David A. Laude

Trapping and detection of ions generated in a high magnetic field electrospray ionization fourier transform ion cyclotron resonance mass spectrometer

The trapping and detection parameters employed with a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer that is interfaced to a high magnetic field electrospray ionization (ES11 source are presented. ES1 occurs at atmospheric pressure in a 1.5-T field, and FTICR detection occurs 25 cm away at 3.0 T in either one of two cells separated by a conductance limit and maintained at pressure differentials of 5 × 105 and 2 × 107 torr, respectively. The continuous electrospray ion current traversing the high- and low-pressure cells is 350 and 100 pA, respectively. Retarding grid studies at the high-pressure cell indicate electrospray ion kinetic energies are controllable from less than an electronvolt to more than 10 eV. These kinetic energies are a function of desolvating capillary-skimmer assembly distance and the skimmer potential. Efficient accumulation of injected ions is accomplished only when the trap-plate potential matches the ion kinetic energy. If this condition is satisfied, the trapped ion cell fills to the ion space charge limit within a few hundred milliseconds. It is concluded that even at the high pressures used, the primary trapping mechanism cannot be solely collision dependent because the rate of ion accumulation is independent of background pressure. However, optimized FTICR excitation conditions for peptides and proteins in the mass range from 103 to more than 106 kDa are found to vary strongly with pressure; this is attributed to large mass- and charge-dependent differences in ion-molecule collision frequency.

Ion trapping and manipulation in a tandem time-of-flight-Fourier transform mass spectrometer

Abstract An external source tandem time-of-flight-Fourier transform mass spectrometer which provides programmed ion kinetic energy manipulation and trapping control is described. Design considerations are discussed and a detailed description of the instrument is provided. Typical ion injection efficiencies of 80–90% are obtained over an injection energy range of 30–500 eV. The instrument is capable of sensitive time-of-flight analysis of ions which have been injected into, and subsequently discharged from, the magnetic field. This allows a diagnostic treatment of ion injection and trapping performance independent of the Fourier transform mass spectrometry (FTMS) experiment. A theoretical treatment of the propagation characteristics of the ions detected in this manner is presented along with supporting data. Also described are new external source FTMS trapping procedures for pulsed injection that provide full control over the mass range of injected ions. Preliminary results for one such procedure are presented. In this example, a 230 dalton mass range is acquired in the trapped-ion cell for pulsed ion injection parameters that would ordinarily limit the acquired mass range to less than 150 daltons.

Simplified application of quadrupolar excitation in Fourier transform ion cyclotron resonance mass spectrometry

A new method for application of quadrupolar excitation to the trapped ion cell of a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer is presented. Quadrupolar excitation is conventionally applied to the two pairs of opposed electrodes that normally perform the excitation and detection functions in the FTICR experiment. Symmetry arguments and numerically calculated isopotential contours within the trapped ion cell lead to the conclusion that quadrupolar excitation can be applied to a single pair of opposed side electrodes. Examples of effective quadrupolar axialization via this method include a sevenfold signal-to-noise enhancement derived from 50 remeasurements of a single population of trapped bovine insulin ions and the selective isolation of a single charge state of horse heart myoglobin after an initial measurement that revealed the presence of 14 charge states.

Radial ion transport due to resistive-wall destabilization in Fourier transform mass spectrometry

Abstract Destabilization of coherent magnetron motion due to loss of ion energy in resistive external circuit elements is found to result in radial ion transport and ultimately ion loss from the trapped-ion cell of Fourier transform mass spectrometers. In contrast to random-walk diffusion and drift in radial electric fields, the resistive-wall destabilization described here does not involve collisions and is therefore independent of system pressure. Instead the mechanism prevails when large ion populations exhibit a significant degree of coherent magnetron motion. In this work a simple model to describe the transport effect is derived and is found to relate the rate of transport directly to ion number, external circuit resistance, and applied trapping potential. Experimental data for ions formed by electron ionization are acquired and found to support the model. Under certain conditions ion loss is shown to occur within a few hundred milliseconds which has important implications for quantitative Fourier transform mass spetrometry experiments that include lengthy collisional stabilization or reaction delays.

Concentric tube vacuum chamber for high magnetic field, high-pressure ionization in a fourier transform ion cyclotron resonance mass spectrometer

A new differential pumping design for external source Fourier transform ion cyclotron resonance mass spectrometry is described. A network of concentric tubes of increasing diameter terminates at a series of conductance limits across which a pressure from atmosphere to low-10−8 torr is achieved. This design permits high-pressure sources to be positioned within the solenoidal superconducting magnet less than 20 cm from the analyzer trapped ion cell. Ionization at high magnetic field offers the advantage of radial ion confinement and consequently delivers enhanced ion current to the trapped ion cell. Ion injection utilizing this vacuum chamber design is simpler than previously reported serial pumping stage designs because elaborate focusing optics to overcome the magnetic mirror effect are unnecessary. Two probe-mounted atmospheric pressure sources are described as evidence of the general applicability of the concentric tube vacuum chamber. An electrospray source that delivers several hundred picoamperes of ion current to the cell yields high-sensitivity spectra of proteins beyond 100 kDa. Improved pumping compared with a prototype concentric tube network configuration now permits mass resolution in excess of 20,000 for the [M + 4H]4+ ion of melittin. The resolution is sufficient to distinguish isotope peaks within a single charge state. A probe-mounted, pulsed-laser ablation source that permits cluster formation in the strong magnetic field is also demonstrated.

Open cell analog of the screened trapped-ion cell using compensation electrodes for Fourier transform ion cyclotron resonance mass spectrometry

Abstract The open cell collinear electrode geometry permits the inclusion of an auxiliary set of electrodes adjacent to the trap electrodes to perform several functions. Here they are used as compensation electrodes that virtually eliminate the radial electric field at the z = 0 midplane of the cell. The function of the compensation electrodes in reducing the radial electric field is analogous to the grounded transmissive screen inserted between the trap electrodes and the trapping volume in the closed screened cell whereby the interior of the cell is shielded from the trapping field. Segmenting the trap electrodes and applying oppositely biased potentials to each set of segments reduces the radial electric field at the z = 0 midplane of the cell by superposition of the opposing electric fields. In addition, dynamic adjustment of the potential well contour is performed by adjusting the relative potentials on each set of electrodes. The supplementary voltage applied to the inner set of compensation electrodes reduces the radial electric field by nearly two orders of magnitude and increases the potential well depth for greater ion capacity. In addition, the potential well assumes increased particle-in-a-box character without increasing the physical size of the cell, thereby reducing the effect of space charge. A FORTRAN program is developed that models the cell geometry and predicts the relationship between trap and compensation electrode voltage required to minimize the radial electric field throughout a specified cell volume. A theoretically optimum ratio of -0.33 V applied to the compensation electrodes for 1.0 V applied to the trap electrodes is predicted and is in close agreement with an experimentally determined optimum ratio of -0.36 V applied to the compensation electrodes for 1.0 V applied to the trap electrodes. This ratio reduces the cyclotron frequency shift from -70.8 Hz V-1 in an uncompensated open cell to -0.50 Hz V-1, a reduction of more than 99%. The radial electric field at the z = 0 midplane of the cell and 90% of the cell radius is reduced 97%, from 0.0139 V mm-1 to 0.0004 V mm-1. The reduction in frequency shift is accomplished without compromising mass accuracy. By collisionally damping ions to the center of the cell, mass accuracy over a one-decade range (60–600 u) approaches the mass accuracy of the hyperbolic cell geometry.

Optimization of a fixed-volume open geometry trapped ion cell for Fourier transform ion cyclotron mass spectrometry

Abstract Several open cylindrical trapped ion cells of fixed volume but varying electrode dimension are evaluated for the Fourier transform ion cyclotron resonance mass spectrometry experiment. In closed geometry cells the z-axis dimension is increased to form elongated cells with reduced radial electric field. In contrast, the aspect ratio for open cells can be increased without increasing the overall cell volume, an important consideration when magnetic field homogeneity is a concern. The increase in aspect ratio is achieved by reducing the relative dimensions of the trap electrodes with respect to the excitation and detection electrodes. The radial electric field magnitude for a fixed-length open cell with aspect ratios ranging from 0.84 to 1.60 is evaluated both theoretically and experimentally. Experimental frequency shifts for fixed-volume cells are reduced from −74.3 to −18.1 Hz V−1, a 411% reduction, by increasing the aspect ratio of an open cell from 1.20 to 1.60 respectively. As an alternative to the present standard open cell with electrodes of equal length, an elongated open cell geometry is optimized for maximized well depth (ion capacity) and minimized radial electric field.

Mechanism for an ion accumulation process in external source fourier transform mass spectrometers

Abstract An ion accumulation effect has been observed in the trapped ion cell of a Fourier transform mass spectrometer during the injection of externally generated ions. The accumulation is unexpected because, in the absence of deceleration in the cell, ions with kinetic energy greater than the trapping potential should pass through the cell or collide with the rear trap plate. Previous suggestions that the trapping mechanism involves collisional damping or radial magnetic field inhomogeneities could not be demonstrated under the conditions employed in this work. We propose, instead, an alternate mechanism for ion accumulation that involves charge exchange between injected ions and neutral analyte molecules present in the analyzer. It is shown that the observed accumulation rates are consistent with known rate constants for charge exchange and are directly proportional to the density of neutral analyte molecules in the analyzer. The energetics of charge reactions are shown to account for the presence of apparent dissociation effects and for the absence of an expected production ion in the spectrum of one analyte.

Selective generation of charge-cependent/independent ion energy distributions from a heated capillary electrospray source

Retarding grid and Fourier transform ion cyclotron resonance (FTICR) mass spectrometry variable trap potential measurements are performed to determine factors that contribute to the kinetic energy distribution of ions formed in an electrospray source that uses a heated capillary for desolvation. The control of ion kinetic energies is achieved by manipulating the skimmer position in the postcapillary expansion and by varying the potential appEed to the skimmer. The selective generation of either charge-dependent or charge-independent ion energy distributions is demonstrated. Charge-dependent energy distributions of electro-sprayed ions are created by sampling ions near the Mach disk of the supersonic expansion and by using a larger diameter skimmer orifice; the FTICR spectra acquired under these conditions exhibit mass-to-charge ratio-dependent mass discrimination determined by the potential used to trap the ions. Charge-independent energies of electrosprayed ions are created by positioning the capillary adjacent to the skimmer to sample thermal ions and by using a smaller skimmer orifice to reduce expansion cooling; under these conditions ion kinetic energy is determined primarily by the skimmer potential and no mass-to-charge ratio-dependence is observed in the selection of optimum FTICR trapping conditions. The ability to select between proteins of different conformation on the basis of kinetic energy differences is demonstrated. For example, a 0.4 V difference in trap potential is observed in the selective trapping of open and closed forms of the +10 charge state of lysozyme. Finally, it is demonstrated that by operating the source under conditions which deliver a beam of ions with charge-independent energies to the cell, it is possible to obtain precursor and product ion signal magnitudes in FTTCR spectra without charge-dependent mass discrimina-tion.

Fourier Transform Ion Cyclotron Resonance Mass Spectrometry in a 20 T Resistive Magnet

We present Fourier transform ion cyclotron resonance (FTICR) mass spectra at a magnetic field of 20 T; more than twice the highest field previously used for FTICR. Our instrument is based on a resistive magnet installed at the National High Magnetic Field Laboratory. The magnet has a 50 mm diameter bore and spatial inhomogeneity of approximately 1000 ppm over a 1 cm diameter spherical volume. However, FTICR mass resolving power far in excess of magnet homogeneity is achieved routinely for ions produced by either electron ionization (EI) or matrix-assisted laser desorption/ionization (MALDI). As examples, we show a MALDI mass spectrum of [M + H] quasimolecular ions of the peptide, human luteinizing hormone-releasing hormone (monoisotopic molecular weight, 1181.6 Da) at mass resolving power, m/delta m > 10,000; and an EI mass spectrum of molecular ions of the platinum cluster compound, Pt4(PF3)8 (average molecular weight, 1484 Da at mass resolving power, m/delta m approximately 20,000. Much better FTICR MS performance is predicted for future NHMFL resistive magnets of higher spatial and temporal homogeneity.