Manipulation of Gaseous Ions with Acoustic Fields at Atmospheric Pressure.

The ability to controllably move gaseous ions is an essential aspect of ion-based spectrometry (e.g., mass spectrometry and ion mobility spectrometry) as well as materials processing. At higher pressures, ion motion is largely governed by diffusion and multiple collisions with neutral gas molecules. Thus, high-pressure ion optics based on electrostatics require large fields, radio frequency drives, complicated geometries, and/or partially transmissive grids that become contaminated. Here, we demonstrate that low-power standing acoustic waves can be used to guide, block, focus, and separate beams of ions akin to electrostatic ion optics. Ions preferentially travel through the static-pressure regions ("nodes") while neutral gas does not appear to be impacted by the acoustic field structure and continues along a straight trajectory. This acoustic ion manipulation (AIM) approach has broad implications for ion manipulation techniques at high pressure, while expanding our fundamental understanding of the behavior of ions in gases.

Characterization of a Low-Temperature Plasma (LTP) Ambient Ionization Source Using Temporally Resolved Monochromatic Imaging Spectrometry.

The low-temperature plasma (LTP) probe is a common plasma-based source used for ambient desorption-ionization mass spectrometry (MS). While the LTP probe has been characterized in detail with MS, relatively few studies have used optical spectroscopy. In this paper, two-dimensional (2D) imaging at selected wavelengths is used to visualize important species in the LTP plasma jet. First, 2D steady-state images of the LTP plume for N2+ (391.2 nm), He I (706.5 nm), and N2 (337.1 nm) emissions were recorded under selected plasma conditions. Second, time-resolved 2D emission maps of radiative species in the LTP plasma jet were recorded through the use of a 200 ns detection gate and varying gate delays with respect to the LTP trigger pulse. Emission from He I, N2+, and N2 in the plasma jet region was found to show a transient behavior (often referred to as plasma bullets) lasting only a few microseconds. The N2+ and He I maps were highly correlated in spatial and temporal structure. Further, emission from N2 showed two maxima in time, one before and one after the maximum emission for N2+ and He I, due to an initial electronic excitation wave and ion-electron recombination, respectively. Third, the interaction of the LTP probe with a sample substrate and an electrically grounded metallic needle was studied. Emission from a fluorophore on the sample substrate showed an initial photon-induced excitation from plasma-generated photons followed by electronic excitation by other plasma species. The presence of a grounded needle near the plasma jet significantly extended the plasma jet lifetime and also generated a long-lived corona discharge on the needle. The effect of LTP operating parameters on emission spectra was correlated with mass-spectral results including reagent-ion signals. Lastly, five movies provide a side-by-side comparison of the temporal behavior of emitting species and insights into the interactions of the emission clouds with a sample surface as well as an external needle. Temporally and spatially resolved imaging provided insights into important processes in the LTP plasma jet, which will help improve analyte ion sampling in LTP-MS.

Unsupervised Reconstruction of Analyte-Specific Mass Spectra Based on Time-Domain Morphology with a Modified Cross-Correlation Approach.

Concomitant species that appear at the same or very similar times in a mass-spectral analysis can clutter a spectrum because of the coexistence of many analyte-related ions (e.g., molecular ions, adducts, fragments). One method to extract ions stemming from the same origin is to exploit the chemical information encoded in the time domain, where the individual temporal appearances inside the complex structures of chronograms or chromatograms differ with respect to analytes. By grouping ions with very similar or identical time-domain structures, single-component mass spectra can be reconstructed, which are much easier to interpret and are library-searchable. While many other approaches address similar objectives through the Pearson's correlation coefficient, we explore an alternative method based on a modified cross-correlation algorithm to compute a metric that describes the degree of similarity between features inside any two ion chronograms. Furthermore, an automatic workflow was devised to be capable of categorizing thousands of mass-spectral peaks into different groups within a few seconds. This approach was tested with direct mass-spectrometric analyses as well as with a simple, fast, and poorly resolved LC-MS analysis. Single-component mass spectra were extracted in both cases and were identified based on accurate mass and a mass-spectral library search.

MODERN PLASMA-BASED DESORPTION/IONIZATION: FROM ATOMS AND MOLECULES TO CHEMICAL SYNTHESIS.

Since the first mass spectrometry (MS) experiments were conducted by Thomson and Aston, plasmas have been used as ionization sources. Historically, plasma ion sources were used for these experiments because they were one of the few known sources of gas-phase ions at the time and they were relatively simple to setup and operate. Since then, developments in plasma ionization have continued to inform and motivate advances in other areas of MS. For example, plasma-desorption MS demonstrated ionization of large peptides and polymers more than 10 years before the first descriptions of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). As a result, significant effort was placed on development of ionization approaches, mass analysis, and detection approaches for very large molecules: even before the advent of ESI and MALDI. Since then, new analytical challenges and opportunities in plasma ionization have arisen. In this review, the emerging trends in plasma-based ionization for several areas of MS will be discussed, including molecular ionization, elemental ionization, hybrid elemental and molecular ion sources, and unique chemical transformations. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.

Cooperative Heteroligand Interaction with G-Quadruplexes Shows Evidence of Allosteric Binding.

Although allosteric binding of small molecules is commonplace in protein structures, it is rather rare in DNA species such as G-quadruplexes. By using CD melting, here, we found binding of the small-molecule ligands PDS and L2H2-6OTD to the telomeric DNA G-quadruplex was cooperative. Mass spectrometry indicated a 1:1:1 ratio in the ternary binding complex of the telomeric G-quadruplex, PDS, and L2H2-6OTD. Compared to the binding of each individual ligand to the G-quadruplex, single-molecule mechanical unfolding assays revealed a significantly decreased dissociation constant when one ligand is evaluated in the presence of another. This demonstrates that cooperative binding of PDS and L2H2-6OTD to the G-quadruplex is allosteric, which is also supported by the mass spectra data that indicated the ejection of coordinated sodium ions upon binding of the heteroligands to the G-quadruplex. The unprecedented observation of the allosteric ligand binding to higher-ordered structures of DNA may help to design more effective ligands to target non-B DNA species involved in many critical cellular processes.

Plasma-Based Ambient Desorption/Ionization Mass Spectrometry for the Analysis of Liquid Crystals Employed in Display Devices.

Liquid-crystal displays (LCDs) are the most frequently used display technology worldwide these days. Due to the rather complex manufacturing process and purity requirements for the chemicals used, quality control and display failure analysis are important analytical tasks. Currently, the state-of-the-art techniques (e.g., high-performance liquid chromatography (HPLC), gas chromatography (GC) coupled to mass spectrometry (MS), time-of-flight secondary ion mass spectrometry (TOF-SIMS), or high-resolution microscopy) are costly and time-consuming. Hence, a new pathway to precisely analyze liquid-crystalline materials and LCDs in their native state is reported. A new approach for direct analysis via plasma-based ambient desorption/ionization mass spectrometry (ADI-MS) offers an inexpensive and faster alternative. In this study, direct analysis in real time (DART), the low-temperature plasma (LTP) probe, and flowing atmospheric-pressure afterglow (FAPA) ADI sources coupled to high-resolution mass spectrometry (HR-MS) are compared based on their capabilities and performance for liquid-crystal analysis. These sources enable direct analyte desorption from a sample surface at ambient conditions and ionize the vaporized analyte molecules in a subsequent step. Primarily, the ionization capabilities of the three ADI sources are compared for individual liquid-crystal standards, mixtures of liquid crystals (LCs), and complex liquid crystal/additive mixtures applied in commercially available LCDs. Furthermore, direct surface analysis from a glass substrate is also performed with ADI-MS to compare their applicability to this type of sample matrix.

Automatic Analyte-Ion Recognition and Background Removal for Ambient Mass-Spectrometric Data Based on Cross-Correlation.

Ambient mass spectrometry is a powerful approach for rapid, high-throughput, and direct sample analysis. Due to the open-air desorption and ionization processes, random fluctuations of ambient conditions can lead to large variances in mass-spectral signals over time. The mass-spectral data also can be further complicated due to multiple analytes present in the sample, background-ion signals stemming from the desorption/ionization source itself, and other laboratory-specific conditions (e.g., ambient laboratory air, nearby hardware). Thus, background removal and analyte-ion recognition can be quite difficult, particularly in non-targeted analyses. Here, we demonstrate the use of a cross-correlation-based approach to exploit chemical information encoded in the time domain to group/categorize mass-spectral peaks from a single analysis dataset. Ions that originate from ambient (or other) background species were readily flagged and removed from spectra; the result was a decrease in mass-spectral complexity by over 70% due to the removal of these background ions. Meanwhile, analyte ions were differentiated and categorized based on their time-domain profiles. With sufficient mass resolving-power and mass-spectral acquisition rate, isolated mass spectra containing ions from the same species in a sample could be extracted, leading to a reduction in mass-spectral complexity by more than 98% in some cases. The cross-correlation approach was tested with different ionization sources as well as reproducible and irreproducible sample introduction. Software built in-house enabled fully automated data processing, which can be performed within a few seconds. Ultimately, this approach provides an additional dimension of analyte separation in ambient mass-spectrometric analyses with information that is already recorded throughout the analysis.

Ambient desorption/ionization mass spectrometry: evolution from rapid qualitative screening to accurate quantification tool.

In this article, some recent trends and developments in ambient desorption/ionization mass spectrometry (ADI-MS) are reviewed, with a special focus on quantitative analyses with direct, open-air sampling. Accurate quantification with ADI-MS is still not routinely performed, but this aspect is considered of utmost importance for the advancement of the field. In fact, several research groups are devoted to the development of novel and optimized ADI-MS approaches. Some key trends include novel sample introduction strategies for improved reproducibility, tailored sample preparation protocols for removing the matrix and matrix effects, and multimode ionization sources. In addition, there is significant interest in quantitative mass spectrometry imaging. Graphical abstract Conceptual diagram of the ambient desorption/ionization mass spectrometry approach with different desorption/ionization probes.

Nanoparticles of metal-organic cages designed to encapsulate platinum-based anticancer agents.

We present a novel design to use metal-organic cages (MOCs) to encapsulate Pt-based anticancer agents for delivery. A fluorescein-conjugated Pt(iv) prodrug of cisplatin is developed for its encapsulation in a cationic MOC via host-guest interactions, which then forms drug-loaded nanoparticles with an anionic polymer.

Formation of Pyrylium from Aromatic Systems with a Helium:Oxygen Flowing Atmospheric Pressure Afterglow (FAPA) Plasma Source.

The effects of oxygen addition on a helium-based flowing atmospheric pressure afterglow (FAPA) ionization source are explored. Small amounts of oxygen doped into the helium discharge gas resulted in an increase in abundance of protonated water clusters by at least three times. A corresponding increase in protonated analyte signal was also observed for small polar analytes, such as methanol and acetone. Meanwhile, most other reagent ions (e.g., O2+·, NO+, etc.) significantly decrease in abundance with even 0.1% v/v oxygen in the discharge gas. Interestingly, when analytes that contained aromatic constituents were subjected to a He:O2-FAPA, a unique (M + 3)+ ion resulted, while molecular or protonated molecular ions were rarely detected. Exact-mass measurements revealed that these (M + 3)+ ions correspond to (M - CH + O)+, with the most likely structure being pyrylium. Presence of pyrylium-based ions was further confirmed by tandem mass spectrometry of the (M + 3)+ ion compared with that of a commercially available salt. Lastly, rapid and efficient production of pyrylium in the gas phase was used to convert benzene into pyridine. Though this pyrylium-formation reaction has not been shown before, the reaction is rapid and efficient. Potential reactant species, which could lead to pyrylium formation, were determined from reagent-ion mass spectra. Thermodynamic evaluation of reaction pathways was aided by calculation of the formation enthalpy for pyrylium, which was found to be 689.8 kJ/mol. Based on these results, we propose that this reaction is initiated by ionized ozone (O3+·), proceeds similarly to ozonolysis, and results in the neutral loss of the stable CHO2· radical. Graphical Abstract ᅟ.

Atmospheric-pressure solution-cathode glow discharge: A versatile ion source for atomic and molecular mass spectrometry.

An atmospheric-pressure solution-cathode glow discharge (SCGD) has been evaluated as an ion source for atomic, molecular, and ambient desorption/ionization mass spectrometry. The SCGD consists of a direct-current plasma, supported in the ambient air in the absence of gas flows, and sustained upon the surface of a flowing liquid cathode. Analytes introduced in the flowing liquid, as an ambient gas, or as a solid held near the plasma are vaporized and ionized by interactions within or near the discharge. Introduction of acidic solutions containing metal salts produced bare elemental ions as well as H2O, OH- and NO3- adducts. Detection limits for these elemental species ranged from 0.1 to 4 ppb, working curves spanned more than 4 orders of linear dynamic range, and precision varied between 5 and 16% relative standard deviation. Small organic molecules were also efficiently ionized from solution, and both the intact molecular ion and fragments were observed in the resulting SCGD mass spectra. Fragmentation of molecular species was found to be tunable; high discharge currents led to harder ionization, while low discharge currents produced stronger molecular-ion signals. Ambient gases and solids, desorbed by the plasma from a glass probe, were also readily ionized by the SCGD. Indeed, strong analyte signals were obtained from solid samples placed at least 2 cm from the plasma. These findings indicate that the SCGD might be useful also for ambient desorption/ionization mass spectrometry. Combined with earlier results that showed the SCGD is useful for ionization of labile biomolecules, the results here indicate that the SCGD is a highly versatile ion source capable of providing both elemental and molecular mass-spectral information.

Kinetic studies on the reaction of cob(II)alamin with hypochlorous acid: Evidence for one electron oxidation of the metal center and corrin ring destruction.

Kinetic and mechanistic studies on the reaction of a major intracellular vitamin B12 form, cob(II)alamin (Cbl(II)), with hypochlorous acid/hypochlorite (HOCl/OCl-) have been carried out. Cbl(II) (Co(II)) is rapidly oxidized by HOCl to predominately aquacobalamin/hydroxycobalamin (Cbl(III), Co(III)) with a second-order rate constant of 2.4×107M-1s-1 (25.0°C). The stoichiometry of the reaction is 1:1. UHPLC/HRMS analysis of the product mixture of the reaction of Cbl(II) with 0.9mol equiv. HOCl provides support for HOCl being initially reduced to Cl and subsequent H atom abstraction from the corrin macrocycle occurring, resulting in small amounts of corrinoid species with two or four H atoms fewer than the parent cobalamin. Upon the addition of excess (H)OCl further slower reactions are observed. Finally, SDS-PAGE experiments show that HOCl-induced damage to bovine serum albumin does not occur in the presence of Cbl(II), providing support for Cbl(II) being an efficient HOCl trapping agent.

Tunable Ionization Modes of a Flowing Atmospheric-Pressure Afterglow (FAPA) Ambient Ionization Source.

Plasma-based ambient desorption/ionization sources are versatile in that they enable direct ionization of gaseous samples as well as desorption/ionization of analytes from liquid and solid samples. However, ionization matrix effects, caused by competitive ionization processes, can worsen sensitivity or even inhibit detection all together. The present study is focused on expanding the analytical capabilities of the flowing atmospheric-pressure afterglow (FAPA) source by exploring additional types of ionization chemistry. Specifically, it was found that the abundance and type of reagent ions produced by the FAPA source and, thus, the corresponding ionization pathways of analytes, can be altered by changing the source working conditions. High abundance of proton-transfer reagent ions was observed with relatively high gas flow rates and low discharge currents. Conversely, charge-transfer reagent species were most abundant at low gas flows and high discharge currents. A rather nonpolar model analyte, biphenyl, was found to significantly change ionization pathway based on source operating parameters. Different analyte ions (e.g., MH(+) via proton-transfer and M(+.) via charge-transfer) were formed under unique operating parameters demonstrating two different operating regimes. These tunable ionization modes of the FAPA were used to enable or enhance detection of analytes which traditionally exhibit low-sensitivity in plasma-based ADI-MS analyses. In one example, 2,2'-dichloroquaterphenyl was detected under charge-transfer FAPA conditions, which were difficult or impossible to detect with proton-transfer FAPA or direct analysis in real-time (DART). Overall, this unique mode of operation increases the number and range of detectable analytes and has the potential to lessen ionization matrix effects in ADI-MS analyses.

Atmospheric-pressure ionization and fragmentation of peptides by solution-cathode glow discharge.

Modern "-omics" (e.g., proteomics, glycomics, metabolomics, etc.) analyses rely heavily on electrospray ionization and tandem mass spectrometry to determine the structural identity of target species. Unfortunately, these methods are limited to specialized mass spectrometry instrumentation. Here, a novel approach is described that enables ionization and controlled, tunable fragmentation of peptides at atmospheric pressure. In the new source, a direct-current plasma is sustained between a tapered metal rod and a flowing sample-containing solution. As the liquid stream contacts the electrical discharge, peptides from the solution are volatilized, ionized, and fragmented. At high discharge currents (e.g., 70 mA), electrospray-like spectra are observed, dominated by singly and doubly protonated molecular ions. At lower currents (35 mA), many peptides exhibit extensive fragmentation, with a-, b-, c-, x-, and y-type ion series present as well as complex fragments, such as d-type ions, not previously observed with atmospheric-pressure dissociation. Though the mechanism of fragmentation is currently unclear, observations indicate it could result from the interaction of peptides with gas-phase radicals or ultraviolet radiation generated within the plasma.

Antiferromagnetically Coupled Dimeric Dodecacopper Supramolecular Architectures of Macrocyclic Ligands with a Symmetrical µ6-BO3(3-) Central Moiety.

Reactions between 2,6-diformyl-4-alkyl(R)-phenol (R = CH3 or C(CH3)3) and 1,3-diamino-2-hydroxypropane (1,3-DAP) in the presence of copper(II) salts (Cu(BF4)2·6H2O, Cu(ClO4)2·6H2O/H3BO3/Ar) and triethylamine (TEA) in a single pot result in self-assembly of dimeric dodecacopper supramolecular architectures of 30-membered hexatopic macrocyclic ligands (H6L4 and H6L5) with unique and fascinating structures having the BO3(3-) anion as the central species bonded to all six copper centers in a symmetrical fashion (µ6-BO3(3-)). A number of closely related macrocyclic hexacopper complexes are reported: {[Cu6(L4)(µ6-BO3)(µ-H2O)(C3H7NO)2(BF4)][BF4]2·3C3H7NO}2 (1) (DMF = C3H7NO), {[Cu6(L4)(µ6-BO3)(µ-C3H7NO)3][ClO4]3·3C3H7NO}2 (2), {[Cu6(L5)(µ6-BO3)(µ-OH)(H2O)3(C3H7NO)][BF4]2·6C3H7NO·4C2H5OH·2H2O}2 (3), {[Cu6(L5)(µ6-BO3)(µ-CH3OH)(CH3OH)2][ClO4]3·10H2O}2 (4), and {[Cu6(L5)(µ6-BO3)(µ-CH3CO2)(µ-CH3O)(CH3OH)][BF4]·13CH3OH·8H2O}2 (5). A polymeric side product {[Cu2(H2L2)(CH3OH)(BF4)][BF4]}n (6), involving a 2 + 2 macrocyclic ligand, was also isolated and structurally characterized. Complex 6 involves dinuclear copper(II) units linked through BF4(-) anions to form a novel 1D single-chain polymeric coordination compound. This appears to be the first report in which a central BO3(3-) species is linked to six copper(II) ions held together by a single macrocyclic ligand through three µ1,1-O(BO3(3-)) and three µ1,3-O(BO3(3-)) bridges. In complexes 1-5 the BO3(3-) is present in the center of the macrocyclic cavity and is bonded to all six metal centers arranged in a benzene-like hexagonal array. In the hexagonal array there are alternate double (µ-alkoxide and µ1,3-O(BO3(3-))) and (µ-phenoxide and µ1,1-O(BO3(3-))) bridges between the Cu(II) centers. The symmetrical hexa-bridging nature of µ6-BO3(3-) is unprecedented in transition metal complex chemistry, and along with alkoxide and phenoxide bridges in the equatorial plane provides effective pathways for an overall antiferromagnetic exchange interaction between six copper(II) centers. In 1, 3, and 5 the BO3(3-) moiety is produced in one step (synthetic) by an unusual copper(II)-macrocycle complex catalyzed hydrolysis of BF4(-) ion in methanol. In 2 and 4 the central species (BO3(3-)) comes from boric acid (H3BO3) which is added to reaction mixture of Cu(ClO4)2/H6L4/H6L5 under inert conditions to confirm the identity of the central species.

Pulse radiolysis and ultra-high-performance liquid chromatography/high-resolution mass spectrometry studies on the reactions of the carbonate radical with vitamin B12 derivatives.

The reactions of the carbonate radical anion (CO3 (.) (-) ) with vitamin B12 derivatives were studied by pulse radiolysis. The carbonate radical anion directly oxidizes the metal center of cob(II)alamin quantitively to give hydroxycobalamin, with a bimolecular rate constant of 2.0×10(9) M(-1) s(-1) . The reaction of CO3 (.) (-) with hydroxycobalamin proceeds in two steps. The second-order rate constant for the first reaction is 4.3×10(8) M(-1) s(-1) . The rate of the second reaction is independent of the hydroxycobalamin concentration and is approximately 3.0×10(3) s(-1) . Evidence for formation of corrinoid complexes differing from cobalamin by the abstraction of two or four hydrogen atoms from the corrin macrocycle and lactone ring formation has been obtained by ultra-high-performance liquid chromatography/high-resolution mass spectrometry (UHPLC/HRMS). A mechanism is proposed in which abstraction of a hydrogen atom by CO3 (.) (-) from a carbon atom not involved in the π conjugation system of the corrin occurs in the first step, resulting in formation of a Co(III) C-centered radical that undergoes rapid intramolecular electron transfer to form the corresponding Co(II) carbocation complex for about 50 % of these complexes. Subsequent competing pathways lead to formation of corrinoid complexes with two fewer hydrogen atoms and lactone derivatives of B12 . Our results demonstrate the potential of UHPLC combined with HRMS in the separation and identification of tetrapyrrole macrocycles with minor modifications from their parent molecule.

Plasma-based ambient desorption/ionization mass spectrometry: state-of-the-art in qualitative and quantitative analysis.

Ambient desorption/ionization mass spectrometry (ADI-MS) aims to enable direct analysis of gaseous, liquid, and/or solid samples under ambient conditions. In ADI-MS, different types of desorption/ionization sources are classified according to their basic method of operation, namely spray-based, laser-based, or plasma-based. This review discusses many of the plasma-based techniques coupled to mass spectrometry in terms of their current performance in fast qualitative screening and quantitative analysis. Critical aspects, for example sample preparation and introduction, quantification, and matrix effects, are addressed. Furthermore, the applicability of plasma-based sources to portable mass spectrometers and their capabilities in imaging experiments are summarized. The applications discussed are of two types. In one, direct screening is performed without any or with minimal sample pretreatment. Samples with low matrix content are qualitatively analyzed without interferences. The other, more challenging applications, namely samples with high matrix content and most quantitative analysis, typically require sample preparation ranging from simple dilution to extensive multi-step procedures.

Autonomous in situ analysis and real-time chemical detection using a backpack miniature mass spectrometer: concept, instrumentation development, and performance.

A major design objective of portable mass spectrometers is the ability to perform in situ chemical analysis on target samples in their native states in the undisturbed environment. The miniature instrument described here is fully contained in a wearable backpack (10 kg) with a geometry-independent low-temperature plasma (LTP) ion source integrated into a hand-held head unit (2 kg) to allow direct surface sampling and analysis. Detection of chemical warfare agent (CWA) simulants, illicit drugs, and explosives is demonstrated at nanogram levels directly from surfaces in near real time including those that have complex geometries, those that are heat-sensitive, and those bearing complex sample matrices. The instrument consumes an average of 65 W of power and can be operated autonomously under battery power for ca. 1.5 h, including the initial pump-down of the manifold. The maximum mass-to-charge ratio is 925 Th with mass resolution of 1-2 amu full width at half-maximun (fwhm) across the mass range. Multiple stages of tandem analysis can be performed to identify individual compounds in complex mixtures. Both positive and negative ion modes are available. A graphical user interface (GUI) is available for novice users to facilitate data acquisition and real-time spectral matching.

Halo-shaped flowing atmospheric pressure afterglow: a heavenly design for simplified sample introduction and improved ionization in ambient mass spectrometry.

The flowing atmospheric-pressure afterglow (FAPA) is a promising new source for atmospheric-pressure, ambient desorption/ionization mass spectrometry. However, problems exist with reproducible sample introduction into the FAPA source. To overcome this limitation, a new FAPA geometry has been developed in which concentric tubular electrodes are utilized to form a halo-shaped discharge; this geometry has been termed the halo-FAPA or h-FAPA. With this new geometry, it is still possible to achieve direct desorption and ionization from a surface; however, sample introduction through the inner capillary is also possible and improves interaction between the sample material (solution, vapor, or aerosol) and the plasma to promote desorption and ionization. The h-FAPA operates with a helium gas flow of 0.60 L/min outer, 0.30 L/min inner, and applied current of 30 mA at 200 V for 6 W of power. In addition, separation of the discharge proper and sample material prevents perturbations to the plasma. Optical-emission characterization and gas rotational temperatures reveal that the temperature of the discharge is not significantly affected (<3% change at 450 K) by water vapor during solution-aerosol sample introduction. The primary mass-spectral background species are protonated water clusters, and the primary analyte ions are protonated molecular ions (M + H(+)). Flexibility of the new ambient sampling source is demonstrated by coupling it with a laser ablation unit, a concentric nebulizer, and a droplet-on-demand system for sample introduction. A novel arrangement is also presented in which the central channel of the h-FAPA is used as the inlet to a mass spectrometer.