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Koeberl M.,James Cook University | Clarke D.,Australian National Measurement Institute | Lopata A.L.,James Cook University
Journal of Proteome Research | Year: 2014

Food allergies are increasing worldwide and becoming a public health concern. Food legislation requires detailed declarations of potential allergens in food products and therefore an increased capability to analyze for the presence of food allergens. Currently, antibody-based methods are mainly utilized to quantify allergens; however, these methods have several disadvantages. Recently, mass spectrometry (MS) techniques have been developed and applied to food allergen analysis. At present, 46 allergens from 11 different food sources have been characterized using different MS approaches and some specific signature peptides have been published. However, quantification of allergens using MS is not routinely employed. This review compares the different aspects of food allergen quantification using advanced MS techniques including multiple reaction monitoring. The latter provides low limits of quantification for multiple allergens in simple or complex food matrices, while being robust and reproducible. This review provides an overview of current approaches to analyze food allergens, with specific focus on MS systems and applications. © 2014 American Chemical Society.

Farrance I.,RMIT University | Frenkel R.,Australian National Measurement Institute
Clinical Biochemist Reviews | Year: 2012

The Evaluation of Measurement Data - Guide to the Expression of Uncertainty in Measurement (usually referred to as the GUM) provides general rules for evaluating and expressing uncertainty in measurement. When a measurand, y, is calculated from other measurements through a functional relationship, uncertainties in the input variables will propagate through the calculation to an uncertainty in the output y. The manner in which such uncertainties are propagated through a functional relationship provides much of the mathematical challenge to fully understanding the GUM. The aim of this review is to provide a general overview of the GUM and to show how the calculation of uncertainty in the measurand may be achieved through a functional relationship. That is, starting with the general equation for combining uncertainty components as outlined in the GUM, we show how this general equation can be applied to various functional relationships in order to derive a combined standard uncertainty for the output value of the particular function (the measurand). The GUM equation may be applied to any mathematical form or functional relationship (the starting point for laboratory calculations) and describes the propagation of uncertainty from the input variable(s) to the output value of the function (the end point or outcome of the laboratory calculation). A rule-based approach is suggested with a number of the more common rules tabulated for the routine calculation of measurement uncertainty.

Kazlauskas R.,Australian National Measurement Institute
Handbook of Experimental Pharmacology | Year: 2010

Anabolic steroids have been studied for over 50 years and during that time numerous compounds with a variety of functional groups have been produced and many have been published. Of these only a small number have been introduced to the pharmaceutical market. WADA has continued the work begun by the IOC banning the use of these agents within sport as performance enhancing substances. Athletes, however, continue to use these anabolic steroids but tighter testing and the introduction of unannounced sample collection has made this form of cheating harder. In order to try to evade detection, athletes who continue to dope are having to resort to the use of a far more dangerous form of drug - the designer steroid. These steroids are manufactured to closely resemble existing known compounds, but with sufficient chemical diversity to ensure that their detection by the WADA accredited laboratories is more difficult. A worrying feature of the use of these compounds is that no data is available to evaluate either the efficacy or the safety of these substances. Many such drugs are now being made in clandestine ways (as demonstrated by the recent BALCO case) and then passed on to athletes who become the guinea pigs determining the potential of the substances as doping agents. Methods for the detection of these new compounds are being developed using emerging techniques such as gas chromatography or liquid chromatography attached to a variety of mass spectrometry instruments. This technology as well as vigilance by laboratories and enforcement agencies can all help in early detection of designer steroids being used for doping. © 2009 Springer-Verlag Berlin Heidelberg.

Li Y.,Australian National Measurement Institute
CPEM Digest (Conference on Precision Electromagnetic Measurements) | Year: 2010

Precision DC voltage dividers with ratings up to 1000 kV have been built using the 150 kV resistor module developed at the National Measurement Institute, Australia (NMIA). The structure of the 150 kV resistor module and the measurement techniques for evaluating its performance are described. The method for evaluating voltage ratio errors at voltages up to 1000 kV is discussed. It is shown that a ratio error of less than 5 μV/V at 150 kV and less than 100 μV/V at 1000 kV can be achieved. © 2010 IEEE.

Small G.W.,Australian National Measurement Institute
CPEM Digest (Conference on Precision Electromagnetic Measurements) | Year: 2010

The design of the NMIA-BIPM calculable cross capacitor includes the requirement that the main electrodes be geometrically true cylinders to within 100 nm over all but the last 50 mm at each end of their length. After much experimentation, techniques have been developed that result in the fabrication of electrodes that comfortably meet this requirement. © 2010 IEEE.

Georgakopoulos D.,Australian National Measurement Institute
IEEE Transactions on Instrumentation and Measurement | Year: 2011

Providing the traceability of alternating-current (ac) voltage measurements by means of a stepwise-approximated sine wave (SASW) produced by a programmable Josephson voltage standard (PJVS) is an attractive alternative to the conventional ac voltage standards based on thermal voltage converters, because a programmable Josephson standard has a calculable output voltage that does not drift with time. This paper investigates two aspects of uncertainties in the measurement of ac voltage using a sine wave generated by a PJVS with a lock-in amplifier as a null detector. First, the uncertainty introduced by transitions between successive voltage levels of the SASW on the fundamental and root-mean-square values is examined. Second, the lock-in amplifier response to the harmonics of this synthesized sine wave is discussed. Experimental evaluation shows that harmonics that are not rejected by the lock-in amplifier can cause a systematic error when measuring the ac-direct-current difference of a thermal converter with the synthesized sine wave from 0.5 to 3.0 μV/V, depending on the number of samples per period of the SASW. Furthermore, it is shown that this error can be reduced to 0.3 μV/V by calibrating the lock-in amplifier using a distorted signal having a similar harmonic content to the synthesized sine wave. © 2006 IEEE.

Ballico M.,Australian National Measurement Institute
International Journal of Thermophysics | Year: 2011

The replacement of ITS-90 temperature measurements by direct thermodynamic temperature measurements based on radiometric techniques in the temperature range above 1000°C has been proposed by many national measurement laboratories. This article reports on work at NMIA to develop a simple and robust traceability scheme for thermodynamic temperature, based on the use of photometers and a Thermogage furnace with a graphite tube element modified to improve its temperature uniformity and emissivity. A simple luminance meter was constructed using a commercial photometer and pairs of precision apertures to view the rear of the blackbody cavity. This photometer was calibrated against NMIA reference illuminance lamps, and relative spectral responsivity measurements were used to determine the color-temperature correction between the lamps and the Thermogage blackbody. Thermodynamic temperature determinations made using various combinations of apertures and photometers showed a range of less than 0.2°C at 1700°C, consistent with the calculated uncertainty of 0.29°C (k = 2). ITS-90 measurements made by NMIA's LP5 and HTSP primary radiation thermometers with an uncertainty of 0.16°C (k = 2), are consistent with the thermodynamic measurements. It is suggested that routine thermodynamic temperature determinations can now be made with an effort comparable to that required to realize the ITS-90 above 1000°C. © 2011 Springer Science+Business Media, LLC.

There is a recognised need for standardisation of protocols for vector genome analysis used in vector manufacturing, to establish dosage, in biodistribution studies and to detect gene doping in sport. Analysis of vector genomes and transgene expression is typically performed by qPCR using plasmid-based calibrants incorporating transgenic sequences. These often undergo limited characterisation and differ between manufacturers, potentially leading to inaccurate quantification, inconsistent inter-laboratory results and affecting clinical outcomes. Contamination of negative samples with such calibrants could cause false positive results. We developed a design strategy for synthetic reference materials (RMs) with modified transgenic sequences to prevent false positives due to cross-contamination. When such RM is amplified in transgene-specific assays, the amplicons are distinguishable from transgene’s amplicons based on size and sequence. Using human erythropoietin as a model, we produced certified RM according to this strategy and following ISO Guide 35. Using non-viral and viral vectors, we validated the effectiveness of this RM in vector genome analysis in blood in vitro. The developed design strategy could be applied to production of RMs for other transgenes, genes or transcripts. Together with validated PCR assays, such RMs form a measurement tool that facilitates standardised, accurate and reliable genetic analysis in various applications.Gene Therapy advance online publication, 21 July 2016; doi:10.1038/gt.2016.47. © 2016 Macmillan Publishers Limited

MacKay L.G.,Australian National Measurement Institute | Kazlauskas R.,Australian National Measurement Institute
Analytical and Bioanalytical Chemistry | Year: 2011

Currently a large range of pure substance reference materials are available for calibration of doping-control methods. These materials enable traceability to the International System of Units (SI) for the results generated by World Anti-Doping Agency (WADA)-accredited laboratories. Only a small number of prohibited substances have threshold limits for which quantification is highly important. For these analytes only the highest quality reference materials that are available should be used. Many prohibited substances have no threshold limits and reference materials provide essential identity confirmation. For these reference materials the correct identity is critical and the methods used to assess identity in these cases should be critically evaluated. There is still a lack of certified matrix reference materials to support many aspects of doping analysis. However, in key areas a range of urine matrix materials have been produced for substances with threshold limits, for example 19-norandrosterone and testosterone/epitestosterone (T/E) ratio. These matrix-certified reference materials (CRMs) are an excellent independent means of checking method recovery and bias and will typically be used in method validation and then regularly as quality-control checks. They can be particularly important in the analysis of samples close to threshold limits, in which measurement accuracy becomes critical. Some reference materials for isotope ratio mass spectrometry (IRMS) analysis are available and a matrix material certified for steroid delta values is currently under production. In other new areas, for example the Athlete Biological Passport, peptide hormone testing, designer steroids, and gene doping, reference material needs still need to be thoroughly assessed and prioritised. © 2011 Her Majesty the Queen in Right of Australia, as represented by the National Measurement Institute.

Goebel C.,Australian National Measurement Institute
Drug Testing and Analysis | Year: 2011

Low molecular weight luteinizing hormone (LMWLH) receptor agonists could be of interest as a potential doping substance for athletes. These orally active compounds induce the production of endogenous hormones such as testosterone in a similar way to LH. A method for the detection of these compounds needs to be direct as their effect - the excess production of endogenous hormones - cannot be proven by analysis techniques which test for endogenous hormones. In order to detect a broad range of potential LMWLH receptor agonists, a precursor ion monitoring liquid chromatography tandem mass spectrometry method was developed. The method was tested against a selection of urine samples to ascertain potential problems with background analytes interfering with the compounds of interests. Selected compounds were extracted with an established methodology from urine to determine suitability of implementing into general screening methodologies. The two available LMWLH receptor agonists could be detected at concentrations of 100ng/ml in urine samples. This establishes a basic precursor ion monitoring method suitable for screening purposes for the detection of LMWLH receptor agonists in urine samples. © 2011 John Wiley & Sons, Ltd.

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