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Conventional mass spectrometry (MS)-based analytical methods for small carbohydrate fragments (oligosaccharides, degree of polymerization 2-12) are time-consuming due to the need for an offline sample pretreatment such as desalting. Herein, we report a new paper spray ionization method, named desalting paper spray (DPS), which employs a piece of triangular filter paper for both sample desalting and ionization. Unlike regular paper spray ionization (PSI) and nanoelectrospray ionization (nanoESI), DPS-MS allows fast and sensitive detection of oligosaccharides in biological samples having complex matrices (e.g., Tris, PBS, HEPES buffers, or urine). When an oligosaccharide sample is loaded onto the filter paper substrate (10 × 5 mm, height × base) made mostly of cellulose, oligosaccharides are adsorbed on the paper via hydrophilic interactions with cellulose. Salts and buffers can be washed away using an ACN/H 2 O (90/10 v/v ) solution, while oligosaccharides can be eluted from the paper using a solution of ACN/H 2 O/formic acid (FA) (10/90/1 v/v/v ) and directly spray-ionized from the tip of the paper. Various saccharides at trace levels (e.g., 50 fmol) in nonvolatile buffer can be quickly analyzed by DPS-MS (<5 min per sample). DPS-MS is also applicable for direct detection of oligosaccharides from glycosyltransferase (GT) reactions, a challenging task that typically requires a radioactive assay. Quantitative analysis of acceptor and product oligosaccharides shows increased product with increased GT enzymes used for the reaction, a result in line with the radioactivity assay. This work suggests that DPS-MS has potential for rapid oligosaccharide analysis from biological samples.

Proteinaceous toxins are harmful proteins derived from plants, bacteria, and other natural sources. They pose a risk to human health due to infection and also as possible biological warfare agents. Paper spray mass spectrometry (PS-MS) with wipe sampling was used to detect proteins from surfaces as a potential tool for identifying the presence of these toxins. Proteins ranging in mass between 12.4 and 66.5 kDa were tested, including a biological toxin simulant/vaccine for Staphylococcal enterotoxin B (SEBv). Various substrates were tested for these representative proteins, including a laboratory bench, a notebook cover, steel, glass, plant leaf and vinyl flooring. Carbon sputtered porous polyethylene (CSPP) was found to outperform typical chromatography paper used for paper spray, as well as carbon nanotube (CNT)-coated paper and polyethylene (PE), which have been previously shown to be well-suited for protein analysis. Low microgram quantities of the protein toxin simulant and other test proteins were successfully detected with good signal-to-noise from surfaces using a porous wipe. These applications demonstrate that PS-MS can potentially be used for rapid, sample preparation-free detection of proteins and biological warfare agents, which would be beneficial to first responders and warfighters.

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.

Fentanyl and its analogues play a major role in the current opioid epidemic. In particular, these highly potent opioids have become a health hazard due to their use as additives in street drugs. Consequently, rapid on-site procedures for the analysis of this class of seized drugs are needed, especially considering the reported backlog of drug samples, which must undergo identification and confirmation tests to validate the presence of an illicit substance. Paper based devices are cheap sampling and analysis vehicles that have been shown capable of allowing rapid identification and confirmation of drugs of abuse. Modifying paper substrates by imprinting nanoparticles enables surface enhanced Raman spectroscopy (SERS) as well as a second analysis from the same substrate, namely paper spray ionization mass spectrometry. While such a procedure has been described for laboratory use, these illicit drug samples are typically collected in the field and this is where testing should be done. We combine paper SERS and paper spray MS on field-portable and commercial off-the-shelf (COTS) devices for the rapid and low-cost identification and confirmation of fentanyl and its analogues, enabling in situ analysis at the point of seizure of suspect samples. The commercial nature of both instruments moves this technology from the academic realm to a setting where the criminal justice system can realistically utilize it. The capabilities of this single-substrate dual-analyzer technique are further examined by sampling a variety of surfaces of forensic interest.

In this study, the direct analysis of doping agents in urine samples with no sample preparation by a modified paper spray mass spectrometry (PS-MS) methodology has been demonstrated for the first time. We have described a paper surface treatment with trichloromethylsilane using a gas-phase reaction to increase the ionization of target compounds. This approach was applied for the analysis of two classes of banned substances in urine samples: anabolic agents (trenbolone and clenbuterol) and diuretics (furosemide and hydrochlorothiazide). Under optimized conditions, the developed methods presented satisfactory repeatability, and an analysis of variance showed linearity without lack-of-fit. Highly sensitive detections as low as sub-nanogram per milliliter levels, which is below the minimum required performance levels proposed by the World Anti-Doping Agency, have been reached using the hydrophobic PS-MS analysis without any preconcentration and cleanup step.

A new approach using paper spray ionization mass spectrometry (PSI-MS) for the analysis of steroid hormones in wastewater samples has been demonstrated. Triangular papers containing paraffin barriers as microfluidic channels were used to direct the sample solution to the paper tip, preventing the sample from spreading over the corners of the paper. The method was used to analyze the hormones levonorgestrel and algestone acetophenide in industrial wastewaters. Analytical curves presented a correlation coefficient ( R 2 ) above 0.99. Limits of quantification were below 2.3 ppm and limits of detection below 0.7 ppm. Values of precision (coefficient of variation) and accuracy (relative error) were less than 15% for all analyses. Recovery results ranged from 82% to 102%. Levonorgestrel was also analyzed by high-performance liquid chromatography coupled to mass spectrometry in order to compare the analytical performance with PSI-MS. No statistically significant differences were found between both methods. This study demonstrates the usefulness of PSI-MS for rapid analysis of hormones in industrial wastewater samples and also indicates its potential to be employed as a simple and reliable analytical method in environmental sciences.

Determining bacterial identity at the strain level is critical for public health to enable proper medical treatments and reduce antibiotic resistance. Herein, we used liquid chromatography, ion mobility, and tandem MS (LC-IM-MS/MS) to distinguish Escherichia coli ( E. coli ) strains. Numerical multivariate statistics (principal component analysis, followed by linear discriminant analysis) showed the capability of this method to perform strain-level discrimination with prediction rates of 96.1% and 100% utilizing the negative and positive ion information, respectively. The tandem MS and LC separation proved effective in discriminating diagnostic lipid isomers in the negative mode, while IM separation was more effective in resolving lipid conformational biomarkers in the positive ion mode. Because of the clinical importance of early detection for rapid medical intervention, a faster technique, paper spray (PS)-IM-MS/MS, was used to discriminate the E. coli strains. The achieved prediction rates of the analysis of E. coli strains by PS-IM-MS/MS were 62.5% and 73.5% in the negative and positive ion modes, respectively. The strategy of numerical data fusion of negative and positive ion data increased the classification rates of PS-IM-MS/MS to 80.5%. Lipid isomers and conformers were detected, which served as strain-indicating biomarkers. The two complementary multidimensional techniques revealed biochemical differences between the E. coli strains confirming the results obtained from comparative genomic analysis. Moreover, the results suggest that PS-IM-MS/MS is a rapid, highly selective, and sensitive method for discriminating bacterial strains in environmental and food samples.

Cannabinoids present a unique set of analytical challenges. An increasing number of states have voted to decriminalize recreational marijuana use, creating a need for new kinds of rapid testing. At the same time, synthetic compounds with activity similar to THC, termed synthetic cannabinoids, have become more prevalent and pose significant health risks. A rapid method capable of detecting both natural and synthetic cannabinoids would be useful in cases of driving under the influence of drugs, where it might not be obvious whether the suspect consumed marijuana, a synthetic cannabinoid, or both. Paper spray mass spectrometry is an ambient ionization technique which allows for the direct ionization of analyte from a biofluid spot on a piece of paper. Natural cannabinoids like THC, however, are labile and rapidly disappear from dried sample spots, making it difficult to detect them at clinically relevant levels. Presented here is a method to concentrate and preserve THC and synthetic cannabinoids in urine and oral fluid on paper for analysis by paper spray mass spectrometry. Sesame seed oil was investigated both as a means of preserving THC and as part of a technique, termed paper strip extraction, wherein urine or oral fluid is flowed through an oil spot on a strip of paper to preconcentrate cannabinoids. This technique preserved THC in dried biofluid samples for at least 27 days at room temperature; paper spray MS/MS analysis of these preserved dried spots was capable of detecting THC and synthetic cannabinoids at low ng/mL concentrations, making it suitable as a rapid screening technique. The technique was adapted to be used with a commercially available autosampler.

Paper spray mass spectrometry is a method for the direct analysis of biofluid samples in which extraction of analytes from dried biofluid spots and electrospray ionization occur from the paper on which the dried sample is stored. We examined matrix effects in the analysis of small molecule drugs from urine, plasma, and whole blood. The general method was to spike stable isotope labeled analogs of each analyte into the spray solvent, while the analyte itself was in the dried biofluid. Intensity of the labeled analog is proportional to ionization efficiency, whereas the ratio of the analyte intensity to the labeled analog in the spray solvent is proportional to recovery. Ion suppression and recovery were found to be compound- and matrix-dependent. Highest levels of ion suppression were obtained for poor ionizers (e.g., analytes lacking basic aliphatic amine groups) in urine and approached -90%. Ion suppression was much lower or even absent for good ionizers (analytes with aliphatic amines) in dried blood spots. Recovery was generally highest in urine and lowest in blood. We also examined the effect of two experimental parameters on ion suppression and recovery: the spray solvent and the sample position (how far away from the paper tip the dried sample was spotted). Finally, the change in ion suppression and analyte elution as a function of time was examined by carrying out a paper spray analysis of dried plasma spots for 5 min by continually replenishing the spray solvent. Graphical Abstract ᅟ.

On-line coupling of electrochemistry (EC) to mass spectrometry (MS) is a powerful approach for identifying intermediates and products of EC reactions in situ. In addition, EC transformations have been used to increase ionization efficiency and derivatize analytes prior to MS, improving sensitivity and chemical specificity. Recently, there has been significant interest in developing paper-based electroanalytical devices as they offer convenience, low cost, versatility, and simplicity. This report describes the development of tubular and planar paper-based electrochemical cells (P-EC) coupled to sonic spray ionization (SSI) mass spectrometry (P-EC/SSI-MS). The EC cells are composed of paper sandwiched between two mesh stainless steel electrodes. Analytes and reagents can be added directly to the paper substrate along with electrolyte, or delivered via the SSI microdroplet spray. The EC cells are decoupled from the SSI source, allowing independent control of electrical and chemical parameters. We utilized P-EC/SSI-MS to characterize various EC reactions such as oxidations of cysteine, dopamine, polycyclic aromatic hydrocarbons, and diphenyl sulfide. Our results show that P-EC/SSI-MS has the ability to increase ionization efficiency, to perform online EC transformations, and to capture intermediates of EC reactions with a response time on the order of hundreds of milliseconds. The short response time allowed detection of a deprotonated diphenyl sulfide intermediate, which experimentally confirms a previously proposed mechanism for EC oxidation of diphenyl sulfide to pseudodimer sulfonium ion. This report introduces paper-based EC/MS via development of two device configurations (tubular and planar electrodes), as well as discusses the capabilities, performance, and limitations of the technique.

Currently, all assays measuring acetylcholinesterase (AChE) activity following a suspected nerve agent exposure leverage methodologies that fail to identify the agent. This limits the overall effectiveness and ability to administer proper countermeasures. As such, there is an urgent need to identify novel, rapid, and more comprehensive approaches to establish AChE activity, including identification of the toxicant. Paper spray mass spectrometry was used to monitor the activity of acetylcholinesterase, both in-solution and on modified hydrophobic paper surface. Hydrophobic paper surfaces were prepared using vaporized trichloro(3,3,3-trifluoropropyl)silane. In both approaches, mixtures of diluted human whole blood with and without VX were mixed with a non-endogenous AChE specific substrate, 1,1-dimethyl-4-acetylthiomethylpiperidinium (MATP+). Formation of the cleaved MATP+ product was monitored over time and compared to MATP+ to determine relative AChE activity. This on-substrate assay was effective at determining AChE activity and identifying the toxicant; however, determination of AChE activity in-solution proceeded at a slower rate. The on-substrate assay serves as a pioneering example of an enzymatic reaction occurring on the surface of a paper spray ionization ticket. This work broadens the range of applications relating to paper spray ionization-based clinical diagnostic assays. Graphical Abstract ᅟ.

Suzuki-Miyaura cross-coupling is one of the most powerful strategies for constructing biaryl compounds. However, classic Suzuki-Miyaura coupling suffers from hour-scale reaction time and competitive protodeboronation. To address these problems, a mild nonaqueous potassium trimethylsilanolate (TMSOK)-assisted Suzuki-Miyaura coupling strategy was designed for the microsynthesis of biaryls in paper spray ionization (PSI). Due to the acceleration power facilitated by microdroplet chemistry in reactive PSI, the microsynthesis of biaryls by reactive PSI was accomplished within minutes with comparable yields to the bulk, showing good substrate applicability from 32 Suzuki-Miyaura reactions of aryl bromides and aryl boronic acid/borates bearing different substituents. Based on the above TMSOK-assisted Suzuki-Miyaura coupling strategy, we further developed a high-sensitivity and selective PSI mass spectrometry (MS) method for quantitative analysis of aryl bromides, a class of environmentally persistent organic pollutants that cannot be directly detected by ambient mass spectrometry due to their low ionization efficiency. In situ derivatization of aryl bromides was achieved with aryl borates bearing quaternary ammonium groups in PSI. The proposed PSI-MS method shows good linearity over the 0.01-10 μmol L -1 range with low detection limits of 1.8-4.8 nmol L -1 as well as good applicability to the rapid determination of six aryl bromides in three environmental water samples. The proposed PSI-MS method also shows good applicability to brominated flame retardants (polybrominated diphenyls/diphenyl esters). Overall, this study provides a simple, rapid, low-cost, high-sensitivity, and high-selectivity strategy for trace aryl bromides and other brominated pollutants in real samples with minimal/no sample pretreatment.

This study proposes a new direct and fast method of analysis employing paper spray mass spectrometry (PS-MS). The paper used in the proposed method was modified with molecularly imprinted polymers (MIP) to create a specific site for cocaine analysis in oral fluid. MIP membrane was successfully synthetized and employed. The developed method showed to be linear in a concentration range from LOQ to 100 ng mL -1 . The experimental value of LOQ obtained was 1 ng mL -1 . The inter-day and intra-day precision and accuracy of the PS-MS method presented values lower than 15%. The total recoveries were also evaluated. The PS-MS method for the analysis of cocaine in oral fluid showed to be very promising and the validation parameters showed a good correlation with the literature. Graphical abstract ᅟ.

Paper spray tandem mass spectrometry is used to identify and quantify eight individual amphetamines in whole blood in 1.3 min. The method has been optimized and fully validated according to forensic toxicology guidelines, for the quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), and 4-fluoroamphetamine (4-FA). Additionally, a new concept of intrinsic and application-based selectivity is discussed, featuring increased confidence in the power to discriminate the amphetamines from other chemically similar compounds when applying an ambient mass spectrometric method without chromatographic separation. Accuracy was within ±15% and average precision was better than 15%, and better than 20% at the LLOQ. Detection limits between 15 and 50 ng/mL were obtained using only 12 μL of whole blood. Graphical abstract ᅟ.

A method is presented for the direct quantitative analysis of therapeutic drugs from dried blood spot samples by mass spectrometry. The method, paper spray mass spectrometry, generates gas phase ions directly from the blood card paper used to store dried blood samples without the need for complex sample preparation and separation; the entire time for preparation and analysis of blood samples is around 30 s. Limits of detection were investigated for a chemically diverse set of some 15 therapeutic drugs; hydrophobic and weakly basic drugs, such as sunitinib, citalopram, and verapamil, were found to be routinely detectable at approximately 1 ng/mL. Samples were prepared by addition of the drug to whole blood. Drug concentrations were measured quantitatively over several orders of magnitude, with accuracies within 10% of the expected value and relative standard deviation (RSD) of around 10% by prespotting an internal standard solution onto the paper prior to application of the blood sample. We have demonstrated that paper spray mass spectrometry can be used to quantitatively measure drug concentrations over the entire therapeutic range for a wide variety of drugs. The high quality analytical data obtained indicate that the technique may be a viable option for therapeutic drug monitoring.

The determination of the age of an ink entry from a questioned document is often a major problem and a controversial issue in forensic sciences. Therefore, it is important to understand the aging process of the different components found in ink. The aim of this work is to characterize the degradation processes of methyl violet and ethyl violet, two typical ballpoint dyes by using laser desorption/ionization (LDI) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS), and to evaluate the possible application of the method to forensic examination of documents. The mass spectrometric methods were first tested and were found to be adequate for the purpose of this work. Moreover, it is possible to analyze the dye from a stroke directly from the paper (LDI-MS), so the sample preparation is minimized. The degradation of the dyes methyl violet and ethyl violet in strokes from a ballpoint pen was studied under laboratory conditions influenced by different factors such as light, wavelength of light, heat, and humidity. Then, strokes from the same ballpoint were aged naturally in the dark or under the influence of light over one year and then analyzed. The results show that the degradation of these dyes strongly depends on light fluence. Humidity also increases degradation, which can be explained by the basicity of the paper. The influence of heat on the degradation process was found to be rather weak. It was also observed that the dyes from the ink strokes did not show significant degradation after one year of storage in the dark. In conclusion, the storage conditions of a questioned document and the initial composition of the dyes in the ink have to be known for correct interpretation of the age of an ink entry. Measurements over longer periods of time are necessary to follow the degradation of dyes exempt from light exposure. LDI was found adequate and very useful for the analysis of ballpoint dyes directly from paper without further pretreatment.

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 (RuCl 3 ). The PS(+)-MS revealed the formation of products from the oxidation of alcohol 1 . RuCl 3 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.

The recent developments on fieldable miniature mass spectrometers require efforts to produce easy-to-use and portable alternative tools to assist in point-of-care analysis. In this paper, the reagent-pencil (RP) technology, which has been used for solvent-free deposition of reagents in paper-based microfluidics, was combined with paper spray ionization mass spectrometry (PS-MS). In this approach, named RP-PS-MS, the PS triangular piece of paper was written with the reagent pencil, consisting of mixtures of graphite and bentonite (used as a support) and a reactive compound, and allowed to react with a given analyte from a sample matrix selectively. We conducted typical applications as proof-of-principles to verify the methodology's general usefulness in detecting small organic molecules in distinct samples. Hence, various aldehydes (2-furaldehyde, valeraldehyde, and benzaldehyde) in spiked cachaça samples (an alcoholic drink produced from fermentation/distillation of sugarcane juice) were promptly detected using a reagent pencil doped with 4-aminophenol (the reactive compound). Similarly, we recognized typical ginsenosides and triacylglycerols (TAGs) in ginseng aqueous infusions and soybean oil samples, respectively, using lithium chloride as the reactive compound. The results indicate that the reagent-pencil methodology is compatible with PS-MS and provides an easy and fast way to detect target analytes in complex samples. The advantage over the usual solution-based deposition of reagents lies in the lack of preparation or carrying different specific solutions for special applications, which can simplify operation, especially in point-of-care analysis with fieldable mass spectrometers.

In this study, we report the use of pyrolysis-GCxGC/MS profiles for an optimized treatment of data issued from pyrolysis-GC/MS combined with the automatic deconvolution software Automated Mass Spectral Deconvolution and Identification System (AMDIS). The method was illustrated by the characterization of marker compounds of East Asian handmade papers through the examination of pyrolysis-GCxGC/MS data to get information which was used for manually identifying low concentrated and co-eluting compounds in 1D GC/MS data. The results showed that the merits of a higher separation power for co-eluting compounds and a better sensitivity for low concentration compounds offered by a GCxGC system can be used effectively for AMDIS 1D GC/MS data treatment: (i) the compound distribution in pyrolysis-GCxGC/MS profiles can be used as “peak finder” for manual check of low concentration and co-eluting compound identification in 1D GC/MS data, and (ii) pyrolysis-GCxGC/MS profiles can provide better quality mass spectra with observed higher match factors in the AMDIS automatic match process. The combination of 2D profile with AMDIS was shown to contribute efficiently to a better characterization of compound profiles in the chromatograms obtained by 1D analysis in focusing on the mass spectral identification.Graphical abstract [ABSTRACT FROM AUTHOR]

Fentanyl and its related synthetic analogs have recently become more readily available as a growing threat to public safety, such as pain relief and anesthetics. Sources of fentanyl are more likely to be illicitly manufactured than pharmaceutically manufactured and are often laced with other opioids, which ultimately increases the potency of fentanyl and results in an increased number of overdose deaths. The methods used to detect these compounds safely and quickly are of high interest due to their extreme potency. This study investigates the use of paper spray mass spectrometry (PS-MS), which is a simple atmospheric ionization process that can be used as a rapid study (60 s) with limited sample preparation and sample handling. PS-MS can be utilized with a synthetic microporous polyolefin silica matrix substrate, known as Teslin, which is manufactured by PPG Industries. The main characteristic of paper spray ionization with the Teslin substrate is the hydrophobicity, which is useful for a fast and direct analysis requiring only 1 μg of the sample. The application of this novel synthetic substrate to PS-MS has been illustrated with a fentanyl analog screening kit (FAS Kit), which was designed by the Centers for Disease Control (CDC) for the screening of 212 evolving synthetic opioids, including more than 190 fentanyl analogs. The comparable fragmentation with precursor molecule mass data from this study can be useful in improving the accurate detection and structural characterization of complex samples with a minimum interference of the isobaric components.

One limitation in the growing field of ambient or direct analysis methods is reduced selectivity caused by the elimination of chromatographic separations prior to mass spectrometric analysis. We explored the use of high-field asymmetric waveform ion mobility spectrometry (FAIMS), an ambient pressure ion mobility technique, to separate the closely related opiate isomers of morphine, hydromorphone, and norcodeine. These isomers cannot be distinguished by tandem mass spectrometry. Separation prior to MS analysis is, therefore, required to distinguish these compounds, which are important in clinical chemistry and toxicology. FAIMS was coupled to a triple quadrupole mass spectrometer, and ionization was performed using either a pneumatically assisted heated electrospray ionization source (H-ESI) or paper spray, a direct analysis method that has been applied to the direct analysis of dried blood spots and other complex samples. We found that FAIMS was capable of separating the three opiate structural isomers using both H-ESI and paper spray as the ionization source.

Squamous intraepithelial lesion is an abnormal growth of epithelial cells on the surface of the cervix that may lead to cervical cancer. Analytical protocols for the determination of squamous intraepithelial lesions are in high demand, since cervical cancer is the fourth most diagnosed cancer among women in the world. Here, paper spray ionization mass spectrometry (PSI-MS) is used to distinguish between healthy (negative for intraepithelial lesion or malignancy) and diseased (high-grade squamous intraepithelial lesion) blood plasmas. A total of 86 blood samples of different women (49 healthy samples, 37 diseased samples) were collected, and the plasmas were prepared. Then, 10 μL of each plasma sample was deposited onto triangular papers for PSI-MS analysis. No additional step of sample preparation was necessary. The interval-successive projection algorithm linear discriminant analysis (iSPA-LDA) was applied to the PSI mass spectra, showing six ions (mostly phospholipids) that were predictive of healthy and diseased plasmas. Values of 77% accuracy, 86% sensitivity, 80% positive predictive value (PPV), and 75% negative predictive value (NPV) were achieved. This study provides evidence that PSI-MS may potentially be used as a fast and simple analytical technique for the early diagnosis of cervical cancer.

Paper spray ionization has arisen relatively recently as a complement and alternative to electro- and nanospray ionization with silica capillaries. A majority of the work in the present literature focuses on the chemical aspect of paper spray. In order to study the physical and phenomenological facet of its implementation, we measured current and voltage distributions of Taylor cones. To study transport phenomena on filter paper, we addressed the behavior of large, sparingly soluble tetraalkylammonium ions, which are usually used as mobility standards, in paper spray. The variation of intensity with time of monomers and dimers of these ions was measured with a differential mobility analyzer and compared with that produced by contamination in the paper. At the same time, we evaluated the proficiency of different paper spray techniques for protein analysis using nano spray as a reference. Experiments suggest that Taylor cones in paper spray are subject to hysteresis, whereas transport phenomena in the porous substrate notably affects the ionization of the sample. Additionally, we observed that paper spray tends to favor lower charge states in proteins. [ABSTRACT FROM AUTHOR]

We randomly selected 100 journal articles published in five proteomics journals in 2019 and manually examined each of them against a set of 13 criteria concerning the statistical analyses used, all of which were based on items mentioned in the journals' instructions to authors. This included questions such as whether a pilot study was conducted and whether false discovery rate calculation was employed at either the quantitation or identification stage. These data were then transformed to binary inputs, analyzed via machine learning algorithms, and classified accordingly, with the aim of determining if clusters of data existed for specific journals or if certain statistical measures correlated with each other. We applied a variety of classification methods including principal component analysis decomposition, agglomerative clustering, and multinomial and Bernoulli naïve Bayes classification and found that none of these could readily determine journal identity given extracted statistical features. Logistic regression was useful in determining high correlative potential between statistical features such as false discovery rate criteria and multiple testing corrections methods, but was similarly ineffective at determining correlations between statistical features and specific journals. This meta-analysis highlights that there is a very wide variety of approaches being used in statistical analysis of proteomics data, many of which do not conform to published journal guidelines, and that contrary to implicit assumptions in the field there are no clear correlations between statistical methods and specific journals.

Surface treatment of biological tissue sections improves detection of peptides and proteins for mass spectrometry imaging. However, liquid surface treatments can result in diffusion of surface analytes and fragile tissue sections can be easily damaged by typical washing solvents. Here, we present a new surface washing procedure for mass spectrometry imaging. This procedure uses solvent wetted fiber-free paper to enable local washing of tissue sections for mass spectrometry imaging and tissue profiling experiments. In addition, the method allows fragile tissues that cannot be treated by conventional washing techniques to be analyzed by mass spectrometry imaging., (© The Author(s) 2011.)