Herbert H. Hili, Jr., William F. Siems, and Robert H. St. Louis
Department of Chemistry Washington State University Pullman, WA 99164-4630
Dennis 0. McMinn
Department 01 Chemistry
Gonzaga University Spokane, WA 99258-0001
I
When a gaseous ion at atmospheric pressure is placed in a constant electric field, it accelerates down the field until it collides with a neutral molecule, accelerates again until it has another collision, and so forth. This chaotic sequence of accelerations and collisions at the molecular level translates into a constant ion velocity over macroscopic distances. The ratio of the ion velocity to the magnitude of the electric field is called the ion mobility, and separation of ions on the basis of mobility differences is called ion mobility spectrometry (IMS). Because it can measure ion currents below lo-'* A, IMS is highly sensitive as a detection technique. The combination of moderate separating power with trace-level sensitivity has led to applications of the ion mobility spectrometer as a stand-alone monitor and a chromatographic detector. When it emerged as an analytical 0003-2700~901A362-1201/$02.50/0 @ 1990 American Chemical Society
technique in the early 19708, IMS was also known by two other names: gaseous electrophoresis and plasma chromatography. The term gaseous electrophoresis emphasized the strong analogy between the mobility experiment and traditional liquid-phase electrophoresis (many of the key equations are identical), whereas the term plasma chromatography referred to the chromatogram-like separations of ions that can be achieved with IMS. These terms were confusing, however, because both electrophoresis and chromatography must be stretched beyond
REPORT the meanings they generally have to apply to separation of ions on the basis of mobility. On the other hand, the term mass spectrometry is a wellaccepted use of the word spectrometry, denoting a method for gas-phase separation of ions. Thus ion mobility spectrometry seems to better represent the standing of the method in the hierarchy of separation techniques. IMS was discussed by F. W. Karasek in a 1974 REPORT (I)that reviewed the development of mobility theory and the emerging analytical applications of IMS for detection of trace quantities of
gaseous organic compounds at atmospheric pressure. The advantages of IMS are the same today as they were then-this technique offers high sensitivity, instrumental simplicity, low cost, analytical flexibility, and realtime monitoring capability. IMS researchers in the 1970s gathered fundamental data about the technique and its potential applications. Response ions were identified (2),mobility constants were measured (3), temperature effecta were investigated (4), and ion mass-to-mobility correlations were made (5).Explosives, chemical warfare agents, drugs of abuse, and atmospheric and workplace pollutants were found to produce strong IMS responses. It waa soon realized that a variety of operating modes were available. For example, hy monitoring positive background reactant ions, one can gain essentially the same information from IMS as that obtained from a flame ionization detector (6),whereas monitoring electron current with nitrogen gas in the spectrometer yields a response similar to that of the electron capture detector (7). In addition, the instrument can be tuned to perform selective mobility monitoring (8). Investigators in the 1980s pioneered new techniques for ionization, for adding trace dopants to the spectrometer
ANALYTICAL CHEMISTRY, VOL. 62. NO. 23, DECEMBER 1, 1990
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REPORT
rigura 1.
ion mobility spectrometer with an atmospheric pressure ion drin tube, "NI ionization. and capillary column sample
introduction. Shaded areas am c " i c materials. Guard rinps are fashioned Of thin stainless steel and til snugly against the inner wail of me cwamic tube; an electrical lead from ea& g w d ring passes throuch me ceramic wail. The haler for me ~ S N I foil is of stainless steel and is electrically m n e c w to me first gusrd ring. som coiiectw and hii bider we pertorated to allow passaga of drin gas. A 6ata system with a n w w i g i t a l (AID) conversion and timing functions, as well BS a scanning sqwswave generator (SSQ) for FT mode operation. occupy I10 slots in a pe4onal computer.
to tailor ita response to specific classes of compounds, and for sampling from vapor and condensed phases. New signal-processing methods, including a Fourier transform mode, were developed, and the importance of avoiding overload in the detector was realized. Engineering developments provided IMS-based detectors and alarms in both hand-held and stand-alone configurations. Expanded uses in chromatographic detection included the use of supercritical fluids and liquids as well as vapor mobile phases. Franklin GNO Corporation, the original developer and supplier of IMS equipment, was reorganized as PCP, Inc., and today a handful of new IMS manufacturers are targeting the broad, but as yet largely untapped, range of monitoring 1202A
applications. The growing interest in IMS as an analytical method warrants an update on the technique and its potential for the 1990s. Bask prfnclples The ion mobility spectrometer. A typical IMS system is shown in Figure 1. The heart of the instrument is the drift tube, which provides a region of constant electric field where ions are created and allowed to migrate. In the design shown, the tube is built from a stack of metal guard rings separated by thin insulators; each ring is connected to a node in a string of electrical resistors. This arrangement provides a smooth progression of voltages from one ring to the next when a supply voltage is connected across the whole
ANALYTICAL CHEMISTRY. VOL. 62. NO. 23. DECEMBER 1. 1990
string. A steady flow of ambientpresaure drift gas, usually NP or air, sweeps through the drift tube and minimizes the buildup of impurities that could otherwise react with ions and distort mobility spectra. Gates, fabricated from thin parallel wires, are used to block or pass ions traveling in the drift field. The ion paths terminate at the collector, a simple metal screen or plate. Many ion mobility spectrometers contain an aperture grid close to the collector to capacitively decouple the collector from approaching ions. A number of additional compooenta are needed to provide drift field high voltage, control the drift tube temperature and drift gas flow rate, generate timing signals for the gates, isolate gate timing signals from the high voltage of
the drift field, amplify the ion signal as it arrives at the collector, and provide signal averaging or other signal procerising for the amplifier output. The ion mobility spectrum. The output spectrum is generated by first forming ions from the sample and then measuring ion migration in the electric field. The selection of ionization method is important because the ions formed and the ionization efficiency (and hence the quantitative measure of an analyte) depend on this choice. Once formed, each ion migrates at its own characteristic velocity down the constant electric field in the drift tube. The qualitative information from the experiment is usually reported as the spectrum of ion arrival times at the collector. Figure 2 shows a typical signalaveraged ion mobility spectrum of a small peptide, L-leu-L-met-L-phe, introduced in liquid methanoywater using an electrified spray to produce ions. The gate is pulsed open for 0.3 ms, admitting a mixture of ions to the drift tube, and the collector current is monitored. The y-axis shows the ion current from the collector, and the x-axis records the arrival times of ions. Under normal IMS conditions, ions migrate at velocities between 1 and 10 m/s, producing arrival time peaks in the 330-ms range. Thus, after the collector current is monitored for -30 ms, the gate can be opened to admit another ion pulse and the experiment can be repeated. Repetitions are commonly averaged to increase the signal-to-noise ratio (S/N); 512 repetitions were averaged to obtain the spectrum in Figure 2. Peaks with arrival times of P 9 ms correspond to background ions produced from the solvents used for sample introduction, whereas peaks in the 10-16-ms range correspond to product ions derived from the peptide.
- Ion moblllty spectrum of a small peptide. sample was InIrDduCed In metbnol/water using an electrifiedspray n ~ b ~ l l ~ l ~ o n l i ~ ~ l MlUrCB
IMS ueaks are tvuicallv rather broad examole. C1- reactant ions have been compared with t h i range of possible used ‘to increase sensitivity to explodrift times, and the amount of qualitasives (15-Z7), NH: reactant ions have tive information available from IMS is been found to enhance selectivity and less than that from MS and IR specsimplify IMS response to amines (169, trometry but more than that from and (acetone)ZH+ reactant ions have flame ionization and electron capture been used by Spangler and co-workers detection. to ionize organophosphonates with Ion formation. Although positive specificity in hand-held detectors (19). and negative gas-phase ions for IMS Ion migration. After formation, have been produced by a variety of ions are accelerated in the direction of methods, including photoionization the field between collisions with drift (9), laser multiphoton ionization (10, gas molecules. The energy gained from II), thermionic emission (12),and the electric field is randomized by coronaspray (13), the most common these collisions, and the combination of ionization source used is still radioacacceleration and collision results in a tive 63Nifoil. Using such a source, one constant average ion velocity ( u d ) that can produce background ions from niis directly proportional to the electric trogen gas: field (E).
+
N, 8-- Nl+ 8’-+ e(1) where 8- is the beta particle emitted from the 63Nisource and 8’- is the beta particle after some of ita energy has been used in ionization of the nitrogen molecule. The primary N : ion is too short-lived to appear -in the mobility spectrum. but it begins a series of ionmolecule reactions with trace amounta of H 2 0 , NHR,NO, or sample (if in sufficiently high concentration) in the drift gas. In the absence of sample, the resultina stable secondm ion clusters have Tbeen identified & (HzO).NH:, (HzO).NO+. and (HnOLH+. These background ions are normally called “reactant ions” in IMS because they undergo further ion-molecule reactions with neutral gas-phase analytes to produce analyte “product ions.” Similarl%,thermalizedelectrons produced during the primary ionization process can undergo capture reactions with electronegative analytes to form negative product ions. When 0, is present in the drift gas, a negative reactant ion cluster, (H20),0, or (H20), ( C O Z ) ~ ~ is ; , formed and negative product ions are produced by ionmolecule reactions. For IMS cell temperatures > 100 OC, (H20),0-, :HzO),CO;, CN-, C1-, and NO; are also present (14). The ion-molecule reactions that, occur in chemical ionization MS can be used to help predict responses in IMS. Detailed investigations of ion-molecule reactions under the ambient pressure and electric field conditions common in IMS are scant, however. An important variation of IMS ionization that can be used to enhance the sensitivity or selectivity of the technique for particular classes of compounds or to simplify the response for certain analytes involves the modification of reactant ion populations by ~adding t i ~ ~ carefully controlled concentrations of dopanta to the drift gas. For
ud = KE
(2)
The proportionality constant K is called the ion mobility and is usually computed in units of cm2V-1 s-1 K = ud/E= L2/Vtd (3) whereL is the ion drift distance in centimeters, V i s the voltage drop across L. and t d is the time it takes the ion to traverse L. In a review of ion mobility theory, Revercomb and Mason (20) have given the fundamental relationship between ion mobility and collision processes at the molecular level:
K = (3q/16N)(2rr/kT)L” X ( m + M/mM)1/2(1/Q) (4, where q is the charge on the ion, N is the number density of the drift gas, k is Boltzmann’s constant, T is absolute temperature, m is the mass of the ion, M is the mass of the drift gas, and fl is the collision cross section of the ion in the drift gas. When the instrument operating Conditions are held constant (constant T and P,and thus constant N), the mobility depends only on ion charge, reduced mass, and collision cross section:
K
(5)
01 q/pL“Q
+
where p = mM/(m M). For ions much more massive than the drift gas molecules, p is nearly equal to the drift gas mass M , and K varies only with q and fl. Collision cross section is determined by ionic size..shaDe. . . and uolarizabilitv. Reduced ion mobility constant. Because analytical IMS is generally performedat ambient pressureandat a variety of temperatures, comparisons are facilitated by reporting a quantity as nearly independent of T and P as possible. Because the number density, N,of Equation 4 increases with increasing P and with decreasing T,mo-
ANALYTICAL CHEMISTRY, VOL. 62, NO. 23. DECEMBER l , 1990
a
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REPORT bility values are normally adjusted to standard conditions, 273 "C and 760 Torr. The adjusted value is called the reduced mobility constant (KO)and is calculated from: KO= K(273/7')(P/760) (6) Although KOis expected to be a temperature-dependent quantity (arising from the T'"term and the temperature dependence of !l in Equation 4), minimal change has been found in KO over the range 85-220 "C for a variety of product ions (2,21). Inherent in the defmition of reduced mobility is the idea that the ratio of drift times for any two ions is independent of temperature and pressure. Reduced mobilities and drift time ratios can also vary if the ions contributing to a mobility peak are a composite of cluster ions whose proportions change with temperature and pressure (22). Instrumentationand w r a t h Drift tube. Gwd performance can he obtained with a wide range of guard ring diameters, thicknesses, and separations as long as the electric field experienced by the ions remains constant within a few percent (23).The stacked design has numerous parts and can he tedious to build. A one-piece construction based on a uniform resistive coating on a nonconductive substrate has been used successfully (24). The operating conditions most frequently adjusted are temperature, drift voltage, and drift gas flow rate. Although IMS resolving power decreases with increasing temperature, higher temperatures reduce ion cluster formation and interferences from contamination. Resolution loss from elevated temperatures may be countered by increasing drift voltage, as long as the initial pulse width is not the dominant contributor to peak width. At very high drift fields, considerably above the 200-350 V/cm typical of present systems, Equations 2 and 4 are no longer valid (20). Adequate drift gas flows, on the order of hundreds of milliliters per min-
Table 1.
Gates
Signal averaging Hardware monltoring
One aperture Two
Fourier transform
One aperture or two gates
-
pacitive response of the collector to approaching ions. Peaks are significantly broadened if the aperture grid is omitted. Sample introduction. An ion mobility spectrometer is relatively easy to overload with analyte, and sample size must be controlled with care. Symptoms of overloading include disappearance of reactant ion peaks, appearance of multiple analyte peaks from formation of dimer product ions and other cluster ions, and peaks that persist for long times. An overloaded instrument must be given time to be swept clear by the drift gas flow (sometimes days in the case of gross overloading). For many analytes, appropriate sample sizes are in the range of a few picograms to a few nanograms. From the standpoint of sample size, capillary GC has proven to be a particularly good match for IMS. Instruments intended for vapor-monitoring applications often incorporate membrane inlet systems (27) to moderate both the class and amount of sample introduced into the detector. Although vapor-phase samples are most common, condensed phases can also he introduced in the spectrometer using nebulization/ionization techniques (13).Effluents from supercritical fluid chromatography (SFC) (2% LC (29), and capillary electrophoresis (30) have been introduced to the ion mobility spectrometer in this way. For these applications, however, the reactant ions described above are probably no longer present but are modified by the reagents contained in the condensed mobile phase. Operational problems not yet entirely solved include incomplete breakup of solvent clusters and long-term stability of the nebulization/ionization process. Operating modes. The two basic types of data from IMS instrumentation are generation of complete mobility spectra of the ion population of the instrument and selective monitoring for the appearance of ions having drift times within some specified range. There are also three basic modes of operation: signal averaging (or one-gate),
Modes and lyplcal electronic operating conditions for IMS Mode
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ute with most tube designs, are needed to continuously sweep contaminanta and analytes from the spectrometer and minimize peak broadening and sensitivity loss resulting from ion-molecule reactions in the drift space. When spectrometers are not gas tight, the drift flow also helps to reduce unwanted diffusion of ambient vapors into the spectrometer. loa gates. Gates are used to block or pass ions traveling in the drift field. The most common design is a planar array of thin parallel wires oriented perpendicular to the ion drift. When the gate is closed, voltage on nearestneighbor wires is ( V , - V J 2 ) and ( V , t VJ2). where V , is the voltage of the drift field in the plane of the gate and V, is the gate closure voltage. When V, is large enough, essentially all the ions are collected on the gate wires. To open the gate, the voltage on all the gate wires is pulsed to V,. A n alternative design uses two closely positioned planar m a y s (15). The "downstream"array (closest to the collector) is kept at a constant voltage, V,, and the voltage on the upstream array is changed to open and close the gate. For positive ions, a voltage somewhat above V , allows ions to pass; if the voltage is below V,, ions are collected on the upstream array and the gate is closed. If V , is too small, ions can leak through the gate. On the other hand, V , can become so large that the region immediately upstream of the gate becomes significantly depleted of ions, a condition known as the gate depletion effect (25,26).A plot of sensitivity versus V , has a rather broad maximum where the closure electric field is 1-10 times the drift electric field. Many ion mobility spectrometers contain an aperture grid. This grid has a parallel wire construction similar to a gate, although all the wires are maintained at the same potential (typically 5-25 V aboveground for positive ions). The aperture grid is positioned as closely as possible to the collector (typically 0.5 mm) and reduces theca-
+ +
sample pulre
CondItlon8 Cycle tlme Amplller galn (VIA)
0.2-0.5 ms 0.5 ms (gate 1) 0.5-20 ms (gate 2)
5-50 ms 5-50 ms
10"- 10'2
Square-wave chlrp
0.25-10 s
10~-10"
ANALYTICAL CHEMISTRY. VOL. 62, NO, 23. DECEMBER 1, 1990
10*-10'~
Amplller 1180 t h e
0.1 ms 2s 10 ms (two gates) 0.1 ms (one gat(
Figure 3.
Gas chromatogram with ion Arociw 1248
mobility detection of
spiked with 4.4‘dibromoblphenyi. (4Mobilnv monlmrlng ol drlR t i m a behreen 2.2 and 10.0 m.Arrow demtes me 4,4‘dlbm&l-
phenyl peak. (b) SrmldeasMlve mnhwlng ol drill times. (Adaptsd wlth pamlrslonfrom SI. LOUIS. R. H.: HIII. H. H.. Jr. J. Hi@ Resola. chrp me*. 1990, is, 62832).
hardware monitoring (or two-gate! and Fourier transform (25).Each mod can perform spectral or monitoring ea perimenta, and each combination has different signal generation, gate configuration, amplification, and data processing requirements (Table I). Signal averaging, the fastest way to acquire ion mobility spectra, involves periodically pulsing the gate and recording the current arriving at the collector in real time. (If the drift tube contains two gates, as in Figure 1, the gate c l m r to the collector is kept permanently open.) The resulting ion mobility spectrum can be monitored with either an oscilloscope or a data acquisition system (if enhancement of S/N or a permanent record is desired). If signal averaging is applied, a few tens to a few hundreds of spectra are typically averaged. When IMS is used to monitor the output of another analytical technique (e.g., chromatography), integration of a portion of the stored spectrum may be desirable. In the hardware-monitoring mode, as in the signal-averaging mode, the entrance gate is opened to admit a pulse
of ions. After a measured interval, the exit gate opens for a short period (selective monitoring, as in Figure 3b) or a long period (nonselective monitoring, as in Figures 3a and 4). The chromatogram-like output of the amplifier indicates the quantity of ions having drift times within the selected range, and the amplifier output can be passed directly to an integrator or chart recorder. Spectra can be generated by sweeping the delay time between entrance and exit gates. Although hardware monitoring is quite slow for gathering spectra, ita instrumentation is the simplest of the IMS modes because a slow amplifier is used and no processing of collector signal is required. Because the S/N can alwavs he increased by averaging for longer periods of time or. equivalentlv. bv filtering with longer time cons&ts,-one m u 2 be sure to compare equal time periods for data collection when evaluating S/N characteristics of different methods. Thus, for a given duration of data acquisition, the one-gate and two-gate modes produce comparable S/N. FT-IMS uses a quare-wave generator caoable of a linear freauencv ram^. or &rp, to drive entrance ahd eiit gates simultaneously. The amplifier output must then be digitized and Fourier transformed. For a given data acquisition time, the FT mode produces a modest SIN advantage of XZ-XlO compared with the signal-averaging mode. Although signal-averaging and hardware-monitoring spectra often
show peak broadening because of ionmolecule reactions downstream of the entrance gate, the FT mode does not show this effect. However, it requires additional hardware and software as well as longer signal-proceasing times. Analytical characterhrtics Separation efficiency. For IMS, like other separation methods, the ratio of the spatial variance of the sample zone at the end of the separation to the length of the separator provides a convenient measure of separation efficiency. This measure is the theoretical plate height H.
H = 2 l L = (ud2i u,2)lL
(7) The total sDatial variance is divided into contribitions from diffusion (od2) and from initial Dulse width and other sources ( ~ 2The ) . spatial variances can be related to the transport equations for ion motion (31).A minim- value for H is obtained hy considering only diffusion broadening:
Hmi. = 2ikTLIqV (8) Here, q is the Townsend energy factor, a monotonicallv increasine function of Elprepresenting the ratio-of the mean agitation energy of the ion to the mean thermal energy of the molecules in the drift tube (32). Physically, 8 accounts for the energy pumped into the ions from the electric field, giving them not only a net velocity V d but also greater random kinetic energy than the surrounding neutral molecules. With an E
L I
1.15
0.20
I
0
I
I
0.28
0.34 Density (gimL)
0.39
40
50 60 70 Time (min)
80
0.456
0.543
100
110 120
I
I
10
20
30
Figure 4. Supercrlticai fluid c latogram of polydimethy obtained using ion mcbiiity detection. (Mapted wlth p”861on
90
ne oligomers
lrwn Monl~ey,M. A.: Slems. W. F.: Hill, H. H., Jr. J. auWnatog. iW0, 505.
215-25.)
ANALYTICAL CHEMISTRY, VOL. 62, NO. 23, DECEMBER 1. 1990
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REPORT of 200 Vlcm, T of 150 "C, and 1 atm pressure, 7 is approximately 2.1. The maximum number of theoretical plates possible for IMS can be determined from
N,. = LIH,, = qV127kT (9) and is a function of the charge on the ion, the voltage across the tube, the temperature, and the Townsend factor. Note that separation efficiency increases as drift field energy (qv) increases relative to random thermal energy (kT). With typical values of V = 3500 V and T = 150 OC, N,, is on the order of 18 000 for singly charged ions. However, because ug in Equation I is usually about the same magnitude as Ud, the actual number of theoretical plates is most often considerably below NmmSpangler and co-workers have found that N goes through a maximum of 1700 as the drift field is varied around 100 Vlcm in a miniature ion mobility spectrometer cell (33), although the value of about 3800 exhibited by the product ion peaks in Figure 2 is more typical of larger tubes. Resolution. Following the chromatographic definition, IMS resolution, R, is defined as the ratio of the separation of two ion peaks in a drift time spectrum to the average width of the peaks,
R = (td2 - td1)/2(uCl + ut2) (10) where each ut is the temporal counterpart of the spatial u in Equation I ((I = UdUt). From the expression for the number of theoretical plates (vw = L/a = td/Uc), it is easy to derive a useful relation for resolution (33)
R = ttAtdl/?d)(fi/4) = (bdm)(@/4) (11) where the barred quantities refer to averages. Using an experimentally determined value of N for a particular instrument and set of operating conditions, in conjunction with a table of reduced mobility values ( 3 ) , one can predict how well two analytes might be resolved by the instrument. For a resolution of 1.00 and the NmaX of 18OOO value calculated above, it is apparent that KOvalues must differ by at least 3%to be fully resolved by IMS; in actual instruments. 10%differences are typical. Minimum detectability. Defined as the mass flowrate required to produce an analytical signal three times the root mean square (rms) noise of the system, the minimum detectability of IMS is
D,,, = 3N,,,kF (12) where D,," is the minimum detectability in moles per second, N,,, is the root 12061
-
ionization method. With 63Ni ionization, efficiencies in the 10-3-10-5 range are often found. Electrospray ionization has been estimated to have an efficiency as high as 0.4 to nearly 1.0 (34, 35);this result should be possible with IMS as well as with MS. With coronaspray ionization, an efficiency > 0.01 can be achieved for caffeine. Thus with q in the range 1.04.OOO01, detection efficiency ranges from about lo-' down to In a typical signal-averaging experiment of 1 s duration, Nrm8 is on the order of 1.5 X and
Dmi,= 3 X
in IMS moved from fundamental studies toward applications to specific
analytical problems. mean square noise of the system in amperes, F is Faraday's constant (96500 coulombs per mole), and t is the overall detection efficiency measured as the ratio of the flow rate of ions detected (moles per second) to the flow rate of molecules in the sampled stream (moles per second). Detection efficiency (6) can be divided into several components: = (fq)(f,)(f()(cd)
(13)
where e. is the fraction of neutrals transferred from the sampling stream to the spectrometer, (, is the ionization efficiency of the source, L, is the efficiency of ion transport through the drift tube, and ( d accounts for intensity loss from diffusion, gate depletion, and electronic time constants. Approximate efficiencies for signal-averaging IMSarefn=1.0,q=0.5,andq=0.3. Ionization efficiency depends on the
ANALYTICAL CHEMISTRY, VOL. 62. NO. 23. DECEMBER 1, 1990
lo-''
molls (14)
Minimum detectability may be further reduced by additional signal averaging and by multiplexing. AIso, multiply charged ions have increased detectability by a factor equal to their numher of charges. In practice, 3 X 10-17 molls bas not been achieved but the method routinely operates below 3X molls (36).
I n the 198Os, work
f
to 3 X
IMS appllcatlons In the 198Os, work in IMS moved from fundamental studies toward applications to specific analytical problems, and the ion mobility spectrometer was used both as a stand-alone spectrometer and as a chromatographic detector. Motivated by the adverse effects of surface contamination in semiconductor manufacturing processes, Carr used thermal desorption and a carrier gas to transport trace contaminants to the ion mobility spectrometer for detection (37). Lawrence and co-workers of the Canadian National Research Council have applied IMS to the detection of explosives (16) and drug particulates on the hands of emergency room patients suspected of drug overdose (38). They have also used the technique as a screening procedure for the identification of wood products (39). Kolaitis and Lubman studied the ionization of various purine and pyrimidine bases and their ribose sugars, amino acids, vitamins, antidepressant drugs, and catecholamines using laser desorption with IMS (40,41). The real-time monitorine caDabilities and simple hardware n&ds i f IMS have motivated Environmental Technologies Group (formerly Bendix Environmental Systems Division) and Graseby Dynamics of England to develop portable stand-alone alarms and field monitors. To improve the portability of these systems, a miniaturized ion mobility spectrometer was developed (33,42)using continuously recirculating carrier and drift gases. A dimethylsilicone membrane inlet (27)re-
~ p ~ G C , S F C , a n d L C . I o n m o b i l i t y comparable to that of an electron capture detector chromatographic tracing. Figure 3b shows the same chromatogram when the detector is set to monitor the mobility window specific to bromide ion. The unidirectional flow ion mobility detector has also been interfaced successfully to a supercritical fluid chromatograph (28). Advantages of IMD after SFC include sensitive detection of compounds that do not contain chromophores (50). compatibility with a wide range of mobile phases (50, and an electron capture-like response under pressure-programmed conditions (52,53).Figure 4 shows a supercritical fluid chromatogram of polydimethylsilicone oligomers in which individual oligomers of > 3000 amu were detected using the ion mobility detector. A more complete review of IMS as a detection method for SFC is available (54).
O n e challenge facing researchers in the 1990s
detectors have been designed speeifically to meet the stringent demands of detection after capillary GC (13,47). By using a unidirectional gas flow, a reduced ionization cell volume, and direct capillary sample introduction, it has been possible to minimize peak broadening in the detector. The ion mobility detector has been used for the determination of naphthalenes in gasoline (13, 48); hydrocarbons in petroleum ether (47);fatty acid methyl esters in cabbage extract (48); and o p i a h , barbiturates, h e d i e p i n o n e s , and tricyclic antidepressanta in urine (49). As a chromatographic detector, the p i t i v e ion mode provides a response similar to that of the flame ionization detector but with greater sensitivity (36). The nonselective negative ion mode response is similar to that provided by the electron capture detector. Tunable selectivity, an important capability of ion mobility detection (IMD), is possible in either mode by monitoring a specific mobility window. Figure 3a shows a gas chromatogram of Aroclor 1248 (a mixture of polychlorinated biphenyls) spiked with 4,4'-dibromobiphenyl for which response is
IMS in the 1990s One challenge facing researchers in the 1990s is the use of the ion mobility spectrometer as a chromatographic detector for the determination of compounds separated by LC or other liquid-phase methods such as capillary
is the use of IMS
for chromatographic detection. duces clustering complications from ambient water and ammonia. Continuous IMS monitoring of toxic chemicals in the industrial environment has been studied by Dam (43) and by Watson and Kohler (44). In work directed toward monitoring NOz, SOz,HCl, and H2S in stack gases, Eiceman and co-workers have encountered difficulties in quantifying analytes in complex and dynamic mixtures (45). Difficulties of this type are typical of IMS under conditions of changing background matrix or sample overload (46) and must always be kept in mind as a possible problem with stand-alone applications. Matrix and overload problems generally are not experienced when highresolution chromatography is used for sample introduction. Microcolumn separations and IMS detection are an excellent match from the standpoint of sample size and simplicity as well as detector sensitivity.Work in our own laboratories has been directed primarily toward developing the ion mobility spectrometer as a detector following
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electrophoresis or ion chromatography. A significant step toward this goal was the recent development of a coronaspray ionization source for IMS (131. By introducing the effluent from a liquid stream into the spectrometer via an electrically charged capillary, ion mobility spectra from nonvolatile neutral and ionic compounds dissolved in liquids have been obtained (29. 30). Although simple liquid chromatographic separations have been reponed (29), some difficult operational problems remain. Reactant ions and analyte response factors vary considerably with small changes in geometry of the coronaspray source. Also, the high temperaturesand highdrift gasflowratesneeded to break up solvent clusters have led to problems with sample decomposi. tion, corona instability, and detector noise. The considerable practical potential of IMS for monitoring applications remains largely untapped, in spite of ita high sensitivity, low cost, small size, and versatility. This lack of development is largely a result of initial discouragement caused by overload and matrix problems. It must be recognized that IMS functions best with trace levels of analytes that make only minor perturbations of drift tube conditions. Each application presents challenges such as analyte sensitivity and volatility as well as matrix interferences, and must be considered individually. The powerful techniques of preseparation by membranes, selective adsorption, and chromatographic inlets coupled with reactant ion modifications are helpful in many cases. Some fundamental problems remain in developing IMS. The resolving power of existing instruments seems to be less than expected on the basis of diffusion and initial pulse width (55), and the reason for this is not understood. The extra broadening may be attributable to ion-molecule reactions in the drift space, inhomogeneity of the electric field, or even coulombic repulsion. The FT mode should be able to probe reactions in the drift space, but it has not yet been used for this purpose. Other detection modes, such as an organophosphorus selective configuration that would simulate the nitrogenlphosphorus detector (56),have been proposed but not yet implemented. Finally, recent articles on peak shape analysis (55) and a second.derivative algorithm for separation of overlapping peaks (57) are reminders that several powerful signal-processing techniques are not fully used in IMS. Although IMS is considered an old technology, in many ways it is new technology waiting to be discovered. Ita
ANALYTICAL CHEMISTRY, VOL. 62, NO. 23. DECEMBER 1, 1990
low detection limits and simplicity of design assure IMS a strategic position in analytical chemistry between universal nonspecific detectors, such as flame ionization and electron capture, and the more powerful qualitative techniques, such as MS. IMS research in the authom' laboratory has been sponsored in part by a grsnt from the Public Health Service (GM29523). The authors are most grateful to Glenn E. Spangler for his careful critical reading of this manuscript and many helpful suggestions.
References (1) Karasek, F. W. Anal. Chem. 1974,46,
710 A-I17 A. (2) Carroll, D. I.; Dzidic, I.; Stillwell, R. N.;
Homing, E.C. A w l . Chem. 1975, 47,
195659. (3) Shumate, C.; St. Louis, R.H.; Hill, H. -~H., Jr. J. Chromatogr. 1986,373,141'13.
(4) Karasek,F. W.;Kane,D. M. J.Chromatog?. Sei. 1972,10,613-77. (5) Griffin, G. W.;Dzidic, I.; Carroll, D. I.; Stillwell, R. N.; Homing, E. C. Anal. Chem. 1973,45,120&09. ( 6 ) Karasek, F. W.; Hill, H. H., Jr.; Kim, S. H.: Rokushika. S. J. Chromatow. - 1977. i35132~9. (7) Karasek, F.W.; Spangler, G . E. In,Electmn Capture: Theory and practrce in Chromatography; Zlatis, A.; Poole, C. F., Eds.: ELsevler:Amsterdam. 1981:Chapter 15,pp. 377406. (8) Baim, M. A,; Hill, H. H., Jr. Anal. Chem. 1982,54,38-43. (9) Baim, M. A,; Eatherton, R. L.; Hill, H. H., Jr. Anal. Chem. 1983,55,1761-66. (10) Lubman, D.M.; Kronick, M. N. Anal. Chem. 1982,54.154651. 111) , ~Kolaitia. ~ , L.:, Lubman. D. M. A n d . Chem. 1986,58,1993-2001: ler, G . E.; Kim, S. H.; Epstein, J.; (12) S c a m a ~D., N.; Carrico, J. P., ~ r pro. ceedings of the 1988 CRDEC Scientific Conference on Chemmd Defense Res e a k h ; CRDEC: Aberdeen Proving Ground, MD, 1988;US.Patent 4 839 143, June 13,1989;US.Patent 4 928033,May 22,1990. (13) Shumate, C. B.; Hill, H. H., Jr. Anal. Chem. 1989,61,601-06. (14) Carr,T. W . Anal. Chem. 1979,5I,70& 11. (15) . ~. Prodor. C. J.: Todd. J. F. Anal. Chem. 1984,56,1794-97. ' (16)Lawrence, A. H.; Neudorfl, P. Anal. Chem. 1988.60, I-. (17) Spangler, G . E.;Carrico, J. P.; Camp nn D. N. J. Test.Eoal. 1985,13(3),23P bell, ~
~~
-".
(18) Kim, S.H.; Karasek, F. W. Anal. Chem. 1977,50,152-55. (19) Spangler, G. E.;Campbell, D. N.; Carrico. J. P. Presented at the 1983 Pittsburgh Conference and Exposition on Analytical Chemistry, Atlantic City. NJ. March 1983 U.S. Patent 4 551 624. November 5,1985. (20) Revercomb, H. E.; Mason, E. A. A d . Chem. 1975,47,970-83. (21) Lubman, D. M. Anal. Chem. 1984,56, 1298-1302. (22) Preston, J. M.; Rajadhyax, L. Anal. Chem. 1988,60,31-34. (23) Spangler, G. E.; Coben, M. J. In Plasma Chromatography; Carr, T. W., Ed.; Plenum Press: New York, 1984;p. 6. (24) Carrico, T.F.; Sickenberger, D. W.; Spangler, G . E.; Vora, K. N. J. Phys. E. ~~~~~~~~
~
~
~
~
Sei. Instrum. 1983,16,1058-62. (25) Knorr, F. J.; Eatherton, R. L.; Siems, W. F.; Hill, H. H., Jr. Anal. Chem. 1985,
(40) Kolaitis, L.; Luhman, D. M. Anal. Chem. 1986,58,2137-42. (41) Lubman, D. M. Re". Sei. Instrum. 1988,59,55741.
(26) Aaronson, E. A. Technical Report No. SAND87-0072UC-32. 1987: Sandia Cor-
(42) Carrico, J. P.; Davis, A. W.; Campbell, D. N.; Roehl, J. E.; Sims, G. R.; Spangler, G . E.; Vors, K. N.; White, R. J. Am. Lab.
S 7 A~W "A R ".,
poration, Albuquerque.
(27) Spangler, G. E.; Carrico, J. P. Int. J . Mass Spectrom. Ion Phys. 1983,52,26781.
(28) Eatherton, R. L.; Morrissey, M. A,; Siems,W. F.; Hill, H. H., Jr. J.HighResolut. Chromatogr. Chromtogr. Commun. 1986.9, 1 W O . (29) McMinn, D. G.; Kinzer, J.; Shumate, C. B.; Siems, W. F.; Hill, H. H., Jr. J . Microcolumn Sep. 1990.2,188-92. (30) Hallen, R. W.; Shumate, C. B.; Siems, W. F.; Tsuda, T.; Hill, H. H., Jr. J. Chromotogr. 1989,480,23345. (31) Spangler, G . E.; Collins, C. I. Anal. Chem. 1975,47,403-07. (32) MeDaniel, E. W. CollisionPhenomena in Ionized Goses:Wile": New York. 1 9 6 4
Feb. 1986,152,155-57; 1 5 9 4 3 . (43) Dam, R. J. In Plasma Chromatography; Carr, T. W., Ed.; Plenum Press: New York, 1984; pp. 174-214. (44) Watson, W. M.; Kohler, C. F. Enuiron. Sci. Technol. 1979,13(10), 124143. (45) Eiceman, G . A,; Leasure, C. S.; Vandiver, V. J. Anal. Chem. 1986,58,7680. (46) Metro, M. M.; Keller, R. A. J . Chromatogr. Sei. 1973,11,520-24. (47) St. Louis, R. H.; Siems, W. F.; Hill, H. H., Jr. J. Chromatogr. 1989,479, 221-
-. 31.
(48) St. Louis, R. H.;Siems, W. F.; Hill, H. H., Jr. LCIGC 1988,9,810-14. (49) Eathertan, R. L. PBD. dissertation, Washington State University, 1987.
(50)Rokushika, S.;Hatano, H.; Hill, H. H., Jr. Anal: Chem. 1981.59.8-12: (51) Mornssey, M. A. Ph.D, Dissertation, Washington State University, 1988. (52) Tarver, E.; Hill, H. H., Jr. Presented a t the Western ACS Convention, Loa Angeles, 1988. (53) St. Louis, R. H.;Hill, H. H., Jr. CRC
Chromatography
Crit. Re". Anal. Chem. 1990,21(5), 321-
55. (54) Hill, H. H., Jr.; Morrissey, M.A. In 13-45. 137) Carr. T. W. Thin Solid Films 1977.45. . . ii5-22.;, (38)Nan]], A. A.; Lawrence, A. H.; Mikhael, N. Z. J. Torrcal. Clin. Toxicol. 1987, 25(6),501-15. (39) Lawrence, A. H.; Elias, L. Presented a t
the 3rd Chemical Congress of North America, Toronto, June 1988.
Modern Supercritical Fluid Chromatog-
raphy; White, C. M., Ed.; Huthig: Heidelher ,1988; p. 95. (55) sser, M.L. J. Appl. Phys. 1988, 63(10), 4823-31. 3. Statutory Invention (56) Wahltjen, H. Registration H41 Jan 5,1988. (57) Roehl, J. E. 0 Eng. 1985,24,985-90.
8,
I Packings 0 Silicas NUCLEOSILa and POLYGOSIL@ 0 Aluminium oxide 0 Cellulose, Polyamide
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H. H. Hill, Jr. (left),professor of analytical chemistry at WSU, receiued his B.S. degree (1970)from Rhodes College (Memphis),his M.S. degree (1973)from the Uniuersity of Missouri, Columbia,and his Ph.D. (1975)from Dalhousie Uniuersity. Before joining W S U in 1976,he studied IMS in F. W . Karasek's Laboratory at the Uniuersity of Waterloo. His research interests include analytical instrumentation for trace organic analysis using IMS, SFC, flame ionization detection, simultaneous deriuatization and extraction, and MS. William F. Siems (second from left) receiued his Sc.B. degree (1966)from Brown Uniuersity and his Ph.D. in physical chemistry (1974)from WSU, where he is a research associate and lecturer. His research interests include data acquisition, signal processing, and instrument deuelopment. Robert H. St. Louis (third from left), currently a research chemist in the Physical and Analytical Diuision of Tennessee Eastman Chemicals, receiued his Ph.D. i n chemistry from W S U in 1990.His research interests include the use of IMS as a detector following capillary GC and SFC, chromatographic interfacing technology, and applications and fundamental studies of subambient LC. Dennis G. McMinn (right),professorand chair of the Department of Chemistry at Gonzaga Uniuersity, receiued his B S c . degree from the Uniuersity of Alberta in 1966 and his Ph.D. in organic chemistry from the Uniuersity of Minnesota i n 1970. He taught undergraduate chemistry at Carleton College for four years before joining Gonzaga Uniuersity in 1974. His research interests include chromatographic detectors and the application of IMS to liquid systems. ANALYTICAL CHEMISTRY, VOL
0 Cartridge system 0 Preparative columns 0 Columns for special applications
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