How constant momentum acceleration decouples energy and space focusing in distance-of-flight and time-of-flight mass spectrometries.

Resolution in time-of-flight mass spectrometry (TOFMS) is ordinarily limited by the initial energy and space distributions within an instrument's acceleration region and by the length of the field-free flight zone. With gaseous ion sources, these distributions lead to systematic flight-time errors that cannot be simultaneously corrected with conventional static-field ion-focusing devices (i.e., an ion mirror). It is known that initial energy and space distributions produce non-linearly correlated errors in both ion velocity and exit time from the acceleration region. Here we reinvestigate an old acceleration technique, constant-momentum acceleration (CMA), to decouple the effects of initial energy and space distributions. In CMA, only initial ion energies (and not their positions) affect the velocity ions gain. Therefore, with CMA, the spatial distribution within the acceleration region can be manipulated without creating ion-velocity error. The velocity differences caused by a spread in initial ion energy can be corrected with an ion mirror. We discuss here the use of CMA and independent focusing of energy and space distributions for both distance-of-flight mass spectrometry (DOFMS) and TOFMS. Performance characteristics of our CMA-DOFMS and CMA-TOFMS instrument, fitted with a glow-discharge ionization source, are described. In CMA-DOFMS, resolving powers (FWHM) of greater than 1000 are achieved for atomic ions with a flight length of 285 mm. In CMA-TOFMS, only ions over a narrow range of m/z values can be energy-focused; however, the technique offers improved resolution for these focused ions, with resolving powers of greater than 2000 for a separation distance of 350 mm.

Extension of the focusable mass range in distance-of-flight mass spectrometry with multiple detectors.

RATIONALE: Distance-of-flight mass spectrometry (DOFMS) is a velocity-based mass separation technique in which ions are spread across a spatially selective detector according to m/z. In this work, we investigate the practical mass range available for DOFMS with a finite-length detector. METHODS: A glow-discharge DOFMS instrument has been constructed for the analysis of atomic ions. This instrument was modified to accommodate two spatially selective ion detectors, arranged co-linearly, along the mass-separation axis of the analyzer. With this geometry, each detector covers a different portion of the distance-of-flight spectrum and ions are detected simultaneously at the two detectors. The total flight distance covered by the two detectors is 106 mm and simulates DOF detection across a broad mass range. RESULTS: DOFMS theory predicts that ions of all m/z values are focused at a single flight time, but at m/z-dependent flight distances. Therefore, ions that are detected across a wide portion of the DOF axis should all yield the same peak widths. With a focal-plane camera detector and a micro-channel plate/phosphor-screen detection assembly, we found simultaneous, uniform focus of (40)Ar(2)(+) and of (65)Cu(+) and (63)Cu(+) with the ions spread 82 mm across the DOF axis. This detection length, combined with the current instrument geometry, allows for a simultaneously detectable m/z value of 4:3 (high mass-to-low mass). CONCLUSIONS: These results are the first experimental verification that constant-momentum acceleration (CMA)-DOFMS provides energy focus across an extended detection length. Evidence presented demonstrates that DOFMS is amenable to detection with (at least) a 100-mm detector surface. These results indicate that DOFMS is well suited for detection of broader mass ranges.

Distance-of-flight mass spectrometry: a new paradigm for mass separation and detection.

Distance-of-flight mass spectrometry (DOFMS) offers the advantages of physical separation of ions, array detection of ions, focusing of initial ion energy, great simplicity, and a truly unlimited mass range. DOFMS instrumentation is similar to that of time-of-flight mass spectrometry (TOFMS) and shares its ion-source versatility, batch analysis, and rapid spectral-generation rate. With constant-momentum ion acceleration and an ion mirror, there is a time at which ions of all mass-to-charge values are energy focused at their particular distances along the flight path. A pulsed field orthogonal to the flight path drives the ions to reach the detector array at this specific time. Results from a 0.29-m proof-of-principle instrument verify the theoretically predicted energy focus and demonstrate how the range of mass-to-charge values that impinge on the detector array can be readily changed. DOFMS could be combined sequentially with TOFMS to enable simultaneous scanless tandem mass spectrometry.

Liquid sampling-atmospheric pressure glow discharge (LS-APGD) ionization source for elemental mass spectrometry: preliminary parametric evaluation and figures of merit.

A new, low-power ionization source for the elemental analysis of aqueous solutions has recently been described. The liquid sampling-atmospheric pressure glow discharge (LS-APGD) source operates at relatively low currents (<20 mA) and solution flow rates (<50 µL min(-1)), yielding a relatively simple alternative for atomic mass spectrometry applications. The LS-APGD has been interfaced to what is otherwise an organic, LC-MS mass analyzer, the Thermo Scientific Exactive Orbitrap without any modifications, other than removing the electrospray ionization source supplied with that instrument. A glow discharge is initiated between the surface of the test solution exiting a glass capillary and a metallic counter electrode mounted at a 90° angle and separated by a distance of ~5 mm. As with any plasma-based ionization source, there are key discharge operation and ion sampling parameters that affect the intensity and composition of the derived mass spectra, including signal-to-background ratios. We describe here a preliminary parametric evaluation of the roles of discharge current, solution flow rate, argon sheath gas flow rate, and ion sampling distance as they apply on this mass analyzer system. A cursive evaluation of potential matrix effects due to the presence of easily ionized elements indicate that sodium concentrations of up to 50 µg mL(-1) generally cause suppressions of less than 50%, dependant upon the analyte species. Based on the results of this series of studies, preliminary limits of detection (LOD) have been established through the generation of calibration functions. While solution-based concentration LOD levels of 0.02-2 µg mL(-1) are not impressive on the surface, the fact that they are determined via discrete 5 µL injections leads to mass-based detection limits at picogram to single-nanogram levels. The overhead costs associated with source operation (10 W d.c. power, solution flow rates of <50 µL min(-1), and gas flow rates <10 mL min(-1)) are very attractive. While further optimization in the source design is suggested here, it is believed that the LS-APGD ion source may present a practical alternative to inductively coupled plasma sources typically employed in elemental mass spectrometry.

Resolution and mass range performance in distance-of-flight mass spectrometry with a multichannel focal-plane camera detector.

Distance-of-flight mass spectrometry (DOFMS) is a velocity-based mass-separation technique in which ions are separated in space along the plane of a spatially selective detector. In the present work, a solid-state charge-detection array, the focal-plane camera (FPC), was incorporated into the DOFMS platform. Use of the FPC with our DOFMS instrument resulted in improvements in analytical performance, usability, and versatility over a previous generation instrument that employed a microchannel-plate/phosphor DOF detector. Notably, FPC detection provided resolution improvements of at least a factor of 2, with typical DOF linewidths of 300 µm (R((fwhm)) = 1000). The merits of solid-state detection for DOFMS are evaluated, and methods to extend the DOFMS mass range are considered.

Liquid sampling-atmospheric pressure glow discharge ionization source for elemental mass spectrometry.

A new, low power ionization source for elemental MS analysis of aqueous solutions is described. The liquid sampling-atmospheric pressure glow discharge (LS-APGD) operates by a process wherein the surface of the liquid emanating from a 75 µm i.d. glass capillary acts as the cathode of the direct current glow discharge. Analyte-containing solutions at a flow rate of 100 µL min(-1) are vaporized by the passage of current, yielding gas phase solutes that are subsequently ionized in the <5 W (maximum of 60 mA and 500 V), ~1 mm(3) volume, plasma. The LS-APGD is mounted in place of the normal electrospray ionization source of a Thermo Scientific Exactive Orbitrap mass spectrometer system without any other modifications. Basic operating characteristics are described, including the role of discharge power on mass spectral composition, the ability to obtain ultrahigh resolution elemental isotopic patterns, and demonstration of potential limits of detection based on the injection of aliquots of multielement standards (S/N > 1000 for 5 ng mL(-1) Cs). While much optimization remains, it is believed that the LS-APGD ion source may present a practical alternative to high-powered (>1 kW) plasma sources typically employed in elemental mass spectrometry, particularly for those cases where costs, operational overhead, simplicity, or integrated elemental/molecular analysis considerations are important.

C60 secondary ion mass spectrometry with a hybrid-quadrupole orthogonal time-of-flight mass spectrometer.

A hybrid quadrupole orthogonal time-of-flight mass spectrometer optimized for matrix-assisted laser desorption ionization (MALDI) and electrospray ionization has been equipped with a C 60 cluster ion source. This configuration is shown to exhibit a number of characteristics that improve the performance of traditional time-of-flight secondary ion mass spectrometry (TOF-SIMS) experiments for the analysis of complex organic materials and, potentially, for chemical imaging. Specifically, the primary ion beam is operated as a continuous rather than a pulsed beam, resulting in up to 4 orders of magnitude greater ion fluence on the target. The secondary ions are extracted at very low voltage into 8 mTorr of N 2 gas introduced for collisional focusing and cooling purposes. This extraction configuration is shown to yield secondary ions that rapidly lose memory of the mechanism of their birth, yielding tandem mass spectra that are identical for SIMS and MALDI. With implementation of ion trapping, the extraction efficiency is shown to be equivalent to that found in traditional TOF-SIMS machines. Examples are given, for a variety of substrates that illustrate mass resolution of 12,000-15,600 with a mass range for inorganic compounds to m/ z 40,000. Preliminary chemical mapping experiments show that with added sensitivity, imaging in the MS/MS mode of operation is straightforward. In general, the combination of MALDI and SIMS is shown to add capabilities to each technique, providing a robust platform for TOF-SIMS experiments that already exists in a large number of laboratories.

MS/MS methodology to improve subcellular mapping of cholesterol using TOF-SIMS.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) can be utilized to map the distribution of various molecules on a surface with submicrometer resolution. Much of its biological application has been in the study of membrane lipids, such as phospholipids and cholesterol. Cholesterol is a particularly interesting molecule due to its involvement in numerous biological processes. For many studies, the effectiveness of chemical mapping is limited by low signal intensity from various biomolecules. Because of the high energy nature of the SIMS ionization process, many molecules are identified by detection of characteristic fragments. Commonly, fragments of a molecule are identified using standard samples, and those fragments are used to map the location of the molecule. In this work, MS/MS data obtained from a prototype C60(+)/quadrupole time-of-flight mass spectrometer was used in conjunction with indium LMIG imaging to map previously unrecognized cholesterol fragments in single cells. A model system of J774 macrophages doped with cholesterol was used to show that these fragments are derived from cholesterol in cell imaging experiments. Examination of relative quantification experiments reveals that m/z 147 is the most specific diagnostic fragment and offers a 3-fold signal enhancement. These findings greatly increase the prospects for cholesterol mapping experiments in biological samples, particularly with single cell experiments. In addition, these findings demonstrate the wealth of information that is hidden in the traditional TOF-SIMS spectrum.