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

Funding Information: Research funding: This project 18HLT08 MEDDII has received funding from the EMPIR programme co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme. Publisher Copyright: © 2022 the author(s), published by De Gruyter, Berlin/Boston.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.publishersversionpublishe

Assessment of drug delivery devices working at microflow rates

Funding Information: Research funding: This work performed under the 18HLT08 MeDD II project has received funding from the EMPIR program co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation program. For more information on the project refer to the website www.drugmetrology.com . Publisher Copyright: © 2022 the author(s), published by De Gruyter, Berlin/Boston.Almost every medical department in hospitals around the world uses infusion devices to administer fluids, nutrition, and medications to patients to treat many different diseases and ailments. There have been several reports on adverse incidents caused by medication errors associated with infusion equipment. Such errors can result from malfunction or improper use, or even inaccuracy of the equipment, and can cause harm to patients' health. Depending on the intended use of the equipment, e.g. if it is used for anaesthesia of adults or for medical treatment of premature infants, the accuracy of the equipment may be more or less important. A well-defined metrological infrastructure can help to ensure that infusion devices function properly and are as accurate as needed for their use. However, establishing a metrological infrastructure requires adequate knowledge of the performance of infusion devices in use. This paper presents the results of various tests conducted with two types of devices.publishersversionpublishe

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

Investigations on the Influence of Total Water Hardness and pH Value on the Measurement Accuracy of Domestic Cold Water Meters

In the framework of the ongoing EMPIR Joint Research Project (JRP) 17IND13 Metrology for real-world domestic water metering (Metrowamet), a main task is to investigate the influence of realistic operation conditions, that is, typical water qualities (suspended particles, degree of hardness, and pH value), on the measurement accuracy. For this purpose, two representative types of cold water meters were investigated in more detail. Initially, the cold water meters were calibrated and then subjected to an accelerated wear test with water of different pH values and degrees of hardness. The accelerated wear tests were designed to reproduce the realistic use and service life of a cold water meter. Subsequently, the cold water meters were re-calibrated to assess the influence of the different water qualities on the measurement accuracy. One of the results was that the measurement accuracy of the water meters investigated was not strongly affected by the water quality. The practical realisation and the measurement results are reported in this paper

Investigations for the realization and dissemination of the ‚Volume of Water‘ scale with the aid of laser-optical and conventional measurement procedures

Die Physikalisch-Technische Bundesanstalt (PTB) ist das nationale Metrologie-Institut und technische Oberbehörde des Bundesministeriums für Wirtschaft und Technologie (BMWi). Als diese technische Oberbehörde der Bundesrepublik Deutschland hat sie den gesetzlichen Auftrag, neben der Darstellung der SI-Einheiten, die Sicherung der internationalen Vergleichbarkeit zu gewährleisten. Aus diesem Grund werden Ringvergleiche (RV) zwischen den metrologischen Staatsinstituten bzw. zwischen ihren auf Normale rückgeführten Prüfeinrichtungen (Normalmessanlagen, NMA) durchgeführt. Für einen geplanten europäischen Ringvergleich im Bereich ‚Volumen von Wasser‘, welcher an den bereits abgeschlossenen Ringvergleich CCM.FF-K1 angelehnt ist, wurden im Rahmen der vorliegenden Arbeit konventionelle Durchflusssensoren aber auch ein neuartiges, auf der Laser-Doppler-Velozimetrie (LDV) basierendes, Messverfahren für ihre Verwendung als Vergleichsnormale zur Volumenstrom-bestimmung charakterisiert. Klassische LDV-Systeme messen die lokale Geschwindigkeit einer Rohrströmung nur auf einem Messpfad (Mittelpfad) und stellen deshalb nur wenige Informationen bei gestörten bzw. unsymmetrischen Anströmbedingungen zur Verfügung. Die Vorraussetzung für die Verwendung der LDV-Messtechnik war somit die Entwicklung einer neuartigen, patentierten 2D-Fensterkammer und der dazu- gehörigen Strahlverfolgungsrechnung. Mit dem vorgestellten Messaufbau ist es erstmalig möglich, das komplette Geschwindigkeitsprofil - mit seinen drei Geschwindigkeitskomponenten - vollflächig über den gesamten Rohrquerschnitt zu erfassen. In diesem Kontext wird erstmalig im Rahmen dieser Arbeit eine ausführliche, quantitative Analyse der Messunsicherheitsbilanz ("Bottom-up-Methode") für die Volumenstromermittlung mit LDV-Messtechnik präsentiert. Bei den konventionellen Durchflusssensoren (DFS) wurden, auf Grund umfangreicher Untersuchungen zur Wiederholbarkeit und Reproduzierbarkeit, mit dem Magnetisch-Induktiven Durchflusssensor (MID), dem Coriolis-Massen-durchflusssensor (CMD) und dem Ultraschall-Durchflusssensor (USD), drei Messgeräte im Hinblick auf die Eignung als Vergleichsnormale analysiert. Entgegen der determinierten Annahme, dass Durchflusssensoren keine Abhängigkeit vom Strömungsprofil besitzen und somit die Darstellung und Weitergabe der Skala ‚Volumen von Wasser‘ identisch sind, erfolgt in dieser Arbeit erstmals eine klare Trennung zwischen Darstellung und Weitergabe der Skala ‚Volumen von Wasser‘, da gerade das Strömungs-profil einen der größten Unsicherheitstreiber auf die Messabweichung der DFS darstellt und darüber hinaus jede NMA ein anders geartetes Geschwindigkeitsprofil besitzt. Das Ergebnis des geplanten Ringvergleichs ist der so genannte Key Comparison Reference Value (KCRV). Die Aussage, inwieweit der ermittelte Wert jedes Teilnehmers mit dem errechneten KCRV zusammenpasst, gibt eine Auskunft über dessen Messstandard. Da es keine zwingende Vorschrift für die Bildung dieses Referenzwertes gibt, werden im Rahmen der Arbeit mögliche mathematische bzw. statistische Methoden zur Auswertung des geplanten RV untersucht.The Physikalisch-Technische Bundesanstalt (PTB) is the National Metrology Institute of Germany and the highest technical authority of the Bundesministerium für Wirtschaft und Technology (Federal Ministry of Economics and Technology, BMWi). As this highest technical authority of the Federal Republic of Germany, it has the legal mandate - in addition to the realization of the SI units - to guarantee international comparability. For this reason, interlaboratory comparisons are carried out among the national metrology institutes and/or among their testing devices which have been traced back to standards (standard measuring devices). For a planned European interlaboratory comparison in the field of ‚Volume of Water‘ which will be carried out on the basis of the already concluded interlaboratory comparison CCM.FF-K1, conventional flowrate sensors - but also a novel measurement procedure based on Laser Doppler Velocimetry (LDV) - were characterized within the scope of this work with regard to their use as comparison standards for volume determination. Classical LDV systems measure the local velocity of a pipe flow only on one measurement path (medium path) and provide, therefore, only little information about disturbed or asymmetrical upstream flow conditions. The prerequisite for the use of the LDV measuring technique was thus the development of a novel, patented 2D window chamber and of the associated ray tracing calculation. The presented measuring set-up allows the complete velocity profile - with its three velocity components - to be determined for the first time holohedrally over the whole pipe cross-section. In this context, a detailed quantitative analysis of the uncertainty balance ("Bottom-up method") for volume flow determination with LDV measuring technique is, for the first time, presented within the scope of this work. In the case of the conventional flowrate sensors, three measuring instruments - the Electromagnetic flowmeter (EFM), the Coriolis mass flowmeter (CMF) and the Ultrasonic flowmeter (UFM) - were (due to detailed investigations of the repeatability and reproducibility) analyzed in view of their suitability as comparison standards for volume flow determination. Contrary to the determinate assumption that flowrate sensors are not dependent on the flow profile, and that the realization and dissemination of the ‚Volume of Water‘ scale are, thus, identical, this work will present - for the first time - a clear separation between the realization and the dissemination of the ‚Volume of Water‘ scale, because it is exactly the flow profile which decisively contributes to the uncertainty of the flow sensors. In addition, each standard measuring device has a different velocity profile. The result of the planned interlaboratory comparison is the so-called Key Comparison Reference Value (KCRV). The statements as to which extent the value determined by each participant agrees with the calculated KCRV provides information about the respective measurement standard. As a mandatory prescription regarding the formation of this reference value does not exist, possible mathematical and statistical methods for the assessment of the planned interlaboratory comparison will be investigated within the scope of this work

RISE Test Facilities for the Measurement of Ultra-Low Flow Rates and Volumes with a Focus on Medical Applications

In the framework of the ongoing EMPIR JRP 18HLT08 Metrology for Drug Delivery (MeDDII), a main task is to improve dosing accuracy and enable traceable measurements of volume, flow and pressure of existing drug delivery devices and in-line sensors operating, in some cases, at ultra-low flow rates. This can be achieved by developing new calibration methods and by expanding existing metrological infrastructure. The MeDDII project includes, among other issues, investigations on fast changing flow rates, physical properties of liquid mixtures and occlusion phenomena to avoid inaccurate measurement results and thus improve patient safety. This paper describes the extension of an existing measurement facility at RISE and the design and construction of a new measurement facility to be able to carry out such investigations. The new measurement facility, which is based on the dynamic gravimetric method, is unique worldwide in respect of the lowest measurable flow rate. The gravimetric measuring principle is pushed to the limits of what is feasible. Here, the smallest changes in the ambient conditions have a large influence on the measurement accuracy. The new infrastructure can be used to develop and validate novel calibration procedures for existing drug delivery devices over a wide flow rate range. The extension of the measurement facilities also enables inline measurement of the pressure and the dynamic viscosity of Newtonian liquids. For this purpose, it is ensured that all measurements are traceable to primary standards

RISE Test Facilities for the Measurement of Ultra-Low Flow Rates and Volumes with a Focus on Medical Applications

In the framework of the ongoing EMPIR JRP 18HLT08 Metrology for Drug Delivery (MeDDII), a main task is to improve dosing accuracy and enable traceable measurements of volume, flow and pressure of existing drug delivery devices and in-line sensors operating, in some cases, at ultra-low flow rates. This can be achieved by developing new calibration methods and by expanding existing metrological infrastructure. The MeDDII project includes, among other issues, investigations on fast changing flow rates, physical properties of liquid mixtures and occlusion phenomena to avoid inaccurate measurement results and thus improve patient safety. This paper describes the extension of an existing measurement facility at RISE and the design and construction of a new measurement facility to be able to carry out such investigations. The new measurement facility, which is based on the dynamic gravimetric method, is unique worldwide in respect of the lowest measurable flow rate. The gravimetric measuring principle is pushed to the limits of what is feasible. Here, the smallest changes in the ambient conditions have a large influence on the measurement accuracy. The new infrastructure can be used to develop and validate novel calibration procedures for existing drug delivery devices over a wide flow rate range. The extension of the measurement facilities also enables inline measurement of the pressure and the dynamic viscosity of Newtonian liquids. For this purpose, it is ensured that all measurements are traceable to primary standards

Methods for Sampling Biogas and Biomethane on Adsorbent Tubes after Collection in Gas Bags

Biogas is a renewable energy source with many different production pathways and numerous excellent opportunities for use; for example, as vehicle fuel after upgrading (biomethane). Reliable analytical methodologies for assessing the quality of the gas are critical for ensuring that the gas can be used technically and safely. An essential part of any procedure aimed at determining the quality is the sampling and transfer to the laboratory. Sampling bags and sorbent tubes are widely used for collecting biogas. In this study, we have combined these two methods, i.e., sampling in a gas bag before subsequent sampling onto tubes in order to demonstrate that this alternative can help eliminate the disadvantages associated with the two methods whilst combining their advantages; with expected longer storage stability as well as easier sampling and transport. The results of the study show that two parameters need to be taken into account when transferring gas from a bag on to an adsorbent; the water content of the gas and the flow rate used during transfer of the gas on to the adsorbent

Gas flow measurement of evaporated liquid nanoflows

Following the miniaturisation of fluidic components, the demand for traceable measurements of micro and nanoflows is increasing in various technological fields such as pharmaceuticals, biotechnology and automotive industry. Gravimetric flow measurement methods are accurate at microflows and above, but have a lower limit of about 5nLmin−1. Several alternative approaches have been developed to circumvent this limit. Here a measurement setup and proof of principle is presented for a method measuring the gas flows generated by complete evaporation of liquid ethanol nanoflows. The gas flow measurement is based on the well-established method of determining the pressure drop across a geometrically precisely defined circular opening in the molecular flow regime. Liquid flow rates from a syringe pump in the range of 5nLmin−1 to 200nLmin−1 are measured with an expanded uncertainty as low as 340pLmin−1 at instantaneous flow rates. Strategies to further improve accuracy are discussed.The financial support by the Sweden’s Innovation Agency (VINNOVA) , grant number 2020-04318, is gratefully acknowledged.</p