Corona discharge in charge reduction electrospray mass spectrometry

Corona discharge is applied to charge reduction electrospray mass spectrometry for the analysis of complex mixtures of biological molecules. Recent work has described a method of charge reduction (reducing the charge states of analyte ions generated by the electrospray process) employing the radioactive isotope 210Po to produce neutralizing species. A variation to this approach is presented, in which charge neutralization is mediated by ions produced in a corona discharge. Varying the corona discharge voltage controls the current and the degree of charge reduction, providing predominantly singly charged ions that are detected by a commercial electrospray time-of-flight mass spectrometer. This technique provides charge reduction for the simplification of ESI spectra, without need for any radioactive material.     

Dual needle corona discharge to generate stable bipolar ion for neutralizing electrosprayed nanoparticles

The performances of dual needle corona discharge (NCD) as bipolar ion source to neutralize the electrospray (ES) particles were characterized and optimized. The NCD was constructed from a tungsten needle and grounded mesh electrode in the needle-to-plane configuration. The dual NCD created a bipolar ion environment by mixing the balanced concentration of positive and negative ions produced by each NCD. The dual NCD was placed in an electrospray aerosol generator (EAG) apparatus to reduce the charge state of the ES particles. Polystyrene latex (PSL) suspensions having the particle size range of 96–256 nm were used as the precursor solution for the electrospray process. Some characterizations to the NCD were carried out to obtain optimum operating voltage and air flow rate. The size distribution and charge fraction of the electrospray PSL (ES-PSL) particles exiting the EAG were also investigated. The result showed the dual NCD could generate stable bipolar ions by mixing positive and negative ions with balanced concentration. The bipolar ions from the dual NCD were capable of neutralizing and reducing the charge state of highly charged ES-PSL particles larger than 100 nm. The EAG, equipped with the dual NCD, could generate ES-PSL particles with stable concentration and consistent size distribution. The charge fraction calculation of the ES-PSL particles showed that more than 80% of the particles exiting the EAG were positively charged.     

Comparison between an unipolar corona charger and a polonium-based bipolar neutralizer for the analysis of nanosized particles and biopolymers

In this work we present results on the charging efficiency of nanoparticles by means of a corona based unipolar charging unit. This device was designed to replace a Po210 bipolar charger unit in a commercial electrospray aerosol generator (TSI Mod 3480). The charging efficiency has been investigated for negative and positive charged particles of various chemical composition in the size range between 5 and 18 nm. The corona current has been found to be the most influential operation parameter on the charging efficiency. With a positive electrospray droplet charge and a negatively-biased corona needle, a rapidly decreasing yield of singly positively charged aerosol particles with increasing corona current was found. An increasing yield of negatively charged particles was observed with increasing current of the corona process. Providing appropriate corona settings nanoparticles with charge levels similar to these obtained with a Po210 charger were found. At optimal corona settings the yield of singly charged particles was found to be two to four times higher for negative and positive particles compared to bipolar charging. This gain in the charging efficiency increases directly the sensitivity of analysis and enhances all measurement and manipulation processes of airborne nanoparticles for which electrical charging is required.     

Detecting large biomolecules from high-salt solutions by fused-droplet electrospray ionization mass spectrometry

A novel fused-droplet electrospray ionization (FD-ESI) source was developed to generate peptide and protein ions. The sample solution was first ultrasonically nebulized to form fine aerosols. The aerosols were then purged into a glass reaction chamber via nitrogen. Charged methanol droplets were continuously generated through electrospraying the acidic methanol solution from a capillary, which was located at the center of the reaction chamber. As the sample aerosols entered the reaction chamber, they fused with the charged methanol droplets from which electrospray proceeded continuously. The mass spectra of peptide and protein that FD-ESI-MS produced were practically identical to those that conventional ESI-MS produced. However, FD-ESI-MS resulted in an extremely high salt tolerance. Cytochrome c ions were detected in the solutions that contained 10% (w/w; 1.709 M) NaCl or 2.5% (425 mM) NaH2PO4. As with those obtained from the solution that lacked NaCl and NaH2PO4, the width of cytochrome c ion peaks remained nearly unchanged.     

Secondary ionization of chemical warfare agent simulants: atmospheric pressure ion mobility time-of-flight mass spectrometry

For the first time, the use of a traditional ionization source for ion mobility spectrometry (radioactive nickel ((63)Ni) beta emission ionization) and three alternative ionization sources (electrospray ionization (ESI), secondary electrospray ionization (SESI), and electrical discharge (corona) ionization (CI)) were employed with an atmospheric pressure ion mobility orthogonal reflector time-of-flight mass spectrometer (IM(tof)MS) to detect chemical warfare agent (CWA) simulants from both aqueous- and gas-phase samples. For liquid-phase samples, ESI was used as the sample introduction and ionization method. For the secondary ionization (SESI, CI, and traditional (63)Ni ionization) of vapor-phase samples, two modes of sample volatilization (heated capillary and thermal desorption chamber) were investigated. Simulant reference materials, which closely mimic the characteristic chemical structures of CWA as defined and described by Schedule 1, 2, or 3 of the Chemical Warfare Convention treaty verification, were used in this study. A mixture of four G/V-type nerve simulants (dimethyl methylphosphonate, pinacolyl methylphosphonate, diethyl phosphoramidate, and 2-(butylamino)ethanethiol) and one S-type vesicant simulant (2-chloroethyl ethyl sulfide) were found in each case (sample ionization and introduction methods) to be clearly resolved using the IM(tof)MS method. In many cases, reduced mobility constants (K(o)) were determined for the first time. Ion mobility drift times, flight times, relative signal intensities, and fragmentation product signatures for each of the CWA simulants are reported for each of the methods investigated.     

Monodispersed decomposition of charged jets of dielectrics

The conditions under which a corona discharge in air can be used to obtain a series of charged monodispersed drops of a dielectric liquid are studied. The charge on the drops, which is characterized by the output current, can be varied over wide limits depending on the position of the jet in the interelectrode space and the voltage of the electrodes. It was confirmed experimentally and numerically that it is best to precharge the cylindrical part of the jet in the field of the corona and then to separate the jet into charged drops by the method of induced capillary decomposition.Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 58, No. 6, pp. 938–943, June, 1990.     

Charge reduction electrospray mass spectrometry

A new mass spectrometric technique, charge reduction electrospray mass spectrometry (CREMS), allowing the analysis of complex mixtures of biological molecules is described. The charge state of ions produced by electrospray ionization may be reduced in a controlled manner to yield predominantly singly charged ions through reactions with bipolar (i.e., both positively and negatively charged) ions generated using a 210Po alpha particle source. The electrospray-generated multiply charged ions undergo charge reduction in a "neutralization chamber" positioned before the entrance nozzle to the mass spectrometer. The ions are detected using a commercial orthogonal electrospray time-of-flight mass spectrometer, although the neutralization chamber can be adapted to virtually any mass analyzer. The CREMS results obtained exhibit a signal intensity drop-off with increasing oligonucleotide size similar to that observed with matrix-assisted laser desorption/ionization mass spectrometry. Proton-transfer reactions were found to be responsible for reducing charge on proteins and oligonucleotides in both positive and negative ion mode.     

Sheathless capillary electrophoresis/electrospray ionization mass spectrometry using a pulled bare fused-silica capillary as the electrospray emitter

It has always been assumed that electrical contact at the capillary outlet is a necessary requirement when coupling capillary electrophoresis (CE) with electrospray ionization mass spectrometry (ESI-MS). In this study, we used a pulled bare-capillary tip as the ESI emitter, but neither was it coated with any electrically conductive materials nor was a high external voltage applied on its outlet. In this paper, we demonstrate that this straightforward approach may be used to generate multiply charged ions of proteins and peptides through electrospray ionization. Our results indicate that peptides and proteins, including bradykinin, cytochrome c, myoglobin, and tryptic digest products that elute from a pulled bare-capillary tip can be detected directly by ESI-MS using the tapered bare-capillary interface. Thus, we have demonstrated that CE and ESI-MS may be combined successfully without the need to modify the outlet of the capillary tip with an electrically contacting material.     

Features of the capillary breakup of jets of dielectric viscous liquids with surface charges

An investigation is reported of the forced capillary breakup of a jet of charged viscous liquid in a corona discharge field.Translated from Inzhenerno-fizicheskii Zhurnal, Vol. 60, No. 4, pp. 576–582, April, 1991.     

High-throughput proteomics using high-efficiency multiple-capillary liquid chromatography with on-line high-performance ESI FTICR mass spectrometry

We report on the design and application of a high-efficiency multiple-capillary liquid chromatography (LC) system for high-throughput proteome analysis. The multiple-capillary LC system using commercial LC pumps was operated at a pressure of 10,000 psi to deliver mobile phases through a novel passive feedback valve arrangement that permitted mobile-phase flow path switching and efficient sample introduction. The multiple-capillary LC system uses several serially connected dual-capillary column devices. The dual-capillary column approach eliminates the time delays for column regeneration (or equilibration) since one capillary column was used for a separation while the other was being washed. Several serially connected dual-capillary columns and electrospray ionization (ESI) sources were operated independently and can be used either for "backup" operation or for parallel operation with other mass spectrometers. This high-efficiency multiple-capillary LC system utilizes switching valves for all operations, enabling automated operation. The separation efficiency of the dual-capillary column arrangement, optimal capillary dimensions (column length and packed particle size), capillary regeneration conditions, and mobile-phase compositions and their compatibility with electrospray ionization were investigated. A high magnetic field (11.4 T) Fourier transform ion cyclotron resonance (FTICR) mass spectrometer was coupled on-line with this high-efficiency multiple-capillary LC system using an ESI interface. The capillary LC provided a peak capacity of approximately 650, and the 2-D capillary LC-FTICR analysis provided a combined resolving power of > 6 x 10(7) components. For yeast cytosolic tryptic digests > 100,000 polypeptides were detected, and approximately 1,000 proteins could be characterized from a single capillary LC-FTICR analysis using the high mass measurement accuracy (approximately 1 ppm) of FTICR, and likely more if LC retention time information were also exploited for peptide identification.     

Coronaspray nebulization and ionization of liquid samples for ion mobility spectrometry

Ion mobility spectrometry after electrospray nebulization and ionization was investigated as a method for the detection of components dissolved in liquids. While electrosprary operating conditions proved promising, greater sensitivity was achieved when the electric potential applied to the sample introduction needle was increased above breakdown potential and a corona discharge was established. Passing the liquid through the corona discharge established a "coronaspray" that efficiently nebulized and ionized the solvent and analytes. In this initial investigation of coronaspray ion mobility spectrometry (CIMS), ion current as a function of potential, temperature, and liquid flow rate was studied; several IMS spectra were obtained; and a continuous monitoring mode of operation was demonstrated. The results from this study indicated that CIMS has potential as a versatile and sensitive detection method for a variety of analytical procedures involving liquid flowing streams such as flow injection analysis, liquid chromatography, capillary zone electrophoresis, and field flow fractionation.     

Electrically controlled generator of micron and submicron water aerosol

A generator of micron and submicron water aerosol of combination (condensation and electrogasdynamic) type is described. In this generator, a steam-gas jet flowing via horizontal capillary from a container with supersaturated steam is subjected to the effect of corona discharge. Attention is called to the importance of taking into account the orientation of the capillary and position of the corona electrode relative to the steam-gas jet. It is found that the parameters of aerosol particles during the condensation of steam-gas jet significantly depend on the intensity of corona discharge. An explanation of observed phenomena is given within the assumption of competition between the forms of condensation in the steam-gas jet, namely, homogeneous condensation, heterogeneous condensation on ions of corona discharge, and heterogeneous condensation on water film fragments formed at the capillary exit section under the effect of electric field. The prevailing forms of condensation are determined in various modes of generator operation depending on the ambient temperature and the intensity of corona discharge.     

Sheathless capillary electrophoresis/electrospray mass spectrometry using a carbon-coated tapered fused-silica capillary with a beveled edge.

A tapered capillary tip containing a beveled edge was developed for use in sheathless capillary electrophoresis/electrospray mass spectrometry (CE/ESI-MS). The optimal flow rate of a 75-microm-i.d., 90-microm-o.d. beveled tapered capillary tip was similar to a conventional flat tapered tip with a 25-microm orifice. Using a mixture of coptisine, berberine, and palmatine chloride, the sheathless CE/ ESI-MS sensitivity of a beveled 75 microm tapered tip capillary was found to be similar to a 25 microm flat tip. Although both tips offer similar CE/ESI-MS sensitivity, the beveled tapered capillary tip is more rugged and durable than a conventional 25-microm tapered capillary because of the larger outside diameter and inside diameter. To make electrical contact, the capillary tip was smeared with paint marker followed by the application of a carbon coating using a graphite pencil. Using this refined carbon-coating procedure, the capillary tip can be operated with aprotic solvents.     

Electrohydrodynamic atomization (EHDA) of high-conductivity pure solvent

ABSTRACT

In this study, the effects of flow rate, liquid conductivity and neutralizer strength on the operating and output characteristics are examined for an Electrohydrodynamic atomization (EHDA)-based aerosol generator system, designed and built in our laboratory. Ethylene glycol is used for generating the droplets. It is seen that stable cone-jet mode could be obtained for solvent conductivity as high as 240 μS/cm. While the output number concentration was found to increase with both flow rate and conductivity, the mean particle diameters decreased with increasing conductivity and increased with flow rate. The mean droplet size and output number concentration are found to be about three times more sensitive to changes in conductivity as compared to that of flow rate in the range of 26–150 μS/cm. It is also observed that throughput from the system is strongly dependent on the strength of the charge neutralizer. In the present setup, 8 μCi ²⁴¹Am bipolar neutralizer in axisymmetric configuration was found to be sufficient to neutralize the generated droplets.     

Generating multiply charged protein ions by ultrasonic nebulization/multiple channel-electrospray ionization mass spectrometry.

An ultrasonic nebulization/multiple channel electrospray ionization (USN/MC-ES) source, which generates multiply charged peptides and proteins ions, was developed. The source is an ultrasonic nebulizer that is connected to a multiple channel electrospray ionization source. Aerosols were formed by ultrasonically nebulizing the sample solution. The aerosols were then purged into the central channel of a seven-channel ES source via nitrogen gas. A methanol solution that contained 1% trifluroacetic acid was electrosprayed through the outlying six electrosprayers. Detection of multiply charged peptide and protein ions indicated that electrospray was generated from the charged droplet containing analyte. The sample aerosol appeared to fuse with the charged methanol droplet in the air. Then electrospray ionization of the analyte occurred from the newly formed droplet. The peptide and protein prepared in deionized water were detected by this USN/MC-ES-MS. By varying the electrospray solvents, the signals of certain components in the mixture were selectively suppressed.     

Design and Optimization of a Corona Discharge Ion Source for Supercritical Fluid Chromatography Time-of-Flight Mass Spectrometry

The interfacing of capillary column supercritical fluid chromatography (SFC) to time-of-flight mass spectrometry (TOFMS) through atmospheric pressure chemical ionization (APCI) was investigated. An ion source chamber and a new, flexible, and efficient transfer line from the SFC to the TOFMS system were designed to accommodate the requirements of this study. Ionization of analytes was performed using a corona discharge needle. The interface was equipped with two multiple-axis translation stages for positioning of the transfer line tip and the discharge needle inside the ion chamber. The investigations were oriented toward the optimization of parameters which have a strong effect on the intensity and stability of the analyte signal, including background stability, corona discharge needle positioning in the ion source, transfer line tip and discharge needle relative positioning, curtain gas and makeup gas flow interactions, ion chamber temperature, and elution pressure of analytes from the SFC system.     

Open-tubular capillary electrochromatography coupled with electrospray ionization mass spectrometry for peptide analysis

In this study, the open-tubular electrochromatographic (OT-CEC) migration behavior of various peptides has been characterized using etched and chemically (n-octadecyl- and cholesterol-) modified capillaries, interfaced to an electrospray ionization mass spectrometer through a sheath liquid configuration. The stationary phases were fabricated by etching the inner wall of the fused-silica capillary and then chemically modifying the new surface through a silanization/hydrosilation reaction. Unlike some other OT-CEC stationary-phase preparation methods, leaching of the immobilized stationary phase and subsequent contamination of the electrospray ion source was largely avoided with this novel surface modification technology. The influence of the immobilized organic phases and those of the buffer electrolytes (pH, the type and content of organic solvent) on the retention and separation of the selected peptides was investigated. Significant peptide retention was found even at very low pH with both types of stationary phases, under conditions whereby the electrophoretic migration dominated the separation process. Due to the effective coverage of the etched surface by a silanization/hydrosilation reaction, adverse adsorption of charged analytes onto the capillary wall was minimized. As a result, very efficient and highly reproducible peptide separations were achieved over a broad pH range. Moreover, peptide-specific multizoning effects were observed. The origin of this novel phenomenon was explored. Compared to capillary electrophoresis electrospray ionization mass spectrometry system, much higher detection sensitivity could be obtained, since a larger amount of sample could be injected and stacked at the head of the open-tubular capillary column without deteriorating the separation performance. On the basis of these observations, these procedures have been adapted to allow the analysis of tryptic peptides generated from proteins.     

Modular ion mobility spectrometer for explosives detection using corona ionization

Ion mobility spectrometry (IMS) has become the most widely used technology for trace explosives detection. A key task in designing IMS systems is to balance the explosives detection performance with size, weight, cost, and safety of the instrument. Commercial instruments are, by and large, equipped with radioactive (63)Ni ionization sources which pose inherent problems for transportation, safety, and waste disposal regulation. An alternative to a radioactive source is a corona discharge ionization source, which offers the benefits of simplicity, stability, and sensitivity without the regulatory problems. An IMS system was designed and built based on modeling and simulation with the goal to achieve a lightweight modular design that offered high performance for the detection of trace explosives using a corona ionization source. Modeling and simulations were used to investigate design alternatives and optimize parameters. Simulated spectra were obtained for 2,4,6-trinitrotoluene (TNT) and cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX) and showed good agreement with experimentally measured spectra using a corona ionization source. The reduced mobilities for TNT and RDX obtained with corona ionization were 1.53 and 1.46 cm(2)/(V s), respectively, and this agreed well with literature values.     

Design and characterization of a multisource hand-held tandem mass spectrometer

A wireless-controlled miniature rectilinear ion trap mass spectrometer system, total weight with batteries 5.0 kg, consuming less than 35 W of power, and having dimensions of 22 cm in length by 12 cm in width by 18 cm in height, is characterized. The design and construction of the mass spectrometer including mass analyzer, vacuum system, electronics system, and data acquisition and processing systems, is detailed. The mass spectrometer is compatible with various types of ionization sources including a glow discharge electron impact ionization source used in the internal ionization mode, and various atmospheric pressure ionization sources, including electrospray ionization, atmospheric pressure chemical ionization, and desorption electrospray ionization, which are employed for external, atmospheric pressure ionization. These external sources are coupled to the miniature mass spectrometer via a capillary interface that is operated in a discontinuous fashion (discontinuous atmospheric pressure interface) to maximize ion transport. The performance of the mass spectrometer for large and small molecules is characterized. Limits of detection in the parts-per-billion range were obtained for selected compounds examined using both the internal ionization and external ionization modes. Tandem mass spectrometry and fast in situ analysis capabilities are also demonstrated using a variety of compounds and ionization sources. Protein molecules are analyzed as the multiply protonated molecules with mass/charge ratios up to 1500 Da/charge.     

Atmospheric pressure air direct current glow discharge ionization source for ion mobility spectrometry

A new atmospheric pressure air direct current glow discharge (DCGD) ionization source has been developed for ion mobility spectrometry (IMS) to overcome the regularity problems associated with the conventional (63)Ni source and the instability of the negative corona discharge. Its general electrical characteristics were experimentally investigated. By equipping it to IMS, a higher sensitivity was obtained compared to that of a (63)Ni source and corona discharge, and a linear dynamic range from 20 ppb to 20 ppm was obtained for m-xylene. Primary investigations showed that alkanes, such as pentane, which are nondetectable or insensitively detectable with (63)Ni-IMS, can be efficiently detected by DCGD-IMS and the detection limit of 10 ppb can be reached. The preliminary results have shown that the new DCGD ionization source has great potential applications in IMS, such as online monitoring of environment pollutants and halogenated compounds.