detector of choice when high precision is important (as in PMS). Its principal drawback for PMS applications is the relatively low sensitivity resulting from unit gain; in general, the Faraday cup is useful (in fact, preferred in PMS) for detecting components of concentration down to approximately 10 parts per million (ppm) in a gas sample at atmospheric pressure. To extend the dynamic range, a secondary electron multiplier (SEM) is often offered as an optional second detector on a PMS. Here, the ion beam impinges upon an electroemissive surface, from which secondary electrons are accelerated to one or more electroemissive “dynodes”. The resulting electron cascade can provide gains of up to 108 electrons from a single ion. This can extend LODs down to well below 1 ppm in favorable cases. The detector has a very fast response time (on the order of nanoseconds), but it is not as stable as a

Faraday cup. There are both long-term deteriorations in gain and short-term variations (“noise”); the latter in particular may compromise precision. Eventually (typically less often than annually), amplification degrades to a point where the SEM must either be replaced or reactivated, requiring instrument downtime. Because emission of secondary electrons is dependent upon the velocity, mass, and charge of the incident ions, the SEM exhibits some mass discrimination. Insofar as this bias changes as the multiplier “ages”, recalibration of relative sensitivities for sample components of differing mass will be required (see below). Data Analysis. Data acquisition and analysis are important parts of process monitoring; feedback must be rapid to provide real-time control. With modern computers, the rate-limiting step is generally acquisition rather than processing. Thus, any of several statistical tools can be used to extract relative concentrations from mass spectral intensity data. These are generally transparent to the user of commercial instruments, buried in the software which both controls the instrument (including tuning and calibration functions) and deals with the data (including acquisition and presentation to a user and/or to a distributed control system). Still, the choices made by the programmer will affect the operation and performance of the instrument. Least-squares analysis is the most common quantitation approach. This requires acquisition and storage of reference spectra of pure components and analysis of calibration mixtures for determination of relative responses (sensitivities) to each component. Mixture spectra are then treated as linear combinations of the (sensitivity-adjusted) reference spectra. The concentrations returned are thus those values which, when multiplied by the corresponding reference spectra and relative sensitivities and then summed for each m/z, provide the smallest sum-squares difference between the calculated and experimentally measured mixture spectra. (Because of the difficulty of precisely controlling parameters such as electron emission from the hot filament in EI MS, nearly all analyses utilize normalized spectra to determine relative concentrations rather than attempting to determine absolute analyte concentrations from absolute signal intensities; relative concentrations are generally sufficient for process analysis.) Alternative quantitation approaches, including partial least squares, principal components analysis, and neural network treatments, can also be employed. Detailed discussion and comparison of the principles of these methods lie outside the scope of this review; the interested reader is referred to some excellent general reviews.49,50 One key way in which these methods differ from conventional least squares is that they use extensive mixture training sets (i.e., data from large numbers of mixtures of known composition) rather than singlecomponent reference spectra with just one or a few reference mixture(s) for calibration. This initial training can be time-consuming but reduces the reliance on a relatively small number of reference spectra. Continuous “retraining” can occur by addition of data to the training set. The alternative methods have been used widely in optical spectroscopy,51 but their relative merits for interpreting mass spectra (with their intrinsic “histogram” character and potential for long-term drift in relative intensities and “tuning” due to the effects of source contamination) have apparently not been addressed. For neural nets, extraction of many outputs

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(concentrations) from complex data is not the “norm” but does appear to be feasible.52 As noted above, the rate-limiting step for “real-time” analysis using any PMS quantitation method is data acquisition. Three independent experimental parameters must be addressed: integration times for each signal measurement, the number of replicate measurements at each m/z, and the number of m/z’s to monitor. The first two factors (integration time and replicates) have an obvious influence on the balance between precision and analysis time. The selection of m/z ratios to be monitored in a SIM acquisition (parametrization) has a more subtle effect. Simultaneous analysis requires monitoring at least one ion signal (i.e., one m/z) from the spectrum of each component of interest (e.g., at least six different signals must be monitored for simultaneous determination of six components). Accuracy and precision can often be enhanced by monitoring more than this minimum, but monitoring too many signals compromises the precision/speed tradeoff by more than just increasing acquisition time. Attempting to fit data which contributes to the noise but does not constitute an informative signal can actually degrade accuracy and precision. Thus, if a target accuracy and/or precision is attainable, there will be an optimum subset of m/z’s in the spectrum that ought to be monitored to achieve it. Factors to consider in selecting that subset include relative signal intensities in reference spectra, interference (overlap) among the spectra of various components, relative concentrations, and the required precision. Although some manufacturers provide algorithms to select the best peak to monitor for each component, routines to select the best overall subset are not widely available. Discerning the optimum based on a “brute force” evaluation and comparison of all possibilities is impractical for complex mixtures, because the number of possibilities increases very rapidly with spectral and mixture complexity (e.g., there are over 106 possible parametrizations when considering signals at 20 different m/z’s in a simple binary mixture53). Furthermore, as noted above, the true “optimum” is likely to depend on concentration; the best parametrization for determining trace “A” in “B” may not be the best for determining trace B in A. Because wide swings in concentration are not the norm in a process environment, this concentration dependence will not preclude there being an optimum parametrization for a given stream, but it may limit the applicability of a given parametrization, adding to the impracticality of a brute force approach. Empirical parametrization algorithms have met with some success but have not yet proven to be widely applicable.54-56 A “genetic algorithm”57,58 may offer an alternative approach to identifying those m/z’s for which intensity is best correlated with component concentration in a partial least-squares training set. However, such a treatment has yet to be reported for PMS. Once questions of quantitation methodology have been decided (at time of purchase) and the m/z parametrization for a given application has been determined, routine operation may proceed with little operator intervention. Even fault detection and calibration checks may be automated, although there are aspects of calibration and preventative maintenance that require periodic operator intervention. The period of that intervention constitutes an important figure of merit for evaluation of a particular instrument. Certain aspects

Table 3. Typical Applications of Process Mass Spectrometry Blaser et al.12 portable instrumentation environmental air monitoring environmental water monitoring aerosol monitoring fermentation monitoring reaction monitoring

Nicholas60 fermentation steel production ultrapure gas analysis acetonitrile and ammonia synthesis glass manufacture environmental monitoring

of routine maintenance (e.g., changing filaments or pump oil) require some (usually brief) downtime but can be scheduled for convenient periods; a typical maintenance interval for these may be 6 months. The interval for calibration is less clear and far more applicationdependent. In general, mass axis calibration for the common magnetic and quadrupole instruments is quite stable and requires little attention following initial setup (user-transparent, proprietary software routines may be used by some vendors to enhance x-axis reproducibility for SIM acquisitions). The same is not true of the intensity calibration. To begin with, regulation of the emission current for ionizing electrons (in conventional EI sources) is difficult. Even at fixed current, “filament wander” (slight physical movement of the hot filament) may cause significant drift of absolute intensities; this will generally have little effect on relative intensities and thus on calculated relative concentrations. However, during extended operation of an ion source, insulating deposits inevitably build up on various metal surfaces and conductive films may be deposited on insulators. These distort the electric fields in the source, potentially affecting ion and/or electron energies and often reducing ion signals. If all signals are attenuated proportionately, calculations of relative concentrations will again not be affected. Calibration problems arise when the effects of source contamination are mass-dependent. In such cases, even calculations of relative concentrations will be subject to error, regardless of the method of calculation. The simplest mode of compensation is to recalculate relative sensitivities by reanalyzing the calibration mixture(s). This can be done automatically, on-line (by using one or more port(s) of a sampling valve for “calibration gas(es)”). Unfortunately, this procedure will provide rigorous correction only in cases where all ions of a given compound are affected equally, a condition best met when monitoring just one ion per compound. When more than one ion is monitored from the spectrum of each compound, the correction afforded by adjusting sensitivities is only approximate. Ultimately, reference spectra of individual compounds or training sets must be re-acquired; the instrument operating parameters must be adjusted (i.e., voltages must be “retuned”); and/ or the source must be cleaned. Most vendors provide software for “autotuning”; the sophistication and effectiveness of these routines vary widely. Mathematical compensation for tuning drift has also been attempted,59 but operator intervention at some point is inevitable. Applications of Process Mass Spectrometry As noted above, exhaustive review of the burgeoning applications of process MS lies outside the scope of this discussion. It is instructive, however, to consider the section titles from two recent attempts at such a task (Table 3).12,60 [It is interesting to note that among 157 references in the Mass Spectrometry section of the most

1200 Ind. Eng. Chem. Res., Vol. 38, No. 4, 1999 Table 4. Components of an Ethylene Oxide Stream Analyzed by Process MS62 component

MW (monoisotopic)

concentrationa

ethylene chloride (C2H5Cl) methyl chloride (CH3Cl) ethylene oxide (C2H4O) carbon dioxide (CO2) argon (Ar) oxygen (O2) ethane (C2H6) nitrogen (N2) ethylene (C2H4) methane (CH4)

64.008 49.992 44.026 43.990 39.962 31.990 30.047 28.006 28.031 16.031

0.03 ( 0.02 ppm 1.25 ( 0.02 ppm 2.51 ( 0.0059% 5.80 ( 0.0124% 0.37 ( 0.0010% 7.89 ( 0.0125% 0.35 ( 0.0029% 53.43 ( 0.0502% 29.47 ( 0.0339% 0.11 ( 0.0041%

a

Mean of 100 samples.

recent “Applications Review” of “Process Analytical Chemistry”,12 over half cite various meetings proceedings. This reflects the dynamic growth and developmental status of the field (perhaps convoluted with the publication reticence of many industrial researchers).] The titles give some flavor of the breadth of potential applications but may disguise the fact that the majority of PMS applications invoke the natural compatibility of MS with volatiles analysis. For example, one of the most extensive applications of PMS is for the critical control of ethylene oxide (EO) production,61,62 wherein the mass spectrometer typically determines 10 components simultaneously (Table 4), ranging in concentration from over 50% (N2) to less than 1 ppm (ethylene chloride). Control is critical in this system because high reaction rates and competitive markets combine to make optimum operation occur not far from an explosive threshold. Furthermore, even traces of some constituents (especially those containing chlorine) can poison system catalysts. The example illustrates that “mass overlaps” (contributions to the signal at a given m/z from two or more components) can be tolerated, provided that there is a measurable and reproducible difference in component spectra. Note, for example, that two components (N2 and ethylene) have nominal molecular weight (MW) 28 and two others (EO and CO2) have nominal MW 44. As noted above, process mass analyzers rarely have the resolution necessary to distinguish the small differences between the exact masses of such isobaric pairs. Nevertheless, distinction of the isobars in the EO stream is not difficult, because in each case at least one member of the pair has other peaks in the spectrum (e.g., at m/z 27 for ethylene or 43 for EO) for which there is no interference from the isobaric counterpart. In fact, simultaneous analysis is feasible even when there is complete spectral overlap, provided that spectral distinctions are significant relative to the precision of the measurement. For example, the high precision of a process mass spectrometer has enabled simultaneous monitoring of the isomers pentane and isopentane,53,55 even though these C5H12 compounds have the same exact mass and complete spectral overlap (every peak in the mass spectrum of pentane also appearsswith slightly but reproducibly different intensitysin the spectrum of isopentane; Figure 4). The concentrations in the simple binary mixtures of Figure 4 range from 0.1 to 0.9 mole fraction (isopentane), with relative errors ranging from 0.2 to 16%. While this accuracy is generally poorer than that evident in Table 4, the difference is due more to complications from handling liquid samples than to the difficulties associated with isomers in general; a similar plot for 1-butene/isobutylene mixtures54 shows much smaller errors (0.02-2.3%, relative).

Figure 4. Mass spectra of (a) n-pentane and (b) isopentane. (c) Validation plot of calculated versus actual isopentane concentration for a series of binary n-pentane/isopentane mixtures. Calculated values were based on the best least-squares fit for the mixture spectra. The line is the theoretical (45°) curve. See ref 55 for a more detailed discussion.

The pentane example illustrates another point subtly evident from inspection of Table 3: while dominated by analysis of traditional “volatiles”, reported applications are by no means limited to these. Sampling of liquid streams offers an added challenge, because variance in sampling or volatilizing liquids can compromise the high precision needed for PMS. Nevertheless, Townshend et al.63 have shown that quasi-batch sampling (involving “total vaporization” of a small liquid aliquot in a heated expansion volume prior to MS sampling of the vapor) can provide precision (∼6% RSD) comparable to that of headspace analysis for trace (ppm) analysis of volatile liquids. A similar liquid sampler was used for PMS of a hydrocarbon stream in a synthetic rubber plant, providing faster response than that of process gas chromatography (GC), with comparable or better accuracy and precision.64 Liquid hydrocarbon mixtures have also been sampled by continuous infusion into a heated “flash vaporizer” where they are mixed with hot helium and then swept to a sampling T (like that pictured in Figure 1).55 Precision comparable to headspace analysis was achieved. The careful heat tracing and avoidance of leaks and reactive surfaces that are essential parts of any process analysis application make cooperation

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between analytical chemists and engineers especially critical in designing an analyzer interface for PMS of liquid streams. Indeed, it is often and fairly remarked that the quality of the interface can determine the success of any process analyzer application. In light of the extra challenges attendant upon sampling liquid streams, it is perhaps remarkable that continuous MS monitoring has also been applied to direct analysis of aerosols and airborne particulates.65 These applications generally invoke relatively “exotic” ionization techniques. For example, as noted above, thermal ionization was used for environmental monitoring of UO2 and I2 particles in a nuclear facility.38 This unusual application (relative to more “conventional” environmental applications, as in the analysis of respiratory and other gases in a coal mine60 or submarine66 or air sampling from an atmospheric probe67) utilized a magnetic mass analyzer with multiple detectors to determine isotope ratios as small as 0.007 with 10% RSD on micron-sized particles containing just 0.1% UO2. Sub-ppm LOD’s were reported. An additional “dimension” of information can be derived in systems using separate lasers to determine particle size (by scattering68 or aerodynamics69) and composition (by laser vaporization/ionization MS). Time-of-flight mass spectrometers are employed in these cases, providing the rapid data acquisition needed to capture transient signals deriving from single particles. The systems can be used for analysis of both organic and inorganic particles but have to date been used for environmental monitoring rather than process control. While direct PMS analysis of solids is exceptional, “inferential” measurementsswherein control of a process generating an involatile product is accomplished by monitoring volatile feedstocks, intermediates, or offgasessconstitute a major class of applications. Examples may be drawn from the metals industry, where on-line monitoring of steel blast furnace off-gases and reagent gas-mixing stations60 or aluminum potline smelter emissions70 can be used to optimize plant efficiency. Monitoring the composition and purity of reagent gases is particularly critical in the electronics industry, where PMS has been used to control various chemical vapor deposition,71-73 molecular beam epitaxy,74 and plasma etching73 processes. The complex processing associated with electronics devices and their relative intolerance of flaws suggests a high value added. However, this market is also aggressively competitive, making precise and cost-effective process control absolutely essential. Reaction rates (and therefore optimum gas composition) vary during the course of many of the deposition and etching reactions, reflecting changes in the device surface and even other surfaces in the reaction chamber. Thus, it is generally not sufficient to carefully regulate the flows of gases and their purity; feedback is essential for high product consistency and optimum efficiency. In this environment, the electronics industry was one of the first to embrace PMS for on-line control.75 A wide range of reagents can be monitored, including simple gases (like H2 and NH373) and more complex and/or corrosive reagents (like SiH4, SiF4, and HCl) and intermediates.72,75 The mass spectrometer can also sense leaks in the reagent lines,71 a critical function in systems where sub-ppm contamination by components of air can compromise product quality. Besides true process monitoring and control, PMS has played a crucial role in

elucidating the mechanisms of important deposition and etching reactions (e.g., refs 74 and 76), thereby facilitating modeling and “off-line” optimization of these processes. Another important area of inferential PMS applications is the monitoring of bioreactors. Here again, the product of commerce (e.g., biosynthetic pharmaceuticals) may be involatile and so not subject to direct PMS analysis (alcohol fermenters represent important systems for which direct product analysis by MS is also feasible). In comparison with other on-line monitoring techniques (such as optical density probes, microscopy, and liquid chromatography), PMS is particularly useful for applications requiring fast response and multicomponent capabilities.77 When speed is critical, direct MS analysis of the headspace is often preferable to MIMS analysis of the broth because it removes the possibility of sample carryover due to membrane contamination and improves response and cycle times. For example, direct headspace analysis of the oxygen consumed and the carbon dioxide formed in fermentation processes has been used to determine the respiratory quotient of cells,78 a measure of viability. In similar work, the activity of nitrogen-fixing bacteria was measured by direct mass spectrometric sampling of nitrogen, oxygen, argon, carbon dioxide, and water.79 Nitrogen uptake rates agreed with those measured by acetylene reduction assays and on-line cell growth measurements. In such cases, the enhanced speed of the MS measurements facilitates optimum timing of events such as the harvesting of reactor mixtures for the most productive use of raw materials and reactor time. Furthermore, in many instances PMS measurements are far more sensitive than traditional approaches. For example, the number of viable animal cells in a reactor could be determined by PMS monitoring of oxygen uptake, whereas conventional methods using paramagnetic oxygen sensors were not sufficiently sensitive.80 For monitoring trace components in complex biological systems (e.g., in flavors monitoring81), the reduced background and resulting low LOD’s afforded by selective MIMS can make it the method of choice.10 Although rapid, noninvasive sampling can be challenging, MIMS has been used successfully to monitor even metabolism rates in living systems. Response times vary widely, depending on the type and geometry of membrane and other elements of the sampling system. For example, a simple stainless steel perforated capillary covered with a silicone membrane provided response times ranging from 50 s to a few minutes in metabolic studies of wheat stalks82 and aquatic plants.83 Such response times have proven adequate for fully automated control of a fermentation system for ethanol production;84 a membrane probe immersed directly in the broth provides the (inferential) feedback needed to control glucose concentrations for maximum ethanol yield84 much more quickly than does an alternative off-line liquid chromatographic method.85 When response times are too long for optimum control, it is possible to get reproducible results using pulsed sample delivery to the membrane and monitoring the composition of the permeate gas before steady state is reached.86 Quantitative information can be derived by measuring at a fixed delay after the pulse onset, by measuring the rate of approach to steady state, or (with repetitive pulsing) by measuring the phase shift between the sample pulse and the measured ion intensities. The speed of analysis can be significantly en-

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hanced. For example, when MIMS was used to monitor and control the production of penicillin, a cycle time of around 11 min was achieved by measuring away from steady state.87 This was adequate for controlling the broth composition, whereas the 40-min time required for full equilibration would have resulted in a cycle time too long to be useful. Other industrial applications of MIMS for bioreactors include instances where MIMS is used for process optimization by one-time determination of reaction kinetics constants (such as the vmax/km ratio in an enzymatic system following Michaelis/Menten kinetics88) rather than for true process control. For example, the dependences of the products, rates, and efficiencies of photolysis reactions on solvent composition and light intensity were determined using MIMS.89 The experiment can also provide valuable insight into the identity of side products, as in a study of fungal fermentation reaction broths.90 There are many other instances where on-line MS has been used to characterize reaction processes for subsequent control by simpler technologies. For example, an on-line mass spectrometer was coupled with Fourier transform infrared spectrometry to simultaneously characterize the catalyst surface and volatile products and intermediates in the catalytic reduction of NO by ammonia on vanadia/titania surfaces.91 In a similar mechanistic study, a precisely positionable gas microsampling capillary was used to probe reactions very close to the catalyst surface, thereby eliminating effects of dilution and wall-induced artifacts and allowing better modeling of the chemistry of simple heterogeneous catalytic reactions (e.g., the reduction of H2 on Pt).92 Another important class of examples is the analysis of engine exhaust for real-time monitoring of the effects of varying engine parameters (like the fuelto-air ratio). A wide range of emissions can be monitored, including unburnt fuel, pyrolyzed or partially oxidized hydrocarbons,93 and sulfur-containing species (for which some selectivity can be achieved using a xenon chemical ionization source34). These are extremely complex systems, in many cases requiring a concurrent chromatographic separation step (e.g., ref 94). Not surprisingly, the same requirement for preseparation generally pertains to direct analysis of jet95 and automobile96 fuels and their combustion/conversion products. Although traditionally considered to be relatively slow, GC/MS analyses can be accomplished relatively quickly (on the order of a few minutes or less) using new short-column GC techniques.47,95 Indeed, the chromatography can occur so rapidly with short-column GC that the microsecond spectral acquisition times achievable with a time-of-flight mass spectrometer may be necessary to ensure detection and resolution of narrow chromatographic peaks. Summary and Outlook Authors of at least two recent PMS reviews11,60 have included discussion aimed at facilitating decision-making concerning adoption of PMS. In essence, the decision should rest on the need for rapid feedback for process control, to achieve optimum efficiency, safety, productivity, and/or product quality. Where specifications are tight and unforgiving (e.g., the quality specifications in manufacturing electronic microcircuits or the safety requirements for competitive operation of an ethylene oxide plant), the edge offered by rapid, detailed analyti-

cal feedback is essential. Even in these cases, the choice of an analyzer type (IR, Raman, GC, MS, ...) and even of a vendor will generally be case-specific. For the rapid analysis of volatiles in complex mixtures, PMS will seldom be rivaled. The impediment posed by the intrinsic complexity of the PMS analyzer is more perceived than real; electronics advances have enabled extended, essentially unattended operation (e.g., Didden and Duisings reported monitoring a hydrocarbon stream for 3 months without recalibration of their quadrupole mass spectrometer64). Where the speed of analysis can be exploited for multiplexing, even the impediment posed by the initial capital outlay can be readily amortized. The simplicity and speed of time-of-flight analyzers and the potential for high sensitivity (especially with storedion sources) may lower the capital barrier even further and may enable applications with fast gas chromatography where true simultaneous analysis is not feasible. As one of a family of powerful and reliable on-line analyzers, the process mass spectrometer seems destined to play an increasingly prominent roll in the manufacturing industries of the 21st Century. Acknowledgment This work was supported in part by the National Science Foundation (Grant EEC-9528067) and by the University of Tennessee Measurement and Control Engineering Center (an NSF Industry/University Cooperative Research Center). Literature Cited (1) Ponton, J. W. Chemical Process Control in the 1990’s. Chem. Ind. 1993, 315-318. (2) DesJardin, M. A.; Doherty, S. J.; Gilbert, J. R.; LaPack, M. A.; Shao, J. Better Understanding of Plant and Pilot Plant Operations using On-line Mass Spectrometry. Process Control Qual. 1995, 6, 219-227. (3) Henry, C. Electrospray Continues to Evolve. Anal. Chem. 1997, 69, 427A-432A. (4) Clarke, J. A Review of On-line Analysis. Anal. Chim. Acta 1986, 190, 1-11. (5) Adams V. H. Process Mass Spectrometry. ISA Calgary ’89 Symposium, Calgary, 1989; ISA: Research Triangle Park, NC, 1989; Paper 89-0344, pp 389-400. (6) Cochet, L.; Heitz, G.; Jorre, D.; Thomas, F. Application of Mass Spectrometry in Iron and Steel Industry. Recent Dev. Mass Spectrosc. Proc. Int. Conf. Mass Spectrosc. 1970, 367-376. (7) Fjeldsted, J. C. Considerations for Using a Laboratory Mass Spectrometer for On-Line Monitoring. Adv. Instrum. Proc. 1990, 45 (2), 549-555. (8) Koch, M. On the Conversion of a Mass Selective Detector for Gas Chromatography/Mass Spectrometry Application to StandAlone, On-Line, Real-Time Mass Spectrometry Application. Rev. Sci. Instrum. 1994, 65 (9), 2808-2818. (9) Lewis, G. Mass Spectrometers Move On Line. InTech 1989, 36 (12), 45-47. (10) Bauer, S. J.; Cooks, R. G. MIMS for Trace Level Determination of Organic Analytes in On-line Process Monitoring and Environmental Analysis. Am. Lab. 1993, 25 (16), 36-51. (11) Walsh, M. R.; LaPack, M. A. On-line Measurements using Mass Spectrometry. ISA Trans. 1995, 34, 67-85. (12) Blaser, W. W.; Bredeweg, R. A.; Harner, R. S.; LaPack, M. A.; Leugers, A.; Martin, D. P.; Pell, R. J.; Workman, J.; Wright, L. G. Process Analytical Chemistry. Anal. Chem. 1995, 67, 47R70R. (13) Beebe, K. R.; Blaser, W. W.; Bredeweg, R. A.; Chauvel, J. P.; Harner, R. S.; LaPack, M. A.; Leugers, A.; Martin, D. P.; Wright, L. G.; Yalvac, E. D. Process Analytical Chemistry. Anal. Chem. 1993, 65, 199R-216R. (14) Kotiaho, T. On-Site Environmental and In Situ Process Analysis by Mass Spectrometry. J. Mass Spectrom. 1996, 31, 1-15.

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Received for review November 19, 1997 Revised manuscript received March 28, 1998 Accepted August 17, 1998 IE9707984