A multimicrospray nebulizer for microwave-induced plasma mass spectrometry

We have developed a nebulizer, called a multimicrospray nebulizer (MMSN), that efficiently introduces analytes for plasma mass spectrometry and plasma emission spectrometry. In this nebulizer, both the sample solution and the nebulizer gas are divided into several streams to produce a multispray. That is, the MMSN is a nebulizer that contains several micronebulization units, each unit including an orifice for passing the nebulizer gas and a capillary for introducing a sample solution. The microspray from each micronebulization unit can be operated at a microliter per minute sample uptake rate to achieve high nebulization efficiency. The multimicrospray nebulizer is capable of introducing more analyte to the plasma compared with a single-orifice micronebulizer, which has a very low sample uptake rate. In this work, an MMSN with three orifices was found to be suitable for microwave-induced plasma mass spectrometry (MIP-MS). The sample uptake rate can be varied within a range of 5-250 microL/min. Therefore, the nebulizer is unique in its ability to deal with various sample volumes and provide high nebulization efficiency. The sensitivity for all elements obtained with the MMSN was higher than that obtained with a conventional concentric nebulizer (CCN), which is difficult to achieve with other types of microintroduction nebulizers. For most elements, the MIP-MS sensitivity was improved about 2-fold at a sample uptake rate of 150 microL/min, a much lower rate than that for the CCN (usually 0.5-1.5 mL/min). The sensitivity for arsenic was improved by a factor of 5. The relative standard deviation was found to be less than 2.0%.     

Interface for direct and continuous sample-matrix deposition onto a MALDI probe for polymer analysis by thermal field flow fractionation and off-line MALDI-MS

A simple interface based on an oscillating capillary nebulizer (OCN) is described for direct deposition of eluate from a thermal field-flow fractionation (ThFFF) system onto a matrix-assisted laser desorption/ionization (MALDI) probe. In this study, the polymer-containing eluent from the ThFFF system was mixed on-line with MALDI matrix solution and deposited directly onto a moving MALDI probe. The result was a continuous sample track representative of the fractionation process. Subsequent off-line MALDI-mass spectrometry analysis was performed in automated and manual modes. Polystyrene samples of broad polydispersity were used to characterize the overall system performance. The OCN interface is easy to build and operate without the use of heaters or high voltages and is compatible with any MALDI probe format.     

Automated high-throughput infusion ESI-MS with direct coupling to a microtiter plate

This paper describes the design and application of instrumentation for automated high-throughput infusion ESI-mass spectrometry. The approach, based on a subatmospheric ESI interface, allows sample introduction from a commercially available microtiter plate without the need for a separate fluid delivery system. The microtiter plate was placed vertically on a three-dimensional translation stage in front of the sampling ESI interface. A single, 7-cm, 20-microm-i.d. fused-silica capillary (total volume, 70 nL), with a tapered tip, served as a combination of sample delivery and spraying capillary. The tapered tip of the capillary was enclosed in a subatmospheric chamber attached in front of the orifice of the mass spectrometer. The sample aspiration rate (flow rate) was regulated by computer-controlled pneumatic valves, which allowed fast switching of the pressure in the subatmospheric ESI chamber. A flow-through wash device was positioned between the microtiter plate and the ESI interface. This design allowed alternate filling of the capillary with (a) sample from the wells and (b) wash solution from the wash device. Sample turnaround times of 10 s/sample, with a 120-nL sample consumption/analysis, and a duty cycle (percentage of total analysis time spent acquiring data) of 40% were achieved. The infusion system was demonstrated in the analysis of preparative HPLC fractions from a small molecule combinatorial library.     

一刀切约束下的二维装箱问题高效求解算法

目的 为实现大规模物料的快速剪裁切割,对考虑一刀切约束的二维装箱问题进行研究,并构建相应的改进优先度算法IPH(Improved Priority Algorithm,IPH).方法 IPH能够在不需要任何迭代搜索下,直接进行剩余空间分割与填充.为此,发展PH算法中的优先度放置规则,并以最大化生成大空间面积和最小化生成小空间面积为基础,设计改进砌砖式空间分割策略.结果 针对标准数据集的对比实验表明,IPH能够在较短时间内完成大规模算例的高效求解,并首次获得了多个算例的最优填装效果.结论 基于概率较优的启发式求解方法,能够实现无迭代优选下的一刀切二维装箱问题直接求解,且运算效果令人满意.     

A microwave-powered thermospray nebulizer for liquid sample introduction in inductively coupled plasma atomic emission spectrometry

A new thermospray nebulizer based on the absorption of microwave radiation (MWTN) by aqueous solutions of strong acids is presented for the first time. To this end, a given length of the sample capillary is placed inside the cavity of a focused microwave system. A small piece of a narrower capillary tubing is connected at the tip of the sample capillary, outside the microwave cavity, to build up pressure. Drop size distributions of primary aerosols are exhaustively measured in order to evaluate the influence of several experimental variables (microwave power, liquid flow, irradiation length, inner diameter of the outlet capillary, nature and concentration of the acid) on the characteristics of the primary aerosol that are related to the emission signal. These experiments have been performed mainly to increase our understanding of the microscopic process of this new type of aerosol generation. A standard Meinhard nebulizer was employed for comparison. Under the best conditions the entire aerosol volume is contained in droplets smaller than 20 μm compared with 45% of the volume of the aerosol generated by the Meinhard. Hence, higher analyte and aerosol transport rates are to be expected for the MWTN compared with the Meinhard nebulizer. As any highly efficient nebulizer, MWTN requires a desolvation unit. For solutions 0.75 M in strong acid, the new nebulizer improves sensitivity (1.0-2.8 times), limits of detection (1.2-3.0 times), and background equivalent concentration (0.9-2.0 times) as compared to the standard Meinhard nebulizer, features many of the advantages of the conventional thermospray nebulizer, and overcomes some of its drawbacks (MWTN does not show corrosion problems and works at lower pressure, the aerosol characteristics are not modified when the PTFE capillary is replaced).     

Microfluidic serial dilution circuit

In vitro evolution of RNA molecules requires a method for executing many consecutive serial dilutions. To solve this problem, a microfluidic circuit has been fabricated in a three-layer glass-PDMS-glass device. The 400-nL serial dilution circuit contains five integrated membrane valves: three two-way valves arranged in a loop to drive cyclic mixing of the diluent and carryover, and two bus valves to control fluidic access to the circuit through input and output channels. By varying the valve placement in the circuit, carryover fractions from 0.04 to 0.2 were obtained. Each dilution process, which is composed of a diluent flush cycle followed by a mixing cycle, is carried out with no pipeting, and a sample volume of 400 nL is sufficient for conducting an arbitrary number of serial dilutions. Mixing is precisely controlled by changing the cyclic pumping rate, with a minimum mixing time of 22 s. This microfluidic circuit is generally applicable for integrating automated serial dilution and sample preparation in almost any microfluidic architecture.     

Pseudolinear gradient ultrahigh-pressure liquid chromatography using an injection valve assembly

The use of ultrahigh pressures in liquid chromatography (UHPLC) imposes stringent requirements on hardware such as pumps, valves, injectors, connecting tubing, and columns. One of the most difficult components of the UHPLC system to develop has been the sample injector. Static-split injection, which can be performed at pressures up to 6900 bar (100,000 psi), consumes a large sample volume and is very irreproducible. A pressure-balanced injection valve provided better reproducibility, shorter injection time, reduced sample consumption, and greater ease of use; however, it could only withstand pressures up to approximately 1000 bar (15,000 psi). In this study, a new injection valve assembly that can operate at pressures as high as 2070 bar (30,000 psi) was evaluated for UHPLC. This assembly contains six miniature electronically controlled needle valves to provide accurate and precise volumes for introduction into the capillary LC column. It was found that sample volumes as small as several tenths of a nanoliter can be injected, which are comparable to the results obtained from the static-split injector. The reproducibilities of retention time, efficiency, and peak area were investigated, and the results showed that the relative standard deviations of these parameters were small enough for quantitative analyses. Separation experiments using the UHPLC system with this new injection valve assembly showed that this new injector is suitable for both isocratic and gradient operation modes. A newly designed capillary connector was used at a pressure as high as 2070 bar (30,000 psi).     

In situ visualization and characterization of aerosol droplets in an inductively coupled plasma

Laser-scattering techniques are utilized for the first time to visualize the aerosol droplets in an inductively coupled plasma (ICP) torch from the nebulizer tip to the site of analytical measurements. The resulting images provide key information about the spatial distribution of the aerosol introduced by direct injection and conventional sample introduction devices: (1) a direct injection high-efficiency nebulizer (DIHEN); (2) a large-bore DIHEN; and (3) a MicroFlow PFA nebulizer with a PFA Scott-type spray chamber. Moreover, particle image velocimetry is used to study the in situ behavior of the aerosol before interaction with the plasma, while the individual surviving droplets are explored by particle tracking velocimetry. Directly introduced aerosols are highly scattered across the plasma torch as a result of their radial motion, indicating less than optimum sample consumption efficiency for the current direct injection devices. Further, the velocity distribution of the surviving droplets demonstrates the importance of the initial droplet velocities in complete desolvation of the aerosol for optimum analytical performance in ICP spectrometries. These new observations are critical in the design of the next-generation direct injection devices for lower sample consumption, higher sensitivity, lower noise levels, suppressed matrix effects, and developing smart spectrometers.     

Ausbau eines Sektormagnet-RGA zu einem PC-gestützten quantitativen Massenspektrometer

With careful sampling system design and in-situ calibration, Residual Gas Analyzers (RGAs) are becoming an important tool for quantitative Gas Analysis. RGAs were previously thought of as only “cheap and dirty” qualitative instruments for detecting leaks and/or contaminants in vacuum systems. This paper presents design features of RGA sampling systems which should be considered when specifying or building a mass spectrometer sampling system. Important design features are described including non-fractionating, fast time response sampling system design, onboard calibration standards, multiple sample points and remote operation. PC control of both the sampling system and the RGA provides for important features including automatic peak position tuning, spectrum de-convolution, composition analysis based on actual calibration gas standards, and automatic round-robin sampling and data logging. Applications of such integrated sampling systems currently operating at industrial and government facilities performing continuous on-line monitoring and self calibration are also described. All mass spectrometer/RGA sampling systems consist of the same basic subsystems including high vacuum pump/fore pump combination, the mass analyzer instrument including sensor head, control electronics and display, sample inlet valves and flow restrictions, and possibly a sample withdrawal/roughing pump. Although the basics of the system are the same, the finer details of sampling system design are frequently ignored, which make the simpler, less expensive sampling systems inadequate for quantitative gas analysis. Some of these important details which should be considered when writing a specification for a mass spectrometer sampling system are reviewed here.     

Structure and properties of refractory compounds deposited by electron beam evaporation

This work reports on the structure and properties of the refractory compounds TiC, ZrC, TiB₂, ZrB₂, TiCZrC, TiCTiB₂ and TiCTiB₂ Co. The deposits were prepared by direct evaporation of TiB₂, ZrB₂, ZrC, TiC and cobalt from single and multiple water-cooled copper crucibles using electron beam heating. TiC and ZrC deposits were also prepared by the activated reactive evaporation process. The vapors were condensed on a molybdenum or tantalum substrate at various deposition temperatures ranging from 650 to 1600 °C. The deposition rate was varied from 0.08 to 6 μm min^?1The deposits were characterized by optical microscopy, scanning and transmission electron microscopy, X-ray and electron diffraction and microhardness determinations. With direct evaporation the deposits contained decomposition products in addition to the parent phases. The composition of the deposits was dependent on temperature of deposition, composition of the evaporant billet and to a small extent the rate of deposition. Deposition temperature, rate of deposition and the composition of the deposit influenced the preferred orientation and the microhardness of the deposits. Surface and fracture cross section morphology and microstructure varied with deposition temperature. The data represent an extensive characterization of refractory compound deposits made by high rate physical vapor deposition processes.     

Thimble glass frit nebulizer for atomic spectrometry

A thimble-shaped glass frit nebulizer has been developed for atomic spectrometry. The thimble glass frit was pressurized internally by gases such as helium (He) or argon (Ar) while the test solution was applied externally to the frit. The pressurized gas exited through the pores of the glass frit and shattered the thin liquid film flowing on the surface of the thimble-shaped device to form small droplets. A small spray chamber surrounded the nebulizer to remove the large droplets. Small droplets were then introduced into inductively coupled plasmas (ICP) sustained in either Ar or He. To reduce the memory effect noted in the frit-type nebulizers, a clean-out system was also devised. Detection limits, signal-to-background ratios (S/B), precision, memory effects, noise power spectra (NPS), and particle size distributions measured with the new nebulizer were compared to those of disk and cylindrical glass frit nebulizers and the commonly used pneumatic nebulizer for Ar ICP atomic emission spectrometry (AES). Analytical performance was also measured for He ICP by using frit-type nebulizers and an ultrasonic nebulizer.     

An Efficient Sampling Technique for Bayesian Inference With Computationally Demanding Models

In the environmental sciences, a large knowledge base is typically available on an investigated system or at least on similar systems. This makes the application of Bayesian inference techniques in environmental modeling very promising. However, environmental systems are often described by complex, computationally demanding simulation models. This strongly limits the application of Bayesian inference techniques, because numerical implementation of these techniques requires a very large number of simulation runs. The development of efficient sampling techniques that attempt to approximate the posterior distribution with a relatively small parameter sample can extend the range of applicability of Bayesian inference techniques to such models. In this article a sampling technique is presented that tries to achieve this goal. The proposed technique combines numerical techniques typically applied in Bayesian inference, including posterior maximization, local normal approximation, and importance sampling, with copula techniques for the construction of a multivariate distribution with given marginals and correlation structure and with low-discrepancy sampling. This combination improves the approximation of the posterior distribution by the sampling distribution and improves the accuracy of results for small sample sizes. The usefulness of the proposed technique is demonstrated for a simple model that contains the major elements of models used in the environmental sciences. The results indicate that the proposed technique outperforms conventional techniques (random sampling from simpler distributions or Markov chain Monte Carlo techniques) in cases in which the analysis can be limited to a relatively small number of parameters.     

Temperature-controlled confocal Raman microscopy to detect phase transitions in phospholipid vesicles

Optical-trapping confocal Raman microscopy enhances the capabilities of traditional Raman spectroscopy for the analysis of small particles by significantly reducing the sampling volume and minimizing background signal from the particle surroundings. Chemical composition and structural information can be obtained from optically trapped particles in aqueous solution without the need for labeling or extensive sample preparation. In this work, the challenges of measuring temperature dependent changes in suspended particles are addressed with the development of a small-volume, thermally conductive sample cell attached to a temperature-controlled microscope stage. To demonstrate its function, the gel to liquid-crystalline phase transitions of optically trapped lipid vesicles, composed of pure 1,2-ditridecanoyl-sn-glycero-3-phosphocholine (DTPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), were detected by changes in Raman spectra of the lipid bilayer. The Raman scattering data were found to correlate well with differential scanning calorimetry (DSC) results.     

Minimization of transition metal interferences with hydride generation techniques

A new hydride generator has been characterized for use with the acid-NaBH(4) hydride generation systems based on the insertion of a capillary tube into the sample introduction channel of a standard Meinhard nebulizer. The acidic sample and the tetrahydroborate solution are mixed at a merge point 1.5 cm from the end of the nebulizer orifice. Nebulization of the reaction solutions into a 0.7 mL tubular "spray chamber" follows a very short mixing time (less than 0.012 s) of the reagents. This approach permits 10?000 μg/mL Ni(2+) or Cr(3+) to be present in the sample solution without producing any interferences. Additionally, in the presence of Fe(3+) added as a "releasing agent", 5000 μg/mL Co(2+) or 160 μg/mL Cu(2+) can also be tolerated without interference. An 80 ± 2% generation efficiency is attained for the test element selenium. A detection limit of 6 μg/L (3σ(b)) is achieved with ICP-AES detection. Precision of replicate measurements at the 12 μg/L level varies from 5 to 12% relative standard deviation.     

Characterization of copper nucleation and growth from aqueous solution on aluminum: A transmission electron microscopy study of copper cementation

A novel technique was developed for the direct observation of copper precipitate nuclei forming on aluminium surfaces by cementation. This technique involves the preparation of thin electron-transparent aluminum films by vapor deposition in vacuum onto cleaved NaCl crystal blanks. Following aqueous CuSO₄ solution contact of an exposed aluminum film surface area, the films with attached copper nuclei were examined by transmision and scanning electron microscopy. For conditions which promoted optimum deposit growth kinetics, the initial faceted polyhedral nuclei developed microdendritic precipatates which led to the growth of massive dendritic deposits. The details of microdendrite arm structures were directly observed in the transmission electron microscope. By systematically varying the residual grain structure of the aluminum films, it was demonstrated that grain size and grain structure do not affect the disposition and morphology of the initial precipitates. Furthermore, in single-crystal aluminum films containing dislocations it was not possible to show any consistent association of nucleation or nuclei with the emergence sites of individual dislocations. The principal feature of the substrate which influences precipitation as a result of the electrochemical cementation reaction seems to be crystallographic orientation, and this is consistent with observations of the growth and structure of conventional electrodeposits.     

Bayesian benchmarking with applications to small area estimation

It is well-known that small area estimation needs explicit or at least implicit use of models (cf. Rao in Small Area Estimation, Wiley, New York, 2003). These model-based estimates can differ widely from the direct estimates, especially for areas with very low sample sizes. While model-based small area estimates are very useful, one potential difficulty with such estimates is that when aggregated, the overall estimate for a larger geographical area may be quite different from the corresponding direct estimate, the latter being usually believed to be quite reliable. This is because the original survey was designed to achieve specified inferential accuracy at this higher level of aggregation. The problem can be more severe in the event of model failure as often there is no real check for validity of the assumed model. Moreover, an overall agreement with the direct estimates at an aggregate level may sometimes be politically necessary to convince the legislators of the utility of small area estimates.     

High-efficiency on-line solid-phase extraction coupling to 15-150-microm-i.d. column liquid chromatography for proteomic analysis

The ability to manipulate and effectively utilize small proteomic samples is important for analyses using liquid chromatography (LC) in combination with mass spectrometry (MS) and becomes more challenging for very low flow rates due to extra column volume effects on separation quality. Here we report on the use of commercial switching valves (150-microm channels) for implementing the on-line coupling of capillary LC columns operated at 10,000 psi with relatively large solid-phase extraction (SPE) columns. With the use of optimized column connections, switching modes, and SPE column dimensions, high-efficiency on-line SPE-capillary and nanoscale LC separations were obtained demonstrating peak capacities of approximately 1000 for capillaries having inner diameters between 15 and 150 microm. The on-line coupled SPE columns increased the sample processing capacity by approximately 400-fold for sample solution volume and approximately 10-fold for sample mass. The proteomic applications of this on-line SPE-capillary LC system were evaluated for analysis of both soluble and membrane protein tryptic digests. Using an ion trap tandem MS it was typically feasible to identify 1100-1500 unique peptides in a 5-h analysis. Peptides extracted from the SPE column and then eluted from the LC column covered a hydrophilicity/hydrophobicity range that included an estimated approximately 98% of all tryptic peptides. The SPE-capillary LC implementation also facilitates automation and enables use of both disposable SPE columns and electrospray emitters, providing a robust basis for automated proteomic analyses.     

Ultratrace and isotope analysis of long-lived radionuclides by inductively coupled plasma quadrupole mass spectrometry using a direct injection high efficiency nebulizer

The direct injection high efficiency nebulizer (DIHEN) was explored for the ultrasensitive determination of long-lived radionuclides ((226)Ra, (230)Th, (237)Np, (238)U, (239)Pu, and (241)Am) and for precise isotope analysis by inductively coupled plasma mass spectrometry (ICPMS). The DIHEN was used at low solution uptake rates (1-100 μL/min) without a spray chamber. Optimal sensitivity (e.g., (238)U, 230 MHz/ppm; (230)Th, 190 MHz/ppm; and (239)Pu, 184 MHz/ppm) was achieved at low nebulizer gas flow rates (0.16 L/min), high rf power (1450 W), and low solution uptake rates (100 μL/min). The optimum parameters varied slightly for the two DIHENs tested. The detection limits of long-lived radionuclides in aqueous solutions varied from 0.012 to 0.11 ng/L. The sensitivity of the DIHEN was improved by a factor of 3 to 5 compared with that of a microconcentric nebulizer (MicroMist used with a minicyclonic spray chamber at a solution uptake rate of 85 μL/min) and a factor of 1.5 to 4 compared with that of a conventional nebulizer (cross-flow used with a Scott type spray chamber at a solution uptake rate of 1 mL/min). The precision of the DIHEN ranged from 0.5 to 1.7% RSD (N = 3) for all measurements at the 10 ng/L concentration level (～3 pg sample size). The sensitivity decreased to 10 MHz/ppm at a solution uptake rate of 1 μL/min. The precision was about 5% RSD at a sample size of 30 fg for each long-lived radionuclide by the DIHEN-ICPMS method. The oxide to atom ratios were less than 0.05 (except ThO(+)/Th(+) ) and decreased under the optimum conditions in the following sequence: ThO(+)/Th(+) > UO(+)/U(+) > NpO(+)/Np(+) > PuO(+)/Pu(+) > AmO(+)/Am(+) > RaO(+)/Ra(+). Atomic and oxide ions were used as analyte ions for ultratrace and isotope analyses of long-lived radionuclides in environmental and radioactive waste samples. The analytical methods developed were applied to the determination of long-lived radionuclides and isotope ratio measurements in different radioactive waste and environmental samples using the DIHEN in combination with quadrupole ICPMS. For instance, the (240)Pu/(239)Pu isotope ratio was measured in a radioactive waste sample at a plutonium concentration of 12 ng/L. This demonstrates a main advantage of DIHEN-ICPMS compared with α-spectrometry, which cannot be used to selectively determine (239)Pu and (240)Pu because of similar α energies (5.244 and 5.255 MeV, respectively).     

Writing on Superhydrophobic Nanopost Arrays: Topographic Design for Bottom-up Assembly

A well-known property of superhydrophobic surfaces, such as an array of hydrophobic nanoposts, is to allow only limited surface contact of a liquid to the tips of the nanoposts. Herein we demonstrate that material deposition from solution, whether solid precipitation, surface adsorption or colloidal adhesion in static system, or dynamic "writing", can be limited to these specific areas of the surface when in this nonwetting state. As an example of solid precipitation, we show that nucleation of CaCO(3) results in the growth of small, uniform, amorphous deposits (which can merge and recrystallize) instead of disordered, large crystals due to the abundance of identical, small heterogeneous nucleation sites. The growth of amorphous CaCO(3) can be used to trap molecules from solution, as a potential application for controlled drug release. To demonstrate the localized surface adsorption, we show that chemical functionalization of the post tips can make them "sticky" for specific attachment of species (such as colloidal particles) from solution. The electrostatic charge and relative size ratio of the particle/post diameters control the attachment of particles to the post tips with great specificity. Dynamic conditions have also been shown for writing using droplets translated across the nonwetting surface at controlled speeds during deposition. These methods offer unprecedented control over the heterogeneous nucleation and localized growth of crystals from solution and avoid nonspecific adsorption. There is selective control of colloidal or molecular attachment to the nanopost tips, whereby the contact area, time of contact, and tip surface chemistry for reaction are all independently tunable parameters.     

Infrared laser ablation sample transfer for MALDI imaging

An infrared laser was used to ablate material from tissue sections under ambient conditions for direct collection on a matrix assisted laser desorption ionization (MALDI) target. A 10 μm thick tissue sample was placed on a microscope slide and was mounted tissue-side down between 70 and 450 μm from a second microscope slide. The two slides were mounted on a translation stage, and the tissue was scanned in two dimensions under a focused mid-infrared (IR) laser beam to transfer material to the target slide via ablation. After the material was transferred to the target slide, it was analyzed using MALDI imaging using a tandem time-of-flight mass spectrometer. Images were obtained from peptide standards for initial optimization of the system and from mouse brain tissue sections using deposition either onto a matrix precoated target or with matrix addition after sample transfer and compared with those from standard MALDI mass spectrometry imaging. The spatial resolution of the transferred material is approximately 400 μm. Laser ablation sample transfer provides several new capabilities not possible with conventional MALDI imaging including (1) ambient sampling for MALDI imaging, (2) area to spot concentration of ablated material, (3) collection of material for multiple imaging analyses, and (4) direct collection onto nanostructure assisted laser desorption ionization (NALDI) targets without blotting or ultrathin sections.