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R Graham Cooks

Publications and source records attributed to R Graham Cooks.

At least 19 recordsLinked to original sources
PubMed2007

Monitoring diet effects via biofluids and their implications for metabolomics studies.

The effect of diet on metabolites found in rat urine samples has been investigated using nuclear magnetic resonance (NMR) and a new ambient ionization mass spectrometry experiment, extractive electrospray ionization mass spectrometry (EESI-MS). Urine samples from rats with three different dietary regimens were readily distinguished using multivariate statistical analysis on metabolites detected by NMR and MS. To observe the effect of diet on metabolic pathways, metabolites related to specific pathways were also investigated using multivariate statistical analysis. Discrimination is increased by making observations on restricted compound sets. Changes in diet at 24-h intervals led to predictable changes in the spectral data. Principal component analysis was used to separate the rats into groups according to their different dietary regimens using the full NMR, EESI-MS data or restricted sets of peaks in the mass spectra corresponding only to metabolites found in the urea cycle and metabolism of amino groups pathway. By contrast, multivariate analysis of variance from the score plots showed that metabolites of purine metabolism obscure the classification relative to the full metabolite set. These results suggest that it may be possible to reduce the number of statistical variables used by monitoring the biochemical variability of particular pathways. It should also be possible by this procedure to reduce the effect of diet in the biofluid samples for such purposes as disease detection.

Alloxan↗
PubMed2006

Thermal formation of homochiral serine clusters and implications for the origin of homochirality.

Spontaneous assembly of amino acids into vapor-phase clusters occurs on heating the solid compounds in air. In comparison to the other amino acids, serine forms clusters to an unusual extent, showing a magic number octamer on sublimation; this octamer can be ionized and characterized by mass spectrometry. Two isomers of the vapor-phase serine octamer are generated, the minor one at 130 degrees C and the major at 220 degrees C. The higher temperature cluster shows a strong homochiral preference, as confirmed by isotopic labeling experiments. This serine cluster, like that generated earlier from solution in electrospray ionization experiments, undergoes gas-phase enantioselective substitution reactions with other amino acids. These reactions transfer the chirality of serine to the other amino acid through enantioselective incorporation into the octamer. Other serine pyrolysis products include alanine, glycine, ethanolamine, and small dipeptides, and many of these, too, are observed to be incorporated into the thermally formed serine octamers. Chiral chromatographic analysis confirmed that L-serine sublimation produced DL-alanine, glycine, and ethanolamine, while in the presence of hydrogen sulfide, L-serine yielded L-cysteine. The data demonstrate that sublimation of serine under relatively mild conditions yields chirally enriched serine octamers and that the chiral preference of the starting serine can be transferred to other compounds through cluster-forming chemical reactions.

Gas Chromatography-Mass Spectrometry↗
PubMed2006

Droplet dynamics and ionization mechanisms in desorption electrospray ionization mass spectrometry.

A droplet pickup and other mechanisms have been suggested for the ionization of biomolecules like peptides and proteins by desorption electrospray ionization. To verify this hypothesis phase Doppler particle analysis was used to study the sizes and velocities of droplets involved in DESI. It was found that impacting droplets typically have velocities of 120 m/s and average diameters of 2-4 microm. Small differences in sprayer construction influence the operating conditions at which droplets of these dimensions are produced. Under these conditions, the kinetic energy per impacting water molecule is less than 0.6 meV and sputtering through momentum transfer during collisions or ionization by other electronic processes is unlikely. Droplets arrive at the surface with velocities well below the speed of sound in common materials, thereby excluding the possibility of ionization by shockwave formation. Some droplets appear to roll along the surface, increasing contact time and presumably the amount of material that is taken up into droplets during conditions typical of the DESI experiment.

Journal Article↗
PubMed2006

Handheld rectilinear ion trap mass spectrometer.

A shoebox-sized, 10-kg, handheld mass spectrometer, Mini 10, based on a rectilinear ion trap mass analyzer has been designed, built, and characterized. This instrument has evolved from a decade-long experimental and simulation program in mass spectrometer miniaturization. The rectilinear ion trap has a simplified geometry and high trapping capacity, and when used with a miniature and ruggedized pumping system, it allows chemical analysis while the instrument is being carried. Compact electronics, including an air core RF drive coil, were developed to control the instrument and to record mass spectra. The instrument runs on battery power, consuming less than 70 W, similar to a laptop computer. Wired and wireless networking capabilities are implemented. The instrument gives unit resolution and a mass range of over m/z 500. Tandem mass spectrometry capabilities are implemented using collision-induced dissociation, and they are used to provide confirmation of chemical structure during in situ analysis. Continuous monitoring of air and solution samples is demonstrated, and a limit of detection of 50 ppb was obtained for toluene vapor in air and for an aqueous naphthalene solution using membrane sample introduction.

Journal Article↗
PubMed2006

Multiplexed rectilinear ion trap mass spectrometer for high-throughput analysis.

A multichannel mass spectrometer based on the rectilinear ion trap (RIT) analyzer was designed and constructed for simultaneous high-throughput analysis of multiple samples. The instrument features four parallel ion source/mass analyzer/detector channels assembled in a single vacuum chamber and operated using a common set of control electronics, including a single rf amplifier and transformer coil. This multiplexed RIT mass spectrometer employs an array of four millimeter-sized ion traps (x(o) = 5.0 mm and y(o) = 4.0 mm, where x(o) and y(o) are the half-distances in the x and y dimensions, respectively). Mass spectra are acquired from four different samples simultaneously. The available mass/charge range is m/z 15-510 with excellent linearity of the mass calibration (R2 = 0.999 999). The peak width is less than 0.3 mass/charge units at m/z 146, corresponding to a resolution of approximately 500. Simultaneous MS/MS of ions due to four compounds (3-fluoroanisole, 4-fluoroanisole, 2-fluorobenzyl alcohol, 2,6-dimethylcyclohexanone) with the same nominal molecular radical cation but distinctive fragmentation patterns was demonstrated. Isolation and fragmentation efficiencies were approximately 25 and approximately 75%, respectively, measured in the typical case of the molecular radical cation of acetophenone. Preacquisition differential data were obtained by real-time subtraction of the ion signals from two channels of the multiplexed mass spectrometer. The differential experiment presented offers proof of principle of comparative mass spectra in high-throughput screening applications while reducing data storage requirements.

Computer Simulation↗
PubMed2006

Principal component analysis of urine metabolites detected by NMR and DESI-MS in patients with inborn errors of metabolism.

Urine metabolic profiles of patients with inborn errors of metabolism were examined with nuclear magnetic resonance (NMR) and desorption electrospray ionization mass spectrometry (DESI-MS) methods. Spectra obtained from the study of urine samples from individual patients with argininosuccinic aciduria (ASA), classic homocystinuria (HCY), classic methylmalonic acidemia (MMA), maple syrup urine disease (MSUD), phenylketonuria (PKU) and type II tyrosinemia (TYRO) were compared with six control patient urine samples using principal component analysis (PCA). Target molecule spectra were identified from the loading plots of PCA output and compared with known metabolic profiles from the literature and metabolite databases. Results obtained from the two techniques were then correlated to obtain a common list of molecules associated with the different diseases and metabolic pathways. The combined approach discussed here may prove useful in the rapid screening of biological fluids from sick patients and may help to improve the understanding of these rare diseases.

Case-Control Studies↗
PubMed2006

Ion trajectory simulation for electrode configurations with arbitrary geometries.

A multi-particle ion trajectory simulation program ITSIM 6.0 is described, which is capable of ion trajectory simulations for electrode configurations with arbitrary geometries. The electrode structures are input from a 3D drawing program AutoCAD and the electric field is calculated using a 3D field solver COMSOL. The program CreatePot acts as interface between the field solver and ITSIM 6.0. It converts the calculated electric field into a field array file readable by ITSIM 6.0 and ion trajectories are calculated by solving Newton's equation using Runge-Kutta integration methods. The accuracy of the field calculation is discussed for the ideal quadrupole ion trap in terms of applied mesh density. Electric fields of several different types of devices with 3D geometry are simulated, including ion transport through an ion optical system as a function of pressure. Ion spatial distributions, including the storage of positively charged ions only and simultaneous storage of positively/negatively charged ions in commercial linear ion traps with various geometries, are investigated using different trapping modes. Inelastic collisions and collision induced dissociation modeled using RRKM theory are studied, with emphasis on the fragmentation of n-butylbenzene inside an ideal quadrupole ion trap. The mass spectrum of 1,3-dichlorobenzene is simulated for the rectilinear ion trap device and good agreement is observed between the simulated and the experimental mass spectra. Collisional cooling using helium at different pressures is found to affect mass resolution in the rectilinear ion trap.

Journal Article↗
PubMed2006

Enhanced desorption ionization using oxidizing electrosprays.

A signal enhancement of two orders of magnitude was achieved when reactive desorption electrospray ionization (DESI) was used to investigate copper(II) dibutyl dithiocarbamate, Cu(II)(bu2dtc)2, found in a specialized polymer. Cu(II) was oxidized to Cu(III) during the DESI experiment by oxidants in the spray solvent. Such oxidants could be present or formed during electrospray (e.g., O2) or deliberately added to the spray solvent (this approach is called reactive DESI). When a strong oxidizing agent (e.g., iodine) was added to the spray solvent, the signal increased by two orders of magnitude relative to the pure solvent spray. The correlation between the standard reduction potential of the oxidant and the signal intensity and signal to noise ratio of the product ion for various reagents, was tested and discussed. The observed DESI enhancements in rates of oxidation are not observed in homogeneous solution. The major peaks in the collision induced dissociation (CID) spectrum of the complex ion Cu(III)(bu2dtc)2]+ were identified using isotopic distributions and MS3 data.

Journal Article↗
PubMed2006

Detection Technologies. Ambient mass spectrometry.

A recent innovation in mass spectrometry is the ability to record mass spectra on ordinary samples, in their native environment, without sample preparation or preseparation by creating ions outside the instrument. In desorption electrospray ionization (DESI), the principal method described here, electrically charged droplets are directed at the ambient object of interest; they release ions from the surface, which are then vacuumed through the air into a conventional mass spectrometer. Extremely rapid analysis is coupled with high sensitivity and high chemical specificity. These characteristics are advantageously applied to high-throughput metabolomics, explosives detection, natural products discovery, and biological tissue imaging, among other applications. Future possible uses of DESI for in vivo clinical analysis and its adaptation to portable mass spectrometers are described.

Animals↗
PubMed2006

Coupling desorption electrospray ionization with ion mobility/mass spectrometry for analysis of protein structure: evidence for desorption of folded and denatured States.

A desorption electrospray ionization (DESI) source has been coupled to an ion mobility time-of-flight mass spectrometer for the analysis of proteins. Analysis of solid-phase horse heart cytochrome c and chicken egg white lysozyme proteins with different DESI solvents and conditions shows similar mass spectra and charge state distributions to those formed when using electrospray to analyze these proteins in solution. The ion mobility data show evidence for compact ion structures [when the surface is exposed to a spray that favors retention of "nativelike" structures (50:50 water:methanol)] or elongated structures [when the surface is exposed to a spray that favors "denatured" structures (49:49:2 water:methanol:acetic acid)]. The results suggest that the DESI experiment is somewhat gentler than ESI and under appropriate conditions, it is possible to preserve structural information throughout the DESI process. Mechanisms that are consistent with these results are discussed.

Absorption↗
PubMed2006

Resonant ac dipolar excitation for ion motion control in the Orbitrap mass analyzer.

A dipolar ac signal applied to the split outer electrode of an Orbitrap mass spectrometer at the axial resonance frequency causes excitation of ion axial motion and either eventual ion ejection from the trap, if applied in phase with ion motion, or de-excitation, if applied 180 degrees out of phase. Both de-excitation and excitation may be achieved mass-selectively. The extent of ion axial de-excitation depends on the ac amplitude and on the number of cycles applied; sufficient de-excitation can be accomplished such that the ion signal cannot be observed above baseline noise. After de-excitation, the ions remain trapped and in rapid orbital (but not axial) motion, which allows them to be re-excited coherently by application of a second ac waveform allowing the signal again to be observed. Both broad-band and narrow-band waveforms have been used to de-excite and to re-excite ion motion. Using narrow-band waveforms, selective de-excitation and re-excitation can be performed with unit mass selection, leaving an adjacent 13C isotopic peak unaffected. The origin and potential applications of these new capabilities is delineated.

Journal Article↗
PubMed2006

Novel linear ion trap mass analyzer composed of four planar electrodes.

A novel linear ion trap mass analyzer was developed using just four elongated planar electrodes, mounted in parallel, and employing an RF potential for ion trapping in the radial and axial directions. Mass analysis was achieved using the mass-selective instability scan with ion ejection in the radial direction. The performance of this new device was characterized in comparison with the 6-electrode rectilinear ion trap (RIT) from which it is derived. The 4-electrode trap gives optimum performance in an asymmetric geometry, just like the original optimized 6-electrode RIT. The strong RF fringing fields at the ends of the RF rods account for axial ion trapping without use of extra electrodes or an axial DC voltage. Field calculations and simulations have been carried out to study the trapping potential inside RITs with various configurations. Demonstrated capabilities include analysis of externally injected ions with mass resolution in excess of 1000 and a mass/charge range of 650 Th as well as tandem mass spectrometry capabilities. The geometric simplicity and performance characteristics of the 4-electrode RIT make it particularly attractive in the development of next generation miniaturized mass spectrometers.

Journal Article↗
PubMed2006

Direct monitoring of toxic compounds in air using a portable mass spectrometer.

A portable tandem mass spectrometer, capable of performing atmospheric pressure chemical ionization (APCI) using a direct atmospheric inlet, is applied to the real-time monitoring of toxic compounds in air. Analytes of interest include dimethyl methylphosphonate, arsine, benzene, toluene, pyridine and vinyl acetate. The detection, identification and quantification of organic and inorganic compounds in air is demonstrated using short analysis times (<5 seconds) with detection limits in the low ppb (v/v) levels and linear dynamic ranges of several orders of magnitude. Highly specific detection and identification is achieved, even when the analyte is a trace component in a complex mixture including such interferents as fuels, lubricants, and cleaners. The effects of environmental conditions, including temperature and humidity, are delineated. Receiver operating characteristic (ROC) curves are presented to show the trade-off between false positive and false negative detection rates. Tandem mass spectrometry based both on collision-induced dissociation and on selective atmospheric pressure ion/molecule reactions is also used to increase selectivity and sensitivity.

Air Pollutants↗
PubMed2006

Desorption electrospray ionization with a portable mass spectrometer: in situ analysis of ambient surfaces.

Desorption electrospray ionization (DESI) is implemented on a portable mass spectrometer and used to demonstrate in situ detection of active ingredients in pharmaceutical preparations, alkaloids in plant tissues, explosives, chemical warfare agent simulants and agricultural chemicals from a variety of surfaces; air monitoring applications using DESI are also introduced.

Acetamides↗