Limitations and insights regarding atmospheric mercury sampling using gold.

BACKGROUND: Atmospheric mercury (Hg) concentrations are quantified primarily through preconcentration on gold (Au) cartridges through amalgamation and subsequent thermal desorption into an atomic fluorescence spectrometry detector. This procedure has been used for decades, and is implemented in the industry-standard atmospheric Hg analyzer, the Tekran 2537. There is ongoing debate as to whether gaseous elemental mercury (Hg0) or total gaseous mercury (TGM, Hg0 + HgII) is measured using Au cartridges. The raw Hg signal processing algorithms for the Tekran 2537 analyzer have also been questioned. The objective of this work was to develop a better understanding of what forms of Hg are collected on gold cartridges through the use of permeation tube-based calibrators, that release known amounts of Hg0 and HgII. The potential differences between different Tekran analyzer models (i.e., 2537B versus 2537X) Hg signal processing algorithms, and Hg0 calibration methods were also investigated. RESULTS: Experiments were performed using Hg0 and HgII permeation calibrators. Validation tests showed that the HgII calibrator produced a reproducible and stable HgII permeation rate (2.2 ± 0.2 pg min-1). Results of HgII sampling and analysis using Au amalgamation showed the gold cartridges measured up to 75 % HgII, with the value at the beginning of the HgII measurement being much lower (as low as 10 %) due to HgII adsorption on analyzer surfaces and the Tekran particulate filter. Furthermore, thermal desorption of Hg from Au reduced only 80 % of HgII to Hg0, resulting in additional HgII that was not measured by the analyzer. By adding a thermolyzer upstream of the analyzer, 97 % of HgII was measured as Hg0. Additionally, Hg0 measurements using Tekran 2537 B and X models using a newly developed signal processing algorithm, different peak integration methods, and two Hg0 sources were compared. Results showed the 2537X model was not affected by the integration type, while the 2537B model was. Bell jar calibration based on the Dumarey equation resulted in 6 % ± 7 % (mean ± SD) underestimation of measured Hg0 concentrations compared to the calibration with a permeation calibrator. SIGNIFICANCE: Gold cartridges measured an atmospheric Hg fraction somewhere between Hg0 and TGM due to HgII adsorption and inefficient reduction of HgII to Hg0 during thermal desorption from Au. Since HgII in ambient air can be 25 % of total Hg, distinguishing between Hg0 and TGM is important. The use of a thermolyzer or a cation exchange membrane upstream of gold cartridges is recommended to enable TGM or Hg0 measurements, respectively. Observations showed that traceable multipoint calibrations of atmospheric Hg measurements are needed for Hg quantification, and that different Hg0 calibration methods can produce significantly different results for measured atmospheric Hg concentrations.

90Y SIR-Spheres Activity Measurement with New SIROS D-Vial Delivery Kit.

A new 90Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate-to-activity conversion factor to assay 90Y SIR-Spheres activity in the new SIROS kit. Methods: Eight D-vials with initial 90Y activities from 1.2 to 6.6 GBq within acrylic shields were assayed with dose calibrators and exposure-rate meters until activities decayed to approximately 0.1 GBq. The dose calibrator settings resulting in the lowest median activity errors and the best-fit slope of exposure rate versus activity were identified. Results: SIROS D-vial 90Y activity can be accurately and reliably estimated directly using setting 51 × 10 on both the CRC-15R and the CRC-55tR dose calibrators (errors within ±0.5%) and indirectly with an exposure-rate reading at 30 cm using conversion factor 0.664 ± 0.003 GBq/(mR/h) (R 2 = 0.985). Conclusion: Dose calibrator settings and exposure-rate-to-activity conversion factor for 90Y activity assays with new SIROS kit should be updated from legacy V-Vial parameters to avoid an approximately 10% underestimation.

National programme for the reliability of ionizing radiation measurements based on inter-laboratory comparisons (ILCs): ILC n°2 'radiopharmaceutical activities'.

A national Inter-Laboratory Comparisons (ILCs) programme was organized in Italy in 2022 by the Italian National Institute of Ionizing Radiation Metrology (INMRI), belonging to ENEA (Italian National Agency for New Technologies, Energy and Sustainable Economic Development), under the auspices of the Ministry of Enterprises and Made in Italy (Mimit ex MiSe). Within this ILCs programme, six inter-laboratory comparisons were organized, including the ILC-2 which focused on activity measurements carried out with radionuclide calibrators commonly used in the nuclear medicine departments of the participants. The focus was on three short-lived radionuclides - 99mTc, 18F, 177Lu - commonly employed in nuclear medicine for both diagnostic and therapeutic purposes. All presented results were compared with the reference values provided by ENEA-INMRI to ensure the traceability of measurements to the national primary activity standards. The observed deviation from the reference values of the measured activity were mainly within ± 10% (100% for 18F, 91.7% for 99mTc, 100% for 177Lu). The En statistical estimator was used to assess the participants' ability to estimate uncertainty in the provided activity values. The obtained values revealed that, in certain instances, the involved laboratories did not achieve the correct results for En (with failure rates of 22.7%, 16.7%, 12.5% for 18F, 99mTc, 177Lu, respectively), despite deviations from the reference values falling within the ± 10%. The aim of ILC-2 was to harmonize the activity measurements in the country within the field of nuclear medicine for the specific radionuclides studied and enhance the measurement capabilities of the participants.

Activity standard and calibrations for 227Th with ingrowing progeny.

Thorium-227 was separated from its progeny and standardized for activity by the triple-to-double coincidence ratio (TDCR) method of liquid scintillation counting. Confirmatory liquid scintillation-based measurements were made using efficiency tracing with 3H and live-timed anticoincidence counting (LTAC). The separation time and the efficiency of the separation were confirmed by gamma-ray spectrometry. Calibrations for reentrant pressurized ionization chambers, including commercial radionuclide calibrators, and a well-type NaI(Tl) detector are discussed.

Feasibility study of radioactivity estimation of 99mTc and 123I-labeled radiopharmaceuticals using shielded syringes.

This study investigates the feasibility of estimating the radioactivity of radiopharmaceuticals using shielded syringes. The radioactivities of 99mTc-MDP, 99mTc-HMDP, 99mTc-ECD, 99mTc-MAG3, and 123I-IMP were measured using a dose calibrator. Correlation coefficients and regression equations were obtained from the radioactivity in the shielded and unshielded syringes. 99mTc-MDP was also measured for residual radioactivity after the administration. The correlation coefficients of 99mTc-MDP, 99mTc-HMDP, 99mTc-ECD, 99mTc-MAG3, and 123I-IMP were rs = 0.9998, rs = 0.9997, rs = 0.9999, rs = 0.9998, and rs = 0.9888, respectively. The regression equations were y = 0.0364x + 0.0913, y = 0.0349x + 0.0273, y = 0.0343x - 0.0018, y = 0.0522x + 0.1215, and y = 0.0383x + 0.0058, respectively. The correlation coefficient for the residual radioactivity of 99mTc-MDP was rs = 0.9887 and the regression equation was y = 0.1505x + 0.0853. The radioactivity of 99mTc- and 123I-labeled radiopharmaceuticals in shielded syringes was accurately measured. It was suggested that the measuring shielded syringes could provide an estimate of the actual radioactivity.

Quantitative real-time PCR analysis of four genetically modified soybean events using plasmid and genomic DNA calibrators.

A calibration curve is required for reliable and accurate quantitative real-time PCR analysis of genetically modified (GM) organisms, necessitating the use of reference materials as calibrators. In this study, two types of DNA calibrators-plasmid DNA (pDNA) and genomic DNA (gDNA)-were used to quantify four GM soybean events (SYHT0H2, MON87751, DAS-44406-6, and DAS-81419-2). The PCR efficiency and linearity for the calibrators adhered to the CODEX guidelines. The conversion factor (Cf) was calculated as the ratio of copies of GM events to those of endogenous genes using the pDNA calibration curve. To assess the accuracy and repeatability of these assays, quantification at GM levels of 3% and 1% was performed. Based on our results, we believe that the pDNA calibrator assessed in this study can be used as a reference material for GMO quantitative analysis and can replace gDNA, especially considering the ease of management and advantages of mass production. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01392-0.

A metagenomics method for the quantitative detection of bacterial pathogens causing hospital-associated and ventilator-associated pneumonia.

IMPORTANCE: The management of ventilator-associated pneumonia and hospital-acquired pneumonia requires rapid and accurate quantitative detection of the infecting pathogen. To this end, we propose a metagenomic sequencing assay that includes the use of an internal sample processing control for the quantitative detection of 20 relevant bacterial species from bronchoalveolar lavage samples.

Development of an LC-MS/MS method for absolute quantification of IgG4 by evaluating dependence on the digestion efficiency using a non-cleavable/dually-cleavable internal calibrator set.

The measurement of serum IgG4 levels is mandatory for the diagnosis of IgG4-related disease, but no widely accepted reference material exists due to a lack of consensus on the standard assay. Therefore, we developed here an LC-MS/MS method for absolute quantification of IgG4 in a purified IgG sample, addressing a concern over the reliability depending on the proteolytic digestion efficiency. Our method uses internal calibrator sets containing unique amino acid sequences within IgG4, each of which comprises non-cleavable and dually-cleavable peptides labeled with different numbers of isotopes for mass separation, to determine digestion efficiency. Surrogate peptides generated by trypsin or lysyl endopeptidase digestion were selected based on selectivity, stability, and identifiability. IgG4 quantification using synthetic calibrator peptides showed high precision across the two conditions with different peptidases (relative differences ≤6.1%), even with low digestion efficiencies (<20%), which was within the interday precision under an established condition (% coefficient of variation ≤6.9%, digestion efficiencies >90%, n = 5). These results indicate that the LC-MS/MS method for quantifying IgG4 is robust against digestion efficiency variations and is applicable to validating an IgG4 reference material.

Comparison of calibration coefficients for a vinten ionization chamber simulated using four Monte Carlo methods.

The Vinten 671 ionization chamber (VIC) was modelled using Monte Carlo (MC) programs EGSnrc, Penelope, and TOPAS. Several national measurement institutes have VICs with well-characterized response relationships and have measured calibration coefficients for many radionuclides. Twelve radionuclides with various decay emissions were assessed as well as 14 monoenergetic photon sources and 10 monoenergetic electron sources. Calibration coefficients were calculated based on the energy deposited in the simulated VIC nitrogen gas volume and compared to experimental values from the literature.

New Synthetic Partial Discharge Calibrator for Qualification of Partial Discharge Analyzers for Insulation Diagnosis of HVDC and HVAC Grids.

A synthetic partial discharge (PD) calibrator has been developed to qualify PD analyzers used for insulation diagnosis of HVAC and HVDC grids including cable systems, AIS, GIS, GIL, power transformers, and HVDC converters. PD analyzers that use high-frequency current transformers (HFCT) can be qualified by means of the metrological and diagnosis tests arranged in this calibrator. This synthetic PD calibrator can reproduce PD pulse trains of the same sequence as actual representative defects (cavity, surface, floating potential, corona, SF6 protrusion, SF6 jumping particles, bubbles in oil, etc.) acquired in HV equipment in service or by means of measurements made in HV laboratory test cells. The diagnostic capabilities and PD measurement errors of the PD analyzers using HFCT sensors can be determined. A new time parameter, "PD Time", associated with any arbitrary PD current pulse i(t) is introduced for calibration purposes. It is defined as the equivalent width of a rectangular PD pulse with the same charge value and amplitude as the actual PD current pulse. The synthetic PD calibrator consists of a pulse generator that operates on a current loop matched to 50 Ω impedance to avoid unwanted reflections. The injected current is measured by a reference measurement system built into the PD calibrator that uses two HFCT sensors to ensure that the current signal is the same at the input and output of the calibration cage where the HFCT of the PD analyzer is being calibrated. Signal reconstruction of the HFCT output signal to achieve the input signal is achieved by applying state variable theory using the transfer impedance of the HFCT sensor in the frequency domain.

Sulfonamide drugs: Low-cost spectrofluorometric determination using a computer monitor calibrator for detection.

A possibility of the use of a common monitor calibrator as a portable and inexpensive tool for the fluorometric determination of sulfonamide drugs after their reaction with fluorescamine was examined. The luminescence measurements with a calibrator are based on irradiation of a test sample by the device lamp with a broadband spectrum in the visible and near UV regions and simultaneous registration of the secondary radiation by the device detector. Two types of cuvettes with black light absorbing sides eliminating the reflected self-radiation were tested. The commercially available Eppendorf-type black plastic microtubes ("LightSafe") were suggested as a good option for such measurements. It was shown that a monitor calibrator can be applied for optimization of the determination conditions. By the example of sulfanilamide and sulfamethazine, it was shown that the procedure should be carried out at pH 4-6 and fluorescamine concentration of 200 µmol L-1, and 40 min of the interaction. The limit of detection of sulfanilamide and sulfamethazine using a monitor calibrator is 0.9 µmol L-1 and 0.8 µmol L-1, respectively, which is comparable with their spectrophotometric determination.

Activity Measurement of 44Sc and Calibration of Activity Measurement Instruments on Production Sites and Clinics.

44Sc is a promising radionuclide for positron emission tomography (PET) in nuclear medicine. As a part of the implementation of a production site for 44Sc, precise knowledge of the activity of the product is necessary. At the Paul Scherrer Institute (PSI) and the University of Bern (UniBE), 44Sc is produced by enriched 44CaO-target irradiation with a cyclotron. The two sites use different techniques for activity measurement, namely a dose calibrator at the PSI and a gamma-ray spectrometry system at UniBE and PSI. In this work, the 44Sc was produced at the PSI, and samples of the product were prepared in dedicated containers for onsite measurements at PSI, UniBE, and the Institute of Radiation Physics (IRA) in Lausanne for precise activity measurement using primary techniques and for the calibration of the reference ionization chambers. An accuracy of 1% was obtained for the activity measurement, allowing for a precise calibration of the dose calibrator and gamma-ray spectrometry of the two production sites. Each production site now has the capability of measuring 44Sc activity with an accuracy of 2%.

Comparison and calibration of methods for ambient reactive mercury quantification.

Gaseous oxidized mercury (GOM) is the dominant form of atmospheric mercury (Hg) deposited and sequestered within ecosystems. Thus, accurate, calibrated measurements of GOM are needed. Here, two active membrane-based collection systems (RMAS) were used to determine GOM and particulate-bound Hg (PBM), as well as reactive Hg (RM = GOM + PBM), and compared with two dual-channel systems (DCS) and a Tekran 2537/1130 speciation system. The DCS measured operationally defined GOM by difference, using concentrations of gaseous elemental Hg (GEM) and total gaseous Hg. One DCS was linked to a custom-built, automated calibration system that permeated GEM, HgBr2, or HgCl2. The five systems were co-located for one-year to develop a dataset that would allow for understanding limitations of each system, and assessing measurement accuracy and long-term precision of the calibrator. The Tekran system measured ~14.5 % of the GOM measured by the other systems. The USU and UNR DCS and RMAS were significantly correlated, but the DCS was 50 and 30 % higher, respectively, than the RMAS. The calibrator performed consistently in the field and lab, and the DCS fully recovered GOM injected by the calibrator. Since the uncalibrated DCS measured the same concentrations as the calibrated DCS, they are both accurate methods for measuring RM and/or GOM. Some loss occurred from the RMAS membranes. SYNOPSIS: Accurate and calibrated measurements of atmospheric reactive mercury using membranes and two dual-channel systems.

Comparison of Commercial Low Molecular Weight Heparin and Homemade Anti-Xa Calibrators to a Commercial Specific Anti-Xa Calibrator for Plasma Rivaroxaban Quantification by Anti-Xa Oral Anticoagulant Plasma Concentration Chromogenic Assay.

OBJECTIVE: The main concern about measuring the concentration of rivaroxaban by anti-Xa assay in some laboratories is the lack of a commercial specific calibrator in emergencies. Therefore, this study aimed at providing a homemade anti-Xa calibrator and commercial low molecular weight heparin (LMWH) anti-Xa calibrator. METHODS: The anti-Xa plasma concentration of rivaroxaban was measured in 70 patients using a commercial specific anti-Xa calibrator, a commercial LMWH anti-Xa calibrator, and a homemade anti-Xa calibrator. RESULTS: We demonstrated a significant correlation and agreement (P < .001) between LMWH-calibrated anti-Xa and the commercial specific calibrator. A significant correlation (P < .001) was found between homemade calibrated anti-Xa made by normal pooled plasma and that calibrated with a commercial specific drug. The nonspecific homemade and LMWH calibrators had excellent agreement (P < .001) and can be used interchangeably. CONCLUSION: Our data showed that for estimating rivaroxaban concentrations, the LMWH calibrator could be used as an alternative calibrator in the anti-Xa assay.

Fully synthetic phosphorylated Tau181, Tau217, and Tau231 calibrators for Alzheimer's disease diagnosis.

Background: The calibrator in immunoassay plays an essential role in diagnosing Alzheimer's disease (AD). Presently, the most well-studied biomarkers for AD diagnosis are three phosphorylated Tau (p-Tau): p-Tau231, p-Tau217, and p-Tau181. Glycogen synthase-3beta (GSK3ß)-phosphorated Tau-441 is the most commonly used calibrator for p-Tau immunoassays. However, the batch-to-batch inconsistency issue of the commonly used GSK3ß-phosphorylated Tau-441 limits its clinical application. Methods: We have successfully generated and characterized 61 Tau monoclonal antibodies (mAbs) with distinct epitopes by using the hybridoma technique and employed them as capture or detection antibodies for p-Tau immunoassays. Through chemical synthesis, we synthesized calibrators, which are three peptides including capture and detection antibody epitopes, for application in immunoassays that detect p-Tau231, p-Tau217, and p-Tau181. The novel calibrators were applied to Enzyme-linked immunosorbent assay (ELISA) and Single-molecule array (Simoa) platforms to validate their applicability and establish a range of p-Tau immunoassays. Results: By employing the hybridoma technique, 49 mAbs recognizing Tau (1-22), nine mAbs targeting p-Tau231, one mAb targeting p-Tau217, and two mAbs targeting p-Tau181 were developed. Peptides, including recognition epitopes of capture and detection antibodies, were synthesized. These peptides were used as calibrators to develop 60 immunoassays on the ELISA platform, of which six highly sensitive immunoassays were selected and applied to the ultra-sensitive Simoa platform. Remarkably, the LODs were 2.5, 2.4, 31.1, 32.9, 46.9, and 52.1 pg/ml, respectively. Conclusion: Three novel p-Tau calibrators were successfully generated and validated, which solved the batch-to-batch inconsistency issue of GSK3ß-phosphorylated Tau-441. The novel calibrators exhibit the potential to promote the standardization of clinical AD diagnostic calibrators. Furthermore, we established a series of highly sensitive and specific immunoassays on the Simoa platform based on novel calibrators, which moved a steady step forward in p-Tau immunoassay application for AD diagnosis.

Comparative Analysis on the Effect of Surface Reflectance for Laser 3D Scanner Calibrator.

The calibrator is one of the most important factors in the calibration of various laser 3D scanning instruments. The requirements for the diffuse reflection surface are emphasized in many national standards. In this study, spherical calibrator and plane calibrator comparative measurement experiments were carried out. The black ceramic standard sphere, white ceramic standard sphere, metal standard sphere, metal standard plane, and white ceramic standard plane were used to test the laser 3D scanner. In the spherical calibrator comparative measurement experiments, the results indicate that the RMS of the white ceramic spherical calibrator with a reflectance of approximately 60% is 10 times that of the metal spherical calibrator with the reflectance of approximately 15%, and the RMS of the black ceramic spherical calibrator with reflectance of approximately 11% is of the same order as the metal spherical calibrator. In the plane calibrators comparative measurement experiments, the RMS of the flatness measurement is 0.077 mm for the metal plane calibrator with a reflectance of 15%, and 2.915 mm for ceramic plane calibrator with a reflectance of 60%. The results show that when the optimal measurement distance and incident angle are selected, the reflectance of the calibrator has a great effect on the measurement results, regardless of the outlines or profiles. Based on the experiments, it is recommended to use the spherical calibrator or the standard plane with a reflectance of around 18% as the standard, which can obtain reasonable results. In addition, it is necessary to clearly provide the material category and surface reflectance information of the standard when calibrating the scanner according to the measurement standard.

Primary standardization of 212Pb activity by liquid scintillation counting.

An activity standard for 212Pb in equilibrium with its progeny was realized, based on triple-to-double coincidence ratio (TDCR) liquid scintillation (LS) counting. A Monte Carlo-based approach to estimating uncertainties due to nuclear decay data (branching ratios, beta endpoint energies, γ-ray energies, and conversion coefficients for 212Pb and 208Tl) led to combined standard uncertainties ≤ 0.20 %. Confirmatory primary measurements were made by LS efficiency tracing with tritium and 4παß(LS)-γ(NaI(Tl)) anticoincidence counting. The standard is discussed in relation to current approaches to 212Pb activity calibration. In particular, potential biases encountered when using inappropriate radionuclide calibrator settings are discussed.

Lot verification practices in Ontario clinical chemistry laboratories - Results of a patterns-of-practice survey.

Objectives: Verifying new reagent or calibrator lots is crucial for maintaining consistent test performance. The Institute for Quality Management in Healthcare (IQMH) conducted a patterns-of-practice survey and follow-up case study to collect information on lot verification practices in Ontario. Methods: The survey had 17 multiple-choice questions and was distributed to 183 licensed laboratories. Participants provided information on materials used and approval/rejection criteria for their lot verification procedures for eight classes of testing systems. The case study provided a set of lot comparison data and was distributed to 132 laboratories. Responses were reviewed by IQMH scientific committees. Results: Of the 175 laboratories that responded regarding reagent lot verifications, 74% verified all tests, 11% some, and 15% none. Of the 171 laboratories that responded regarding calibrator lot verifications, 39% verified all calibrators, 4% some, and 57% none. Reasons for not performing verifications ranged from difficulty performing parallel testing to high reagent cost. For automated chemistry assays and immunoassays, 23% of laboratories did not include patient-derived materials in reagent lot verifications and 42% included five to six patient materials; 58% of laboratories did not include patient-derived materials in calibrator lot verifications and 23% included five to six patient materials. Different combinations of test-specific rules were used for acceptance criteria. For a failed lot, 98% of laboratories would investigate further and take corrective actions. Forty-three percent of laboratories would accept the new reagent lot in the case study. Conclusion: Responses to the survey and case study demonstrated variability in lot verification practices among laboratories.

A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer's Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration.

Neurofilament light chain (Nf-L) is a well-known biomarker for axonal damage; however, the corresponding circulating Nf-L analyte in cerebrospinal fluid (CSF) is poorly characterized. We therefore isolated new monoclonal antibodies against synthetic peptides, and these monoclonals were characterized for their specificity on brain-specific intermediate filament proteins. Two highly specific antibodies, ADx206 and ADx209, were analytically validated for CSF applications according to well-established criteria. Interestingly, using three different sources of purified Nf-L proteins, a significant impact on interpolated concentrations was observed. With a lower limit of analytical sensitivity of 100 pg/mL using bovine Nf-L as the calibrator, we were able to quantify the Nf-L analyte in each sample, and these Nf-L concentrations were highly correlated to the Uman diagnostics assay (Spearman rho = 0.97, p < 0.001). In the clinical diagnostic groups, the new Nf-L ELISA could discriminate patients with Alzheimer's disease (AD, n = 20) from those with frontotemporal lobe dementia (FTD, n = 20) and control samples with subjective cognitive decline (SCD, n = 20). Henceforth, this novel Nf-L ELISA with well-defined specificity and epitopes can be used to enhance our understanding of harmonizing the use of Nf-L as a clinically relevant marker for neurodegeneration in CSF.