National Metrology Institute Of Japan Research Articles

Calibration and measurement capability evaluation for 1 MN hydraulic force standard machine newly installed at NMIJ

Abstract Social safety is predicated on accurately evaluated force standards and a system for force traceability. National Metrology Institute of Japan, the body responsible for managing Japan's national force standards, has implemented a new 1 MN hydraulic force standard machine. In this paper, we assess the calibration and measurement capability of this new force standard machine using five different force measuring instruments. Our findings confirm that its capability is less than 1×10−4 relative, demonstrating its adequate performance as one of the national force standards.

Air kerma reference field with high energy photons using a 15 MeV electron beam from a clinical linear accelerator.

In the medical and nuclear fields, there are environments where exposure to photons with energies above several MeV can result in problems. The National Metrology Institute of Japan has developed a high-energy photon field using a 15 MeV electron beam of a clinical linear accelerator with a copper target and an aluminium filter unit to facilitate dosimeter calibration in terms of air kerma. To determine the air kerma rate, the energy fluence distribution at a reference point was calculated, and both calculations and experiments evaluated the effective energy and spatial dose distribution. Moreover, to validate the air kerma measurement, two commercial cavity chambers were calibrated in a developed photon field. The results obtained exhibited a 4% difference compared with those in a Co-60γ-ray reference field.

B-202 Improving Performance of an LC-MS C-peptide Reference Method

Abstract Background C-peptide is a useful biomarker for distinguishing among different types of diabetes and is a proxy measure of endogenous insulin production, useful in diabetes management. Additionally, C-peptide tests can be used to diagnose non-diabetic hypoglycemia and insulinoma. However, differences among clinical assays can limit the application of C-peptide testing. To address this issue, efforts are underway to standardize manufacturer assays with serum-based secondary reference materials where values are assigned by a reference LC-MS method. Clinical evidence suggests that patients with diabetes can benefit from residual beta-cell function, yet many clinical assays have high variability at lower levels of C-peptide. Here we explore different approaches for improving sensitivity and selectivity of C-peptide reference measurements with a focus at the lower end of the measurement range. Methods Two methods were developed to evaluate and determine the most effective approach. The first method involved spiking serum samples with isotope-labeled c-peptide (Sigma) and then enriching and enzymatically digesting them. The enrichment process included removing abundant serum proteins by using methanol, followed by centrifugation and filtration through C18 cartridges. The resulting solution was then passed through a strong anion-exchange column after correcting its pH with ammonium formate buffer. The eluent was evaporated, and the residue was dissolved in ammonium carbonate buffer. Enzymatic digestion was performed by adding dithiothreitol and iodoacetamide followed by addition of Glu-C. The digested peptides were then analyzed by LC-MS/MS (QTRAP 6500+) in MRM mode. The second method followed the same steps as the first method, except that the evaporation and digestion step were skipped, and MRM was performed on the intact C-peptide chain. Two separate calibration curves were constructed for each method using isotope labeled c-peptide (Sigma) and certified reference material (National Metrology Institute of Japan) as native c-peptide. Results The first method, which measures intact C-peptide using MRM, had a slope of 1.14 and an intercept of −0.01 nmol/L (Deming regression, R = 0.917) when compared to the reference method. The method demonstrated CV within 0.4%–11.9%. The second method, which quantifies digested peptides, showed a slope of 1.02 and an intercept of −0.21 nmol/L compared to the reference method (Deming regression, R = 0.995). The method demonstrated CV within 4.4–20.0%. Controlling the three MRM transitions improved the specificity and accuracy of the results. For the first method two MRM transitions were adequate. Both methods showed no significant matrix effects. The first method is simpler to implement due to a smaller number of separation steps. Conclusion We have explored two new alternative workflows for C-peptide quantitation that include first, an enzymatic digestion then MRM quantitation and second, MRM quantitation of intact C-peptide. To improve the analytical performance of the methods, further optimization is still required.

Development of matrix-based reference materials for 17 beta-estradiol by the recommended reference method of ID-LC-MS/MS.

We developed and evaluated two-level, namely 2017011 and 2017012, serum-based reference materials (RMs) for 17 beta-estradiol (17 β-E2) by the reference method of isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) from the remaining serum samples after routine clinical tests, to help improve clinical routine testing and provide the traceability of results. This paper describes the development process of these RMs. The National Metrology Institute of Japan (NMIJ) certified reference material (CRM) 6004-a was used as the primary RM for the measurement of 17 β-E2. These serum-based RMs showed satisfactory homogeneity and stability. They also assessed the commutability between the reference method and the three routine clinical immunoassay systems. Besides, a collaborative study was carried out in five reference laboratories, all of which had been accredited by the China National Accreditation Service for Conformity Assessment (CNAS) in accordance with ISO/WD 15725-1. Statistical analysis of raw results and uncertainty assessment obtained certified values: 2017011 was 445.2 ± 39.0pmol/L, and 2017012 was 761.9 ± 35.5pmol/L.

Accelerator-driven photon reference field for replacement of 137Cs γ-ray

A transition to a mechanical source for x-ray reference field is desired to replace high-activity Co-60 and Cs-137 gamma-ray sources for enhancing nuclear security and safety management. The National Metrology Institute of Japan (NMIJ) developed a new photon reference field using an electron beam from a linac with energy less than 1 MeV. The effective energy of the photon field is comparable with Cs-137 gamma-ray. The air kerma rate in the reference field was validated by comparing a commercial cavity ionization chamber to the NMIJ standard reference field. The calibration constants were consistent within 0.8% for every relative extended uncertainty (k = 2).

The pressure effect on the line profiles observed in the [formula omitted] band of acetylene: Revisited

In our previous paper [K. Iwakuni et al., Phys. Rev. Lett.117, 1439026 (2018)] the ortho-para dependence of the pressure effects was reported for the ν1+ν3 band of acetylene measured by dual-comb spectroscopy. Sears and coworkers [E.C. Gross et al., J. Chem. Phys.154, 054305 (2021)] reevaluated the profile parameters for some lines of this band by comb-referenced laser spectroscopy, and pointed out that the ortho-para phenomenon must be a consequence of the use of Voigt function as the profile function, with the Doppler widths fixed at their theoretical values. Thus, we have remeasured this band with two improved spectrometers, the comb-locked laser spectrometer of the National Metrology Institute of Japan and another dual-comb spectrometer of Yokohama National University, and analyzed the lines by using the speed-dependent Voigt function as the profile function with several options. By the present work, we confirm the fact pointed out by Sears and coworkers, and present some remaining problems in the experimental determination of the line profile parameters.

Primary measurement standards for trace moisture in multiple gases: extension of gas species to He and O2

The National Metrology Institute of Japan developed a multi-gas trace-moisture generator which was designed for generating trace water vapor (trace moisture) in multiple gases. Using this system, we previously developed primary measurement standards for trace moisture in N2 (10 nmol mol−1–5 μmol mol−1) and Ar (10 nmol mol−1–1 μmol mol−1). In this study, we have extended the target gas species; trace-moisture standards in He and O2 in the rage of 10 nmol mol−1 − 1 μmol mol−1 were developed. The relative expanded uncertainty (k = 2) of the trace-moisture standard in He was 0.74 %–5.7 %, and that in O2 was 0.78 %–8.9 %. In addition, we have improved stability of the flow rate of the diluent gas by controlling the temperature around the flow measurement/control systems and re-evaluated the uncertainty of the trace-moisture standards in N2 and Ar. The updated relative expanded uncertainty (k = 2) of the trace-moisture standard in N2 and Ar is 0.41 %–2.6 % and 0.73 %–2.6 %, respectively. The uncertainty budgets of the standards in these four gases are presented. The trace-moisture standard in N2 developed using the multi-gas trace-moisture generator was confirmed to be consistent with the standards realized by other generators, whose international comparability were already ensured. A commercial moisture analyzer (MA) based on the cavity ring-down spectroscopy (CRDS) was connected to the multi-gas trace-moisture generator as a device under test, and its performance was evaluated by comparing the readings with the standard values. The MA showed lower accuracy and stability in the measurement of moisture in He when it was used in the default setting, whereas it performed well in N2. This performance difference is related to the pressure-broadening coefficient of water, which depends on the gas species. We estimated the pressure-broadening coefficients of water by N2, Ar, He and O2 and discuss the gas-type dependence of the performance of CRDS-based MAs.

Primary microvibration standards down to 10−3 m s−2 at low frequency

The reliability of microvibration measurements is important in some applications, such as infrastructure health monitoring. Thus, it is necessary to develop a vibration standard based on ISO16063-11 for microvibrations. In this study, the low-frequency standard vibration calibration system in the National Metrology Institute of Japan was upgraded to be compatible with small input vibrations down to an amplitude of 10−3 m s−2. A low-noise reference vibration measurement system and a precise signal processing method were integrated to reduce the background noise contribution, which is a dominant uncertainty source in the field of microvibration calibration. The developed system could calibrate the sensitivity of a low-noise accelerometer down to 10−3 m s−2, between 0.1 Hz and 100 Hz. This paper reports the calibration demonstration using a servo accelerometer and the evaluated uncertainty budget. The estimated calibration uncertainty was 0.1% for a normal calibration process with an excitation of 10 m s−2, and it was 2.1% for a microvibration calibration process with an excitation of 10−3 m s−2.

Evaluation of the long-term stability of arsenic species in certified reference materials: certification of arsenobetaine, As(V), and dimethylarsinic acid in NMIJ CRMs 7901-a, 7912-a, and 7913-a.

The long-term stabilities of arsenobetaine (AsB), arsenate (As(V)), and dimethylarsinic acid (DMA), which are arsenic (As) compounds in certified reference materials (CRMs), namely, NMIJ CRMs 7901-a, 7912-a, and 7913-a, were monitored. The CRMs were developed and certified by the National Metrology Institute of Japan (NMIJ) and the National Institute of Advanced Industrial Science and Technology (AIST) in 2009 to prepare a calibrant for the speciation analysis of As species. The CRMs were prepared from high-purity reagent powders as raw materials, and each reagent was dissolved in water or diluted acid. The certification of the CRMs for AsB, As(V), and DMA was conducted by NMIJ. The concentration of total As was determined by more than three independent analytical techniques. Then, the obtained As concentrations were converted into the concentration of each chemical species, and the mass fractions of each certified value were certificated. The long-term stability of As species in the CRMs under storage was performed by liquid chromatography-inductively coupled plasma-mass spectrometry, and this report presents data on long-term stability that occurred approximately 13years. The obtained monitoring results were evaluated using both measurement results with uncertainty and a statistical parameter method, complying with ISO Guide 35. According to the results, the long-term stability of all mass fractions was confirmed.

Report on the CCM.T-K2.1 Key Comparison, Measurand Torque: 10 kN∙m and 20 kN∙m, Final Report

Main textThe comparison of torque in the range of 10 kN m and 20 kN m was organized and conducted between two laboratories, the National Metrology Institute of Japan (NMIJ) in the National Institute of Advanced Industrial Science and Technology (AIST) in Japan, and the National Metrology Institute of South Africa (NMISA) in South Africa. This comparison aims to link the national torque standards in South Africa to CCM.T-K2 so that NMISA can achieve the degree of equivalence (DOE) of the CMCs of its torque standards. NMIJ, which had joined CCM.T-K2 key comparison in 2008, played a role of a link laboratory. The results of this comparison showed a good agreement in the NMISA's results with the KCRV.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/.The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Trace-moisture measurement using cavity ring-down spectroscopy at NMIJ

Trace-moisture standards traceable to the International System of Units (SI) used for the performance test of trace-moisture analyzers and trace-moisture measurement systems based on cavity ring-down spectroscopy (CRDS) developed at the National Metrology Institute of Japan (NMIJ) are briefly reviewed. The magnetic-suspension-balance/diffusion-tube humidity generator, which was the first generator used for the trace-moisture standard developed at NMIJ, is presented. Three measurement systems based on CRDS, which are wavelength-meter-controlled CRDS, dual-laser CRDS, and miniaturized CRDS, are presented. The performance of the three CRDS systems were evaluated using the SI-traceable trace-moisture standards.

Key comparison BIPM.RI(I)-K4 of the absorbed dose to water standards of the NMIJ, Japan, and the BIPM in 60Co gamma radiation

Main textA new key comparison of the standards for absorbed dose to water of the National Metrology Institute of Japan (NMIJ), Japan, and the Bureau International des Poids et Mesures (BIPM) was carried out in the 60Co radiation beam of the BIPM in February 2022. The comparison result, based on the calibration coefficients for two transfer standards and evaluated as a ratio of the NMIJ and the BIPM standards for absorbed dose to water, is 0.9952 with a combined standard uncertainty of 4.0 parts in 103. The result agrees within the uncertainties with the comparison carried out in 2009. The results are analysed and presented in terms of degrees of equivalence, suitable for entry in the BIPM key comparison database.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/.The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Precise high resistance comparison between the NMIJ traveling dual source bridge and the NIST adapted Wheatstone bridge

A precise high resistance comparison was performed between the traveling dual source bridge developed by the National Metrology Institute of Japan (NMIJ) and the adapted Wheatstone bridge of the National Institute of Standards and Technology (NIST) from 10 MΩ to 100 TΩ at NIST. The NMIJ traveling bridge was shipped to NIST Gaithersburg and was installed right next to the NIST bridge and these bridges alternately measured the resistance ratio of the high resistance standards, without moving the location of the resistors inside the temperature controlled air-bath. Having the bridges and resistance standards in the same location for the comparison decreased the transportation and temperature coefficient effects on the resistance standards, contributing to the excellent agreement of the measured values. The NMIJ traveling bridge used an 8.5-digit digital multimeter and a relay switch box to determine a resistance ratio by measuring the ratio of the voltages applied to the resistors. The comparison was started from 10 MΩ based on the same 1 MΩ standard resistor calibrated using a NIST two-terminal cryogenic current comparator bridge, and standard resistors from 10 MΩ to 100 TΩ were calibrated by repeating 10:1 scaling measurements with both systems. Excellent agreement was obtained within the uncertainty of all resistance ranges and the difference between both systems was less than 1 μΩ Ω−1 up to 1 TΩ and the degrees of equivalence for 10 TΩ and 100 TΩ were less than 6 μΩ Ω−1.

Characterization and Value Assignment of a Monoclonal Antibody Reference Material, NMIJ RM 6208a, AIST-MAB.

Monoclonal antibodies have been established as the largest product class of biopharmaceuticals. Since extensive characterization is required for development and quality control of monoclonal antibody, a widely available reference material (RM) is needed. Herein, a humanized IgG1κ monoclonal antibody reference material, RM 6208-a, AIST-MAB, was established by the National Metrology Institute of Japan, National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). The monoclonal antibody solution was produced as a pharmaceutical grade using a Chinese hamster ovary-derived cell line. The assigned indicative value represents the concentration of the antibody with a heterotetrameric structure including oligomeric forms, determined by an amino acid analysis using isotope dilution mass spectrometry, and their homogeneity and stability were assessed. In addition to antibody concentration, various physicochemical properties, including peptide mapping data, charge variants, and aggregates, were examined. This RM is intended for use in validation of analytical procedures and instruments such as a system suitability test for quantification of antibody. It is also intended for comparing and evaluating the results of antibody analyses across analytical methods and analytical laboratories such as inter-laboratory comparison. Both the material and the set of data from our study provide a tool for an accurate and reliable characterization of product quality attributes of monoclonal antibodies in biopharmaceutical and metrology communities.

1134-P: Interlaboratory Standardization of C-Peptide Assays Using Certified Reference Material Corrected for Peptide Modifications

The standardization of C-peptide assays is highly desirable objective. Our groups have employed the use of a Certified Reference Material (CRM) to calibrate their respective measurement procedures and comparison studies have demonstrated good agreement between the two laboratories [Figure]. Although it was the original choice, The National Metrology Institute of Japan (NMIJ) CRM has not always been available. However, a new material from Cerilliant (C-161-0.1ML) proved equally well defined. Both materials include known amounts of pure C-peptide and small amounts of deamidated and pyroglutamated forms (Cerilliant Lot# FN0422195.6% modified; NMIJ CRM 6901-b, Lot# 058 1.9% modified) . The C-peptide CRMs from Cerilliant and from NMIJ behave identically when the mass concentration of the unmodified C-peptide is used to assign calibrator concentrations. To avoid potential bias, we conclude that the mass concentration of unmodified C-peptide (not the mass concentration of total C-peptide) in CRM should be used when making calibrators for mass spectrometry C-peptide assays to achieve comparable patient results. Variation in the relative amount of modified C-peptide is an obstacle to standardization, especially when comparing mass spectrometry-based assays with immunoassays, which use total C-peptide for calibration. Disclosure Z.Wu: Employee; Quest Diagnostics. K.Kabytaev: None. J.Mu: None. S.Connolly: None. M.J.Mcphaul: Employee; Quest Diagnostics. R.R.Little: None. Funding NIH/NIDDK (1UC4DK096587-01)

Precise sinusoidal signal extraction from noisy waveform in vibration calibration

Precise extraction of sinusoidal vibration parameters is essential for the dynamic calibration of vibration sensors, such as accelerometers. However, several standard methods have not yet been optimized for large background noise. In this work, signal processing methods to extract small vibration signals from noisy data in the case of accelerometer calibration are discussed. The results show that spectral leakage degrades calibration accuracy. Three methods based on the use of a filter, window function, and numerical differentiation are investigated to reduce the contribution of the calibration system noise. We demonstrate the effectiveness of these methods with theoretical calculations, simulations, and experiments. The uncertainty of microvibration calibration in the National Metrology Institute of Japan is reduced by two orders of magnitudes using the proposed methods. We recommend to use a combination of numerical differentiation and either a time-domain window function or a bandpass filter for most accelerometer microvibration sensitivity calibrations. For suppressing the effects of line noise, adjusting the data set length is also effective.

Applicable Measuring Range of Two-Electrode Type Commercial Electrolytic Conductivity Meter for Accurate Determination of Electrolytic Conductivity

Applicable measuring range of electrolytic conductivity (EC) for commercially available two-electrode type EC meter was examined. The measurement error caused by a gap in ECs between the measurement sample and the standard solution was also evaluated. Seven potassium chloride (KCl) solutions including certified reference materials (CRMs) manufactured by the National Metrology Institute of Japan (NMIJ) were measured, and the cell constants observed for commercial EC meters as well as the effect of electrode polarization were compared in detail under strict temperature control. The effect of electrode polarization can be sufficiently small if the frequency is properly selected. In the case of KCl standard solution with concentrations of 0.1 mol kg-1 (1 S m-1) or less, the obtained cell constants were almost identical to those of declared ones. However, in the case of KCl standard solution with concentrations of 0.5 mol kg-1 (5 S m-1) or more, the obtained cell constants showed 2-10% higher than those of declared ones. From these results, the calibration by standard solution with closer EC to the measurement solution is especially important if about 1% accuracy of measurement by commercial EC meter is required in higher EC range such as 5 S m-1 or more.

Development of back-illuminated thin silicon diode applied to fast neutron sensor in active personal dosimeter

A back-illuminated thin Si diode was developed for fast neutron sensor in active personal neutron dosimeter for detecting fast neutrons below 1 MeV. Neutron response functions for the fast neutron sensor with the back-illuminated thin Si diode were evaluated based on measurements of monoenergetic neutron beams at the National Metrology Institute of Japan and Monte Carlo simulations using the Particle Heavy Ion Transport Code System in the neutron energy over 500 keV. The lower limit of neutron detection energy was decreased to 500 keV and neutron detection efficiencies were increased several times over other fast neutron sensors. It is possible to measure neutron doses in the neutron energy range of 500 keV–1 MeV using this novel fast neutron sensor, but the neutron doses were undetectable using other fast neutron sensors. The neutron detection efficiencies were closer to the personal dose equivalent conversion curve than those for other fast neutron sensors in this neutron energy range. Neutron doses of individuals employed at a nuclear facility were evaluated using the active personal neutron dosimeter, which consists of both the novel fast and slow neutron sensors.

Evaluation of automatic sub-multiple mass calibration for sub-milligram weights at NMIJ

Mass standards are essential for the precise measurement of mass. Due to the increasing demand for small mass measurements, it is essential to be able to disseminate the sub-milligram mass standard from the National Metrology Institutes. Recently, the National Metrology Institute of Japan has developed an apparatus for mass calibration of sub-milligram weights by automatically transporting the weights. Consequently, the masses of the weights can be calibrated accurately and reliably. Sub-multiple calibration is often used for accurate mass calibration of weights smaller than 1 kg. In this study, by combining this method with the developed apparatus, the mass calibration uncertainty of sub-milligram weights was improved. The mass calibrations of 0.1 mg, 0.2 mg, and 0.5 mg weights were performed with standard uncertainties of 0.019 µg, 0.023 µg, and 0.040 µg, respectively. These uncertainties were smaller than the calibration uncertainties obtained by manually transporting sub-milligram weights to an ultra-micro balance.

Challenges of an optical pressure standard in medium vacuum measurements

Optical pressure standards (OPS) using Fabry-Perot (FP) cavities can measure a wide pressure range with high accuracy. National metrology institute of Japan (NMIJ) is developing an OPS for the pressure range of 1 Pa–100 kPa. In this study, the target uncertainty of the OPS, the challenges for measuring below 100 Pa, and its current specifications in the range from 10 Pa to 120 kPa are reported. In addition, the methods for solving the challenges to achieve the target uncertainty is considered.