Triazine herbicides are widely used in agricultural production. However, their environmental persistence and mobility pose potential threats to ecological safety and human health. Herein, a novel analytical method integrating stir bar sorptive extraction (SBSE) with airflow-assisted thermal desorption dielectric barrier discharge ionization mass spectrometry (AFA-TD-DBDI-MS), an ambient ionization mass spectrometry (AMS), was developed for the sensitive determination of triazine herbicides. A hydroxyl-functionalized covalent organic framework (COF-HF) was synthesized and used to fabricate COF-HF-coated stir bars via physical adhesion. The as-prepared stir bars exhibited outstanding extraction performance toward triazine herbicides, and the underlying adsorption mechanism was systematically investigated. The established COF-HF-based SBSE-AFA-TD-DBDI-MS method demonstrated good linearity (R² ≥ 0.9957), satisfactory recoveries (91.31%-98.81%), good repeatability (RSD ≤ 8.49%), and low limits of detection (0.0061-0.0312 ng/mL). This study provides a rapid and efficient strategy for monitoring trace triazine pollutants in environmental water and serum matrices.

Direct ionization ion trap mass spectrometry (ITMS) consistently faces challenges from matrix interference, necessitating highly specific analytical strategies to ensure reliable compound identification. However, the performance of tandem mass spectrometry (MS/MS) in conventional ITMS systems, which primarily rely on collision-induced dissociation (CID) for ion activation-is often constrained by the low-mass cutoff (LMCO) effect and suboptimal fragmentation efficiency. To address these limitations, we developed a portable ITMS platform that integrates both beam-type collision-induced dissociation (bCID) and CID technologies. In this platform, a flared ion guide serves dual roles as an ion transfer device and a collision cell for bCID. Compared with a parallel square-rod ion guide, the flared design-without compromising instrument portability shortens the dissociation time from 40 to 20 ms and increases the total dissociation efficiency by approximately 10%. Experimental results demonstrated that the bCID activation method effectively alleviates the LMCO restriction, while simultaneously improving fragmentation efficiency and analytical throughput, particularly for low-mass fragments. Furthermore, bCID provides greater flexibility in modulating fragment ion abundance through dissociation voltage adjustment and exhibits a distinct advantage in dissociating molecules containing strong chemical bonds. In the analysis of complex matrices such as hair and serum, bCID enhanced the signal-to-noise (S/N) ratios for compounds including tramadol, metonitazene and brodifacoum compared to CID. This enhancement was achieved by strengthening low-mass fragment ion intensities while reducing background noise through the breakdown of matrix-derived interference ions into non-specific fragments. Additionally, the complementary use of CID and bCID offered superior specificity for detecting designer drugs (e.g., etomidate and propoxate) in urine and food additives (e.g., saccharin sodium and benzoic acid) in ham, by generating a sufficient set of diagnostic ions with high abundance and S/N ratios. These findings underscore the importance of incorporating the hybrid dissociation modes into portable ITMS systems for on-site analysis of complex samples.

The rapid, on-site quantification of psychoactive substances in hair remains a major challenge in safety and security screenings, largely due to severe matrix interference and the limited sensitivity of field-deployable instrumentation. This study presents a novel portable mass spectrometry platform coupled with a carrier-gas-assisted thermal desorption (TD) system to evaluate three widely used atmospheric pressure ionization interfaces: dielectric barrier discharge ionization (DBDI), atmospheric pressure chemical ionization (APCI), and disposable electrospray ionization (dESI). A comparative analysis of 18 illicit drugs under optimized conditions revealed that TD-DBDI achieved decision-relevant sensitivity for most analytes, providing the best or comparable limits of detection in approximately 89% of cases while exhibiting the least pronounced matrix effects. While TD-APCI proved uniquely effective for cannabinoids, it was compromised by significant background interference from co-desorbed contaminants. In contrast, dESI showed high sensitivity for standard solutions but suffered critical signal suppression (> 70%) in hair matrices. By elucidating the distinct ionization mechanisms and matrix-related behaviors of each interface, this work establishes a rapid, sensitive screening protocol for trace-levels of opioids, stimulants, and metabolites in hair. The presented method offers a practical tool for on-site applications, including forensic analysis, border security, and public health surveillance.

Proton transfer reaction mass spectrometry (PTR-MS) is a rapid and highly sensitive technique for the detection of volatile organic compounds and has been increasingly used in the fields of environmental monitoring, medicinal diagnosis and food industry. The large size and heavy weight of conventional PTR-MS devices limit their on-site application for real-time and rapid analysis. In this work, a miniaturized PTR-MS instrument with a total weight of 25 kg was developed on the basis of a portable ion trap mass spectrometer, which was characterized by the use of a small hollow-cathode discharge for hydroxonium ion generation and a compact ion funnel as the drift tube. For this instrument, mass resolution, ion isolation and fragmentation efficiencies, and sensitivity have been investigated in detail with helium and nitrogen as buffer gases. Compared with nitrogen buffer gas, when helium buffer gas was used, the mass resolution of protonated acetone ions doubled, whereas the ion fragmentation efficiency could be increased by a factor of 17. With helium buffer gas, the limits of detection for acetone, benzene, and toluene were found to be 1 ppbv, 0.5 ppbv, and 0.1 ppbv, respectively, and linear calibration curves for these compounds were established across concentration ranges spanning at least two orders. Under the optimal vacuum pressures of 1.5 mbar and 2.5 mbar, the gas consumption rates for helium and nitrogen were 81 mL min-1 and 60 mL min-1, respectively. In addition, the sample injection flow rate exerted a pronounced influence on the detection sensitivity and response time of the system.

Synthetic cannabinoids are a new class of synthetic psychoactive substances. By slightly modifying their chemical structures, new types of compounds could be derived, and it was precisely by taking advantage of this feature that unscrupulous elements were able to evade legal regulation through structural modification. However, mass spectrometry, as a mainstream detection instrument, was found to have obvious limitations in the coverage of its mass spectrometry libraries, which were constructed by relying on data from actual tests and information on known compounds in commercial databases. Due to the difficulty in obtaining standards for novel synthetic cannabinoids, the data in the mass spectrometry library could not be rapidly updated. To address the above problems, a deep learning-based mass spectrometry library prediction and expansion method was proposed in this study, combined with a similarity search algorithm, aiming to achieve the rapid prediction of mass spectrometry data for novel synthetic cannabinoids and the quick identification of novel synthetic cannabinoids.

Owing to their excellent vacuum compatibility, compact design, and suitability for tandem mass spectrometry, ion trap mass spectrometers have emerged as a focal point in recent mass spectrometry research. However, factors such as matrix effects, low ion transmission efficiency, and space charge limitations within the ion trap significantly constrain its overall performance, rendering it still inferior to that of chromatography – mass spectrometry (LC– MS/MS or GC– MS/MS) tandem systems. In light of the susceptibility of ion traps to space charge effects, this study adopts a Q-Trap-based analytical approach to enhance target ion utilization and mitigate space charge – induced limitations within the ion trap. The experimental results indicate that an injection time of 1 ms yields optimal signal intensity and resolution in the Q storage & filter mode. Compared to the Q filter mode, the signal-to-noise ratio (S/N) of 6-MAM (m/z 165) in the Q storage & filter mode is improved by approximately threefold, while the S/N of MDMA (m/z 135) and cocaine (m/z 220) increases by at least twofold.

RATIONALE:In electrospray ionization mass spectrometry (ESI-MS) systems, two critical challenges persist: (1) under-expanded supersonic jets at the atmospheric pressure interface (API) cause ion losses and reduced transmission efficiency; (2) residual solvents and charged droplets entering vacuum stages lead to contamination and elevated chemical noise, degrading analysis accuracy. METHODS:A dual-channel off-axis ion funnel with a deflection electrode (DC-OFIDE) was developed to address these challenges. This device integrates three core components: an ion drift channel (IDC), an ion funnel channel (IFC), and a deflection electrode. The IDC and IFC are separated by conjoined gaps. Ions within the gas stream emanating from the API are extracted from the IDC via a deflection field, while a retarding axial field prolongs ions' residence time, ensuring efficient transfer to the IFC. This DC-OFIDE features an enlarged entrance aperture (Φ18 mm) to accommodate a multi-capillary interface, enhancing compatibility with high-conductance sample introduction systems. RESULTS:Compared with the original conventional ion funnel (CIF), the DC-OFIDE achieved a threefold enhancement in caffeine ion intensity and a broader m/z transmission window. It demonstrated robust neutral and droplet suppression, maintaining 80% ion intensity even under tripled serum volume infused. In drug screening of hair samples, baseline noises in drug ion peaks were reduced by 36%-82%, with a quadrupled signal-to-noise ratio improvement observed for 6-monoacetylmorphine. CONCLUSIONS:This DC-OFIDE significantly enhances ion transmission efficiency and chemical noise suppression in ESI-MS, establishing its potential for high-fidelity analysis of complex samples.

Molecular information can be acquired from sample surfaces in real time using a revolutionary molecular imaging technique called mass spectrometry imaging (MSI). The technique can concurrently provide high spatial resolution information on the spatial distribution and relative proportion of many different compounds. Thus, many scientists have been drawn to the innovative capabilities of the MSI approach, leading to significant focus in various fields during the past few decades. This review describes the sampling protocol, working principle and applications of a few non-ambient and ambient ionization mass spectrometry imaging techniques. The non-ambient techniques include secondary ionization mass spectrometry and matrix-assisted laser desorption ionization, while the ambient techniques include desorption electrospray ionization, laser ablation electrospray ionization, probe electro-spray ionization, desorption atmospheric pressure photo-ionization and femtosecond laser desorption ionization. The review additionally addresses the advantages and disadvantages of ambient and non-ambient MSI techniques in relation to their suitability, particularly for biological samples used in tissue diagnostics. Last but not least, suggestions and conclusions are made regarding the challenges and future prospects of MSI.

Abstract Small linear ion trap mass spectrometers are often combined with direct ionization mass spectrometry (DIMS) techniques for detection and analysis. However, DIMS is susceptible to the working environment and matrix effects, resulting in reduced sensitivity, which places high demands on the performance of tandem mass spectrometry of small linear ion trap mass spectrometers. Therefore, the effects of vacuum pressure, collision q-value, collision voltage, and collision time on the dissociation efficiency of the ion trap are experimentally explored in this paper to enhance the performance of tandem mass spectrometry for small linear ion trap mass spectrometers. The findings indicate that as the vacuum pressure increases, dissociation efficiency first increases rapidly and then remains stable, and the peak dissociation efficiency of 56% is attained at a vacuum pressure of 0.31 mTorr. Increasing the collision q value, dissociation efficiency first increased slowly, then increased rapidly, and finally remained almost unchanged. When the collision q value was increased from 0.26 to 0.35, dissociation efficiency increased from 9% to 56%. Meanwhile, the maximum collision voltage corresponding to the optimal dissociation efficiency gradually decreases as the collision q value increases. With the increase in collision time, dissociation efficiency increases rapidly and then remains stable. Therefore, studying the factors affecting dissociation efficiency points the way to enhancing the efficacy of tandem mass spectrometry with small linear ion trap mass spectrometers.

The capillary is a widely used atmospheric pressure interface in mass spectrometers that may be heated to enhance the desolvation of ions. In this study, the ion transmission efficiency of a portable ion trap mass spectrometer was investigated using capillaries with different inner diameters and temperatures, different vacuum pressures, and different ion optics designs. Due to the incomplete desolvation and the space charge effect inside the miniature ion funnel, the increase of ion intensities with the inner diameter of the capillary leveled off when the inner diameter of the capillary was larger than 0.37 mm. With the increase of capillary temperature, the ion intensities first increase due to better desolvation and then decrease due to greater diffusion loss. The optimal temperature of the capillary increases with the inner diameter of the capillary and the mass-to-charge ratio of ion. In addition, the pressures of different vacuum stages also exerted remarkable effects on the sensitivity of the portable mass spectrometer. From the perspective of instrument miniaturization, optimal transmission efficiency can be obtained when the first-stage vacuum pressure is maintained from 4 to 6 mbar. For a capillary with an inner diameter of 0.37 mm, the background of mass spectrum can be significantly reduced by replacing the pinhole behind the ion funnel with an off-axis skimmer.

Portable ion trap mass spectrometers, especially for those with continuous atmospheric pressure interfaces, usually implement vacuum pumps with limited power for miniaturization, which leads to high vacuum pressures and reduced resolutions. In this study, two three-stage high-resolution ion isolation methods of SWIFT - AC frequency sweep - SWIFT and SWIFT - RF voltage ramp - SWIFT were proposed. Compared to the 2.8 m/z isolation resolution of the traditional SWIFT ion isolation method, higher isolation resolutions of 2.2 m/z and 1.5 m/z have been achieved by SWIFT - AC frequency sweep - SWIFT and SWIFT - RF voltage ramp - SWIFT ion isolation methods at an isolation efficiency of 40 %. In addition, our detailed experiments showed that all ion isolation methods can obtain higher isolation resolution under the conditions of lower vacuum pressure, higher isolation q value, and stronger axial confinement potential barrier, like which the mass resolution behaves. In order to inspect the effectiveness of the high-resolution isolation method, the control experiments of hair samples spiked with drugs had been conducted. The signal-to-noise ratio of O6-monoacetylmorphine can be improved by a factor of 2.4 using the SWIFT - RF voltage ramp - SWIFT ion isolation method. Our research results indicate that the performance of ion trap tandem mass spectrometry can be effectively improved by using the three-stage highresolution ion isolation methods.

直接电离质谱具有快速、原位、实时离子化等优势,被广泛用于毒品、爆炸物、食品添加剂等成分的检测.直接电离源与质谱真空的耦合通常是通过毛细管或分离锥等窄小导孔实现的,导致离子传输效率大幅降低,成为提高仪器灵敏度的主要瓶颈.本研究基于脉冲直流电喷雾离子源与快筛质谱联用平台,探究了扩口和平口毛细管中喷雾电压、喷针位置、喷针内径、毛细管入口内径对仪器性能的影响.流体仿真和离子轨迹模拟结果表明,扩口毛细管因径向气流分布范围宽,扩大了可聚焦喷雾羽流面积,提高了直接电离源到质谱锥口之间的离子传输效率.与传统的平口毛细管相比,入口内径6 mm的扩口毛细管大气压接口搭配20μm喷针内径,可将10μg/L甲基苯丙胺离子信号强度提高3.3倍,甲基苯丙胺、3,4-亚甲双氧甲基苯丙胺、氯胺酮、可卡因、O6-单乙酰吗啡等5种常规毒品在毛发中的信噪比均有明显提升.本研究表明,采用扩口毛细管无需对仪器进行大规模修改,易与直接电离源相结合,可显著提高仪器灵敏度.

Ambient ionization mass spectrometry (AIMS) is an emerging onsite rapid detection technique that has been applied in the area of public security. AIMS measurements of samples with complex matrices are characterized by poor reproducibility and complexity. Low reproducibility and complex background cause imprecise screening for trace drugs in hair. In this work, a rapid screening method of methamphetamine in hair is proposed. Firstly, the generalized weighted robust principal component analysis (GWRPCA) algorithm is used to remove background and extract the analytical signals. The similarity scores between the analytical signals and standard mass spectrum of methamphetamine were calculated based upon an improved Pearson's correlation coefficient combined with the preset matching threshold to achieve rapid screening of methamphetamine in hair. The results show that this method accurately screens for this drug hair and identifies actual false positives with 100% accuracy when the analyte threshold was 0.1 ng/mg and the matching threshold was 0.6. This study provides technical support for the rapid screening for drug abuse by AIMS.

As a rapid and highly sensitive technique for detection of volatile organic compounds (VOCs), proton transfer reaction mass spectrometry (PTR-MS) is increasingly used in environment, medical, and safety fields. However, the large size and weight of conventional PTR-MS limit its in situ application for real-time and rapid analysis. In this study, a small PTR-MS setup was built based on ion trap MS. It adopted an ion funnel as the drift tube, which consisted of 30 electrodes of 1 mm in thickness and 1.2 mm in each gap distance. The PTR ion source of this setup had a hollow cathode structure, of which the glow discharge turn-on voltage was about 450 V. The PTR ion source exit electrodes of skimmer structure were optimized in taper orifice diameter, angle and height, by which the signal of H30+(H20) was improved about 38 times compared to the ring structure electrode. In addition, the distributions of protonated water clusters H30+(H20)n (n=1, 2, 3, 4) were examined with different direct-current (DC) field and radio-frequency (RF) voltages of the ion funnel. The maximum intensity of H30+(H20) signal was obtained with the DC field of 43 V/cm and RF voltage of 77 V. The optimized system had a limit of detection about 10-12-10-9 (V/V) for different VOCs (Methanol, acetonitrile, ethanol, acetone and ethyl acetate). Moreover, the PTR-MS developed here could identify molecules with close mass numbers, such as ethyl acetate and butyric acid, by the help of the tandem mass spectrometry of ion trap.

单细胞质谱分析能够获得单个细胞的代谢图谱,揭示细胞之间的异质性,在肿瘤学研究中具有重要价值.该文采用单细胞质谱和机器学习技术,建立了膀胱癌细胞亚型的鉴别方法.基于所采集的单细胞代谢数据,分别使用线性判别分析、随机森林、支持向量机、逻辑回归建立了机器学习分类模型,并进行了模型的性能评估.结果表明,各机器学习模型均具有良好的膀胱癌细胞分型能力,分类准确率 ≥94.9％,灵敏度 ≥88.6％,特异度 ≥93.3％.其中,随机森林算法的分类准确率达100％,模型的受试者工作特征曲线下面积达1.该方法实现了膀胱癌单细胞的代谢物检测及细胞亚型区分,也为更广泛的单细胞代谢组学研究提供了参考.

In food safety monitoring, on-site and simultaneous detection of a variety of insecticides with different concentrations in the same matrix is necessary. However, the task remains challenging. In this study, a novel nitrogen and sulfur co-doped carbon dot (N, S-CD) was synthesized and used as a QuEChERS clean-up reagent to reduce matrix interferences in the determination of insecticides in vegetables. In addition, a portable mass spectrometer (mu-MS) was employed, without chromatography separation, to directly de-termine neonicotinoids, carbamates, and benzopyrazole insecticides (with acetamiprid, imidacloprid, thi-amethoxam, fipronil, and carbofuran as models) in the pretreated samples. The N,S-CD mu-MS method exhibited effective clean-up performance with satisfactory matrix effects between -15.2% and 15.7%. The recoveries of spiked vegetable samples ranged from 82.2% to 109.7% for the five target insecticides, and the relative standard deviations (RSDs) ranged from 3.8% to 16.5%. The linear ranges were from 2.0 to 5.0 ng/g, with low detection limits (LOD) from 0.5 to 1.0 ng/g. Moreover, the total pretreatment and de-tection time was within 20 min. Thus, the incorporation of N,S-CD with QuEChERS extraction, together with the portable mu-MS system, could be a promising and feasible strategy for on-site, rapid, and simul-taneous detection of various insecticides in vegetables.(c) 2022 Elsevier B.V. All rights reserved.

The abuse of fentanyl and its analogs has caused a large number of deaths worldwide. Due to the rapid development of new fentanyl analogs, the standard mass spectral library is generally incomplete. The spectra obtained by different mass spectrometers by electrospray ionization (ESI) cannot be used across platforms, resulting in the hysteretic detection of novel fentanyl analogs. This paper reports a machine learning classification model based upon a hybrid similarity search. For the purpose of the identification of fentanyl analogs with different mass spectrometers, a mass spectral library based on the conserved fragmentation behavior (CFB) of fentanyl analogs was established. The results show that the identification accuracy of fentanyl analogs by two mass spectrometers is 100%, and the accuracy of classification model is 97.85%. Furthermore, the model may be applied to linear ion trap mass spectrometry (LIT-MS) and quadrupole time-of-flight mass spectrometry (Q-TOF-MS) with classification accuracies of 100 and 98.17%, respectively. This study provides promising technical support for the real-time and cloud computing detection of unknown fentanyl analogs.

Objective: The increasing demand for unraveling cellular heterogeneity has boosted single cell metabolomics studies. However, current analytical methods are usually labor-intensive and hampered by lack of accuracy and efficiency. Methods: we developed a first-ever automated single cell mass spectrometry system (named SCMS) that facilitated the metabolic profiling of single cells. In particular, extremely small droplets of sub nano-liter were generated to extract the single cells, and the underlying mechanism was verified theoretically and experimentally. This was crucial to minimize the dilution of the trace cellular contents and enhance the analytical sensitivity. Based on the precise 3D positioning of the pipette tip, we established a visual servoing robotic micromanipulation platform on which single cells were sequentially extracted, aspirated, and ionized, followed by the mass spectrometry analyses. Results: With the SCMS system, inter-operator variability was eliminated and working efficiency was improved. The performance of the SCMS system was validated by the experiments on bladder cancer cells. MS and MS2 analyses of single cells enable us to identify several cellular metabolites and the underlying inter-cell heterogeneity. Conclusion: In contrast to traditional methods, the SCMS system functions without human intervention and realizes a robust single cell metabolic analysis. Significance: the SCMS system upgrades the way how single cell metabolites were analyzed, and has the potential to be a powerful tool for single cell metabolomics studies.

According to the Report of Drug Situation in China (2020), the growth rate of the number of drug abusers in China has decreased, but the number of drug abusers is still large. An efficient screening method is necessary for controlling drug abuse. As an important type of biological sample, urine is widely used for the rapid screening of drug addicts. However, because of the complex composition, low content, and strong interference from the body's metabolism, the detection of drugs in urine remains a challenge. Traditional rapid screening techniques such as immunocolloidal gold analysis have a high false positive rate and insufficient quantitative capability. In addition, laboratory mass spectrometry methods require complicated time-consuming sample pre-processing and strict environmental conditions, and hence, are unsuitable for on-site rapid analysis. In recent years, various direct ionization mass spectrometry techniques such as direct analysis in real time (DART), desorption electrospray ionization (DESI), and dielectric barrier discharge ionization (DBDI) have advanced rapidly. These techniques have been applied to public safety, food safety, environmental detection, etc. In contrast to traditional ionization mass spectrometry methods, these direct ionization techniques allow for the in situ analysis of samples with simple or no pretreatment; moreover, they have the advantages of high analytical efficiency and sensitivity. In particular, pulsed electrospray ionization has the characteristics of less sample demand, compact, lightweight equipment, and no carrier gas. This paper presents a rapid method based on pulsed electrospray ionization mass spectrometry for the detection of urine samples. A rapid detection platform comprising a probe electrospray ionization source, a portable linear ion trap mass spectrometer (MS), and their coupling interface is adopted. The probe electrospray ion source includes a conducting metal wire, plastic handle, and silica glass capillary, whose tip has an inner diameter of 50 μm. The guide rail at the coupling interface is used to align the probe with the sample inlet of the portable mass spectrometer and maintain a distance of 10 mm between the probe tip and the sample inlet of the MS. The spray voltage of the probe electrospray ion source and the temperature of the MS inlet capillary are optimized at 1.8 kV and 205 ℃, respectively. In addition, rapid and efficient pretreatment techniques for urine samples have been developed. Buffer salts used for pH regulation and liquid-liquid extraction based on ethyl acetate were adopted for the pretreatment process. The linearity of the detection ability and the linear ranges of various drug-spiked solutions were also investigated. The results showed that the correlation coefficients for the quantitative detection of methamphetamine, ketamine, methylenedioxymethamphetamine (MDMA), and cocaine were greater than 0.99 at concentrations ranging from 1 to 100 ng/mL. Moreover, the limits of detection (LODs) for the five conventional drug-spiked urine were 0.5-30 ng/mL. The spiked recoveries ranged from 56.1% to 103.7%, with relative standard deviations (RSDs) of 9.0%-27.8%, implying that the combination of the instruments and the pretreatment method can lead to good accuracy. To validate the performance of the rapid detection method, 40 positive and 110 negative urine samples were tested and analyzed. The overall accuracy was over 99%, and the five conventional drugs in urine samples could be detected within 20 s. The research findings of this work could promote the development of rapid detection technology, accelerate the popularization and application of ambient direct ionization mass spectrometry, and improve the services of on-site law enforcement.