Characterization Of Reference Materials Research Articles

Compensation of isotope ratio mismatch in double isotope dilution inductively coupled plasma mass spectrometry (ID-ICP/MS)

Abstract Exact-matching double isotope dilution inductively coupled plasma mass spectrometry (ID-ICP/MS) is widely used to characterize reference materials (RMs) in elemental analysis. In this technique, achieving exactly matching isotope ratios for the sample and calibration blends is regarded as an important prerequisite for obtaining accurate measurement results. However, meeting this condition requires multiple time-consuming iterative measurements. In the current study, an alternative approach that can avoid lengthy iterative procedures while maintaining the accuracy of the ID-ICP/MS results was successfully investigated. We examined the effects of an extensively wide range of inexact-matching isotope ratios (approximately 75%–130%) in double ID-ICP/MS for elements with a wide mass range. Our experimental study, using gravimetrically prepared samples of Ca, Cd, Cu, Fe, Hg, Mg, Ni, Pb, and Zn, demonstrated that, despite deliberately introducing mismatching of isotope ratios, the accuracy of the ID-ICP/MS results remained consistent with relative measurement bias of typically less than 0.5%. The absence of a systematic bias due to deviations in the sample blend isotope ratios from the target ratios of the calibration blends revealed that the variability due to an isotope ratio mismatch was sufficiently compensated for. Furthermore, the expanded measurement uncertainties were sufficiently small with negligible variations observed across the different matching ratios. Typically, they were less than 1%, except for Fe, Hg, Pb, and Zn which were less than 2%. This assertion is also supported by theoretically calculated error magnification factors. Consequently, it is feasible to directly utilize the marginally estimated mass fraction of the analyte of interest without extensive iterative measurements. The findings of this study provide robust data for ID-ICP/MS, allowing to circumvent lengthy iterative procedures while maintaining the accuracy and precision of the measurement results, particularly in the characterization of RMs for elemental analysis.

Characterization of Reference Materials for CYP3A4 and CYP3A5: A (GeT-RM) Collaborative Project

Pharmacogenetic testing for CYP3A4 is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials are currently available for many of the CYP3A4 variants included in clinical tests. To address this need, the Division of Laboratory Systems, CDC-based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 30 DNA samples derived from Coriell cell lines for CYP3A4. Samples were distributed to five volunteer laboratories for genotyping using a variety of commercially available and laboratory-developed tests. Sanger and next-generation sequencing were also utilized by some of the laboratories. Whole-genome sequencing data from the 1000 Genomes Projects were utilized to inform genotype. Twenty CYP3A4 alleles were identified in the 30 samples characterized for CYP3A4: CYP3A4∗4, ∗5, ∗6, ∗7, ∗8, ∗9, ∗10, ∗11, ∗12, ∗15, ∗16, ∗18, ∗19, ∗20, ∗21, ∗22, ∗23, ∗24, ∗35, and a novel allele, CYP3A4∗38. Nineteen additional samples with preexisting data for CYP3A4 or CYP3A5 were re-analyzed to generate comprehensive reference material panels for these genes. These publicly available and well-characterized materials can be used to support the quality assurance and quality control programs of clinical laboratories performing clinical pharmacogenetic testing.

Development and characterization of reference materials for EGFR, KRAS, NRAS, BRAF, PIK3CA, ALK, and MET genetic testing.

Along with the dramatic development of molecular diagnostic testing for the detection of oncogene variations, reference materials (RMs) have become increasingly important in performance evaluation of genetic testing. In this study, we built a set of RMs for genetic testing based on next-generation sequencing (NGS). Solid tumor tissues were selected as the samples of RMs for preparation. NGS was used to determine and validate the variants and the mutation frequency in DNA samples. Digital PCR was used to determine the copy numbers of RNA samples. The performance of the RMs was validated by six laboratories. Thirty common genetic alterations were designed based on these RMs. RMs consisted of a positive reference, a limit of detection reference, and a negative reference. The validation results confirmed the performance of the RMs. These RMs may be an attractive tool for the development, validation, and quality monitoring of molecular genetic testing.

Certified reference material for coal in accordance with the PN-EN ISO 17034:2017-03 standard and ISO GUIDE 35:2017

Abstract Due to an absence of domestic certified reference materials for coal on the Polish market, an attempt was made to manufacture a new and innovative product tailored to its needs. The chosen candidate material was hard coal acquired from Poland’s coal mines. A single reference material unit consisted of 50g of an analytical hard coal sample with a grain size below 0.2 mm. A manufacturing method was developed enabling production of matrix reference materials addressing the needs of the domestic solid fuel market, and was directed at research laboratories carrying out analyses of solid fuels for the energy and coking sectors. The adapted manufacturing scheme of a certified reference material for coal was presented with a description of the chosen critical steps of the process and discussion of the obtained results in terms of homogeneity, stability, characterisation of the reference material as well as assigned values to particular properties and their uncertainty budget. The results obtained during homogeneity, short-term and long-term stability assessments as well as reference material characterisation confirmed the feasibility of the investigated certified coal reference material manufacturing process. The obtained levels of relative expanded uncertainties of the measurements confirmed the feasibility of the manufactured certified reference material for establishing and maintaining metrological traceability of measurement results. The presented research establishes a base for planning out production of additional reference materials as well as providing the know-how for designing manufacturing schemes for reference materials for solid fuels, or waste related materials like fly ash, or furnace waste.

Characterization of reference materials for in situ U–Pb dating of columbite group minerals by LA-ICP-MS

A new ID-TIMS 206Pb/238U age of Coltan139 is reported. Newly characterized reference materials (ZKW and DDB) are introduced for in situ U–Pb dating of columbite group minerals by LA-ICP-MS.

A comprehensive evaluation of sulfur isotopic analysis (δ34S and δ33S) using multi-collector ICP-MS with characterization of reference materials of geological and biological origin

Sulfur isotope ratios are often used as biogeochemical tracers to gain understanding of abiotic and biological processes involved in the sulfur cycle in both modern and ancient environments. There is however a lack of matrix-matched well-characterized isotopic reference materials that are essential for controlling the accuracy and precision. This study therefore focused on expanding and complementing the currently available sulfur isotope ratio data by providing the bulk sulfur isotopic composition, as determined using multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), for a comprehensive set of commercially and/or readily available biological and geological reference materials. A total 7 isotopic reference materials and 41 elemental reference materials were studied. These reference materials include standards of terrestrial and marine animal origin, terrestrial plant origin, human origin, and geological origin. Different sample preparation protocols, including digestion and subsequent chromatographic isolation of S, were evaluated and the optimum approach selected for each matrix type. For achieving enhanced robustness, the sample preparation and sulfur isotope ratio measurements were done at two different laboratories for selected reference materials, while at one of the laboratories the measurements were additionally performed using two different MC-ICP-MS instruments. Determined δ34SVCDT and δ33SVCDT values compared well between the different laboratories, as well as between the different generation MC-ICP-MS instruments, and for standards that were previously characterized, our data are similar to literature values. The δ34SVCDT ranges determined for the different categories of the reference materials – terrestrial animal origin: +2 to +9‰, marine animal origin: +15 to +20‰, human origin: +6 to +10‰, terrestrial plant origin: −20 to +7‰, and geological origin: −12 to +21‰ – fit the expected values based on previous studies of similar types of matrices well. No significant mass-independent fractionation is observed when considering the expanded uncertainties for Δ33SV-CDT.

Development of Measurement Procedures for the Characterization of Reference Materials for Carbohydrate Composition of Dairy Products

This article studies the development of measurement procedures based on various methods for a comprehensive analysis of the carbohydrate composition of food systems. The basis of the primary reference measurement procedure (PRMP) is the method of iodometric titration based on the ability of iodine to oxidize aldosaccharides to the corresponding uronic acids in an alkaline medium. The accuracy of the PRMP was improved by optimizing the measurement parameters, including the method of high-performance liquid chromatography with refractometric detection (HPLC/RD), and by establishing their possible variation limit based on a multifactorial experiment. The application of the PRMP made it possible to measure the mass fraction of carbohydrates (total sugar) as the sum of the mass fractions of reducing and non-reducing sugars in milk and dairy products, grain and milk products, low-lactose and lactose-free products, including those used for preparing baby food. In order to further detail the carbohydrate composition, highly selective methods were developed for measuring the mass fractions of lactose and galactose by the spectrophotometric (enzymatic) method, and the mass fractions of mono- and disaccharides by the HPLC/RD method in milk and dairy products. It was found that the measurement results of both the total content of carbohydrates and individual mono- and disaccharides in the samples of milk and dairy products obtained by various methods (iodometric titration, HPLC/RD, enzymatic method, refractometry, IR spectroscopy, calculation method) are consistent with each other subject to the stated uncertainties. Thus, the applicability of the developed PRMP in combination with other methods for conducting an in-depth analysis of the carbohydrate composition of milk and dairy products was confirmed. The developed procedures were used to characterize reference materials for the composition of dairy products (3 types), mono- and disaccharides (9 types).

Characterization of Reference Materials for TPMT and NUDT15: A GeT-RM Collaborative Project

Pharmacogenetic testing is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials are currently available for many of the TPMT and NUDT15 variants included in clinical tests. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention-based Genetic Testing Reference Material (GeT-RM) coordination program, in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 19 DNA samples derived from Coriell cell lines. DNA samples were distributed to four volunteer testing laboratories for genotyping using a variety of commercially available and laboratory developed tests and/or Sanger sequencing. Of the 12 samples characterized for TPMT, newly identified variants include TPMT∗2, ∗6, ∗12, ∗16, ∗21, ∗24, ∗32, ∗33, and ∗40; for the 7 NUDT15 reference material samples, newly identified variants are NUDT15∗2, ∗3, ∗4, ∗5, ∗6, and ∗9. In addition, a novel haplotype, TPMT∗46, was identified in this study. Preexisting data on an additional 11 Coriell samples, as well as some supplemental testing, were used to create comprehensive reference material panels for TPMT and NUDT15. These publicly available and well-characterized materials can be used to support the quality assurance and quality control programs of clinical laboratories performing clinical pharmacogenetic testing.

Metrological Traceability of Coomet Reference Materials. Part. 2. Characterization of Reference Materials

Metrological Traceability of Coomet Reference Materials. Part. 2. Characterization of Reference Materials

Characterization of Reference Materials for Spinal Muscular Atrophy Genetic Testing: A Genetic Testing Reference Materials Coordination Program Collaborative Project

Spinal muscular atrophy (SMA) is an autosomal recessive disorder predominately caused by bi-allelic loss of the SMN1 gene. Increased copies of SMN2, a low functioning nearly identical paralog, are associated with a less severe phenotype. SMA was recently recommended for inclusion in newborn screening. Clinical laboratories must accurately measure SMN1 and SMN2 copy number to identify SMA patients and carriers, and to identify individuals likely to benefit from therapeutic interventions. Having publicly available and appropriately characterized reference materials with various combinations of SMN1 and SMN2 copy number variants is critical to assure accurate SMA clinical testing. To address this need, the CDC-based Genetic Testing Reference Materials Coordination Program, in collaboration with members of the genetic testing community and the Coriell Institute for Medical Research, has characterized 15 SMA reference materials derived from publicly available cell lines. DNA samples were distributed to four volunteer testing laboratories for genotyping using three different methods. The characterized samples had zero to four copies of SMN1 and zero to five copies SMN2. The samples also contained clinically important allele combinations (eg, zero copies SMN1, three copies SMN2), and several had markers indicative of an SMA carrier. These and other reference materials characterized by the Genetic Testing Reference Materials Coordination Program are available from the Coriell Institute and are proposed to support the quality of clinical laboratory testing.

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.

Stable carbon isotope diagnostics of mammalian metabolism, a high-resolution isotomics approach using amino acid carboxyl groups.

The carbon isotopic compositions of amino acids are increasingly measured to characterize diets and metabolic response to diets. We report a new high-resolution system to measure the stable carbon isotopic composition of carboxyl atoms within amino acids. The automated system used HPLC to separate amino acids followed by addition of ninhydrin for decarboxylation and transfer of the evolved CO2 to a stable isotope ratio mass spectrometer for δ13CCARBOXYL measurement. The ninhydrin reaction was conducted at acidic pH (1.5) and elevated temperature (160 oC) giving yields close to 100% for most common amino acids. Eight mammalian keratin samples from herbivores (kudu and caribou), omnivores (humans) and carnivores (bowhead and humpback zooplanktivorous whales) were analysed with this new system. The data provide an initial calibration of reference materials to be used in studies of this type and is the first report of carboxyl carbon isotope distributions in mammals. Results showed widespread 13C enrichments in both essential and non-essential amino acid carboxyl groups, likely linked to decarboxylation of amino acids during normal metabolism. Analyses of non-essential amino acid isotope profiles showed (1) consistent and general taxon-level metabolic differences between the herbivore, human and whale samples, (2) marked differences among individual humans, ruminants and whales (3) evidence for gluconeogenesis in the wildlife samples, and (4) extensive 13C enrichment likely associated with fasting in the humpback whale sample. Future mammalian research related to the metabolism of growth, reproduction, aging and disease may benefit from using this technique. Values obtained for internationally available samples USGS42 and USGS43 (Tibetan and Indian human hair) provide a first characterization of reference materials for δ13CCARBOXYL profiles.

Continuous-wave coherent Raman spectroscopy for improving the accuracy of Raman shifts.

Raman spectroscopy is an appealing technique that probes molecular vibrations in a wide variety of materials with virtually no sample preparation. However, accurate and reliable Raman measurements are still a challenge and require more robust and practical calibration methods. We demonstrate the implementation of a simple low-cost continuous-wave (cw) stimulated Raman spectroscopy scheme for accurate and high-resolution spectroscopy. We perform shot noise-limited cw stimulated Raman scattering as well as cw coherent anti-Stokes Raman scattering on polystyrene samples. Our method enables accurate determination of Raman shifts with an uncertainty below 0.1 cm-1. The setup is used for the characterization of reference materials required for the calibration of Raman spectrometers. Compared with existing standards, we provide an order of magnitude improvement of the uncertainty of Raman energy shifts in a polystyrene reference material.

Characterization of Reference Materials for Genetic Testing of CYP2D6 Alleles: A GeT-RM Collaborative Project

Pharmacogenetic testing increasingly is available from clinical and research laboratories. However, only a limited number of quality control and other reference materials currently are available for the complex rearrangements and rare variants that occur in the CYP2D6 gene. To address this need, the Division of Laboratory Systems, CDC-based Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Cell Repositories (Camden, NJ), has characterized 179 DNA samples derived from Coriell cell lines. Testing included the recharacterization of 137 genomic DNAs that were genotyped in previous Genetic Testing Reference Material Coordination Program studies and 42 additional samples that had not been characterized previously. DNA samples were distributed to volunteer testing laboratories for genotyping using a variety of commercially available and laboratory-developed tests. These publicly available samples will support the quality-assurance and quality-control programs of clinical laboratories performing CYP2D6 testing.

Development of transfer measurement standards in the form of high-purity metals

The article studies the development of transfer measurement standards in the form of high-purity metals (Ag, Cd, Co, Cr, Cu, Fe, Ge, Mn, Mo, Ni, Pb, V, Zn). The evaluation of the mass fraction of the main component (MDOK) is performed by an indirect method (100 %o minus the sum of impurities). The impurity composition of the reference measurement standard materials was determined by mass spectrometry with inductively coupled plasma, reductive and oxidative melting using the State primary measurement standard of mass (molar) fraction and mass (molar) concentration of the component in liquid and solid substances and materials, based on coulometry, GET 176. The relative expanded uncertainty of MDOK (k = 2, P = 0,95) in the reference measurement standards was less, than 0,01 %o, in gravimetrically prepared solutions of the reference measurement standard it was less than 0,05 %o in most cases. The solutions of the reference measurement standards were used in the determination of certified values of metal mass fraction and mass concentration in reference materials for composition of mono-element solutions of approved types. The relative expanded uncertainty of certified values (k = 2, P = 0,95) of reference materials variedfrom 0,22 %o to 0,54 %o. Thus, it was demonstrated that metals can be used as reference measurement standards for storing a unit of the mass fraction of the main component and transferring it during characterization of reference materials for composition of solutions of the corresponding chemical elements. This work was performed within the research project «Research in the field of measurements of physicochemical composition and properties of substances, aimed at the development of State transfer measurement standards in the form of high-purity substances for reproduction and transfer of the units, characterizing chemical composition of solid substances» under the code «Purity» (2015-2017) and research and development project «Research in the field of measurements ofphysicochemical composition and properties of substances, aimed at the development of State transfer measurement standards in the form of high-purity substances for reproduction and transfer of the units, characterizing the chemical composition of solid substances and the development of reference measurement procedures» under the code «Purity-2» in the field of physicochemical measurements of composition and properties of inorganic components in solid substances (metals and salts) and food safety indicators under the code «Purity-2b» (2017-2019).

Complete dissolution of solid matrices using automated borate fusion in support of nuclear decommissioning and production of reference materials

Accurate measurement of natural and anthropogenic radionuclide concentrations is of critical importance to end users in the nuclear sector to ensure correct classification prior to storage, recycling, reprocessing or disposal. Uncertainties in the characterisation of solid matrices and materials could lead to safety, quality and financial implications. Robust sample preparation methods are vital, in particular effective sample digestion, as under-estimated chemical yield recovery results in a corresponding under-estimation of activity levels. Borate fusion has been proven to effectively digest a range of complex sample matrices in the geosciences but is not used routinely elsewhere. In this study, we describe an automated procedure for borate fusion of multiple matrices encountered in nuclear decommissioning, containing diverse radionuclides over a range of activity concentrations. The impact of digestion flux, sample mass and sample to flux ratios are described, as well as the subsequent separation and measurement techniques. The results contribute to accurate and precise measurement of radionuclides in various matrices, as well as to characterisation of reference materials, providing greater confidence in nuclear industry programmes worldwide.

GGR Biennial Critical Review: Analytical Developments Since 2014

This GGR biennial critical review covers developments and innovations in key analytical methods published since January 2014, relevant to the chemical, isotopic and crystallographic characterisation of geological and environmental materials. In nine selected analytical fields, publications considered to be of wide significance are summarised, background information is provided and their importance evaluated. In addition to instrumental technologies, this review also presents a summary of new developments in the preparation and characterisation of rock, microanalytical and isotopic reference materials, including a précis of recent changes and revisions to ISO guidelines for reference material characterisation and reporting. Selected reports are provided of isotope ratio determinations by both solution nebulisation MC‐ICP‐MS and laser ablation‐ICP‐MS, as well as of radioactive isotope geochronology by LA‐ICP‐MS. Most of the analytical techniques elaborated continue to provide new applications for geochemical analysis; however, it is noted that instrumental neutron activation analysis has become less popular in recent years, mostly due to the reduced availability of nuclear reactors to act as a neutron source. Many of the newer applications reported here provide analysis at increasingly finer resolution. Examples include atom probe tomography, a very sensitive method providing atomic scale information, nanoscale SIMS, for isotopic imaging of geological and biological samples, and micro‐XRF, which has a spatial resolution many orders of magnitude smaller than conventional XRF.

Development and Characterization of Reference Materials for Genetic Testing: Focus on Public Partnerships.

Characterized reference materials (RMs) are needed for clinical laboratory test development and validation, quality control procedures, and proficiency testing to assure their quality. In this article, we review the development and characterization of RMs for clinical molecular genetic tests. We describe various types of RMs and how to access and utilize them, especially focusing on the Genetic Testing Reference Materials Coordination Program (Get-RM) and the Genome in a Bottle (GIAB) Consortium. This review also reinforces the need for collaborative efforts in the clinical genetic testing community to develop additional RMs.

LC–MS/MS analysis of steroids in the clinical laboratory

Liquid chromatography–tandem mass spectrometry (LC–MS/MS) is a powerful tool that is changing the way we analyse steroids in the clinical laboratory. It is already opening up the field of steroid analysis in endocrinology and is providing new applications for individual steroids and panels of steroids in different clinical conditions. LC–MS/MS is now well-accepted technology and is increasingly being used to replace problematic immunoassay methods because of greater sensitivity and specificity. Improved sample preparation, modern chromatography methods, and sensitive, faster scanning mass spectrometers have all played a role in improving LC–MS/MS. LC–MS/MS is also playing a key role in improving the quality of assays through the development of reference measurement procedures, characterisation of reference materials and multi-site calibration programmes. There is increasing interest in multiplexing steroid assays into panels of diagnostic tests to aid and improve the diagnosis and monitoring of disease.

A calibration strategy for LA-ICP-MS using isotope dilution for solid reference materials

An isotope dilution method for the quantitative analysis of trace elements in biological samples and for the characterization of reference materials for the analysis of biological samples by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-ID-MS) has been tested.