Stable Electrospray Research Articles

Influence of Solvent Relative Permittivity in Swab Spray Mass Spectrometry.

The influence of solvent properties on ion generation by swab spray ionization was investigated. The ability of a variety of solvents of different relative permittivity, surface tension, and viscosity to form a stable and reproducible electrospray was examined. It is demonstrated that in swab spray ionization, a crucial balance between solvent composition, applied potential, and the solvent flow fed to the swab head must be maintained. The solvent composition was found to significantly affect the shape of the Taylor cone and the emerging cone jet, which eventually have an impact on the resulting ion yield. The results indicate that the relative permittivity of solvents measured under standard conditions is the main factor governing jet shaping, and consequently, the ionization efficacy. Short jets, which are required for maximum ion yield, were observed for solvents with relative permittivity εr higher than 25. Solvents exhibiting lower relative permittivity required the addition of 20% to 60% methanol to limit the jet length and to avoid the ineffective dripping pulsation. The observed effects were compared to conventional electrospray ionization and paper spray ionization.

Direct ESI-MS of Ionic Liquids Using High-Pressure Electrospray From Large-Bore Emitters Made of Micropipette Tips.

Electrospray ionization mass spectrometry of neat undiluted ionic liquid (IL) and the analysis of protein with the doping of IL were performed using high-pressure electrospray. The use of disposable micropipette tips as emitters eased the handling of viscous and easy-to-clog samples and improved the reproducibility of the measurement. A high-pressure operation enabled the stable electrospray of the highly conductive IL from these relatively large bore emitters. The measurement of the current-voltage relationship of 1-ethyl-3-methylimidazolium tetrafluoroborate (Emim BF4) revealed an unusual negative differential resistance that has not been seen in the typical atmospheric or high-pressure electrospray. Mass spectrometric analysis of this IL also showed the characteristic response of various ion species with the emitter voltage. When added to the commonly used protein solution, the mass spectrum also showed protein peaks that correspond to the adduction of fluoroboric acid molecules (HBF4).

Features and advantages of electrospray in an insulating liquid

Electrospraying can be performed in both liquid and air media. We have found that electrospraying in insulating liquids is more stable under a wide range of applied voltages compared to that in air. The stability of the spray in insulating materials indicates a significant relationship between electrical interaction and spray stability within liquid media. The electrospray in air diminished with an increase in the applied voltage from 3 to +4 kV, while that in n-hexane generated a fine spray even at applied voltages exceeding +9 kV. The absence of corona discharge in a spray nozzle immersed in liquid n-hexane contributed to achieving a stable electrospray process with a narrow size distribution. However, in air, voltage-induced corona discharge caused by the ionization of atmospheric molecules (such as N2 and O2) led to a decrease in the stability of the electrospray. To elucidate the differences between the dynamic processes of electrospraying in air and n-hexane, we conducted measurements using high-speed camera imaging, analyzed the size distribution of charged droplets, and assessed circuit current.

A Microfluidic-Fabricated Rod Sprayer for Nanoelectrospray Mass Spectrometry.

The nanoelectrosprayer is a key device in the hyphenation of nanoLC-ESI-MS, and its development plays a crucial role in pushing forward the mining depth of biological discovery and industrialization of omics science. In this work, a new type of nanoelectrospray emitter, a rod sprayer, was developed based on microfluidic manufacture. Due to its porous silica structure, the rod sprayer in effect worked as a multinozzle sprayer, which is composed of a bunch of micrometer sized spray channels. Without the need for sophisticated microfabrication equipment, a superclean environment, or a complicated assembling process, such sprayer rods can be facilely fabricated in a mass production style: 3,600 rods with excellent monodispersity have been fabricated in 1 h, and rod sprayers thus made have demonstrated excellent intraday, interday, and interbatch reproducibilities: RSD = 1.9, 4.9, and 6.1%, respectively. The rod sprayer can generate stable electrospray in a wide voltage range from 2.6 to 3.2 kV and flow rates from 50 to 1000 nL/min, covering typical flow rates of subnanoLC, nanoLC, to microLC, and work steadily even under complex matrix environments (e.g., Hank's balanced salt solution containing sodium, magnesium, and calcium ions) without clogging. Meanwhile, the rod sprayers exhibited 200-1800% ionization efficiency enhancement in comparison with commonly used tapered tip emitters, for small molecule drugs, peptides, and proteins, respectively, and provided a broadened linear dynamic range of 4 orders of magnitude. The excellent characteristics of the rod sprayer, together with its small size and mass production capacity, should provide a high quality, high durability, high consistency, and disposable use-supported nanoelectrospray solution for MS-based bioanalyses.

High flow rate electrospray cooling performance of water–ethanol mixtures

Electrospray (ES) is an effective approach for cooling high-power density devices, owing to its desirable features such as uniform droplet diameter, suppression of droplet rebound, and low power consumption. Despite its excellent thermal properties, water has not been extensively employed as a working fluid in ES setups due to difficulties in establishing a stable ES mode. In this study, ES cooling performance of high flow rate water–ethanol mixtures is investigated. The stable region of the cone-jet mode is identified by capturing the meniscus profile and detecting the corona discharge. The study investigates the effect of ES variables, including flow rate (20 mlhr −100 mlhr), applied voltage (5.30 KV − 12.15 KV), and working fluid including pure ethanol (xH2O= 0 %), mixture I (xH2O= 35 %), and mixture II (xH2O= 70 %), on the cooling performance within the stability region. The results show that raising the flow rate from 20 mlhr to 100 mlhr augments the onset voltage of the cone-jet mode in each fluid. In the case of pure ethanol and mixture I, the end voltage corresponding to the multi-jet mode increases with the rise in flow rate. However, As a result of the heightened surface tension, no multi-jet mode is observed for mixture II, and only the occurrence of corona discharge defines the end voltage. In the single-phase regime, the cooling behavior only depends on the flow rate, owing to the thick liquid layer formed on the heated surface. However, it has been revealed that when the mixture water volume fraction increases up to 70 %, the critical heat flux rise is approximately82 % (Q = 20 mlhr), 148 % (Q = 60 mlhr), and 167 % (Q = 100 mlhr), at the onset voltage and 98 % (Q = 20 mlhr), 131 % (Q = 60 mlhr), and 147 % (Q = 100 mlhr), at the end voltage due to the improved thermal properties of the fluid. Next, the effect of each ES variable on cooling performance is investigated separately. Based on the results, an increase in the flow rate from 40 mlhr to 80 mlhr leads to an approximately 70 % rise in the critical heat flux for both mixture I and mixture II. Additionally, increasing the mixture water volume fraction from 35 % to 70 % results in an approximately 29 % rise in the critical heat flux, attributed to the larger latent heat of mixture II. In the transition regime, mixture II demonstrates superior performance compared to mixture I by suppressing the rebounding effect and enhancing the cooling performance. This improvement is due to the rise in the image force caused by the increase in water volume fraction. However, this enhancement is more significant at the lower flow rate due to the shorter impact time.

A 3D-printed sub-atmospheric pressure electrospray ionization source for robust, facile, and flexible mass spectrometry analysis.

The operation and performance of electrospray ionization (ESI) is affected by the surrounding environment. In this study, a compact sub-atmospheric pressure ESI (SAP-ESI) source was designed and fabricated using the 3D printing method. This source has a simple structure and is easy to operate, as the sample solution and auxiliary gas are continuously sucked into the source through the pressure difference. The compact and enclosed ionization chamber can reduce the fluctuation of the surrounding gas flow to ensure a remarkably stable (< 3%) electrospray. Moreover, the source can offer variable SAP conditions for ESI analysis. The yield of analyte ions increases with decreasing pressure, while the production of background ions is suppressed under these conditions. In the analysis of protein samples, SAP-ESI can increase the yield and charge state of ions, which may be due to the reduction of proton transfer between charged proteins and surrounding gas. The SAP-ESI source was then used to continuously monitor the extract aqueous solution of tea leaves, and to detect the carbendazim residues on the apple surface by coupling with the liquid extraction surface analysis technique. Experimental results demonstrate that the developed SAP-ESI is a stable, practical, and versatile ionization technique.

Capillary self-aspirating electrospray ionization (CSESI) for convenient and versatile mass spectrometry analysis

Electrospray ionization (ESI) is one of the most widely used ionization techniques, and its simplification can benefit many interested users. In this study, sample introduction by capillary action was studied and used to develop a simple ESI source called capillary self-aspirating electrospray ionization (CSESI). A conventional CSESI source requires only a common capillary of appropriate diameter in addition to the support of high voltage (HV). No pumps and sample loading is needed because the solution can spontaneously climb across the capillary by capillary action. With the proper modification of the glass capillary, the operation of CSESI can be further simplified and efficient. Specifically, cold plasma processing of the capillary creates a more hydrophilic surface that can facilitate sample introduction. Moreover, sputtering a thin platinum layer on the capillary tip makes the application of HV more convenient, and it also eliminates the influence of air bubbles in the capillary to ensure a sustained and stable electrospray. Overall, CSESI exhibits multiple desirable features such as simple structure, self-aspiration ability, low sample consumption, and inherent physical filtration capability. Apart from the routine ESI-MS analysis, it has also been applied in real-time monitoring of the oxidative dimerization of 8-methyl-1,2,3,4-tetrahydroquinoline, as well as direct analysis of muddy soil solutions without pretreatment.

Analysis of Peptides and Proteins by Native and SDS Capillary Gel Electrophoresis Coupled to Electrospray Ionization Mass Spectrometry via a Closed-Circuit Coaxial Sheath Flow Reactor Interface.

A simple and widely applicable coaxial sheath flow reactor interface (CSFRI) is introduced for easy and robust connection of liquid-phase microseparation methods to mass spectrometric detection, especially for capillary gel electrophoresis analysis of proteins and peptides including SDS-protein complexes. The interface readily accommodated post-column reactions prior to MS detection. It was demonstrated that this novel closed-circuit connection allowed the utilization of non-MS friendly buffer components without significant ion suppression and supported stable electrospray. In SDS capillary agarose gel electrophoresis mode, addition of γ-cyclodextrin to the sheath liquid efficiently removed the SDS content of the sample and the background electrolyte in the flow reactor section by inclusion complexation, while maintaining good separation efficiency and decreasing ion suppression.

Stable electrospray signal on a microfabricated glass chip with three-dimensional open edge and tiered depth geometries

This paper presents the microfabrication and performance of a three-dimensional electrospray ionization (ESI) emitter tip made from glass, which achieves stable current signals important for chemical analysis. Our novel microfabrication process and custom-built signal conditioning hardware provides the advantage of providing accurate features and steady signals. The fabrication process relies on standard microfabrication techniques (i.e., deposition, photolithography, and wet etching). This fabrication method involves the novel application of two layers of positive and negative photoresists in addition to Parafilm® wax tape. Open edge and tiered depth details were successfully created from a multilayer planar mask. This is a benefit for integrated miniaturized and microfluidic systems that often require micro features for their functionality but relatively large millimeter size features for their physical periphery. We demonstrate the fundamental performance of electrospray with this microfluidic chip. The emitter tip was fixed on a linear axis stage with high resolution (10 μm) to finely control the tip distance from a metal counter electrode plate. A custom printed circuit board system was built to safely control four voltages applied to the microchip ports from a single high voltage power supply. To readily form the electrospray, non-aqueous solvents were used for their low viscosity and a constant voltage of +2.7 kV was applied to the sheath electrospray microchannel. The liquid being sprayed was 80/20 (v/v) methanol/acetonitrile with 0.1% acetic acid in the sheath microchannel and with ammonium acetate (10–40 mM) in its remaining microchannels. The electrospray signal was measured in response to varying the distance (1.4 to 1.6 mm) between the electrospray emitter tip and a metal counter electrode plate in addition to the varying concentration of the background electrolyte, ammonium acetate. Stable and repeatable electrospray signal showed linear relationships with emitter tip distance and concentration (r2 ≥ 0.95).

High-Throughput and Rapid Screening of Drugs of Abuse in Saliva by Multi-Segment Injection Using Solid-Phase Microextraction-Automated Microfluidic Open Interface-Mass Spectrometry.

There is great demand for analytical methods capable of providing high-throughput and rapid screening, especially for anti-doping and clinical point-of-care applications. In this work, automated microfluidic open interface-mass spectrometry (MOI-MS) was used for coupling with high-throughput, automated solid-phase microextraction (SPME) to achieve this objective. The design of the MOI-MS interface provides a continuous and stable electrospray fluid flow to the MS without introducing any bubble, a feature that we exploit to introduce the concept of multi-segment injection for the determination of multiple samples in a single MS run. By eliminating the need to start a new MS run between sample assays, the developed approach provides significantly simplified protocols controlled by programmed software and increased reproducibility. Furthermore, the biocompatible SPME device, which utilizes coating consisting of hydrophilic-lipophilic balanced particles embedded in a polyacrylonitrile (PAN) binder, can be directly used for biological sample analysis, as the PAN acts as both a binder and a matrix-compatible barrier, thus enabling the enrichment of small molecules while eliminating interferences associated with the presence of interfering macromolecules. The above design was employed to develop a fast, quantitative method capable of analyzing drugs of abuse in saliva samples in as little as 75 s per sample. The findings indicate that the developed method provides good analytical performance, with limits of detection ranging between 0.05 and 5 ng/mL for analysis of 16 drugs of abuse, good calibration linear correlation coefficients (R2 ≥ 0.9957), accuracy between 81 and 120%, and excellent precision (RSD% < 13%). Finally, a proof-of-concept experiment was performed to demonstrate the method's suitability for real-time analysis in anti-doping applications.

Coupling capillary electrophoresis-electrospray ionization mass spectrometry with sheathless interface for drug analysis

Capillary electrophoresis-mass spectrometry （CE-MS） combines the advantages of capillary electrophoresis， such as the high separation efficiency and low sample consumption， and the high detection sensitivity of mass spectrometry and the ability for providing the structural information for structure elucidation of unknown components. However， the interface technology for coupling capillary electrophoresis and mass spectrometry is still not well resolved. In the present work， we explored the application of the sheathless CE-MS interface which was prepared by gold foil-wrapped CE separation column tip directly as a spray electrode for the analysis of five tyrosine kinase inhibitors， namely sunitinib， imatinib mesylate， gefitinib， dasatinib and erlotinib. This interface integrates separation and electrospray ionization in one capillary， which is easy to manufacture， low in cost， and can be produced in batches. We found that using the nonaqueous CE separation mode can not only achieve baseline separation of five tyrosine kinase inhibitors， but also obtain stable mass spectrometry signals. First， we investigated the effect of the electrolyte solution composition on the separation. The optimized background electrolyte composition was obtained： 2% （v/v） acetic acid and 5 mmol/L ammonium acetate in acetonitrile-methanol （80∶20， v/v）. Under optimized conditions， the five kinase inhibitors could be baseline separated， meantime， the sheathless interface could also maintain stable electrospray for a long time. The relative standard deviation （RSD） values of the intraday and interday repeatability of the analyte retention times were less than 0.5% and 0.8%， respectively， and the RSD value between interface batches is less than 2.6%. Compared with CE-MS with aqueous phase， the separation column efficiency of the five tyrosine kinase inhibitors under nonaqueous phase conditions is higher， the detection sensitivity is higher， and the absolute detection limit reaches amol level. In addition， we evaluated the sheathless interface with various organic acids， such as palaflin A， salvianolic acid C， and rosmarinic acid， as well as hydrophobic macrolide antibiotics， azithromycin， erythromycin， and sporin A， good separation effect and mass spectrometric detection results can be obtained.

Stably electrospraying highly conductive sodium chloride aqueous solution coated with outer ionic liquid using coaxial capillary

Concentrated aqueous solutions with high conductivity have been proven difficult to be stably electrosprayed mainly due to their large surface tension, which will easily trigger air discharge. The ionic liquid with lower surface tension is involatile, viscous, and highly conductive and can easily achieve stable electrospray. This paper presents a more convenient method to ionize the concentrated aqueous solution than the previous attempts and proves the feasibility of coaxially electrospraying two highly conductive liquids (∼1 S/m). Our method utilizes a coaxial capillary to coat the highly conducting concentrated sodium chloride (NaCl) aqueous solution (0.67 S/m) with a thin layer of immiscible ionic liquid to form a compound cone and achieve the stable coaxial electrospray. The compound cone remains static at a suitable flow rate (0.1–1 nl/s) of the ionic liquid. At a higher or lower flow rate, the compound cone elongates or shrinks and eventually vibrates. Due to the high conductivity of both liquids, the spray current does not follow the current scaling law. The spray current is mostly dominated by the NaCl solution and counterintuitively decreases as the flow rate of the ionic liquid increases due to the frequent vibration of the compound cone. The highly conducting thin layer of the ionic liquid is the key to achieving stable coaxial electrospray. It lowers the surface tension of the compound cone and shields the external electric field acting at the inner aqueous solution; thus, the air discharge of the aqueous solution is suppressed, and the stable compound cone can be formed.

A novel single step solid-phase extraction combined with bromine derivatization method for rapid determination of acrylamide in coffee and its products by stable isotope dilution ultra-performance liquid chromatography tandem triple quadrupole electrospray ionization mass spectrometry

This work aimed to establish a novel determination method for acrylamide in coffee and its products by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Acrylamide in samples were prepared by a single-step solid-phase extraction clean-up using mixed mode sorbents. The bromine derivatization efficiency of acrylamide and its internal standard were improved at an acidic condition. After derivation, the retention capability of acrylamide and its resistance to interference were significantly improved. The limit of detection (LOD) and the limit of quantification (LOQ) were 1.2 and 4 μg/kg for roasted and instant coffees, while they were 0.24 and 0.8 μg/kg for ready-to-drink coffees. The average recoveries for acrylamide ranged from 99.3 to 102.2% in coffee and its products. All the results showed that the developed method was simple, quick, specific and suitable for screening and determination of acrylamide in batch samples of coffee and its products.

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.

Electrospray mechanism for quantum dot thin-film formation using an electrohydrodynamic jet and light-emitting device application

A novel electrohydrodynamic (EHD) electrospray coating mechanism was proposed for the continuous fabrication of large-area quantum dot (QD) thin films for high-performance light-emitting diodes (LEDs). The size of QD droplets was systemically controlled using the stable EHD electrospray mode from a mixed solvent, which is a crucial factor for the formation of large and smooth QD thin films. The minimum amount of material consumption was achieved during the process by applying the unique coating system. A QD-LED device based on electrodeposited QDs showed a maximum luminance of 12,082 cd m−2, maximum current efficiency of nearly 4.0 cd A−1, and maximum EQE of 1.86%. This system demonstrates not only high reproducibility but could also pave the way for commercializing high-quality QD-LED devices.

Discharge current of water electrospray with electrical conductivity under high-voltage and high-flow-rate conditions

Recently, several attempts have been made to implement electrospray for electrostatic precipitators (EPs) to reduce water consumption and prevent dust from being rescattered from dry EPs. In particular, the electrospray droplet size in EPs should be sufficiently large to collect dust in the exhaust gas flow, which requires a considerably larger electrospray flow rate than that required for typical applications. In addition, in the case of water electrospray, a high supply voltage is required because of its high surface tension. In this study, the characteristics of water-based electrospray were investigated under a high voltage and high flow rate. Three types of fluids—distilled water, tap water, and saline solution—were used to test for different conductivities under an electric charge with a negative current. The corona discharge and spray trajectories were visualized to determine the spray stability. To verify the influence of the spray current, the waveform of the electrospray was also analyzed under both dry- and wet-spray conditions. From this comparison, a portion of the spray current was estimated out of the total discharge current, which is the sum of the corona discharge and the spray current. The flow rate and voltage of the test were limited at 20 mL/min and −50 kV, respectively. In contrast with previous low flow rate studies, our results showed that the discharge current increased rapidly under flow rates above 6 mL/min, leading to arc discharge. Thus, it is important to adjust the flow and conductivity to guarantee stable and efficient water-based electrosprays.

3-Bromopyruvate regulates the status of glycolysis and BCNU sensitivity in human hepatocellular carcinoma cells

Chloroethylnitrosoureas (CENUs) are bifunctional antitumor alkylating agents, which exert their antitumor activity through inducing the formation of dG-dC interstrand crosslinks (ICLs) within DNA double strand. However, the complex process of tumor biology enables tumor cells to escape the killing triggered by CENUs, as for instance with the detoxifying activity of O6-methylguanine DNA methyltransferase (MGMT) to accomplish DNA damage repair. Considering the fact that most tumor cells highly depend on aerobic glycolysis to provide energy for survival even in the presence of oxygen (Warburg effect), inhibition of aerobic glycolysis may be an attractive strategy to overcome the resistance and improve the chemotherapeutic effects of CENUs. Especially, 3-bromopyruvate (3-BrPA), a small molecule alkylating agent, has been emerged as an effective glycolytic inhibitor (energy blocker) in cancer treatment. In view of its tumor specificity and inhibition on cellular multiple targets, it is likely to reduce the chemoresistance when chemotherapeutic drugs are combined with 3-BrPA. In this study, we investigated the effects of 3-BrPA on the chemosensitivity of two human hepatocellular carcinoma (HCC) cell lines to the cytotoxic effects of l,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the underlying molecular mechanism. The sensitivity of SMMC-7721 and HepG2 cells to BCNU was significantly increased by 2 h pretreatment with micromolar dosage of 3-BrPA. Moreover, 3-BrPA decreased the cellular ATP and GSH levels, and extracellular lactate excreted by tumor cells, and the effects were more effective when 3-BrPA was combined with BCNU. Cellular hexokinase-II (HK-II) activity was also reduced after exposure to the treatment of 3-BrPA plus BCNU. Based on the above results, the effects of 3-BrPA on the formation of dG-dC ICLs induced by BCNU was investigated by stable isotope dilution high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The results indicated that BCNU produced higher levels of dG-dC ICLs in SMMC-7721 and HepG2 cells pretreated with 3-BrPA compared to that without 3-BrPA pretreatment. Notably, in MGMT-deficient HepG2 cells, the levels of dG-dC ICLs were significantly higher than MGMT-proficient SMMC-7721 cells. In general, these findings revealed that 3-BrPA, as an effective glycolytic inhibitor, may be considered as a potential clinical chemosensitizer to optimize the therapeutic index of CENUs.

Glycolytic inhibition by 3-bromopyruvate increases the cytotoxic effects of chloroethylnitrosoureas to human glioma cells and the DNA interstrand cross-links formation

DNA interstrand cross-links (ICLs) are essential for the antitumor activity of chloroethylnitrosoureas (CENUs). Commonly, CENUs resistance is mainly considered to be associated with O6-methylguanine-DNA methyltransferase (MGMT) within tumors. Bypassing the MGMT-mediated resistance, to our knowledge, herein, we first utilized a novel glycolytic inhibitor, 3-bromopyruvate (3-BrPA), to increase the cytotoxic effects of l,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to human glioma cells based on the hypothesis that blocking energy metabolism renders tumor cells more sensitive to chemotherapy. We found 3-BrPA significantly increased the cell killing by BCNU in human glioma SF763 and SF126 cell lines. Significantly decreased levels of extracellular lactate, cellular ATP and glutathione (GSH) were observed after 3-BrPA treatment, and the effects were more remarkable with 3-BrPA in combination with BCNU. Considering that the role of ATP and GSH in drug efflux, DNA damage repair and drug inactivation, we determined the effect of 3-BrPA on the formation of dG-dC ICLs induced by BCNU using stable isotope dilution high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). As expected, the levels of lethal dG-dC ICLs induced by BCNU were obviously enhanced after 3-BrPA pretreatment. Based on these results, 3-BrPA and related glycolytic inhibitors may be promising to enhance the cell killing effect and reverse the clinical chemoresistance of CENUs and related antitumor agents.

Spray-Capillary: An Electrospray-Assisted Device for Quantitative Ultralow-Volume Sample Handling.

The analysis of low-volume samples provides valuable insight into complex biological systems. However, the proteomic and metabolomic analysis of low-volume samples remains challenging due to the lack of simple, efficient, and reproducible microsampling techniques. We have developed an electrospray-assisted device for quantitative low-volume sample extraction, referred to here as "Spray-Capillary". Stable electrospray was achieved through a chemically etched tip from a long (e.g., 50 cm) capillary with a conductive sheath flow. This electrospray provided the driving force to quantitatively draw low-volume samples into the capillary. We evaluated the precision and accuracy of sample injection volumes using our spray-capillary as the electrospray voltage, capillary ID, and column length were varied. Our results demonstrate that spray-capillary allows for reproducible and quantitative microsampling with low injection flow rates (as low as 15 pL/s). Furthermore, spray-capillary can be directly coupled with capillary zone electrophoresis (CZE) for separation. Overall, spray-capillary is a simple microsampling device that holds great potential for high-throughput quantitative omics analysis of ultralow-volume samples.

Anthropogenic influences on dissolved organic matter transport in high arsenic groundwater: Insights from stable carbon isotope analysis and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

In East and Southeast Asia, the health of over 100 million people is threatened by the consumption of groundwater containing high concentrations of arsenic (>10 μg L−1), which is released from sediments through reductive dissolution of arsenic-bearing iron/manganese oxides. Dissolved organic matter (DOM) is known to play a crucial role in the process of arsenic mobilization in shallow aquifers, and its availability and reactivity are key factors controlling the variation of arsenic concentrations in groundwater. However, it is unclear how human activities influence the transport of DOM and how the transportation affects the DOM molecular properties in high arsenic groundwater. This study provides insights on the sources and molecular compositions of DOM in groundwater from the Jianghan Plain, central China, a newly discovered area with seasonal fluctuations in arsenic concentrations in shallow groundwater. Monitoring of water levels and stable carbon isotope compositions in groundwater from different depths and canal water over a year indicated that terrestrial DOM was the dominant source, accounting for 54.2%–85.5% of groundwater DOM. Electrospray ionization combined with ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry revealed that canal water infiltration transferred aliphatic, tannin-like and leached aromatic DOM from sediments into groundwater. Therefore, groundwater recharge through irrigation using canal water not only inputs terrestrial DOM, but also accelerates the release of sedimentary DOM. Furthermore, carboxylic-rich alicyclic molecule (CRAM)-like DOM that is derived from biomolecules has the highest proportion (60.1%–65.5%) among the identified DOM structures. And, it might be reused in biochemical processes during arsenic mobilization, suggesting a third source of groundwater DOM in addition to canal water and sediments. The findings in this study advance the understanding on transport processes and molecular properties of DOM in high arsenic groundwater under extensive anthropogenic influences.