CONSTANT-MOMENTUM ACCELERATION TIME-OF-FLIGHT MASS SPECTROMETRY WITH ENERGY FOCUSING
Article ID: AMS 723
Running title: CMA-TOFMS WITH ENERGY FOCUSING
First author: DENNIS ET AL.
Published on line xxxx xx, xxxx
Received: June 7, 2013
Revised: July 31, 2013
Accepted: July 31, 2013
(Footnote:)
Correspondence to: Gary M. Hieftje; e-mail:
Electronic Supplementary Material
The online version of this article contains supplementary material, which is available to authorized users.
Supplementary Material: Supplementary material associated with this article may be found in the online version at doi:10.1016/j.jasms.xxxx.xx.xxx
Constant-Momentum Acceleration Time-of-Flight Mass Spectrometry with Energy Focusing
Elise A. Dennis,1, Steven J. Ray,1, Alexander W. Gundlach-Graham,1, Christie G. Enke,1,2, Charles J. Barinaga,3, David W. Koppenaal,3, Gary M. Hieftje1
1Department of Chemistry, Indiana University, Bloomington, Indiana, IN 47405, USA
2Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New MexicoNM, 87131, USA
3Pacific Northwest National Laboratory, Richland, Washington,WA 99352, USA
Abstract
Fundamental aspects of constant-momentum acceleration time-of-flight mass spectrometry (CMA-TOFMS) are explored as a means to improve mass resolution. By accelerating all ions to the same momentum, rather than to the same energy, the effects of the initial ion spatial and energy distributions upon the total ion flight time are decoupled. This decoupling permits the initial spatial distribution of ions in the acceleration region to be optimized independently, and energy focus, including ion turn-around-time error, to be accomplished with a linear-field reflectron. Constant-momentum acceleration also linearly disperses ions across time according to mass-to-charge (m/z) ratio, instead of the quadratic relationship between flight time and m/z found in conventional TOFMS. Here, CMA-TOFMS is shown to achieve simultaneous spatial and energy focusing over a selected portion of the mass spectrum. An orthogonal-acceleration time-of-flight system outfitted with a reduced-pressure dc DC glow discharge (GD) ionization source is used to demonstrate CMA-TOFMS with atomic ions. The influence of experimental parameters such as the amplitude and width of the time-dependent CMA pulse on mass resolution is investigated, and a useful CMA-TOFMS focusing window of 2 to 18 Da is found for GD-CMA-TOFMS.
Keywords: Time-of-flight, Mass spectrometry, Constant-momentum acceleration, Glow
Discharge, Turn-around time
Words: 187/250
Introduction
Recent studies in time-of-flight mass spectrometry (TOFMS) have aimed to improve mass resolution [1-–4], which is especially important for biomolecule or complex-sample analysis. In the conventional constant-energy acceleration (CEA) approach to TOFMS, all ions are provided the same energy and separate according to their m/z-dependent velocities, yielding a quadratic relationship between m/z and flight time. Thus, in CEA-TOFMS, mass resolution is defined as t/2Δt, where t represents the flight time and Δt the peak width of a single m/z. Mass resolution can be improved by either lengthening flight time or reducing the detected temporal spread of ions at a single m/z. Recently, several investigators have pursued the former strategy by developing multi-turn [5-–7] and multi-pass [8] TOFMS systems that greatly increase t by lengthening the field-free flight path. Commercially available TOFMS instruments equipped with these technologies can achieve full-width half-maximum (FWHM) resolving powers of 40,000 to 100,000 on flight paths of ten 10 meters or more [1, 9, -10], a marked improvement over single-pass (i.e., reflectron) TOFMS [1, 9]. Although multi-pass and multi-turn TOFMS instruments offer improved resolution, they have limited applicability to transient analyses when both high resolution and high sensitivity are needed. This limitation is due to both the increased flight time associated with such analyses, which can be on the order of milliseconds [5], and the transport efficiency of ions through the instrument, which can be as low as 20% percent [5]. Therefore, shrinking peak width, Δt, without lowering the spectral acquisition rate or instrument sensitivity from a single-pass TOFMS setup is a more desirable approach.
This preferred route to improved resolution can be achieved with constant momentum acceleration (CMA) rather than traditional ion focusing methods in TOFMS. In 1953, Wolff and Stephens reported the first CMA time-of-flight system [11]. In their spectrometer, ions were accelerated to a constant momentum by applying a transient electric field such that all ions were still within the acceleration region at the terminus of the acceleration pulse. Although their CMA-TOFMS was limited by experimental constraints to mass resolution levels comparable to CEA-TOFMS in the same instrument, the authors pointed out two significant advantages of CMA-TOFMS. First, acceleration of ions to a constant momentum yields a linear dependence between flight time and m/z. This linear dependence greatly simplifies m/z calibration, but, more importantly, provides a constant temporal separation between adjacent isotopes across the entire mass spectrum; in conventional TOFMS, unit-mass temporal spacing decreases with increasing m/z value. Second, acceleration by CMA overcomes the so-called “turn-around-time error” that plagues CEA-TOFMS [12]. These advantages have enticed several researchers to explore the benefits of CMA in velocity-based mass separations [13-–24]. Techniques employing a combination of CEA and CMA have been studied as well [25-–27].
In 2007, Enke and Dobson [18] showed that CMA, in combination with a linear-field reflectron, can be used to provide energy focusing at a particular instant known as the energy-focus time (tef). At tef, ions of various m/z achieve energy focus at m/z-dependent positions along the flight path. This focusing strategy has been employed in distance-of-flight mass spectrometry (DOFMS), where m/z is measured based upon the distance traveled at tef [16, 18-–22]. In the present article, the benefits of the CMA-focusing strategy developed for DOFMS are explored for CMA-TOFMS. Ultimately, we aim to construct a TOFMS instrument that offers both CMA- and CEA-TOFMS modes of operation, so the benefits of both methods are available. However, before this combined instrument can be fully implemented, the fundamental principles of energy-focusing CMA-TOFMS should be explored. Theory and design considerations of CMA-TOFMS are included here, along with supporting experimental results.
Theoretical Considerations
Although CMA-TOFMS and traditional CEA-TOFMS are architecturally similar, several differences make the two complementary. In CMA-TOFMS, impulse acceleration drives an ion packet into a field-free (FF) drift region where ions separate according to their m/z-dependent velocities. After flying through the FF region, ions enter an electrostatic mirror, which is used to compensate for initial ion energies. After ions are reflected, they return to the FF region and arrive at the temporally selective detector. Clearly, the experimental structure of the two TOFMS techniques is quite similar. However, in the CMA-TOFMS strategy used here, energy focus is achieved for all m/z at the same instant in time, but at m/z-dependent positions along the drift path. As a result, a TOF detector located at a specific distance along the flight region will observe ions of only a single m/z (or window of m/z) in focus; ions with m/z outside this window will be out-of-focus and exhibit poorer mass resolution. Constant-momentum acceleration TOFMS as implemented here is, therefore, a technique to improve mass resolution over a selected m/z window whereas, in contrast, CEA-TOFMS provides complete mass-spectral coverage with similar, albeit lower, mass resolution for all ions of m/z within the spectrum.
The acceleration of ions to the same momentum is achieved experimentally by using a time-dependent field that is shorter in duration than the time required for ions to exit the acceleration region [18]. Ions that remain in the acceleration region at the terminus of the pulse experience the same electrostatic field for the same period of time. Thus, ions of the same m/z gain the same energy, regardless of their initial positions within the acceleration region. This is in sharp contrast to CEA-TOFMS where the final energy of ions of the same m/z after acceleration is a convolution of their initial energy and position. Ions of different m/z within the CMA-TOFMS ion packet will receive m/z-dependent energies that are inversely proportional to m/z, whereas all m/z values in CEA-TOFMS receive the same energy. These two factors preclude the use of conventional space-focusing strategies in CMA-TOFMS.
Two considerations permit CMA-TOFMS to achieve high resolving power. First, CMA acceleration does not suffer the turn-around-time errors that CEA-TOFMS does. Turn-around-time error refers to the acceleration delay experienced by an ion with initial velocity opposite from the flight region, as well as the flight-time error and loss in mass resolution that result [12]. When CMA is used, the momentum “kick” that an ion receives is independent of its position in the extraction region and its direction of motion. Of course, any initial energy ions possess along the mass-separation axis is not directly compensated during CMA; this energy, either in the direction toward or away from the flight tube, is corrected downstream by the reflectron. In particular, because energy disparities for iso-mass ions lead to energy-dependent penetration depths in the reflectron, ions spend different times in the reflectron based on their initial velocities. A forward-moving ion penetrates deeper into, and spends more time in the reflectron than an ion with zero or rearward initial velocity. Overall, an initial-energy-dependent residence time in the reflectron exists for ions accelerated to a constant momentum, and initial energies for all m/z values can be focused at the tef with the linear-field reflectron. Second, the energy-focusing strategy used in CMA-TOFMS reproduces the initial spatial width of the ion beam at the detector surface. Because space focusing is not employed in CMA-TOFMS, the initial spatial distribution of isomass ions defines the limiting peak width [12, 16]. When ion optics are employed to focus the incoming ion beam and limit the initial spatial width of the ion beam, high mass resolution can be achieved.
Experimentally, the width of the acceleration region and limitations in the high-voltage pulse duration and amplitude define the CMA conditions. Because CMA-TOFMS is intended to examine only a limited window of m/z values, it is desirable to provide greatest energy to the lowest m/z of interest, hereafter referred to as the “target m/z.” Under these conditions, ions with a lower m/z than the target value exit the acceleration region before the pulse termination and undergo constant-energy acceleration. The target m/z and ions of greater m/z do not exit the acceleration region before the pulse termination and experience CMA acceleration. The maximum CMA pulse field (Ep) can be calculated from [18]:
(1)
where Δs denotes the distance from the packet center to the acceleration-region exit, τ the pulse duration, (m/z)target the target m/z, and q the elementary charge. Equation 1 assumes the ions possess no initial velocity along the acceleration axis. However, because ions clearly will possess some initial velocity distribution and because that distribution is often unknown and ion-source-dependent, it is probable that ions having an initial velocity oriented towards the flight tube could exit before the end of the acceleration pulse Ep. Also, ions can possess an initial position such that they could exit prior to the acceleration pulse terminus. For these reasons, a value 95% of that calculated from Equation 1 is recommended [18]. While Equation 1 assumes a CMA pulse of rectangular shape, any high-voltage pulse of appropriate duration would suffice for CMA as long as imparted momentum remains consistent.
Conventional TOFMS and CMA-TOFMS both employ ion mirrors for energy compensation; however, the reflectron functions differently in the two techniques. Because momentum, rather than energy, is constant in CMA-TOFMS, ions penetrate the reflectron to mass-dependent depths and, for a given charge state, spend the same time in the reflectron. Momentum differences that arise from initial energy distributions prior to acceleration also cause ions of a single m/z to penetrate slightly farther or shorter into the reflectron. Correction for initial ion-energy disparities with a reflectron is the largest contributor to enhanced mass resolution in CMA-TOFMS without the use of space-focusing techniques.
When a linear-field reflectron is used with CMA, ion velocities are focused at tef [18], which can be calculated as:
(2)
where EP represents the acceleration field in the CMA region, τ the duration of the CMA pulse, and EM the field in the single-stage, linear-field ion reflectron. With a TOF detector, ions of only a single m/z will strike the detector at tef, which leads to a reduced focusable mass range compared to with CEA-TOFMS. However, by adjustment of instrument parameters, tef can be tuned to bring any desired m/z to the stationary TOF detector in focus. Figure 1 illustrates tef for three ions of different m/z, as well as the degree of ion focus for each m/z upon detection. Though only a single m/z can be detected at tef in a given CMA-TOFMS experiment, the energy focus provides enhanced resolution over a finite m/z window.
[Figure 1 around here]
Figure 1.: Schematic representation of a CMA experiment for three m/z values. The target mass (shown in red) impacts the time-of-flight detector at tef and a narrow peak is observed in the mass spectrum. Ions of greater m/z than the target, shown by the blue trace, do not reach the detector at tef and defocus prior to detection. Ions with m/z less than the target, shown in the green trace, impact the detector before the tef occurs. Therefore, the peaks observed with CMA-TOFMS are shown in the shaded orange box and the inset to the top left of the figure.
The TOF of each m/z to a detector located at the exit of the field-free region can be calculated from [18]:
(3)
where s0 is the initial ion location in the acceleration region, Δs0 is the width of the ion packet, and LFF is the length of the field-free region [18]. Equation 3 shows the linear dependence between TOF and m/z in CMA-TOFMS. This relationship means that at higher m/z values the time-of-flight axis is expanded compared to with CEA-TOFMS analysis, where a square-root dependence causes reduced mass spacing. Calibration of the m/z-axis is accomplished using Equation 3; however, only those ions of m/z greater than the target m/z should be included in the calibration, because ions of lower m/z are typically accelerated to a constant energy rather than momentum. Further, mass resolving power (RP) calculated according to the convention m/Δm can be determined to be tsep/Δt; where tsep is the ion flight time minus the time spent in the reflectron (because no mass separation occurs therein) [16, 18].
In a CMA-TOFMS experiment, the TOF required for a specific target m/z to reach the TOF detector located at LFF (Equation 3) is set equal to tef (Equation 2). In this case, the electrostatic field within the reflectron that is required to focus the target m/z onto the detector at tef is:
(4)
Implicit in this equation is the requirement that EM 4EP in order to achieve CMA focusing for any region of the mass spectrum.
Experimental
Minor instrumental changes are required to convert a traditional orthogonal-acceleration, reflectron CEA-TOFMS system to CMA operation: the reflectron must be modified to support a linear electrostatic field and either the acceleration pulse must be shortened or the acceleration region must be lengthened; both strategies were employed here. The linear-field reflectron is required in order to achieve tef detection according to the strategy of Enke and Dobson [18]. Overall, the experimental constraints on pulse potential and duration set a minimum acceleration region length, which must often be extended for ions of lower m/z [18].
A mechanical drawing (AutoCAD®) of the modified orthogonal-acceleration time-of-flight system (R.M. Jordan) used for CMA-TOFMS studies is presented as Figure 2; this TOFMS instrument has been described previously [28-–30]. The total field-free flight path, from the first grounded, gridded electrode (G1) to the microchannel plate detector, is 43 cm. This system has been used for proof-of-principle studies with a dc DC glow-discharge (GD) ion source. Operating parameters for both the mass spectrometer and ion source are compiled in the supplementary material.
[Figure 2 around here]
Figure 2.: Mechanical drawing of the 43-cm orthogonal-acceleration TOFMS instrument used in this study. The plasma skimmer cone and reduced-pressure dc DC glow-discharge cell are not shown, but they reside before the ion optics, which are shown in grey at the top left of the illustration. The ion beam is orthogonally accelerated in the acceleration region (orange) and is shown in light green. A cross section of the field-free flight tube is shown along with the ion steering plates (yellow) and reflectron (blue) located within. A set of three parallel grids (dark green) are located 15 mm in front of the microchannel plate detection system (red, white) and act as a retarding-potential analyzer.
Glow-Discharge Ion Source
A reduced-pressure, direct-current GD was sustained between a pin-type metal sample (cathode) and the skimmer cone of the mass spectrometer. Metal-cathode samples were 12-mm thick and 7.4 mm in diameter. An O-ring sealed the discharge chamber and held the cathode at a distance of 2 mm from the skimmer cone, which contained a 0.8-mm diameter orifice through which ions were sampled. The GD was maintained in an argon (>99% purity, Airgas Inc., Radner, PA, USA) atmosphere at pressures between 0.4 and 1 Torr. The GD was current-limited to 10-–30 mA at a voltage of about -–1000 V. All data were produced with non-standardized brass samples.