18HLT08 MEDDII: Metrology for drug delivery

• Unité de recherche: METAS
• Numéro de projet: F-5135.30116

Mots-clé (Anglais)

Microflow, nanoflow, drug delivery, flow sensors, traceability, infusion pumps, pain control pumps, infusion pump analysers, multi infusion systems.

Description succincte (Anglais)

The overall aim of this project is to improve dosing accuracy and to enable the traceable measurement of volume, flow and pressure in existing drug delivery devices and in-line sensors operating at very low flow rates. This will be achieved through the development of new calibration methods and by expanding the existing metrological infrastructure. This project will also investigate fast changing flow rates, which are step changes between two flow rates within a second, the physical properties of mixtures of liquids and occlusion phenomena in multi-infusion systems in order to prevent inaccurate measurement results and thus to improve patient safety.

This is a joint research project carried out in the framework of the European Metrology Programme for Innovation and Research (EMPIR) (see:http://www.euramet.org/research-innovation/empir/). The EMPIR initiative is co-funded by the European Unions's Horizon 2020 research and innovation programme and the participating states. METAS is one of the project partners in the project.

Objectifs du projet (Anglais)

The overall objective of this project is to enable traceable measurements of the volume, flow rate and pressure of existing drug delivery devices (and other medical devices, like infusion pump analysers and organ-on-a-chip) and in-line sensors that work at a flow rate lower than 100 nL/min. This project will also investigate fast changing flow rates, liquid mixing behaviour and occlusion phenomena in multi-infusion systems in order to improve the dosing accuracy in each infusion line.

The specific objectives of the project are:

1. To develop new traceable techniques for generating and measuring the response or delay time of drug delivery devices regarding changes in flow rate, from 5 nL/min to 100 nL/min, using Newtonian liquids (WP1). For steady flow rates an uncertainty of 1 % (k=2) or better is expected, whereas for fast changing flow rates an uncertainty of 2 % (k=2) or better is expected. The techniques developed will be used to characterise and validate the different response times of at least 3 different types of drug delivery devices (including infusion analysers) (WP3 and WP4) and one type of flow sensor, to accurately measure the administered flow and volume with the required uncertainties.
2. To upgrade the existing flow facilities and knowledge of the partner NMIs in order to enable the traceable in-line measurement of the dynamic viscosity of Newtonian liquids, as a function of the flow rate and pressure difference, with a target uncertainty value of 2 % (k=2). The measurement uncertainty will be validated using Newtonian liquids with traceable dynamic viscosity calibration. Additionally, tests with non-Newtonian liquids will be performed in order to prove the concept. To calibrate transfer standards for the in-line measurement of dynamic viscosity and other physical properties of liquids, in order to use these transfer standards for flow measurement and to determine the mixing behaviour of different liquids.
3. To develop and validate novel calibration procedures for existing medical flow devices (e.g. infusion pumps, pain controllers and infusion pump analysers) with traceability to a primary standard and with a target uncertainty value of 2 % (k=2) for a range of 5 nL/min up to 600 ml/min and also to develop a proof-of-concept on-chip microfluidic pump used as a transfer standard in drug discovery and organ-on-a-chip applications for flow rates lower than 100 nL/min.
4. To design and develop a multi-infusion system containing check valves, with several options for testing how liquids, with different viscosities mix and flow and how this affects drug concentration. The flow rates and pressures will be traceably calibrated in all infusion lines, as well as at the outlet of the syringe pump, to be able to analyse the effects of pressure-equalising devices and to detect occlusion phenomena and bad mixing configurations.
5. To facilitate the take up of the technology and measurement infrastructure developed in the project by the measurement supply chain (i.e. accredited laboratories, instrumentation manufacturers, etc.), standards developing organisations (ISO/TC 30, ISO/TC 48, ISO/TC/SC 62D, ISO/TC 69, ISO/TC 76, ISO/TC 84, ISO/TC 150, ISO/TC 210) and end-users (i.e. hospitals and health centres).