Ion capture from an external nano-electrospray ionization source in an electrostatic linear ion trap has been effected by in-trap potential lift so as to avoid a time-dependent frequency drift of trapped ions. This phenomenon was observed when using mirror switching for capturing ions and compromised the mass resolution when using Fourier transform techniques for mass determination. A dual image charge detection approach was also implemented to compensate for losses in mass resolution associated with increasing the length of the electrostatic trap to accommodate the lift region. The potential lift approach for ion capture led to no detectable frequency shifts, thereby enabling the achievement of pressure limited theoretical resolutions. For example, a resolution of roughly 11,000 M/Delta M FWHM was observed for a carborane anion population of average m/z= 520 at a transient length of 125 ms. The use of the dual detector approach led to an increase (similar to 12%) in the ion frequencies used for mass analysis, which more than compensated for the effect of increasing the length of the electrostatic trap. Although the implementation of the potential lift approach and dual detectors were successful in their objectives, these changes resulted in a narrower m/z range for a single ion injection event relative to mirror switching. Furthermore, the dual detector approach resulted in a higher noise floor and a more complicated frequency spectrum due to asymmetries in the electric fields of the ion trap. (C) 2016 Elsevier B.V. All rights reserved.

Ion capture from an external nano-electrospray ionization source in a Fourier transform electrostatic linear ion trap has been effected by mirror-switching. This capture method can suffer from time-dependent frequency shifts in the measured ion motion, which compromises mass resolution when using Fourier transform techniques for mass determination. This phenomenon was determined to be a result of the transient voltage recovery of the power supplies used for mirror-switching in response to a pulsed capacitive load, for which several examples are shown. A circuit, based on the AD210AN isolation amplifier, was fabricated to compensate for the voltage perturbation induced by mirror-switching by superimposing the inverted perturbation to the electric field of the opposing reflectron. In doing so, the dependence of the ions path length and frequency on the power supply output was greatly reduced throughout data acquisition. With this circuit enabled, no frequency shifts were observed in the mass spectrum when using mirror-switching, and thus pressure-limited theoretical resolutions were achieved. For example, an absorption mode resolving power of greater than 50,000 M/Delta M FWHM was observed for iodide (m/z 126.9) at a transient length of 300 milliseconds. The use of mirror-switching led to a much greater m/z range than in-trap potential lift for a single ion injection which is demonstrated via simulation and experimental results. This correction method is simple to implement and does not require user intervention once properly tuned. (C) 2016 Elsevier B.V. All rights reserved.

We describe a new method for isolating ions in quadrupole ion traps using an excitation waveform generated by mixing a broadband waveform generated by frequency modulation (FM) with a sine-wave at the secular frequency of the ion to be isolated. In terms of resolution and efficiency, the mixed FM method exhibits performance nearly identical to isolation using the apex of the Mathieu stability diagram. A disadvantage of the mixed FM method is that isolations require additional time relative to apex-based methods. This disadvantage is shared by other methods that involve application of multi-frequency waveforms such as stored waveform inverse Fourier transform (SWIFT). An advantage of the mixed FM technique (also shared with other tailored waveform approaches), is applicability to a much larger m/z range than apex-based methods. Indeed, the mixed FM technique performs identically to SWIFT in many respects. While the mixed FM technique is not nearly as flexible as SWIFT in terms of the frequency content of the generated waveforms, the mixed FM technique is much simpler to implement as it requires only two function generators and a frequency mixer. Tuning important parameters of the waveform such as notch frequency, notch width, and excitation bandwidth is also facilitated with the mixed FM technique. (C) 2014 Elsevier B.V. All rights reserved.

A variety of ion traps are used in mass spectrometry. A key feature shared by most of them is the ability to perform tandem mass spectrometry (MS/MS). The Orbitrap is perhaps the most notable ion trap in which MS/MS has yet to be performed. An electrostatic linear ion trap (ELIT) is analogous to an orbitrap in that ions are trapped using solely electrostatic fields. However, the relatively simple ion motion within an ELIT facilitates analysis of fragment ions produced within the device. In this report, we describe an ELIT to which we have added a target for surface induced dissociation (SID). When combined with our previously described method for isolating a precursor ion trapped in an ELIT,1 this apparatus enables MS/MS to be performed. Measurement of product ion m/z is facilitated by the fact that the ELIT is isochronous over the energy range of 1850-2000 eV so that changes to ion energy during SID do not cause major m/z shifts. We demonstrate MS/MS by isolating and dissociating each compound in a four component mixture of tetraalkylphosphonium cations. We also discuss the optimization of collision energy and the length of time that the SID target is available for collision, two parameters that are important in the performance of these experiments.

•A novel isolation method for ions stored in an electrostatic ion trap has been developed.•The method requires no hardware modifications to the electrostatic ion trap.•The method requires minimal additional electronics.

A Fourier transform electrostatic linear ion trap (FT-ELIT) is a mass analyzer consisting of a field free region with a reflectron on each side. Ions bounce back and forth and a signal is generated using a centrally located image charge pickup electrode. In this report we describe a technique for injecting packets of ions produced by dim sources such as electrospray ionization (ESI) into an FT-ELIT. The technique involves accumulating and thermalizing ions in a collision cell. The collision cell is equipped with a set of electrodes that enables the creation of an axial electric field that is used to concentrate the accumulated ions near the exit. Further concentration is achieved by reducing the potential on the exit lens of the collision cell prior to ion ejection. We demonstrate that these concentration techniques significantly increase signal intensity. We also use ion optical simulations to show that the signal intensity increases because the concentration increases the spatial charge density of the injected ion cloud not only by compressing the ion cloud in the collision cell, but also by decreasing the time required to eject the ions from the collision cell. We also demonstrate that the concentration techniques do not broaden the kinetic energy distribution of the injected ions; therefore, the concentration does not degrade resolution. Using these injection techniques, we are able to analyze ions produced by ESI ranging from 300 to 2200 m/z in a single injection with high signal-to-noise ratio using FT-ELIT. (C) 2014 Elsevier B.V. All rights reserved.

A novel hybrid tandem mass spectrometer is presented that combines a linear quadrupole ion trap (QLIT) with a linear electrostatic ion trap (ELIT), which is composed of opposing ion mirrors. The QLIT is used both as an accumulation device for the pulsed injection of ions into the ELIT and as a collision cell for ions released from the ELIT and back into the QLIT. Ions are subjected to mass analysis in the ELIT via Fourier transformation of the time-domain signal obtained from an image current measurement using a pick-up electrode in the field-free region of the ELIT. The nondestructive nature of ion detection and the relatively straightforward axial entrance and exit of ions into and from the ELIT allow for the execution of nondestructive tandem mass spectrometry experiments whereby both the initial mass spectrum and the product ion spectrum are obtained on the same initial ion population. The timed pulsing of a deflection electrode, in conjunction with the release of ions from the ELIT, allows for the selection of precursor ions for recapture by the QLIT. The transfer of ions back and forth between the QLIT and ELIT is illustrated with Cs ions, the selection of precursor ions is demonstrated with isotopes of tetraoctylammonium cations, and complete nondestructive tandem mass spectrometry experiments are demonstrated with a mixture of angiotensin II and bradykinin cations. With the current apparatus, the efficiency for the process of recapturing ions and then reinjecting them into the ELIT is 35%-40%. The instrument is capable of isolating an ion from a neighbor with a mass as close as 1 part in 500, with negligible loss of the desired species.

In Fourier transform mass spectrometry, it is well-known that plotting the spectrum in absorption mode rather than magnitude mode has several advantages. However, magnitude spectra remain commonplace due to difficulties associated with determining the phase of each frequency at the onset of data acquisition, which is required for generating absorption spectra. The phasing problem for electrostatic traps is much simpler than for Fourier transform ion cyclotron resonance (FTICR) instruments, which greatly simplifies the generation of absorption spectra. Here, we present a simple method for generating absorption spectra from a Fourier transform electrostatic linear ion trap mass spectrometer. The method involves time shifting the data prior to Fourier transformation in order to synchronize the onset of data acquisition with the moment of ion acceleration into the electrostatic trap. Under these conditions, the initial phase of each frequency at the onset of data acquisition is zero. We demonstrate that absorption mode provides a 1.7-fold increase in resolution (full width at half maximum, fwhm) as well as reduced peak tailing. We also discuss methodology that may be applied to unsynchronized data in order to determine the time shift required to generate an absorption spectrum.

Means to allow for the application of a dipolar DC pulse to the end-cap electrodes of a three-dimensional (3-D) quadrupole ion trap for as short as a millisecond to as long as hundreds of milliseconds are described. The implementation of dipolar DC does not compromise the ability to apply AC waveforms to the end-cap electrodes at other times in the experiment. Dipolar DC provides a nonresonant means for ion acceleration by displacing ions from the center of the ion trap where they experience stronger rf electric fields, which increases the extent of micro-motion. The evolution of the product ion spectrum to higher generation products with time, as shown using protonated leucine enkephalin as a model protonated peptide, illustrates the broad-band nature of the activation. Dipolar DC activation is also shown to be effective as an ion heating approach in mimicking high amplitude short time excitation (HASTE)/pulsed Q dissociation (PQD) resonance excitation experiments that are intended to enhance the likelihood for observing low m/z products in ion trap tandem mass spectrometry.

Recognizing that the sensitivity of NMR is influenced by factors such as conductance and dielectric constant of the sample, we propose the receiving efficiency R to characterize how efficiently the NMR signal can be observed from a unit transverse magnetization in a sample under optimal probe tuning and matching conditions. Conveniently, the relative receiving efficiency can be defined as the ratio of the NMR signal induced by a unit transverse magnetization in a sample of interest and a reference solution. Based on the reciprocal relationship between excitation and observation in NMR, the relative receiving efficiency can be correlated with the 90° pulse length (τ90). In the special case of perfect probe tuning (impedance matched to 50Ω), R is inversely proportional to τ90. Application of the NMR receiving efficiency in quantitative analysis potentially enables a single external concentration reference for almost any sample, eliminating the need to know its exact chemical composition or detailed electromagnetic properties.

An experiment designed to collect a saturation transfer double difference (STDD) NMR spectrum using a solenoid microcoil NMR difference probe is reported. STDD‐NMR allows the investigation of ligand‐biomolecule binding, with moderate concentration requirements for unlabeled molecular targets and the ability to discern binding events in the presence of non‐binding ligands. The NMR difference probe acquires the signals from two different samples at once, and cancels common signals automatically through a mechanism of switching between parallel excitation and serial acquisition of the sample signals. STDD spectra were acquired on a system consisting of human serum albumin and two ligands, octanoic acid and glucose. The non‐binding ligand, glucose, was cancelled internally through phase cycling, while the protein signal was subtracted automatically by the difference probe. The proton NMR resonance signal from octanoic acid remained in the double difference spectrum. This work demonstrates that the double difference can be performed both internally and automatically through the utilization of the solenoid microcoil NMR difference probe and STDD‐NMR pulse sequence, resulting in a clean signal from the binding ligand with good protein background subtraction and an overall favorable result when compared to the conventional approach. Copyright © 2008 John Wiley & Sons, Ltd.

Aircraft-based vertical flux measurements fill a gap in the spatial domain for studies of biosphere–atmosphere exchange. To acquire valid flux data, a determination of the deviation from the mean vertical wind, w′, is essential. When using aircraft platforms, flux measurements are subject to systematic and random errors from airflow distortion caused by the lift-induced upwash ahead of the aircraft. Although upwash is typically considered to be a constant quantity over periods used for calculating fluxes, it can vary significantly over short (and longer) periods due to changes in aircraft lift. The characterization of such variations in upwash are of undeniable importance to flux measurements, especially when real-time computations of w′ are required. In this paper, the variability in upwash was compared to the calculated upwash from the model of Crawford et al. (Boundary-Layer Meteorol, 80:79–94, 1996) using data taken during a long-period (phugoid mode) free oscillation of the aircraft. The cyclic variation of lift during the free oscillation offers an ideal scenario in which to acquire in-flight data on the upwash that is present, as well as to test the capability of upwash correction models. Our results indicate that while this model corrects for much of the mean upwash, there can be significant variations in upwash on a time scale that is important to flux measurements. Our results suggest that use of the measured load factor could be an easily implemented operational constraint to minimize uncertainty in w′ due to changing upwash from changing aircraft lift. We estimate, using the phugoid data, and from variations in aircraft attitude and airspeed in flux-measurement configuration, that the uncertainty in w caused by variable upwash is approximately ± 0.05 m s−1.

A new difference probe for nuclear magnetic resonance (NMR) spectroscopy is presented. The difference probe uses two saddle-shaped coils to excite and detect two samples simultaneously. The samples are held in a specially modified 3-mm NMR tube with an Ultem plastic disk to separate the samples. The probe’s resonant circuit contains two crossed diodes that passively switch the relative phase of each coil during the NMR experiment. The result is a difference spectrum from the two samples. The degree of cancellation of common signals was determined to be approximately 90%, and the application of the probe to relaxation-edited difference spectroscopy for identifying protein–ligand interactions was demonstrated using glutathione and glutathione S-transferase binding protein.

This chapter discusses the practical aspects of carrying out high-resolution nuclear magnetic resonance (NMR) experiments to investigate drug-DNA complexes. In addition to the large number of recent studies based on the NMR analysis of the solution structure of the drug-DNA complexes, there have been a substantial number of structural studies based on X-ray crystallographic analysis of such complexes. Once crystals have been obtained that diffract well, this approach has the advantage that high-resolution structures can often be determined in a more direct fashion compared to the NMR approach. Several important differences remain, however, between structure determination in solution and in the solid state. First, in case of nucleic acids, their conformation is frequently different in the solid and solution state, because of hydration and/or crystal packing effects. Second, it is considerably easier to explore the effects of changing temperature and salt conditions, in solution to learn something, about the kinetics of interaction, between the drug and the DNA. Third, studies to examine the stoichiometry of various drug-DNA complexes are more easily carried out in solution than in the solid state. For these reasons, much can be learned from the structural analysis carried out in solution that is complementary to the information available from the X-ray crystallographic studies.