Characterization and application of a self‐aspirating electrospray source with pneumatic‐assisted ionization

A single gas‐assisted electrospray ion source developed for ambient mass spectrometry is introduced in this paper. Simultaneous self‐aspiration and electrospray could be achieved by using a constant sheath gas flow supplied from a mini air pump. A gas dynamic study of the spray module is carried out for structural optimization. The entire device exhibits a simplified design and has been systematically characterized through both simulated and experimental investigations. According to the results, the ion source exhibited satisfactory stability and the ability for quantitative operation in routine electrospray ionization mass spectrometry. Furthermore, the ion source can be operated as a desorption electrospray ionization source to perform direct desorption/ionization of the solid samples. The versatile source described here appears to provide a practical approach to perform ambient mass spectrometry analysis with unrestricted sampling operation, and the extensive gas dynamic studies together with the experimental characterization are believed to be helpful in building self‐aspirating spray devices. Copyright © 2017 John Wiley & Sons, Ltd.     

Continuous‐flow extractive desorption electrospray ionization coupled to normal phase separations and for direct lipid analysis from cell extracts

Normal phase liquid chromatography is a common mode for chiral separations. Many chiral amines are used as drugs or are important intermediates for drug synthesis. Electrospray ionization mass spectrometry is well known for its high sensitivity. However, when using normal phase liquid chromatography, electrospray ionization is hampered by the poor ionization efficiency of analytes from organic eluents. Continuous‐flow extractive desorption electrospray ionization, which introduces the eluents through a hypodermic needle into the electrospray plume is demonstrated here for its success to interface normal phase liquid chromatography to mass spectrometry detection. Such an approach was shown to be as or more sensitive than ultraviolet detection for a selected set of aromatic amine‐functionalized enantiomers. Also demonstrated is the direct infusion of cell extracts to monitor phospholipids from three different bacterial cells. Despite their presence in non‐electrospray‐ionization‐friendly extraction solvents, continuous‐flow extractive desorption electrospray ionization enabled the sensitive detection of phospholipids and the ability to tune ion forms through incorporation of different spray modifiers.     

Portable electrospray ionization mass spectrometry (ESI-MS) for analysis of contaminants in the field

Hitherto analysis of chemicals in the field using mass spectrometry (MS) has been limited to analysis of non-polar and thermally stabile organic compounds using either a direct gas leak or a membrane inlet as MS interface. Recently, Professor R. Graham Cooks’ group demonstrated that miniature mass spectrometers operating at elevated pressures (>0.13?Pa (1?·?10^?3??Torr)) can be combined with electrospray ionization (ESI) for analysis of polar as well as thermally labile organic compounds. We present a simple miniaturized ESI unit for analysis of small liquid samples using miniature mass spectrometry. The ESI unit operates without pumps and supplementary sheath gases, which makes it very simple to handle in the field. 20–30?µL of sample solution is simply dropped into a small cavity in the ESI unit, where after the spray is initiated by applying high voltage to it. The miniaturized ESI unit was tested in combination with a miniature mass spectrometer (the Mini 10 developed by Professor R. Graham Cooks, Purdue University, IN) and we found that common herbicides (Atrazine, Prometryne, Terbutryne and Triadimefone) could be detected with detection limits around 1?mg?L^?1 and with a quantitative reproducibility of +/?30%. These characteristics, although high for environmental samples, are comparable to detection limits obtained with other ESI units used with miniature mass spectrometers and represent an early step forward towards a future field instrument. A major advantage of the capillary spray cell is its direct compatibility with micro extraction techniques for sample pre-concentration.     

Analysis of lipids with desorption atmospheric pressure photoionization‐mass spectrometry (DAPPI‐MS) and desorption electrospray ionization‐mass spectrometry (DESI‐MS)

In this article, the effect of spray solvent on the analysis of selected lipids including fatty acids, fat‐soluble vitamins, triacylglycerols, steroids, phospholipids, and sphingolipids has been studied by two different ambient mass spectrometry (MS) methods, desorption electrospray ionization‐MS (DESI‐MS) and desorption atmospheric pressure photoionization‐MS (DAPPI‐MS). The ionization of the lipids with DESI and DAPPI was strongly dependent on the spray solvent. In most cases, the lipids were detected as protonated or deprotonated molecules; however, other ions were also formed, such as adduct ions (in DESI), [M‐H]⁺ ions (in DESI and DAPPI), radical ions (in DAPPI), and abundant oxidation products (in DESI and DAPPI). DAPPI provided efficient desorption and ionization for neutral and less polar as well as for ionic lipids but caused extensive fragmentation for larger and more labile compounds because of a thermal desorption process. DESI was more suitable for the analysis of the large and labile lipids, but the ionization efficiency for less polar lipids was poor. Both methods were successfully applied to the direct analysis of lipids from pharmaceutical and food products. Although DESI and DAPPI provide efficient analysis of lipids, the multiple and largely unpredictable ionization reactions may set challenges for routine lipid analysis with these methods. Copyright © 2012 John Wiley & Sons, Ltd.     

Direct monitoring of drug degradation by easy ambient sonic-spray ionization mass spectrometry: the case of enalapril

Using enalapril maleate as a test case, the ability of ambient mass spectrometry, namely, via easy ambient sonic‐spray ionization mass spectrometry (EASI‐MS), to perform direct monitoring of drug degradation has been tested. Two manufacturing processes were investigated (direct compression and wet granulation), and the formation of degradation products was measured via both EASI‐MS and high‐performance liquid chromatography with ultraviolet detection for a total period of 18 months. Both techniques provide comparable results, which indicate that direct analysis by ambient mass spectrometric techniques presents a viable alternative for drug degradation monitoring with superior simplicity, throughput, and reliability (no sample manipulation), and comparable quantitative results. In terms of qualitative monitoring, the full mass spectra with intact species provided by EASI‐MS allow for comprehensive monitoring of known and unknown (or unexpected) degradation products. Copyright © 2011 John Wiley & Sons, Ltd.     

Continuous flow-extractive desorption electrospray ionization: Analysis from “non-electrospray ionization-friendly” solvents and related mechanism

Due to their low polarities and dielectric constants, analytes in solvents such as hexane, chloroform, and ethyl acetate exhibit poor electrospray ionization (ESI) efficiency. These are deemed to be “non-ESI-friendly” solvents. Continuous flow extractive desorption electrospray ionization (CF-EDESI) is a novel ambient ionization technique that was recently developed in our group to manipulate protein charge distributions. Here we demonstrate its potential for ionizing analytes from non-ESI-friendly solvents. This feature makes CF-EDESI attractive to the general analytical community due to its apparent potential in lipidomics, normal phase separations, and hyphenation of mass spectrometry with HPLC-NMR systems. In this context, interest was subsequently initiated to discern mechanistic aspects of CF-EDESI. To achieve this, mechanistic experiments associated with a seemingly similar ambient ionization technique, extractive electrospray ionization (EESI), were emulated to compare CF-EDESI and EESI. Analysis of a series of fatty acids in multiple solvents in the negative ionization mode revealed differences between the two techniques. Whereas EESI has been previously shown to operate via extraction of analytes into the spray solvent, data presented here for CF-EDESI point toward a liquid-liquid mixing process to facilitate ionization. Further, a partial factorial design experiment was performed to evaluate the effects of different experimental variables on signal intensity. Sample flow rate was confirmed to be among the most significant factors to affect sensitivity. As a whole, the work presented provides greater insight into a new ambient ionization process, which exhibits expanded capabilities over conventional ESI; in this case, for direct analysis from non-ESI-friendly solvents.     

Fast Screening of Chicken Egg Lysozyme in White Wine Products by Extractive Electrospray Ionization Mass Spectrometry

Fast detection of trace lysozyme,one of the most important food allergens in white wine samples,was achieved by extractive electrospray ionization mass spectrometry without sample pretreatment in this ...     

Direct identification of prohibited substances in cosmetics and foodstuffs using ambient ionization on a miniature mass spectrometry system

Significantly simplified work flows were developed for rapid analysis of various types of cosmetic and foodstuff samples by employing a miniature mass spectrometry system and ambient ionization methods. A desktop Mini 12 ion trap mass spectrometer was coupled with paper spray ionization, extraction spray ionization and slug-flow microextraction for direct analysis of Sudan Reds, parabens, antibiotics, steroids, bisphenol and plasticizer from raw samples with complex matrices. Limits of detection as low as 5 μg/kg were obtained for target analytes. On-line derivatization was also implemented for analysis of steroid in cosmetics. The developed methods provide potential analytical possibility for outside-the-lab screening of cosmetics and foodstuff products for the presence of illegal substances.     

Polarization induced electrospray ionization mass spectrometry for the analysis of liquid,viscous and solid samples

In this study, a polarization‐induced electrospray ionization mass spectrometry (ESI‐MS) was developed. A micro‐sized sample droplet was deposited on a naturally available dielectric substrate such as a fruit or a stone, and then placed close to (~2 mm) the orifice of a mass spectrometer applied with a high voltage. Taylor cone was observed from the sample droplet, and a spray emitted from the cone apex was generated. The analyte ion signals derived from the droplet were obtained by the mass spectrometer. The ionization process is similar to that in ESI although no direct electric contact was applied on the sample site. The sample droplet polarized by the high electric field provided by the mass spectrometer initiated the ionization process. The dielectric sample loading substrate facilitated further the polarization process, resulting in the formation of Taylor cone. The mass spectral profiles obtained via this approach resembled those obtained using ESI‐MS. Multiply charged ions dominated the mass spectra of peptides and proteins, whereas singly charged ions dominated the mass spectra of small molecules such as amino acids and small organic molecules. In addition to liquid samples, this approach can be used for the analysis of solid and viscous samples. A small droplet containing suitable solvent (5–10 µl) was directly deposited on the surface of the solid (or viscous) sample, placed close the orifice of mass spectrometer applied with a high voltage. Taylor cone derived from the droplet was immediately formed followed by electrospray processes to generate gas‐phase ions for MS analysis. Analyte ions derived from the main ingredients of pharmaceutical tablets and viscous ointment can be extracted into the solvent droplet in situ and observed using a mass spectrometer. Copyright © 2015 John Wiley & Sons, Ltd.     

实时直接分析质谱新技术及其应用

由于不需要复杂的样品前处理过程,并具有实时、原位分析等特点,常压敞开式离子化技术成为近年来质谱研究的热点之一.实时直接分析(direct analysis in real time,DART)是近年来出现的一种常压敞开式离子化新技术,在食品安全、环境监测、爆炸物检测以及生物医药等诸多研究领域均有广泛的应用.本文简单介绍了常压敞开式离子化方法的发展,DART的基本原理和研究现状.进而介绍了我国质谱研究人员在基于DART的质谱仪器改进、联用技术以及生物药物等检测分析方面取得的新进展和新成果.     

Direct Determination of Creatinine in Urine and Analysis of Pure Aniline by Extractive Electrospray Ionization Mass Spectrometry

The direct mass spectrometric determination of highly concentrated analytes in human urine was demonstrated using extractive electrospray ionization without sample dilution or complex preparation. By increasing the distance between the extractive electrospray source and ion inlet of the mass spectrometer from 5 millimeters to 15 centimeters, the fraction of free analyte ions and charged microdroplets introduced into the mass spectrometer was substantially reduced. Consequently, detector saturation, instrument contamination, and space charge effects were greatly diminished for the analysis of highly concentrated samples. Under the optimized experimental conditions, pure aniline and creatinine (>1 millimolar) in human urine were directly characterized by extractive electrospray ionization without any pretreatment. The urinary creatinine concentrations from two adults were 424 ± 30 and 635 ± 32 micrograms per milliliter and were in good agreement with those obtained by a spectrophotometric method based on the Jaffe reaction. The results show that extractive electrospray ionization is suitable for the direct determination of highly concentrated analytes or even pure compounds, allowing rapid characterization of samples in the chemical industry and clinical studies.     

芹菜素的电喷雾萃取电离串联质谱

采用实验室自制的电喷雾萃取电离源(EESI),结合串联质谱(MSn)技术,对芹菜素这一典型的黄酮类活性化合物的质谱行为进行了研究。实验表明,在正、负离子检测模式下,该化合物均能得到较好的EESI-MS信号,且在负离子检测模式下灵敏度更高。通过对比芹菜素的EESI-MS和电喷雾电离质谱(ESI-MS)谱图发现,芹菜素在EESI-MS和ESI-MS中的裂解规律相似,但是EESI是一种比ESI更软的电离模式。根据对芹菜素EESI-MS特征碎片离子的分析,提出了芹菜素在EESI-MS中裂解的基本规律,为EESI-MS技术用于分析、鉴定复杂基质中痕量芹菜素奠定了理论和实验基础。     

固相基底电喷雾电离质谱分析固状与粘稠状药物的基质效应

固状与粘稠状辅剂常用于制造颗粒、片剂、胶囊或膏状药品,并能有效地保持药效成分活性的稳定性。基于固相基底的敞开式电喷雾电离质谱技术已被发展用于药品的直接分析。然而,固状与粘稠状基质对药物分子直接质谱检测的影响规律还不明确。该研究构建了不同黏度和不同溶解度的基质体系,采用木签(牙签)为代表的固相基底电喷雾电离质谱考察了几种模式药物分子在固状与粘稠状基质中的质谱响应规律。结果发现,易溶解的基质电离产生显著的离子干扰和抑制效应,而难溶的基质尽管不产生离子干扰,但在溶剂作用下可变成粘稠状从而抑制药物的离子化。进一步研究表明,药物分子的质谱信号随着基质的黏度增加(1~500 cP)呈幂函数降低(r 2>0.95)。该研究将增进理解固体与粘稠样品直接质谱分析的基质效应与信号响应规律。     

Plasma-source mass spectrometry for speciation analysis: state-of-the-art

Current and emerging capabilities of plasma-source mass spectrometry (PS-MS) as it is employed for elemental speciation analysis are reviewed. Fundamental concepts and their advantageous aspects, experimental conditions, and analytical performance are described and illustrated by recent examples from the literature. Novel instrumentation, techniques, and strategies for inductively-coupled plasma mass spectrometry (ICP-MS), microwave-induced plasma (MIP) mass spectrometry, glow-discharge (GD) mass spectrometry, and electrospray ionization (ESI), among others, are described. The use of ionization sources that provide tunable ionization, others that can be modulated between different sets of operating conditions, and others used in parallel is also examined.     

Alleviation of ion suppression effect in sonic spray ionization with induced alternating current voltage

In this study, alleviation of ion suppression effect in sonic spray ionization mass spectrometry (SSI‐MS) was investigated. Ion suppression effect was firstly compared between electrospray ionization (ESI) and conventional SSI, and more severe ion suppression effect was observed with SSI. Ion suppression effect of SSI was also found difficult to be alleviated by simply optimizing major parameters. Alternatively, we found that with the assistance of an alternating current (AC) voltage with low amplitude, the ion suppression effect was greatly alleviated (comparable with conventional ESI). That AC voltage was applied outside the SSI spray tip, and no direct contact between the electrode and spray solution was necessary. Besides the alleviation of the ion suppression effect, this newly‐developed method, termed as induced electrosonic spray ionization (IESSI), appeared to preserve similar charge state distribution with SSI for protonated cytochrome c, hemoglobin, and bradykinin. IESSI could also obtain significantly improved ion intensities (~1000‐fold over conventional SSI). In addition, tolerance of concentrated salts for IESSI‐MS was investigated through the analysis of cytochrome c in the presence of concentrated sodium chloride (NaCl) or ammonium acetate (NH₄OAc). Copyright © 2014 John Wiley & Sons, Ltd.     

原位电离与小型质谱在公共安全领域的应用

质谱作为一种具有高准确度、高灵敏度、高选择性的检测仪器,在公共安全领域有着重要的应用前景。公共安全领域的需求主要涉及毒品、毒物、爆炸物等化学物质的现场快速检测,因其影响广泛,检测结果需非常准确。作为实验室分析仪器,质谱的准确性和速度能满足公共安全的应用需求,但作为现场快速检测的仪器仍需要一定改进。现场快速检测一方面要求检测仪器的小型化,另一方面要求样品前处理的简单化,以使整个检测流程可以无需专业人员来完成。对于检测仪器的小型化,小型质谱的开发在近20年得到了充分发展;对于样品前处理的简单化,研究者发明了原位电离技术,使得基质复杂的被分析物无需前处理即可进行质谱检测。该文首先介绍了原位电离技术的发展及其在公共安全领域的应用,特别是对解吸附电喷雾电离、实时直接分析电离、激光烧蚀电喷雾电离、纸喷雾电离与纸毛细管喷雾电离等典型原位电离技术的原理、性能及在公共安全领域的应用进行了详细介绍,并讨论了几种原位电离现场定量方法。然后,对原位电离小型质谱的发展进行了综述,从最初的小型化离子阱,到仅能检测可挥发有机物的小型质谱,再到可检测非挥发性物质的常规大气压电离源小型质谱,最后发展成为有原位电离源的小型质谱,历经20年的发展使得原位电离小型质谱得以出现和提升。并列举了原位电离小型质谱在毒品现场检测与吸毒人员排查、爆炸物现场侦察、食品安全之农用化学品检测、药物质量检查等公共安全领域的应用。最后,对原位电离小型质谱的发展进行了展望,指出原位电离与小型质谱相结合是小型质谱发展的必然趋势,未来需使用更加智能化的原位电离小型质谱,结合云数据平台,实现更方便广泛的应用。     

Laser spray: electric field-assisted matrix-assisted laser desorption/ionization

A new liquid chromatography/mass spectrometry interface, the laser spray, has been developed. Explosive vaporization and mist formation occur when an aqueous solution effusing out from the tip of the stainless-steel capillary is irradiated from the opposite side of the capillary by a 10.6 microm infrared laser. Weak ion signals could be detected when the plume was sampled through the ion sampling orifice. When a high voltage (3-4 kV) was applied to the stainless-steel capillary, strong ion signals appeared. The ion abundances were found to be orders of magnitude greater than those obtained by conventional electrospray ionization in the case of aqueous solutions. The present method is regarded as an electric-field assisted form of matrix-assisted laser desorption/ionization in which the liquid chromatographic solvent (water, etc.) acts as a liquid matrix. Laser spray ionization is expected to become a versatile method for biological mass spectrometry because this method is compatible with the natural solvent, water.     

Research Advances in Ambient Ionization and Miniature Mass Spectrometry

The development and applications of ambient ionization and miniature mass spectrometry are current research focus in chemical measurement. The analytical technology based on the combination of ambient ionization and miniature mass spectrometry can bypass chromatographic separation and eliminate or simplify sample pretreatment process. The protocol can reverse the labor-intensive and time-consuming drawbacks of traditional analytical methodologies, and realize rapid, on-site analysis with high sensitivity and high throughput. In this paper, the research progress and applications of ambient ionization and miniature mass spectrometry in the fields of food safety, consumer product safety, public security, life sciences and environmental monitoring, are reviewed, and future trends and prospects are discussed, which may provide technical guidance for the researchers engaged in relevant fields.     

Accurate mass measurements by Fourier transform mass spectrometry in the study of advanced glycation end products/peptides

The Maillard reaction occurring between sugars and amino groups is important in living systems. When amino groups belonging to protein chains are involved, the Maillard reaction has been invoked as responsible for protein cross-linking and the production of 'toxic' compounds. The reaction leads to the production of a heterogeneous group of substances, usually called advanced glycation end products (AGEs). Classical analytical approaches, such as spectroscopic (ultraviolet, fluorescence) and mass spectrometric (matrix-assisted laser desorption/ionization, liquid chromatography/electrospray ionization mass spectrometry) methods, have shown that the digestion mixture is highly complex. However, there are clear differences between the digestion mixtures of glycated and unglycated human serum albumin (HSA). In the former case, possible glycated peptides belonging to the AGE peptide class may be identified. Tandem mass spectrometric experiments on selected species seemed to be promising as regards structural information, but it was thought of interest to undertake the present investigation, based on liquid chromatography/electrospray ionization Fourier transform mass spectrometry, in order to obtain definitive results on their elemental composition. Using this approach, about 20 glycated peptides were detected and their possible structures were postulated by examining the known sequence of HSA.     

电喷雾萃取电离质谱快速测定牙膏胶体中的二甘醇

将自行研制的电喷雾萃取电离源(EESI)和LTQ XL质谱仪耦合, 建立了选择性离子化快速测定牙膏胶状纳米级复杂基质样品中微量二甘醇的EESI-MS方法. 实验结果表明, 二甘醇与NH4+, Na+和K+离子在一级质谱中形成特征非共价配合物, 其它大量组分如纳米粒子及胶质等对测定无干扰. 该方法的样品消耗量约0.1 g, 灵敏度高, 单个样品的分析时间不到2 min, 可用于牙膏胶体中低含量二甘醇的选择性快速测定.