Metrological traceability is not always a straight line

The two most important concepts in metrology are certainly “traceability to standards” and “measurement uncertainty evaluation”. So far the questions related to these concepts have been reasonably solved in the metrology of “classical quantities”, but for the introduction of metrological concepts in new fields, such as chemistry and biology, a lot of problems remain and must be solved in order to support international arrangements. In this presentation, the authors want to develop the strategy implemented at Laboratoire national de métrologie et d’essais (LNE) in metrology in chemistry and biology. The strategy is based on: (1) pure solutions for calibration of analytical instruments, (2) use of certified reference materials (matrix reference materials), and (3) participation to proficiency testing schemes. Examples will be presented in organic and inorganic chemistry. For laboratory medicine, proficiency testing providers play an important role in the organization of External Quality Assessment Schemes. For the time being, the reference value or the assigned value of the comparison is calculated with the results obtained by the participants. This assigned value is not often traceable to SI units. One of the methods suggested by LNE is to ensure the metrological traceability to SI units of the assigned value for the more critical quantities carried on analytes by implementing the Joint committee for traceability in laboratory medicine reference methods.     

Uncertainty analysis of theoretical methods for adiabatic temperature rise determination in calorimetry

The main methods for the determination of the temperature rise in calorimetric experiments corrected of heat losses to surroundings (called adiabatic temperature rise) are described thereafter. This corrected temperature rise is obtained analytically from experimental temperature–time curves. The general scheme reported by Henri Régnault and Leopold Pfaundler for the first time in the 19th century is considered as the basis for all methods elaborated afterwards. A bibliographical study raised five methods including Régnault–Pfaundler’s. These methods have been applied on five experimental temperature–time curves obtained with an isoperibolic reference gas calorimeter at the French national metrology and testing institute (LNE) on combustion of pure methane. This paper deeply details a new analytical method elaborated at LNE exposing best heat transfer phenomena representation occurring in the water bath calorimeter. A comparative study of the five methods of the temperature rise determination and of their associated uncertainties is here presented.     

Metrological Assurance of Biodevices: The New Method of Calibration of Biochemical Analyzers

Abstract

Medical diagnostics and therapy use an extensive amount of electronics, optoelectronics, and laser devices. For their reliable functioning, calibration is unavoidable. Biochemical analyzers, which work on principles of absorptional spectrophotometry, became most widely present in medical biochemical laboratories. Construction of these devices is such, that in most cases, it does not allow calibration by usual methods, using neutral density (ND) filters as standards. For this reason, it was necessary to create a solution that could be used as a mean of comparison or even as a standard solution for methods of calibration of biochemical analyzers. In this article, the metrological characterization of solutions that are developed is presented, and the measuring uncertainty (ISO 1993) of methods used for calibration is estimated.

The method that is developed provides metrological traceability to the primary spectrophotometric standard. With this method, metrological assurance in the field of the spectrophotometry in medical laboratories is completed.     

Principles of analytical calibration/quantification for the separation sciences

Calibration is an operation whose main objective is to know the metrological status of a measurement system. Nevertheless, in analytical sciences, calibration has special connotations since it is the basis to do the quantification of the amount of one or more components (analytes) in a sample, or to obtain the value of one or more analytical parameters related with that quantity. Regarding this subject, the aim of analytical calibration is to find an empiric relationship, called measurement function, which permits subsequently to calculate the values of the amount (x-variable) of a substance in a sample, from the measured values on it of an analytical signal (y-variable). In this paper, the metrological bases of analytical calibration and quantification are established and, the different work schemes and calibration methodologies, which can be applied depending on the characteristic of the sample (analyte+matrix) to analyse, are distinguished and discussed. Likewise, the different terms and related names are clarified. A special attention has been paid to those analytical methods which use separation techniques, in relation with its effect on calibration operations and later analytical quantification.     

Metrological concept for comparable measurement results under the European water framework directive: demonstration of its applicability in elemental analysis

Within the scope of a project of the “European Association of National Metrology Institutes??(EURAMET), a European metrological dissemination system (network) providing traceable reference values assigned to matrix materials for validation purposes is described and put to the test. It enables testing laboratories (TL) to obtain comparable results for measurements under the “EU Water Framework Directive 2000/60/EC??(WFD) and thus, to comply with a core requirement of this very directive. The dissemination system is characterized by the fact that it is available to all laboratories throughout Europe which intend to perform measurements in the context of the WFD and that it can ensure sustainable metrological traceability to the International System of Units (SI) as a reference point for the measurement results. This dissemination system is set up in a hierarchical manner and links up the level of the national metrology institutes (NMI) with that of the TLs via an intermediate level of calibration laboratories (CL) by comparison measurements. The CLs are expert laboratories with respect to the measurement of the analytes considered here (within the project, the CLs are called potential calibration laboratories (PCL)) and are additionally involved in the organization of comparison measurements within the scope of regional quality assurance (QA) systems. Three comparison measurements have been performed to support the approach. A total of about 130 laboratories participated in this exercise with the focus on the measurement of the priority substances Pb, Cd, Hg, and Ni defined in the WFD. The elemental concentrations in the water samples roughly corresponded to one of the established environmental quality standards (EQS), the annual average concentration (AA-EQS), which is defined in the daughter Directive 2008/105/EC of the WFD. It turned out that a significant number of TLs still need to improve their measurement methods in order to be able to fulfill the minimum requirements of the WFD, in particular, with regard to the elements Cd and Hg probably due to their low EQS values. Furthermore, it became obvious that the hierarchical dissemination system suggested here actually corresponds to the measuring capabilities of the three participating groups (NMIs, PCLs, and TLs).     

Reference materials for PCDD and PCDF analysis: production and verification of the contents of twelve congeners in iso-octane reference solutions

Summary The Community Bureau of Reference (BCR) of the Commission of the European Communities has produced standard solutions of PCDDs and PCDFs (dirty dozen) to guarantee proper calibration and traceability of results in the certification of these compounds in matrix materials. The purity of each individual isomer has been evaluated on the initial crystals using several analytical methods. Solvents have been checked for impurities. The entire procedure of preparation of the twelve solutions has been performed under strict metrological conditions and will be published elsewhere. All results and the preparation procedure followed are described. The solutions are not certified, but may be obtained from BCR together with an analytical report.     

Achieving traceability in chemical measurement—a metrological approach to proficiency testing

ISO/IEC 17025 requires that testing laboratories establish the traceability of their measurements, preferably to the SI units of measurement. The responsibility for establishing traceability lies with each individual laboratory and must be achieved by following a metrological approach.The results of measurements made in such a way are traceable to the standards used in method validation and to the calibration standards used during the measurement process. If these standards are traceable to SI then the measurements will also be traceable to SI.Participation in appropriate proficiency studies (an ISO/IEC 17025 requirement) enables laboratories to demonstrate the comparability of their measurements. If the materials used for the studies have traceable assigned values, then proficiency testing also provides information about measurement accuracy and confirms, or otherwise, that appropriate traceability has been established. This paper will report on a new approach for the establishment of traceable assigned values for chemical testing proficiency studies. The work is conducted at a "fit for purpose" level of measurement uncertainty, with costs contained at a level similar to previous "consensus" based proficiency studies. By establishing traceable assigned values in a cost effective way, NARL aims to demonstrate the added value of the metrological approach to participant laboratories.     

Traceability system for elemental analysis

A complete metrological traceability system for measurement results of chemical analysis was set up. Core components are pure substances (national standards) characterised at the highest metrological level, primary solutions prepared from these pure substances and secondary solutions deduced from the primary solutions and intended for sale. The relative uncertainty of the element mass fraction of the primary substances and solutions is < 0.01 and < 0.05%, respectively. For the certification of transfer solutions and for stability testing, a precision measurement method for element contents has been developed by means of optical emission spectrometry (ICP OES) by which uncertainties between 0.1 and 0.05% can be achieved. The dissemination to field laboratories is effected with the aid of a calibration laboratory of the German Calibration Service (DKD) which certifies the element content of the secondary solutions with an uncertainty ≤ 0.3%. Calibration with these solutions enables the user to establish traceability of his measurement results to the International System of Units (SI). Currently, the system comprises Cu, Fe, Bi, Ga, Si, Na, K, Sn, W, and Pb.     

The impact of metrological traceability on the validity of creatinine measurement as an index of renal function

When the calibration of a routine measurement procedure is traced back to metrological higher order, a significant discrepancy can occur between the analytical conditions of the routine measurement and the analytical conditions that were used in the clinical studies upon which the decision-making criteria are based. This can lead to serious interpretation errors with possible dramatic consequences for patients. The calibration of the creatinine Jaffé method is an excellent example of the importance of medical traceability. The compensated Jaffé method correlated accurately with the reference method and the compensated Jaffé creatinine clearance (CrCl), Cockroft and Gault and MDRD with the ⁵¹Cr EDTA clearance. The Schwartz estimate based upon the compensated Jaffé and enzymatic method overestimated, while uncompensated Jaffé slightly underestimated glomerular filtration rate (GFR). The situation in children is complex since serum creatinine concentrations are much lower in infants, rendering tubular secretion relatively more important. Low-molecular weight proteins have been suggested to replace serum creatinine as a marker for GFR. -trace protein, cystatin C, and ₂-microglobulin showed good correlation with GFR. However, care should be taken in patients presenting with some malignant tumors, since significant increases of cystatin C in patients with metastatic melanoma or colorectal cancer has been reported.Presented at the 9th Conference on Quality in the Spotlight, 18-19 March 2004, Antwerp, Belgium     

New Electrochemical Sensor of Prolonged Application for Metformin Determination Based on Hydrated Ruthenium Dioxide‐Carbon Black‐Nafion Modified Glassy Carbon Electrode

Metformin (MET) is an antidiabetic drug most commonly used in treatment of diabetes mellitus type 2 (T2D). Adsorptive stripping voltammetric method using carbon black – hydrated ruthenium dioxide – Nafion modified glassy carbon electrode (CB‐RuO₂‐Nafion GC electrode) have been developed for metformin determination in pharmaceutical formulations. By using ruthenium dioxide, electrode's lifespan was extended to at least 3 weeks (change of metrological parameters estimated as 3–4 %) what is an excellent result concerning other solutions previously described in the literature. Moreover the fabrication of the sensor is simple and fast. Deposition step was carried out at the potential 0 mV for 15 s. The best results were obtained in 0.05 M acetate buffer (pH 4.6). Important aspect was fixed MET : Cu(II) ratio equal to 1 : 8, otherwise linear dependence between register current and MET concentration could not be obtained. In addition, a significant improvement in the parameters of the calibration curve was obtained. Limit of detection was equal to 0.7 μM. Developed method was successfully applied in analysis of 2 pharmaceuticals products and in wastewater and river water. Accuracy of the method was estimated using recoveries, which were in the range 101–110 %. In order to adapt developed system into hydrodynamic conditions, amperometry in hydrodynamic transport conditions and flow injection analysis (FIA) measurements have been conducted. Conducted FIA measurements prove that developed method has potential for application in automized flow systems without frequent calibration.     

Towards future reference systems for GM analysis

Despite the fact that the measurement unit for the quantification of GMOs in food and feed products has not yet been unambiguously agreed upon in Europe, international trade requires reliable GMO analysis measuring comparably the GMO content of products. The two reference systems, based either on mass fractions or on copy number ratios, and their metrological traceability chains are presented and discussed. It is concluded that, properly established and expressed, measurement results in copy number ratios can provide a metrologically sound reference system. In this case, certified reference materials used for calibration and quality control can be independent of each other and the uncertainty derived from calibration can correctly be included in the overall uncertainty of the GMO measurement. However, further efforts are required to establish this metrological system.     

Strategies implemented at LNE to establish the traceability of environmental measurements

LNE is actively involved in the development of reference procedures in the domains of organic and inorganic chemistry and in gas analysis. Moreover, production of certified reference materials (CRMs), certification of calibration standards, and providing reference values for proficiency testing schemes (PTS) are fields well settled to ensure the traceability of measurements in environmental monitoring. The paper presents some representative examples of these activities recently realised in our laboratory. Presented at BERM-11, October 2007, Tsukuba, Japan.     

Metrological traceability chain for PCBs: I.N.Ri.M. activity

Metrology in chemistry has its own features, which distinguish it from classical metrology: due to the lack of primary methods applicable in routine measurements, metrological traceability of measurement results can be achieved by using in a proper way suitable certified reference materials (CRMs), which can assure a direct relation to a reference. This article deals with the activity of the Italian National Institute of Metrological Research (Istituto Nazionale di Ricerca Metrologica—I.N.Ri.M.) on the analysis of various polychlorinated biphenyls congeners in organic solution by means of gas-chromatography coupled with mass spectrometry. The metrological traceability approach in the quantification step is pursued via calibration solutions prepared by gravimetrically diluting a CRM. The uncertainty for the calibration solutions was evaluated taking into account all the relevant contributions.     

气相分子吸收光谱仪的计量校准方法

建立一种科学合理且可操作性强的气相分子吸收光谱仪校准方法。从仪器的工作原理及结构入手,对该类仪器提出了检出限、线性相关系数、定量重复性等性能评价参数。利用国家相关标准物质对其检出限的测量不确定度进行了评定,统一了校准方法,有力地保证了测量数据的准确性、溯源性。对计量技术机构开展该类仪器的校准工作规范的制定有一定的指导意义。     

浅谈便携式余氯分析仪的校准

对便携式余氯分析仪提出了计量性能要求及校准方法,并验证了方法的可行性,对计量检定机构开展校准工作及今后规程的制定有一定的指导意义.     

The future demand for geological reference materials

Geological RMs (G-1 and W-1) were introduced in 1951 for the purpose of validating the accuracy of silicate rock analysis by dc arc spectrography. Since then the introduction of an array of other spectrographic methods has greatly enhanced research into geological processes. The range of elements that could be determined was expanded, and the detection limits for measurement was lowered repeatedly through the years. The development and use of reference materials was critically important in supporting this rapid expansion of geological research. Essentially, all RMs are of importance to the geosciences community since G-1 and W-1 have been prepared and distributed by national geological institutions, first by the USGS or the CRPG, rather than by national metrology institutions. These geological institutions are not yet certifying their RMs according to ISO Guides. The International Association of Geoanalysts (IAG) is seeking to meet this higher metrological requirement. Since the inception of the IAG certification program in 2003, five powdered silicate rock materials have been issued to meet the demand with respect to calibration, method validation, traceability, etc. for whole rock major and trace element analysis. The introduction of microanalytical techniques nearly decades ago and the more recent advent of MC-ICP-MS have become new driving forces in geochemical research. The first opened the possibility of performing in situ elemental composition studies at the ??m scale. The second led to the discovery of small isotope composition variations of mass- and non-mass-dependent processes in ??non-traditional?? stable isotopes (e.g., Fe, Cu, Zn, Mo, W, and Hg) through cosmo- and geochemical processes. Coupling the two techniques expands in situ analysis to isotopic studies. These developments have created great demand for (certified) RMs for both isotope ratio and microanalytical measurements for the geochemical community that is not yet being met. Homogeneity at a ??m scale and unmatched matrices of the natural minerals or synthetic doped glasses hamper the progress in certification of RMs for the microanalytical measurement community. A challenge for the production of isotope RMs is to prepare an RM solution with an isotopic composition similar to the natural systems under investigation. Refined cadmium and nickel metals, for example, have fractionated isotopic compositions far above the range observed in natural systems of interest. Yet, the calibration RM cannot fulfill its purpose when the uncertainty of its isotopic composition exceeds that of the unknowns being measured against it. In this regard, the IAG has recently certified a calibration solution for the determination of Os isotopic ratios. It is also working through member organizations, USGS, and MPI for Geochemistry (Mainz) to develop appropriate microanalytical standards. In addition to these current and future challenges, establishing metrological traceability of geological reference materials in the absence of starting points developed by national metrology institutions is a major issue that needs attention in all future certifications.     

The use of certified reference materials in the Romanian traceability scheme

 For ensuring the traceability and uniformity of measurement results, the main objectives of national metrology programmes in chemistry are to calibrate and verify measuring instruments, to evaluate the uncertainty of measurement results and to intercompare the analytical results, etc. The concept of traceability has developed recently in chemical measurements, thus, an attempt to implement the principles of metrological traceability especially by appropriateness calibration using composition certified reference materials (CRMs) is underlined. Interlaboratory comparisons are also a useful response to the need for comparable results. The paper presents some aspects and practices in the field of spectrometric measurement regarding the metrological quality of the traceability by calibrating the instruments using suitable and reliable CRMs. The uncertainty of results, as a measure of the reliability that can be placed on them, has been adequately described in different documents and, as a consequence, some examples of evaluating the measurement uncertainty are described. The relationship between uncertainty and traceability, as two fundamental concepts of metrology which are intimately linked, is underlined. Received: 12 November 1999 / Accepted: 10 December 1999     

Assuring the reliability of mass spectrometry for the routine determination of traces of doping in horse-urine

Summary This paper describes an analytical method using a nuclear-related technique for the detection of forbidden doping substances in the urine of race horses. The proposed method, adapted from the Méthode Alcaline Sur C-18 developed by the French Laboratoire de Contr?le Antidopage, is based on gas chromatography separation followed by mass spectrometry (GC-MS). The method was validated for caffeine, identified as the most frequent doping substance in the Brazilian horseracing activity. This validation is also a major requirement to achieve ISO/IEC 17025 laboratory accreditation. The validation has led to several metrological challenges because the decisions are largely based on qualitative results (“false-positive” and/or “false-negative”) and the degree of accuracy, as well as the traceability had to be determined in the absence of certified matrix reference materials.     

Inter-laboratory comparisons: Determination of actinides in excreta

Inter-laboratory tests are a means of assessing the analytical coherence of medical laboratories. In radiotoxicology, this kind of exercise makes it possible to keep up with laboratory know-how and with the evolution and relative performances of analytical techniques (precision and reproducibility). However, the goal of the laboratories taking part in these annual exercises is not only to check the accuracy of their results. The analytical discussions and the chance to compare experiences enrich the group's general competence.French biologists have been organizing annual radiotoxicology intercomparison exercises since 1978. The exercises are carried out within the framework of a working group (GT1) operating under the aegis of the French Atomic Energy Commission's (CEA) Medical Coordinator. Using reports and diagrams which present the results obtained by the participants in the form of syntheses, the authors describe how the exercises for determining actinides in excreta (urine and faeces) are organized, how the results are evaluated in terms of the analytical methods used, and the improvements made in analytical and metrological performance.Up until 1985, these exercises were limited to French laboratories. Since then, the exercises have acquired an international dimension, opening up to include interested foreign radiochemists, initially from European laboratories, and now from laboratories worldwide. At the present time, 35 laboratories representing 9 countries take part regularly in these intercomparison exercises.     

Neutron activation analysis: A primary method of measurement

Neutron activation analysis (NAA), based on the comparator method, has the potential to fulfill the requirements of a primary ratio method as defined in 1998 by the Comité Consultatif pour la Quantité de Matière — Métrologie en Chimie (CCQM, Consultative Committee on Amount of Substance — Metrology in Chemistry). This thesis is evidenced in this paper in three chapters by: demonstration that the method is fully physically and chemically understood; that a measurement equation can be written down in which the values of all parameters have dimensions in SI units and thus having the potential for metrological traceability to these units; that all contributions to uncertainty of measurement can be quantitatively evaluated, underpinning the metrological traceability; and that the performance of NAA in CCQM key-comparisons of trace elements in complex matrices between 2000 and 2007 is similar to the performance of Isotope Dilution Mass Spectrometry (IDMS), which had been formerly designated by the CCQM as a primary ratio method.