Automated nanoliter solution deposition for total reflection X-ray fluorescence analysis of semiconductor samples

In this study, a BioDot BioJet dispensing system was investigated as a nanoliter sample deposition method for total reflection X-ray fluorescence (TXRF) analysis. The BioDot system was programmed to dispense arrays of 20 nL droplets of sample solution on Si wafers. Each 20 nL droplet was approximately 100 μm in diameter. A 10 × 10 array (100 droplets) was deposited and dried in less than 2 min at room temperature and pressure, demonstrating the efficiency of the automated deposition method. Solutions of various concentrations of Ni and Ni in different matrices were made from stock trace element standards to investigate of the effect of the matrix on the TXRF signal. The concentrations were such that the levels of TXRF signal saturation could be examined. Arrays were deposited to demonstrate the capability of drying 100 μL of vapor phase decomposition-like residue in the area of a typical TXRF detector.     

Improving the signal intensity and sensitivity of MALDI mass spectrometry by using nanoliter spots deposited by induction-based fluidics

A new contact-free, small droplet deposition method using an induction-based fluidics (IBF) technique to dispense nanoliter drops is described and evaluated for sample preparation in matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The signal intensities available when using nanoliter spots are greater than those obtained with normal, microliter spots when the same amount of analyte is used. When using an ionic-liquid matrix, the improvement in sensitivity is equal to the concentration enhancement that was achieved by using smaller quantities of matrix. When using a conventional solid matrix, however, the increase in signal intensity shows a more complicated relationship to concentration. The approach of nanoliter deposition also supports multiple spotting to increase sample concentration and, thus, sample signal intensity. Nanoliter spotting not only improves the signal intensity and sensitivity achieved by MALDI-MS but also allows a major fraction of trace samples to be saved for other experiments, thus expanding the application of MALDI-MS to biological studies where sample quantity is limited.     

An electrochemical enrichment procedure for the determination of heavy metals by total-reflection X-ray fluorescence spectroscopy

An electrolytic separation and enrichment technique was developed for the determination of trace elements by total-reflection X-ray fluorescence spectroscopy (TXRF). The elements of interest are electrodeposited out of the sample solution onto a solid, polished disc of pure niobium which is used as sample carrier for the TXRF measurement. The electrochemical deposition leads to a high enrichment of the analytes and at the same time to a removal of the matrix. This results in substantially improved detection limits in the lower picogram per gram region. The deposited elements are directly measured by TXRF without any further sample preparation step. The homogeneous thin layer of the analytes is an ideal sample form for TXRF, because scattered radiation from the sample itself is minimized. The proposed sample preparation method is useful particularly for the analysis of heavy metals in liquid samples with for TXRF disturbing matrices, e.g. sea water.     

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.     

Semiconductor applications of nanoliter droplet methodology with total reflection x-ray fluorescence analysis

In this study, the nanoliter dried spot method was applied to semiconductor contamination analysis to enhance vapor phase decomposition processes with total reflection X-ray fluorescence detection. Nanoliter-sized droplets (10 and 50 nl) were deposited onto native silicon oxide wafer surfaces in a clean room environment from both single and multielemental standards containing various concentrations of iron in different matrices. Direct comparisons were made to droplets formed by conventional VPD with similar iron standards. Nanoliter dried spots could be reproducibly deposited and dried in air with typical drying times ranging from 20 s to 2 min depending on the nanoliter volume deposited, compared to VPD spots which have drying times ranging from tens of minutes to several hours. Both types of residues showed a linear relationship between Fe intensity and mass deposited. Variable angle experiments showed that both nanoliter and VPD deposits of single element standards were film-like in character, while residues formed from much more complex matrices and higher mass loadings were particulate in character. For the experimental conditions used in this study (30 kV, 100 mA), typical TXRF spectral Fe limits of detection were calculated to be on the order of picograms or ∼1×10¹⁰ atoms/cm² for a 0.8 cm² X-ray excitation beam area for both nanoliter dried spots and VPD spots prepared from single elemental standards. Calculated Fe detection limits for 200 mm diameter silicon wafers used in this study were in the ∼1×10⁸ atoms/cm² range. By using nanoliter sized droplets, the required sample volume is greatly reduced resulting in higher sample throughput than with conventional VPD methods.     

Analytical approaches for Hg determination in wastewater samples by means of total reflection X-ray fluorescence spectrometry

At present, there is a considerable interest in Hg monitoring in wastewater samples due to its widespread occurrence and the high toxicity of most of its compounds. Hg determination in water samples by means of total reflection X-ray fluorescence spectrometry (TXRF) entails some difficulties due to the high vapor pressure and low boiling point of this element that produce evaporation and loss of Hg from the surface of the reflector during the drying process, commonly used for sample preparation in TXRF analysis.The main goal of the present research was to develop a fast and simple chemical strategy to avoid Hg volatilization during the analysis of wastewater samples by TXRF spectrometry. Three different analytical procedures were tested for this purpose: (i) increasing the viscosity of the wastewater sample by adding a non-ionic surfactant (Triton^® X-114), (ii) Hg immobilization on the quartz reflectors using the extractant tri-isobutylphosphine (Cyanex 471X) and (iii) formation of a stable and non-volatile Hg complex into the wastewater sample. The best analytical strategy was found to be the formation of a Hg complex with thiourea (pH = 10) before the deposition of 10 μL of sample on the reflector for following TXRF analysis. Analytical figures of merit such as linearity, limits of detection, accuracy and precision were carefully evaluated. Finally, the developed methodology was applied for the determination of Hg in different types of wastewater samples (industrial effluents, municipal effluents from conventional systems and municipal effluents from constructed wetlands).     

Optimization of TXRF measurements by variable incident angles

Variable incident angles in TXRF instrumentation open up new possibilities in the field of analytical quality assurance of TXRF measurements as well as the possibility of optimizing the measurement angle with respect to the sample carrier. Measurements on the same sample with different incident angles allow a check to be made on the behavior of the internal standard and the elements under investigation within the sample, which makes quantification more reliable, even for difficult samples. This is demonstrated on the example of standard reference material NIST 1633a comparing the relative fluorescence intensities of the elements K, Ti and Fe obtained from a sample prepared from a suspension and a digestion of the SRM material, respectively. Furthermore, it will be shown how the measurement conditions for different sample carrier materials such as quartz and acrylic glass can be optimized by measuring angular-dependent signal and background intensities.     

Picoliter solution deposition for total reflection X-ray fluorescence analysis of semiconductor samples

A deposition system capable of delivering picoliter quantities of solution in programmable arrays was investigated as a method for sample preparation for total reflection X-ray fluorescence (TXRF) spectroscopy. Arrays of trace metals in solution were deposited on Si wafers. The array deposits provide a capability of depositing closely spaced (100 μm or less), typically 5–20 μm diameter droplets in an area that can be matched to the analysis spot of the TXRF detector. The dried depositions were physically characterized and the effect of deposition type and matrix on the TXRF signal was investigated.     

Comparison of synchrotron radiation total reflection X-ray fluorescence excitation–detection geometries for samples with differing matrices

The linear polarization of synchrotron radiation (SR) in the orbital plane leads to a background reduction in total reflection X-ray fluorescence (TXRF) analysis if a side-looking detector is used. The optimum orientation of the sample carrier in a SR-TXRF experiment, however, is determined by a trade-off between the exploitation of the linear polarization, the efficiency of excitation and the solid angle of detection and depends on the nature and size of the sample. SR-TXRF measurements on different sample types and using different reflector orientations have been carried out at the Hamburger Synchrotronstrahlungslabor bending magnet beamline L. A NIST standard water sample, a steel sample and an oil standard were analyzed with both a horizontal and a vertical sample carrier orientation. Strongly scattering samples led to lower detection limits with a horizontal reflector whereas weakly scattering samples showed lower detection limits with a vertical reflector configuration. On an intentionally contaminated wafer absolute detection limits of 6.6 fg for Ni could be extrapolated.     

Sapphire sample carriers for silicon determination by total-reflection X-ray fluorescence analysis

Sapphire is presented as a new sample carrier material for total-reflection X-ray fluorescence spectrometry (TXRF). A comparison with conventional sample carrier materials such as quartz glass, Perspex®, glassy carbon and boron nitride demonstrates that sapphire has all the physical and chemical properties required for TXRF micro and trace analysis. Moreover, sapphire sample carriers allow the determination of silicon in many matrices in a comparatively simple way. Especially for airborne particulate matter, acid digestion can be avoided by cool-plasma ashing of suitable filter materials directly on the sample carrier. This technique has been successfully applied to environmental samples.     

Investigation of element distribution and homogeneity of TXRF samples using SR-micro-XRF to validate the use of an internal standard and improve external standard quantification

Total reflection X-ray fluorescence analysis (TXRF) offers a nondestructive qualitative and quantitative analysis of trace elements. Due to its outstanding properties TXRF is widely used in the semiconductor industry for the analysis of silicon wafer surfaces and in the chemical analysis of liquid samples. Two problems occur in quantification: the large statistical uncertainty in wafer surface analysis and the validity of using an internal standard in chemical analysis. In general TXRF is known to allow for linear calibration. For small sample amounts (low nanogram (ng) region) the thin film approximation is valid neglecting absorption effects of the exciting and the detected radiation. For higher total amounts of samples deviations from the linear relation between fluorescence intensity and sample amount can be observed. This could be caused by the sample itself because inhomogeneities and different sample shapes can lead to differences of the emitted fluorescence intensities and high statistical errors. The aim of the study was to investigate the elemental distribution inside a sample. Single and multi-element samples were investigated with Synchrotron-radiation-induced micro X-ray Fluorescence Analysis (SR-μ-XRF) and with an optical microscope. It could be proven that the microscope images are all based on the investigated elements. This allows the determination of the sample shape and potential inhomogeneities using only light microscope images. For the multi-element samples, it was furthermore shown that the elemental distribution inside the samples is homogeneous. This justifies internal standard quantification.     

Improvement of total reflection X-ray fluorescence analysis of low Z elements on silicon wafer surfaces at the PTB monochromator beamline for undulator radiation at the electron storage ring BESSY II

Several different total reflection X-ray fluorescence (TXRF) experiments were conducted at the plane grating monochromator beamline for undulator radiation of the Physikalisch-Technische Bundesanstalt (PTB) at the electron storage ring BESSY II, which provides photon energies between 0.1 and 1.9 keV for specimen excitation. The lower limits of detection of TXRF analysis were investigated for some low Z elements such as C, N, O, Al, Mg and Na in two different detection geometries for various excitation modes. Compared to ordinary XRF geometries involving large incident angles, the background contributions in TXRF are drastically reduced by the total reflection of the incident beam at the polished surface of a flat specimen carrier such as a silicon wafer. For the sake of an application-oriented TXRF approach, droplet samples on Si wafer surfaces were prepared by Wacker Siltronic and investigated in the TXRF irradiation chamber of the Atominstitut and the ultra-high vacuum TXRF irradiation chamber of the PTB. In the latter, thin C layer depositions on Si wafers were also studied.     

Application of total reflection X-ray fluorescence in angle scan mode to establish the location of arsenic contamination in silicon and silicon oxide,respectively

Experiments have been carried out using total reflection X-ray fluorescence (TXRF) to determine the location of arsenic cross-contamination on or in silicon and silicon oxide, respectively, caused during argon-implantation. TXRF has been applied at varying angles of incidence — the so-called angle scan mode. By comparing the angle scan curves of implanted samples with those of a wafer, spin-coated with arsenic, at which arsenic is certainly located on top of the silicon surface, clear differences are observed. This indicates the presence of arsenic embedded in the subsurface. These observations are confirmed by Rutherford backscattering measurements, by modeling As-implantation profiles for low implantation energies as well as by step-by-step oxide etching followed by standard TXRF analysis. This fast and non-destructive application of TXRF angle scan appears a useful method for qualitative depth profiling.     

A new technique for the deposition of standard solutions in total reflection X-ray fluorescence spectrometry (TXRF) using pico-droplets generated by inkjet printers and its applicability for aerosol analysis with SR-TXRF

A new technique for the deposition of standard solutions on particulate aerosol samples using pico-droplets for elemental determinations with total reflection X-ray fluorescence spectrometry (TXRF) is described. It enables short analysis times without influencing the sample structure and avoids time consuming scanning of the sample with the exciting beam in SR-TXRF analysis. Droplets of picoliter volume (∼ 5–130 pL) were generated with commercially available and slightly modified inkjet printers operated with popular image processing software. The size of the dried droplets on surfaces of different polarity namely silicone coated and untreated quartz reflectors, was determined for five different printer types and ten different cartridge types. The results show that droplets generated by inkjet printers are between 50 and 200 μm in diameter (corresponding to volumes of 5 to 130 pL) depending on the cartridge type, which is smaller than the width of the synchrotron beam used in the experiments (< 1 mm at an energy of 17 keV at the beamline L at HASYLAB, Hamburg). The precision of the printing of a certain amount of a single element standard solution was found to be comparable to aliquoting with micropipettes in TXRF, where for 2.5 ng of cobalt relative standard deviations of 12% are found. However, it could be shown that the printing of simple patterns is possible, which is important when structured samples have to be analysed.     

Electro-deposition as a sample preparation technique for total-reflection X-ray fluorescence analysis

A one-step sample preparation by electro-deposition for total-reflection X-ray fluorescence (TXRF) analysis has been developed using a common three-electrode arrangement with a rotating disc as the working electrode. Several elements such as Cr, Mn, Fe, Co, Ni, Cu, Zn, Ag, Cd, Pb, As and U have been determined simultaneously in saline matrix. A special electrode tip has been constructed as a holder for the TXRF sample carrier, which consists of polished glassy carbon. The influence of parameters such as time, pH value, and trace element concentration on the deposition yield has been examined for 14 elements. From repeatability studies, the uncertainty in deposition yields at the 95% confidence level has been found to be less than 20% for most of these elements. Typical detection limits range from 5 to 20 ng/l under the experimental conditions applied here. By an appropriate choice of the reference element and by calculation of yield factors, reliable quantification can be achieved directly by internal standardization. First results obtained for the standard reference material CRM 505 are presented.     

Electrospray sample deposition for matrix-assisted laser desorption/ionization (MALDI) and atmospheric pressure MALDI mass spectrometry with attomole detection limits

Electrospray sample deposition was explored for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). In this method, nanoliter volumes of matrix/analyte mixture were electrosprayed from a high voltage biased (1-2 kV) fused-silica capillary onto a grounded MALDI plate mounted 100-500 microm from the capillary outlet. Electrospray deposition with these conditions produced sample spots 200-300 microm in diameter thus matching the laser spot size. Varying spray voltage and distance resulted in different crystal sizes and volatilization rates for alpha-cyano-4-hydroxycinnamic acid matrix. Best results were obtained when the sample was deposited as wet droplets as opposed to deposition as dried solid. Under 'wet-spray' conditions, 2-4 microm diameter crystals were formed and detection limits for several neuropeptides were 0.7-25 amol. Samples could be pre-concentrated on the plate by spraying continuously and allowing sample to evaporate in a small spot. Sample volumes as large as 580 nL were deposited yielding a detection limit of 35 pM for neurotensin 1-11. Electrospray sample deposition yielded similar results when using atmospheric pressure-MALDI coupled with a quadrupole ion trap mass spectrometer, except that the sensitivity was approximately seven-fold worse.     

Comparison of conventional and total reflection excitation geometry for fluorescence X-ray absorption spectroscopy on droplet samples

X-ray absorption fine structure (XAFS) experiments in fluorescence mode have been performed in total reflection excitation geometry and conventional 45°/45° excitation/detection geometry for comparison. The experimental results have shown that XAFS measurements are feasible under normal total reflection X-ray fluorescence (TXRF) conditions, i.e. on droplet samples, with excitation in grazing incidence and using a TXRF experimental chamber. The application of the total reflection excitation geometry for XAFS measurements increases the sensitivity compared to the conventional geometry leading to lower accessible concentration ranges. However, XAFS under total reflection excitation condition fails for highly concentrated samples because of the self-absorption effect.     

Considerations on the ideal sample shape for Total Reflection X-ray Fluorescence Analysis

Total Reflection X-ray Fluorescence analysis (TXRF) is widely used in semiconductor industry for the analysis of silicon wafer surfaces. Typically an external standard is used for the calibration of the spectrometer. This is sensitive to errors in quantification. For small sample amounts the thin film approximation is valid, absorption effects of the exciting and the detected radiation are neglected and the relation between sample amount and fluorescence intensity is linear. For higher total sample amounts deviations from linearity have been observed (saturation effect). These deviations are one of the difficulties for external standard quantification.A theoretical determination of the ideal TXRF sample shape is content of the presented work with the aim to improve the calibration process and therefore the quantification.The fluorescence intensity emitted by different theoretical sample shapes was calculated, whereby several parameters have been varied (excitation energy, density, diameter/height ratio of the sample). It was investigated which sample shape leads to the highest fluorescence intensity and exhibits the lowest saturation effect. The comparison of the different sample shapes showed that the ring shape matches the ideal TXRF sample shape best.     

Total reflection X-ray fluorescence analysis with chemical microchip

A chemical microchip, which has a flat region on the surface, was recently designed for total reflection X-ray fluorescence (TXRF) analysis. A sample solution was introduced from an inlet by a microsyringe and flowed into a microchannel. Finally it overflowed from the well-type microchannel on the flat region. The sample solution on this region was dried, and then measured by TXRF. The TXRF spectra could be measured with a low background level. This preliminary result indicated that the edge of the well-type channel would not cause a serious problem for TXRF analysis. In addition, a good linear relationship was obtained for Zn Kα in Zn standard solution. This suggests that quantitative analysis by TXRF is feasible in combination with a chemical microchip.     

Microanalytical method development for Fe, Cu and Zn determination in colorectal cancer cells

Microanalytical methods suitable for the determination of Fe, Cu in HT-29 (human colon adenocarcinoma) cells treated with different iron compounds (Fe(II) sulfate, Fe(III) chloride, Fe(III) citrate and Fe(III) transferrin) and cultured in medium supplemented or not with 10% (v/v) fetal calf serum (FCS) by total reflection X-ray fluorescence spectrometry (TXRF) and simultaneous graphite furnace atomic absorption spectrometry (GF-AAS) were developed. The developed TXRF method was also suitable for Zn determination in the samples. The main advantage of the proposed methods is the execution of all sample preparation steps following incubation and prior to the elemental analysis in the same Eppendorf tubes. Sample preparation was performed at microscale (115 μL sample volume) with 65% nitric acid and 30% hydrogen peroxide. According to scanning electron microscopic measurements, the organic matrix of the cell samples could be eliminated to the extent that accurate results were obtained for Cu and Fe by analyzing the same samples by TXRF and GF-AAS. Concerning the iron uptake, HT-29 cells incubated in FCS-free medium contained Fe in cca. 5-50 times higher amounts compared to cells cultured in FCS supplemented medium. Pronounced differences in the iron uptake compared to the iron supply (inorganic vs. organic chelated as well as iron(II) vs. iron(III)) were observed in the case of cell lines incubated in FCS-free medium.