Paper Spray Research Articles

Pressure-Sensitive Adhesive Combined with Paper Spray Mass Spectrometry for Low-Cost Collection and Analysis of Drug Residues.

Illicit drug use causes over half a million deaths worldwide every year. Drugs of abuse are commonly smuggled through customs and border checkpoints and, increasingly, through parcel delivery services. Improved methods for detection of trace drug residues from surfaces are needed. Such methods should be robust, fieldable, sensitive, and capable of detecting a wide range of drugs. In this work, commercially produced paper with a pressure-sensitive adhesive coating was utilized for the collection and analysis of trace drug residues by paper spray mass spectrometry (MS). This modified substrate was used to combine sample collection of drug residues from surfaces with rapid detection using a single paper spray ticket. The all-in-one ticket was used to probe different surfaces commonly encountered in forensic work including clothing, cardboard, glass, concrete, asphalt, and aluminum. A total of 10 drugs (acetyl fentanyl, fentanyl, clonazolam, cocaine, heroin, ketamine, methamphetamine, methylone, U-47700, and XLR-11) were evaluated and found to be detectable in the picogram range using a benchtop mass spectrometer and in the low nanogram range using a portable ion trap MS. The novel approach demonstrates a simple yet effective sampling strategy, allowing for rapid identification from difficult surfaces via paper spray mass spectrometry.

Hand-powered ionization methods for the mass spectrometric detection of small molecules

Miniaturization of ambient ionization source is of great importance to the popularization of mass spectrometry. However, current ambient ionization sources are typically connected to several accessory equipment such as high voltage power supply, gas cylinders, and injection pumps. We report hand-powered ionization methods for mass spectrometric detection of small molecules based on a piezoelectric element that transforms hand mechanical energy into electrical energy. The piezoelectric element only weighs 39 g and lengths 9 cm, and no extra accessory equipment is needed. Paper spray, nanoelectrospray, and pin-to-funnel discharge powered by the piezoelectric elements were achieved, and several small molecule standards, including drugs, herbicides, etc., were detected and confirmed using these devices with a benchtop mass spectrometer. In addition, terbuthylazine (a herbicide) on the surface of a tomato was detected using the hand-powered pin-to-funnel discharge coupled with a miniature mass spectrometer, which indicates a potentially broader application of these methods in the on-site detection field. The methods described here are low-cost, user-friendly, miniatured, and versatile. Although efforts are still needed for the improvement of the performance, the piezoelectric element shows the alternative pathway of the miniaturization of ambient ionization.

Simultaneous optimization of paper spray substrates and solvents for hydrophilic and hydrophobic molecules

Paper spray mass spectrometry is an ambient ionization technique capable of the direct ionization of analyte from a bio-fluid spot on a paper substrate. Different solvents and types of paper can have different interactions with the analytes of interest; therefore, they can significantly impact the analyte signal and the assay as a whole. In this study, we examined the effects of substrate-solvent composition on signal intensity, blank signal intensity, and signal-to-blank ratio for a variety of pharmaceutical drugs, illicit drugs, chemical warfare agent (CWA) simulants, and CWA hydrolysis products. The analytes were prepared either neat or spiked into human plasma and deposited on a variety of modified paper substrates. Extraction occurred with a range of different solvents. Optimizing the substrate-solvent combination improved the signal-to-blank ratio for all compounds ranging from 1 to 7,964 factor improvement, with the substrate providing a more impactful improvement. Aprotic solvents, such as tetrahydrofuran and ethyl acetate, tended to produce optimal signal-to-blank ratios, while carbon sputtered and glass fiber substrates were the top paper substrates. The research presented herein illustrates the need for systematic optimization of substrate and spray solvent combinations to achieve the best detection limits for paper spray analysis.

In Situ Construction of COF-Based Paper Serving as a Plasmonic Substrate for Enhanced PSI-MS Detection of Polycyclic Aromatic Hydrocarbons.

Accurate detection, quantitation, and differentiation of polycyclic aromatic hydrocarbons (PAHs) and their isomers in diverse samples is elusive for paper spray ionization mass spectrometry (PSI-MS). To address these issues, herein, for the first time, we propose to fabricate a novel, flexible, and stable paper substrate based on covalent organic frameworks (COFs) via an in situ method under room temperature in air. After embedding gold nanoparticles (AuNPs), this paper substrate (COFs-paper) could further serve as a multifunctional plasmonic matrix (AuNPs-COFs-paper) for dual-wavelength laser-assisted PSI-MS detection of PAHs and feasible paper surface-enhanced Raman scattering (pSERS)-aided isomer discrimination. Taking advantage of the synergistic effect between the AuNPs and COFs present on the novel AuNP-embedded COFs-paper substrate, a satisfied LOD of 0.50 ng/μL for phenanthrene was realized, which improved almost 300 times compared with the naked-paper matrix, and the regression coefficient R2 was up to 0.999. Real sample corn oil-containing PAHs can be efficiently detected and identified using this technique. The established platform has promising potential for on-site chemical analysis with portable PSI-MS and pSERS instruments.

Combining the Katritzky Reaction and Paper Spray Ionization Mass Spectrometry for Enhanced Detection of Amino Acid Neurotransmitters in Mouse Brain Sections.

This work describes the development of a system that combines a derivatization protocol based on the Katritzky reaction with paper spray ionization mass spectrometry (PSI-MS) for the analysis of amino acid neurotransmitters in mouse brain tissues. The system is relatively simple, consisting of spraying the derivatization solution onto a mouse brain section mounted on a glass slide, applying a small volume of solvent to moisten the sample, pressing a triangular paper onto the sample surface to transfer the sample constituents to the paper surface, and using the paper as a substrate for PSI-MS analysis. The Katritzky reaction facilitated the ionization of the amino acids by reacting a pyrylium salt with the amino group of the analytes, forming very stable pyridinium cations, which greatly increased the sensitivity of the PSI-MS analysis. Most of the intensities of the amino acids modified by the Katritzky reaction were more than 10 times greater than the nonderivatized ones. The system was applied for the analysis of brain sections obtained from mice with Parkinson's disease, and the amino acids gamma-aminobutyric acid (GABA) and glycine (Gly), two compounds very well-known in studies of Parkinson's disease, were readily detected. The results suggest that the Katritzky reaction combined with PSI-MS might offer a significant advance in the knowledge on protocols that improve the sensitivity of detection of crucial biological compounds.

Femtoamp and picoamp modes of electrospray and paper spray ionization

Sub nanoampere ionization was investigated using glass emitters and paper spray substrates. An electrometer was set up to measure ionization current as low as 20 fA, while the ion trap mass spectrometer was operated to analyze ion current as low as 1 ion per second. Femto amp (100 s fA) ionization currents were generated using glass emitters with 90 nm tip or 4 μm tips. Using the 4 μm emitter tips, both the fA mode and the regular nanoESI mode were generated. Mass spectra produced by the fA mode ESI were >3 order of magnitude less intense than those produced by nanoESI mode. Beyond generating ESI type of ions, fA mode ESI generates native cytochrome c charge states without using any buffering agent. Femto amp ionization was also observed when conducting paper spray ionization, as well as when ionizing dry paper substrate without solvent. Ultra-low current ionization allowed direct analysis of undiluted sample matrices without carryover contamination. Samples collected and stored on a dried paper substrate were analyzed with no sample preparation.

Measuring the Chemical Evolution of Levitated Particles: A Study on the Evaporation of Multicomponent Organic Aerosol.

Single-particle levitation methods provide an effective platform for probing the physical properties of atmospheric aerosol via micrometer-sized particles. Until recently, chemical composition measurements on levitated particles were limited to spectroscopy, yielding only basic chemical information. Here, we describe, benchmark, and discuss the applications of an approach for probing the physical properties and chemical composition of single levitated particles using high-resolution mass spectrometry (MS). Using a linear quadrupole electrodynamic balance (LQ-EDB) coupled to paper spray mass spectrometry, we report accurate measurements of the evolving size within 5 nm (using broadband light scattering) and relative composition (using MS) of evaporating multicomponent levitated particles in real time. Measurements of the evaporation dynamics of semivolatile organic particles containing a range of n-ethylene glycols (n = 3, 4, and 6) in various binary and ternary mixtures were made under dry conditions and compared with predictions from a gas-phase diffusion evaporation model. Under assumptions of ideal mixing, excellent agreement for both size and composition evolution between measurements and models were obtained for these mixtures. At increased relative humidity, the presence of water in particles causes the assumption of ideality to break down, and the evaporative mass flux becomes a function of the mole fraction and activity coefficient. Through compositionally resolved evaporation measurements and thermodynamic models, we characterize the activity of organic components in multicomponent particles. Our results demonstrate that the LQ-EDB-MS platform can identify time-dependent size and compositional changes with high precision and reproducibility, yielding an effective methodology for future studies on chemical aging and gas-particle partitioning in suspended particles.

Desalting paper spray mass spectrometry (DPS-MS) for rapid detection of glycans and glycoconjugates

The detection of glycans and glycoconjugates has gained increasing attention in biological fields. Traditional mass spectrometry (MS)-based methods for glycoconjugate analysis are challenged with poor sensitivity when dealing with complex biological samples. We developed a desalting paper spray mass spectrometry (DPS-MS) strategy to overcome the issue of signal suppression of carbohydrates in salted buffers. Glycans and glycoconjugates (i.e., glycopeptides, nucleotide sugars, etc.) in non-volatile buffer (e.g., Tris buffer) can be loaded on the paper substrate from which buffers can be removed by washing with ACN/H2O (90/10 v/v) solvent. Glycans or glycoconjugates can then be eluted and spray ionized by adding ACN/H2O/formic acid (FA) (10/90/1 v/v/v) solvent and applying a high voltage (HV) to the paper substrate. Our results showed that DPS-MS is applicable for direct detection of intact glycopeptides and nucleotide sugars as well as determination of glycosylation profiling of antibody, such as NIST monoclonal antibody IgG (NISTmAb). NISTmAb was deglycosylated with PNGase F to release N-linked oligosaccharides. Twenty-six N-linked oligosaccharides were detected by DPS-MS within a 5-min timeframe without the need for enrichment or derivatization. This work demonstrates that DPS-MS allows fast and sensitive detection of glycans/oligosaccharides and glycosylated species in complex matrices and has great potential in bioanalysis.

Schirmer paper tear sampling of human eye diseases for paper spray mass spectrometry analysis

Paper spray mass spectrometry (PSMS) is a powerful analytical technique for direct analysis of human body fluids. Schirmer paper is commonly used to collect human tears in clinical examination. In this work, Schirmer paper was used for noninvasive sampling and storing of healthy and disease-infected human tears, and was then performed PSMS for direct tear analysis under both positive and negative detection modes. 24 healthy tear samples, 34 tear samples of meibomain gland dysfunction, 44 tear samples of senile cataract, and 32 tear samples of allergic conjunctivitis were investigated in this work. Screening potential biomarkers of different eye diseases were carried out by combining multivariate analysis methods. 41 positive ions and 53 negative ions were proposed to be potential biomarkers in this work. The capacity of Schirmer paper for storing tear sample at different temperatures was investigated. The present study shows that direct coupling Schirmer PSMS with multivariate analysis could be a simple, rapid, and in vivo method for screening the biomarkers from human tears that involved different eye diseases.

Characterizing the Dyes of Pre-Columbian Andean Textiles: Comparison of Ambient Ionization Mass Spectrometry and HPLC-DAD

The complex and colorful textiles of ancient Peru have long been a focus of technical study, particularly to characterize the sources of the wide variety of dyes utilized by these Andean artisans. This manuscript describes the characterization of the dyes of both primary (red, blue, and yellow) and secondary (purple, orange, and green) colors sampled from textiles spanning five major civilizations: the Paracas Necropolis, the Nazca, the Wari, the Chancay, and the Lambayeque, all from Peru. All but the Paracas Necropolis samples were part of technical conservation studies of the ancient South American textiles collections of the Michael C. Carlos Museum. Analysis of the dyes was carried out utilizing direct analysis in real time time-of-flight mass spectrometry (DART-MS) and paper spray MS. To validate these ambient ionization MS methods, the samples were further investigated using high-performance liquid chromatography (HPLC) with ultraviolet-visible diode array detection (DAD). These results show that ambient ionization MS methods are simple and fast for characterization of the general classes of dyes, e.g., plant reds vs. insect reds, and indigoids in blues and greens. Due to the myriad possible sources of yellow dyes and their tendency to undergo oxidative decomposition, positively identifying those components in these yarns was difficult, though some marker compounds and flavonoid decomposition products were readily identified by ambient ionization mass spectrometry.

Paper Spray Mass Spectrometry on the Analysis of Phenolic Compounds in Rhynchelytrum repens: A Tropical Grass with Hypoglycemic Activity.

The characterization of plant compounds with pharmacological activity is a field of great relevance in research and development. As such, identification techniques with the goal of developing new drugs or even validating the bioactive properties of extracts must be explored in order to further expand the knowledge of plant extract composition. Most works in this field employ HPLC, when exploring non-structural and cell wall carbohydrates from Rhynchelytrum repens. Phenolic compounds were studied by classical chromatography techniques and UV-vis spectrophotometry, with C-glycosylated flavonoids being detected but with no further details regarding the chemical structure of these compounds. In this work we employ paper spray ionization mass spectrometry (PS-MS) for the evaluation of the chemical profile of R. repens methanol extract. Positive ionization mode identified 15 compounds, belonging to flavonoids, fatty acids, and other classes of compounds; negative mode ionization was able to identify 20 compounds comprising the classes of quinic acids, stilbenes and flavonoids. PS-MS proved effective for the evaluation of R. repens extracts, making it possible to identify a total of thirty-five compounds. The bioactive properties attributed to R. repens were confirmed by the identification and characterization of compounds identified by PS-MS.

A new quantitative drug checking technology for harm reduction: Pilot study in Vancouver, Canada using paper spray mass spectrometry.

IntroductionDrug checking services for harm reduction and overdose prevention have been implemented in many jurisdictions as a public health intervention in response to the opioid overdose crisis. This study demonstrates the first on‐site use of paper spray mass spectrometry for quantitative drug checking to address the limitations of current on‐site drug testing technologies.MethodsPaper spray mass spectrometry was used to provide on‐site drug checking services at a supervised consumption site in the Downtown Eastside of Vancouver, British Columbia, Canada during a 2‐day pilot test in August 2019. The method included the targeted quantitative measurement of 49 drugs and an untargeted full scan to assist in identifying unknown/unexpected components.ResultsDuring the pilot, 113 samples were submitted for analysis, with 88 (78%) containing the client expected substance. Fentanyl was detected in 45 of 59 expected fentanyl samples, and in 50 (44%) samples overall at a median concentration of 3.6% (w/w%). The synthetic precursor of fentanyl, 4‐anilino‐N‐phenethyl‐piperidine (4‐ANPP), was found in 74.0% of all fentanyl samples at a median concentration of 2.2%, suggesting widespread poor manufacturing practices. Etizolam was detected in 10 submitted samples anticipated to be fentanyl at a median concentration of 2.5%. No clients submitting these samples expected etizolam or a benzodiazepine in their sample. In three instances, it was co‐measured with fentanyl, and in seven cases it was detected alone.Discussion and ConclusionsThe quantitative capabilities and low detection limits demonstrated by paper spray mass spectrometry offer distinct benefits over existing on‐site drug checking methods and harm reduction services.

Exploration of the Soft Ionization Performance of Paper Spray Mass Spectrometry

Exploration of the Soft Ionization Performance of Paper Spray Mass Spectrometry

On-Surface Alcohol Oxidation Monitored by Paper Spray Mass Spectrometry: The Role of Ruthenium as Catalyst.

Paper spray ionization mass spectrometry (PS-MS) is employed herein as a convenient platform to investigate an on-surface catalytic process, that is, the oxidation of alcohols induced by ruthenium salts. The tag-charged benzyl alcohol 1 (m/z 166), used as a suitable prototype starting substrate, is quickly oxidized by tert-butyl hydroperoxide (TBHP) in an on-surface process catalyzed by ruthenium trichloride (RuCl3). The PS(+)-MS revealed the formation of products from the oxidation of alcohol 1. RuCl3 and TBHP played a crucial role in this process since when salts of other metals (platinum, palladium, and iron) and another oxidizing agent (hydrogen peroxide) are employed, no reaction is observed. Moreover, UV radiation and heating accelerate the on-surface alcohol 1 oxidation. Finally, an exciting possibility is to employ PS-MS to investigate similar organic catalytic reactions to accelerate them and detect unstable intermediates, indiscernible in the condensed phase.

Mass spectrometry with paper spray ionization in analysis of the Arrabidaea chica leaf tea

The species Arrabidaea chica (Humb. & Bonpl.) B. Verl. (Bignoniaceae) is a plant native to tropical forests, popularly known as pariri or crajiru, and it is widely used in folk medicine to treat inflammatory diseases, anemias, skin diseases and to assist in the treatment of leukemia. Because of the widespread use of the plant, concern with its quality and effectiveness is fundamental. This study demonstrates the application of mass spectrometry with ionization by paper spray (PS-MS) as a chemical characterization method to evaluate the presence of the active principles in teas prepared by infusion from commercial samples of the medicinal plant Arrabidaea chica by infusion. The analyses of the samples were performed in two periods: 24 hours and 15 days after the preparation of the teas. Compounds referring to the class of substances 3-deoxythocyanidins were detected without any pre-treatment of the sample or chromatographic separation to provide valuable information for the evaluation and quality control of this product. Significant changes in the m/z signals of greater intensity, referring to the class of 3-deoxythocyanidins, were observed in the mass spectra, and multivariate analysis corroborated the degradation of this class of substances with time, resulting in a probable loss of the quality and effectiveness of the tea.

Point-of-Care Test Paper for Exhaled Breath Aldehyde Analysis via Mass Spectrometry.

Volatile organic compounds (VOCs) from exhaled breath (EB) are considered to be promising biomarkers for lung diseases. A convenient and sensitive point-of-care (POC) testing method for EB VOCs is essential. Here, we developed a POC test paper for the analysis of EB aldehydes, which are potential biomarkers for lung cancer. A probe molecule, 4-aminothiophenol (4-ATP), was anchored on a paper substrate to specifically capture gas-phase aldehydes through the Schiff base reaction. Meanwhile, thin-film reaction acceleration was utilized to increase capture efficiency. By directly coupling the test paper to a mass spectrometer through paper spray, high sensitivity (0.1 ppt) and a wide quantification linear range (from 10 ppt to 1 ppm) were obtained. Analysis of EB from lung cancer patients with the test paper showed a significant increase in several reported aldehyde markers compared to EB from healthy volunteers, indicating the potential of this method for sensitive, low-cost, and convenient lung cancer screening and diagnosis.

Paper spray ionization coupled to Fourier Transform Ion Cyclotron Resonance Mass Spectrometry as a tool to fight the counterfeiting of medicines

Analyses of illicit drugs and medicines in forensic laboratories require constant improvements and updates in protocols and analytical techniques in order to follow the new trends employed by illicit producers. Therefore, applying reliable and fast techniques to perform the chemical profiling of seized samples, allowing for detection of the different types of falsification performed, is an urgent measure. In this study, Paper Spray Ionization (PSI) coupled to Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) was used for determining the chemical profiling of 92 samples of counterfeit medicines and ecstasy tablets. Afterwards, all the samples were evaluated using principal component analysis (PCA) to distinguish their chemical composition. From the results, different strategies for medicine counterfeiting were identified, such as changing the API and employing a mixture of substances to produce distinct medicines. Cross contamination of medicines with cocaine and 3,4-methylenedioxymethamphetamine (MDMA) was also detected. Moreover, the compounds cassaidine and glyceryl nonivamide were identified in all three classes of the seized medicines analyzed. Such compounds act as new markers in illicit production, not reported before in counterfeit medicines. The majority of ecstasy tablets contained MDMA and ethylone in their composition. Using PSI-MS combined with chemometrics, substances present in the seized medicines and ecstasy tablets could be detected through a simple, fast, and reliable procedure. Therefore, it was possible to connect the substances present in the seized material according to their chemical profiling, thus producing important evidence for police intelligence, which constitutes a great tool to be employed in forensic laboratories.

A fast and direct determination of bisphenol S in thermal paper samples using paper spray ionization mass spectrometry.

Concerns about human health regarding the large use of bisphenol A in thermal papers have led to its replacement by bisphenol S. Analyses of bisphenols require several sample pretreatment steps, which are laborious, expensive, and time-consuming. A paper spray ionization mass spectrometry (PSI-MS) was developed to detect and quantify bisphenol S in three different brands of thermal papers commercially available. Parameters such as paper size, and paper position relative to the mass spectrometer inlet were evaluated. The analyses were performed in selected ion monitoring mode on a linear ion trap mass spectrometer. The developed method presented absolute recovery values ranging from 92.2 to 109.04%, accuracy values from -1.2 to 9.0%, and inter assay precision from 1.8 to 5.6% and enabled LOD as low as 5 ng g-1. The concentration of bisphenol S in all of the three brands of BPA-free thermal papers evaluated ranged from 1.36 to 6.77 μg g-1, and the concentrarion of BPA ranged from 6.56 to 16.4 μg g-1 in all samples of thermal paper evaluated. The PSI-MS method described here was comparable to the conventional ones, such as liquid chromatography coupled with mass spectrometry and gas chromatography coupled with mass spectrometry described in the literature. The present study proved to be practical, fast, and efficient for the direct determination of bisphenol S in thermal papers. Furthermore, the methodology here described showed to be a promising alternative to replace the classical methods for determination of bisphenol S, due to its simplicity, and no needing of any sample pretreatment.

Rapid Diagnosis of Prostate Cancer Disease Progression Using Paper Spray Ionization Mass Spectrometry.

The limitation of prostate specific antigen (PSA) for prostate cancer (PC) diagnosis is well-recognized. The Gleason score (GS) has been the most widely used grading system for prostate tumor differentiation and represents the best-established prognostic indicator for prostate cancer progression. However, a rapid and sensitive noninvasive diagnostic marker that differentiates GS-based prostate cancer disease progression is needed. As PC is becoming a leading cause of cancer related death for men in the U.S. and worldwide, an immediate need exists for an improved, sensitive, noninvasive, and rapid diagnostic test for PC screening. Here, we employed paper spray ionization-mass spectrometry (PSI MS)-based global metabolomics of urine liquid biopsies to distinguish between healthy (negative for any prostate specific health problems) and progressive PC states (low grade PC such as GS6 and high-grade PC such as GS7, GS8, and GS9). For PSI-MS-based direct untargeted metabolic investigation, a raw urine sample was directly pipetted onto a triangular paper substrate, without any additional sample preparation. Multivariate statistical analysis revealed distinct GS-specific metabolic signatures compared to a healthy control. Variable importance in projection from partial least-squares-discriminant analysis showed distinct metabolic patterns that were correlatively elevated with progressive disease and could serve as biomarkers for diagnosis of prostate cancer risk categorization.

High-throughput determination of flavanone-O-glycosides in citrus beverages by paper spray tandem mass spectrometry

A fast and accurate methodology for the quantification of the most abundant flavanone glycosides in citrus beverages has been developed. The approach relies on the use of paper spray mass spectrometry, which allows to record data in few minutes and without sample pre-treatment. The experiments have been carried out in Multiple Reaction Monitoring scan mode, in order to obtain the best specificity and sensitivity. The analytical parameters were all satisfactory. The results coming from the analysis of real samples were compared to the data obtained by the commonly used chromatographic method, proving the robustness of the proposed approach.