EXPRESS: Landmark Publications in Analytical Atomic Spectrometry: Fundamentals and Instrumentation Development.

The almost-two-centuries history of spectrochemical analysis has generated a body of literature so vast that it has become nearly intractable for experts, much less for those wishing to enter the field. Authoritative, focused reviews help to address this problem but become so granular that the overall directions of the field are lost. This broader perspective can be provided partially by general overviews but then the thinking, experimental details, theoretical underpinnings and instrumental innovations of the original work must be sacrificed. In the present compilation, this dilemma is overcome by assembling the most impactful publications in the area of analytical atomic spectrometry. Each entry was proposed by at least one current expert in the field and supported by a narrative that justifies its inclusion. The entries were then assembled into a coherent sequence and returned to contributors for a round-robin review.

High-Throughput Nanoparticle Characterization via Glow Discharge Optical Emission Spectroscopy Elemental Mapping.

Nanoparticle (NP) characterization is critical in many fields due to the use of NPs in numerous applications. Traditional NP characterization techniques, however, are limited by low sample throughput, and few can measure the size and elemental composition. Furthermore, sample throughput limitations are compounded in elemental mapping (EM) techniques for obtaining NP spatial distribution. Glow discharge optical emission spectroscopy (GDOES) EM can provide large area maps directly and cost-effectively from solid samples within tens of seconds. Here, GDOES EM is demonstrated for the first time for NP characterization in terms of mass, elemental composition, and size/structure dimensions. The effects of GD pulsed power, pressure, and sample substrate were studied, and optimized conditions resulted in limits of detection at single pg levels. While this is not at the level of single nanoparticle sensitivity, size differentiation of Ag and Au nanoparticles was successfully demonstrated between 5 and 100 nm, while the internal dimensions of complex core-shell NPs were also identified through the optical emission changes as a function of time.

Quantitative Analysis of Exhaled Breath Collected on Filter Substrates via Low-Temperature Plasma Desorption/Ionization Mass Spectrometry.

Breath analysis has attracted increasing attention in recent years due to its great potential for disease diagnostics at early stages and for clinical drug monitoring. There are several recent examples of successful development of real-time, in vivo quantitative analysis of exhaled breath metabolites via mass spectrometry. On the other hand, current mass spectrometer accessibility limitations restrict point-of-care applications. Here now, an offline method is developed for quantitative analysis of exhaled breath collected on inexpensive filter substrates for direct desorption and ionization by using low-temperature plasma-mass spectrometry (LTP-MS). In particular, different operating conditions of the ionization source were systematically studied to optimize desorption/ionization by using glycerol, a low volatility compound. Applications with respect to propofol, γ-valprolactone, and nicotine analysis in exhaled breath are demonstrated in this study. The effects of several filter substrate properties, including filter material and pore size, on the analyte signal were characterized. Cellulose filter papers performed best with the present analytes. In addition, filters with smaller pores enabled a more efficient sample collection. Furthermore, sample-collection flow rate was determined to have a very significant effect, with slower flow rates yielding the best results. It was also found that filters loaded with sample can be successfully stored in glass vials with no observable sample loss even after 3 days. Limits of detection under optimized conditions are shown to be competitive or significantly better compared with relevant techniques and with additional benefits of cost-efficiency and sample storage capabilities.

Field-Switching Repeller Flowing Atmospheric-Pressure Afterglow Drift Tube Ion Mobility Spectrometry.

In this work, a field-switching (FS) technique is employed with a flowing atmospheric pressure afterglow (FAPA) source in drift tube ion mobility spectrometry (DTIMS). The premise is to incorporate a tip-repeller electrode as a substitute for the Bradbury-Nielsen gate (BNG) so as to overcome corresponding disadvantages of the BNG, including the gate depletion effect (GDE). The DTIMS spectra were optimized in terms of peak shape and full width by inserting an aperture at the DTIMS inlet that was used to control the neutral molecules' penetration into the separation region, thus preventing neutral-ion reactions inside. The FAPA and repeller's experimental operating conditions including drift and plasma gas flow rates, pulse injection times, repeller positioning and voltage, FAPA current, and effluent angle were optimized. Ion mobility spectra of selected compounds were captured, and the corresponding reduced mobility values were calculated and compared with the literature. The 6-fold improvements in limit of detection (LOD) compared with previous work were obtained for 2,6-DTBP and acetaminophen. The enhanced performance of the FS-FAPA-DTIMS was also investigated as a function of the GDE when compared with FAPA-DTIMS containing BNG.

Three-Dimensional Mass Spectral Imaging of Polymers Via Laser-Assisted Micro-Pyrolysis Program with Flowing Atmospheric-Pressure Afterglow Ambient Mass Spectrometry.

Herein, a novel diode laser-assisted micro-pyrolysis program (LAMP) technique is demonstrated and coupled with flowing atmospheric-pressure afterglow ambient mass spectrometry for instantaneously profiling polymers and polymer additives. Laser power modulation allows thermal separation of additives and different pyrolysis products, as shown through positive- and negative-mode high-resolution mass spectra and Kendrick mass defect plots of homopolymers, copolymers, polymer blends, and complex polymer samples. LAMP allows much faster temperature control through real-time duty cycle changes and gives significantly better spatial confinement compared to typical resistive heating pyrolysis approaches. Finally, MS imaging, with lateral and depth resolution, is demonstrated for a complex polymer pressure-sensitive adhesive tape sample.

Instantaneous Differentiation of Functional Isomers via Reactive Flowing Atmospheric Pressure Afterglow Mass Spectrometry.

Ambient mass spectrometry (AMS) allows direct desorption and ionization of analytes in real time with minimal-to-no sample preparation. However, it may present inadequate capabilities for differentiating isomers. Here, a reactive flowing atmospheric-pressure afterglow (reactive-FAPA) AMS source is developed for rapid isomer differentiation by derivatization of analytes in real time. The effects of the reactive-FAPA operating conditions on the reagent and product ions were studied and optimized for highly volatile and non-volatile model compounds with different carbonyl functional groups. In addition, two functional isomers of valproic acid (VPA) metabolites, 4-ene VPA and γ-valprolactone, are successfully differentiated for the first time by incorporating methylamine (MA) reagent vapor into the plasma effluent used for desorption/ionization. Reactive-FAPAMS for 4-ene VPA shows only detectable peaks of the protonated acylation product [M + MA-H2O + H]+, while for γ-valprolactone, it shows detectable peaks for both protonated acylation product [M + MA-H2O + H]+ and protonated intermediate [M + MA + H]+. A method for quantitative characterization of mixtures of 4-ene VPA and γ-valprolactone is also developed and validated. In addition, reactive-FAPAMS also shows better detection sensitivity compared to nonreactive-FAPAMS for some larger analyte types, such as UV filters and steroids. The limit of detection (LOD) of pregnenolone acetate in reactive-FAPAMS is 310 ng/mL, which is about 10 times better than its LOD in nonreactive-FAPA.

Flowing atmospheric-pressure afterglow drift tube ion mobility spectrometry.

In this work, the flowing atmospheric-pressure afterglow (FAPA) ambient desorption/ionization source has been coupled with stand-alone Drift Tube Ion Mobility Spectrometry (DTIMS) for the first time. A tip repeller electrode, modified to allow higher bias potential still below the Townsend's breakdown, was implemented at the FAPA/DTIMS interface to overcome the opposing potentials and facilitate ion transmission. The effect of the lab-built DTIMS and FAPA's operating conditions (such as plasma voltage, current, gas flow rate, repeller's potential and positioning, FAPA orientation, etc.) on the signal of selected analytes was studied, for both gas-phase injection and desorption. The FAPA reactant ion peak (RIP) reduced mobility coefficient (K0) corresponds to protonated water clusters (H2O)nH+. The FAPA-DTIMS spectra of several selected compounds showed that their K0 agrees with literature values. Moreover, quantitative characterization of acetaminophen and 2,6-di-tert-butylpyridine (2,6-DTBP) based on desorption or gas-phase injection yield limits of detection (LODs) of 0.03 µg and 18 ppb, respectively.

Laser assisted sampling vs direct desorption flowing atmospheric pressure afterglow mass spectrometry of complex polymer samples: Forensic implications for pressure sensitive tape chemical analysis.

Flowing atmospheric pressure afterglow (FAPA) mass spectrometry (MS) is an easy-to-use, cost-effective, and potentially portable technique that allows direct desorption/ionization from samples with little-to-no sample preparation for real-time chemical analysis. However, it has limitations regarding analytes with low desorption efficiency, such as polymers. Here, laser assisted sampling (LAS) is developed and coupled to FAPA MS to allow access to a wider range of chemical information from polymer samples. This is achieved through laser-induced pyrolysis conditions that provide a much higher degree of spatio-temporal control compared to typical pyrolysis techniques. LAS FAPA MS, together with direct desorption FAPA MS, is implemented on pressure sensitive adhesive (PSA) tape samples, which are often found at crime scenes and recovered as forensic evidence. Comparative PSA tape examination is typically performed to assess any differences in the comparison of unknown and known samples and provide an evidentiary association between suspects and crime scenes in forensic applications. PSA tape samples from several manufacturers of duct, masking, and electrical tape were analyzed from the adhesive and backing side. Direct desorption FAPA provides top-surface selectivity and the tape mass spectra are dominated by more peaks at lower m/z, many of which correspond to polymer additives. LAS gives access to sampling from all of the tape layers and the FAPA mass spectra is extended to higher m/z, while polymer fragmentation patterns are evident. Principal components analysis (PCA) was implemented to assess the ability of each technique to distinguish and categorize identified tape classes within the sampled population. The complementary nature of the resulting mass spectra from direct desorption vs LAS FAPA was evident from the PCA as different tape brands sub-sets were discriminated by each technique. The differentiation obtained by combining both methods is already competitive, or better, than conventional techniques, with the additional benefits of AMS.

Low-Temperature Plasma Probe Mass Spectrometry for Analytes Separated on Thin-Layer Chromatography Plates: Direct vs Laser Assisted Desorption.

Thin-layer chromatography (TLC) is a widespread technique because it allows fast, simple, and inexpensive analyte separations. In addition, direct analysis of the compounds separated on TLC plates via mass spectrometry (MS) has been shown to provide high sensitivity and selectivity while avoiding time-consuming sample extraction protocols. Here, direct desorption low-temperature plasma-mass spectrometry (LTP-MS) as well as diode laser assisted desorption (LD) LTP-MS are studied for direct spatially resolved analysis of compounds from TLC plates. Qualitative and quantitative characterization of amino acids, pharmaceuticals, and structural isomers were performed. The nature of the TLC plate stationary phase was found to have a significant influence, together with the analyte's characteristics, on the desorption efficiency. Tandem MS is shown to greatly improve the limits of detection (LODs). Direct desorption LTP-MS, without external thermal assisted desorption, demonstrates its best performance with cellulose TLC plates (LODs, 0.01 ng/mm2 to 2.55 ng/mm2) and restricted performance with normal-phase (NP) TLC plates (several analytes without observable signal). LD LTP-MS, with systematic optimization of irradiance and focal point diameter, is shown to overcome the direct-desorption limitations and reach significantly improved LODs with NP TLC plates (up to ×1000 better). In addition, a wide-ranging characterization of amino acid analytical figures of merit with LD LTP-MS shows that LODs from 84 pg/mm2 down to 0.3 pg/mm2 are achieved on NP TLC plates.

Real-Time Quantitative Analysis of Valproic Acid in Exhaled Breath by Low Temperature Plasma Ionization Mass Spectrometry.

Real-time analysis of exhaled human breath is a rapidly growing field in analytical science and has great potential for rapid and noninvasive clinical diagnosis and drug monitoring. In the present study, an LTP-MS method was developed for real-time, in-vivo and quantitative analysis of γ-valprolactone, a metabolite of valproic acid (VPA), in exhaled breath without any sample pretreatment. In particular, the effect of working conditions and geometry of the LTP source on the ions of interest, protonated molecular ion at m/z 143 and ammonium adduct ion at m/z 160, were systematically characterized. Tandem mass spectrometry (MS/MS) with collision-induced dissociation (CID) was carried out in order to identify γ-valprolactone molecular ions (m/z 143), and the key fragment ion (m/z 97) was used for quantitation. In addition, the fragmentation of ammonium adduct ions to protonated molecular ions was performed in-source to improve the signal-to-noise ratio. At optimum conditions, signal reproducibility with an RSD of 8% was achieved. The concentration of γ-valprolactone in exhaled breath was determined for the first time to be 4.83 (±0.32) ng/L by using standard addition method. Also, a calibration curve was obtained with a linear range from 0.7 to 22.5 ng/L, and the limit of detection was 0.18 ng/L for γ-valprolactone in standard gas samples. Our results show that LTP-MS is a powerful analytical platform with high sensitivity for quantitative analysis of volatile organic compounds in human breath, and can have potential applications in pharmacokinetics or for patient monitoring and treatment. Graphical Abstract ᅟ.

Use of radiofrequency power to enable glow discharge optical emission spectroscopy ultrafast elemental mapping of combinatorial libraries with nonconductive components: nitrogen-based materials.

Combinatorial chemistry and high-throughput techniques are an efficient way of exploring optimal values of elemental composition. Optimal composition can result in high performance in a sequence of material synthesis and characterization. Materials combinatorial libraries are typically encountered in the form of a thin film composition gradient which is produced by simultaneous material deposition on a substrate from two or more sources that are spatially separated and chemically different. Fast spatially resolved techniques are needed to characterize structure, composition, and relevant properties of these combinatorial screening samples. In this work, the capability of a glow discharge optical emission spectroscopy (GD-OES) elemental mapping system is extended to nitrogen-based combinatorial libraries with nonconductive components through the use of pulsed radiofrequency power. The effects of operating parameters of the glow discharge and detection system on the achievable spatial resolution were investigated as it is the first time that an rf source is coupled to a setup featuring a push-broom hyperspectral imaging system and a restrictive anode tube GD source. Spatial-resolution optimized conditions were then used to characterize an aluminum nitride/chromium nitride thin-film composition spread. Qualitative elemental maps could be obtained within 16.8 s, orders of magnitude faster than typical techniques. The use of certified reference materials allowed quantitative elemental analysis maps to be extracted from the emission intensity images. Moreover, the quantitative procedure allowed correcting for the inherent emission intensity inhomogeneity in GD-OES. The results are compared to quantitative depth profiles obtained with a commercial GD-OES instrument.

Real-time, in vivo monitoring and pharmacokinetics of valproic acid via a novel biomarker in exhaled breath.

Extractive electrospray ionization mass spectrometry is shown to allow real-time, in vivo drug monitoring and pharmacokinetic measurement in a non-invasive, pain-free manner as demonstrated by the mass spectral measurement of a novel exhaled breath biomarker for valproic acid, a medication used to control epilepsy.

Simultaneous sampling of volatile and non-volatile analytes in beer for fast fingerprinting by extractive electrospray ionization mass spectrometry.

By gently bubbling nitrogen gas through beer, an effervescent beverage, both volatile and non-volatile compounds can be simultaneously sampled in the form of aerosol. This allows for fast (within seconds) fingerprinting by extractive electrospray ionization mass spectrometry (EESI-MS) in both negative and positive ion mode, without the need for any sample pre-treatment such as degassing and dilution. Trace analytes such as volatile esters (e.g., ethyl acetate and isoamyl acetate), free fatty acids (e.g., caproic acid, caprylic acid, and capric acid), semi/non-volatile organic/inorganic acids (e.g., lactic acid), and various amino acids, commonly present in beer at the low parts per million or at sub-ppm levels, were detected and identified based on tandem MS data. Furthermore, the appearance of solvent cluster ions in the mass spectra gives insight into the sampling and ionization mechanisms: aerosol droplets containing semi/non-volatile substances are thought to be generated via bubble bursting at the surface of the liquid; these neutral aerosol droplets then collide with the charged primary electrospray ionization droplets, followed by analyte extraction, desolvation, ionization, and MS detection. With principal component analysis, several beer samples were successfully differentiated. Therefore, the present study successfully extends the applicability of EESI-MS to the direct analysis of complex liquid samples with high gas content.

Material ejection and redeposition following atmospheric pressure near-field laser ablation on molecular solids.

Near-field laser ablation (NF-LA) coupled with mass spectrometry (MS) is very promising for highly spatially resolved chemical analyses on various substrates at atmospheric pressure, for example, in materials and life science applications. Although nanoscale sample craters can be produced routinely, no molecular mass spectra of ablated material from craters of

What can we learn from ambient ionization techniques?

Ambient mass spectrometry-mass spectrometric analysis with no or minimal effort for sample preparation-has experienced a very rapid development during the last 5 years, with many different methods now available for ionization. Here, we review its range of applications, the hurdles encountered for its quantitative use, and the proposed mechanisms for ion formation. Clearly, more effort needs to be put into investigation of matrix effects, into defining representative sampling of heterogeneous materials, and into understanding and controlling the underlying ionization mechanisms. Finally, we propose a concept to reduce the number of different acronyms describing very similar embodiments of ambient mass spectrometry.

Exploring fluorescence and fragmentation of ions produced by electrospray ionization in ultrahigh vacuum.

Fluorescence spectroscopy and mass spectrometry have been extensively used for characterization of biomaterials, but usually separately. An instrument combining fluorescence spectroscopy and Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS) has been developed to explore both fluorescence and mass spectrometric behavior of ions produced by electrospray ionization (ESI) in ultra high vacuum (<5 x 10(-9) mbar). Using rhodamine 6G (R6G) as a sample, the instrument was systematically characterized. Gas-phase fluorescence and mass spectral signal of the same ion population are detected immediately after each other. Effects of gas pressure, ion density, and excitation laser power on the fluorescence signal intensity and mass spectral fragmentation patterns are discussed. Characteristic times of ion photodissociation in ultra high vacuum were recorded for different irradiation powers. Photofragmentation patterns of rhodamine 6G ions in the Penning trap of an FTICR spectrometer obtained by photoinduced dissociation (PID) with visible light and sustained off-resonance irradiation collision-induced dissociation (SORI-CID) were compared. The lowest energy dissociation fragment of rhodamine 6G ions was identified by relating PID patterns of rhodamine 6G and rhodamine 575 dyes at various irradiation powers. The unique instrument provides a powerful platform for probing the intramolecular relaxation mechanisms of nonsolvated ions when interacting with light, which is of great fundamental interest for better understanding of their physical and chemical properties.

Rapid detection of melamine in untreated milk and wheat gluten by ultrasound-assisted extractive electrospray ionization mass spectrometry (EESI-MS).

A novel method based on ultrasound-assisted EESI-MS has been developed and applied to rapidly detect the presence of melamine in raw milk, wheat gluten and milk powder with no or minor sample pre-treatment; the high sample throughput and figures of merit make it specially useful for screening melamine levels well below the current safety limit in various food matrices.

Detection of diethyl phthalate in perfumes by extractive electrospray ionization mass spectrometry.

Recent findings suggest that long-term exposure to diethyl phthalate (DEP), one of the widely used phthalate esters, can lead to serious health problems. Most perfumes contain non-negligible amounts of DEP. Rapid and sensitive detection of DEP in perfumes is thus of increasing importance. A novel procedure based on extractive electrospray ionization mass spectrometry (EESI-MS) has been developed for fast detection and identification of DEP in perfumes without the need for any sample pretreatment. The limit of determination for DEP in perfume was less than 100 ppb using tandem mass spectrometry on a commercial quadrupole time-of-flight mass spectrometer. The dynamic range of this method was about 4 orders of magnitude. A single sample analysis was completed within a few seconds, providing a rapid way to obtain semiquantitative information on the DEP content in perfumes. This study shows that both volatile and nonvolatile analytes (e.g., amino acids) in liquids can be directly sampled by neutral desorption, providing a convenient way for high-throughput screening of target compounds using EESI-MS.

Fast polymer fingerprinting using flowing afterglow atmospheric pressure glow discharge mass spectrometry.

Flowing afterglow atmospheric pressure glow discharge mass spectrometry (FA-APGD-MS) was used to interrogate different polymer species such as biopolymers, synthetic homo- and co-polymers. The main advantages of FA-APGD-MS for polymer samples include speed (<30 s per sample) and analysis at atmospheric pressures. Moreover, there are essentially no restrictions as to the kind of polymer sample that can be analyzed because FA-APGD-MS can deal with liquid and solid (soluble or insoluble) bulk polymers and granulates, irrespective of their conductivity, without requiring any sample preparation prior to analysis. We will discuss the mechanism of ion formation as well as the limitation of the accessible mass range (m/z < 500) in view of what type of information can be gained from the mass spectra obtained. Monomer units and some fragments were detected for homopolymers, e.g.cis-polyisoprene (IR), poly(ethylene glycol) (PEG), poly(ethylene terephthalate) (PET), which allowed identification of the polymer composition. The mass spectra obtained were further processed using principal component analysis (PCA) for a better visualization and assessing of mass-spectral reproducibility. Combination with PCA even allowed differentiation of pectin, amylopectin, and cellulose, chemically very similar polysaccharides whose characteristic differences lie in the nature of the glycosidic linkage. Finally, we were able to detect and identify phthalate plasticizers, bis(2-ethylhexyl) phthalate (BEHP) and dibutyl phthalate (DBP), present in poly(vinyl chloride)-based food wraps.