A simple method based on that described in the international standard NF ISO 5017 is implemented to determine the apparent porosity of samples of limestone. Its effectiveness is demonstrated and the points to be particularly controlled (drying, soaking, wiping) to avoid gross errors are highlighted depending on the type of porosity (thin or wide). This study shows that the standard NF ISO 5017 established for dense shaped refractory products is also well suited for solid rock with homogeneous structure having a true porosity of less than 45 %. This standard properly implemented for rock samples allows one to determine their apparent porosity with a standard uncertainty of about 0.1 %.
Key words
limestone
apparent porosity
gravimetric method
uncertainty in measurement
Abstract
The kilogram is the last unit of the International System of Units (SI) still defined by an artefact, namely the International Prototype of the Kilogram (IPK). Comparisons carried out over 100 years between IPK, its official copies and national prototypes have revealed a mass change (in relative term) of five parts in 108. After a brief history of the unit of mass, this paper underlines the need to redefine the kilogram with reference to a fixed numerical value of a fundamental constant. It explains why the Planck constant h was chosen and gives the last results obtained with watt balance experiments nowadays able to link h to a macroscopic mass to within a few parts in 108. Finally, it proposes a possible route for the national metrology institute for the mise en pratique of the kilogram after its redefinition.
Key words
unit of mass
kilogram
redefinition of the kilogram
planck constant
watt balance
Abstract
LNE has set up a new national standard in gas flowrate measurement between 0.2 mg·s-1 and 200 mg·s-1 of nitrogen or dry air to calibrate automatically Molbloc laminar flowmeters. This paper describes the metrological qualification of this standard based on the dynamic gravimetric method: optimization of the method to reduce the uncertainty by a factor of 2 compared to those obtained with the LNE old gravimetric benches, participation to an interlaboratory comparison to validate this result. The uncertainty calculation is developed up to the calibration of a Molbloc laminar flowmeter.
Key words
dynamic gravimetric method
reference bench
uncertainty
comparison
calibration
Abstract
Until 2012, micro- and nano-flow rate measurements traceability was a problem, due to the lack of references at and below 1 mL·h-1. For drug delivery by infusion, uncertainty on real delivered flow rate can cause injuries or even death. Quality of volumetric dosing has to be closely controlled. Exact delivered volume and stability are critical parameters, particularly for drugs requiring low blood concentration for toxicity reasons, such as vasoactive and anesthetics. To meet this need, the national metrology laboratories LNE-CETIAT, DTI, IPQ, METAS and VSL have developed, in the scope of the European Research Project in Metrology “EMRP/HLT07 MeDD – Metrology for Drug Delivery”, calibration benches for flow rates from 600 mL·h-1 down to 600 nL·h-1. This article presents the work done at LNE-CETIAT in the scope of this project, including qualification of a calibration facility for flow rates from 1 mL·h-1 to 10 L·h-1, and temperature assessment of microflowmeters and drug delivery devices.
Key words
drug delivery devices
liquid micro-flow
gravimetric calibration
metrology for drug delivery
At micro and nano-scale liquid flow rates, calibration is critical, especially for applications such as volumetric dosing and drug delivery. In particular, for drugs with a very short half-life (in the order of one minute), or for drugs that require a very low blood concentration for toxicity reasons, such as vasoactive or anaesthetic drugs, the exact amount of volume administered as well as the stability of the flow rate are crucial.
OBJECTIVES
Establishment of an infrastructure for calibration of drug delivery systems for flows up to 10-100 nl/min
Development of transfer standards for on-site calibration of drug delivery equipment
Performance evaluation of drug delivery devices, dependence on operating conditions and clinical characteristics
Provision of a good practice guide for drug dispensing and improved calibration services for drug delivery devices
SUMMARY AND RESULTS
Until 2012, however, metrological traceability for these very low flow ranges was only validated in Europe from 16 l/min upwards.
Image
CETIAT microflow reference
The national metrology laboratories LNE-CETIAT, DTI, IPQ, METAS, and VSL developed primary calibration methods covering a range of liquid flow rates from 10 l/h to 10 nl/min as part of the European metrology research project “HLT07 Metrology for Drug Delivery – MeDD.” These national references have been validated by comparing the measurement results obtained with a Coriolis mass flow meter and a syringe pump (see figure opposite). These results have led to the submission of new calibration possibilities (CMC, Calibration and Measurement Capabilities) that are unprecedented for these flow ranges.
Image
Validation of developed national references (comparison of measurements with a syringe pump)
The influence of several physical parameters such as temperature, back pressure, viscosity, and flow pulsations was studied. It was thus demonstrated that Coriolis mass flow meters are less sensitive to the physical parameters studied and therefore constitute transfer standard flow meters suitable for establishing metrological traceability for medical devices.
With regard to infusion devices, several characteristics were tested: start-up time, flow stability, and response time to occlusion, depending on the presence of accessories such as valves, needles, and tubing, and depending on physical parameters such as temperature and liquid viscosity.
The results obtained showed that infusion drug delivery devices are sensitive to conditions of use, particularly at low flow rates and for larger volume syringes. In addition, the start-up time under certain conditions (very low flow rates) can be as long as several tens of minutes.
Throughout this project, the results and knowledge acquired were disseminated to the scientific and medical communities via various media. Initially, a website (www.drugmetrology.com) was created, providing direct and public access to communications related to the project. A workshop organized by the “MeDD” consortium and bringing together members of the scientific and medical communities was held in Utrecht (Netherlands) in May 2015, providing an opportunity to present the results of this project and discuss the implementation of traceable metrological approaches for infusion devices. A guide to good infusion practices was also drafted and made available on the project website.
PUBLICATIONS AND COMMUNICATIONS
BATISTA E., FILIPE E., BISSIG H., PETTER H.T., LUCAS P., OGHEARD F. and NIEMANN A.K., “European research project on microflow measurements – MEDD”, 9th International Symposium on Fluid Flow Measurement, Arlington, United States of America, April 14th-17th 2015.
BISSIG H., PETTER H.T., LUCAS P., BATISTA E., FILIPE E., ALMEIDA N., RIBEIRO L.F., GALA J., MARTINS R., SAVANIER B., OGHEARD F., NIEMANN A.K., LÖTTERS J. and SPARREBOOM W., “Primary standards for measuring flow rates from 100 nl/min to 1 ml/min – gravimetric principle”, Biomedical Engineering / Biomedizinische Technik, 60, 4, 2015, 301–316, DOI: 10.1515/bmt-2014-0145.
DAVID CH., MELVAD C., BISSIG H. and BATISTA E., “Research interlaboratories comparison for small liquid flow rates (2g/h to 600g/h)”, 16th Flow Measurement Conference (FLOMEKO), Paris, France, September 24th-26th 2013.
OGHEARD F., BATISTA E., BISSIG H., PETTER H.T., LUCAS P. and NIEMANN A.K., “Metrological assessment of micro flow-meters and drug delivery devices in the scope of the "MeDD" EMRP project”, 17e Congrès international de métrologie, Paris, France, September 21st-24th 2015, DOI: 10.1051/metrology/20150009004.
LUCAS P., SNIJDER R.A., TIMMERMAN A.M.D.E., BATISTA, E., BISSIG H. and OGHEARD F., “Best Practice Guide”, Version: 13-05-2015.
PARTNERS
VSL,
CETIAT,
CMI,
DTI,
IPQ,
METAS,
TUBITAK,
FH Lubeck,
UMC Utrecht
The preparatory work for the new definition of the kilogram was carried out using experiments conducted in a vacuum, whereas mass measurements using the International Prototype Kilogram (IPK) were carried out in air. So it became necessary to develop standards and methods for linking measurements in air with mass measurements in vacuum. This was in order to establish the value of Planck's constant in line with the current definition of the kilogram, on the one hand, and subsequently to ensure the dissemination of the unit of mass in a vacuum to end users, on the other.
OBJECTIVES
Develop and evaluate artefacts suitable for determining Planck's constant and Avogadro's constant in order to ensure traceability to the IPK and ultimately enable the dissemination of the kilogram after its redefinition.
Provide the appropriate procedures and apparatus for mass transfer between vacuum experiments (Kibble balance and vacuum mass comparators) and open-air experiments (comparison with the IPK and dissemination of the unit to end users).
Develop and adapt surface analysis techniques, e.g. X-ray photoelectron spectroscopy (XPS), ellipsometry, contact angle spectrometry (CAS) and surface layer models for contaminant accumulation on mass standards (including silicon spheres).
Assess the mass stability of properly preserved mass artefacts and develop the metrological infrastructure necessary for the maintenance (in the medium term) of the mass unit and its dissemination on the basis of various realisations (via a set of artefacts that can be stored in several national metrology laboratories and key comparisons).
Develop and validate methods for reproducible cleaning (to less than 5 μg) of primary mass standards, including optimisation of non-contact cleaning techniques such as the use of UV-activated ozone and gas plasma techniques.
Identify and evaluate the components of uncertainty inherent in the implementation and their propagation throughout the chain of dissemination for the kilogram and its multiples and submultiples.
SUMMARY AND RESULTS
Before the redefinition of the unit of mass in 2018, the International Prototype Kilogram was stored and used in air. Research work to achieve this redefinition of the unit of mass was carried out using watt balance and Avogadro experiments, which led to measurements being taken in vacuum. It was therefore clear that the redefined kilogram would be materialised in vacuum and would therefore require the transfer of the ‘primary’ kilogram standards from vacuum to air in order to ensure traceability for end users. This would add additional sources of error that needed to be controlled, such as the sorption of surface contaminants and water layers, to already complex measurement procedures. The EMRP project ‘Development of a practical means of disseminating the redefined kilogram (NewKILO)’ led to the development of new mass standards, new methods for cleaning and monitoring them, and procedures and equipment for transferring mass standards between vacuum and air. More generally, the aim was for the results of this project to help ensure that the redefinition brings benefits to the end-user community.
The LNE-Cnam Joint Metrology Laboratory (LCM) was involved in all work packages of this project. The following results only concern the project results to which the laboratory contributed.
With regard to the development and evaluation of artefacts, in order to ensure traceability to the watt balance and Avogadro experiments, the project partners defined the following characteristics for the material:
- low magnetic susceptibility (< 2×10-4) for use in the watt balance;
- a hardness of HV > 200 to facilitate machining and polishing;
- chemical resistance to corrosion and oxidation;
- a homogeneous material without porosity, cavities or trapped gases to ensure long-term stability.
Based on these properties, different materials were selected and compared.
Among the many studies undertaken to characterise these materials, the LCM assessed surface roughness after mirror polishing using an optical roughness tester: no direct link was found with mass stability, but it certainly affects sorption effects.
Image
Mass comparator M-one 6V
With regard to the development of procedures and appropriate equipment for mass transfer between vacuum experiments and open-air experiments, the LCM participated in measurements of the sorption coefficient as a function of pressure. It worked more specifically on platinum-iridium. The work showed that there was no variation in mass between 0,1 Pa and 0,001 Pa.
In order to validate and evaluate the reproducibility of the air/vacuum transfer method for mass standards, a comparison of gravimetric measurements of mass standards subjected to air/vacuum/air cycles was undertaken. This comparison was carried out on two groups of three masses. In the first group, two masses were kept in air, one of which had to be cleaned before weighing, while the third was kept in a nitrogen atmosphere. In the second group, all three masses were kept in air. The LCM participated in the measurements related to this group. The sorption coefficients calculated by the various national laboratories differ by up to an order of magnitude. These differences can be explained by the fact that each laboratory uses its own sorption artefacts, which may differ in particular in terms of their polishing.
LCM participated in one of the studies concerning mass transfer between vacuum and/or air and nitrogen. Three different cycles were applied to Pt-Ir and then analysed by TDS (thermo desorption mass spectrometry) at LCM in order to determine their advantages and disadvantages.
Image
Plasma cleaning device
For mass stability studies, particularly during storage, cleaning and transport of masses, in 2014 the LCM set up a plasma cleaning device, integrated into the introduction chamber of the TDS device. A study of the effect of different cleaning methods was conducted. The application of air plasma cleaning to Pt-Ir artefacts previously cleaned with ethanol or isopropanol demonstrated the effectiveness of this method, particularly on carbon and hydrocarbon compounds. A gravimetric study observed a variation in the mass of the Pt-Ir artefacts depending on the cleaning process used (BIPM cleaning-washing or plasma air). A series of comparisons was made before and after the two cleaning processes. After each cleaning, a rapid increase in mass was observed, which stabilised after a few hours.
A comparison of acetone and ethanol adsorption on PtIr, iridium and AuPtAgCu alloy surfaces was performed. The adsorption of both acetone and ethanol is lower on pure iridium than on PtIr. With regard to the quaternary alloy AuPtAgCu, the very high adsorption of acetone suggests high surface porosity, which makes it unsuitable for use as a mass standard.
Another aspect of the work concerned medium-term storage and transfer of standards between laboratories with a primary realisation operating under vacuum. In order to evaluate the storage and transfer protocol, the LCM participated in measurements on a set of masses. There is no significant advantage to storing masses in a neutral gas; in fact, it is more advantageous in terms of mass stability to store masses in air. The current method of storing masses in air is therefore recommended.
PUBLICATIONS AND COMMUNICATIONS
PLIMMER M.D., DU COLOMBIER D., IRAQI HOUSSAINI N., SILVESTRI Z., PINOT P. and HANNACHI R., “Apparatus to measure adsorption of condensable solvents on technical surfaces by photothermal deflection”, Review of Scientific Instruments, 2012, 83, 11, DOI: 10.1063/1.4767245.
SILVESTRI Z., AZOUIGUI S., BOUHTIYYA S., MACÉ S., PLIMMER M.D., PINOT P., TAYEB-CHANDOUL F. and HANNACHI R., “Thermal desorption mass spectrometer for mass metrology”, Review of Scientific Instruments, 2014, 85, 4, DOI: 10.1063/1.4870921.
DAVIDSON S., BERRY J., SILVESTRI Z., HOGSTROM R. and GREEN R., “Addressing the requirements for the practical implementation and ongoing maintenance of the redefined kilogram”, 22nd IMEKO TC3 International Conference on Measurement of Force, Mass and Torque 2014, Held Together with TC5 and TC22, Cape Town, South Africa, 3-5 February 2014.
SILVESTRI Z., BOUHTIYYA S., PINOT P. and DAVIDSON S., “How to disseminate the mass unit for the new kilogram?”, International Congress of Metrology, Paris, France, Poster, 21-24 September 2015, DOI: 10.1051/metrology/20150018003.
