Metrology Programme Research Articles

APMP Pilot Study on High Transmittance Haze

Abstract This article presents the results of the Asia Pacific Metrology Programme (APMP) pilot comparison on high transmittance haze (TH), specifically TH >40 %. Various methods, including ASTM D1003, ISO 14782, the double beam method, and the double compensation method were employed. The results revealed that ASTM D1003 is still influenced by failure to compensate for sphere throughput, even in high TH artefacts. In contrast, the other methods exhibit good consistency, as expected. This article also analyses the total transmittance (TT) and diffuse transmittance (DT) obtained using the double compensation method, theoretically capable of determining accurate TT, DT, and TH, discussing the possibility of inconsistency in the reflectance between the sphere wall and the white plate affecting the agreement.

Evaluation of on-site calibration procedures for SKYNET Prede POM sun–sky photometers

Abstract. To retrieve columnar intensive aerosol properties from sun–sky photometers, both irradiance and radiance calibration factors are needed. For the irradiance the solar calibration constant, V0, which denotes the instrument counts for a direct normal solar flux extrapolated to the top of the atmosphere, must be determined. The solid view angle, SVA, is a measure of the field of view of the instrument, and it is important for obtaining the radiance from sky diffuse irradiance measurements. Each of the three sun-photometer networks considered in the present study (SKYNET, AERONET, WMO GAW) adopts different protocols of calibration, and we evaluate the performance of the on-site calibration procedures, applicable to every kind of sun–sky photometer but tested in this analysis only on SKYNET Prede POM01 instruments, during intercomparison campaigns and laboratory calibrations held in the framework of the Metrology for Aerosol Optical Properties (MAPP) European Metrology Programme for Innovation and Research (EMPIR) project. The on-site calibration, performed as frequently as possible (ideally monthly) to monitor changes in the device conditions, allows operators to track and evaluate the calibration status on a continuous basis, considerably reducing the data gaps incurred by the periodic shipments for performing centralized calibrations. The performance of the on-site calibration procedures for V0 was very good at sites with low turbidity, showing agreement with a reference calibration between 0.5 % and 1.5 % depending on wavelengths. In the urban area, the agreement decreases between 1.7 % and 2.5 %. For the SVA the difference varied from a minimum of 0.03 % to a maximum of 3.46 %.

Preparation of multicomponent mixtures to support carbon metrology

The Reference Gas Laboratory (LGR) of Portuguese Institute for Quality (IPQ) is participating in the project – Metrology Support for Carbon Capture Utilization and Storage (MetCCUS) under the new European Partnership on Metrology Program (EPM).The goal of this project is to develop a metrological infrastructure that enables monitoring and detection of carbon dioxide leaks in energy and industrial processes, in transport networks and also allow the support of a better understanding of the life cycle of carbon dioxide.The contribution of LGR involves the preparation of certified reference materials (CRM) to allow the measurement of impurities in CO2 with the associated uncertainties and metrological traceability. The study is focused on the impurities: SO2, H2S, CO, O2 and CH4. This work also involves the study of interferents based on the analytical methods used. These CRM will provide support for the calibration and validation of instrumentation used in carbon capture processes.

Implementation of ICRU report 90 to re-evaluate the dosimetry standards in Taiwan

The purpose of this investigation is to re-evaluate primary dosimetry standards at the National Radiation Standard Laboratory (NRSL/INER) according to the recommendation of the International Commission on Radiation Units and Measurements Report 90 (ICRU Report 90). These standards are air kerma (Kair) in X-rays, 60Co and 137Cs beams, absorbed dose to water (DW) in 60Co beam, as well as reference air kerma (RAKR) in 192Ir beam for brachytherapy in Taiwan.However, the Consultative Committee for Ionizing Radiation (CCRI) summarized the expected changes in ICRU Report 90 to primary standards. These include modifications to the mean excitation energy of water (Iw) and graphite (Ig), the application of the density effect correction for graphite, new combined correction factors and the uncertainty related to the average energy required to create an ion pair in air (Wair), improved calculations of the stopping power, and the adoption of renormalized photoeffect cross-section. The recommendations of the CCRI were adopted for recalculation regarding correction factors and radiation-matter interaction constants for NRSL/INER primary standards. Furthermore, a newer version of Monte Carlo software and the alternative measurements with new ionization chambers (ICs) of a similar design were used to reassess the impact on the NRSL/INER standards. Consequently, the impact of the new ICRU recommendation on dosimetry standards ranged from -0.8% to 0.1%. The changes to the primary standards are in good correlation with similar changes implemented for the BIPM primary standards. For international comparisons of these standards, adoption of the ICRU Report 90 would not change significantly the degree of equivalence stated in the Asia-Pacific Metrology Programme (APMP) key and supplementary comparison database considering the impacts of the BIPM standards in the comparisons of APMP.RI(I)-K3, APMP.RI(I)-K1.1, APMP.RI(I)-K4, APMP.RI(I)-K8 and APMP.RI(I)-S3. Therefore, the NRSL/INER has formally implemented the re-evaluation standards on the 1st January 2024.

On the accuracy of the gradient method for determining the mean integral refractive index of air for large-scale dimensional measurements

The results of the analysis of the accuracy capabilities of the gradient method for determining the mean integral value of the group refractive index of air along the path of the laser radiation propagating on the surface atmospheric layer are presented. The mean integral refractive index of air is used in precision laser ranging as a correction to the results of large-scale dimensional measurements, taking into account the difference between the speed of the laser radiation propagation in the atmosphere and the speed of light in vacuum. The performed analysis includes a critical review of publications underpinning this method, and the prospects for its use in high-precision laser measurements of horizontal baselines of up to 5 km long with an expanded uncertainty of less than or equal to 1 mm are considered. This method has been studied in the framework of the Project 18 SIB01 GeoMetre “Large-Scale Dimensional Measurements for Geodesy” executed in accordance with the European Metrology Programme for Innovation and Research (EMPIR).

Proficiency testing for event-specific quantification of genetically modified maize MON87427: Performance assessment based on the metrologically traceable reference values as assigned values

The Asia Pacific Metrology Program and the Accreditation Cooperation joint Proficiency Testing (PT) program for the quantification of genetically modified maize MON87427 was organized by the National Institute of Metrology, China, to enhance the measurement accuracy and metrological traceability in the region. Certified reference materials were employed as test samples; metrologically traceable certified reference values served as PT reference values (PTRVs) for evaluating the participants results. The consensus values obtained from the participants were higher than the assigned values, potentially due to the systematic effects of DNA extraction process. The participants' relatively poor overall performance by the ζ-score compared with z-score demonstrates their need to thoroughly investigate quantification bias to elevate the measurement capability of genetically modified (GM) content and deepen their understanding of uncertainty estimation. This program confirmed the importance of using metrologically traceable reference values instead of consensus values as PTRV for reliable performance assessment.

Influence of Printing Angulation on the Accuracy (Trueness and Precision) of the Position of Implant Analogs in 3D Models: An In Vitro Pilot Study

Background: With CAD-CAM, dental models are often fabricated by additive manufacturing (AM) methods. Dental models for implant prostheses involve the manual placement of analogs, which could affect their final fit. Therefore, in this experimental in vitro study, the accuracy of the analogs’ position in models printed using AM methods was examined by comparing three different printing orientations. Methods: An STL file was obtained by scanning a master model with an implant placed in the maxillary left central incisor position. Three study groups (n = 10) with varying printing orientation parameters were obtained (0, 45, and 90 degrees). They were digitalized with a laboratory scanner and evaluated with an analysis metrology program. Differences between 3D datasets were measured using the RMS for trueness and SD RMS for precision. The data were statistically analyzed using the ANOVA test at a significance level of p < 0.05, followed by the Bonferroni post hoc test. Results: The 45-degrees group showed the best results. Regarding trueness, statistically significant differences were found between the 45- and 90-degrees groups (p < 0.005). In terms of precision, statistically significant differences appeared between the 45- and 0-degrees groups (p < 0.011) and between the 45- and 90-degrees groups (0.003). Conclusions: The printing angulation parameter affects the accuracy of 3D-printed models. Implant models manufactured at 45 degrees of printing angulation are more accurate than those printed at 0 or 90 degrees.

Socialization of Law Number 2 of 1981 and Law Number 8 of 1999 to Make it Happen Orderly Measuring Trade Through Tera and Retracting Measurement Tools and Education of Traders in Berastagi Market and Students of SMA Negeri 2 Kabanjahe

Sustainable Development Goals (SDGs) is a global action plan agreed upon by world leaders, including Indonesia, to end poverty, reduce poverty and protect the environment. SDGs contain 17 goals and 169 targets which are expected to be achieved by 2030. Universities are expected to help the government in strengthening SDGs programs. One of the 9th SDGs programs is "Building resilient infrastructure, increasing inclusive and sustainable industry, and encouraging innovation. In line with the 9th SDGs program, the people of North Sumatra Province who are highly dependent on agricultural livelihoods need innovation and empowerment programs to increase their efficiency and productivity. The Karo Regency area in North Sumatra Province has been developed into production centers for agricultural products such as vegetables and fruit. Berastagi is a fruit and vegetable producing center as well as a tourist area. As a producer and tourism center, the government has designated the Berastagi fruit market as an orderly market. However, it was found that the weighing measuring instruments owned by traders at the Berastagi fruit market did not have a valid stamp and had expired stamps, which resulted in a decrease in regional levy income for Karo Regency. Apart from that, the transfer of the D3 Metrology and Instrumentation study program in 2022 from FMIPA to USU's Faculty of Vocational Studies is not yet well known to the public, resulting in a decline in student interest in entering the D3 Metrology and Instrumentation study program, which has been proven to be far below the quota accepted in the 2023 new student admission achievement pathway. For this reason, through the community service program in 2023, it is necessary to introduce the D3 Metrology and Instrumentation study program through socialization activities on Law Number 2 of 1981 concerning Re-Terra and Re-Terra and Law Number 8 of 1999 concerning Consumer Protection, education on Re-Terra of Measuring Instruments. Weigh measuring instruments and carrying out re-testing of weighing measuring instruments for students and teachers at SMA Negeri 2 Kabanjahe and re-calibrating measuring measuring instruments owned by traders at the Berastagi fruit market and it is hoped that students and teachers at SMA Negeri 2 Kabanjahe will become informants about the importance of measuring instruments. repeat weighing measurements and have an interest in becoming a translatorthrough studying at the D3 Metrology and Instrumentation study program, USU Vocational Faculty.

Metrology supporting the European regulation for radiation protection.

The European Association of National Metrology Institutes (EURAMET) within its research programme European Metrology Programme for Innovation and Research (EMPIR) funded project EMPIR 19NET03 supportBSS that contributes to the establishment of a European Metrology Network (EMN) for Radiation Protection (RP). The EMN-RP was established in September 2021 with the intent to work as a meeting point for the metrology community and all stakeholders in the field of ionising radiation regulation, thus providing quality assurance for measurements in each of the exposure situations contemplated in the European Legislation. Within project EMPIR 19NET03, work package 3 aims at the preparation of a Strategic Research Agenda (SRA) by identifying the metrology needs to support the European legislation and regulation in Radiation Protection and of two Roadmaps for metrology services, one under the European Council Directive 2013/59/EURATOM and the other under the EURATOM Treaty. Following a Gaps Workshop held in September 2020 and a second internal workshop that took place in April 2022, a questionnaire was prepared for distribution to the stakeholders, e.g. RP platforms and authorities, academia, industry, among other, together with an accompanying paper. In this paper, the authors present the state of the art of European legislation in RP, address the importance of metrology, the practices and activities that need metrology to meet the requirements set in the regulations, emphasise the need for quality assured measurements in all fields, highlight the stakeholders contributions in their specific area and show their vision of the EMN-RP.

Effect of print orientation, storage conditions, and storage time on intaglio surface accuracy of implant surgical guides fabricated by using a stereolithography technology

The accuracy of printed implant surgical guides can be affected by different factors that negatively impact the planned implant position. How print orientation, storage time, and conditions influence manufacturing accuracy remains uncertain. The purpose of this in vitro study was to evaluate the influence of print orientation, storage conditions, and storage time on the intaglio surface accuracy of implant surgical guides manufactured by using a stereolithography (SLA) printer. A tooth-supported maxillary implant surgical guide design (control file) was used to fabricate the specimens (N=40, n=10). Four groups were created based on the print orientation used: 0 (Group 0), 45 (Group 45), 70 (Group 70), and 90 degrees (Group 90). The specimens were fabricated using an SLA printer (Form 3B+) and a biocompatible dental resin (Surgical Guide Resin V1) following the manufacturer's recommended protocol. Each group was divided into 2 subgroups based on the storage conditions: light (L subgroup) and dark (D subgroup) settings. Each specimen was digitized by using a desktop scanner (Medit T710) at days 0, 1, 7, and 14. The control file and each digitized specimen were superimposed by using the best-fit technique with a metrology program (Geomagic Control X). The root mean square (RMS) error was used to calculate the discrepancies between the control files and specimen files. Three-way ANOVA and pairwise comparison Tukey tests were used to analyze trueness. The Levene test was used to assess precision (α=.05). Significant trueness discrepancies were found among the groups tested (P<.001), but no significant differences were found among the subgroups (P=.100) and the storage times analyzed (P=.609). Additionally, the Tukey test showed significant RMS error mean value discrepancies between Group 0 and Group 45 (P<.001), Group 0 and Group 90 (P<.001), Group 45 and Group 70 (P<.001), and Group 70 and Group 90 (P<.001). The Levene test revealed significant SD discrepancies among the groups tested (P<.05). The trueness and precision of the intaglio surface of the implant surgical guides manufactured by using the printer and material tested were affected by the print orientation. However, storage conditions over a 14-day period did not impact the intaglio accuracy of the specimens.

Involvement and use of European Metrology Programme for Innovation and Research EMPIR in the Czech Metrology Institute – a positive example of the use of European cooperation

The Czech Metrology Institute (CMI) has been the national metrology institute of the Czech Republic since 1993. The significant development of the CMI's fundamental metrology departments and the gradual growth of the CMI's scientific and research capacities are linked to its successful participation in the European Metrology Research Programme (EMRP) and the European Metrology Programme for Innovation and Research (EMPIR). In total, 28 countries have participated in the EMPIR Programme, with Switzerland, Norway, Serbia, Bosnia and Herzegovina, Turkey and the UK in addition to the EU Member States. The necessary organisational and administrative background for the realisation of the EMPIR Programme was provided by EURAMET e.V., a European Regional Metrology Organisation operated as a non-profit association under German law. The most important benefit of the Programme for the CMI and the Czech Republic is the successful implementation of the research results of individual EMPIR projects. Within the framework of this implementation of the EMPIR results in the CMI, 6 new state measurement standards of the Czech Republic have already been established and another 4 are in the stage of preparation for announcement. Furthermore, 23 new or significantly modified measurement methods have been developed based on the results within the CMI and are now provided as a service by the CMI. Finally, participation in the EMPIR projects has been used to train 42 new CMI scientists in various fields of measurement. If to add to this the use of the results of the former EMRP Programme, it can be concluded that the development of metrology at the CMI over the last 10 years has been strongly conditioned by successful participation in European Metrology Programmes and the ability of the CMI to subsequently apply the results of individual projects to its laboratory practice.

Development and evaluation of primary calibration methods in underwater acoustics in a frequency range from 1 Hz to 100 Hz

The project entitled “Metrology for Low Frequency Sound and Vibration” (“INFRA-AUV”), currently active within the European Metrology Programme for Innovation and Research (EMPIR). Measurement of seismic and infrasound activity is very important for monitoring natural extreme events. Low frequency sound and vibration monitoring technologies are well-established, but the sensors are often used for specific and local applications only and lack traceability. This project aims to establish both the first primary measurement standards for low frequency sound (in both air and water) and vibration. The aim of the task “Development and Evaluation of Primary Calibration Methods in Underwater Acoustics in a Frequency Range from 0.5 Hz to 100 Hz” is to develop and evaluate candidate calibration techniques in underwater acoustics for use as primary standards in frequency range of interest. These methods will be evaluated in terms of their limitations, uncertainty contributions and calibration results. The pressure coupler reciprocity method is based on the hydrophone, a transducer and projector which are calibrated inside a relatively small coupling chamber where the acoustic field is homogenous. Through a series of electrical measurements of voltage and current, the acoustic sensitivity of the three devices may be calculated traceable to electrical primary units.

Wear at the implant-framework interface between titanium implant platform and the additively manufactured titanium and cobalt-chromium frameworks.

To measure the wear at the implant interface between the Grade 4 titanium (Ti) of the implant and frameworks fabricated using two additively manufactured alloys (Ti alloy and cobalt-chromium [Co-Cr]) pre- and post-artificial aging. Three-unit frameworks supported by two implants were additively manufactured (Atlantis; Dentsply Sirona) using Ti and Co-Cr dental alloys. Two implants (OsseoSpeed EV, Astra Tech; Dentsply Sirona) were torqued on each non-engaging framework. The assembled implant-frameworks were secured into polyurethane foam blocks. Groups were created based on the material and surface assessed: framework (Ti-framework and Co-Cr-framework groups) and implant (Ti-implant group). Two subgroups were created depending on the location: premolar (PM) and molar (M). Computed tomography images were obtained pre- (as manufactured) and post-simulated mastication procedures. The pre- and post-simulated mastication files of each specimen were aligned using the best-fit algorithm using a metrology program. Wear was measured by calculating the volumetric discrepancies at the implant interface on 64 measurement points per area analyzed. Three-way ANOVA and Tukey tests were used to analyze the data (α=0.05). The mean volumetric discrepancy values ranged from 0.8 to 3.1µm among all the subgroups tested. The group (framework vs. implant) (p<0.001) and tooth location (p<0.001) were significant factors of the mean volumetric discrepancy values obtained. The framework group presented with significantly lower volumetric discrepancy mean values (1µm) compared with the implant group (3µm), whereas the premolar area obtained significantly lower mean volumetric discrepancy values (1.9µm) compared with the molar location (2.3µm). Volumetric discrepancies were found at the implant-framework interface tested between the pre- and post-artificial aging measurements ranging from 1 to 3µm after 1,200,000 cyclic loading that simulated approximately 12 months of function.

APMP supplementary international comparison of activity measurement of Cs-134 and Cs-137 in brown rice

Main textThe supplementary international comparison of activity measurement of Cs-134 and Cs-137 in brown rice (APMP.RI(II)-S3.Cs-134.Cs-137) was carried out within the framework of the Asia-Pacific Metrology Programme (APMP). The matrix of the sample was brown rice grain harvested in autumn 2011, after the accident at the Fukushima Daiichi Nuclear Power Plant. No spiking was applied to the sample. Eight institutes reported their measurement results. Averages of the reported results and their associated uncertainties were obtained using the power-moderated mean. This report describes the supplemental comparison reference value, the degree of equivalence of the results, the procedure of the comparison and the sample preparation and measurements by the participants.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).

Final report on APMP.EM-K2 key comparison of resistance standards at 10 MΩ and 1 GΩ

Main textIn order to link the National Metrology Institutes (NMI) organized in Asia Pacific Metrology Programme (APMP) to the key comparison CCEM-K2, APMP.EM-K2 key comparison was piloted by the Korea Research Institute of Standards and Science (KRISS), beginning in July 2010 and completed July 2014 with the participation of 13 National Metrology Institutes (NMIs). The results of this key comparison for 10 MΩ and 1 GΩ standards indicate good agreement among the 13 participating NMIs despite the long comparison period. Agreement is well within the level of confidence of 95%.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 CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Final report of APMP comparison of mass standards APMP.M.M-K5 (Sub-) multiples mass key comparison

Main textThis report describes a key comparison of mass standards APMP.M.M-K5, conducted between 19 participating members of the Asia-Pacific Metrology Programme (APMP). The APMP.M.M-K5 comparison was launched during the 13th meeting of the Technical Committee for Mass and Related Quantities APMP-TCM (2012).Two sets of stainless steel weights with five nominal mass values: 2 kg, 200 g, 50 g, 1 g, and 200 mg were used as travelling standards. These nominal values were chosen as they followed the nominal values of CCM.M-K5. The aim of the comparison is to verify the consistency of 2 kg, 200 g, 50 g, 1 g and 200 mg stainless steel mass standards among members of APMP-TCM.The program was piloted by the National Institute of Metrology, P.R. China (NIM). All the participants have provided their support and help to successfully organize and run the comparison. The nominated 19 participants have been divided into five petals and the corresponding five sets of transfer standards have been circulated within the groups simultaneously. The pilot laboratory measured the volumes and the magnetic properties of the standards before the circulation and had reported these values to the participants. The pilot laboratory has also verified the stability of all travelling standards for more than one year. The set of five weights was circulated among all the participating laboratories in August 2015 and received back from the last participant in August 2016. The final report of this comparison is being given in this document.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).

Trueness and Precision of Eight Intraoral Scanners with Different Finishing Line Designs: A Comparative In Vitro Study.

This study aimed to evaluate the accuracy in terms of trueness and precision of eight intraoral scanners (IOS) and the effect of different finishing line designs on the IOS's accuracy. Three printed models of the maxillary arch with maxillary right first molar virtually prepared with chamfer, shoulder, and vertical preparation designs were used as master models in this study. Each model was scanned 30 times with each IOS: Medit i700, Planscan Emerald S, CEREC Primescan, TRIOS 3, CS3600, MEDIT i500, Heron 3Disc, and Cerec Omnicam. The trueness was measured by superimposition of the scanned dataset made with IOS and the scanned dataset made with a lab scanner (In Lab Medit T710) that was used as a reference and the deviation was measured and expressed as a color-coded map by the metrology program (Medit compare, version 2.3.5.892), while precision was measured by the superimposition of the scans of each IOS on each other.The data were analyzed statistically using repeated measure analysis of variance (ANOVA) test, one-way ANOVA test, and Bonferroni test at significance level of 0.05. The tested IOS showed significant differences in trueness and precision. Medit i700 and CEREC Primescan recorded the highest precision with no significant difference between them, while Medit i700 recorded the highest trueness as compared to other IOS. Each IOS showed significant differences in trueness and precision with the three finishing line designs except CEREC Primescan and Heron 3 disc that showed no significant difference in trueness with the three finishing line designs and CS3600 that showed no significant difference in precision with the three finishing line designs. A significant difference in accuracy was found among the tested IOS and the type of finishing line design had a significant effect on IOS's accuracy.

APMP-APLAC joint proficiency testing programs for elemental analysis in food with metrological reference values: Assessment of participants' performance considering measurement uncertainties

The Asia Pacific Metrology Program (APMP) and the Asia Pacific Laboratory Accreditation Cooperation (APLAC) joint Proficiency Testing (PT) programs for toxic elements such as cadmium (Cd) and lead (Pb) or nutritional elements such as iron (Fe) and zinc (Zn) in food were organized by the Korea Research Institute of Standards and Science (KRISS) with the aim of enhancing the quality of measurement and metrological traceability in various economies of the Asia Pacific region by evaluating the performance with rigorous evaluation. Three APMP-APLAC joint PT programs for elemental analyses were carried out by KRISS sequentially, where candidate certified reference materials (CRMs) were used as the PT materials and metrologically traceable certified reference values (RVs) were used as the PT assigned values for the evaluation of participants' results, which allows reliable evaluation of participant performance. This article describes the operation of the PTs and the overall performance of the participating laboratories. The effectiveness of these joint PT programs and trends in PT performance assessment are also discussed. These PT programs confirm the significant importance of using the metrologically traceable RVs instead of the consensus values from participants as the PT assigned value for reliable assessment. The lack of understanding of the concept of coverage factor, degree of freedom, standard uncertainty, and expanded uncertainty was revealed by some participants in these PT programs. Interpreting the zeta-scores or En scores, which are derived by using measurement uncertainties, in conjunction with the z-scores is highly meaningful for assessing participants' ability in measurement capabilities and measurement uncertainty evaluation. Assessment of participants' performance considering measurement uncertainties helps the participants to check how reasonable their measurement uncertainty estimation was. The results of PTs also demonstrated that these PT programs are useful for improving the measurement capability of the laboratories, whereas more capability-building in uncertainty evaluation is required for further improvement.

Detection, characterization, and spatial mapping of nucleated cavitation for drug delivery: From in-vitro-, through in-vivo to the clinic

Cavitation-nucleation agents that stabilize gas bubbles, be they micro or nano in scale, allow for consistent and reliable induction of cavitation compared to endogenous nuclei. When these agents are used in conjunction with an ultrasound system that can perform simultaneous image-guidance to target tumors, focused ultrasound delivery to cause cavitation, and imaging of cavitation emissions as a treatment monitor, a complete drug delivery system is possible that can enhance the penetration and distribution of oncology agents into solid tumors. Development of novel, clinical cavitation agents requires, from their early prototyping through to their ultimate product release, that the detection and characterization of their cavitation performance is considered. Additionally, the methods and equipment used to detect and image cavitation both in preclinical and clinical drug delivery systems must be similarly assessed to ensure that the cavitation “dose” estimated from the agents is understood in precision to ensure reliable drug delivery. To achieve these objectives, OxSonics continues to develop, alongside its new bubble formulations, a cavitation metrology program that investigates cavitation performance and quantification, cavitation test articles and protocols, validation of these methods, and equipment calibration and qualification. This talk explores all the aspects of this from the prototyping stage to clinical deployment.

Calibration of insulin pumps based on discrete doses at given cycle times.

One application in the medical treatment at very small flow rates is the usage of an Insulin pump that delivers doses of insulin at constant cycle times for a specific basal rate as quasi-continuous insulin delivery, which is an important cornerstone in diabetes management. The calibration of these basal rates are performed by either gravimetric or optical methods, which have been developed within the European Metrology Program for Innovation and Research (EMPIR) Joint Research Project (JRP) 18HLT08 Metrology for drug delivery II (MeDDII). These measurement techniques are described in this paper, and an improved approach of the analytical procedure given in the standard IEC 60601-2-24:2012 for determining the discrete doses and the corresponding basal rates is discussed in detail. These improvements allow detailed follow up of dose cycle time and delivered doses as a function of time to identify some artefacts of the measurement method or malfunctioning of the insulin pump. Moreover, the calibration results of different basal rates and bolus deliveries for the gravimetric and the optical methods are also presented. Some analysis issues that should be addressed to prevent misinterpreting of the calibration results are discussed. One of the main issues is the average over a period of time which is an integer multiple of the cycle time to determine the basal rate with the analytical methods described in this paper.