Biomedical Engineering / Biomedizinische Technik最新文献

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.

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.

The effect of the presence of an air bubble, inside an infusion line, on the time (Tnew) needed for a new medication to reach the patient after a syringe exchange was studied in this paper. If an air bubble escapes through an air filter, then a sudden drop in pressure occurs, causing a relaxation of the compressible part of the syringe, followed by a gradual restoration of the flow rate in the line. We modeled this phenomenon mathematically and measured it experimentally in vitro. In an example with a pump flow rate of 5 mL/h and an air bubble of 1 cm length inside an infusion line (diameter 1 mm) with an air filter, both theory and experiment yield an additional increase of at least 600% in delay time if a naive estimate (based on the size of the bubble alone) is replaced by a more realistic estimate incorporating compressibility. Furthermore, we show that an air bubble in a line without air filter may increase Tnew by a factor 2, depending on the initial position of the air bubble. We conclude that an air bubble in an infusion line causes delays that may not be expected by health care professionals.

The significance of Metrology in infusion therapy and diagnostics, both critical in health care safety and quality, is discussed in this article. Although infusion therapy is the most used form of drug administration, infusion errors are often made with reported dramatic effects in different applications, especially in neonatology. Adverse incidents, morbidity, and mortality have often been traced back to poor or inaccurate dosing. For critical infusion applications to vulnerable patients, well-controlled medication administration might be accomplished by improved dosing accuracy, traceable measurement of volume, flow, and pressure in existing drug delivery devices and in-line sensors operating at very low flow rates. To this end, the contribution of recently upgraded metrological infrastructures in European Metrology Institutes to a safer infusion therapy in health care is described in detail. Diagnostics, on the other hand is a sector characterized by rapid developments further triggered recently by the necessity for the management and prevention of infectious diseases like COVID-19. In this context, the impact of metrology in future large-scale commercialization of next generation diagnostics (e.g., point-of-care) is highlighted. Moreover, the latest contributions of Metrology in the development of traceable testing methods and protocols to ensure the sensitivity and accuracy of these devices are described.

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.

Microfluidic devices are becoming increasingly important in various fields of pharmacy, flow chemistry and healthcare. In the embedded microchannel, the flow rates, the dynamic viscosity of the transported liquids and the fluid dynamic properties play an important role. Various functional auxiliary components of microfluidic devices such as flow restrictors, valves and flow meters need to be characterised with liquids used in several microfluidic applications. However, calibration with water does not always reflect the behaviour of the liquids used in the different applications. Therefore, several National Metrology Institutes (NMI) have developed micro-pipe viscometers for traceable inline measurement of the dynamic viscosity of liquids used in flow applications as part of the EMPIR 18HLT08 MeDDII project. These micro-pipe viscometers allow the calibration of any flow device at different flow rates and the calibration of the dynamic viscosity of the liquid or liquid mixture used under actual flow conditions. The validation of the micro-pipe viscometers has been performed either with traceable reference oils or with different liquids typically administered in hospitals, such as saline and/or glucose solutions or even glycerol-water mixtures for higher dynamic viscosities. Furthermore, measurement results of a commercially available device and a technology demonstrator for the inline measurement of dynamic viscosity and density are presented in this paper.

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.

Accurately measuring flow rates is a key requirement in many medical applications such as infusion and drug delivery systems. A major drawback of current systems is the low resolution of the sensors in the low flow rate regime. In this article, we present a method based on Holographic PIV/PTV that has been used for the first time to measure flow rates in the range of a few nL/min. Our method requires a very simple setup that combines lensless holography with particle velocimetry. For flow rates in the 70 to 200 nL/min range, the highest uncertainty was 5.6% (coverage factor k=2). This is an open-source project; the CAD designs and software source code are available at https://github.com/gui-miotto/holovel.

The presence of a non-return valve in an infusion set-up is expected to affect the time-of-arrival of new medication in a patient after syringe exchange. Using Computational Fluid Dynamics (CFD) we have studied the flow through a typical non-return valve, focusing on two separate effects: (A) the overall delay in the time-of-arrival, and (B) timing effects due to the distortion of the Poiseuille flow profile in the non-return valve. The results show that (A) the additional delay in time-of-arrival of new medication, caused by the non-return valve alone, corresponds to the delay that would be caused by 11.2 cm of extra infusion line instead of the valve, and that (B) the non-Poiseuille flow profile inside the non-return valve gives rise to an extra slow wash-out of the last portion of the remnant fluid of the old medication. We conclude that awareness of these extra delays may be important for clinicians in certain time-critical situations.