Unlocking the Molecular Variations of a Micron-Scale Amyloid Plaque in an Early Stage Alzheimer's Disease by a Cellular-Resolution Mass Spectrometry Imaging Platform.

Uncovering the molecular changes at the site where Aß is deposited plays a critical role in advancing the diagnosis and treatment of Alzheimer's disease. However, there is currently a lack of a suitable label-free imaging method with a high spatial resolution for brain tissue analysis. In this study, we propose a modified desorption electrospray ionization (DESI) mass spectrometry imaging (MSI) method, called segmented temperature-controlled DESI (STC-DESI), to achieve high-resolution and high-sensitivity spatial metabolomics observation by precisely controlling desorption and ionization temperatures. By concentrating the spray plume and accelerating solvent evaporation at different temperatures, we achieved an impressive spatial resolution of 20 µm that enables direct observation of the heterogeneity around a single cell or an individual Aß plaque and an exciting sensitivity that allows a variety of low-abundance metabolites and less ionizable neutral lipids to be detected. We applied this STC-DESI method to analyze the brains of transgenic AD mice and identified molecular changes associated with individual Aß aggregates. More importantly, our study provides the first evidence that carnosine is significantly depleted and 5-caffeoylquinic acid (5-CQA) levels rise sharply around Aß deposits. These observations highlight the potential of carnosine as a sensitive molecular probe for clinical magnetic resonance imaging diagnosis and the potential of 5-CQA as an efficient therapeutic strategy for Aß clearance in the early AD stage. Overall, our findings demonstrate the effectiveness of our STC-DESI method and shed light on the potential roles of these molecules in AD pathology, specifically in cellular endocytosis, gray matter network disruption, and paravascular Aß clearance.

Miniature mass spectrometer signal processing based on ensemble empirical mode decomposition feature enhancement.

RATIONALE: The high sensitivity of the miniature mass spectrometer plays an irreplaceable role in rapid on-site detection. However, its analysis accuracy and stability should be improved due to the influence of sample pretreatment and use environment. The present study investigates the processing effects of ensemble empirical mode decomposition (EEMD) feature enhancement methods on the determination coefficient (R2 ) and relative standard deviation (RSD) of caffeine mass spectrometry (MS) signals. METHODS: This paper employs the EEMD method combined with polynomial curve fitting to enhance the characteristics of seven caffeine mass spectrum signals with different concentrations and 15 groups of caffeine mass spectrum signals with the same concentration, and the wavelet analysis method was used for comparative verification. The determination coefficient and RSD of the two methods were compared. RESULTS: We found the EEMD method's capability in adaptively decomposing caffeine mass spectrum signals is better than wavelet analysis method. The determination coefficient of the EEMD enhanced feature is better than 0.999, and the RSD is better than 2%, and both are better than wavelet analysis methods. CONCLUSIONS: The feature enhancement processing using the EEMD method has significantly improved the determination coefficient and RSD of the sample curve, improving the accuracy and stability of the data and providing a new way for miniature mass spectrometer signal processing.

Online hyphenation of in-capillary aptamer-functionalized solid-phase microextraction and extraction nanoelectrospray ionization for miniature mass spectrometry analysis.

Direct mass spectrometry (MS) analysis is vital to chemical and biological investigations. However, measuring complex samples is challenging due to matrix interference, resulting in compromised MS performance. In this study, an integrated experimental protocol has been developed, combining in-capillary aptamer-functionalized solid-phase microextraction (SPME), extraction nanoelectrospray ionization (nanoESI), and miniature MS analysis. The established method was applied to analyze caffeine in electronic cigarette liquid and beverage samples as proof-of-concept demonstrations. A custom SPME strip fabricated with caffeine-binding aptamers was prepared with an immobilization density of up to 0.812 nmol cm-2. Critical parameters affecting the effects of extraction, desorption, and ionization were optimized. A novel transition ion ratio-based strategy with enhanced quantitation accuracy was developed. The analytical performance of the proposed method was evaluated under optimized conditions. Acceptable recoveries of 87.5-111.5% with relative standard deviations of 3.1-6.1% and satisfactory sensitivity with limits of detection of 1.5 and 3 ng mL-1 and limits of quantitation of 5 and 10 ng mL-1 were obtained, respectively. The developed approach demonstrates a promising potential for rapid on-site applications with appealing analytical performance and efficiency.

Serum metabolomic abnormalities in survivors of non-severe COVID-19.

Metabolic reprogramming is a distinctive characteristic of SARS-CoV-2 infection, which refers to metabolic changes in hosts triggered by viruses for their survival and spread. It is current urgent to understand the metabolic health status of COVID-19 survivors and its association with long-term health consequences of infection, especially for the predominant non-severe patients. Herein, we show systemic metabolic signatures of survivors of non-severe COVID-19 from Wuhan, China at six months after discharge using metabolomics approaches. The serum amino acids, organic acids, purine, fatty acids and lipid metabolism were still abnormal in the survivors, but the kynurenine pathway and the level of itaconic acid have returned to normal. These metabolic abnormalities are associated with liver injury, mental health, energy production, and inflammatory responses. Our findings identify and highlight the metabolic abnormalities in survivors of non-severe COVID-19, which provide information on biomarkers and therapeutic targets of infection and cues for post-hospital care and intervention strategies centered on metabolism reprogramming.

Suspect Screening of Fentanyl Analogs Using Matrix-Assisted Ionization and a Miniature Mass Spectrometer with a Custom Expandable Mass Spectral Library.

The reliable identification of fentanyl and its analogs is of great significance for public security. However, with the growing prevalence of fentanyl compounds, current analytical strategies cannot fully meet the need for fast and high-throughput detection. In this study, a simple, rapid, and on-site analytical protocol was developed based on a miniature mass spectrometer. A dramatically simplified workflow was implemented using matrix-assisted ionization, bypassing complex sample pretreatment and chromatographic separation. The tandem mass spectrometry (MS/MS) capability afforded by the miniature ion trap mass spectrometer facilitated the investigation of fragmentation patterns for 49 fentanyl analogs during collision-induced dissociation, revealing valuable information on marker fragment ions and characteristic neutral loss. Calculations on Laplacian bond order values further verified the mass spectrometric behavior. A computation-assisted expandable mass spectral library was constructed in-house for fentanyl compounds. Smart suspect screening was carried out based on the full-scan MS and MS/MS data. The present study demonstrates an appealing potential for forensic applications, enabling streamlined screening for the presence of illicit fentanyl compounds at the point of seizures of suspect samples.

Post-Chromatographic Dicationic Ionic Liquid-Based Charge Complexation for Highly Sensitive Analysis of Anionic Compounds by Ultra-High-Performance Supercritical Fluid Chromatography Coupled with Electrospray Ionization Mass Spectrometry.

A green analytical strategy has been developed for the analysis of 10 perfluorinated compounds (PFCs) incorporating supramolecular solvent (SUPRAS)-based extraction and ultra-high-performance supercritical fluid chromatography (UHPSFC)-tandem mass spectrometry. The SUPRAS was prepared through self-assembly of reverse micelles by mixing heptanol, tetrahydrofuran, and water at optimized volume ratios. An imidazolium-based germinal dicationic ionic liquid (DIL), 1,1-bis(3-methylimidazolium-1-yl) butylene difluoride ([C4(MIM)2]F2), was dissolved in the make-up solvent of UHPSFC and introduced post-column but before the electrospray ionization source. After chromatographic separation on a Torus DIOL analytical column (100 mm × 2.1 mm, 1.7 µm), the PFC analytes associated with the DIL reagent through charge complexation. The formation of positively charged complexes resulted in improved ionization efficiency and analytical sensitivity. Enhancement in signal intensity by one to two magnitudes was achieved in the positive ionization mode compared to the negative ionization mode without using the dicationic ion-pairing reagent. The developed protocol was applied to 32 samples of real textiles and 6 samples of real food packaging materials, which exhibited great potential for the analysis of anionic compounds.

Accelerated air-assisted in-syringe extraction and needle spray ionization coupled with miniature mass spectrometry: A streamlined platform for rapid on-site analysis.

The present study reports on a streamlined analytical platform for rapid, straightforward, and on-site sample analysis using a miniature mass spectrometer with adequate tandem mass spectrometry (MS/MS) capability. An "all-in-one" workflow is developed combining accelerated air-assisted in-syringe extraction, sorbent-packed membrane clean-up, and needle spray ionization with an in-house built syringe assembly. A custom-made metal needle with a sharp, thin, and conical tip of micrometer-scale served as an integral component of the syringe assembly. This needle was capable of both aspirating a high-speed airflow for a highly efficient in-syringe extraction and performing stable electrospray for direct miniature mass spectrometry analysis. As a proof-of-concept demonstration, the developed protocol was implemented for the identification of 40 adulterated cosmetic ingredients and validated in terms of sensitivity, linearity, matrix effect, and recovery. A custom expandable mass spectral library was established in-house for smart suspect screening. Compound search and identification were conducted following a two-stage strategy using the full-scan MS and MS/MS data. The methodology demonstrates excellent potential for outside-the-laboratory chemical analysis by reducing the high time and labor costs associated with traditional sample preparation and chromatographic separation procedures, which would meet product quality and safety inspection requirements for on-site compliance check and regulatory enforcement at the testing sites such as supermarkets, department stores, wholesale markets, and roadside stalls.

Selective and sensitive analysis by reactive easy ambient sonic-spray ionization: Synergistic combination of non-polar spray solvent and dicationic ionic liquid.

The present study reports the first conception to incorporate a non-polar solvent, dichloromethane, as the spray solution in easy ambient sonic-spray ionization (EASI) for mass spectrometry (MS) analysis of hydrophobic compounds. An imidazolium-based dicationic ionic liquid (DIL) at a low concentration of 20 µM was used in combination with dichloromethane. A reactive EASI strategy was implemented, by which the overall positively charged associated complexes of anionized perfluorinated compounds (PFCs) were formed in the presence of the DIL. In positive ionization mode, 19- and 6-fold enhancements in signal intensity were witnessed for the analysis of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) respectively, compared to that in negative ionization mode with no dicationic ion-pairing reagent. The limits of detection (LODs) and quantitation (LOQs) are 0.5 and 0.8 µg/m2 for PFOA and 0.4 and 0.6 µg/m2 for PFOS, respectively. The developed method allowed direct ambient analysis of samples in their native conditions and was applied to the analysis of PFCs in a variety of real textile, popcorn bucket, and oil-proof hamburger wrapping paper samples.

Direct analysis in real time coupled with quadrupole-Orbitrap high-resolution mass spectrometry for rapid analysis of pyrethroid preservatives in wooden food contact materials.

A methodology is presented for the determination of four pyrethroid (PYR) preservatives in wooden food contact materials (FCMs) using direct analysis in real time (DART) coupled with quadrupole-Orbitrap high-resolution mass spectrometry (Q-Orbitrap HRMS). The sampling mode and critical parameters of the DART-Q-Orbitrap HRMS protocol were systematically investigated. Good linearity was achieved for the four analytes with correlation coefficients all greater than 0.99. The limits of detection (LODs) and limits of quantitation (LOQs) of the method were in the range of 0.04-0.20 mg kg-1 and 0.10-0.50 mg kg-1, respectively. The mean recoveries ranged from 72.1% to 82.7% with relative standard deviations (RSDs) from 5.2% to 11.8% at three spiked levels. The developed method was proved to be suitable for rapid screening of PYRs in complex wooden FCM samples to ensure product safety and consumer health.

Direct Mass Spectrometry Analysis Using In-Capillary Dicationic Ionic Liquid-Based in Situ Dispersive Liquid-Liquid Microextraction and Sonic-Spray Ionization.

The current study reports on a direct mass spectrometry (MS) analysis method using in-capillary dicationic ionic liquid (DIL)-based in situ dispersive liquid-liquid microextraction (DLLME) and sonic-spray ionization (SSI). The developed method merged extraction, enrichment, ionization, and detection of perfluorinated compounds (PFCs) in environmental water into a single step. A microliter-scale ternary fluidic system was designed and integrated into a disposable pulled capillary, in which an imidazolium-based germinal DIL reagent activated an in situ metathesis reaction. A penetrating slug-flow microextraction (SFME) process was subsequently initiated with significantly enhanced interfacial areas and mass transfer rates for the analytes of interest, the mechanism of which was revealed by simulations. An SSI assembly was in-house built, and it enabled a Venturi self-pumping using a stream of nitrogen gas flow coaxial to the capillary under atmospheric pressure to automatically spray at the tip of the capillary. The in situ formed DIL could bind with anionic PFC analytes to generate a positively charged complex, which benefits a signal increase of 1 to 2 orders in magnitude in the positive ion mode than in the negative ion mode for most analytes. The high sensitivity allowed the measure of sub-ppb (parts per billion) levels of PFCs in the environmental water samples. The developed method is a promising protocol for MS analysis because of unprecedented ease, significantly enhanced sensitivity, and potentially high sample throughput.

Graphene and AuNPs based electrochemical aptasensor for ultrasensitive detection of hydroxylated polychlorinated biphenyl.

An electrochemical aptasensor for ultrasensitive detection of hydroxylated polychlorinated biphenyl (OH-PCB) was developed. In this work, the sulfydryl aptamer selected for OH-PCB was easily immobilized on the surface of the modified glassy carbon electrode via Au-S bond due to incorporation of gold nanoparticles/poly dimethyl diallyl ammonium chloride-graphene composite. The fabrication process of the electrochemical aptasensor was characterized by electrochemical impedance spectroscopy and cyclic voltammetry. The peak currents obtained by differential pulse voltammetry decreased with the increasing of OH-PCB concentrations. The current responded approximately logarithmically to the OH-PCB concentration ranging from 2.9 × 10-11 M to 2.9 × 10-7 M with excellent linear correlation performance. The detection limit of OH-PCB was estimated as low as 5.3 × 10-12 M. The developed method had been successfully applied to analyzing lake water. Particularly, the method of the electrochemical aptasensor opens up a new perspective in environmental monitoring by the aptamer identification.

Fast optimization method of designing a wideband metasurface without using the Pancharatnam-Berry phase.

Arbitrary control of electromagnetic waves remains a significant challenge although it promises many important applications. Here, we proposed a fast optimization method of designing a wideband metasurface without using the Pancharatnam-Berry (PB) phase, of which the elements are non-absorptive and capable of predicting the wideband and smooth phase-shift. In our design method, the metasurface is composed of low-Q-factor resonant elements without using the PB phase, and is optimized by the genetic algorithm and nonlinear fitting method, having the advantages that the far field scattering patterns can be quickly synthesized by the hybrid array patterns. To validate the design method, a wideband low radar cross section metasurface is demonstrated, showing good feasibility and performance of wideband RCS reduction. This work reveals an opportunity arising from a metasurface in effective manipulation of microwave and flexible fast optimal design method.

Rapid identification of regulated organic chemical compounds in toys using ambient ionization and a miniature mass spectrometry system.

Rapid, on-site analysis was achieved through significantly simplified operation procedures for a wide variety of toy samples (crayon, temporary tattoo sticker, finger paint, modeling clay, and bubble solution) using a miniature mass spectrometry system with ambient ionization capability. The labor-intensive analytical protocols involving sample workup and chemical separation, traditionally required for MS-based analysis, were replaced by direct sampling analysis using ambient ionization methods. A Mini ß ion trap miniature mass spectrometer was coupled with versatile ambient ionization methods, e.g. paper spray, extraction spray and slug-flow microextraction nanoESI for direct identification of prohibited colorants, carcinogenic primary aromatic amines, allergenic fragrances, preservatives and plasticizers from raw toy samples. The use of paper substrates coated with Co3O4 nanoparticles allowed a great increase in sensitivity for paper spray. Limits of detection as low as 5µgkg-1 were obtained for target analytes. The methods being developed based on the integration of ambient ionization with miniature mass spectrometer represent alternatives to current in-lab MS analysis operation, and would enable fast, outside-the-lab screening of toy products to ensure children's safety and health.

Surface electromagnetic wave excitation and diffraction by subwavelength slit with periodically patterned metallic grooves.

Based on the theoretical formalism derived from the diffraction theory and electromagnetic boundary condition [Phys. Rev. Lett. 167401 (2003)], we investigate numerically the diffraction behavior of light passing through a subwavelength metallic slit-grooves structure, slit surrounded symmetrically by a finite array of grooves at the output surface. The diffraction dependence with the geometrical parameters, groove depth, width and number is analyzed in detail. It is found that variant profile of angle spectra and beaming intensity can be obtained in the far field by tuning the geometrical parameters. Numerical analysis shows that these diffraction behaviors are associated with different excitation states of surface electromagnetic wave.