The invention relates to portable devices and methods for measuring coagulation time, such as for example prothrombin time or activated partial thromboplastine time.
In case of atrial fibrillation, deep venous thrombosis, pulmonary embolism or after replacement of cardiac valve, taking medication is necessary to maintain normal blood fluidity. The most commonly used drugs are heparin and warfarin. Heparin is administrated subcutaneously or intravenously. Heparin activates a plasmatic protein, the antithrombin III that is a natural inhibitor of protease implicated in the coagulation cascade (factors VIIa, XIa, IXa, Xa, IIa). The rate of inactivation of these proteases by AT-III increases 1000-fold due to the binding of heparin. Warfarin decrease blood coagulation by interfering with vitamin K metabolism by inhibiting the effective synthesis of biologically active forms of the Vitamin-K-dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S and protein Z. Warfarin has the advantage that it may be taken orally. However dosing warfarin is complicated by the fact that it is known to interact with many commonly used medications and other chemicals that may be present in appreciable quantities in food. But with both medications, dangerous side effects such as bleeding exist. Therefore in order to optimize the therapeutic effect and minimize risks for the patient, close monitoring of the degree of anticoagulation is required by blood testing. Two coagulation test measures are routinely used: the prothrombin time and the activated partial thromboplastin time. Both tests measure clotting time to evaluate a patient's baseline haemostatic state or to monitor the response to anticoagulant therapy as well as the overall function and status of the coagulant system. Prothrombin time is tested when warfarin is used and activated partial thromboplastin time when heparin is used. These tests are mainly done in hospital with relatively large laboratory instrument of complex technology and therefore must be done by qualified personnel. These types of tests are expensive and can be done only once a month approximately. Another possibility is to use point-of-care device. In this case the patient can perform the test by himself. This allows a better control over time as the test can be done daily. However, even if it has been shown self-management improves the quality of oral anticoagulation [1], this method is little used. This is mainly due to the cost of the test strips and to the complexity of use of the actual devices. Therefore new easy of use and inexpensive point-of-care devices and methods for blood coagulation testing are needed.
Methods for coagulation measurement using portable device are described in the following patents
The present invention simultaneously concerns an alternative and an improvement with respect to state-of-the-art coagulometers.
To this effect it relates to a system to measure blood coagulation related parameters comprising one first channel adapted to contain a blood sample, the system containing, at least partially, an expandable material which is able to increase its volume when activated by an exciting source, said system furthermore comprising several excitable regions distributed close to said first channel, in such a way that, when one of said excitable region is activated, said expandable material increases to such an extend that the channel cross section is reduced at a location situated at or near to said excitable region.
Preferred embodiments of the system according to the invention are defined in the dependent claims.
The invention furthermore relates to the use of a system to measure blood coagulation related parameters as defined above. Wherein the coagulation time is based on the distance made by the liquid along the channel before being stopped, said liquid being moved by a sequential activation of the exciting elements.
The inventive concept is based on the measurement of the displacement of blood along a channel. The displacement is driven by the closing of a channel located in a material that can change its volume when activated by an exciting factor. The device includes a permanent and a disposable part. The disposable part is in contact with blood and contains the channel in which the blood will move. The permanent part contains an electronic that will trigger the activation of the material and measure the displacement. It also contains a screen to read the result of the test. In the rest of this document, expansible material will be described as PDMSXB, i.e. Expancel beads dispersed into a PDMS matrix, and activation mean as heat produced by the resistance of an electric circuit. Naturally this description can apply to any material having the property to change its volume when activated by an exciting factor.
The invention will be better understood below with an example illustrated by the following figures:
The following numerical references are used in the figures
The disposable part 12 is formed by the superposition of the following layers: a PCB layer 1, a PDMS layer 2, a PDMSXB layer 4, a protective layer 4 and a cover layer 5. The resistances 9 producing heat to activate the material are printed on the PCBlayer 1. The channel network in which the blood is displaced is molded in the POMS or in the PDMSXB layer. The protective layer is preferably biocompatible with blood and/or ensure thermal isolation of the blood against the heated material. The protective layer can consist of the superposition of two layers, one ensuring thermal isolation and the other biocompatibility. The protective layer covering the PDMS and the one covering the PDMSXB are not necessarily the same. The cover layer closes the channel but preferably contain an inlet hole that connect the channel to the outside in order to let the blood enter the device and an outlet hole The disposable part is preferably adapted to the sensing mean incorporated to the permanent part, for example, if optical mean is used, the disposable is preferably transparent to the light used by, for example, containing a window.
The channel network preferably has the following properties:
The channel network may also have the following properties:
The resistance printed on the PCB preferably has the following properties:
Description of the functioning: sample of blood is taken from the patient, for example with a lancet. The sample is placed on the cover hole and is aspired inside the device by capillary forces or by a pumping mechanism (FIGS. 6.b & 7.a). The sample of blood fills the different channel until their narrowing where it is stopped due to change in fluidic resistance. At this stage, it may be mixed with chemical reactive needed to perform the test. The resistances placed upstream the narrowing are heated and this part of the channels is progressively closed and a volume of blood corresponding to the size of the resistance is push forward in the channel (FIGS. 6.c & 7.b). This allows controlling the volume of blood to be analyzed. The resistances are then heated one after the other along a channel, with a controlled amount of time between each successive heating (FIGS. 6.d-e & 7.c). The resistances are heated simultaneously along the different channels, in order to compare the coagulation time in the different channel, i.e. the coagulation time of blood mixed with different chemical. As long as blood has not coagulated, it may be push forward by the closing of the channel, but once coagulated it stays in place and the channel may not be closed (FIGS. 6.f & 7.d). Coagulation time is calculated by determining, for example optically, where the clot stays and at what time the corresponding resistance was heated.
In order to avoid direct contact of the blood with the activated region, another fluid that is non miscible with blood may be placed upstream of the blood in the channel. This other fluid is therefore the one that is displaced by the closing of the channel, and its displacement induces blood displacement (
Of course the present invention is not limited to the embodiments discussed above.
Number | Date | Country | Kind |
---|---|---|---|
05111343.9 | Nov 2005 | EP | regional |
Filing Document | Filing Date | Country | Kind | 371c Date |
---|---|---|---|---|
PCT/IB2006/054432 | 11/24/2006 | WO | 00 | 4/29/2008 |