First Distance-of-Flight Instrument: Opening a New Paradigm in Mass Spectrometry
A new instrumental concept, distance-of-flight mass spectrometry (DOFMS), is demonstrated experimentally. In DOFMS the mass-to-charge ratio of ions is determined by the distance each ion travels during a fixed time period; the mass spectrum is then recorded with a position-sensitive detector. The DOF approach provides a new way to separate and quantify components of complex samples. Initial results are demonstrated with a glow discharge ion source and a microchannel plate–phosphor screen detector assembly for atomic ion determination. This detection system demonstrated mass spectral peak widths of approximately 0.65 mm, corresponding to resolving powers of approximately 400–600 for a number of elemental samples.
Key wordsMass spectrometry Instrumentation Glow discharge
Since the development of the first mass spectrograph over 90 years ago , numerous methods and instruments have been developed to separate and determine ions of varying mass-to-charge ratio (m/z). Currently, mass spectrometry (MS) can be accomplished by electrostatic and magnetic dispersion (sector-field MS), radio-frequency stability and filtering (quadrupoles and ion traps), resonance frequency determination (Fourier-transform ion cyclotron resonance and Orbitrap® MS), or velocity-based separation (time-of-flight MS). These mature MS technologies are routinely employed in a range of applications from biomolecule analysis to elemental isotope determination, and are often coupled with each other to achieve tandem MS analysis [2, 3]. In the present paper, we describe the first implementation of a new form of MS, termed distance-of-flight mass spectrometry (DOFMS), and suggest potential benefits of this new mass separation technique.
Distance-of-flight mass spectrometry is akin to time-of-flight mass spectrometry (TOFMS) in that both techniques separate ions of different m/z based upon an imparted m/z-dependent velocity. In TOFMS, each ion is given the same energy (thus achieving a m/z-dependent velocity), and the m/z of each ion is calculated from the time required for it to traverse a known distance to a single detector. Conversely, in DOFMS the m/z of an ion is measured based on the spatial location of each ion at a specific time after the initial acceleration. As a useful analogy, DOFMS is to TOFMS as thin-layer chromatography is to elution chromatography (e.g., LC). TOFMS measures ions as they come off the “column”, whereas DOFMS measures how far the ions travel after a specific separation time. Whereas TOFMS disperses ions in time, DOFMS disperses ions in space.
Like TOFMS, DOFMS is a velocity-based mass separation technique and thus offers a number of advantages over alternative MS approaches. Namely, TOFMS and DOFMS both have theoretically unlimited mass ranges, can generate thousands of complete mass spectra per second, and are simple in design and construction. For these reasons, TOFMS instruments are emerging as analyzers of choice for complex chromatographic detection . DOFMS, however, also enjoys several potential advantages over TOFMS that stem from detecting ions distributed in space, as opposed to detecting their temporal distribution at a single point. First, fast detectors and analog-to-digital converters (ADCs) requisite to high-resolution TOFMS are limiting due to both performance and high cost —DOFMS obviates the need for such devices. Further, by distributing ion flux across a number of discrete detectors, pulse pile-up issues often troublesome in TOFMS are alleviated. In addition, the possible incorporation of discrete charge-detector arrays [8, 9] offers substantial dynamic range improvements over state-of-the-art TOFMS detector technology, while also reducing mass bias inherent to current TOFMS detection [10, 11]. In both DOFMS and TOFMS ions arrive at the detectors intermittently as ion bunches are accelerated out of the source region. However, with DOFMS and a charge-detector array, the signal does not have to be collected and processed for each bunch; the signal from any number of ion bunches can accumulate on the detector between readouts of the charge. The duty factor in DOFMS can reach unity depending on the mass range analyzed. Finally, because DOFMS is a spatially dispersive technique, the possibility exists for simultaneous non-destructive collection of several ions of interest (with essentially no upper mass limit). To date, spatially dispersive MS has been achieved with sector-field instruments that are limited by magnetic-field requirements for high-mass analysis and the physical limitations as to detector arrangement and placement.
In the present work, the first experimental realization of DOFMS is reported. A glow discharge ion source is used to produce atomic ions, which are then separated according to DOFMS principles and imaged onto a position-sensitive ion detector. The field-free flight path of this instrument is just 30 cm. Results from this proof-of-principle instrument demonstrate the feasibility of DOFMS, and demonstrate a mass resolving power greater than 400 (at full width at half maximum, FWHM) for a number of atomic elements. A glow discharge was employed for the detection of atomic ions predominantly because of its simple, reliable design and the resulting straightforward mass spectra. However, DOFMS as a mass separation method is amenable to all ion sources currently available, including molecular ion sources. In fact, planar ion sources such as matrix-assisted laser desorption/ionization (MALDI) or secondary ion mass spectrometry (SIMS) are particularly well suited to DOFMS because they produce ions with a defined spatial distribution—work toward coupling DOFMS to alternative ion sources is underway. In our current instrumental configuration, the particular detector type employed limits instrument performance, so future development of DOFMS detectors and applications are being considered.
1 Instrument Design and Experimental
1.1 Glow Discharge Ion Source
Atomic ions were generated by a direct current, reduced-pressure argon glow discharge (GD) between an energized conductive sample and a grounded anode . The metal sample being analyzed served as the GD cathode and was fixed by an o-ring seal to an anode with a 9.5-mm-diameter orifice; the distance between the cathode and anode was 0.5 mm. A controlled flow of argon (>99% purity, Airgas Inc., Radner, PA) was bled into the GD chamber (1st vacuum stage) via a needle valve to maintain a constant pressure of 0.7 Torr. The GD operating potential was typically −1000 V, supporting a current of 10 mA. Non-standardized steel, brass, bronze, and lead samples were obtained from the Edward G. Bair Mechanical Services Facility in the Chemistry Department of Indiana University and held by vacuum against the GD interface to serve as analytes for proof-of-principle studies.
1.2 Vacuum System
Ions were introduced into the mass analysis chamber via a differentially pumped interface. The glow discharge chamber (1st stage) was evacuated with an Edwards E2M30 rotary-vane pump (Edwards, Crawley, UK). A LECO® nickel skimmer cone with 1-mm orifice separated the 1st and 2nd stages of the vacuum system. A pressure of 0.4 mTorr was maintained in the 2nd vacuum stage with an Edwards EXT250H turbomolecular pump backed by an Edwards RV3 rotary-vane pump. The mass analysis chamber (3rd stage) was separated from the 2nd stage by a conductance-limiting orifice (1 mm diameter) and a pressure of 0.5 μTorr was maintained in the 3rd stage with an Edwards STP 451 turbomolecular pump backed by an Edwards RV12 rotary-vane pump.
1.3 Ion Optics
Operating conditions for ion optics in DOFMS instrument
Operating voltage (V)
1.4 Constant-Momentum Acceleration and Field-Free Drift Region
After transmission and focusing of the primary ion beam, ions were orthogonally accelerated into a field-free region. Constant-momentum acceleration was achieved by electrostatically pulsing a repeller plate to create a time-dependent linear acceleration field in the CMA region short enough that all ions are still within the extraction region at the cessation of the pulse . The CMA region was 22.86 mm long; a +500 V, 1 μs nominally square voltage pulse was applied to the CMA repeller to achieve CMA extraction (high voltage pulser—DEI GRX, Directed Energy, Inc., Boulder, CO; high voltage power supply—Bertan 210-01R, Bertan Associates, Inc., Hicksville, NY). The repetition rate of the CMA pulse was typically 10 kHz. Timing was controlled by a BNC 556 pulse generator (Berkeley Nucleonics Corporation, San Rafael, CA) operated remotely under LabVIEW® (version 8.6, National Instruments, Austin, TX) control. Following CMA extraction, ions drift according to their spontaneous drift trajectories  through a 30-cm field-free region and turn around in an 11-cm linear-field reflectron.
1.5 Distance-of-Flight Extraction and Detection
The MCP–phosphor detection assembly comprised two 25-mm-diameter MCP plates (Photonis USA, Inc, Sturbridge, MA) stacked in the chevron configuration. A metalized phosphor screen (4-cm active area, P43 phosphorescent compound, Beam Imaging Solutions INC., Mead, CO) was positioned 2.5 mm above the top MCP. The MCP stack was operated with −1700 V at the front MCP and ground potential on the back MCP; a voltage divider compensated for resistance mismatch of the two MCPs and power was supplied by a Bertan 205A-05R high voltage power supply. The phosphor screen was biased to +3000 V with a Bertan 205-30B supply.
1.6 Mass Spectrum Acquisition
In order to obtain a DOF mass spectrum, an optical image of the DOFMS lines appearing on the phosphor plate was captured photographically. Quantitative images of DOF mass spectra were recorded with an intensified charge-coupled device (ICCD) camera (512 × 512 pixels, PiMax 2, Roper Scientific, Inc., Trenton, NJ) fitted with a conventional camera lens (AF Nikkor, F = 50 mm, f/1.8, Nikon Inc., Torrance, CA) through a Plexiglas® viewport positioned directly above the DOF detector. A digital SLR camera (Canon Rebel XT) was also used to capture qualitative images. Line spectra were extracted from the ICCD image by generating 15 line profiles of intensity vs. pixel number with Origin® (OriginPro 8.1, OriginLab Corporation, Northampton, MA) software and averaging these line profiles.
2 Results and Discussion
Figure 6 demonstrates measured peak widths of 0.6–1 mm (FWHM) for each isotope and little m/z dependence is observed, as would be expected. These peak widths correspond to a minimum resolving power of approximately R (FWHM) = 400 for ions across the elemental mass range, which is sufficient to fully resolve isotopes separated by a single mass unit. The characteristic peak shape is also retained for all m/z investigated, with pedestals that become more evident with increasing m/z.
The spatial widths of the DOFMS lines observed with the current MCP–phosphor detection system (cf. Figure 6) are a convolution of the actual ion packet width, the secondary electron spread in the MCP stack, the electron spread from the MCP to the phosphor, the resolution of the phosphor, and the resolution of the ICCD camera employed to image the phosphor. Notably, the secondary electron spread through a chevron MCP stack results in as large as a 10-fold increase in electron cloud diameter compared to the impacting ion beam .
Distance-of-flight mass spectrometry represents a new paradigm in mass spectrometry—the spatial dispersion and simultaneous detection of ions of unlimited m/z. This technology is well suited for analysis of atomic ions as demonstrated here, but is also primed for the analysis of large molecules and for chromatographic detection.
The MCP–phosphor detector assembly employed in this first implementation of DOFMS dramatically limits instrument performance. Although our MCP–phosphor assembly has proven adequate for demonstrating DOFMS principles, substantial enhancements are expected by employing a flat detector with better sensitivity and spatial resolution. Recently, discrete charge-detector arrays were developed and coupled to sector-field focal plane mass spectrometers [18, 19, 20]. These detection systems consist of a linear array of charge-collecting micro-scale Faraday strips with operational amplifiers to integrate and amplify charge resulting from ion strikes, with all components fabricated on a single silicon monolith . Incorporation of such state-of-the-art array detector technology is a natural progression for DOFMS because it enables simultaneous, high-dynamic-range detection on a time scale suitable for chromatographic detection . Specifically, by controlling gain levels of the individual channels across which ion peaks are spread, array detector sensitivities can be adjusted so ion flux differences at least as great as six orders of magnitude could be detectable simultaneously. This broad dynamic range could prove critical for characterization of complex mixtures such as crude oil, whole blood, or other biological samples. In addition, charge detectors are ideal for heavy mass detection because response is proportional solely to ion charge, and they therefore exhibit no appreciable mass bias. Interest in heavy mass detection (and possible collection) includes analysis of moieties such as intact proteins or viruses.
A technological consideration of DOFMS detection is that simultaneous m/z determination over a broad mass range requires an extended spatially selective detector. Currently, we are characterizing a 2.1-cm-long array of 1696 charge detectors; another group reported development of a 12-cm-long array of 9600 channels . Continued advances in semiconductor fabrication technology should provide DOF detectors of sufficient length to obtain truly simultaneous DOF detection across a wide mass range. The incorporation of existing solid-state spatially sensitive detector technology will lead to complex mass spectral analysis by DOFMS in the near future.
The authors are grateful to the Indiana University Edward G. Bair Mechanical Instrumentation Facility for construction of the DOFMS instrument. This work was supported in part by Laboratory Directed Research & Development (LDRD) funds from Pacific Northwest National Laboratory (operated by Battelle Memorial Institute under contract to the US Department of Energy), by the US Department of Energy through federal grant number DE-FG02-98EF14890, and by the Lilly Endowment-Indiana MetaCyt Initiative.
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