Traceable Reference Materials Research Articles

Step Change in Improving the Accuracy of Nitrous Oxide Reference Materials for Underpinning Atmospheric Composition Measurements.

We have employed a new approach to quantify the amount fraction of nitrous oxide in a synthetic air matrix gas used to prepare high-accuracy reference materials of the same component. Until now, this was the largest contributor to the measurement uncertainty of nitrous oxide in air reference materials at atmospheric amount fractions (∼330 nmol mol-1), as identified in a recent international comparison. A novel preconcentration method has resulted in a measurement of 363 pmol mol-1 of nitrous oxide in a synthetic air matrix gas with an expanded uncertainty of 27 pmol mol-1. This represents a significant breakthrough as using these developments with an optimized dilution hierarchy (to minimize the gravimetric uncertainty) promises to result in SI traceable reference materials with expanded uncertainties as low as 0.032% relative (k = 2). This supports the World Meteorological Organization-Global Atmosphere Watch network compatibility goal for underpinning atmospheric observations.

Growth and characterization of gold nanoislands & quantum dots on marker-based SiO2/Si substrate for SEM resolution intercomparison studies

A scanning electron microscope (SEM) is the powerhouse tool of nanoscience & nanotechnology and the high resolution is one of the important parameters that decide the instrument’s quality. The reference materials (RM) like gold nanoislands or tin spheres on carbon substrate separated by a nanogap are often used to get the practically attainable resolution of the SEM instrument. Such RM contains millions of gold nanoislands and nanogaps but all of these RMs are non-traceable. Hence the practically obtained high resolution of an SEM remains doubtful unless and until intercompared with traceable RM. The development of a new SEM resolution test specimen sample with localized markers for the identification of a traceable critical dimension of a nanogap on a user-friendly SiO2/Si or Si3N4/Si chip is reported here. First, thin films of gold with thickness < 5 nm (ultra-thin film) and of about 10 nm (thin film) were deposited on a pre-patterned marker SiO2/Si chip to form the gold nanoparticles (Au NPs) by thermal annealing technique. The high-resolution SEM images show the formation of gold quantum dots (Au QDs) (average particle diameter <D> ∼ (18 ± 1) nm and average gap between two particles <S> ∼ (6 ± 1) nm) and gold nano-islands (Au NIs) (<D> ∼ (101 ± 3) nm and <S> ∼ (104 ± 2) nm). FESEM images show densely packed nano-islands exhibiting spherical geometry which is explained using dewetting mechanism followed by Ostwald ripening and coalescence resulting formation of Au QDs and Au NPs. Further, these marker-based resolution test chips can be used in inter or intra-comparison studies due to pre-patterned markers. First-time development of QDs on marker chip gives access to a particular nanogap among the millions of nanogaps present on the substrate, this type of RM will be used for inter-laboratory comparison studies in the future.

Some pitfalls in the uncertainty evaluation of isotope delta reference materials

The Guide to the Expression of Uncertainty in Measurement (GUM) provides a framework for evaluating analytical data and characterizing their dispersion in a consistent manner. This is of eminent importance in the case of reference materials and their recommended values that are used for calibration of further measurements. The proper propagation of uncertainties for those data is essential. Guidance is provided in the GUM on how to calculate the combined standard uncertainty for a mean value or central value based on multiple individual measurements including their calibration uncertainty. However, according to published data, the guidance provided by GUM is not always properly applied in practice. Several published studies show calculated uncertainties much lower than those of input quantities. This may be caused by improper handling of the propagation of uncertainty components, thereby breaking the traceability chain for reported values. A simple check method using conventional statistical means is proposed to detect and to avoid such mistakes related to calibration uncertainties. It is intended to help to ensure a proper uncertainty propagation, to maintain a system of reliable and traceable reference materials. A spreadsheet is provided for the implementation of such a check. Example calculations for published data are presented.

Metrological generation of SI-traceable gas-phase standards and reference materials for (semi-) volatile organic compounds

EN 16516 sets specifications for the determination of emissions into indoor air from construction products. Reliable, accurate and International System of Unit (SI)-traceable measurement results of the emissions are the key to consumer protection. Such measurement results can be obtained by using metrologically traceable reference materials. Gas-phase standards of volatile organic compounds (VOCs) in air can be prepared by a variety of dynamic methods according to the ISO 6145 series. However, these methods are not always applicable for semi-VOCs (SVOCs) due to their high boiling point and low vapour pressure. Therefore, a novel dynamic gas mixture generation system has been developed. With this system gas-phase standards with trace level VOCs and SVOCs in air can be prepared between 10 nmol mol−1 and 1000 nmol mol−1. The VOCs and SVOCs in this study have normal boiling points ranging from 146 °C to 343 °C. Metrologically traceable reference materials of the gas-phase standard were obtained by sampling of the VOC gas-phase standard into Tenax TA® sorbent material in SilcoNert® coated stainless steel tubes. Accurately known masses between 10 ng and 1000 ng per VOC were sampled. These reference materials were used to validate the dynamic system. Furthermore, the storage and stability periods of the VOCs in the reference materials were determined as these are crucial characteristics to obtain accurate and SI-traceable reference materials. In a round robin test (RRT), the reference materials were used with the aim of demonstrating the feasibility of providing SI-traceable standard reference values for SVOCs for interlaboratory comparison purposes. Based on the results from the validation, the storage and stability studies and the RRT, gas-phase standards and reference materials of VOCs and SVOCs with relative expanded uncertainties between 5% and 12% (k = 2) have been developed. These reference standards can be used as calibrants, reference materials or quality control materials for the analysis of VOC emissions.

Photocatalytic activity of nanoparticles: the development of the standardized measurement for physiological conditions

Recently a new International Standard for testing nanomaterial photocatalytic activity under physiological conditions was issued by Technical Committee 229 (Nanotechnologies) of the International Organization for Standardization (ISO 20814:2019 Nanotechnologies-Testing the photocatalytic activity of nanoparticles for NADH oxidation). The document offers a robust, high throughput photocatalytic assay using a bio-compatible indicator nicotinamide amide dinucleotide (NAD) and provides a screening tool to gauge nanomaterial potency for phototoxicity. This paper describes the measurement principles behind this assay, the scope of the standard and its validation through an interlaboratory comparison study using a traceable standard reference material (SRM 1898).

Bilateral comparison of primary reference materials (PRMs) containing methanol, ethanol and acetone in nitrogen

A range of oxygenated volatile organic compounds (OVOCs) are present in the atmosphere as a result of direct emissions and as products of atmospheric oxidation. Long-term measurements are important to understand changes to these emission sources and atmospheric oxidation processes. Accurate and stable traceable gaseous primary reference materials are needed to underpin rigorous quality assurance and quality control at monitoring stations such as those organised by the World Meteorological Organization Global Atmosphere Watch (WMO-GAW) programme. The development of a capability for providing traceable primary reference materials (PRMs) of OVOCs is of paramount importance due to the increasing prevalence of these compounds in the urban atmosphere and also because there is currently no Central Calibration Laboratory (CCL) for these components within the WMO-GAW programme. This EURAMET bilateral comparison demonstrates the measurement compatibility (≤ 3%) for three OVOCs (methanol, ethanol and acetone) at nominally 5 µmol mol−1 between two National Metrology Institutes: the National Physical Laboratory (NPL), UK and the Van Swinden Laboratorium (VSL), the Netherlands. The comparison shows that a gravimetric method for value assignment is applicable to acetone but that a more complicated procedure must be employed to value assign methanol and ethanol due to corrections for adsorption effects, which can be as large as 10 % of the nominal value. This work demonstrates the importance of making appropriate corrections to ensure the accuracy of these reference materials. NPL and VSL used different approaches to make these corrections providing confidence and independent verification. This work supports new calibration and measurement capabilities for methanol, ethanol and acetone in the range of 1 μmol mol−1 –10 μmol mol−1 with expanded uncertainties of 6.9 % (3 %), 7.3 % (3 %) and 1.7 % (2 %) for NPL (VSL), respectively, to be realized in the key comparison database and supports the development of the required traceability infrastructure to underpin long-term global measurements of these OVOCs.

Preparing Laboratories for Interconnected Health Care.

In an increasingly interconnected health care system, laboratory medicine can facilitate diagnosis and treatment of patients effectively. This article describes necessary changes and points to potential challenges on a technical, content, and organizational level. As a technical precondition, electronic laboratory reports have to become machine-readable and interpretable. Terminologies such as Logical Observation Identifiers Names and Codes (LOINC), Nomenclature for Properties and Units (NPU), Unified Code for Units of Measure (UCUM), and SNOMED-CT can lead to the necessary semantic interoperability. Even if only single “atomized” results of the whole report are extracted, the necessary information for correct interpretation must be available. Therefore, interpretive comments, e.g., concerns about an increased measurement uncertainty must be electronically attached to every affected measurement result. Standardization of laboratory analyses with traceable standards and reference materials will enable knowledge transfer and safe interpretation of laboratory analyses from multiple laboratories. In an interconnected health care system, laboratories should strive to transform themselves into a data hub that not only receives samples but also extensive information about the patient. On that basis, they can return measurement results enriched with high-quality interpretive comments tailored to the individual patient and unlock the full potential of laboratory medicine.

Expansion of SI Traceable Reference Materials by Quantitative Nuclear Magnetic Resonance Spectroscopy

Expansion of SI Traceable Reference Materials by Quantitative Nuclear Magnetic Resonance Spectroscopy

Estimating Uncertainty in Wisconsin's Evidential Breath Alcohol Measurements.

Breath alcohol measurement accuracy and precision quantification is a critical component of impaired driving prosecution and is required for laboratory accreditation. The Chemical Testing Section of Wisconsin's Department of Transportation conducted a bottom-up study to quantify uncertainty of breath alcohol measurements conducted on Intoximeter's EC/IR II instrument. After an exercise in combined uncertainty source identification, individual input values were either reported from National Institute of Standards and Technology traceable reference materials or quantified using instrument data from 2014 to 2018. From input values, an expanded uncertainty value of 4.58 × 10-3 g/210L was found that encompasses all identified sources with a 95% confidence interval.

Determining modified reaction parameters for the real-time measurement of BTEX in biogas and nitrogen using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS)

The increasing demand for high-quality biogas and the reduction of reliance on natural gas have driven the need for a well-defined framework to ensure conformity and quality of biogas by the introduction of traceable reference materials and methods across the community. Furthermore, there is a great need to quantify critical trace impurities in biogas. Here, we perform real-time measurements on reference gas standards containing trace hydrocarbons in biogas that are traceable to the international system of units using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS). There are limited data on reaction rate constants in biogas matrices for SIFT-MS, and here we use the traceable gas standards to determine and compare the reaction rate constants of trace hydrocarbons in biogas and nitrogen. Here, we modify SIFT-MS constants for biogas avoiding the current 30 % bias and prevent the overestimation in the concentration of hydrocarbon amount fractions.

Conventional and new traceability schemes of organic standards for safe water supply in Japan

Metrological traceability to the International System of Units (SI) is required to ensure reliability of analytical results. For this purpose, SI-traceable standard solutions of respective analytes are essential for common analytical methods such as chromatography. However, it is not so easy to fulfill demands due to the existence of a vast number of targets, especially in the case of organic analysis. Because high-purity organic materials which are raw materials of standard solutions must be characterized by compound-independent methods, the mass balance approach (subtraction method) and the primary methods of measurement (e.g. the freezing point depression method and titrimetry) are used. Recently, quantitative NMR (qNMR) has been popularized.The National Metrology Institute of Japan, the National Institute of Advanced Industry, Science and Technology (NMIJ/AIST) has been supplying many types of reference materials including high-purity organic materials and organic standard solutions. In 2015, the demand of traceable reference materials for drinking water analyses rose by an amendment of a notification under the Waterworks Act of Japan. In this manuscript, NMIJ’s efforts such as supplying certified reference materials and providing calibration services in this field are outlined. Among them, direct characterization of multi-components standard solutions by qNMR/chromatography or post-column reaction gas chromatography is an efficient approach to realize new traceability schemes without the step of a purity assessment of each reference material.

Evaluation of droplet digital PCR and next generation sequencing for characterizing DNA reference material for KRAS mutation detection

KRAS gene mutations are predictive markers of non-response to anti-epidermal growth factor receptor. An increasing number of techniques are being developed to detect KRAS mutations. To obtain consistent and comparable results, a traceable reference material (RM) is necessary for validation the routinely used method. However, a lack of reference methods is a main impediment for deriving traceability and measurement comparability. In this study, droplet digital PCR (ddPCR) and next generation sequencing (NGS) were evaluated. No cross- reactivity was detected with any of the probe by ddPCR. The measured fraction of KRAS mutant allele by ddPCR and NGS agreed with the prepared value by gravimetrical dilution (concordance (k) >0.95 and >0.93 for ddPCR and NGS, respectively). The reliable limit of quantification (LOQ) was 0.1% and 1% for ddPCR and NGS, respectively. In conclusion, the validated ddPCR and NGS are suitable to characterize the KRAS RM due to the high specificity and accuracy. Verification of the LOD of three commercial kits by using the NIM-KRAS-8 RM showed that the LOD was inconsistent with the claimed LOD of the kits (1%) for some assays. This indicates a traceable RM was important for setting up the criteria regarding the LOD for the commercial kit.

Analytical barriers in clinical B-type natriuretic peptide measurement and the promising analytical methods based on mass spectrometry technology.

B-type natriuretic peptide (BNP) is a circulating biomarker that is mainly applied in heart failure (HF) diagnosis and to monitor disease progression. Because some identical amino acid sequences occur in the precursor and metabolites of BNP, undesirable cross-reactions are common in immunoassays. This review first summarizes current analytical methods, such as immunoassay- and mass spectrometry (MS)-based approaches, including the accuracy of measurement and the inconsistency of the results. Second, the review presents some promising approaches to resolve the current barriers in clinical BNP measurement, such as how to decrease cross-reactions and increase the measurement consistency. Specific approaches include research on novel BNP assays with higher-specificity chemical antibodies, the development of International System of Units (SI)-traceable reference materials, and the development of structure characterization methods based on state-of-the-art ambient and ion mobility MS technologies. The factors that could affect MS analysis are also discussed, such as biological sample cleanup and peptide ionization efficiency. The purpose of this review is to explore and identify the main problems in BNP clinical measurement and to present three types of approaches to resolve these problems, namely, materials, methods and instruments. Although novel approaches are proposed here, in practice, it is worth noting that the BNP-related peptides including unprocessed proBNP were all measured in clinical BNP assays. Therefore, approaches that aimed to measure a specific BNP or proBNP might be an effective way for the standardization of a particular BNP form measurement, instead of the standardization of "total" immunoreactive BNP assays in clinical at present.

Peptide selection for the quantification of P-III-NP in human serum by mass spectrometry.

Procollagen III amino-terminal propeptide (P-III-NP) is currently monitored in human doping control as a biomarker for growth hormone administration and also in clinical diagnostics using immunoassays. Drawbacks to this approach have been highlighted and research is ongoing to develop a mass spectrometric method to complement these methods. However, a lack of traceable reference material, the presence of post-translational modifications (PTMs), and small blood concentration complicate the development of targeted analytical methods for P-III-NP quantification. Tryptic digest products of P-III-NP were assessed by liquid chromatography/mass spectrometry (LC/MS). In silico digestion was used to predict P-III-NP peptides for MS analysis; however, these excluded PTMs. With a priori knowledge of PTMs, we associated experimental P-III-NP peptides with those derived by in silico digestion. Synthesized P-III-NP peptides, hT1 (human) and T5 (human/bovine), were used to develop sensitive micro- and nano-flow LC/MS methods to analyse P-III-NP originating from human serum semi-quantitatively. P-III-NP peptides, T1 and T5, were identified using high-resolution accurate MS (HRAMS). PTMs modified the mass of observed peptides. N-terminal pyroglutamation (pE) in T1 and several hydroxylated prolines (hP) in T5 (G-X-hP motif) were observed. With PTM, hT1 and T5 were observed in a digest of immuno-captured P-III-NP by LC/MS. Using a semi-quantitative approach, hP-III-NP at basal concentrations of 2ng/mL (50pmol) could be estimated from a 200-μL sample volume. Consideration of PTMs is needed to identify P-III-NP peptides produced by digestion with trypsin. The information presented here now gives the most appropriate peptide sequences for synthesizing suitable reference materials required for quantification of human P-III-NP in blood and evidences methodology that is sufficiently sensitive to develop a quantitative method.

FAST AND SIMPLE METHOD FOR SIMULTANEOUS DETERMINATION OF BENZOIC ACID AND ACESULFAME-K IN SOFT DRINKS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY-DIODE ARRAY DETECTOR: METHOD VALIDATION AND UNCERTAINTY EVALUATION

Classified as food additives, the use of benzoic acid and acesulfame K to preserve foods is finite due to health and environmentreason.In this study, anefficient and fast method for simultaneous determination of benzoic acid and acesulfame-K in soft drinks was validated using high performance liquid chromatography with diode array detector (HPLC-DAD) on a C18 column. The method showed results satisfaction as the coefficient determination for benzoic acid and acesulfame-K were 0.9998 and 0.9991 respectively. The LOD for both compounds found at 0.02 mg/kg and the LOQ were found at 0.07 and 0.06 mg/kg for benzoic acid and acesulfame-K respectively. The recovery studies proved that the method has a good recovery ranging from 96103% for both benzoic acid and acesulfame-K with %RSD varies from 1.6 - 4.6% at different concentrations. The validated method then applied to the inter-laboratory comparison sample conducted by the National Quality Control Laboratory for Drug and Food (NQCLDF), Indonesia, using traceable standard reference materials. Uncertainty evaluation using bottom-up approach showed that the method has reasonable uncertainty value with uncertainty budget derived from weighing process, recovery studies, method precision, calibration curve and standard solution. The uncertainty value (k=2, in confidence level 95%) for benzoic acid was found to be 4% at reported concentration of 343 mg/kg and for acesulfame-K was found to be 6.5% at reported concentration of 195 mg/kg. In conclusion, the validated method offered a simple and fast method, as well as economical reagents consumption indicating its possible application as an alternative method for a routine analysis.

A traceable reference for direct comparative assessment of total naphthenic acid concentrations in commercial and acid extractable organic mixtures derived from oil sands process water

ABSTRACTThe advantage of using naphthenic acid (NA) mixtures for the determination of total NA lies in their chemical characteristics and identification of retention times distinct from isobaric interferences. However, the differing homolog profiles and unknown chemical structures of NA mixtures do not allow them to be considered a traceable reference material. The current study provides a new tool for the comparative assessment of different NA mixtures by direct reference to a single, well-defined and traceable compound, decanoic-d19 acid. The method employed an established liquid chromatography time-of-flight mass spectrometry (LC/QToF) procedure that was applicable both to the classic O2 NA species dominating commercial mixtures and additionally to the O4 species known to be present in acid extractable organics (AEOs) derived from oil sands process water (OSPW). Four different commercial NA mixtures and one OSPW-derived AEOs mixture were comparatively assessed. Results showed significant difference among Merichem Technical, Aldrich, Acros, and Kodak commercial NA mixtures with respect to “equivalent to decanoic-d19 acid” concentration ratios to nominal. Furthermore, different lot numbers of single commercial NA mixtures were found to be inconsistent with respect to their homolog content by percent response. Differences in the observed homolog content varied significantly, particularly at the lower (n = 9–14) and higher (n = 20–23) carbon number ranges. Results highlighted the problem between using NA mixtures from different sources and different lot numbers but offered a solution to the problem from a concentration perspective. It is anticipated that this tool may be utilized in review of historical data in addition to future studies, such as the study of OSPW derived acid extractable organics (AEOs) and fractions employed during toxicological studies.

Development and evaluation of a suite of isotope reference gases for methane in air

Abstract. Measurements from multiple laboratories have to be related to unifying and traceable reference material in order to be comparable. However, such fundamental reference materials are not available for isotope ratios in atmospheric methane, which led to misinterpretations of combined data sets in the past. We developed a method to produce a suite of synthetic CH4-in-air standard gases that can be used to unify methane isotope ratio measurements of laboratories in the atmospheric monitoring community. Therefore, we calibrated a suite of pure methane gases of different methanogenic origin against international referencing materials that define the VSMOW (Vienna Standard Mean Ocean Water) and VPDB (Vienna Pee Dee Belemnite) isotope scales. The isotope ratios of our pure methane gases range between −320 and +40 ‰ for δ2H–CH4 and between −70 and −40 ‰ for δ13C–CH4, enveloping the isotope ratios of tropospheric methane (about −85 and −47 ‰ for δ2H–CH4 and δ13C–CH4 respectively). Estimated uncertainties, including the full traceability chain, are &lt; 1.5 ‰ and &lt; 0.2 ‰ for δ2H and δ13C calibrations respectively. Aliquots of the calibrated pure methane gases have been diluted with methane-free air to atmospheric methane levels and filled into 5 L glass flasks. The synthetic CH4-in-air standards comprise atmospheric oxygen/nitrogen ratios as well as argon, krypton and nitrous oxide mole fractions to prevent gas-specific measurement artefacts. The resulting synthetic CH4-in-air standards are referred to as JRAS-M16 (Jena Reference Air Set – Methane 2016) and will be available to the atmospheric monitoring community. JRAS-M16 may be used as unifying isotope scale anchor for isotope ratio measurements in atmospheric methane, so that data sets can be merged into a consistent global data frame.

Acceptance criteria for environmental radionuclide measurement traceability

It is insufficient for laboratories to claim measurement traceability simply through the possession of standard reference materials, traceable reference materials, or instrument calibrations because of the potential for improper use. Independent testing of measurement traceability is the only mean by which it is truly demonstrated. The National Institute of Standards and Technology’s (NIST) radiochemistry intercomparison program evaluates environmental measurement traceability and it must have the highest confidence in its reference values. Verification measurements provide NIST with confidence in the reference values. However, it is proposed that a simple t test based on the PT test results be used to independently evaluate the accuracy of the reference values.

Strategies for building reference standards for autoantibodies.

Producing robust, certified, traceable reference material for autoantibody testing is a vital element in maintaining the validity of results that are generated in the daily clinical laboratory routine. This is a huge challenge because of the high number of variables involved in the detection and measurement of the autoantibodies. The production of such materials is time consuming and needs rigorous attention to detail; this is best achieved by an overarching independent body who will oversee the process in a “not for profit” manner. Much effort has been made to build international standards for quantitative and qualitative assays based on monoclonal antibodies, obtained from affinity purification and plasmapheresis. The big challenge is to respect individual differences in immune response to the same antigen. A promising ongoing initiative is the construction of pools with monospecific samples from different individuals.

The design and implementation of regional creatine kinase/lactate dehydrogenase detection standardization

Objective To design and implement the standardization scheme of creatine kinase(CK)/lactate dehydrogenase(LDH) detection based on the present situation of clinical laboratory in Jiaxing, and attempt to reduce the imprecision and bias of the results in different clinical laboratories, obtain the traceable results. Methods According to the requirements of traceability in clinical laboratory, the CK/LDH standardization scheme was explored in Jiaxing from 2012, October to 2013, February,CK/LDH national reference material GBW09167, GBW09168 and serum pool were as samples for accuracy verification and impression in 33 local hospitals; then the reference materials GBW(E)03061 was as calibrator, while the GBWE03060 was performed as calibration verification material during the tests, the SOP for calibration made by the clinical quality control center was operated in calibration; as a result a scientific, practical standard scheme was developed. Results The equipment of clinical labrotories in Jiaxing are all imported, the laboratory management is well.However the bias of CK is -7%-12% and the bias of LDH is above -22%-15%. And then the standardization scheme was implemented in 6 Laboratories in which CV was less than 2%, and high-quality data of 5 laboratories are as follows:imprecision of CK and LDH in different labs were reduced from 4.95%-6.55% to 1.81%-2.33% and 5.75%-11.68% to 1.39%-1.80% individually， bias for CK is reduced from -0.84 %-6.23% to -0.15%-2.44% ; while in lactate dehydrogenase test, the bias is decreased from -10.18%-0.34% to -3.07%-0.58% . Conclusion Using the commutable and traceable reference material as calibrator, strengening the laboratory management such as making a calibration SOP will be a effective methods to realize the standardization in measurement.（Chin J Lab Med，2014,37：947-950） Key words: Creatine kinase; Lactate dehydrogenases; Reference standards; Laboratories, hospital; Research design