Lab on a chip for detecting Clara cell protein 16 (CC16) for potential screening of the workers exposed to respirable silica aerosol.

Early detection of pulmonary responses to silica aerosol exposure, such as lung inflammation as well as early identification of silicosis initiation, is of great importance in disease prevention of workers. In this study, to early screen the health condition of the workers who are exposed to respirable silica dusts, an immunoassay lab on a chip (LOC) was designed, developed and fully characterized for analyzing Clara cell protein 16 (CC16) in serum which has been considered as one of the potential biomarkers of lung inflammation or lung damage due to the respirable silica dusts. Sandwich immunoassay of CC16 was performed on the LOC developed with a custom-designed portable analyzer using artificial serums spiked with CC16 protein first and then human serums obtained from the coal mine workers exposed to the respirable silica-containing dusts. The dynamic range of CC16 assay performed on the LOC was in a range of 0.625-20 ng/mL, and the achieved limit of detection (LOD) was around 0.35 ng/mL. The assay results of CC16 achieved from both the developed LOC and the conventional 96 well plate showed a reasonable corelation. The correlation between the conventional reader and the developed portable analyzer was found to be reasonable, resulting in R2 ~ 0.93. This study shows that the LOC developed for the early detection of CC16 can be potentially applied for the development of a field-deployable point-of-care testing (POCT) for the early monitoring of the field workers who are exposed to silica aerosol.

Aerodynamic size separation of glass fiber aerosols.

The objective of this study was to investigate the efficacy of an aerodynamic separation scheme for obtaining aerosols with nearly monodisperse fiber lengths as test samples for mechanistic toxicological evaluations. The approach involved the separation of aerosolized glass fibers using an Aerodynamic Aerosol Classifier (AAC) or a multi-cyclone sampling array, followed by the collection of separated samples on filter substrates, and the measurement of each sample fiber length distribution. A glass fiber aerosol with a narrow range of aerodynamic sizes was selected and sampled with the AAC or multi-cyclone sampling array in two separate setups. The fiber length and diameter were measured using a field emission scanning electron microscope. The glass fiber aerosol was separated in distinct groups of eight with the AAC and of four with the multi-cyclone sampling array. The geometric standard deviations of the fiber length distributions of the separated aerosols ranged from 1.49 to 1.69 for the AAC and from 1.6 to 1.8 for multi-cyclone sampling array. While the separation of glass fiber aerosols with an AAC is likely to produce two different length fiber groups and the length resolution may be acceptable, the overall mass throughput of these separation schemes is limited.

Highly Sensitive Lab on a Chip (LOC) Immunoassay for Early Diagnosis of Respiratory Disease Caused by Respirable Crystalline Silica (RCS).

Respirable crystalline silica (RCS) produced in mining and construction industries can cause life-threatening diseases such as silicosis, lung cancer, and chronic obstructive pulmonary disease (COPD). These diseases could be more effectively treated and prevented if RCS-related biomarkers were identified and measured at an early stage of disease progression, which makes development of a point of care test (POCT) platform extremely desirable for early diagnosis. In this work, a new, highly sensitive lab on a chip (LOC) immunoassay has been designed, developed, and characterized for tumor necrosis factor α (TNF-α), a protein biomarker that causes lung inflammation due to RCS exposure. The designed LOC device is composed of four reservoirs for sample, enzyme conjugated detection antibody, wash buffer, and chemiluminescence substrate in liquid form, along with three spiral reaction chambers for test, positive control, and negative control. All reservoirs and spiral microchannels were connected in series and designed to perform sequential delivery of immunoassay reagents with minimal user intervention. The developed LOC measured TNF-α concentrations as low as 16 pg/mL in plasma from RCS-exposed rats and also had a limit of detection (LOD) of 0.5 pg/mL in spiked artificial serum. In addition, the analysis time was drastically reduced to about 30 min, as opposed to hours in conventional methods. Successful implementation of a highly sensitive, chemiluminescence-based immunoassay on a preloaded LOC with proper quality control, as reported in this work, can pave the way toward developing a new rapid POCT platform for in-field clinical diagnosis.

Deposition of graphene nanomaterial aerosols in human upper airways.

Graphene nanomaterials have attracted wide attention in recent years on their application to state-of-the-art technology due to their outstanding physical properties. On the other hand, the nanotoxicity of graphene materials also has rapidly become a serious concern especially in occupational health. Graphene naomaterials inevitably could become airborne in the workplace during manufacturing processes. The inhalation and subsequent deposition of graphene nanomaterial aerosols in the human respiratory tract could potentially result in adverse health effects to exposed workers. Therefore, investigating the deposition of graphene nanomaterial aerosols in the human airways is an indispensable component of an integral approach to graphene occupational health. For this reason, this study carried out a series of airway replica deposition experiments to obtain original experimental data for graphene aerosol airway deposition. In this study, graphene aerosols were generated, size classified, and delivered into human airway replicas (nasal and oral-to-lung airways). The deposition fraction and deposition efficiency of graphene aerosol in the airway replicas were obtained by a novel experimental approach. The experimental results acquired showed that the fractional deposition of graphene aerosols in airway sections studied were all less than 4%, and the deposition efficiency in each airway section was generally lower than 0.03. These results indicate that the majority of the graphene nanomaterial aerosols inhaled into the human respiratory tract could easily penetrate through the head airways as well as the upper part of the tracheobronchial airways and then transit down to the lower lung airways, where undesired biological responses might be induced.

Measurement of Transport Properties of Aerosolized Nanomaterials.

Airborne engineered nanomaterials such as single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), functionalized MWCNT, graphene, fullerene, silver and gold nanorods were characterized using a tandem system of a differential mobility analyzer and an aerosol particle mass analyzer to obtain their airborne transport properties and understand their relationship to morphological characteristics. These nanomaterials were aerosolized using different generation methods such as electrospray, pneumatic atomization, and dry aerosolization techniques, and their airborne transport properties such as mobility and aerodynamic diameters, mass scaling exponent, dynamic shape factor, and effective density were obtained. Laboratory experiments were conducted to directly measure mobility diameter and mass of the airborne nanomaterials using tandem mobility-mass measurements. Mass scaling exponents, aerodynamic diameters, dynamic shape factors and effective densities of mobility-classified particles were obtained from particle mass and the mobility diameter. Microscopy analysis using Transmission Electron Microscopy (TEM) was performed to obtain morphological descriptors such as envelop diameter, open area, aspect ratio, and projected area diameter. The morphological information from the TEM was compared with measured aerodynamic and mobility diameters of the particles. The results showed that aerodynamic diameter is smaller than mobility diameter below 500 nm by a factor of 2 to 4 for all nanomaterials except silver and gold nanorods. Morphologies of MWCNTs generated by liquid-based method, such as pneumatic atomization, are more compact than those of dry dispersed MWCNTs, indicating that the morphology depends on particle generation method. TEM analysis showed that projected area diameter of MWCNTs appears to be in reasonable agreement with mobility diameter in the size range from 100 - 400 nm. Principal component analysis of the obtained airborne particle properties also showed that the mobility diameter-based effective density and aerodynamic diameter are eigenvectors and can be used to represent key transport properties of interest.

Efficacy of screens in removing long fibers from an aerosol stream--sample preparation technique for toxicology studies.

Fiber dimension (especially length) and biopersistence are thought to be important variables in determining the pathogenicity of asbestos and other elongate mineral particles. In order to prepare samples of fibers for toxicology studies, it is necessary to develop and evaluate methods for separating fibers by length in the micrometer size range. In this study, we have filtered an aerosol of fibers through nylon screens to investigate whether such screens can efficiently remove the long fibers (L >20 µm, a typical macrophage size) from the aerosol stream. Such a sample, deficient in long fibers, could then be used as the control in a toxicology study to investigate the role of length. A well-dispersed aerosol of glass fibers (a surrogate for asbestos) was generated by vortex shaking a Japan Fibrous Material Research Association (JFMRA) glass fiber powder. Fibers were collected on a mixed cellulose ester (MCE) filter, imaged with phase contrast microscopy (PCM) and lengths were measured. Length distributions of the fibers that penetrated through various screens (10, 20 and 60 µm mesh sizes) were analyzed; additional study was made of fibers that penetrated through double screen and centrally blocked screen configurations. Single screens were not particularly efficient in removing the long fibers; however, the alternative configurations, especially the centrally blocked screen configuration, yielded samples substantially free of the long fibers.

Evaluation of a diffusion charger for measuring aerosols in a workplace.

The model DC2000CE diffusion charger from EcoChem Analytics (League City, TX, USA) has the potential to be of considerable use to measure airborne surface area concentrations of nanoparticles in the workplace. The detection efficiency of the DC2000CE to reference instruments was determined with monodispersed spherical particles from 54 to 565.7 nm. Surface area concentrations measured by a DC2000CE were then compared to measured and detection efficiency adjusted reference surface area concentrations for polydispersed aerosols (propylene torch exhaust, incense, diesel exhaust, and Arizona road dust) over a range of particle sizes that may be encountered in a workplace. The ratio of surface area concentrations measured by the DC2000CE to that measured with the reference instruments for unimodal and multimodal aerosols ranged from 0.02 to 0.52. The ratios for detection efficiency adjusted unimodal and multimodal surface area concentrations were closer to unity (0.93-1.19) for aerosols where the majority of the surface area was within the size range of particles used to create the correction. A detection efficiency that includes the entire size range of the DC2000CE is needed before a calibration correction for the DC2000CE can be created. For diesel exhaust, the DC2000CE retained a linear response compared to reference instruments up to 2500 mm(2) m(-3), which was greater than the maximum range stated by the manufacturer (1000 mm(2) m(-3)). Physical limitations with regard to DC2000CE orientation, movement, and vibration were identified. Vibrating the DC2000CE while measuring aerosol concentrations may cause an increase of ~35 mm(2) m(-3), whereas moving the DC2000CE may cause concentrations to be inflated by as much as 400 mm(2) m(-3). Depending on the concentration of the aerosol of interest being measured, moving or vibrating a DC2000CE while measuring the aerosol should be avoided.

Characterization of a Vortex Shaking Method for Aerosolizing Fibers.

Generation of well-dispersed, well-characterized fibers is important in toxicology studies. A vortex-tube shaking method is investigated using glass fibers to characterize the generated aerosol. Controlling parameters that were studied included initial batch amounts of glass fibers, preparation of the powder (e.g., preshaking), humidity, and airflow rate. Total fiber number concentrations and aerodynamic size distributions were typically measured. The aerosol concentration is only stable for short times (t < 10 min) and then falls precipitously, with concomitant changes in the aerosol aerodynamic size distribution; the plateau concentration and its duration both increase with batch size. Preshaking enhances the initial aerosol concentration and enables the aerosolization of longer fibers. Higher humidity strongly affects the particle size distribution and the number concentration, resulting in a smaller modal diameter and a higher number concentration. Running the vortex shaker at higher flow rates (Q > 0.3 lpm), yields an aerosol with a particle size distribution representative of the batch powder; running the vortex shaker at a lower aerosol flow rate (Q ~ 0.1 lpm) only aerosolizes the shorter fibers. These results have implications for the use of the vortex shaker as a standard aerosol generator.

Toward Developing a New Occupational Exposure Metric Approach for Characterization of Diesel Aerosols.

The extensive use of diesel-powered equipment in mines makes the exposure to diesel aerosols a serious occupational issue. The exposure metric currently used in U.S. underground noncoal mines is based on the measurement of total carbon (TC) and elemental carbon (EC) mass concentration in the air. Recent toxicological evidence suggests that the measurement of mass concentration is not sufficient to correlate ultrafine aerosol exposure with health effects. This urges the evaluation of alternative measurements. In this study, the current exposure metric and two additional metrics, the surface area and the total number concentration, were evaluated by conducting simultaneous measurements of diesel ultrafine aerosols in a laboratory setting. The results showed that the surface area and total number concentration of the particles per unit of mass varied substantially with the engine operating condition. The specific surface area (SSA) and specific number concentration (SNC) normalized with TC varied two and five times, respectively. This implies that miners, whose exposure is measured only as TC, might be exposed to an unknown variable number concentration of diesel particles and commensurate particle surface area. Taken separately, mass, surface area, and number concentration did not completely characterize the aerosols. A comprehensive assessment of diesel aerosol exposure should include all of these elements, but the use of laboratory instruments in underground mines is generally impracticable. The article proposes a new approach to solve this problem. Using SSA and SNC calculated from field-type measurements, the evaluation of additional physical properties can be obtained by using the proposed approach.

Investigation of Aerosol Surface Area Estimation from Number and Mass Concentration Measurements: Particle Density Effect.

For nanoparticles with nonspherical morphologies, e.g., open agglomerates or fibrous particles, it is expected that the actual density of agglomerates may be significantly different from the bulk material density. It is further expected that using the material density may upset the relationship between surface area and mass when a method for estimating aerosol surface area from number and mass concentrations (referred to as "Maynard's estimation method") is used. Therefore, it is necessary to quantitatively investigate how much the Maynard's estimation method depends on particle morphology and density. In this study, aerosol surface area estimated from number and mass concentration measurements was evaluated and compared with values from two reference methods: a method proposed by Lall and Friedlander for agglomerates and a mobility based method for compact nonspherical particles using well-defined polydisperse aerosols with known particle densities. Polydisperse silver aerosol particles were generated by an aerosol generation facility. Generated aerosols had a range of morphologies, count median diameters (CMD) between 25 and 50 nm, and geometric standard deviations (GSD) between 1.5 and 1.8. The surface area estimates from number and mass concentration measurements correlated well with the two reference values when gravimetric mass was used. The aerosol surface area estimates from the Maynard's estimation method were comparable to the reference method for all particle morphologies within the surface area ratios of 3.31 and 0.19 for assumed GSDs 1.5 and 1.8, respectively, when the bulk material density of silver was used. The difference between the Maynard's estimation method and surface area measured by the reference method for fractal-like agglomerates decreased from 79% to 23% when the measured effective particle density was used, while the difference for nearly spherical particles decreased from 30% to 24%. The results indicate that the use of particle density of agglomerates improves the accuracy of the Maynard's estimation method and that an effective density should be taken into account, when known, when estimating aerosol surface area of nonspherical aerosol such as open agglomerates and fibrous particles.

Comparison of diffusion charging and mobility-based methods for measurement of aerosol agglomerate surface area.

We compare different approaches to measure surface area of aerosol agglomerates. The objective was to compare field methods, such as mobility and diffusion charging based approaches, with laboratory approach, such as Brunauer, Emmett, Teller (BET) method used for bulk powder samples. To allow intercomparison of various surface area measurements, we defined 'geometric surface area' of agglomerates (assuming agglomerates are made up of ideal spheres), and compared various surface area measurements to the geometric surface area. Four different approaches for measuring surface area of agglomerate particles in the size range of 60-350 nm were compared using (i) diffusion charging-based sensors from three different manufacturers, (ii) mobility diameter of an agglomerate, (iii) mobility diameter of an agglomerate assuming a linear chain morphology with uniform primary particle size, and (iv) surface area estimation based on tandem mobility-mass measurement and microscopy. Our results indicate that the tandem mobility-mass measurement, which can be applied directly to airborne particles unlike the BET method, agrees well with the BET method. It was also shown that the three diffusion charging-based surface area measurements of silver agglomerates were similar within a factor of 2 and were lower than those obtained from the tandem mobility-mass and microscopy method by a factor of 3-10 in the size range studied. Surface area estimated using the mobility diameter depended on the structure or morphology of the agglomerate with significant underestimation at high fractal dimensions approaching 3.

Particle Collection Efficiency for Nylon Mesh Screens.

Mesh screens composed of nylon fibers leave minimal residual ash and produce no significant spectral interference when ashed for spectrometric examination. These characteristics make nylon mesh screens attractive as a collection substrate for nanoparticles. A theoretical single-fiber efficiency expression developed for wire-mesh screens was evaluated for estimating the collection efficiency of submicrometer particles for nylon mesh screens. Pressure drop across the screens, the effect of particle morphology (spherical and highly fractal) on collection efficiency and single-fiber efficiency were evaluated experimentally for three pore sizes (60, 100 and 180 µm) at three flow rates (2.5, 4 and 6 Lpm). The pressure drop across the screens was found to increase linearly with superficial velocity. The collection efficiency of the screens was found to vary by less than 4% regardless of particle morphology. Single-fiber efficiency calculated from experimental data was in good agreement with that estimated from theory for particles between 40 and 150 nm but deviated from theory for particles outside this size range. New coefficients for the single-fiber efficiency model were identified that minimized the sum of square error (SSE) between the values estimated with the model and those determined experimentally. Compared to the original theory, the SSE calculated using the modified theory was at least one order of magnitude lower for all screens and flow rates with the exception of the 60-µm pore screens at 2.5 Lpm, where the decrease was threefold.

Exposure and emissions monitoring during carbon nanofiber production--Part I: elemental carbon and iron-soot aerosols.

Production of carbon nanofibers and nanotubes (CNFs/CNTs) and their composite products is increasing globally. High volume production may increase the exposure risks for workers who handle these materials. Though health effects data for CNFs/CNTs are limited, some studies raise serious health concerns. Given the uncertainty about their potential hazards, there is an immediate need for toxicity data and field studies to assess exposure to CNFs/CNTs. An extensive study was conducted at a facility that manufactures and processes CNFs. Filter, sorbent, cascade impactor, bulk, and microscopy samples, combined with direct-reading instruments, provided complementary information on air contaminants. Samples were analyzed for organic carbon (OC) and elemental carbon (EC), metals, and polycyclic aromatic hydrocarbons (PAHs), with EC as a measure of CNFs. Transmission electron microscopy with energy-dispersive X-ray spectroscopy also was applied. Fine/ultrafine iron-rich soot, PAHs, and carbon monoxide were production byproducts. Direct-reading instrument results were reported previously [Evans DE et al. (Aerosol monitoring during carbon nanofiber production: mobile direct-reading sampling. Ann Occup Hyg 2010;54:514-31.)] Results for time-integrated samples are reported as companion papers in this Issue. OC and EC, metals, and microscopy results are reported here, in Part I, while results for PAHs are reported in Part II [Birch ME. (Exposure and Emissions Monitoring during Carbon Nanofiber Production-Part II: Polycyclic Aromatic Hydrocarbons. Ann. Occup. Hyg 2011; 55: 1037-47.)]. Respirable EC area concentrations inside the facility were about 6-68 times higher than outdoors, while personal breathing zone samples were up to 170 times higher.

Aerosol monitoring during carbon nanofiber production: mobile direct-reading sampling.

Detailed investigations were conducted at a facility that manufactures and processes carbon nanofibers (CNFs). Presented research summarizes the direct-reading monitoring aspects of the study. A mobile aerosol sampling platform, equipped with an aerosol instrument array, was used to characterize emissions at different locations within the facility. Particle number, respirable mass, active surface area, and photoelectric response were monitored with a condensation particle counter (CPC), a photometer, a diffusion charger, and a photoelectric aerosol sensor, respectively. CO and CO(2) were additionally monitored. Combined simultaneous monitoring of these metrics can be utilized to determine source and relative contribution of airborne particles (CNFs and others) within a workplace. Elevated particle number concentrations, up to 1.15 x 10(6) cm(-3), were found within the facility but were not due to CNFs. Ultrafine particle emissions, released during thermal treatment of CNFs, were primarily responsible. In contrast, transient increases in respirable particle mass concentration, with a maximum of 1.1 mg m(-3), were due to CNF release through uncontrolled transfer and bagging. Of the applied metrics, our findings suggest that particle mass was probably the most useful and practical metric for monitoring CNF emissions in this facility. Through chemical means, CNFs may be selectively distinguished from other workplace contaminants (Birch et al., in preparation), and for direct-reading monitoring applications, the photometer was found to provide a reasonable estimate of respirable CNF mass concentration. Particle size distribution measurements were conducted with an electrical low-pressure impactor and a fast particle size spectrometer. Results suggest that the dominant CNF mode by particle number lies between 200 and 250 nm for both aerodynamic and mobility equivalent diameters. Significant emissions of CO were also evident in this facility. Exposure control recommendations were described for processes as required.

Relationships among particle number, surface area, and respirable mass concentrations in automotive engine manufacturing.

This study investigated the relationships between particle number, surface area, and respirable mass concentration measured simultaneously in a foundry and an automotive engine machining and assembly center. Aerosol concentrations were measured throughout each plant with a condensation particle counter for number concentration, a diffusion charger for active surface area concentration, and an optical particle counter for respirable mass concentration. At selected locations, particle size distributions were characterized with the optical particle counter and an electrical low pressure impactor. Statistical analyses showed that active surface area concentration was correlated with ultrafine particle number concentration and weakly correlated with respirable mass concentration. Correlation between number and active surface area concentration was stronger during winter (R2 = 0.6 for both plants) than in the summer (R2 = 0.38 and 0.36 for the foundry and engine plant respectively). The stronger correlation in winter was attributed to use of direct-fire gas fired heaters that produced substantial numbers of ultrafine particles with a modal diameter between 0.007 and 0.023 mu m. These correlations support findings obtained through theoretical analysis. Such analysis predicts that active surface area increasingly underestimates geometric surface area with increasing particle size, particularly for particles larger than 100 nm. Thus, a stronger correlation between particle number concentration and active surface area concentration is expected in the presence of high concentrations of ultrafine particles. In general, active surface area concentration may be a concentration metric that is distinct from particle number concentration and respirable mass concentration. For future health effects or toxicological studies involving nano-materials or ultrafine aerosols, this finding needs to be considered, as exposure metrics may influence data interpretation.

In situ structure characterization of airborne carbon nanofibres by a tandem mobility-mass analysis.

Carbon nanofibres aerosolized by the agitation of as-produced commercial powder have been characterized in situ by using the differential mobility analyser-aerosol particle mass analyser (DMA-APM) method to determine their structural properties such as the effective density and fractal dimension for toxicology study. The effective density of the aerosolized carbon nanofibres decreased from 1.2 to 0.4 g cm(-3) as the mobility diameters increased from 100 to 700 nm, indicating that the carbon nanofibres had open structures with an overall void that increased with increasing diameter, due to increased agglomeration of the nanofibres. This was confirmed by transmission electron microscopy (TEM) observation, showing that 100 nm mobility diameter nanofibres were predominantly single fibres, while doubly or triply attached fibres were seen at mobility diameters of 200 and 400 nm. Effective densities calculated using Cox's theory were in reasonable agreement with experimental values. The mass fractal dimension of the carbon nanofibres was found to be 2.38 over the size range measured and higher than that of single-walled carbon nanotubes (SWCNTs), suggesting that the carbon nanofibres have more compact structure than SWCNTs.

Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice.

Single-walled carbon nanotubes (SWCNT) are new materials of emerging technological importance. As SWCNT are introduced into the life cycle of commercial products, their effects on human health and environment should be addressed. We demonstrated that pharyngeal aspiration of SWCNT elicited unusual pulmonary effects in C57BL/6 mice that combined a robust but acute inflammation with early onset yet progressive fibrosis and granulomas. A dose-dependent increase in the protein, LDH, and gamma-glutamyl transferase activities in bronchoalveolar lavage were found along with accumulation of 4-hydroxynonenal (oxidative biomarker) and depletion of glutathione in lungs. An early neutrophils accumulation (day 1), followed by lymphocyte (day 3) and macrophage (day 7) influx, was accompanied by early elevation of proinflammatory cytokines (TNF-alpha, IL-1beta; day 1) followed by fibrogenic transforming growth factor (TGF)-beta1 (peaked on day 7). A rapid progressive fibrosis found in mice exhibited two distinct morphologies: 1) SWCNT-induced granulomas mainly associated with hypertrophied epithelial cells surrounding SWCNT aggregates and 2) diffuse interstitial fibrosis and alveolar wall thickening likely associated with dispersed SWCNT. In vitro exposure of murine RAW 264.7 macrophages to SWCNT triggered TGF-beta1 production similarly to zymosan but generated less TNF-alpha and IL-1beta. SWCNT did not cause superoxide or NO.production, active SWCNT engulfment, or apoptosis in RAW 264.7 macrophages. Functional respiratory deficiencies and decreased bacterial clearance (Listeria monocytogenes) were found in mice treated with SWCNT. Equal doses of ultrafine carbon black particles or fine crystalline silica (SiO2) did not induce granulomas or alveolar wall thickening and caused a significantly weaker pulmonary inflammation and damage.

Evaporation kinetics of tetraalkylammonium ions from charged formamide drops.

The rate of ion evaporation from the surface of electrically charged liquid drops may be inferred from observations of the minimum drop charge q present on drops of a given radius R. This critical relation q(R) is measured here from the fossil solid residues left by the drops after complete solvent evaporation. We obtain mobility distributions of singly charged clusters formed by charge-reduced electrosprays of tetra-n-alkylammonium salts (C(n)()H(2)(n)()(+1))(4)N(+) (n = 2-10) dissolved in formamide. These distributions exhibit modulated structures, with each wave being associated with an initial charge state of the clusters prior to charge reduction, from which critical q(R) relations follow. For n from 4 to 7, the behavior is weakly dependent on the length of the alkyl chain. Above n = 7, there is a marked increase in solvation energy of the alkylammonium ions, but drop curvature effects contribute a compensating reduction of the energy barrier for ionization. This curvature effect increases monotonically with n and is probably associated with surface activity. Few clear modulations are seen for n < 3, perhaps because of the decreased role of surface activity in transferring solute into very small drops during the Coulombic breakup of larger drops. For this reason, extension of this technique to small inorganic salts is problematic.

Mass distribution measurement of water-insoluble polymers by charge-reduced electrospray mobility analysis.

1-Methyl-2-pyrrolidone (NMP) seeded with 5% trifluoroacetic acid is identified as a singular buffer, polar enough to produce fine electrospray drops, yet having excellent solubility for many industrial polymers such as polystyrene (PSR) and poly(methyl methacrylate) (PMMA). Four PSR mass standards (M = 9.2, 34.5, 68, and 170 kDa) with narrow mass distributions are electrosprayed from their solutions in this buffer. The high charge on the resulting ions is reduced to unity with a radioactive source, whereby their electrical mobility distributions, determined by a differential mobility analyzer, yield unambiguously their size distribution. Each standard produces (at high solution concentration) several mobility peaks associated with the formation of particles containing from one to six polymer molecules, used to establish a relation Z(M) between electrical mobility Z and polymer mass. Within the indeterminacy given by inaccuracies in the nominal masses of the standards, this relation indicates that the polymers form spherical balls with a density close to the bulk density of polystyrene, as seen previously with poly(ethylene glycol) chains. Good mobility spectra from the same buffer are also obtained for PMMA (M = 49 kDa). Because NMP is less conductive and contains more involatile impurities than common aqueous buffers, the electrospray ions formed tend to carry a small contaminant crust, which distorts the inferred mass distribution unless a high spray quality is achieved.