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The correlation of single-particle imaging and absorption spectroscopy made the development of sizing curves possible and enabled rapid size determination of semiconductor nanocrystals based solely on optical properties. The increasing demand and production of such materials has resulted in a question of comparability between existing models and adequate volume-weighted size-determining measurement techniques. Small-angle X-ray scattering (SAXS) is a well-established method for obtaining nanostructural information from particle systems while operating sample quantities up to a commercial scale with a large amount of statistically based data. This work utilizes laboratory SAXS to characterize cadmium selenide nanocrystals with band edge energies between 1.97 and 3.08 eV. The evaluation of the scattering patterns is based on an indirect Fourier transformation (IFT), while dimensional parameters are derived from the model-free pair distance distribution functions (Dmode and Dg), as well as the modeled volume (Dv) and number (Dn)-weighted size-density distributions. We find that comparable data from Dn agree well with existing X-ray diffraction (XRD) and with transmission electron microscopy (TEM) results described in literature; this qualifies SAXS as an equivalent integral characterization method. Although based on an estimate, the radius of gyration yields equivalent accurate results. Additionally, corresponding volume-weighted data are shown that can be useful when transferring information to other techniques. Dmode parametrization represents the largest estimated size of the sample and implies that particles interact and deviate from the spherical morphology, whereas Dv demonstrates results not considering such effects. A full set of the parameters discussed quantifies the quality of a sample.

Size and shape distributions of gold nanorod samples are critical to their physico-chemical properties, especially their longitudinal surface plasmon resonance. This interlaboratory comparison study developed methods for measuring and evaluating size and shape distributions for gold nanorod samples using transmission electron microscopy (TEM) images. The objective was to determine whether two different samples, which had different performance attributes in their application, were different with respect to their size and/or shape descriptor distributions. Touching particles in the captured images were identified using a ruggedness shape descriptor. Nanorods could be distinguished from nanocubes using an elongational shape descriptor. A non-parametric statistical test showed that cumulative distributions of an elongational shape descriptor, that is, the aspect ratio, were statistically different between the two samples for all laboratories. While the scale parameters of size and shape distributions were similar for both samples, the width parameters of size and shape distributions were statistically different. This protocol fulfills an important need for a standardized approach to measure gold nanorod size and shape distributions for applications in which quantitative measurements and comparisons are important. Furthermore, the validated protocol workflow can be automated, thus providing consistent and rapid measurements of nanorod size and shape distributions for researchers, regulatory agencies, and industry.

In recent years, DNA origami nanorulers for superresolution (SR) fluorescence microscopy have been developed from fundamental proof-of-principle experiments to commercially available test structures. The self-assembled nanostructures allow placing a defined number of fluorescent dye molecules in defined geometries in the nanometer range. Besides the unprecedented control over matter on the nanoscale, robust DNA origami nanorulers are reproducibly obtained in high yields. The distances between their fluorescent marks can be easily analysed yielding intermark distance histograms from many identical structures. Thus, DNA origami nanorulers have become excellent reference and training structures for superresolution microscopy. In this work, we go one step further and develop a calibration process for the measured distances between the fluorescent marks on DNA origami nanorulers. The superresolution technique DNA-PAINT is used to achieve nanometrological traceability of nanoruler distances following the guide to the expression of uncertainty in measurement (GUM). We further show two examples how these nanorulers are used to evaluate the performance of TIRF microscopes that are capable of single-molecule localization microscopy (SMLM).

Quality control of nanoparticle production processes requires traceable calibration methods for size and size distribution which are presented and discussed in this article. The main focus is on the one hand the application of small-angle X-ray scattering for an integral measurement of nanoparticles in liquid suspension and on the other hand scanning electron microscopy in transmission for a microscopic measurement method of nanoparticles prepared on a substrate. In addition, characterization by scanning probe microscopy is covered.

Because procedures of handling and storage of body fluids affect numbers and composition of extracellular vesicles (EVs), standardization is important to ensure reliable and comparable measurements of EVs in a clinical environment. We aimed to develop standard protocols for handling and storage of human body fluids for EV analysis. Conditions such as centrifugation, single freeze–thaw cycle, effect of time delay between blood collection and plasma preparation and storage were investigated. Plasma is the most commonly studied body fluid in EV research. We mainly focused on EVs originating from platelets and erythrocytes and investigated the behaviour of these 2 types of EVs independently as well as in plasma samples of healthy subjects. EVs in urine and saliva were also studied for comparison. All samples were analysed simultaneously before and after freeze–thawing by resistive pulse sensing, nanoparticle tracking analysis, conventional flow cytometry (FCM) and transmission (scanning) electron microscopy. Our main finding is that the effect of centrifugation markedly depends on the cellular origin of EVs. Whereas erythrocyte EVs remain present as single EVs after centrifugation, platelet EVs form aggregates, which affect their measured concentration in plasma. Single erythrocyte and platelet EVs are present mainly in the range of 100–200 nm, far below the lower limit of what can be measured by conventional FCM. Furthermore, the effects of single freeze–thaw cycle, time delay between blood collection and plasma preparation up to 1 hour and storage up to 1 year are insignificant (p>0.05) on the measured concentration and diameter of EVs from erythrocyte and platelet concentrates and EVs in plasma, urine and saliva. In conclusion, in standard protocols for EV studies, centrifugation to isolate EVs from collected body fluids should be avoided. Freezing and storage of collected body fluids, albeit their insignificant effects, should be performed identically for comparative EV studies and to create reliable biorepositories.Keywords: erythrocyte; guideline; plasma; saliva; urine; platelet; cell-derived vesicles(Published: 11 November 2015)Citation: Journal of Extracellular Vesicles 2015, 4: 29260 - http://dx.doi.org/10.3402/jev.v4.29260

In this paper we will provide an overview of methods and instruments developed and applied at the National Metrology Institute of Germany (Physikalisch Technische Bundesanstalt—PTB) for high-precision dimensional (linear and angular) measurements and discuss some challenges for future developments in this important area of metrology.

In future, measurements of extracellular vesicles in body fluids could become a standard diagnostic tool in medicine. For this purpose, reliable and traceable methods, which can be easily applied in hospitals, have to be established. Within the European Metrological Research Project (EMRP) 'Metrological characterization of micro-vesicles from body fluids as non-invasive diagnostic biomarkers' (www.metves.eu), various nanoparticle reference materials were developed and characterized. We present results of an international comparison among four national metrology institutes and a university hospital. The size distributions of five monodisperse and two bimodal spherical particle samples with diameters ranging from 50 nm to 315 nm made out of silica and polystyrene were compared. Furthermore, the stability of the samples was verified over a period of 18 months. While monodisperse reference particle samples above a certain size level lead to good agreements of the size measurements among the different methods, small and bimodal samples show the limitations of current 'clinical' methods. All samples proved to be stable within the uncertainty of the applied methods.

We have developed a lateral standard on the nanometre scale for use with high-resolution optical microscopy techniques [U. Huebner, in: Proceedings of the 5th International Euspen Conference, 2005, pp. 185-188; U. Huebner, in: Optical Fabrication Testing, and Metrology II, Proc. SPIE 5965 (2005) 59651W]. The so-called nanoscale linewidth/pitch standard contains structures in the submicron- and sub-100nm scale and meets the metrological requirements for accurate, easy and traceable optical microscopy measurements. The optical contrast of the pattern in the UV wavelength range makes it suitable for transmission and reflection UV-microscopy and for confocal laser scanning microscopy. The standard can be used for pitch- and linewidth measurements and for quick resolution testing of these instruments. Additionally, the integrated circular gratings provide a new way of calibrating scanning probe microscopes.

A new optical diffractometer has been developed and set up at the Physikalisch-Technische Bundesanstalt (PTB). It offers the possibility of high-accuracy calibrations of the lateral period of gratings (pitch) in the micro- and nanometre scale. The measurement principle is based on a modified Littrow configuration, where the incident and the diffracted laser beams are almost collinear. The grating is mounted on a rotary table, and a high-precision rotary encoder is used to measure its angular positions. The profiles of the diffracted laser beams are recorded by means of a line array image detector. To determine the centre positions of the imaged laser beam profiles, different analysis methods can be applied, among others a new correlation method. A variety of laser wavelengths, ranging from 266 nm to 633 nm, can be used. Due to the optional UV wavelength, the smallest measurable pitch is about 150 nm. Depending on the quality of the sample, the measurement uncertainty can be smaller than 10 pm. For two-dimensional gratings the pitch of the two main and the diagonal directions can be measured and thus, also the angle between the two main grating orientations can be determined.

We have developed a new lateral standard on the nanometre scale for use with the recently introduced high-resolution optical microscopy techniques such as deep ultraviolet microscopy (DUVM) and confocal laser scanning microscopy (CLSM). The standard provides structures in the submicron- and sub-100 nm scale, and meets the metrological requirements for accurate and traceable optical microscopy measurements. It can be used as a length measurement standard (for pitch and linewidth measurements) and for quick resolution and astigmatism testing of all these instruments. Additionally, circular gratings provide a new way for the calibration of scanning probe microscopes.

A new algorithm is presented that evaluates the critical dimension (CD) of nanostructures from scanning electron microscopy (SEM) images. The algorithm is based on the physical modelling of the SEM image formation and evaluates both top and bottom CDs. The SEM intensity profile is modelled by a piecewise-defined continuous function which is approximated to the measured profile extracted from images by means of a least-squares fit. The algorithm is tested in a series of Monte Carlo simulations with respect to a variation of the edge-slope angle and the electron probe diameter. The maximum deviation between the modelled and the simulated top and bottom CDs is smaller than 3 nm. As an application example, measurements of silicon line structures are presented.

We report the initial results of a recent bilateral comparison of linewidth or critical dimension (CD) calibrations on photomask line features between two national metrology institutes (NMIs): the National Institute of Standards and Technology (NIST) in the United States and the Physikalisch-Technische Bundesanstalt (PTB) in Germany. For the comparison, a chrome on glass (CoG) photomask was used which has a layout of line features down to 100 nm nominal size. Different measurement methods were used at both institutes. These included: critical dimension atomic force microscopy (CD-AFM), CD scanning electron microscopy (CD-SEM) and ultraviolet (UV) transmission optical microscopy. The measurands are CD at 50 % height of the features as well as sidewall angle and line width roughness (LWR) of the features. On the isolated opaque features, we found agreement of the CD measurements at the 3 nm to 5 nm level on most features – usually within the combined expanded uncertainties of the measurements.

The edge method for measuring the modulation transfer function(MTF) has recently gained popularity due to its simplicity and appropriateness particularly for digital imaging systems. Often edge test devices made of rather thin metal sheets are used, which are semitransparent to x rays and may generate scattered radiation. The effect of this scattered radiation on the determined MTF was investigated both theoretically (assuming an ideal detector) and experimentally using a CsI-based digital detector. It was found that the MTF increases due to the scattered radiation for all spatial frequencies larger than 0 mm − 1 . The theoretical model developed in this study predicts that the maximum error compared to the true detectorMTF is given by S ∕ A , where A is the attenuated fraction and S is the scattered fraction reaching the detector, relative to the incident radiation. Theoretical and experimental results are in good agreement for radiation qualities corresponding to general radiography (RQA3, RQA5, and RQA7), whereas for chest beam quality (RQA9) the experimentally observed MTF error is larger than predicted by the simple model, possibly because the energy response of the CsI-based detector differs from that of an ideal one. The theoretical MTF error reaches a value of 18% for a 0.25 mm thick lead edge of RQA9. Since the MTF enters squared into the determination of the detective quantum efficiency (DQE), an error of at least 36% in DQE may result when using this edge test device. In conclusion, the use of fully absorbing edge material is advised for MTF determination with the edge method.

A method to measure the X ray intensity pattern in a radiograph of the thorax in the detector plane with high spatial resolution was developed. A special phantom from a dead body was exposed to X rays applying standard examination conditions for thoracic imaging, and the image was stored on industrial X ray film normally used for non-destructive testing. In addition, the thorax of a volunteer was imaged on a high-resolution mammographic screen-film system. Both images were digitised with a high-resolution drum film scanner. The X ray intensity patterns of the thoracic images were calculated for both images using the characteristic curves of the screen-film systems and the scanner. A new method to evaluate the information content in the X ray intensity pattern in the frequency domain is presented. The resulting spatial frequency limits of anatomical structures looking like lines or edges are used to propose requirements for digital thoracic imaging systems.

Zusammenfassung Digitale Rontgendetektoren werden fur Rontgenuntersuchungen immer bedeutsamer. Die Bildqualitat solcher Detektorsysteme hangt nicht nur von den Eigenschaften des Systems, sondern auch vom Strahlenrelief in der Detektorebene ab. In der vorliegenden Arbeit wird ein Verfahren zur hochortsaufgelosten Messung des Strahlenreliefs einer Thoraxaufrahme vorgestellt. Dazu wurde ein spezielles Lungenpraparat in einem Standardaufnahmestand gerontgt. Die Rontgenbilder des Praparates wurden auf industriellem Rontgenfilm, der sonst fur die zerstorungsfreie Materialprufung verwendet wird, aufgezeichnet. Anschliesend wurden sie mit einem hochauflosenden Trommelscanner digitalisiert. Es wurde gezeigt, das Film und Scanner im Ortsfrequenzbereich bis 15 mm −1 vorhandene Bildinformation ubertragen konnen und das beim Digitalisieren keine Artefakte aufgrund von aliasing-Effekten aufgetreten sind. Uber die charakteristischen Kurven von Scanner und Film wurde das Strahlenrelief in der Detektorebene bestimmt. Dieses wurde mit Hilfe eines neuen Verfahrens auf seinen Informationsgehalt im Ortsfrequenzraum untersucht. Daraus ergab sich als Anforderung an digitale Rontgendetektoren fur Rontgenuntersuchungen des Thorax ein Abtastintervall von weniger als 100 μm.

In medical X-ray imaging, film processing is one of the main parameters determining image quality, An important method for controlling film processing is sensitometry. Light sensitometers in which electroluminescent foils serve as light sources are widely used for this purpose. These sensitometers emit light pulse trains of different pulse repetition frequency and different total length, which may cause intermittency effects or give rise to reciprocity law failure. These effects may increase the uncertainty of this sensitometric method to an extent which is no longer tolerable for the intended purpose. The effects were measured for a great number of films of five leading film manufacturers. The results are presented and steps proposed which should be taken to make this kind of sensitometry more reliable.

The European Metrology Research Programme participating countries and the European Union jointly fund a three year project to address the need of the automotive industry for a metrological sound base for exhaust measurements. The collaborative work on particle emissions involves five European National Metrology Institutes, the Tampere University of Technology, the Joint Research Centre for Energy and Transport and the Leibniz Institute for Tropospheric Research. On one hand, a particle number and size standard for soot particles is aimed for. Eventually this will allow the partners to provide accurate and comparable calibrations of measurement instruments for the type approval of Euro 5b and Euro 6 vehicles. Calibration aerosols of combustion particles, silver and graphite proof partially suitable. Yet, a consensus choice together with instrument manufactures is pending as the aerosol choice considerably affects the number concentration measurement. Furthermore, the consortium issued consistent requirements for novel measuring instruments foreseen to replace today’s opacimeters in regulatory periodic emission controls of soot and compared them with European legislative requirements. Four partners are conducting a metrological validation of prototype measurement instruments. The novel instruments base on light scattering, electrical, ionisation chamber and diffusion charging sensors and will be tested at low and high particle concentrations. Results shall allow manufacturers to further improve their instruments to comply with legal requirements.

Zusammenfassung In der vorliegenden Arbeit wird ein digitales Abtast- und Wiedergabesystem („Scanner”) hinsichtlich seiner Eignung zur Digitalisierung und photographischen Wiedergabe von konventionellen medizinischen Rontgenaufnahmen untersucht. Die verwendeten Methoden zur Bestimmung der Ubertragungseigenschaften des Scanners werden beschrieben. Die Ergebnisse lassen das System als knapp ausreichend fur die Reproduktion von Aufnahmen erscheinen, die zuvor mit Film-Folien-Systemen mittlerer Empfindlichkeit aufgenommen wurden, da eine mestechnisch signifikante Erhohung des Bildrauschens hingenommen werden mus. Als Beispiel wird die Reproduktion klinischer Thorax-Aufnahmen diskutiert.

Zusammenfassung In dieser Arbeit wird der Zusammenhang zwischen dem Bildrauschen und der Diagnose von Lungenrundherden in konventionellen Thoraxaufnahmen untersucht. Sie beschreibt ein Verfahren, mit dem Vergleichsaufnahmen mit unterschiedlichem Bildrauschen erzeugt wurden. Originalaufnahmen ohne Befund wurden mit hoher Ortsauflosung digitalisiert, 10 mm grose Rundherde wurden simuliert und in die digitalisierten Aufnahmen eingebaut. Danach erzeugte man von jeder dieser digitalen Aufnahmen eine zweite Aufnahme, indem mit Methoden der digitalen Bildbearbeitung das Wienerspektrum gezielt erhoht wurde. Anschliesend erfolgte die Ausgabe der Aufnahmen mit diesem Zusatzrauschen und der Aufnahmen ohne Zusatzrauschen auf photographischem Film in Originalgrose. Die Diagnose der Rundherde in den Aufnahmen wurde im Rahmen einer ROC-Studie untersucht. Insgesamt 16 Radiologen hatten die Aufgabe, die eingebrachten Rundherde zu diagnostizieren. Die Auswertung der Diagnosen ergibt, das das Bildrauschen gegenuber der anatomischen Hintergrundstruktur von untergeordneter Bedeutung fur die Erkennung der nodularen Strukturen ist: Trotz deutlicher Erhohung des Wienerspektrums ergab sich in der Erkennbarkeit der Rundherde kein signifikanter Unterschied.

Transmission electron imaging with standard scanning electron microscopes (SEMs) can be implemented simply by equipping the SEM with a readily available transmission detector. This mode, called STEM-in-SEM or simply TSEM, is a valuable technique that bridges the gap between SEM and high-voltage transmission electron microscopy. It combines the versatility of a SEM with the advantageous imaging modalities using transmitted electrons. TSEM can replace TEM or high-voltage STEM when atomic resolution is not needed, and it offers new imaging possibilities and applications due to its use of low-energy electrons. The basics of the TSEM technique are summarized. The configuration and the implementation of the transmission detector are introduced. The physics of electron scattering is briefly discussed, which is the basis of the different contrast mechanisms and can be simulated using Monte Carlo methods. Subsequently, we compare some aspects of TSEM with common electron microscopy techniques (TEM, STEM, and SEM). Various TSEM applications are presented, including traceable dimensional measurements, the characterization of different material classes, and special imaging modes.

Zusammenfassung Im Rahmen der Qualitatssicherung in der Rontgendiagnostik werden bei der Abnahme und Kontrolle der Filmverarbeitung Rontgenfilm-Sensitometer eingesetzt. In der vorliegenden Arbeit wird ein Spektrometer vorgestellt, mit dem auf einfache Weise die Emissionsspektren derartiger Sensitometer mit ausreichender Genauigkeit gemessen werden konnen. Mit dem Gerat kann insbesondere gepruft werden, ob die Emissionsspektren den Anforderungen nach DIN 6868 Teil 55 genugen. Es werden das Meβprinzip und die Kalibrierung des Spektrometers beschrieben und Messungen an zwei Sensitometern des Herstellers Victoreen vorgestellt und diskutiert.

Supported by the European Commission and EURAMET, a consortium of 10 participants from national metrology institutes, universities and companies has started a joint research project with the aim of overcoming current challenges in optical scatterometry for traceable linewidth metrology. Both experimental and modelling methods will be enhanced and different methods will be compared with each other and with specially adapted atomic force microscopy (AFM) and scanning electron microscopy (SEM) measurement systems in measurement comparisons. Additionally novel methods for sophisticated data analysis will be developed and investigated to reach significant reductions of the measurement uncertainties in critical dimension (CD) metrology. One final goal will be the realisation of a wafer based reference standard material for calibration of scatterometers.

Stochastic sub-wavelength structures with lateral sizes of below 100 nm and heights of about 250 nm were produced on polymer surfaces by plasma treatment. From these master samples, an embossing nickel tool was manufactured, which, in turn, was used to replicate the master surface form by hot embossing in plastic materials. The geometry of the produced nanostructures was quantified by scanning electron microscopy. The optical surface reflectance of both the master and the replicated samples were measured in the visible wavelength range. A significant reduction of optical reflectance from the expected 4% of untreated surfaces, to less than 0.5% of the master samples, and to values between 1% and 2% of the replicated samples was achieved. The optical reflectance of the stochastic structures was calculated by a finite element-based rigorous solution of the Maxwell equations. The modeled results show a good agreement with experimental data.

In preparation for the international Nano1 linewidth comparison on photomasks between nine national metrology institutes, the National Institute of Standards and Technology (NIST) and the Physikalisch-Technische Bundesanstalt (PTB), initiated a bilateral linewidth comparison in 2008, independent of and prior to the Nano1 comparison in order to test the suitability of the mask standards and the general approach to be used for the Nano1 comparison. This paper reports on the current status of the bilateral comparison. In particular the methods for linewidth metrology applied at NIST and PTB and its major uncertainty contributions will be discussed based on actual measurements results for both of the mask standards chosen for the bilateral comparison.

This paper reports results of an international comparison of one-dimensional (1D) grating pitch calibration by optical diffraction. Comparison results are analysed and discussed following the recommended guidelines for the analysis of CIPM key comparisons. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by SIM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

In preparation of the international Nano1 linewidth comparison on photomasks between 9 national metrology institutes, NIST and PTB have started a bilateral linewidth comparison in 2008, independent of and prior to the Nano1 comparison in order to test the suitability of the mask standards and the general approach to be used for the Nano1 comparison. This contribution describes the rationale of both comparisons, the design of the mask comparison standards to be used and the measurement methods applied for traceable photomask linewidth metrology at NIST and PTB.

Today, various types of high resolution dimensional metrology instrumentation are in use for a quantitative characterisation of micro- and nanostructures. Although sophisticated ultra high resolution microscopic techniques like SEM and AFM are available, optical methods like microscopy and scatterometry are still of interest and are important because they are non-destructive, fast and have a good in-line capability. At PTB different optical tools are used for high-resolution metrology. Our standard instrument for CD metrology is a special UV transmission microscope. A new 193nm microscope is currently under development which will meet future requirements at least for the 32nm node as specified in the ITRS roadmap. A special alternating grazing incidence dark field microscope is used to measure the width of single features down to 100nm. For grating structures, we developed an optical diffractometer for pitch calibrations with an uncertainty down to 10 pm. Recently we realised a DUV scatterometer and ellipsometer capable to measure accurately CD, edge profile, layer thickness, and optical parameters. A versatile EUV scatterometer can be used to characterise absorber structures e. g. on EUV photomasks. For accurate measurements a thorough modelling on the basis of rigorous diffraction calculation is essential, which accounts for both polarisation effects and the 3D geometry of the structures. We use the rigorous coupled wave analysis (RCWA) method and the finite elements (FEM) method. We present an overview of PTB's current and future activities in optical high-resolution metrology and how these systems compare to ultra-high resolution microscopy like SEM or AFM.

A navel optical heterodyne technique for Raman Ramsey spectroscopy of atomic radio frequency resonances is reported. The method allows for high-resolution studies in an atomic beam as well as for the study of collisional velocity diffusion of atoms within an optical Doppler distribution. Our experiments are performed on Zeeman sublevels in the Samarium λ = 570.68 nm (J=1)-(J′=O transition both in an atomic beam and in a vapor; in the latter case rare gas perturbers are added as collision partners. All our experimental findings are in satisfactory agreement with theoretical predictions.

We measured the pitch of a 144-nm pitch, two-dimensional grid in two different laboratories. Optical Diffraction gave very high accuracy for mean pitch and Atomic Force Microscopy measured individual pitch values, gaining additional information about local pitch variation. The measurements were made traceable to the international meter. Optical diffraction gave mean value 143.928 ± 0.015 nm (95% confidence limit, per GUM). AFM gave mean value 143.895 ± 0.079 nm. Individual pitch values had standard deviation 0.55 nm and expanded uncertainty ± 1.1 nm. Mean values measured by the two methods agreed within 0.033 nm. Because this was less than the uncertainty due to random variation in the AFM results, it suggests that the AFM measuring and analysis procedures have successfully corrected all systematic errors of practical significance in microscopy. We also discuss what precision may be expected from the AFM method when it is applied to measure smaller pitches.

A new algorithm for SEM CD evaluation of trapezoidal line structures is presented. It is based on the physical modeling of SEM image formation and allows the assignment of top and bottom structural edge positions to the SEM signal. The SEM image profile is described by a set of piecewise continuous functions which is convoluted with the electron probe intensity profile. The resulting function is fitted to the measured signal profile by a least squares algorithm. The fit returns both top and bottom edge positions as well as the electron probe diameter. The algorithm is verified against three different Monte Carlo simulation programs using different physical models of elastic and inelastic electron scattering and secondary electron generation and transport. The effect of the physical modeling on the evaluated critical dimension is discussed and the absolute CD deviation of the algorithm is determined for different sets of specimen and tool parameters like edge slope angle, beam energy, and electron probe diameter.

Measurement and control of edge profiles and edge angles is increasingly important in advanced lithography. Especially for critical dimension metrology a sophisticated multi-dimensional shape metrology is highly beneficial. Different types of dimensional metrology instrumentation are in use today for edge profile and edge angle measurement. While destructive cross section SEM measurements often serve as reference, AFM and optical scatterometry systems are commonly used for day-to-day or in-line control. Due to the limitations of these metrology systems (AFM: slow, scatterometry: only integral measurements of periodic structures), the evaluation and modelling of top down SEM images is increasingly considered, too. At the PTB both SEM and AFM as well as optical scatterometry are applied for edge angle and/or edge profile metrology, supported by optical transmission microscopy. At the PTB we have realised a new DUV hybrid scatterometer for measurements over the full range of 6025 format masks which combines essential elements of a reflectometer, an ellipsometer, and a diffractometer. In addition to scatterometric measurements this set-up allows to measure the complete Muller-matrix including transmission, polarisation and depolarisation. This new set-up will be presented in detail. Finally we study the possibilities of evaluating high resolution top down SEM images to determine edge angles. The potential of edge angle evaluation using these new analysis procedures will be discussed. We present an overview of the PTB measurement capabilities with an emphasis on newly developed metrology methods and systems.

We are developing a new linewidth standard on the nanometre scale for use in the recently introduced new high-resolution optical microscopy techniques like deep ultraviolet microscopy (UVM) and confocal laser scanning microscopy (CLSM). Different types of high-resolution gratings, etched in amorphous silicon on quartz substrates, have been fabricated and evaluated using state-of-the-art UVM, CLSM, REM and AFM equipment. The produced linewidths range from about 80 nm to 2 μm. The contrast of the pattern in the UV region makes them suitable for transmission and reflection UV and laser scanning microscopy.

The modulation transfer function (MTF) is well established as a metric to characterize the resolution performance of a digital radiographic system. Implemented by various laboratories, the edge technique is currently the most widespread approach to measure the MTF. However, there can be differences in the results attributed to differences in the analysis technique employed. The objective of this study was to determine whether comparable results can be obtained from different algorithms processing identical images representative of those of current digital radiographic systems. Five laboratories participated in a round-robin evaluation of six different algorithms including one prescribed in the International Electrotechnical Commission (IEC) 62220-1 standard. The algorithms were applied to two synthetic and 12 real edge images from different digital radiographic systems including CR, and direct- and indirect-conversion detector systems. The results were analysed in terms of variability as well as accuracy of the resulting presampled MTFs. The results indicated that differences between the individual MTFs and the mean MTF were largely below 0.02. In the case of the two simulated edge images, all algorithms yielded similar results within 0.01 of the expected true MTF. The findings indicated that all algorithms tested in this round-robin evaluation, including the IEC-prescribed algorithm, were suitable for accurate MTF determination from edge images, provided the images are not excessively noisy. The agreement of the MTF results was judged sufficient for the measurement of the MTF necessary for the determination of the DQE.

A variant of the edge method for the determination of the pre-sampled modulation transfer function (MTF) of digital X-ray imaging devices has been developed and accepted as the standard method in the novel DQE measurement standard IEC 62220-1. An opaque tungsten edge-test device accomplishes the ideal step-like profile of the incident X rays. The edge spread function is measured over a large region across the edge transition that enables an accurate MTF measurement including the 'low-frequency drop'. The method has been applied to different state-of-the-art X-ray imaging detectors, a computed radiography, a CsI-based indirect and an Se-based direct flat-panel detector. The MTF measurement results will be presented. In contrast to the opaque edge device, the commonly used semi-transparent edge-test devices produce scatter radiation that deteriorates the incident X-ray profile, which leads to a systematic overestimation of the MTF.

A mobile measurement facility which complies with IEC 62220-1 has been set up to determine the detective quantum efficiency (DQE) of digital X-ray detector systems. Exemplary measurements were performed for two similar CR detector systems, a CsI-based indirect detector and an Se-based direct detector. The standardised radiation quality RQA 5 was applied for measurement and for three of these systems RQA 9 was also applied. A pronounced dependence of DQE on radiation quality was observed for the direct detector, where the DQEs for RQA 5 and RQA 9 differ by a factor of approximately 2. The uncertainty (95% confidence interval) associated with the measured DQE values is within 0.01 and 0.04 depending on, for example, the spatial frequency. Thus, it has been demonstrated that the DQE can be measured accurately and reliably with the accuracy required by the international standard IEC 62220-1. It is now possible to objectively measure and compare DQE values of digital X-ray detector systems.

Former studies by Hoeschen and Buhr indicated a higher total noise in a thorax image than expected from technical noise, i.e. quantum and detector noise. This difference results from the overlay of many small anatomical structures along the X-ray beam, which leads to a noise-like appearance without distinguishable structures in the projected image. A method is proposed to quantitatively determine this 'anatomical noise' component, which is not to be confused with the anatomical background (e.g. ribs). This specific anatomical noise pattern in a radiograph changes completely when the imaging geometry changes because different small anatomical structures contribute to the projected image. Therefore, two images are taken using slightly different exposure geometry, and a correlation analysis based on wavelet transforms allows to determining the uncorrelated noise components. Since the technical noise also differs from image to image, which makes it difficult to separate the anatomical noise, images of a lung phantom were produced on a low-sensitive industrial X-ray film using high-exposure levels. From these results, the anatomical noise level in real clinical thorax radiographs using realistic exposure levels is predicted using the general dose dependence described in the paper text and compared with the quantum and detector noise level of an indirect flat-panel detector system. For consistency testing, the same lung phantom was imaged with the same digital flat-panel detector and the total image noise including anatomical noise is determined. The results show that the relative portion of anatomical noise may exceed the technical noise level. Anatomical noise is an important contributor to the total image noise and, therefore, impedes the recognition of anatomical structures.

The X-ray pattern of a mass of very fine non-distinguishable anatomical structures alters completely from radiograph to radiograph due to the unavoidable movements of the patient during the exposure. The corresponding image component shows noise-like behaviour and is therefore referred to as the anatomical noise. Reducing this component would enhance the quality of the clinical X-ray image and increase the detectability of radiological signal. We have found that by comparing two X-ray images of the same anatomy acquired under slightly different imaging geometry, it is possible to reduce the anatomical noise in one of the image pair. The proposed method, which allows this, is based on the appropriate attenuation in the wavelet domain. The values of attenuating factors for the wavelet coefficients are proportional to the correlation between the corresponding features of both images. This method was tested for different changes in the imaging geometry. In the case of no geometrical changes, only the quantum and the electronic noise are reduced. An effect of de-noising for the investigated images is obvious.

The edge method for measuring the modulation transfer function (MTF) has recently gained popularity due to its simplicity and appropriateness particularly for digital imaging systems. Often edge test devices made of rather thin metal sheets are used, which are semitransparent to x rays and may generate scattered radiation. The effect of this scattered radiation on the determined MTF was investigated both theoretically (assuming an ideal detector) and experimentally using a CsI-based digital detector. It was found that the MTF increases due to the scattered radiation for all spatial frequencies larger than 0 mm(-1). The theoretical model developed in this study predicts that the maximum error compared to the true detector MTF is given by S/A, where A is the attenuated fraction and S is the scattered fraction reaching the detector, relative to the incident radiation. Theoretical and experimental results are in good agreement for radiation qualities corresponding to general radiography (RQA3, RQA5, and RQA7), whereas for chest beam quality (RQA9) the experimentally observed MTF error is larger than predicted by the simple model, possibly because the energy response of the CsI-based detector differs from that of an ideal one. The theoretical MTF error reaches a value of 18% for a 0.25 mm thick lead edge of RQA9. Since the MTF enters squared into the determination of the detective quantum efficiency (DQE), an error of at least 36% in DQE may result when using this edge test device. In conclusion, the use of fully absorbing edge material is advised for MTF determination with the edge method.

The contributors to image noise of two computed radiography (CR) detector systems-a state-of-the-art and a wellchosen laboratory CR image plate-were studied by two different methods. Method 1 analyzes the image noise content of a series of images obtained at a wide range of different X-ray exposure levels. It uses a model to fit the observed exposure dependence of the normalized noise power spectrum (NNPS): It distinguishes between an NNPS component that is independent of the exposure level and mainly due to correlated noise, and an NNPS component which is inversely proportional to the exposure level and consists mainly of quantum noise. Method 2 analyzes several images taken at the same exposure level and distinguishes between correlated noise, which remains unchanged in repeated exposures, and uncorrelated noise which is different in each image. The results of the two methods allowed the relevant noise contributions in CR images to be quantitatively determined. The novel laboratory image plate showed a significant reduction of correlated noise with an accompanying increase in the DQE. The results also served to estimate a possible improvement of DQE if an appropriate flat field correction is made for these CR systems.

The DQEs of four digital X-ray detector systems have been measured in accordance with the new international standard IEC 62220-1: two CR detector systems of the same type, a CsI-based indirect flat panel detector and a selenium-based direct flat panel detector. A mobile measurement set-up complying with IEC 62220-1 has been realized. All equipment used was of a specific design, tested and calibrated. A standardized radiation quality (RQA5) was applied, and the air kerma at the detector entrance was varied between about 1 μGy and 20 μGy. The measurements of the two CR detector systems were performed at different sites using different X-ray generators/tubes and were in agreement within 0.02. The maximum DQE values were obtained for the lowest spatial frequency for which the DQE is required to be reported according to the IEC standard, i.e. at 0.5 mm-1: The maximum DQE value measured was 0.21 for the CR systems, 0.42 for the indirect flat panel detector, and 0.31 for the direct Selenium-based detector. It has been demonstrated that the international standard IEC 62220-1 allows accurate and reliable measurements of the DQE to be conducted. It is now possible to objectively measure and compare DQE values of digital X-ray detector systems.

Several methods for accurately deriving the presampled modulation transfer function (MTF) of a pixelated detector from the image of a slightly slanted edge have been described in the literature. In this paper we report on a simple variant of the edge method that produces sufficiently accurate MTF values for frequencies up to the Nyquist frequency limit of the detector with little effort in edge alignment and computation. The oversampled ESF is constructed in a very simple manner by rearranging the pixel data of N consecutive lines corresponding to a lateral shift of the edge by one pixel. A regular subsampling pitch is assumed for the oversampled ESF, which is given by the original pixel sampling distance divided by the integer number N. This allows the original data to be used for further computational analysis (differentiation and Fourier transform) without data preprocessing. Since the number of lines leading to an edge shift by one pixel generally is a fractional number rather than an integer, a systematic error may be introduced into the presampled MTF. Simulations and theoretical investigations show that this error is proportional to 1/N and increases with spatial frequency. For all frequencies up to the Nyquist limit, the relative error delta MTF/MTF is smaller than 1/(2N). It can thus be kept below a given threshold by suitably selecting N, which furnishes a certain maximum edge angle. The method is especially useful for applications where the presampled MTF is needed only for frequencies up to the Nyquist frequency limit, such as the determination of the detective quantum efficiency (DQE).

A simple variant of the edge method to determine the presampled modulation transfer function (MTF) of digital imaging detectors has been developed that produces sufficiently accurate MTF values for frequencies up to the Nyquist frequency limit of the detector with only a small amount of effort for alignment and computing. An oversampled edge spread function (ESF) is generated from the image of a slanted edge by rearranging the pixel data of N consecutive lines that correspond to a lateral shift of the edge of one pixel. The original data are used for the computational analysis without further data preprocessing. Since the number of lines leading to an edge shift of one pixel is generally a fractional number rather than an integer, a systematic error may be introduced in the MTF obtained. Simulations and theoretical investigations show that for all frequencies up to the Nyquist limit the relative error ∆MTF/MTF is below 1/(2N) and can thus be kept below a given threshold by a suitable choice of N. The method is especially useful for applications where the MTF is needed for frequencies up to the Nyquist frequency limit, like the determination of the detective quantum efficiency (DQE).

There are many aspects that influence and deteriorate the detection of pathologies in X-ray images. Some of those are due to effects taking place in the stage of forming the X-ray intensity pattern in front of the x-ray detector. These can be described as motion blurring, depth blurring, anatomical background, scatter noise and structural noise. Structural noise results from an overlapping of fine irrelevant anatomical structures. A method for measuring the combined effect of structural noise and scatter noise was developed and will be presented in this paper. This method is based on the consideration that within a pair of projections created after rotation of the object with a small angle (which is within the typical uncertainty in positioning the patient) both images would show the same relevant structures whereas the projection of the fine overlapping structures will appear quite differently in the two images. To demonstrate the method two X-ray radiographs of a lung phantom were produced. The second radiograph was achieved after rotating the lung by an angle of about 3. Dyadic wavelet representations of both images were regarded. For each value of the wavelet scale parameter the corresponding pair of approximations was matched using the cross correlation matching technique. The homologous regions of approximations were extracted. The image containing only those structures that appear in both images simultaneously was then reconstructed from the wavelet coefficients corresponding to the homologous regions. The difference between one of the original images and the noise-reduced image contains the structural noise and the scatter noise.

The effects of different film processing conditions on light and x-ray sensitometric responses were compared for a variety of double-emulsion x-ray films. The processing conditions were altered by changes of the developer temperature. Three different exposure variants were applied: x-ray sensitometry using two stepped neutral density attenuators between film and screens, simultaneous double-sided light sensitometry, and single-sided light sensitometry. 13 different types of double-emulsion x-ray films were investigated, among them three asymmetric films. In the special case of exposing the asymmetric films with the single-sided light sensitometer, a method was investigated where each side of the film is exposed at different locations and the sum effect is analyzed. From each sensitometric curve shape two parameters, the logarithmic speed ( log S) and the average gradient (G), were evaluated. The results of this study can be summarized as follows: (1) Single-sided and double-sided light sensitometers revealed almost equal changes of log S when the processing conditions are altered. Thus, single-sided light sensitometers can serve as a substitute for double-sided light sensitometers provided that suited exposure methods are used and appropriate sensitometric parameters are evaluated. (2) Light sensitometry quantitatively indicated changes of the film processing that affect the x-ray speed. Hence, light sensitometry is a useful method to monitor changes in film processing.