Measurement of internal diameters of capillaries and glass syringes using gravimetric and optical methods for microflow applications.

OBJECTIVES: Microflow measurement devices are used in several science and health applications, mainly drug delivery. In the last decade, several new methods based on optical technology were developed, namely the front tracking and interferometric method, in which the knowledge of the inner diameter of the syringe or the capillary used is critical. Only a few National Metrology Institutes (NMIs) can perform inner diameter measurements below 1 mm, which requires expensive technology. Therefore, IPQ, in cooperation with CETIAT, CMI and UNIDEMI, under the EMPIR project 18HLT08 MeDDII - Metrology for Drug Delivery, developed new measurement methods for small inner diameter tubes based on the gravimetric principle and optical methods in order to simplify the apparatus used for this type of measurements without increasing uncertainty. METHODS: The gravimetric experimental setup consists of measuring the liquid volume on a specific length of the glass tube. The optical method used is based on the front track principle that uses a high-resolution camera and ImageJ software, to determine the diameter at both ends of each capillary. RESULTS: To validate the developed methods, a comparison was performed between CETIAT, CMI and IPQ and the results obtained were all consistent. CONCLUSIONS: This work allowed the determination of inner diameter of syringes or capillaries using two different methods with relative expanded uncertainties from 0.1 to 0.5% (k=2), that can be applied for flow measurements using optical technology.

Calibration methods for flow rates down to 5 nL/min and validation methodology.

Improving the accuracy and enabling traceable measurements of volume, flow, and pressure in existing drug delivery devices and in-line sensors operating at very low flow rates is essential in several fields of activities and specially in medical applications. This can only be achieved through the development of new calibrationmethods and by expanding the existing metrological infrastructure to perform micro-flow and nano-flow measurements. In this paper, we will investigate new traceable techniques for measuring flow rate, from 5 nL/min to 1,500 nL/min and present the results of an inter-comparison between nine laboratories for the calibration of two different flow meters and a syringe pump.

Primary standards for measuring flow rates from 100 nl/min to 1 ml/min - gravimetric principle.

Microflow and nanoflow rate calibrations are important in several applications such as liquid chromatography, (scaled-down) process technology, and special health-care applications. However, traceability in the microflow and nanoflow range does not go below 16 µl/min in Europe. Furthermore, the European metrology organization EURAMET did not yet validate this traceability by means of an intercomparison between different National Metrology Institutes (NMIs). The NMIs METAS, Centre Technique des Industries Aérauliques et Thermiques, IPQ, Danish Technological Institute, and VSL have therefore developed and validated primary standards to cover the flow rate range from 0.1 µl/min to at least 1 ml/min. In this article, we describe the different designs and methods of the primary standards of the gravimetric principle and the results obtained at the intercomparison for the upper flow rate range for the various NMIs and Bronkhorst High-Tech, the manufacturer of the transfer standards used.