Ambient Ionization Source Research Articles

Characterizing and alleviating ion suppression effects in atmospheric pressure matrix-assisted laser desorption/ionization.

As a powerful ambient ion source, atmospheric pressure (AP) matrix-assisted laser desorption/ionization (MALDI) enables direct analysis at atmospheric pressure/temperature and minimal sample preparation. With the increasing usage of AP-MALDI sources with Orbitrap instruments, systematic characterization of the extent of ion suppression effect (ISE) in AP-MALDI-Orbitrap mass spectrometry imaging (MSI) is desirable. Recently, a new low-pressure MALDI platform has been introduced that reportedly provided better sensitivity. While extensive research efforts have been devoted to improving spatial resolution, fewer studies focused on the characterization and sensitivity improvement of these MALDI platforms that, coupled with high-resolution Orbitraps, provide powerful strategy for MSI. We compared the analytical performance of AP and low-pressure (subatmospheric) MALDI sources to study the effect of pressure control in the ion source. Using a model peptide/protein mixture, we systematically evaluated the factors influencing ISE. Furthermore, the effect of laser spot size was evaluated through tissue imaging analysis of lipids and neuropeptides. The effects of ion suppression and laser spot size have also been examined by comparing the number of identified molecular species during MSI analysis. Several key operating parameters including source pressure, laser energy, laser repetition rate, and microscopic slide coating materials were optimized to minimize the ISE. Under the optimal conditions, the subatmospheric AP-MALDI-Orbitrap platform with high spatial and mass spectral resolution enabled significantly improved coverage of several lipid and neuropeptide families in the MS analysis of mouse brain tissue sections. The new SubAP-MALDI source coupled with an Orbitrap mass spectrometer was established as a viable platform for in situ endogenous biomolecular analysis with increased sensitivity compared with conventional AP-MALDI sources as evidenced by the confident identification of neuropeptides from mouse brain imaging analyses. The alleviated ISE was key to substantial performance improvement due to optimized intermediate pressure conditions and better ion collection by the ion funnel.

Tandem Analysis by a Dual-Trap Miniature Mass Spectrometer.

Miniature mass spectrometers are of an increasing interest for in-situ analyses, and their coupling with the ambient ionization sources is a valid path for direct analysis of complex samples. In this study, a miniature mass spectrometer using discontinuous atmospheric pressure interface was developed with a dual-LIT (linear ion trap) configuration. The comprehensive scan modes were enabled for tandem mass spectrometry analysis, which are critical for high-quality qualitative and quantitative analysis. A real-time pressure control was implemented to facilitate the ion transfer and collision induced dissociation (CID). Beam-type CID could be performed for tandem analysis at a high number of stages. In-trap CID at high q could also be performed with the fragment ions accumulated in a second trap. A precursor ion scan mode for analyzing target analytes has also been demonstrated.

Triboelectric Nanogenerator (TENG) Mass Spectrometry of Falsified Antimalarials.

RationaleAn epidemic of low‐quality medicines continues to endanger patients worldwide. Detection of such ‘medicines’ requires low cost, ambient ionization sources coupled to fieldable mass spectrometers for optimum sensitivity and specificity. With the use of triboelectric nanogenerators (TENGs), the charge required to produce gas‐phase ions for mass analysis can be obtained without the need for high‐voltage electrical circuitry, simplifying and lowering the cost of next‐generation mass spectrometry instruments.MethodsA sliding freestanding (SF) TENG was coupled to a toothpick electrospray setup for the purposes of testing if falsified medicines could be fingerprinted by this approach. Extracts from both genuine and falsified medicines were deposited on the toothpick and the SF TENG actuated to generate electrical charges, resulting in gas‐phase ions for both active pharmaceutical ingredients and excipients.ResultsOur previous work had shown that direct analysis in real time (DART) ambient mass spectrometry can identify the components of multiple classes of falsified antimalarial medicines. Experiments performed in this study show that a simple extraction into methanol along with the use of a SF TENG‐powered toothpick electrospray can provide similar detection capabilities, but with much simpler and rugged instrumentation, and without the need for compressed gases or high‐voltage ion source power supplies.ConclusionsTENG toothpick MS allows for rapid analyte ion detection in a safe and low‐cost manner, providing robust sampling and ionization capabilities.

A Versatile Integrated Ambient Ionization Source Platform.

The pursuit of high-throughput sample analysis from complex matrix demands development of multiple ionization techniques with complementary specialties. A versatile integrated ambient ionization source (iAmIS) platform is proposed in this work, based on the idea of integrating multiple functions, enhancing the efficiency of current ionization techniques, extending the applications, and decreasing the cost of the instrument. The design of the iAmIS platform combines flowing atmospheric pressure afterglow (FAPA) source/direct analysis in real time (DART), dielectric barrier discharge ionization (DBDI)/low-temperature plasma (LTP), desorption electrospray ionization (DESI), and laser desorption (LD) technique. All individual and combined ionization modes can be easily attained by modulating parameters. In particular, the FAPA/DART&DESI mode can realize the detection of polar and nonpolar compounds at the same time with two different ionization mechanisms: proton transfer and charge transfer. The introduction of LD contributes to the mass spectrometry imaging and the surface-assisted laser desorption (SALDI) under ambient condition. Compared with other individual or multi-mode ion source, the iAmIS platform provides the flexibility of choosing different ionization modes, broadens the scope of the analyte detection, and facilitates the analysis of complex samples. Graphical abstract ᅟ.

Intermediate detection in real time using reactive surface desorption dielectric-barrier discharge ionization mass spectrometry.

Reactive intermediates play key roles for reaction mechanism elucidation. A suitable tool for identifying the key intermediates is crucial and highly desirable. In this study, surface desorption dielectric-barrier discharge ionization (reactive SDDBDI) was developed for characterization of the reactive intermediates. In reactive SDDBDI, the plasma is doped with a reagent before the plasma ions are directed at a cover slip surface bearing another analyte. Different from SDDBDI, reactive SDDBDI can be used both as an ambient ionization source and as a means to produce reagent ions for ambient ion/molecule reactions. The online derivation of 4-aminophenol with trifluoroacetic anhydride demonstrated that reactive SDDBDI can be used for chemical analysis where improved specificity or sensitivity is required. The utility of this approach for real-time detection of reactive intermediate was demonstrated by the Schiff-base and Eberlin reactions. The formed intermediates and products could be readily detected and identified by tandem mass spectrometry. These results indicate that reactive SDDBDI can be used to generate reagent ions that undergo ion/molecule reactions in the open air with an analyte at condensed phase on a surface. Reactive SDDBDI has high-efficiency ion transmission and high MS sensitivity. It is thus a potential tool to perform ambient ion/molecule reactions and detect reactive intermediates.

A Low-Cost, Simplified Platform of Interchangeable, Ambient Ionization Sources for Rapid, Forensic Evidence Screening on Portable Mass Spectrometric Instrumentation

Portable mass spectrometers (MS) are becoming more prevalent due to improved instrumentation, commercialization, and the robustness of new ionization methodologies. To increase utility towards diverse field-based applications, there is an inherent need for rugged ionization source platforms that are simple, yet robust towards analytical scenarios that may arise. Ambient ionization methodologies have evolved to target specific real-world problems and fulfill requirements of the analysis at hand. Ambient ionization techniques continue to advance towards higher performance, with specific sources showing variable proficiency depending on application area. To realize the full potential and applicability of ambient ionization methods, a selection of sources may be more prudent, showing a need for a low-cost, flexible ionization source platform. This manuscript describes a centralized system that was developed for portable MS systems that incorporates modular, rapidly-interchangeable ionization sources comprised of low-cost, commercially-available parts. Herein, design considerations are reported for a suite of ambient ionization sources that can be crafted with minimal machining or customization. Representative spectral data is included to demonstrate applicability towards field processing of forensic evidence. While this platform is demonstrated on portable instrumentation, retrofitting to lab-scale MS systems is anticipated.

Integration of paper spray ionization high-field asymmetric waveform ion mobility spectrometry for forensic applications.

Paper spray ionization (PSI) is an attractive ambient ionization source for mass spectrometry (MS) since it allows the combination of surface sampling and ionization. The minimal sample preparation inherent in this approach greatly reduces the time needed for analysis. However, the ions generated from interfering compounds in the sample and the paper substrate may interfere with the analyte ions. Therefore, the integration of PSI with high-field asymmetric ion mobility spectrometry (FAIMS) is of significant interest since it should reduce the background ions entering the mass analyzer without complicating the analysis or increasing analysis time. Here we demonstrate the integration of PSI with FAIMS/MS and its potential for analysis of samples of forensic interest. In this work, the parameters that can influence the integration, including sampling and ionization by paper spray, the FAIMS separation of analytes from each other and background interferences, and the length of time that a usable signal can be observed for explosives on paper, were evaluated with the integrated system. In the negative ion analysis of 2,4,6-trinitrotoluene (TNT), pentaerythritol tetranitrate (PETN), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), amounts as low as 1ng on paper were readily observed. The successful positive ion separation of a set of illicit drugs including heroin, methamphetamine, and cocaine was also achieved. In addition, the positive ion analysis of the chemical warfare agent simulants dimethyl methylphosphonate (DMMP) and diisopropyl methylphosphonate (DIMP) was evaluated. The integration of PSI-FAIMS/MS was demonstrated for the analyses of explosives in negative ion mode and for illicit drugs and CW simulants in positive mode. Paper background ions that could interfere with these analyses were separated by FAIMS. The compensation voltage of an ion obtained by FAIMS provided an additional identification parameter to be combined with the mass spectrum for each analyte.

Mini 2000: A Robust Miniature Mass Spectrometer with Continuous Atmospheric Pressure Interface

A miniature mass spectrometer with continuous atmospheric pressure interface (CAPI) developed previously in our lab has proved to have high stability and rapid analysis speed. With the aim of achieving smaller size, better performance and easier maintenance, in this study, an upgraded miniature mass spectrometer with CAPI was developed, in which all components were optimized and redesigned into a packaged unit. Using a more powerful pumping system, better analytical performances were obtained for this system. The miniature mass spectrometer has the capability to perform tandem mass spectrometry, and could be coupled with ambient ionization sources for analysis of different samples. Good stability (signal relative standard deviation, RSD < 5%), high sensitivity (limit of detection, LOD 10 ng/mL), better than unit mass resolution, and a broad mass range (from 150 Da to 2000 Da) were obtained. Integrated with a tablet computer for system control, the miniature mass spectrometer has dimensions of 38 cm × 23 cm × 34 cm (length × width × height), and is 13 kg in total weight. The whole system is powered by an adapter with a power consumption of 200 watts in total.

Rapid screening of basic colorants in processed vegetables through mass spectrometry using an interchangeable thermal desorption electrospray ionization source

Thermal desorption electrospray ionization/mass spectrometry (TD–ESI–MS) employing a quickly interchangeable ionization source is a relatively new ambient ionization mass spectrometric technique that has had, to date, only a limited number of applications related to food safety control. With reallocation of resources, this direct-analysis technique has had wider use in food analysis when operated in dual-working mode (pretreatment-free qualitative screening and conventional quantitative confirmation) after switching to an ambient ionization source from a traditional atmospheric pressure ionization source. Herein, we describe the benefits and challenges associated with the use of a TD–ESI source to detect adulterants in processed vegetables (PVs), as a proof-of-concept for the detection of basic colorants. While TD–ESI can offer direct qualitative screening analyses for PVs with detection capabilities lower than those provided with liquid chromatography/UV detection within 30 s, the use of TD–ESI for semi-quantification is applicable only for homogeneous food matrices.

The study of bismuth ions in drinking water at ultratrace levels by a microwave plasma torch coupled with linear ion trap mass spectrometry

A microwave plasma torch (MPT) can be used as a simple and low power-consumption ambient ion source for the metal ions detection.

The Study of Titanium and Zirconium Ions in Water by MPT-LTQ Mass Spectrometry in Negative Mode.

Microwave plasma torches (MPTs) can be used as simple and low power-consumption ambient ion sources. When MPT-mass spectrometry (MPT-MS) is applied in the detection of some metal elements, the metallic ions exhibit some novel features which are significantly different with those obtained by the traditional inductively coupled plasma (ICP)-mass spectrometry (ICP-MS) and may be helpful for metal element analysis. As the representative elements of group IVA, titanium and zirconium are both of importance and value in modern industry, and they have impacts on human health. Here, we first provide a study on the complex anions of titanium and zirconium in water by using the MPT as ion source and a linear ion trap mass spectrometer (LTQ-MS). These complex anions were produced in the plasma flame by an aqueous solution flowing through the central tube of the MPT, and were introduced into the inlet of the mass spectrometry working in negative ion mode to get the feature mass spectrometric signals. Moreover, the feature fragment patterns of these ions in multi-step collision- induced dissociation processes have been explained. Under the optimized conditions, the limit of detection (LOD) using the MS2 (the second tandem mass spectrometry) procedure was estimated to be at the level of 10 μg/L for titanium and 20 μg/L for zirconium with linear dynamics ranges that cover at least two orders of magnitude, i.e., between 0–500 μg/L and 20–200 μg/L, respectively. These experimental data demonstrated that the MPT-MS is a promising and useful tool in field analysis of titanium and zirconium ions in water, and can be applied in many fields, such as environmental control, hydrogeology, and water quality inspection. In addition, MPT-MS could also be used as a supplement of ICP-MS for the rapid and on-site analysis of metal ions.

Carbon Nanotube Fiber Ionization Mass Spectrometry: A Fundamental Study of a Multi-Walled Carbon Nanotube Functionalized Corona Discharge Pin for Polycyclic Aromatic Hydrocarbons Analysis.

Mass spectrometry continues to tackle many complicated tasks, and ongoing research seeks to simplify its instrumentation as well as sampling. The desorption electrospray ionization (DESI) source was the first ambient ionization source to function without extensive gas requirements and chromatography. Electrospray techniques generally have low efficiency for ionization of nonpolar analytes and some researchers have resorted to methods such as direct analysis in real time (DART) or desorption atmospheric pressure chemical ionization (DAPCI) for their analysis. In this work, a carbon nanotube fiber ionization (nanoCFI) source was developed and was found to be capable of solid phase microextraction (SPME) of nonpolar analytes as well as ionization and sampling similar to that of direct probe atmospheric pressure chemical ionization (DP-APCI). Conductivity and adsorption were maintained by utilizing a corona pin functionalized with a multi-walled carbon nanotube (MWCNT) thread. Quantitative work with the nanoCFI source with a designed corona discharge pin insert demonstrated linearity up to 0.97 (R2) of three target PAHs with phenanthrene internal standard. Graphical Abstract ᅟ.

Analysis of hop acids by thin-layer chromatography and the Molecular Ionization Desorption Analysis Source (MIDAS) for mass spectrometry

A thin-layer chromatography ambient mass spectrometry method was developed for the quantitative analysis of hop acids. Hop acids were extracted from three varieties of hop pellets, Apollo, Cluster and Czech Saaz. Reversed-phase thin-layer chromatography provided the optimum stationary phase for separation and ionization. Using standards, a method was developed to separate α-, iso-α- and β-acids by thin-layer chromatography. Each thin-layer chromatography plate was analyzed directly by the Molecular Ionization Desorption Analysis Source (MIDAS). MIDAS is an atmospheric pressure ambient ionization source for mass spectrometry. Quantitative analysis of the hop extracts was made by successive analysis of known amounts of standards and the determination of a response factor. The expected trend of total α-acid content with Apollo>Cluster>Czech Saaz was observed. Variation in the results was attributed to manual TLC plate spotting and not to the ionization source.

Top-Down Atmospheric Ionization Mass Spectrometry Microscopy Combined With Proteogenomics.

Mass spectrometry-based protein analysis has become an important methodology for proteogenomic mapping by providing evidence for the existence of proteins predicted at the genomic level. However, screening and identification of proteins directly on tissue samples, where histological information is preserved, remain challenging. Here we demonstrate that the ambient ionization source, nanospray desorption electrospray ionization (nanoDESI), interfaced with light microscopy allows for protein profiling directly on animal tissues at the microscopic scale. Peptide fragments for mass spectrometry analysis were obtained directly on ganglia of the medicinal leech (Hirudo medicinalis) without in-gel digestion. We found that a hypothetical protein, which is predicted by the leech genome, is highly expressed on the specialized neural cells that are uniquely found in adult sex segmental ganglia. Via this top-down analysis, a post-translational modification (PTM) of tyrosine sulfation to this neuropeptide was resolved. This three-in-one platform, including mass spectrometry, microscopy, and genome mining, provides an effective way for mappings of proteomes under the lens of a light microscope.

Quantitative Analysis of Bisphenol A in Recycled Paper with a Novel Direct Inlet Probe-Atmospheric Pressure Photoionization–IonTrap-MS

A new ambient ion source was developed and its application to real samples has been demonstrated. This ion source is based on a previously build ion source using chemical ionization under atmospheric pressure and extractive electrospray ionization (DIP-APCI/EESI). To enhance the range of analytes, we added to this ion source a photoionization lamp to enable also photoionization, which allows the possibility to analyze polar (EESI), middle (APCI) and non-polar (APPI) analytes with the same source and with no or only a small change of the setup. In comparison with DIP-APCI, this ion source reaches similar analytical limits but shows better sensitivity for some aromatic and non-polar analytes. The analysis of bisphenol A from extracts of recycled paper demonstrates the use of this ion source for real samples. Quantification was possible by the use of a deuterated internal standard that was added to the papers before extraction. Here atmospheric pressure chemical ionization leads to bad results due to ion suppression, whereas atmospheric pressure photoionization shows results that fit to literature values.

Exploration and performance evaluation of microwave-induced plasma with different discharge gases for ambient desorption/ionization mass spectrometry.

Microwave-induced plasma (MIP) with different discharge gases of argon or helium provides significant plasma-based ambient desorption/ionization sources, which have potential applicability in direct analysis of complex samples without any sample pre-treatment. In this study, experiments were conducted to better understand microwave-induced plasma desorption/ionization (MIPDI) sources and the corresponding ionization mechanisms. Emission spectra of microwave-induced argon (MIP-Ar) and helium (MIP-He) plasmas were obtained from the plasma tail flame of a MIP source. Compounds including L-phenylalanine, L-serine, L-valine, urea, 4-acetaminophen, gallic acid and L-ascorbic acid were analyzed using both sources. Polyethylene glycol 400 (PEG400) oligomers were detected by MIP-Ar and MIP-He mass spectrometry at different microwave powers. Mass spectra of higher molecular weight PEGs (including PEG800, PEG1000 and PEG2000) were also acquired using both sources. In the emission spectra, N2 , H-I and O-I species were observed by MIP-Ar/He. In addition, SiO2 , Na-I, Si-I and Si-II species were generated by MIP-He. In the mass spectra of compounds, [M+H]+ , [2M+H]+ , [M+O+H]+ , [M+2O-H]+ and fragment ions were observed. In the mass spectra of PEG400 obtained by MIP-Ar/He at different microwave powers, higher molecular weight oligomers could only be observed with higher microwave power. PEGs with molecular weights as high as 1000Da were also successfully analyzed by MIPDI. According to the different natures of the samples, either MIP-Ar or MIP-He can be chosen as a working ion source for mass spectrometry. The MIPDI source is potentially applicable to the analysis of compounds with high molecular weights, especially polymers with high degree of polymerization (such as PEG2000), which is a challenging issue for the traditional ambient ionization sources. Copyright © 2017 John Wiley & Sons, Ltd.

Comparison of Ambient and Atmospheric Pressure Ion Sources for Cystic Fibrosis Exhaled Breath Condensate Ion Mobility-Mass Spectrometry Metabolomics

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The vast majority of the mortality is due to progressive lung disease. Targeted and untargeted CF breath metabolomics investigations via exhaled breath condensate (EBC) analyses have the potential to expose metabolic alterations associated with CF pathology and aid in assessing the effectiveness of CF therapies. Here, transmission-mode direct analysis in real time traveling wave ion mobility spectrometry time-of-flight mass spectrometry (TM-DART-TWIMS-TOF MS) was tested as a high-throughput alternative to conventional direct infusion (DI) electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) methods, and a critical comparison of the three ionization methods was conducted. EBC was chosen as the noninvasive surrogate for airway sampling over expectorated sputum as EBC can be collected in all CF subjects regardless of age and lung disease severity. When using pooled EBC collected from a healthy control, ESI detected the most metabolites, APCI a log order less, and TM-DART the least. TM-DART-TWIMS-TOF MS was used to profile metabolites in EBC samples from five healthy controls and four CF patients, finding that a panel of three discriminant EBC metabolites, some of which had been previously detected by other methods, differentiated these two classes with excellent cross-validated accuracy. Graphical Abstract ᅟ.

Mini Mass Spectrometer Integrated with a Miniature Ion Funnel.

Previously, a continuous atmospheric pressure interfaced miniature mass spectrometer was developed in our lab. The continuous atmospheric pressure interface improves system robustness, stability, and scan speed, but it also results in limited ion transfer efficiency and reduced mass resolution. To solve these problems, a miniature ion funnel was designed and integrated into the miniature mass spectrometer for the first time. Besides ion transfer efficiency, dimension and power consumption of the ion funnel also need to be considered throughout the design process. After a systematic optimization, the designed miniature ion funnel could increase ion transfer efficiency by more than 10 times, while lowering the background pressure of ion trap by ∼2 times. As a result, sensitivity and mass resolution of the second generation miniature mass spectrometer were improved by 20 times and ∼2 times, respectively, while maintaining its high scan speed and stability. A sensitive and robust mini-MS, capable of coupling with ambient ionization sources would meet the needs of many on-site chemical analysis applications, such as in food, drug, and agricultural administrations, forensic science, homeland security, and etc.

Characterization of an Airborne Laser-Spark Ion Source for Ambient Mass Spectrometry.

An airborne laser plasma is suggested as an ambient ion source for mass spectrometry. Its fundamental physical properties, such as an excellent spatial and temporal definition, high electron and ion densities and a high effective cross section in maintaining the plasma, make it a promising candidate for future applications. For deeper insights into the plasma properties, the optical plasma emission is examined and compared to mass spectra. The results show a seemingly contradictory behavior, since the emitted light reports the plasma to almost entirely consist of hot elemental ions, while the corresponding mass spectra exhibit the formation of intact molecular species. Further experiments, including time-resolved shadowgraphy, spatially resolved mass spectrometry, as well as flow-dependent emission spectroscopy and mass spectrometry, suggest the analyte molecules to be formed in the cold plasma vicinity upon interaction with reactive species formed inside the hot plasma center. Spatial separation is maintained by concentrically expanding pressure waves, inducing a strong unidirectional diffusion. The accompanying rarefaction inside the plasma center can be compensated by a gas stream application. This replenishing results in a strong increase in emission brightness, in local reactive species concentration, and eventually in direct mass spectrometric sensitivity. To determine the analytical performance of the new technique, a comparison with an atmospheric pressure chemical ionization (APCI) source was conducted. Two kitchen herbs, namely, spearmint and basil, were analyzed without any sample pretreatment. The presented results demonstrate a considerably higher sensitivity of the presented laser-spark ionization technique.

Rapid screening and quantification of glucocorticoids in essential oils using direct analysis in real time mass spectrometry.

There is a strong demand to develop a method capable of rapid screening for the adulteration of glucocorticoids (GCs) in cosmetics. An ambient ion source- direct analysis in real time (DART), coupled with quadrupole time of flight mass spectrometry (QTOF MS) was used for the rapid screening of GCs in essential oils. Liquid-liquid extraction was employed prior to the DART-QTOF MS analysis. Calibration curves for eight GCs were obtained using methyltestosterone as an internal standard. MS/MS experiments and accurate mass measurements were carried out to provide reliable and powerful evidence for the adulteration of targeted GCs. Quantification results were obtained in terms of linearity (R(2) for all GCs, 0.986-0.996), sensitivity (limit of detection, 2.0-50ng/mL), and repeatability (RSD, 1.2-6.0%). The entire analytical process can be finished in 5 min, compared with the GC/MS or LC/MS methods for which typical analysis times range from tens of minutes to >1h. In addition, comparison of the performance of DART and ESI ion sources showed that DART possessed a relatively low matrix effect when handling complex samples. A new method for the rapid screening and quantification of GCs in essential oils was developed using DART-QTOF MS. Copyright © 2016 John Wiley & Sons, Ltd.