Herbert H. Hill

Ion mobility–mass spectrometry

This review article compares and contrasts various types of ion mobility-mass spectrometers available today and describes their advantages for application to a wide range of analytes. Ion mobility spectrometry (IMS), when coupled with mass spectrometry, offers value-added data not possible from mass spectra alone. Separation of isomers, isobars, and conformers; reduction of chemical noise; and measurement of ion size are possible with the addition of ion mobility cells to mass spectrometers. In addition, structurally similar ions and ions of the same charge state can be separated into families of ions which appear along a unique mass-mobility correlation line. This review describes the four methods of ion mobility separation currently used with mass spectrometry. They are (1) drift-time ion mobility spectrometry (DTIMS), (2) aspiration ion mobility spectrometry (AIMS), (3) differential-mobility spectrometry (DMS) which is also called field-asymmetric waveform ion mobility spectrometry (FAIMS) and (4) traveling-wave ion mobility spectrometry (TWIMS). DTIMS provides the highest IMS resolving power and is the only IMS method which can directly measure collision cross-sections. AIMS is a low resolution mobility separation method but can monitor ions in a continuous manner. DMS and FAIMS offer continuous-ion monitoring capability as well as orthogonal ion mobility separation in which high-separation selectivity can be achieved. TWIMS is a novel method of IMS with a low resolving power but has good sensitivity and is well intergrated into a commercial mass spectrometer. One hundred and sixty references on ion mobility-mass spectrometry (IMMS) are provided.

Ion Mobility Spectrometry in Analytical Chemistry

Abstract Recent literature relevant to the role of ion mobility spectrometry (IMS) in analytical chemistry is discussed. Included are sections dealing with instrumentation, spectral collection techniques, the theory of ion mobility in gases, and the dynamics of atmospheric pressure ionization. The pros and cons of radioactive ionization, photoionization, laser ionization, surface ionization, and electrofied spray ionization are considered. Analytical applications are separated into the use of IMS as a stand-alone spectrometer, and the use of IMS as a detector following gas, liquid, and supercritical fluid chromatography.

Analysis of explosives using electrospray ionization/ion mobility spectrometry (ESI/IMS).

The analysis of explosives with ion mobility spectrometry (IMS) directly from aqueous solutions was shown for the first time using an electrospray ionization technique. The IMS was operated in the negative mode at 250 degrees C and coupled with a quadrupole mass spectrometer to identify the observed IMS peaks. The IMS response characteristics of trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 2-amino-4,6-dinitrotoluene (2-ADNT), 4-nitrotoluene (4-NT), trinitrobenzene (TNB), cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), cyclo-tetramethylene-tetranitramine (HMX), dinitro-ethyleneglycol (EGDN) and nitroglycerine (NG) were investigated. Several breakdown products, predominantly NO(2)(-) and NO(3)(-), were observed in the low-mass region. Nevertheless, all compounds with the exception of NG produced at least one ion related to the intact molecule and could therefore be selectively detected. For RDX and HMX the [M+Cl(-)](-) cluster ion was the main peak and the signal intensities could be greatly enhanced by the addition of small amounts of sodium chloride to the sprayed solutions. The reduced mobility constants (K(0)) were in good agreement with literature data obtained from experiments where the explosives were introduced into the IMS from the vapor phase. The detection limits were in the range of 15-190 microg l(-1) and all calibration curves showed good linearity. A mixture of TNT, RDX and HMX was used to demonstrate the high separation potential of the IMS system. Baseline separation of the three compounds was attained within a total analysis time of 6.4 s.

Metabolic profiling by ion mobility mass spectrometry (IMMS)

Ion Mobility Mass Spectrometry (IMMS) was evaluated as an analytical method for metabolic profiling. The specific instrument used in these studies was a direct infusion (DI)-electrospray ionization (ESI)—ambient pressure ion mobility spectrometer (APIMS) coupled to a time-of-flight mass spectrometer (TOFMS). The addition of an ion mobility spectrometer to a mass spectrometer had several advantages over direct infusion electrospray mass spectrometry alone. This tandem instrument (ESI-IMMS) added a rapid separation step with high-resolution prior to mass spectrometric analysis of metabolite mixtures without extending sample preparation time or reducing the high through put potential of direct mass spectrometry. Further, IMMS also reduced the baseline noise common with ESI-MS analyses of complex samples and enabled rapid separation of isobaric metabolites. IMMS was used to analyze the metabolome of Escherichiacoli (E. coli), containing a collection of extremely diverse chemical compounds including hydrophobic lipids, inorganic ions, volatile alcohols and ketones, amino and non-amino organic acids, and hydrophilic carbohydrates. IMMS data were collected as two-dimensional spectra showing both mobility and mass of each ion detected. Using direct infusion ESI-IMMS of a non-derivatized methanol extract of an E. coli culture, more than 500 features were detected, of which over 200 intracellular metabolites were tentatively assigned as E. coli metabolites. This analytical method also allowed simultaneous separation of isomeric metabolic features.

Subcutaneous infusions for control of cancer symptoms

Continuous subcutaneous infusions offer a safe, simple, effective alternative to intravenous or intramuscular injections when oral medications cannot be used. They are extremely useful for cancer patients suffering from pain, vomiting, seizures, and other symptoms. Hydromorphone or morphine may be combined with metoclopramide, methotrimeprazine, or haloperidol (in D5W only), in the same pump to control both pain and nausea. Seizures can be controlled by subcutaneous infusion of phenobarbital or midazolam. If proper doses are prescribed and skin irritation is watched for, they can be used safely in the patients home.

Conventional analytical methods for chemical warfare agents

Analytical methods that are currently used for the detection and identification of chemical warfare agents are reviewed and classified by the number of dimensions of information they provide. Single dimensional sensors target specific compounds or classes of compounds. Although they can be less expensive and more portable than multidimensional sensors, multidimensional sensors detect a broader threat spectrum with greater precision and accuracy. The recommendation for analytical field verification during inspections under the Chemical Weapons Convention (CWC) is to use simple two-dimensional analytical methods, such as gas chromatography (GC) or ion mobility spectrometry (IMS), for on-site screening of chemical weapons (CW) agents or to fully equip a modern, mobile analytical laboratory located in an airplane, which can be moved rapidly throughout the world to each inspection site and provide high-quality analytical data on-site.

Analysis of triacylglycerols and whole oils by matrix-assisted laser desorption/ionization time of flight mass spectrometry

Since the introduction of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry the majority of research has focused on developing analytical methods for the qualitative determination of water soluble biomolecules such as proteins, peptides, carbohydrates, and oligonucleotides. This paper, however, reports the use of MALDI for the analysis of triacylglycerols and develops a new sample preparation method for nonpolar analytes. MALDI enables the rapid analyses of triacylglycerol (TAG) standards and mixtures of whole oils. The new method provides excellent shot to shot reproducibility, making quantification possible. Detection limits were in the mid femtomole range and the resolution was around 2000 which easily separated TAGs differing by one double bond. Sensitivity decreased with increasing molecular weight, causing biased results when analyzing complex mixtures with a significant range of molecular weight. In all cases only sodiated molecules and prompt losses of a fatty acid sodium salt were observed in the spectra. From this information it was possible to identify the three fatty acids on the glycerol backbone. Collision-induced dissociation was carried out on a triacylglycerol which proved to be useful for additional structural information, including the corroboration of the fatty acid components. With MALDI the percent compositions of TAGs in a standard olive oil was accurately determined. Finally, MALDI was used to examine the differences in lipid components between aged and fresh onion seeds, showing the potential of the technique for observing changes in lipid components in seeds.

Evaluation of Ultrahigh Resolution Ion Mobility Spectrometry as an Analytical Separation Device in Chromatographic Terms

An ion mobility spectrometer IMS that routinely achieves separation efficiencies in line with the theoretical diffusion limited maximum has been constructed. The theoretical maximum efficiency is a function of the total voltage drop, the temperature, the number of charges on the ion, the initial pulse width, . the length of the spectrometer, and the mobility K of the ion of interest. Despite the fact that our current instrumental setup uses modest voltages and fairly high temperatures, we were able to achieve over 130,000 theoretical plates for a singly charged ion in less than 25 ms. In addition, selectivity can be altered in IMS by . changing the drift gas or by increasing the electric field )1000 Vrcm such that the mobility of ions is no longer a linear function of the electric field. Separation . factors a can be altered by as much as 20% by changing the drift gas in the spectrometer. Finally leucine and isoleucine were separated in less than 23 ms with a resolution of 0.668 demonstrating the separation power of the instru-

Ion mobility-mass spectrometry analysis of isomeric carbohydrate precursor ions

The rapid separation of isomeric precursor ions of oligosaccharides prior to their analysis by mass spectrometry to the nth power (MSn) was demonstrated using an ambient pressure ion mobility spectrometer (IMS) interfaced with a quadrupole ion trap. Separations were not limited to specific types of isomers; representative isomers differing solely in the stereochemistry of sugars, in their anomeric configurations, and in their overall branching patterns and linkage positions could be resolved in the millisecond time frame. Physical separation of precursor ions permitted independent mass spectra of individual oligosaccharide isomers to be acquired to at least MS3, the number of stages of dissociation limited only practically by the abundance of specific product ions. IMS–MSn analysis was particularly valuable in the evaluation of isomeric oligosaccharides that yielded identical sets of product ions in tandem mass spectrometry experiments, revealing pairs of isomers that would otherwise not be known to be present in a mixture if evaluated solely by MS dissociation methods alone. A practical example of IMS–MSn analysis of a set of isomers included within a single high-performance liquid chromatography fraction of oligosaccharides released from bovine submaxillary mucin is described.

Capabilities and limitations of ion mobility spectrometry for field screening applications

The objective of this review is to provide an overview of the capabilities and limitations of ion mobility spectrometry (IMS) as it pertains to field screening. The first section of the review provides a description of the instrument and its operation along with examples of its primary advantages of simplicity, selectivity, and sensitivity. IMS is a simple and potentially inexpensive analytical technique with tunably variable selectivity of response, especially for polar organic compounds, and with sensitivity on the order of 0.1 ppb for most vaporphase compounds. The second section describes the history of IMS as a field-portable technique and discusses some of the difficulties experienced in this capacity. Problems in IMS include competitive ion /molecule reactions, low resolution, a limited dynamic response range, ease of contamination, long residence times in the spectrometer, and concentration-dependent response characteristics. Some of these problems have been solved, while others await further developments in IMS before they cease to limit the utility of IMS in reliable field-portable instruments. Finally, future developments which are needed in order for IMS to reach its full capacity in portable instruments for field monitoring are discussed. These future developments include nontime-of-flight instruments, high-temperature operation, and nonradioactive ionization sources.