Control of Chemical Mass Shifts in the Quadrupole Ion Trap

Linear ion trap mass selectivity with impulse power supply and sinusoidal dipolar ... Rectangular Wave form Driven Digital Ion Trap (DIT) Mass Spectro...
0 downloads 0 Views 77KB Size
Anal. Chem. 2000, 72, 2677-2683

Accelerated Articles

Control of Chemical Mass Shifts in the Quadrupole Ion Trap through Selection of Resonance Ejection Working Point and rf Scan Direction J. Mitchell Wells, Wolfgang R. Plass,† and R. Graham Cooks*

Department of Chemistry, Purdue University, West Lafayette, Indiana 47907-1393

Compound-dependent chemical mass shifts are observed and their origin is elucidated in a modified Finnigan GCQ quadrupole ion trap mass spectrometer. The dependence of chemical mass shifts on ion trap geometry, specifically the center to end-cap spacing, z0, and the size of the apertures in the end caps, is demonstrated. The effects of the working point (qeject value) used for resonance ejection and the direction of the rf mass analysis scan are also studied, and the results are found to be in agreement with a previously proposed model for the chemical mass shift mechanism. It is shown that chemical mass shifts are present when resonance ejection is used, unless the qeject is chosen to correspond to a nonlinear resonance point, where the shifts are removed. The shifts are also removed by performing the mass analysis scan in the reverse direction, i.e., from high mass to low mass.

Quadrupole ion trap mass spectrometers have experienced significant performance improvements in terms of sensitivity, resolution, and mass range in the last two decades, but the accuracy with which they measure mass requires additional development. Commercial instrument specifications for mass accuracy are only (0.1 Da; accuracies of 20-30 ppm have been reported,1 but at least another order of magnitude improvement in accuracy is still required if ion trap mass measurements are to be useful for molecular formula identification. In addition to the large number of factors that have been found to degrade ion trap † On leave from II. Physikalisches Institut, Justus-Liebig Universita ¨t Giessen, 35392, Giessen, Germany. Work done in partial fulfillment of the requirements for the doctoral degree. (1) Wells, J. M.; Gill, L. A.; Ouyang, Z.; Patterson, G. E.; Plass, W.; Badman, E. R.; Amy, J. W.; Cooks, R. G.; Schwartz, J. C.; Stafford, G. C.; Senko, M. W. Proceedings of the 46th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, FL, May 31-June 4, 1998; p 485.

10.1021/ac0002487 CCC: $19.00 Published on Web 06/02/2000

© 2000 American Chemical Society

mass accuracy,2 it has been shown that if the ion trap geometry is not optimized, then certain ions will experience large shifts in their apparent m/z, even under conditions where most ions are measured with normal accuracy. These chemical mass shifts were first observed in the early development of the mass-selective instability scan3 and have been studied by a number of groups.4-8 The phenomenon is removed by the appropriate manipulation of the ion trap geometry, so that commercial ion traps do not exhibit chemical mass shifts for most compounds, although there is recent evidence that the problem is not completely eliminated even in commercial instruments.9,10 Elucidating the underlying cause of chemical mass shifts is an important step in understanding how ion traps measure mass and may lead to improvements in the mass accuracy of commercial instruments. We recently reported on detailed studies of the chemical mass shift phenomenon in a prototype Finnigan ITMS which was modified to allow a continuous change in the ion trap end-cap spacing.8 A mechanism was proposed to account for chemical mass shifts. Briefly, this mechanism involves a delay in ion ejection (2) Cox, K. A.; Cleven, C. D.; Cooks, R. G. Int. J. Mass Spectrom. Ion Processes 1995, 144, 47. (3) Syka, J. E. P. In Practical Aspects of Ion Trap Mass Spectrometry; March, R. E., Todd, J. F. J., Eds.; CRC Press: Boca Raton, FL, 1995; Vol. 1, p 169. (4) Bortolini, O.; Catinella, S.; Traldi, P. Org. Mass Spectrom. 1992, 27, 927. (5) Bortolini, O.; Traldi, P. In Practical Aspects of Ion Trap Mass Spectrometry; March, R. E., Todd, J. F. J., Eds.; CRC Press: Boca Raton, FL, 1995; Vol. 2, p 145. (6) Cleven, C. D.; Cooks, R. G.; Garrett, A. W.; Nogar, N. S.; Hemberger, P. H. J. Phys. Chem. 1996, 100, 40. (7) Gill, L. A.; Wells, J. M.; Patterson, G. E.; Amy, J. W.; Cooks, R. G. Anal. Chem. 1998, 70, 4448. (8) Wells, J. M.; Plass, W. R.; Patterson, G. E.; Ouyang, Z.; Badman, E. R.; Cooks, R. G. Anal. Chem. 1999, 71, 3405. (9) Vachet, R. W.; Hartman, J. A. R.; Callahan, J. H. J. Mass Spectrom. 1998, 33, 1209. (10) McClellan, J. E.; Mulholland, J. J.; Murphy III, J. P.; Yost, R. A. Proceedings of the 47th ASMS Conference on Mass Spectrometry and Allied Topics, Dallas, TX, 1999.

Analytical Chemistry, Vol. 72, No. 13, July 1, 2000 2677

during mass analysis of some hundreds of microseconds, relative to the ideal case, caused by field penetration into the end-cap apertures. This ejection delay can be removed by adding higherorder field components to the trapping field, the effect of which is to offset the effect of the field penetration and so remove the delay. Such higher-order fields are added by increasing the endcap spacing of the trap, hence explaining the observation that chemical mass shifts decrease as the ion trap spacing increases.3,7,11 The ejection delay is also modified by collisions with the neutral bath gas, usually helium, which is used in ion traps to improve trapping efficiency and mass resolution. It was found through simulations and experiments that the probability of a collision that modifies the ejection delay is compound-dependent, hence a difference in collision probability between the ions used to calibrate the mass scale and an analyte will lead to an apparent shift of the analyte. Both the elastic collision cross section,8 which is dominated by the size of the ions, and the propensity of ions to fragment8,10,12,13 have been implicated as important factors in determining the probability of a delay-modifying collision. In this paper we report experiments conducted with a modified Finnigan GCQ ion trap mass spectrometer which aim at testing the proposed chemical mass shift model.8 The geometry of the GCQ ion trap was changed in a number of ways from the commercial device, as detailed below, to test further the effects of ion trap geometry on chemical mass shifts. Previous observations of systematic changes in shift with chemical structure8 were reproduced on the modified GCQ. The influence of resonance ejection, both at the normal qeject and at lower qeject values, and the influence of the direction of the mass analysis scan on chemical mass shifts were studied. EXPERIMENTAL SECTION The experiments reported here were conducted with a Finnigan GCQ ion trap mass spectrometer (Thermoquest Corp., San Jose, CA) which was modified in a number of ways from the commercial configuration. Most significantly, the electrode spacers, which are used to hold the end-cap electrodes in place at a fixed closest-distance from the center (a dimension referred to as z0) of 0.783 cm, were replaced with new spacers which fixed z0 at a value of 0.707 cm. This is the theoretical z0 calculated for a set of electrodes with the hyperbolic cross section of the GCQ electrodes; therefore, this geometry will be referred to here as the “theoretical geometry”. For some experiments, as specified below, the electrode geometry was modified further by increasing the size of the holes in the end caps to 3.0 mm from the commercial value of 1.2 mm or by removing the grounded exit lens, which is embedded in the exit end cap. Another significant change to the commercial GCQ was that the normal instrument control and data acquisition hardware was replaced with the control and acquisition module from a Finnigan LCQ mass spectrometer. This module consists of an embedded 486 microprocessor, which communicates with the host computer (11) Gill, L. A.; Amy, J. W.; Vaughn, W. E.; Cooks, R. G. Int. J. Mass Spectrom. 1999, 188, 87. (12) Brittain, R.; Speltz, D.; Bolton, B. Proceedings of the 41th ASMS Conference on Mass Spectrometry and Allied Topics, San Francisco, CA, May 31-June 4, 1993; p 459. (13) Londry, F. A.; Morrison, R. J. S.; March, R. E. Proceedings of the 45th ASMS Conference on Mass Spectrometry and Allied Topics, Atlanta, GA., 1995; p 1124.

2678

Analytical Chemistry, Vol. 72, No. 13, July 1, 2000

(in this case a PC, Gateway 2000 Inc., North Sioux City, SD) via an Ethernet connection and which controls a number of digital signal processing (DSP) and digital synthesizing (DDS) boards to generate reference signals for the rf and other necessary waveforms and to collect the data from the detector.14 Using this module on the GCQ allows the instrument to be controlled with Finnigan’s proprietary Ion Trap Control Language (ITCL),15 which allows custom scan functions to be written. This capability was necessary for the reverse scan experiments and the resonance ejection experiments described below. For the reverse scan experiments,16 a custom scan function was written that allowed specification of the mass range to be scanned and the qeject to be used for the scan. Ionization was carried out in the standard fashion using Automatic Gain Control to keep the number of ions in the trap constant.17 After ionization, the rf voltage was changed to place the highest mass to be measured at the specified qeject. The rf was then scanned to lower amplitude while the ac was applied across the end caps at the frequency corresponding to the specified qeject. This rf scan from high to low amplitude causes ions to become unstable when they reach the selected qeject in order from high mass to low mass; hence the scan is referred to as a “reverse scan”. The signal resulting from ion ejection was recorded with a conversion dynode/electron multiplier detector and then displayed by the instrument data system. The resonance ejection experiments that measured chemical mass shift as a function of qeject also utilized a custom scan function written in ITCL. This scan function allowed the desired mass range and qeject value to be specified and then scanned the rf while applying the appropriate ac to eject ions at the qeject value of interest. The resulting ion signals were displayed by the instrument data system. Note that, in both the reverse scan experiments and the resonance ejection experiments, the scan functions were written so that the rf scan rate was constant at the standard GCQ value of 90 µs/Th (1 thomson ) 1 Da/charge18) as the qeject was varied. The mass scale for the reverse scan and resonance ejection experiments was calibrated manually by recording spectra for perfluorotributylamine (PFTBA) and then plotting the apparent, data system-derived mass/charge ratio values, defined as the point where the peak height was maximum, for the mass/charge ratio 69, 100, and 131 fragment ions against their exact theoretical masses and fitting a straight line through the data. The equation for the calibration line was then used to calculate the actual measured mass/charge ratio for the analyte ions from their data system mass/charge ratios. Each measured mass/charge ratio value was then compared to the exact theoretical mass of the ion, assuming unit charge in the mass/charge ratio measurement, to calculate the reported chemical mass shifts. For all other experi(14) Schwartz, J. C.; Bier, M. E.; Taylor, D. M.; Zhou, J.; Syka, J. E. P.; James, M. S.; Stafford, G. C. Proceedings of the 43rd ASMS Conference on Mass Spectrometry and Allied Topics, Atlanta, GA, May 21-26, 1995; p 1114. (15) Zhou, J.; Schwartz, J. C. Proceedings of the 43rd ASMS Conference on Mass Spectrometry and Allied Topics, Atlanta, GA, May 21-26, 1995; p 1116. (16) Todd, J. F. J.; Penman, A. D.; Smith, R. D. Int. J. Mass Spectrom. Ion Processes 1991, 106, 117. (17) Stafford, G. C.; Taylor, D. M.; Bradshaw, S. C.; Syka, J. E. P. Proceedings of the 35th ASMS Conference on Mass Spectrometry and Allied Topics, Denver, CO, 1987; p 775. (18) Cooks, R. G.; Rockwood, A. L. Rapid Commun. Mass Spectrom. 1991, 5, 93.

Table 1. Chemical Mass Shifts Observed with Boundary Ejection

compound benzene toluene ethylbenzene n-propylbenzene n-butylbenzene n-pentylbenzene n-hexylbenzene n-heptylbenzene n-octylbenzene tetramethylbenzene nitrobenzene acetophenone dihydrobenzofuran N-ethylaniline 4-ethylaniline 3-ethylaniline 2-ethylaniline b

GCQ shifta

exit hole both holes GCQ ITMS increased increased exit lens shiftb to 3.0 mma to 3.0 mma removeda

-0.08 0.06 0.45 0.59 0.73 0.88 0.89 1.03 1.05

0.03 0.05 0.36 0.64 0.88 0.77 0.98 1.03 1.11

0.48 0.66 0.81 0.31 0.46 0.46 0.34 0.46

0.69 0.83 0.04 0.53 0.37 0.23 0.27

0.17 0.06 0.20 0.47 0.61 0.63 0.77 0.91 0.92

0.05 1.20 1.59 1.86 2.00 2.27 2.53 2.67

0.86 0.88 1.02 1.16 1.17

1.93 0.68

a GCQ shifts recorded with measurement error of (0.10 Th. ITMS shifts recorded with measurement error of (0.05 Th.

ments reported here, the mass scale was calibrated using an ITCL procedure, which calibrated the instrument directly using the mass/charge ratio 69 and 131 ions from PFTBA. The measured analyte mass/charge ratio values were read from the data system display, again at the point where the peak height was maximum, and the measured mass values, assuming unit charge, were then compared to the exact theoretical mass to calculate the chemical mass shift. The error in the mass measurement for both calibration procedures was determined by the fact that eight data points are taken per thomson, and hence, the mass/charge ratio values read from the data system display were only correct to the closest 0.125 Th. Samples were introduced into the ion source of the instrument by placing a small vial of the sample in a Cajon Ultratorr fitting (Cajon Co., Macedonia, OH) located at the head of a 30-m, 250µm-inner diameter, deactivated column (Alltech Applied Sciences, State College, PA) in the GC oven. The column passed from the GC oven into the ion source through a heated transfer line maintained at 275 °C. The headspace vapors of the sample were carried into the ion source by the helium carrier gas, which was set to a flow rate of 60 cm s-1. The ion source temperature was 200 °C. The amount of sample in the ion source could be controlled by controlling the temperature of the oven; for the samples used here, the oven temperature was set to between 30 and 75 °C, depending on the volatility of the sample. The exact amount of sample introduced may have varied from sample to sample, however Automatic Gain Control was used to vary the ionization time so that the number of ions injected into the trap was constant, ensuring that space-charge effects on mass assignment were minimized.17 RESULTS AND DISCUSSION A systematic change in chemical mass shift with ion structure occurred as demonstrated by the shift data for a series of alkylbenzene molecular ions shown in column 1 of Table 1. These data (column 2) were recorded as described in the Experimental Sec-

tion with a theoretical geometry GCQ without resonance ejection; i.e., ion ejection occurred at the stability boundary of qz ) 0.908.19 Column 3 of Table 1 reproduces the chemical mass shifts measured in a theoretical geometry ITMS instrument and reported in ref 8 for comparison to the GCQ data. In general, there is good agreement between the shifts measured with the two instruments, both for the alkylbenzenes and the other compounds listed in Table 1. An important feature of the proposed chemical mass shift model8 is the distortion of the trapping field by the holes drilled in the ion trap end caps. Further study of the effect of end-cap holes on chemical mass shift was conducted by increasing the diameter of the hole in the exit end cap from 1.2 to 3.0 mm. The data in Table 1, column 4 show that this asymmetric geometry change may have slightly lowered the chemical mass shift for the compounds studied (compare columns 2 and 4). Table 1, column 5 shows the chemical shift data recorded when the hole in the entrance end cap was also increased to 3.0-mm diameter. This symmetric change in the trap geometry significantly increased the chemical mass shift for the compounds studied (compare columns 2 and 5). This result is consistent with the proposed chemical mass shift model. The effects of changing the size of the exit end-cap hole and both holes on the delayed ejection of ions from the ion trap are discussed in more detail below. Further disruption of the trapping field could result from the penetration of the conversion dynode and electron multiplier voltages into the ion trapping region. This effect was investigated on the GCQ by removing the exit lens that is embedded in, but electrically isolated from, the exit end cap. This lens is normally held at ground potential and so prevents the penetration of the detector voltages into the trap; if such penetration influences the chemical mass shift, this influence should be observable by measuring shifts with the lens removed. Column 6 of Table 1 shows the chemical shifts measured for alkylbenzenes with the exit lens removed. Note that end caps with 1.2-mm holes were used for these experiments. There is only a small increase in the chemical mass shift, within the error of the measurement, when the lens is absent, indicating that penetration of the detector voltages has only a slight influence on chemical mass shift. The chemical mass shifts presented in ref 8 and in Table 1 were all recorded using the mass-selective instability scan with ejection at the stability boundary of qz ) 0.908.19 The effects of ac resonance ejection during the mass-selective instability scan on chemical mass shifts have been studied in the modified GCQ and are reported here. Table 2 lists the chemical mass shifts measured for a variety of compounds in the theoretical geometry GCQ with resonance ejection at the standard commercial qeject value of 0.902 (resonant frequency, 476 kHz). Comparison of Table 2, column 2 to Table 1, column 2 shows that resonance ejection near the stability boundary leads to chemical mass shifts that are approximately 60-70% larger than those measured with boundary ejection. Since the ejection mechanisms for boundary ejection and resonance ejection are inherently different, a difference in the measured mass shifts is not unexpected. The results of further investigation into the effect of resonance ejection on chemical mass shift for forward mass analysis scans (19) March, R. E.; Hughes, R. J. Quadrupole Storage Mass Spectrometry; John Wiley and Sons: New York, 1989.

Analytical Chemistry, Vol. 72, No. 13, July 1, 2000

2679

Table 2. Chemical Mass Shifts Observed with Resonance Ejection 1.2-mm holesa

3.0-mm holesa

benzene toluene ethylbenzene n-propylbenzene n-butylbenzene n-pentylbenzene n-hexylbenzene n-heptylbenzene n-octylbenzene

0.05 0.19 0.70 0.97 1.23 1.25 1.52 1.66 1.80

-0.08

tetramethylbenzene nitrobenzene acetophenone dihydrobenzofuran N-ethylaniline 4-ethylaniline 3-ethylaniline 2-ethylaniline

0.86 1.16 1.31 0.43 0.84 0.84 0.46 0.71

compound

a

0.95 1.47 1.86 2.00 2.27 2.66 2.80

2.20 0.31

GCQ shifts recorded with measurement error of (0.10 Th.

are shown in Figure 1. These data demonstrate the effect of the qeject value used for mass analysis on the chemical mass shift. The instrument was recalibrated as described above at each new qeject value, and analyte spectra were then recorded. Figure 1 shows the results of this experiment for n-butylbenzene and N-ethylaniline; two data sets recorded on different days are shown for each compound to demonstrate the reproducibility. There are several interesting features in Figure 1 that help elucidate the chemical mass shift phenomenon. Considering the highest qeject values first, the shift is relatively constant as qeject is lowered from the commercial value of 0.902 to qeject ) 0.8. At this qeject, there is a marked decrease in the chemical shift. This decrease is attributed to the fact that, at this point, ion ejection is occurring at a qeject value that is close to a nonlinear resonance point at qz ) 0.78, i.e., a point where one of the higher-harmonic frequencies of ion motion corresponds to an anharmonic side-band frequency caused by the presence of higher-order fields.20 These nonlinear resonances are often termed “black holes” or “black canyons” because they can lead to ion losses during CID experiments.21 They have been studied by several groups,22-24 and it has been shown that if resonance ejection is conducted at one of these points in an ion trap with appropriate higher-order fields, mass resolution is significantly increased due to the more rapid ejection of ions caused by the nonlinear resonance.20,25 The present results show that the nonlinear resonance removes the chemical mass shift by removing the ejection delay described above; all ions of both the calibration compound and the analytes are ejected very rapidly because of the nonlinear resonance. Without any delay in (20) Franzen, J.; Gabling, R. H.; Schubert, M.; Wang, Y. In Practical Aspects of Ion Trap Mass Spectrometry; March, R. E., Todd, J. F. J., Eds.; CRC Press: Boca Raton, FL, 1995; Vol. 1, p 49. (21) Morand, K. L.; Lammert, S. A.; Cooks, R. G. Rapid Commun. Mass Spectrom. 1991, 5, 491. (22) Eades, D. M.; Yost, R. A. Rapid Commun. Mass Spectrom. 1992, 6, 573. (23) Guidugli, F.; Traldi, P.; Franklin, A. M.; Langford, M. L.; Murrell, J.; Todd, J. F. J. Rapid Commun. Mass Spectrom. 1992, 6, 229. (24) Alheit, R.; Kleineidam, S.; Vedel, F.; Vedel, M.; Werth, G. Int. J. Mass Spectrom. Ion Processes 1996, 154, 155. (25) Franzen, J. Int. J. Mass Spectrom. Ion Processes 1993, 125, 165.

2680

Analytical Chemistry, Vol. 72, No. 13, July 1, 2000

ejection, there is not sufficient time for ions to be distinguished by collisions with bath gas; hence no chemical shift is observed. Another nonlinear resonance point exists near qeject ) 0.64, where the chemical mass shift is again observed to decrease significantly for both compounds shown in Figure 1. Below qeject ) 0.65, the shift increases again and is then seen to decrease slowly until qeject ) 0.45 for N-ethylaniline. This slow decrease may be due to the fact that, at low qeject values, it is more likely that fragment ions formed during ejection will remain stable. Fragmentation during the delayed ejection process, and the immediate ejection of the fragment ions due to their instability, is one mechanism for modifying the delay and so causing chemical mass shifts.8-10 A recent report directly observed the formation of fragments during mass analysis at high qeject using a hybrid ion trap/linear quadrupole system and also showed that when resonance ejection is performed at low qeject, no fragment ions are observed.26 The final feature of Figure 1 is the increase in chemical mass shift that occurs for both compounds when the qeject is lowered to 0.45. This increase is reproducible for both compounds. We are as yet unable to provide a satisfactory explanation for this behavior. This qeject value is close to a dodecapole nonlinear resonance point, but it is expected that this should lower the shift via the mechanism described above, not cause it to increase. The slope and intercept of the calibration line change significantly at this qeject value, suggesting that the calibrant ions may be behaving differently. The ejection delay described in ref 8 as the cause of chemical mass shifts was attributed to an oscillation of the ions in to and out of stability during boundary ejection. This oscillation is caused by the fact that, near the end-cap electrodes, the electric field increases less strongly than that in an ideal ion trap due to field penetration into the end-cap holes. Ions that are about to eject due to instability enter the region near the holes where the field is less strongly increasing and become stable again. The amplitude of their oscillation decreases, so that they move away from the end-cap region and become unstable, and the cycle repeats. Wang and Franzen reported a similar type of ejection delay during resonance ejection experiments20 and attributed it to oscillation of the ions in to and out of resonance with the applied ac field. This oscillation is caused by the fact that, in the presence of nonlinear (higher-order) fields, the frequency of ion oscillation is amplitude dependent, i.e., the frequency of the ion motion changes as the ions approach the end caps. These higher-order fields result from machining imperfections, truncation and misalignment of the electrodes, and apertures in the electrodes required for the entrance and egress of electrons and ions, and they cause the trapping field to no longer increase linearly from the center. When negative higher-order fields (i.e., fields that subtract from the quadrupole field on the axis of symmetry) are present in the ion trap, the amplitude-dependent frequency shift experienced by the ions is to lower frequency. During the mass analysis scan, ions are scanned into the ac resonance frequency from a lower frequency. When the ions reach the resonance point, they pick up energy from the ac field and are excited toward the end caps. If the ions experience an (26) Murphy, J. P. I.; Yost, R. A. Rapid Commun. Mass Spectrom. 2000, 14, 270.

Figure 1. Chemical mass shift as a function of the qeject value used in a forward rf scan in a theoretical geometry GCQ with 1.2-mm end-cap holes for n-butylbenzene and N-ethylaniline. Two data sets, one of higher resolution in terms of qeject, are shown for each compound.

amplitude-dependent frequency shift to lower frequency, they shift away from the resonance frequency as they approach the end caps. When they fall off resonance, their oscillation amplitude decreases, and hence their frequency increases again; they are again in resonance with and so are excited by the ac field, and the process is repeated, resulting in a delay in the ion ejection which may last for some hundreds of microseconds. We have used the simulation program ITSIM8,27,28 to study further the ejection delay described above under resonance ejection conditions. Figure 2 illustrates typical ejection profiles for a mass/charge ratio 100 ion as it is scanned into resonance with a dipolar ac voltage of 476 kHz and 3 V(0-p) at a scan rate of 90 µs/Th in several electrode geometries corresponding to those used in the experiments. Figure 2a shows the ejection profile obtained in a theoretical geometry GCQ trap with no holes in the end caps. Upon reaching the resonance ejection point, the ion’s oscillation amplitude increases, and the ion ejects in a few microseconds. When the simulated ion trap is made to correspond to that used in the experiments by adding the effect of 1.2-mm holes in both end caps, the delayed ejection profile seen in Figure 2b is obtained. Now the ion’s oscillation amplitude no longer increases rapidly, and it takes ∼150 µs longer for the ion to eject. When the holes are increased to 3.0 mm, the delay in ejection is increased further to ∼300 µs (Figure 2c), which explains the observation that the chemical mass shift increases when the hole size is increased. The term “ejection delay” is used in the remainder of this paper to refer to this extended period between when the ions begin to become unstable near the center of the trap and increase their oscillation amplitude and when they finally leave the electrode structure. The case where only the exit end cap was increased to 3.0 mm, while the entrance end cap was maintained at 1.2 mm, was also simulated. The result (data not shown) was that the asymmetric geometry change does not increase the ejection delay, which is in agreement with the experimental observation above that this change does not increase (27) Bui, H. A.; Cooks, R. G. J. Mass Spectrom. 1998, 33, 297. (28) Plass, W. R.; Gill, L. A.; Bui, H. A.; Cooks, R. G. J. Phys. Chem. 2000, 104, 5059.

Figure 2. Simulation of the axial motion of a mass/charge ratio 100 ion as a function of time during a mass analysis rf scan with a resonance ejection of 476 kHz and 3 V0-p in (a) a theoretical GCQ trap without end-cap holes, (b) a theoretical GCQ trap with 1.2-mm holes in each end cap, (c) a theoretical GCQ trap with 3.0-mm holes in each end cap, and (d) a commercial GCQ trap with 1.2-mm holes in each end cap.

the chemical mass shift. The asymmetric change in the hole diameters gives rise to higher-order fields of odd orders, and these are known to change the frequency of the ion oscillation less strongly than even orders.20 Hence, their effect on the ejection Analytical Chemistry, Vol. 72, No. 13, July 1, 2000

2681

Figure 3. Spectra for the calibration compound perfluorotributylamine recorded in a theoretical geometry GCQ with 1.2-mm end-cap holes with resonance ejection at qeject ) 0.4 (resonance ejection frequency, 151 kHz) applied during (a) a forward rf scan, i.e., a scan from low mass to high mass, and (b) a reverse rf scan, i.e., a scan from high mass to low mass. Note that the x-axis gives the data system derived, uncalibrated mass scale, and the italicized peak labels give the correct nominal mass of the peaks.

delay is weaker. Only when both holes are increased is the frequency shift sufficiently large to cause the long ejection delay. Note that these illustrative simulations do not include the effects of collisions and are not intended to reproduce the chemical mass shift quantitatively. In the discussion of hole size effects above, the data used to support this observation (Table 1, column 5) were recorded using boundary ejection, but a similar increase in shift with hole size was found for resonance ejection as well, as shown in Table 2, column 3. The final panel of Figure 2 shows the ejection profile in a commercial geometry GCQ trap with 1.2mm holes in both end caps. The ejection delay has been removed by the increase in z0, which has introduced positive higher-order field components and so compensated for the effect of the endcap holes.8 Figure 2 confirms that even though the mechanism for resonance ejection is different from that for boundary ejection, an ejection delay similar to that reported previously for boundary ejection can occur during resonance ejection as well. The theoretical geometry GCQ ion trap with end-cap holes has the appropriate negative higher-order fields to cause the type of ejection delay that leads to the chemical mass shifts shown in Table 2 when resonance ejection is used. This delay can be increased by increasing the size of the end-cap holes or removed by increasing the end-cap spacing, z0. It is important to emphasize again that it is not the ejection delay by itself that is the sole cause of the chemical mass shift. It is the ejection delay, in combination with the collisional modification of this delay as described in ref 8, that causes ions to be distinguished on the basis of elastic collision cross section and/or propensity to fragment. The explanation given above for the observation of chemical mass shifts when resonance ejection is used relies on the fact 2682 Analytical Chemistry, Vol. 72, No. 13, July 1, 2000

that negative higher-order fields introduce an amplitude dependence to the frequency of ion motion that causes ions to shift to lower frequency as they approach the end caps of the trap. This frequency shift introduces a delay in ion ejection during the mass analysis scan because as ions are scanned to higher frequency, they experience the shift to lower frequency, and so they oscillate in to and out of resonance with the applied field. If ions were scanned in the direction opposite to that normally done, i.e., from higher frequency to lower frequency, the shift to lower frequency would actually push the ions into the resonance point, causing them to eject more rapidly; therefore, the reverse scan should eliminate the chemical mass shift by eliminating the ejection delay which causes analytes and calibrants to be distinguished by collisions. It has been shown previously that reverse scanning in a theoretical geometry trap with negative higher-order fields, and the attendant frequency shift to lower frequency, improves resolution over the forward scan,29 and correspondingly that reverse scanning in a commercial geometry trap with positive higher-order fields, and the attendant frequency shift to higher frequency, degrades resolution.29,30 Figure 3 shows spectra recorded with the theoretical geometry GCQ for the calibration compound PFTBA in the forward (a) and reverse (b) scan directions with resonance ejection at qeject ) 0.4, while Figure 4 shows the same data for n-butylbenzene. Note that, in the reverse scan spectra, the abscissa shows the mass/charge ratio scale where the ions appeared and has not been corrected to account for the fact that the scan was in the reverse direction. (29) Wang, M. Proceedings of the 43rd ASMS Conference on Mass Spectrometry and Allied Topics, Atlanta, GA, May 21-26, 1995; p 1121. (30) Williams, J. D.; Cox, K. A.; Cooks, R. G.; McLuckey, S. A.; Hart, K. J.; Goeringer, D. E. Anal. Chem. 1994, 66, 725.

Figure 4. Spectra for n-butylbenzene recorded in a theoretical geometry GCQ with 1.2-mm end-cap holes with resonance ejection at qeject ) 0.4 (resonance ejection frequency, 151 kHz) applied during (a) a forward rf scan, i.e., a scan from low mass to high mass, and (b) a reverse rf scan, i.e., a scan from high mass to low mass. Note that the x-axis gives the data system derived, uncalibrated mass scale, and the italicized peak labels give the correct nominal mass of the peaks. Note also that in the forward scan (a) the molecular ion of n-butylbenzene is labeled with the correct nominal mass of mass/charge ratio 134; however, comparison of these data with the calibration data of Figure 3 shows that the molecular ion actually appears at mass/charge ratio 132.2; i.e., it experiences a chemical shift of 1.8 Th. This shift is reduced to 0.08 Th in the reverse scan.

The labels on the individual peaks identify the actual mass/charge ratios of the peaks. The resolution for both compounds is improved significantly when the rf mass analysis scan is done in the reverse direction (Figures 3b and 4b). More significantly, the chemical mass shift measured for n-butylbenzene is reduced to zero, within the error of the measurement. The chemical mass shifts for acetophenone and nitrobenzene were also found to be zero when the scan was in the reverse direction. These results provide further evidence for the proposed chemical mass shift model. The peak splitting observed in Figures 3 and 4 for the forward scans seems to be dictated by the resonance ejection amplitude used. Preliminary study of this additional variable on chemical mass shifts is underway, and we have evidence that, even under resonance ejection conditions where the peak splitting is eliminated, peaks are still significantly broader in the forward scan than in the reverse, and the chemical mass shifts are still of comparable magnitude to those reported here. CONCLUSIONS Further investigation of chemical mass shifts in ion traps has been conducted and the results support the previously proposed model that the shifts are caused by differentiation of analyte and

calibrant ions by collisions occurring during delayed ejection. This model holds true both for boundary ejection and for resonance ejection, unless the latter is conducted at a nonlinear resonance point. Operating the theoretical geometry ion trap in the reverse scan mode, where high-mass ions are scanned out first, removes the chemical mass shift. Future work will involve further elucidation of the mass shift model and attempts to utilize the chemical mass shift as an additional distinguishing feature of ion structure. ACKNOWLEDGMENT Support for this project was provided by the U.S. Department of Energy, under Contract DE-FG02-94ER14470, and by Thermoquest Corp. through the Purdue University Industrial Associates Program. The authors thank Scott Quarmby, Mike Senko, and Jae Schwartz for their assistance with the instrumentation and Jon Amy, Ethan Badman, and Garth Patterson for helpful discussions. Received for review February 29, 2000. Accepted May 8, 2000. AC0002487

Analytical Chemistry, Vol. 72, No. 13, July 1, 2000

2683