Trace Analysis of C4F7N Insulating Gas Mixtures by Spontaneous Raman Spectroscopy and Gas Chromatography.

2,3,3,3-Tetrafluoro-2-(trifluoromethyl) propanenitrile (C4F7N) is being researched as an alternative to sulfur hexafluoride (SF6) for applications in gas-insulated switchgear. We independently assessed the effectiveness of gas chromatography-mass spectrometry (GC-MS) and a novel method of feedback-assisted multipass cavity spontaneous Raman spectroscopy (SRS) for the trace quantification of impurities in C4F7N and its related byproducts. A total of 14 gases were identified with estimated concentrations as low as 20 ppm (ppm) for C3F6 using GC-MS and 7.4 ppm for CH4 using SRS and as high as 500 ppm for CF4 using GC-MS and 1430 ppm for CO using SRS. While GC-MS is highly effective in selectively detecting and quantifying trace contaminants, it necessitates separate detectors for various gases, such as CH4 and H2. SRS succeeded in detecting CF4 and C2F6 at concentrations of 465 and 100 ppm, respectively, and in placing an upper bound of several hundred ppm for the other analytes. Crucially, SRS holds potential for portability-and thus for field applications-in gas-insulated switchgear equipment diagnostics.

Shake It Off! Acoustic Manipulation of Lipid Vesicles for Mass Spectrometric Analysis.

Analyzing lipid assemblies, including liposomes and extracellular vesicles (EVs), is challenging due to their size, diverse composition, and tendency to aggregate. Such vesicles form with a simple phospholipid bilayer membrane, and they play important roles in drug discovery and delivery. The use of mass spectrometry (MS) allows for broad analysis of lipids from different classes; however, their release from the higher order structural aggregates is typically achieved by chemical means. Mechanical disruption by high frequency surface acoustic waves (SAW) is presented as an appealing alternative to preparing lipid vesicles for MS sampling. In this work, SAWs used to disrupt liposomes allow for the direct analysis of their constituent lipids by employing SAW nebulization with corona discharge (CD) ionization. We explore the effects of duration, frequency, and incorporation of nonpolar lipids, including cholesterol, on the SAW's ability to disrupt the liposome. We also report on the successful MS analysis of liposome-derived lipids along with cytochrome C in solution, thus demonstrating applications to aqueous samples and native MS conditions.

Comparing ELISA and LC-MS-MS: A Simple, Targeted Postmortem Blood Screen.

A comprehensive screening method that is specific, accurate and customizable is necessary in any forensic toxicology laboratory. Most laboratories utilize some form of immunoassay testing as it is reliable and sensitive with minimal sample preparation and is relatively inexpensive to simultaneously screen for multiple classes of drugs with different chemical properties. However, accessibility to more specific technology and instrumentation such as mass spectrometry has increased and therefore using immunoassay as the screening method of choice may be revisited. A screening method for 42 drugs in postmortem blood was developed and validated following the Organization of Scientific Area Committees for Forensic Science guidelines for toxicology method validation. The method was developed using minimal sample preparation of postmortem blood consisting only of a protein precipitation. Only two internal standards were used, which greatly reduces the cost of implementing this method. Limit of detection, interference studies, processed sample stability and ion suppression/enhancement were examined. Additionally, over 100 case samples were analyzed by both the current enzyme-linked immunosorbent assay (ELISA) testing procedure and the proposed liquid chromatography-tandem mass spectrometry (LC-MS-MS) screening method. The comparison determined that the LC-MS-MS method performed as well as or better than the ELISA in nearly all cases. The ability to add additional target drugs increases the laboratory's scope of analysis as well. This method is ideal for forensic laboratories wishing to improve screening while working within budget constraints.

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.

IN SITU MASS SPECTROMETERS FOR APPLICATIONS IN SPACE.

Mass spectrometry (MS) has played a remarkable role in exploring the chemical make-up of our solar system. In situ probes were historically developed to analyze inorganic/elemental compositions while leveraging native ions or harsh ionization methods to aid in exploring astrophysics applications (e.g., heliophysics). The part played by MS is demonstrated in a majority of scientific payloads focused on exploration, particularly at the turn of the century with missions including Cassini-Huygens, Rosetta, and now Mars Science Laboratory. Plasma mass spectrometers have grown more sophisticated to interrogate fundamental inorganic analysis (e.g., solar wind and magnetospheres) including both native ions and neutrals. Cosmic dust floating in-between and orbiting planetary bodies has been targeted by unique sampling via impact ionization. More complex systems rely on landed planetary instrumentation with lessons learned from pioneering missions in the 1970s and 1980s to near neighbors Mars and Venus. Modern probes have expanded applicable target chemicals by recognizing the needs to provide for molecular analyses, extended mass range, and high resolution to provide unequivocal detection and identification. Notably, as the field surrounding astrobiology has gained momentum, so has the in situ detection of complex molecular chemistry including the chemical evolution of organic molecules. Mission context often includes long term timelines from spacecraft launch to arrival and additionally the diverse target environments across various planets. Therefore, customized experimental designs for space MS have been born of necessity. To this point, the development of MS instrumentation on Earth has now far outpaced development for experiments in space. Therefore, exciting developments lie ahead among various international space agencies conducting current and future mission planning with increasingly enhanced instrumentation. For instance, near-neighbor Mars has entertained considerable attention with complex MS instrumentation with laser desorption ionization aboard the Mars Organic Molecule Analyzer instrument. To study comets, the Rosetta mission employs a secondary ionization mechanism. Meanwhile, the various moons of Jupiter and Saturn have intriguing surface and subsurface properties that warrant more advanced analyzer systems. Instrumentation design will continue to evolve as requirements develop and this review serves as a reflection of the contribution of in situ MS to space exploration in the past 20 years and the anticipated contribution yet to come. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.

Inexpensive Ultrasonic Nebulization Coupled with Direct Current Corona Discharge Ionization Mass Spectrometry for Liquid Samples and Its Fundamental Investigations.

The concept of direct mass-spectrometric analysis, especially exploited by ambient desorption/ionization (ADI) methods, provides numerous means for convenient sample analysis. While many simple and versatile ionization sources have been developed, challenges lay in achieving efficient sample introduction. In previous work, a sample introduction method employing direct current corona discharge (CD) coupled to a surface acoustic wave nebulization (SAWN) device enhanced sampling performance for both polar and nonpolar analytes by up to 4 orders of magnitude. In fact, the SAWN-CD method generated a multiply charged peptide ion signal comparable to that of conventional ESI. Unfortunately, the high cost of the SAWN devices themselves limits their accessibility. Herein, we report on an analogous implementation of CD with an inexpensive ultrasonic nebulizer (USN) on the basis of a commercial room humidifier demonstrating equivalent exemplary performance. We subsequently compare the two methods of SAWN-CD and USN-CD in a screening application of milk for the detection of two antibiotic drugs, ciprofloxacin and ampicillin. Finally, we further investigate the relative softness of these CD-coupled acoustic nebulization methods in comparison to that of ESI using a survival yield study of the thermometer ion nitrobenzylpyridinium.

Enabling Isotope Ratio Measurements on an Ion Trap Mass Spectrometer.

For portable, remotely operated systems in space and defense, relaxed vacuum requirements are a strong advantage of ion trap mass analyzers. However, ion traps are believed to have insufficient capability for isotope ratio measurement because they fundamentally restrict sampling capacity. Focusing on modifications to the detection sequence of a digitally driven 3D quadrupole ion trap, operating in resonance ejection mode, we investigated improved performance for isotope ratio precision and accuracy. Due to xenon's inert nature and wide span of isotopes, xenon isotope ratios provide an excellent marker of processes (e.g. radioactive decay and planetary atmospheric escape) which would be ideally measured by in situ mass spectrometry. To target xenon isotope ratio analysis specifically, we implemented data acquisition system modifications for enhanced y-axis resolution measurements and signal filtering. In this manner, we show measurement precision improvements from ~±100 0/00 to ~±0.1 0/00 and accuracy improvements from ~30 0/00 to ~0.5 0/00 for our targeted isotopes of interest.

Enabling Field Asymmetric Ion Mobility Spectrometry Separation of Fentanyl-Related Compounds Using Controlled Humidity.

Due to the widespread abuse of opioids in recent years, the development of quick and reliable methods for analyzing compounds such as fentanyl and its derivatives is increasingly important. Ahead of online mass spectrometric analysis, field asymmetric ion mobility spectrometry (FAIMS) has previously been used for rapid ion prefiltering and demonstrated significantly improved peak capacity with the addition of vapor modifiers to the carrier gas. The application of FAIMS-mass spectrometry (MS) in the analysis of fentanyl and related compounds is presented herein with the use of a water vapor modifier. The inclusion of the water vapor modifier to the FAIMS methodology is made more robust with the incorporation of a humidity sensor. A dramatic improvement in the separation of fentanyl, alfentanil, 4-aminophenyl-1-phenethylpiperidine (4-ANPP), norfentanyl, and heroin has been achieved, and the ability to distinguish the isobars in a mixture, alfentanil and ortho-isopropyl furanyl fentanyl, is demonstrated without lengthy chromatography.

Online Sol-gel Capillary Microextraction-Mass Spectrometry (CME-MS) Analysis of Illicit Drugs.

Providing rapid and sensitive sample cleanup, sol-gel capillary microextraction (CME) is a form of solid phase microextraction (SPME). The capillary format of CME couples easily with mass spectrometry (MS) by employing sol-gel sorbent coatings in inexpensive fused silica capillaries. By leveraging the syringe pump and six-port valve readily available on the commercial MS, we can obviate the need for chromatography for samples as complex as urine in quantitative assays. Two different sol-gel materials were studied as microextraction sorbents: one with a single ligand of octadecyl (C18) and the other with a dual-ligand combination of C18 and phenyl (Phe) groups. The CME-MS method was optimized for flow rate and solvent desorption and studied for overall microextraction performance between the two sorbents studied. We extract illicit drugs including cocaine, heroin, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, and oxycodone, proving good run-to-run reproducibility (RSD% < 10%) and low detection limits (< 10 ng mL-1). The dual-ligand sorbent demonstrated superior performance due to typical hydrophobic properties of C18 as well as potential π-π interactions of the Phe functionality and the aromatic moiety common to many drugs. This study demonstrates the advantage of fine-tuning sol-gel sorbents for application-specific CME-MS. We apply our method to the analysis of various drugs in synthetic and human urine samples and show low carryover effect (~ 5%) and low matrix effect in the presence of the urine matrix. Thus, the sol-gel CME-MS technique described herein stands to be an attractive alternative to other SPME-MS techniques.

Surface Acoustic Wave Nebulization with Atmospheric-Pressure Chemical Ionization for Enhanced Ion Signal.

Many ambient desorption/ionization mass spectrometry (ADI-MS) techniques rely critically on thermal desorption. Meanwhile, the analyte classes that are successfully studied by any particular ADI-MS methods are strongly dependent on the type of ionization source. Generally, spray-based ionization sources favor polar analytes, whereas plasma-based sources can be used for more hydrophobic analytes and are more suitable for molecules with small molar masses. In the present work, classic atmospheric-pressure chemical ionization (APCI) is used. To provide improved desorption performance for APCI, a surface acoustic wave nebulization (SAWN) device was implemented to convert liquid analytes into fine airborne particles. Compared to conventional SAWN that is used solely as an ionization source for liquid samples, the coupling of SAWN and APCI significantly improves ion signal by up to 4 orders of magnitude, reaching comparable ion abundances to those of electrospray ionization (ESI). Additionally, this coupling also extends the applicable mass range of an APCI source, conventionally known for the ionization of small molecules <500 Da. Herein, we discuss cursory evidence of this applicability to a variety of analytes including both polar and nonpolar small molecules and novel peptides that mimic biomolecules upward of 1000 Da. Observed species are similar to ESI-derived ions including doubly charged analyte ions despite presumably different charging mechanisms. SAWN-APCI coupling may thus involve more nuanced ionization pathways in comparison to other ADI approaches.

Ion-Trap-Performance Enhancement Utilizing Pulsed Buffer-Gas Introduction.

A novel means of improving the resolution and total ion signal inside a digitally driven 3D quadrupole ion trap has been studied. Conventional ion-trapping methods occur by injecting helium gas continuously into the trap to kinetically cool ions and improve trapping efficiency. Utilizing a pulsed helium introduction allows for trapping aided by collisional cooling while mitigating ion losses due to gas collisions during ion scan-out. Operating the trap in resonance-ejection mode, we demonstrate that pulsed helium introduction improves the resolution by a factor of ∼2 and that resolution is retained as the total ion signal increases. We also show that ejections at other harmonic secular frequencies under static helium conditions no longer occur during pulsed helium introduction. Improving timing synchronization can lead to the determination of the optimal conditions needed to maximize signal intensity as well as ion ejection.

Differential Mobility Spectrometry for Inorganic Filtration in Nuclear Forensics.

Differential mobility spectrometry (DMS) is applied to the analysis of inorganic mixtures relevant to nuclear forensics. Three primary components of potential radiological dispersal devices (RDDs), cobalt, cesium, and strontium, were studied by DMS to demonstrate rapid sample cleanup when coupled to mass spectrometry. Nanosprayed salt solutions comprised of stable analogs, as proxies to these radioisotopes, and isobaric interferents were introduced to DMS. The DMS effluent was directly coupled to a mass spectrometer to confirm the elemental identity of the separated clusters. DMS dispersion plots demonstrated distinctive elemental separation from both atomic and molecular interferents. These results support the potential use of DMS as a means of rapid separation for inorganic analyses prior to analysis in a field portable mass spectrometer. The mechanism for this process is speculated to involve dynamics of solvent cluster formation under the influence of the alternating high and low electric fields of the DMS.

Detoxification of chlorella supplement on heterocyclic amines in Korean young adults.

Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) have been established as carcinogenic chemicals in Western diet. This study was performed to estimate HCA exposure levels in Korean daily life and to assess the ability of Chlorella vulgaris to detoxify carcinogenic HCAs in a randomized, double blind, placebo-controlled crossover study with chlorella supplement (N=6, all females, age: 27.17±7.73yr) for 2 weeks. We analyzed HCAs in hydrolyzed urine specimens using LC/TOF-MS. As results, urinary levels of MeIQx, PhIP, and IQx-8-COOH were 323.36±220.11ng/L, 351.59±254.93ng/L, and 130.85±83.22ng/L, respectively. Effects of chlorella to reduce urinary MeIQx were marginally significant (before, 430±226.86pg/mL vs. after, 174.45±101.65pg/mL: 0.05

Differential mobility spectrometry-mass spectrometry for atomic analysis.

Analysis and separation of atomic ions within a portable setting are studied in forensic applications of radiological debris analysis. Ion mobility spectrometry (IMS) may be used to show separation of atomic ions, while the related method of differential mobility spectrometry (DMS) has focused on fractionation of primarily molecular components. We set out to investigate DMS as a means for separating atomic ions. We initially derived the differential ion mobility parameter, alpha, from classic empirical IMS data of atomic ions, cesium and potassium, each showing its own distinct form of alpha. These alpha functions were applied to DMS simulations and supported by analytical treatment that suggested a means for a rapid disambiguation of atomic ions using DMS. We validated this hypothesis through the prototype cesium-potassium system investigated experimentally by DMS coupled to mass spectrometry (MS). Such a feature would be advantageous in a field portable instrument for rapid atomic analyses especially in the case of isobaric ions that cannot be distinguished by MS. Herein, we first report this novel method for the derivation of alpha from existing field dependent drift tube ion mobility data. Further, we translate experimental DMS data into alpha parameters by expanding upon existing methods. Refining the alpha parameter in this manner helps convey the interpretation of the alpha parameter particularly for those new to the DMS field.

High-speed digital frequency scanning ion trap mass spectrometry.

A novel means of simultaneous ion injection and mass scanning has been studied. Classic injection methods for ion trap mass spectrometry proceed by loading the trap and scanning out in mutually exclusive time segments. This mode implicitly imparts a duty cycle and acquisition rate limit to ion trap mass analysis. Using digital frequency scanning methods without the use of discrete injection phases, we demonstrate continuous injection and acquisition rates up to 1000 Hz (averaging 400,000 Th/s) in a 3D ion trap configuration showing an alternatively faster control of ions over the classic voltage ramping mass-selective instability scanning method. The digital frequency scanning method may accommodate current advances in high-speed separation [e.g., ultraperformance liquid chromatography (UPLC), two-dimensional gas chromatography (GC×GC), ion mobility spectrometry (IMS), and capillary electrophoresis (CE)] and ion transfer efficiency (e.g., ion funnels). These ion sources may comprise high ion currents with compositions that change quickly and require high-speed mass analysis. Though resolution is compromised with higher acquisition rates, the frequency scanning mode permits a more flexible platform to accomplish the optimal trade-off of speed and mass spectral quality.

Carbon nanotube electron ionization source for portable mass spectrometry.

Cold cathode carbon nanotubes (CNTs) are used in a low-voltage quadrupole ion trap mass spectrometer and shown to be a viable low-power alternative to filament sources for portable mass spectrometry instrumentation. No heating is necessary, and the power consumption depends only on the switching characteristics of the electronics. The CNT electron sources are mounted directly in the ring electrode, and their performance is compared directly with a filament source also mounted in the ring electron. Up to a 5 × 10(-4) Torr CO(2) environment, reflecting conditions expected during operation in a Mars atmosphere, the CNT emitters may provide up to 1 µA of current over more than 200 h.

Time-of-flights and traps: from the Histone Code to Mars.

Two very different analytical instruments are featured in this perspective paper on mass spectrometer design and development. The first instrument, based upon the curved-field reflectron developed in the Johns Hopkins Middle Atlantic Mass Spectrometry Laboratory, is a tandem time-of-flight mass spectrometer whose performance and practicality are illustrated by applications to a series of research projects addressing the acetylation, deacetylation and ADP-ribosylation of histone proteins. The chemical derivatization of lysine-rich, hyperacetylated histones as their deuteroacetylated analogs enables one to obtain an accurate quantitative assessment of the extent of acetylation at each site. Chemical acetylation of histone mixtures is also used to determine the lysine targets of sirtuins, an important class of histone deacetylases (HDACs), by replacing the deacetylated residues with biotin. Histone deacetylation by sirtuins requires the co-factor NAD+, as does the attachment of ADP-ribose. The second instrument, a low voltage and low power ion trap mass spectrometer known as the Mars Organic Mass Analyzer (MOMA), is a prototype for an instrument expected to be launched in 2018. Like the tandem mass spectrometer, it is also expected to have applicability to environmental and biological analyses and, ultimately, to clinical care.