Paul M. Flanigan

Determination of inorganic improvised explosive device signatures using laser electrospray mass spectrometry detection with offline classification.

The mass spectral detection of low vapor pressure, inorganic-based explosive signatures including ammonium nitrate, chlorate, perchlorate, sugar, and the constituents contained within black powder are reported using laser electrospray mass spectrometry. The ambient pressure mass spectrometry technique combining nonresonant, femtosecond laser vaporization with electrospray postionization revealed primary and secondary signatures for trace quantities of inorganic explosives. A mixture of complexation agents in the electrospray solvent enabled the simultaneous detection of vaporized cations, anions, and neutrals in a single measurement. An offline classifier discriminated the inorganic-based explosives based on the mass spectral signatures resulting in high fidelity identification.

Classification of Smokeless Powders Using Laser Electrospray Mass Spectrometry and Offline Multivariate Statistical Analysis

A direct, sensitive, and rapid method for the detection of smokeless powder components, from five different types of ammunition, is demonstrated using laser electrospray mass spectrometry (LEMS). Common components found in powder, such as ethyl centralite, methyl centralite, dibutyl phthalate, and dimethyl phthalate, are detected under atmospheric conditions without additional sample preparation. LEMS analysis of the powders revealed several new mass spectral features that have not been identified previously. Offline principal component analysis and discrimination of the LEMS mass spectral measurements resulted in perfect classification of the smokeless powder with respect to manufacturer.

Quantitative Measurements of Small Molecule Mixtures Using Laser Electrospray Mass Spectrometry

Quantitative measurements of atenolol, tioconazole, tetraethylammonium bromide, and tetrabutylammonium iodide using laser electrospray mass spectrometry (LEMS) reveal monotonic signal response as a function of concentration for single analytes, two- and four-component equimolar mixtures, and two-component variable molarity mixtures. LEMS analyses of single analytes as a function of concentration were linear over ~2.5 orders of magnitude for all four analytes and displayed no sign of saturation. Corresponding electrospray ionization (ESI) measurements displayed a nonmonotonic increase as saturation occurred at higher concentrations. In contrast to the LEMS experiments, the intensity ratios from control experiments using conventional ESI-MS deviated from expected values for the equimolar mixture measurements due to ion suppression of less surface active analytes, particularly in the analysis of the four-component mixture. In the analyses of two-component nonequimolar mixtures, both techniques were able to determine the concentration ratios after adjustment with response factors although conventional ESI-MS was subject to a greater degree of saturation and ion suppression at higher analyte concentrations.

Differentiation of eight phenotypes and discovery of potential biomarkers for a single plant organ class using laser electrospray mass spectrometry and multivariate statistical analysis.

Laser electrospray mass spectrometry (LEMS) coupled with offline multivariate statistical analysis is used to discriminate eight phenotypes from a single plant organ class and to find potential biomarkers. Direct analysis of the molecules from the flower petal is enabled by interfacing intense (10(13) W/cm(2)), nonresonant, femtosecond laser vaporization at ambient pressure with electrospray ionization for postionization of the vaporized analytes. The observed mass spectral signatures allowed for the discrimination of various phenotypes using principal component analysis (PCA) and either linear discriminant analysis (LDA) or K-nearest neighbor (KNN) classifiers. Cross-validation was performed using multiple training sets to evaluate the predictive ability of the classifiers, which showed 93.7% and 96.8% overall accuracies for the LDA and KNN classifiers, respectively. Linear combinations of significant mass spectral features were extracted from the PCA loading plots, demonstrating the capability to discover potential biomarkers from the direct analysis of tissue samples.

Ambient Femtosecond Laser Vaporization and Nanosecond Laser Desorption Electrospray Ionization Mass Spectrometry

Recent investigations of ambient laser-based transfer of molecules into the gas phase for subsequent mass spectral analysis have undergone a renaissance resulting from the separation of vaporization and ionization events. Here, we seek to provide a snapshot of recent femtosecond (fs) duration laser vaporization and nanosecond (ns) duration laser desorption electrospray ionization mass spectrometry experiments. The former employs pulse durations of <100 fs to enable matrix-free laser vaporization with little or no fragmentation. When coupled to electrospray ionization, femtosecond laser vaporization provides a universal, rapid mass spectral analysis method requiring no sample workup. Remarkably, laser pulses with intensities exceeding 10(13) W cm(-2) desorb intact macromolecules, such as proteins, and even preserve the condensed phase of folded or unfolded protein structures according to the mass spectral charge state distribution, as demonstrated for cytochrome c and lysozyme. Because of the ability to vaporize and ionize multiple components from complex mixtures for subsequent analysis, near perfect classification of explosive formulations, plant tissue phenotypes, and even the identity of the manufacturer of smokeless powders can be determined by multivariate statistics. We also review the more mature field of nanosecond laser desorption for ambient mass spectrometry, covering the wide range of systems analyzed, the need for resonant absorption, and the spatial imaging of complex systems like tissue samples.

Laser Electrospray Mass Spectrometry Minimizes Ion Suppression Facilitating Quantitative Mass Spectral Response for Multicomponent Mixtures of Proteins

A comparison of the mass spectral response for myoglobin, cytochrome c, and lysozyme is presented for laser electrospray mass spectrometry (LEMS) and electrospray ionization-mass spectrometry (ESI-MS). Analysis of multicomponent protein solutions using nonresonant femtosecond (fs) laser vaporization with electrospray postionization mass spectrometry exhibited significantly reduced ion suppression effects in comparison with conventional ESI analysis, enabling quantitative measurements over 4 orders of magnitude in concentration. No significant charge reduction was observed in the LEMS experiment while the ESI measurement revealed charge reduction for myoglobin and cytochrome c as a function of increasing protein concentration. Conventional ESI-MS of each analyte from a multicomponent solution reveals that the ion signal detected for myoglobin and cytochrome c reaches a plateau and then begins to decrease with increasing protein concentration preventing quantitative analysis. The ESI mass spectral response for lysozyme from the mixture initially decreased, before increasing, with increasing multicomponent solution concentration.

Determination of inorganic ions in mineral water by gradient elution moving boundary electrophoresis

A sensitive method was developed for the determination of the major inorganic ions in commercial mineral waters using gradient elution moving boundary electrophoresis with capacitively coupled contactless conductivity detection. This application was the first to demonstrate the separation of cations and anions simultaneously using gradient elution moving boundary electrophoresis. Seven ionic analytes (calcium, chloride, magnesium, nitrate, potassium, sodium, and sulfate) were separated in less than 7 min with detection values in the low μmol/L to sub‐μmol/L range. Calculated values of the major ions in three commercial mineral waters were compared to reported values with good correlation. In another application, phosphate and arsenate were separated in less than 2 min with limits of detection of 300 and 140 nmol/L, respectively. For all standard analyses, the RSD for migration times and peak areas were under 3%.

Increasing Protein Charge State When Using Laser Electrospray Mass Spectrometry

AbstractFemtosecond (fs) laser vaporization is used to transfer cytochrome c, myoglobin, lysozyme, and ubiquitin from the condensed phase into an electrospray (ES) plume consisting of a mixture of a supercharging reagent, m-nitrobenzyl alcohol (m-NBA), and trifluoroacetic acid (TFA), acetic acid (AA), or formic acid (FA). Interaction of acid-sensitive proteins like cytochrome c and myoglobin with the highly charged ES droplets resulted in a shift to higher charge states in comparison with acid-stable proteins like lysozyme and ubiquitin. Laser electrospray mass spectrometry (LEMS) measurements showed an increase in both the average charge states (Zavg) and the charge state with maximum intensity (Zmode) for acid-sensitive proteins compared with conventional electrospray ionization mass spectrometry (ESI-MS) under equivalent solvent conditions. A marked increase in ion abundance of higher charge states was observed for LEMS in comparison with conventional electrospray for cytochrome c (ranging from 19+ to 21+ versus 13+ to 16+) and myoglobin (ranging from 19+ to 26+ versus 18+ to 21+) using an ES solution containing m-NBA and TFA. LEMS measurements as a function of electrospray flow rate yielded increasing charge states with decreasing flow rates for cytochrome c and myoglobin. Graphical Abstractᅟ

Multidimensional detection of explosives and explosive signatures via laser electrospray mass spectrometry

Nitro- and inorganic-based energetic material is vaporized at atmospheric pressure using nonresonant, 70 femtosecond laser pulses prior to electrospray post-ionization and transfer into a time-of-flight mass spectrometer for mass analysis. Measurements of a nitro-based energetic molecule, cyclotrimethylenetrinitramine (RDX), adsorbed on metal and dielectric surfaces indicate nonresonant vaporization of intact molecules, demonstrating the universality of laser electrospray mass spectrometry (LEMS) technique for explosives. In addition, RDX is analyzed at a distance of 2 meters to demonstrate the remote detection capability of LEMS. Finally, the analysis and multivariate statistical classification of inorganic-based explosives containing ammonium nitrate, chlorate, perchlorate, black powder, and an organic-based explosive is presented, further expanding the capabilities of the LEMS technique for detection of energetic materials.

High Repetition-Rate, Pulse-Burst Assisted Desorption, Electrospray Post-Ionization Mass Spectrometry

We demonstrate electrospray post-ionization mass spectrometry with an Yb fiber laser producing 500 fs, 50 μJ pulse-bursts, enabling protein, peptide and lipid identification and imaging for the pharmaceutical and biomedical realm.