Accurate calibration of TXRF using microdroplet samples

TXRF has been applied in combination with VPD to the analysis of trace impurities in the native oxide layer of Si wafer surfaces down to the range of 10(8) atoms. cm(-2). Proper quantification of VPD/TXRF data requires calibration with microdroplet standard reference wafers. The precision of calibration function has been evaluated and found to allow quantification at a high level of 3 sigma confidence with microdroplet standard reference.     

Novel methods of TXRF analysis for silicon wafer surface inspection

TXRF became a standard, on-line inspection tool for controlling the cleanliness of polished Si wafers for semiconductor use. Wafer makers strive for an all-over metallic cleanliness of < 10¹⁰ atoms · cm^–2. The all-over cleanliness can be analyzed using VPD/TXRF. For VPD preparation and scanning we have developed an automatic system coupled with TXRF. With synchrotron radiation TXRF we were able to detect 13 fg of Ni in a residual microdroplet, i.e.10⁵ atoms · cm^–2. Received: 8 January 1998 / Revised: 13 July 1998 / Accepted: 30 July 1998     

Direct analysis of Al<Subscript>2</Subscript>O<Subscript>3</Subscript> powders by total reflection X-ray fluorescence spectrometry

A direct analysis procedure for the determination of trace impurities of Ca, V, Cr, Mn, Fe, Ni, Cu, Zn and Ga in Al₂O₃ ceramic powders by total reflection X-ray fluorescence spectrometry (TXRF) is described. The powders were analysed in the form of slurries containing 1–10 mg mL^–1 of powder. The use of the procedure in the case of powders with differing grain size and for different slurry concentrations was investigated. Three different quantification possibilities were compared, namely the use of Al as a matrix component, the use of Fe as a trace element contained in the sample or of Co added in concentrations of 200 g g^–1 as internal standard. The homogeneity of elemental distributions in sample layers deposited on the TXRF quartz carriers by evaporating 5 L of the 10 mg mL^–1 slurries was studied by scanning the 4- to 5-mm-diameter spots of two samples by synchrotron radiation TXRF at Hasylab. For powders with differing graininess but mainly finer than about a few 10 m, no systematic influence of the grain size on the accuracy of the determinations of Ca, V, Fe, Ni, Cu and Zn could be observed. The measurement precision, however, seemed to be limited by inhomogeneous distributions of the trace elements in the samples as testified by the synchrotron radiation TXRF scans. Detection limits of the developed TXRF procedure for Ca, V, Cr, Mn, Fe, Ni, Cu, Zn and Ga were found to be in the 0.3–7 g g^–1 range and were shown to increase slightly with the grain size of the samples. Quantification using Al (matrix) as internal standard led to systematically higher values out of the accuracy required, whereas the other two approaches in all cases led to reliable results.Dedicated to the memory of Wilhelm Fresenius     

Vapor phase decomposition–droplet collection–total reflection X-ray fluorescence spectrometry for metallic contamination analysis on Ge wafers

Ge substrates are recently being reconsidered as a candidate material for the replacement of Si substrates in advanced semiconductor devices. The reintroduction of this material requires reengineering of the standard IC processing steps. In this paper, we present the extension of the methodology of vapor phase decomposition–droplet collection–total reflection X-ray fluorescence spectrometry (VPD–DC–TXRF) for metallic contamination analysis towards Ge substrates. A first step that asked for adaptation was the collection chemistry as the Ge wafers surface is not hydrophobic after the VPD treatment. The contact angle could be significantly increased using a concentrated HCl solution. This chemistry has been proved to perform well in the collection of metals from intentionally contaminated Ge wafers. A second step that needed optimization was the matrix removal method as a sample preparation step prior to the TXRF analysis. First, the upper limits of TXRF on Ge containing solutions have been characterized. The accuracy of TXRF is found to be acceptable for Ge contents lower than 1×10¹⁴ atoms (250 ppb in 50 μL) but decreases systematically with higher Ge contents. Fortunately, Ge can be volatilized at low temperatures as GeCl₄ by the addition of HCl. The parameters within this method have been investigated with respect to the removal of Ge and the recovery of metal traces. Finally, the full VPD–DC–TXRF method has been applied on intentionally contaminated Ge wafers and proved to be very accurate.     

Method and mechanism of vapor phase treatment–total reflection X-ray fluorescence for trace element analysis on silicon wafer surface

Vapor phase treatment (VPT) is a pretreatment with hydrofluoric acid vapor to raise the sensitivity of total reflection X-ray fluorescence spectroscopy (TXRF) for trace metal analysis on silicon wafers. The International Organization for Standardization/Technical Committee 201/Working Group 2 (ISO/TC201/WG2) has been investigating the method to analyze 10⁹ atoms/cm² level of metallic contamination on the silicon wafer surface. Though VPT can enhance the TXRF signal intensity from the metallic contamination, it has turned out that the magnitude of the enhancement varies with the type of methods and the process conditions. In this study, approaches to increase TXRF intensity by VPT are investigated using a fuming chamber in an automated VPD instrument. Higher signal intensity can be obtained when condensation is formed on the sample surface in a humidifying atmosphere and with a decreasing stage temperature. Surface observations with SEM and AFM show that particles with ~ 4 μm in diameter are formed and unexpectedly they are dented from the top surface level.     

Determination of sulfur and selected trace elements in metallothionein-like proteins using capillary electrophoresis hyphenated to inductively coupled plasma mass spectrometry with an octopole reaction cell

The determination of sulfur in biologically relevant samples such as metalloproteins is described. The analytical methodology used is based on robust on-line coupling between capillary electrophoresis (CE) and octopole reaction cell inductively-coupled plasma mass spectrometry (ORC–ICP–MS). Polyatomic ions that form in the plasma and interfere with the determination of S at mass 32 are minimised by addition of xenon to the collision cell. The method has been applied to the separation and simultaneous element-specific detection of sulfur, cadmium, copper, and zinc in commercially available metallothionein preparations (MT) and metallothionein-like proteins (MLP) extracted from liver samples of bream (Abramis brama L.) caught in the river Elbe, Germany. Instrumental detection limits have been calculated according to the German standard procedure DIN 32645 for the determination of sulfur and some simultaneously measured trace elements in aqueous solution. For sulfur detection limits down to 1.3 g L^–1 (³⁴S) and 3.2 g L^–1 (³²S) were derived. For the other trace elements determined simultaneously detection limits ranging from 300 ng L^–1 (⁵⁸Ni) to 500 ng L^–1 (⁶⁶Zn, ⁵⁵Mn) were achieved. For quantification of sulfur and cadmium in a commercially available MT preparation under hyphenated conditions the use of external calibration is suggested. Finally, the need for proper sample-preparation technique will be discussed.     

On-line column preconcentration for the determination of cobalt in sea water by flow-injection chemiluminescence detection

A flow-injection method for the determination of dissolved cobalt(II) in sea water has been studied based on a combination of column preconcentration using 8-quinolinol immobilized on silica gel, fluoride containing metal alkoxide glass (8HQ-MAF) and chemiluminescence detection with a gallic acid-hydrogen peroxide system. Co(II) is selectively recovered from an acidified sample with 8-quinolinol immobilized on silica gel. After elution with dilute hydrochloric acid the resultant eluent is mixed with the reagent solutions, heated to 60^°C and then introduced into the CL cell. The analysis time including the 2-min sample load was 8 min per sea water sample with a corresponding detection limit of 0.62 ngl^-1 (3). The average standard deviation calculated for 10 replicate measurements of artificial sea water samples with a concentration of 10 ngl^-1 cobalt was ±2.1%. The method has been tested with the standard reference sea waters NASS and CASS.     

Application of ETV-ICPMS in semiconductor process control

Submicron semiconductor manufacturing requires ultra-clean processes and materials to achieve high product yields. It is demonstrated that electrothermal evaporation (ETV) in a graphite furnace coupled with ICPMS offers a new possibility for a fast simultaneous analysis of eight elements with detection limits below 0.2 ng/g in conc. hydrofluoric acid and buffered oxide etch (ammonium fluoride/hydrogen fluoride mixture). ETV-ICPMS also comprises significant improvements in the analysis of metal contamination on silicon wafer surfaces with respect to currently used methods. The contaminants on the surface are usually analyzed by total reflexion X-ray fluorescence spectrometry (TXRF) or dissolved by HF vapour (vapour phase decomposition; VPD) or a mixture of hydrofluoric acid and hydrogen peroxide (droplet surface etching, DSE) and analyzed by GFAA or TXRF. ETV-ICPMS combines the advantages of both analytical methods: the multielemental advantage of TXRF and the possibility to analyze light elements like Al, Mg, Na which may not be analyzed by TXRF. With VPD/DSE-ETV-ICPMS detection limits between 0.2 and 2×10⁹ atoms cm^?2 on a 6″ wafer have been achieved in a simultaneous analysis of eight elements. The main advantage of ETV-ICPMS versus conventional ICPMS in both applications — chemical and surface analysis — is its capability to analyze Fe in the sub-ng/g range. As Fe is one of the most important impurities in semiconductor manufacturing ETV-ICPMS is much more useful for semiconductor applications than low-resolution ICPMS. For the present application potassium iodide was used as a modifier. It enhances the sensitivity by a factor of 3–4 and improves the reproducibility significantly.     

Experimental design-based development and single laboratory validation of a capillary zone electrophoresis method for the determination of the artificial sweetener sucralose in food matrices

A capillary zone electrophoresis (CZE) method, optimised chemometrically, underwent a complete in-house validation protocol for the qualification and quantification of sucralose in various foodstuffs. Separation from matrix components was obtained in a dinitrobenzoic acid (3 mM)/sodium hydroxide (20 mM) background electrolyte with a pH of 12.1, a potential of 0.11 kV cm^–1 and a temperature of 22 °C. Detection was achieved at 238 nm by indirect UV. Screening, optimisation and robustness testing were all carried out with the aid of experimental design. Using standard addition calibration, the CZE method has been applied to still, carbonated and alcoholic beverages, yoghurts and hard-boiled candy. The method allows the detection of sucralose at >30 mg kg^–1, with a linearity range of 50–500 mg kg^–1, making it suitable for implementation of the recently amended Sweeteners for use in foodstuffs Directive (European Parliament and Council (2003) Off J L237:3–12), which set maximum usable doses of sucralose for many foodstuffs, most ranging from 200 mg kg^–1 to 450 mg kg^–1.     

New methods for acceleration of meat sample preparation prior to determination of the metal content by atomic absorption spectrometry

Focused microwave-assisted digestion and ultrasound leaching have been applied for the extraction of Pb, Cd, Cr, Cu, Fe, Zn, Ca, and Mg from raw meat. Semimembranous muscle (SM) of raw pig ham was used for optimizing both the digestion and extraction steps by multivariate approaches. The detection and quantification limits were 0.5 and 0.9 g kg^–1 for Pb, 0.06 and 0.1 g kg^–1 for Cd, 0.2 and 1.2 g kg^–1 for Cr, 0.4 and 3 g kg^–1 for Cu, 0.04 and 0.1 mg kg^–1 for Fe, 0.012 and 0.017 mg kg^–1 for Zn, 0.3 and 0.4 mg kg^–1 for Ca, and 0.01 and 0.03 mg kg^–1 for Mg. The precision, expressed as relative standard deviation (RSD), ranged between 2.5 and 9.6% for focused microwave-assisted digestion and between 3.5 and 10.6% for ultrasound leaching. The methods were then compared with a reference method and applied to a certified reference material (bovine muscle 184, from the BCR). The t-test, applied to the results obtained from focused microwave-assisted digestion, revealed that they are in agreement (p>0.01) with the certified and estimated values in the case of Pb, Cd, Cr, Cu, Fe, Ca, Mg, and Zn but not in that of Fe. In the case of ultrasound leaching, only the extraction of Pb, Cu, and Ca was quantitative. The method based on microwave digestion provides more accurate and precise results than ultrasound leaching. These new procedures have many advantages with regards to conventional methods, namely, reduction of the extraction time, simplification of the process, avoidance of chemical emissions to the atmosphere, and no losses of metals by volatilization.     

Detection of metallic trace impurities on Si(100) surfaces with total reflection X-ray fluorescence (TXRF)

Summary The physical principles and analytical capabilities of TXRF are discussed and compared to other surface sensitive techniques. Metallic trace impurities on silicon surfaces are readily identified with detection limits down to 10¹¹ atoms/cm² (10^–4 monolayers). Other advantages are simple sample preparation and the possibility of analyzing insulating layers without charging problems. The method has been applied to quantify coverages of Fe, Ni, Cu and Au on Si(100) surfaces, deposited from intentionally doped solutions (NH₃/H₂O₂ and HF/NH₄F). It turns out that certain metal/solution combinations cause large surface coverages on the silicon wafer, even if the metal concentration in the solution is very low (g/kg range).

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Nachweis von metallischen Spurenverunreinigungen an Si(100)-Oberflächen mit der Totalreflexions-Röntgenfluorescenzanalyse (TXRF)

     

Detection of 2,4,6-trichloroanisole in chlorinated water at nanogram per litre levels by SPME–GC–ECD

A method involving solid-phase micro extraction (SPME) and gas chromatography with electron capture detection (SPME–GC–ECD) has been optimised for identification and quantification of 2,4,6-trichloroanisole (TCA) at ng L^–1 concentrations in disinfected (chlorinated) water samples. A central composite design was used for factorial analysis of four factors, three factors related to the SPME (PDMS fibre) procedure (adsorption time, temperature of the sample during headspace sampling, and desorption time) and one related to the GC operation (the rate of increase of the temperature of the GC oven). Good linearity (linear correlation coefficient greater than 0.999) was observed for TCA concentrations up to 50 ng L^–1, limits of detection and quantification of 0.7 and 2.3 ng L^–1, respectively, and good precision (relative standard deviation 2.8% and 3.4% for 5 and 30 ng L^–1 of TCA, respectively). Besides TCA, this system also enables the detection and quantification of the four trihalomethanes in the g L^–1 concentration range with limits of detection and quantification of approximately 0.3 g L^–1 and 1 g L^–1, respectively.     

Sensitive Determination of Felodipine in Human and Dog Plasma by Use of Liquid–Liquid Extraction and LC–ESI–MS–MS

Summary A sensitive and selective liquid chromatographic method coupled with electrospray ionization tandem mass spectrometry (LC–ESI–MS–MS) has been developed for quantification of felodipine in human and dog plasma. Compounds were separated on a 2.0 mm × 150 mm, 5.0 m particle, C₈ column with 1 m m ammonium acetate–acetonitrile, 20:80, pH 6.0, as mobile phase at a flow rate of 200 L min^–1. Nifedipine was used as internal standard. Plasma samples were extracted with diethyl ether, the centrifuged upper layer was evaporated, the residue was reconstituted with mobile phase, and the reconstituted samples were injected. The analytical column lasted for at least 1000 injections. By use of multiple reaction monitoring (MRM) mode in MS–MS felodipine and nifedipine were detected without severe interference from the human or dog plasma matrix. Felodipine produced a protonated precursor ion ([M + H]⁺) at m/z 384 and a corresponding product ion at m/z 338. And internal standard (nifedipine) produced a protonated precursor ion ([M + H]⁺) at m/z 347 and a corresponding product ion at m/z 315. Detection of felodipine in human and dog plasma was accurate and precise, with a limit of quantification of 0.05 ng mL^–1. The method has been successfully applied to preliminary pharmacokinetic study of felodipine in human and dog plasma.     

Determination of nitrogen in uranium and uranium-oxide by high-temperature gas-extraction

Summary The reducing fusion gas extraction method has been used for the determination of nitrogen in uranium metal and uranium dioxide reference materials at levels of about 10–15g·g^–1. It has been found that when extracting at temperatures above 2700° C the use of a platinum flux is no longer necessary. Pure nitrogen and nitrogen-helium mixtures were used for calibrating the detection unit in the range of 1.5–670 g. The calibration of the extraction was performed with metallic reference materials in the range of 8–331 g N₂ content.

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Bestimmung von Stickstoff in Uran und Uranoxid durch Hochtemperatur-Gasextraktion

Zusammenfassung Die Gasextraktion aus reduzierender Schmelze wurde zur Stickstoffbestimmung in Uranmetall- und Urandioxid-Referenzmaterialien bei Gehalten von 10–15 g·g^–1 angewendet. Bei Temperaturen über 2700° C ist kein Platinbad mehr erforderlich. Zur Eichung der Detektionseinheit im Bereich von 1,5–670 g wurden reiner Stickstoff oder Stickstoff-Helium-Mischungen benutzt. Zur Eichung der Extraktion wurden metallische Referenzmaterialien mit (8–331g) N₂ eingesetzt.

     

Determination of Eupatilin in Human Plasma by High-Performance Liquid Chromatography–Tandem Mass Spectrometry

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric method (LC-MS-MS) for the determination of eupatilin in human plasma has been developed. Eupatilin and an internal standard; (S)-N-(3-{3-fluoro-4-[6-(1-methyl-1H-tetrazol-5-yl)-pyridine-3-yl]-phenyl}-2-oxo-oxazolidin-5-ylmethyl)-acetamide (DA-7867) were extracted from human plasma by liquid-liquid extractionand analyzed on a phenyl-hexyl column using the mobile phase: acetonitrile-ammonium formate (10 mM, pH 3.0) (60:40, /). Analytes were detected using electrospray ionization-tandem mass spectrometry in multiple-reaction monitoring mode. The calibration curve was linear (r = 0.999) over the concentration range: 1.00–500 ng mL^–1 with a lower limit of quantification of 1.0 ng mL^–1 using a 100 L plasma sample. The precision (CV%) of this assay ranged: 2.4–7.0%, relative error: –7.0 to +2.0%. Recoveries of eupatilin ranged: 64.3–65.0%, with that of DA-7867 (internal standard) being 87.0 ± 5.3%.     

High-Performance Liquid Chromatographic Assay of Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) in Human Plasma using a Solid-Phase Extraction Technique

A selective and sensitive liquid chromatographic method was developed for the determination of zonisamide in small volumes of plasma. Zonisamide and the internal standard methyl 4-hydroxybenzoate were extracted from 0.2 mL of plasma with solid-phase extraction columns and eluted with methanol. Analysis of the extracts was performed on a Symmetry C₁₈ column with ultra-violet spectrophotometric detection. The calibration curve was linear over the concentration range of 0.05–5 g mL^–1 in plasma. Recoveries were reasonable for routine analyses; the limit of quantification was 0.05 g mL^–1 with a signal-to-noise ratio of 5. This method could be useful for the pharmacokinetic study of zonisamide in a limited volume of human plasma and for therapeutic drug monitoring.     

Determination of subnanomolar concentrations of cobalt by adsorptive stripping voltammetry at a bismuth film electrode

Procedures for trace cobalt determinations by adsorptive stripping voltammetry at in situ and ex situ plated bismuth film electrodes are presented. These exploit the enhancement of the cobalt peak obtained by using the Co(II)–dimethylglyoxime–cetyltrimethylammonium bromide–piperazine-N,N-bis(2-ethanesulfonic acid) system. The calibration graph for an accumulation time of 120 s was linear from 2 × 10^–10 to 2 × 10^–8 mol L^–1. The relative standard deviation from five determinations of cobalt at a concentration of 5 × 10^–9 mol L^–1 was 5.2%. The detection limit for an accumulation time of 300 s was 1.8 × 10^–11 mol L^–1. The proposed procedure was applied to cobalt determination in certified reference materials and in tap and river water samples.     

Determination of piribedil in pharmaceutical formulations by micellar electrokinetic capillary chromatography

A fast and simple micellar electrokinetic capillary chromatographic method was developed for the analysis of piribedil in pharmaceutical formulations. The effects of buffer concentration, buffer pH, sodium dodecyl sulphate (SDS) concentration, organic modifier, applied voltage and injection time were investigated. Optimum results were obtained with a 50 mM borate buffer at pH 8.0 containing 50 mM SDS by using a fused silica capillary (50 m internal diameter, 72 cm effective length). The sample was injected hydrodynamically for 4 s at 50 mbar pressure and the applied voltage was +30 kV. The detection wavelength was set at 205 nm. Diflunisal was used as an internal standard. The analysis was performed at 25 °C and the total run time was 14 min. The method was suitably validated with respect to linearity range, limit of detection and quantification, precision, accuracy, specificity and robustness. The linear calibration range was 5–100 g mL^–1 and the limit of detection was determined as 1 g mL^–1. The method developed was successfully applied to the determination of piribedil in pharmaceutical formulations. The results were compared with a spectrophotometric method reported in the literature and no significant difference was found statistically.     

High accuracy determination of235U in nondestructive assay standards by gamma spectrometry

High precision gamma spectrometry measurements have been made on five sets of uranium isotope abundance reference materials for nondestructive assay (NDA). These sets are intended for international safeguards use as primary reference materials for the determination of the²³⁵U abundance in homogeneous uranium bulk material by gamma spectrometry. The measurements were made to determine the count rate uniformity of the²³⁵U 185.7 keV gamma-ray as well as the²³⁵U isotope abundance for each sample. Since the samples were packaged such that the U₃O₈ is infinitely thick for the 185.7 keV gamma-ray, the measured count rate was not dependent on the material density. In addition, the activity observed by the detector was collimated to simulate calibration conditions used to measure bulk material in the field. The sample-to-sample variations observed within the 5 sets of samples ranged between 0.005–0.11% (1s) with standard deviations of the mean ranging from 0.01–0.02%. This observed variation appears to be due predominantly to counting statistics and not to material inhomogeneity and/or packaging. The results of this study indicate that accuracy of²³⁵U determinations via gamma spectrometry, in the range of few hundredths of a percent (2), is achievable. The main requirement for achieving this level of accuracy is a set of standards whose²³⁵U isotope abundances are known to within 0.01% (2).     

Some aspects of the high-temperature behavior of bismuth,strontium and barium on silicon surfaces studied by total reflection X-ray fluorescence spectrometry

Thin films of novel dielectric and ferroelectric materials, such as barium strontium titanate (BST) and strontium bismuth tantalate (SBT), which are scheduled for short-term implementation into standard microelectronic device technology, contain elements like Bi, Sr and Ba which may involve risks with regard to device yield and reliability. Therefore, the high-temperature behavior of bismuth, strontium and barium impurities on Si (100) substrates was studied. Intentionally contaminated Si substrates were annealed at 1000°C under different ambient (inert, oxidizing) by rapid thermal annealing (RTA) or in a furnace and analyzed by total reflection X-ray fluorescence spectrometry (TXRF), vapor phase decomposition/TXRF (VPD/TXRF) and electrolytic metal tracer (Elymat) technique. Ba and Sr are incorporated in the existing or growing oxide during rapid thermal annealing (RTA). Cross-contamination due to gas phase transport may occur in the case of Bi, in particular under N₂ atmosphere, but is of no concern in the case of Ba and Sr. All three contaminants do not exert an influence on the minority carrier lifetime on their own. The results illustrate that TXRF and VPD/TXRF are appropriate techniques for such studies.