Candidate Reference Material Research Articles

Practical application of microsphere samples for benchmarking a quantitative phase imaging system.

Quantitative phase imaging (QPI) provides an approach for monitoring the dry mass of individual cells by measuring the optical pathlength of visible light as it passes through cells. A distinct advantage of QPI is that the measurements result in optical path length quantities that are, in principle, instrument independent. Reference materials that induce a well‐defined optical pathlength shift and are compatible with QPI imaging systems will be valuable in assuring the accuracy of such measurements on different instruments. In this study, we evaluate seven combinations of microspheres embedded in index refraction matching media as candidate reference materials for benchmarking the performance of a QPI system and as calibration standards for the optical pathlength measurement. Poly(methyl metharylate) microspheres and mineral oil were used to evaluate the range of illumination apertures, signal‐to‐noise ratios, and focus positions that allow an accurate quantitative optical pathlength measurement. The microsphere‐based reference material can be used to verify settings on an instrument that are suitable for obtaining an accurate pathlength measurement from biological cells. The microsphere/media reference material is applied to QPI‐based dry mass measurements of a population of HEK293 cells to benchmark and provide evidence that the QPI image data are accurate.

Development of a genomic DNA reference material for Salmonella enteritidis detection using polymerase chain reaction

Several rapid methods based on nucleic acids can detect foodborne pathogens, such as Salmonella spp. However, a common reference that enables metrological traceability among measurement results is not available. Reference materials (RM) are thus key to guarantee methodological comparability. This study developed a candidate genomic DNA reference material for Salmonella enteritidis quantification to establish performance conditions and reference values for normalized RM production. The growth of Salmonella enteritidis ATCC® 13076 in Rappaport Vassiliadis selective medium was characterized, and we optimized a method of DNA extraction using cetrimonium bromide (CTAB) and LiCl.In a first stage six concentrations of DNA were prepared with and without yeast RNA (40 ng/μL) to evaluate its effect as a stabilizer in terms of homogeneity and short-term stability. Based on the findings, in a second stage two DNA concentrations were prepared and a reference value with its uncertainty was assigned based on the results of characterization, homogeneity, and stability studies using digital polymerase chain reaction and the gene targets, invA, ttr, and hilA. The material was stable for 9 months at 4 °C, with a expanded uncertainty contribution range of 11%–14%. The novel candidate RM is the first to be developed nationwide and will improve the quality of measurements in the area of food safety.

Specific risks of false decisions in conformity assessment of a substance or material with a mass balance constraint – A case study of potassium iodate

A methodology for the Bayesian evaluation of total specific risks of false decisions on conformity of a substance or material due to measurement uncertainty was developed using Monte Carlo simulations, taking into account the mass balance constraint of the data. As a case study, the measurement results (measured values and associated measurement uncertainty) obtained for testing a potassium iodate batch, being considered as a candidate reference material of potassium iodate purity, were analyzed and discussed for different models of the prior probability density function and the likelihood function. Different scenarios of the risks related to determination of potassium iodate purity were studied, when the direct or indirect test method is applied, as well as when both are used simultaneously.

Development of a reference material for analysing naturally occurring radioactive material from the steel industry

Accurate measurement of naturally occurring radionuclides in blast furnace slag, a by-product of the steel industry, is required for compliance with building regulations where it is often used as an ingredient in cement. A matrix reference blast furnace slag material has been developed to support traceability in these measurements. Raw material provided by a commercial producer underwent stability and homogeneity testing, as well as characterisation of matrix constituents, to provide a final candidate reference material. The radionuclide content was then determined during a comparison exercise that included 23 laboratories from 14 countries. Participants determined the activity per unit mass for 226Ra, 232Th and 40K using a range of techniques. The consensus values obtained from the power-moderated mean of the reported participant results were used as indicative activity per unit mass values for the three radionuclides: A0(226Ra) = 106.3 (34) Bq·kg−1, A0(232Th) = 130.0 (48) Bq·kg−1 and A0(40K) = 161 (11) Bq·kg−1 (where the number in parentheses is the numerical value of the combined standard uncertainty referred to the corresponding last digits of the quoted result). This exercise helps to address the current shortage of NORM industry reference materials, putting in place infrastructure for production of further reference materials.

Development of a certified reference material for anti-β2-glycoprotein I IgG- commutability studies.

In this paper, we describe the steps followed for the development of a certified reference material for immunoglobulin G antibodies against β2-glycoprotein I (also known as apolipoprotein H). These steps include processing of the material, commutability, the impact of dilution, the appropriate reconstitution conditions, homogeneity and stability during transport and storage. We analysed 69 clinical samples from patients suffering from antiphospholipid syndrome with several commercial enzyme-linked immunosorbent assays (ELISA) purchased from in vitro diagnostic manufacturers. Analysis of the results indicated that the candidate reference material can be safely freeze-dried, and that the user should carefully follow the reconstitution instructions as small changes in e.g. temperature may have unwanted effects. The statistical analysis of the commutability studies indicated that the analytical response of the reference material upon dilution is similar to that of clinical samples, and that correlation between results may differ from assay to assay. Finally yet importantly, the presented and developed candidate reference material is commutable for most assays tested, homogeneous and stable. Immunoglobulin G antibodies against β2-glycoprotein I are associated with a higher risk of thrombosis and pregnancy complications. Their measurement is essential for the diagnosis and monitoring of antiphospholipid syndrome. These antibodies are detected by specific immunoassays, routinely used in clinical diagnostics, but various of these methods show enormous variability, in part due to the lack of a reference material.

Determination of glyphosate and AMPA in oat products for the selection of candidate reference materials

The use of reference materials (RMs) is critical for validating and testing the accuracy of analytical protocols. The National Institute of Standards and Technology (NIST) is in initial stages of developing a glyphosate in oats RM. The first aim of this study was to optimize and validate a robust method for the extraction and analysis of glyphosate and aminomethylphosphonic acid (AMPA). The optimized method was used to screen thirteen commercially available oat products to identify candidate RMs. Glyphosate was detected in all samples, with the highest glyphosate mass fraction of 1100 ng/g; lower levels were measured in grains from organic agriculture. AMPA was quantified in nine samples up to 40 ng/g. The findings of this study led to the identification of candidate RMs, with “high” and “low” glyphosate levels. A preliminary stability study determined that glyphosate is stable in oat material at room temperature for six months.

Passive immunisation of convalescent human anti-Zika plasma protects against challenge with New World Zika virus in cynomolgus macaques

Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin administered prior to time of challenge remained present only at very low levels 42 days post-challenge. Absence of de novo antibody responses in passively immunised macaques indicate sterilising immunity compared with naïve challenge controls that exhibited active ZIKV-specific IgM and IgG responses post-challenge. Demonstration that the presence of convalescent anti-ZIKV at levels of 400 IU/mL neutralising antibody protects against virus challenge provides a scientific framework for development of anti-ZIKV vaccines and facilitates regulatory approval.

Elucidation of Affecting Factors in the Analysis of Short-chain Chlorinated Paraffins Using a Candidate Reference Material

Elucidation of Affecting Factors in the Analysis of Short-chain Chlorinated Paraffins Using a Candidate Reference Material

The δ60/58Ni Values of Twenty‐Six Selected Geological Reference Materials

The high‐precision δ60/58Ni values of twenty‐six geological reference materials, including igneous rocks, sedimentary rocks, stream sediments, soils and plants are reported. The δ60/58Ni values of all samples were determined by double‐spike MC‐ICP‐MS (Nu Plasma III). Isotope standard solution (NIST SRM 986) and geological reference materials (BHVO‐2, BCR‐2, JP‐1, PCC‐1, etc.) were used to evaluate the measurement bias and intermediate precision over a period of six months. Our results show that the intermediate precision of Ni isotope determination was 0.05‰ (2s, n = 69) for spiked NIST SRM 986 and typically 0.06‰ for actual samples, and the δ60/58Ni NIST SRM 986 values were in excellent agreement with previous studies. Eighteen high‐precision Ni isotope ratios of geological reference materials are first reported here, and their δ60/58Ni values varied from −0.27‰ to 0.52‰, with a mean of 0.13 ± 0.34‰ (2s, n = 18). Additionally, SGR‐1b (0.56 ± 0.04‰, 2s), GSS‐1 (−0.27 ± 0.06‰, 2s), GSS‐7 (−0.11 ± 0.01‰, 2s), GSD‐10 (0.46 ± 0.06‰, 2s) and GSB‐12 (0.52 ± 0.06‰, 2s) could potentially serve as candidate reference materials for Ni isotope fractionation and comparison of Ni isotopic compositions among different laboratories.

Commutability of reference materials for alkaline phosphatase measurements

Commutability is a prerequisite when using a candidate reference materials (CanRMs) for calibration and trueness control of routine methods or for value transfer from the reference method to end-user calibrators of routine methods through a calibration hierarchy. The CanRMs include commercial general chemistry materials (GCs), enzyme trueness verification materials (ETVs), and secondary reference materials (SRMs). The commutability of CanRMs was evaluated based on the difference in bias and EP14-A3 to investigate their suitability for ALP measurement. A total of 44 fresh individual clinical samples (CSs) and the CanRMs were analyzed by six routine methods (validated methods) and by IFCC primary reference method (comparative method) for the determination of Alkaline Phosphatase (ALP). The commutability was performed based on IFCC working group recommendations for assessing commutability and analyzed according to EP14-A3 guide and difference in bias approach, respectively. The bias of the routine methods was assessed according to CLSI guidelines. The result of commutable materials obtained from the two evaluation approaches are not significantly different. It was observed that the routine methods with lower bias were associated with more commutable CanRMs. None of the CanRMs were suitable for use as commutable RMs. The findings of this study have a number of important implications for future practice.

LA-ICP-MS U[sbnd]Pb geochronology of wolframite by combining NIST series and common lead-bearing MTM as the primary reference material:Implications for metallogenesis of South China

Direct dating of W and WSn deposits by wolframite is more reliable relatively to gangue mineral and important for understanding their timing and genesis. However, such analysis still lacks of homogeneous wolframite standard recently. Due to containing considerable and variable common lead, and inhomogeneous in different grains, the wolframite sample of MTM, which is a promising candidate reference material proposed by previous studies, is not suitable as a primary standard for wolframite UPb dating by LA-ICP-MS using the normal normalization method as zircons. In this contribution, a modified normalization method is established for wolframite UPb dating, in which NIST612 or 614 and MTM are used for correction of PbPb and UPb ratios, respectively. Wolframite UPb dating are performed on the Langcun, Xihuashan, Piaotang, Shamai W or WSn deposits and the Baiganhu ore district, the obtained lower intercept 206Pb/238U ages are comparable with the ages from syngenetic molybdenite, cassiterite, muscovite and the genetically related granites, as well as wolframite by water vapor-assisted ns-LA-ICP-MS UPb dating method. The results of this analysis demonstrate that the robust age for W mineralization can be determined by LA-ICP-MS UPb dating of wolframite using this modified calibration method. Mineralization ages of 125–130 Ma by directly dating of metal minerals for the Langcun W, Jianfengpo Sn and large-size Xianglushan W deposits confirm that there exists an important WSn mineralization event in this period. The close temporal and spatial correlation indicates the granites and W-Cu-Mo-Pb-Zn-Sn mineralization have a genetic relationship with each other and are resulted from the same tectonic-magmatic-hydrothermal events during 140 to 120 Ma in South China.

Preparation of a reference material for crude oil trace elements: Study of homogeneity and stability

Trace elements can be found naturally in crude oil or can be added during the production process, transport, or storage. Due to the complexity of the determination of trace elements in crude oil, which is mainly accomplished using multi-element techniques, many reports have been published describing the optimization of instrumental parameters, the development of procedures for sample preparation, and new sample introduction devices. The goal of such research is to improve the sensitivity, precision, and accuracy of the measurements. In all the cases mentioned above, the use of reference materials (RMs) and certified reference materials (CRMs) is recommended to verify the accuracy of the new methods proposed. This paper describes the development of a natural-matrix reference material for quantification of vanadium, nickel, magnesium, sodium, calcium, strontium, and barium in crude oil. 3 kg of crude oil was processed and distributed into 115 units, each containing 20 g. The homogeneity and stability of the prepared reference material were investigated using atomic absorption spectrometry (AAS), inductively coupled plasma optical emission spectrometry (ICP OES), and inductively coupled plasma mass spectrometry (ICP-MS) techniques. The results were evaluated using standard univariate analysis of variance (ANOVA), regression analysis, and principal component analysis (PCA). Statistical evaluation of the data showed good homogeneity and stability of the candidate reference material under the conditions studied.

Development and characterization of reference materials for trace element analysis of keratinized matrices

Biomonitoring for human exposure to lead, arsenic, mercury, and other toxic metal(loid)s often relies on analyzing traditional biospecimens such as blood and urine. While biomonitoring based on blood and urine is well-established, non-traditional biospecimens such as hair and nails can offer the potential to explore past exposures as well as the advantages of non-invasive collection and ease of storage. The present study describes the production of four reference materials (NYS RMs 18-01 through 18-04) based on caprine horn, a keratinized tissue similar to human hair and nails, intended to serve as a resource for calibration, quality control, and method validation purposes. The elemental content and homogeneity of these candidate reference materials were characterized for 17 elements using inductively coupled plasma mass spectrometry (ICP-MS). Commutability between two or more of the NYS caprine horn RMs and human nails was established for 8 elements (Ba, Ca, Cr, Cu, Mn, Pb, Sr, and Zn) based on analysis by ICP-MS/MS and ICP-optical emission spectrometry. The development and optimization of an ICP-MS/MS instrumental method for the determination of 17 elements in keratinized tissues is described. The method was validated against three certified reference materials based on human hair showing good accuracy and method repeatability better than 25% for all analytes. This study also describes sample preparation issues and addresses common challenges including surface contamination, microwave digestion, matrix effects, and spectral interferences in inorganic mass spectrometry. New York State Department of Health Keratin Matrix Reference Materials. Graphical abstract.

A New Candidate Reference Material for Inorganic Arsenic and Arsenosugars in Hijiki Seaweed: First Results from an Inter-laboratory Study.

An inter-laboratory study was carried out to characterize a candidate hijiki seaweed for its concentrations of total arsenic and water-soluble arsenic compounds, particularly arsenosugar compounds. The candidate material, a dried hijiki seaweed powder, was analyzed by individual techniques in two laboratories. The water-soluble arsenic compounds were separated by anion exchange, and reversed-phase columns, and As(V), DMA and four kinds of arsenosugars, namely glycerol (-OH), phosphate (-PO4), sulfonate (-SO3), and sulfate (-SO4) types were detected by HPLC-ICP-MS. The methods applied were validated by analyzing a second sample, the NMIJ CRM 7405-a hijiki seaweed, which is certified for both total arsenic and As(V). Techniques for the inter-laboratory study, extraction efficiencies under different extraction conditions, some chromatographic techniques and sequential extraction were investigated. The results from the two laboratories for the candidate hijiki material showed good agreement within the measurement uncertainties for total and water-soluble arsenic compounds.

Establishment of the national reference standard for tetanus toxoid in Thailand

The use of reference materials is the basis of standardization and quality control of biologicals such as vaccines produced by different manufacturers and lot-to-lot consistency. The aim of this study was to establish a secondary local and national reference standard of adsorbed tetanus toxoid that can be used for tetanus toxoid vaccine potency testing. Concentrated bulk of tetanus toxoid was adjuvanted and aliquoted before lyophilization. Lyophilized product was tested for biological and physicochemical qualities, including moisture content, identity, appearance, antigen content, degree of adsorption, and sterility. The potency of the candidate reference material was calibrated against the 4th World Health Organization International Standard (WHO IS) for tetanus toxoid by two independent laboratories (BioNet-Asia and Thai National Control Laboratory) using the WHO mouse challenge test. A total of 839 vials with lyophilized tetanus toxoid reference material were produced. Potency was estimated at 115 IU/vial [intra-laboratory geometric coefficient of variation (GCV) of 7 tests was 16.5%] and 112 IU/vial (intra-laboratory GCV of 5 tests was 38.6%) at the two laboratories, with an inter-laboratory GCV of 25.5%. The potency of the candidate standard was assigned a value of 114 IU/vial. The candidate reference standard was approved by The Thai National Central Laboratory (NCL) as the Thai national tetanus toxoid reference standard.

Determination of chromium picolinate and trace hexavalent chromium in multivitamins and supplements by HPLC-ICP-QQQ-MS

Chromium picolinate (CrPic) and trace hexavalent chromium (Cr(VI)) content were characterized in VITA-1 and VITB-1, two new multivitamin and mineral supplement candidate reference materials from National Research Council Canada, by two methods of high performance liquid chromatography inductively-coupled plasma triple quadrupole mass spectrometry. The conditions for the separation of Cr(VI) from EDTA-complexed Cr(III) were optimized such that species interconversions were not observed during analysis. Following extraction with dilute NH4OH in water at pH 10 (for Cr(VI)) or 3:2 acetonitrile:water (for CrPic) and quantification by standard addition, it was concluded that CrPic accounted for 95–96 % of the Cr in VITA-1 and VITB-1, while Cr(VI) was not present above the detection limit of 0.13 μg Cr g−1. Using the two developed methodologies, commercially-available nutritional supplements, in the form of vitamin tablets and dried food supplements, were assessed, and it was determined that CrPic accounted for the majority (92 %–98 %) of the chromium present in the tablets, and that Cr(VI) concentrations were below the detection limit for all samples except for the powdered beets where it accounted for nearly half of the total Cr present.

Evaluation of Uniformity and Stability of Frozen Mixed Serum Potassium Candidate Reference Materials.

We tested the uniformity and stability of candidate reference materials (RMs) for serum potassium and aimed to design RMs with better quality that can meet all clinical test requirements and effectively solve the quantity traceability transfer problem. Three levels of frozen mixed serum potassium candidate RMs were prepared and packed in freezing tubes. RMs were determined in triplicate in 10 vials randomly selected from each level. A one-way analysis of variance was used to evaluate the uniformity using a ratio of the mean squares among groups to mean squares within groups F < F0.05 as the criteria. Stability was studied by synchronization; the short-term stability of the serum potassium in the transport conditions was observed for 30, 15, and 7 days at refrigeration (2 - 8°C), room temperature (18 - 25°C), and 37°C, respectively. By linear regression analysis of variance, the straight line was used as an empirical model. The criterion for judging is |b1| < t0.95, n - 2·sb1. Based on the statistical analysis using SPSS 17, the F values for the homogeneity tests of each level of the frozen mixed serum potassium RMs were 0.247, 0.117, and 0.162. These values were less than F0.05 (9, 20) = 2.39. When the short-term stability of the serum potassium was observed for 30, 12, and 4 days at 2 - 8°C, room temperature, and 37°C, respectively, |b1| < t0.95, n - 2·sb1, and instability was not observed. The three levels of the frozen mixed serum potassium RMs have good uniformity. At 2 - 8°C, room temperature, and 37°C, the stability can be ensured for at least 30, 12, and 4 days, respectively. The serum potassium candidate RMs are sufficiently stable under these transportation conditions.

Reference measurements of mercury species in seafood using isotope dilution inductively coupled plasma mass spectrometry

Species-specific isotope dilution inductively coupled plasma mass spectrometry (SS ID ICP-MS) and high-performance liquid chromatography (HPLC) were used to obtain accurate and SI traceable results for methyl mercury in seafood samples such as clam, oyster and fish homogenate. The mass fractions of (62.3 ± 2.3) μg kg−1, (5.44 ± 0.36) μg kg−1 and (531 ± 19) μg kg−1 were obtained for MeHg (as Hg) in IAEA-461, IAEA-470 and IAEA-476, respectively. Direct isotope dilution mass spectrometry was performed for total mercury content then the content of inorganic mercury in selected samples was obtained by calculation. It was found that the content of inorganic Hg in IAEA-461, IAEA-470, and IAEA-476 was as: 328 μg kg−1, 16 μg kg−1, and 62 μg kg−1, respectively. Mathematical modelling of analytical procedure and evaluation of all parameters influencing final results were adequate for validation of measurement procedure, establishing traceability and estimating expanded uncertainty. Developed procedures were successfully applied in the characterization process of fish homogenate candidate reference material and in the calculation of assigned values in the frame of IAEA-476 inter-laboratory comparison study. Compatibility between obtained results and those derived from the certification campaign, organized by International Atomic Energy Agency on the same sample matrix (<2.6 % difference) further validated performed ID ICP-MS protocols.

High-Sensitivity Measurement of Cr Isotopes by Double Spike MC-ICP-MS at the 10 ng Level.

High-sensitivity and high-precision (2 SD ≤ 0.06‰) measurement of chromium (Cr) isotopes at the 10 ng level was successfully carried out using double spike multiple-collector inductively couple plasma mass spectrometry (MC-ICP-MS). To enhance the signal sensitivity and stability, the Aridus II desolvating nebulizer system was improved by placing its waste gas trap bottle in an ice chamber (5 °C cold trap). This setup, beyond Cr isotope analysis, can be applied to most heavy metal isotope measurements. The sensitivity of the 52Cr signal is ≥300 V mg-1 L (with a 1011Ω amplifier and a 110 μL min-1 uptake rate), an enhancement of ≥1.5 times compared to the Aridus II without the cold trap. In addition, the relative standard deviation of the 52Cr signal varied ≤4% over 8 h, demonstrating high stability. The δ53Cr values of common geological reference materials determined using 10 ng of Cr are in excellent agreement with results measured at 25 ng and 50 ng and are consistent with previous determinations, validating the accurate and precise Cr isotope ratio measurements. An empirical method is proposed to correct for the residual (after subtraction) effect of Fe interference on δ53Cr determination. This method relies on a linear relationship between the [Fe]/[Cr] and δ53Cr shift within one analytical session. Finally, we report the δ53Cr values of 19 new reference materials, ranging from -0.44‰ to 0.49‰. Among them, GSS-7 (-0.44 ± 0.02‰, 2 SD, n = 5), GSS-4 (0.48 ± 0.02‰, 2 SD, n = 5), and GSD-10 (0.49 ± 0.05‰, 2 SD, n = 5) can be used as candidate reference materials for interlaboratory comparisons to complement existing ones that are mostly isotopically unfractionated from the bulk silicate earth.

Preparation of a reserpine certified reference material for calibration and analysis of liquid chromatography

A certified reference material (CRM) for reserpine was investigated by raw material purification, qualitative analysis, quantitative analysis, homogeneity testing, stability testing, characterization, and uncertainty evaluation. The candidate reference material was prepared by recrystallization of purchased reserpine. After purification and drying, the candidate materials were enclosed in brown glass bottles. The chemical composition of the candidate reserpine reference material was confirmed by infrared spectroscopy, high-resolution mass spectrometry, and nuclear magnetic resonance. The homogeneity and stability of several sample bottles of the candidates were studied by stratified random sampling. With the cooperation of eight qualified laboratories, the purity of reserpine was analyzed by a mass balance method (including area normalization, water content, ash content and residual solvent analyses by liquid chromatography) with a certified purity mass fraction of 99.3 % and an expanded uncertainty of 0.5 % (k = 2). This reference material has been identified as a Chinese national-grade secondary CRM, which is numbered GBW(E) 090901, and is expected to be used in the calibration of instruments such as those used for liquid chromatography or method evaluations in food, medicine, environmental, and cosmetic analyses.