EP2697644A1 - Dispositif et procédé pour la détermination du temps de coagulation du sang - Google Patents

Dispositif et procédé pour la détermination du temps de coagulation du sang

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Publication number
EP2697644A1
EP2697644A1 EP12713609.1A EP12713609A EP2697644A1 EP 2697644 A1 EP2697644 A1 EP 2697644A1 EP 12713609 A EP12713609 A EP 12713609A EP 2697644 A1 EP2697644 A1 EP 2697644A1
Authority
EP
European Patent Office
Prior art keywords
blood
coagulation
sample
microspheres
movement
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP12713609.1A
Other languages
German (de)
English (en)
Inventor
Sascha MEYER DOS SANTOS
Sebastian HARDER
Zeno v. GUTTENBERG
Anita ZORN
Ute KLINKHARDT
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Goethe Universitaet Frankfurt am Main
Original Assignee
Goethe Universitaet Frankfurt am Main
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Goethe Universitaet Frankfurt am Main filed Critical Goethe Universitaet Frankfurt am Main
Publication of EP2697644A1 publication Critical patent/EP2697644A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6408—Fluorescence; Phosphorescence with measurement of decay time, time resolved fluorescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G01N33/4905—Determining clotting time of blood
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors

Definitions

  • the present invention is in the field of medical technology. More particularly, the invention relates to an apparatus and method for determining the coagulation time of blood, its use, and a sample vessel associated therewith.
  • Coagulation or coagulation of blood is a necessary process for the maintenance of internal and external bleeding.
  • Coagulation under physiological conditions usually involves two sub-processes.
  • One partial procedure is based on platelets, which usually trigger the coagulation cascade.
  • the thrombocytes In the event of an injury to a blood vessel, the thrombocytes typically attach to the vessel opening, stick together and thus produce the first wound closure.
  • the second process involves the so-called plasmatic coagulation, in which the still loose closure is reinforced by the formation of fibrin threads to form a blood clot, also referred to as thrombus.
  • thrombosis In which a thrombus forms in a vessel and blocks it. Thrombosis often occurs in veins, especially deep leg veins. For example, when the thrombus loosens, it can enter the pulmonary artery via the inferior vena cava and the right atrium of the heart and block it, which can lead to pulmonary embolism.
  • the cause of thrombosis is often a pathological increase in the coagulation ability of the blood, which can be counteracted by anticoagulant drugs such as heparin or argatroban.
  • the coagulation ability of the blood must be investigated, for example by measuring the coagulation time of a blood sample in a suitable device.
  • the correct dosage of anticoagulants is extremely critical, as a excessive lowering of coagulation tendency, in turn, brings about the risk of uncontrolled bleeding even with minor injuries.
  • a particularly reliable and precise monitoring of the coagulation ability of the blood is also necessary before surgical interventions, because it must be ensured that the bleeding of inevitably produced wounds will also come to a safe halt.
  • Another important application is emergency medicine. For example, if an injured person is suspected of having internal bleeding, it is of utmost importance to determine if the blood is sufficiently coagulating. For example, for unknown reasons, the injured person could regularly take anti-coagulant drugs that would then cause increased internal bleeding. For the emergency physician, it would therefore be important, by default, to be able to quickly and reliably check the coagulability of the blood, in order to be able to initiate appropriate countermeasures if necessary.
  • a variety of devices and methods for measuring the coagulability of the blood are known in the prior art. These include a large number of mechanical devices, as described, for example, in EP 0 596 222 A1, in which blood coagulation in a measuring cuvette is measured on an enclosed ball. Other mechanical methods use a test cuvette with a capillary path through which blood is pumped back and forth. The flow rate is measured and in turn provides information about the degree of clotting of the blood, see, for example, US Pat. No. 5,372,946. In other methods, the coagulation is measured optically, for example based on the light transmission of a sample in a capillary, as described for example in WO 89/06803.
  • DE 10 2008 026 009 B4 describes a method for the determination of viscosity using acoustoelectric resonators.
  • the viscoelastic medium as a measuring medium is applied to an acoustoelectric resonator, which - in addition to a most pronounced resonance region - has additional secondary modes closely adjacent in frequency.
  • acoustoelectrical resonators one-tone resonators based on surface acoustic waves (SAW) can be used.
  • SAW surface acoustic waves
  • the admittance curve on the acoustoelectric resonator is measured as a function of the frequency in a frequency range of +/- 10% of the frequency of the most pronounced maximum of the admittance amount. From this measurement can be made in an iterative process on the viscosity of the medium are closed.
  • this document proposes to use the method for characterizing dynamic processes, such as the determination of the coagulation behavior of blood.
  • An advantageous device combines a plurality of properties with each other, including a good reproducibility of the measurement results, ease of use, a fast analysis time and a moderate amount of equipment.
  • the invention has for its object to provide an apparatus and a method having such properties.
  • a device for determining the coagulation time of blood which offers advantages in all these aspects, is defined in claim 1.
  • a corresponding method and use are defined in claims 13 and 17, respectively.
  • Claim 10 defines a sample vessel for use with the apparatus and method of the invention. Advantageous developments are specified in the dependent claims.
  • a device for determining the coagulation time of blood, comprising: a sample vessel for receiving a blood sample, or a receptacle for a sample vessel,
  • a device for generating surface waves which are suitable for mixing a blood sample in the sample vessel
  • a light source suitable for exciting the fluorescence of microspheres contained in the sample vessel
  • blood sample is understood to mean any fluid in which blood is contained, but that also contains other components. may be, in particular calcium chloride for recalcification of the blood and possibly a coagulation simulator, such as kaolin.
  • whole blood is preferably examined within the scope of the invention, it is also possible for some constituents of the blood to be optimally removed in the sample.
  • the sample vessel as such does not necessarily have to be part of the device under protection, but on the contrary, on the contrary, it can be marketed as a disposable article independently of the device as such. In this case, however, the device has a receptacle, ie some type of footprint or support for such a sample vessel, suitable for use with the device.
  • the device according to the invention thus makes it possible to mix the blood sample by surface waves which are coupled into the blood sample. As long as the blood does not coagulate, it is kept in motion by the surface waves, and this movement becomes visible (though not with the naked eye) by the fluorescent microspheres contained in the blood sample, and thus optically observable. However, once coagulation sets in, the fluorescent microspheres will slow down or come to a standstill, which can also be observed, so that the time of coagulation is detectable.
  • the means for monitoring the fluorescent microspheres comprise imaging optics adapted to image an image of the fluorescent microspheres onto an image sensor, and an image analyzer capable of sequencing the movement of the fluorescence on successive images taken by the image sensor To detect microspheres in a blood sample and to determine the time at which the amount of movement falls below a predetermined threshold.
  • the image analysis unit is set up to determine a similarity or correlation of two successive recorded images, and to determine the extent of the movement on the basis of this similarity or correlation.
  • the amount of movement is quantified by the similarity of temporally successive images. It can be seen that the more the current motion is pronounced, the less the two pictures taken in a given time interval will be the less similar and that the similarity will be complete except for fluctuations in the measuring apparatus when the blood is in it contained microspheres to a halt.
  • an analysis of the correlation or a similarity of temporally successive images is a suitable, quantifiable measure by means of which the movement can be monitored and a slowdown or stoppage of the movement can be detected.
  • a further advantage of this embodiment is that suitable image analysis programs that detect and quantify a similarity or correlation between images are already known from other applications and can be adopted for the purposes of the invention.
  • the device for generating surface waves comprises a piezoelectric substrate on which an electrode structure is formed, and an alternating current source which is connected or connectable to the electrode structure.
  • the piezoelectric substrate is made of, for example, lithium niobate (LiNbO 3).
  • the electrode structure comprises at least two comb-like electrode assemblies each having a plurality of parallel fingers at least partially intermeshed, " when an AC current signal is applied to the two comb-like electrode assemblies, an electric field is generated between the adjacent electrode fingers and the piezoelectric effect results to a corresponding excitation voltage deflection of the piezoelectric material and - at a suitable frequency of the AC signal - to generate surface waves.
  • a particular advantage of the device according to the invention is that it is highly miniaturized. This applies on the one hand for the apparatus construction itself, which can be kept extremely small and compact and therefore ideal for a portable device that can be used outside of medical laboratories, for example, directly at the bedside, in care facilities, in emergency vehicles or in the home Environment of a patient.
  • Another aspect of miniaturization concerns the required amount of the blood sample. It has been shown that the method according to the invention can be carried out very successfully using blood samples which contain only 5 ⁇ l of whole blood, ie a drop of blood.
  • the Probengefpier therefore preferably has a receiving volume of less than 40 ⁇ , preferably less than 20 ⁇ .
  • the ability of the device according to the invention to produce meaningful and reproducible results with very small blood sample volumes is particularly advantageous in animal experiments on small animals such as mice, which have only a small amount of blood.
  • the sample vessel consists of a biocompatible polymer material, wherein in particular polydimethylsiloxane has proven to be advantageous.
  • the invention includes a sample vessel for use in a device according to any of the embodiments described above, prefilled with fluorescent microspheres and having an inlet for filling blood.
  • This sample container may be, in particular, a disposable product.
  • pre-filled indicates that the sample vial can already be pre-filled with the microspheres and stored in this pre-filled condition by the user Calcium chloride as Recalcmentsreagenz and possibly a coagulation stimulator, such as kaolin, prefilled.
  • the sample vessel prefilled with microspheres is pre-pressurized with a negative pressure, so that it can suck in the appropriate amount of blood during its use, without the need for elaborate pipetting or the like.
  • a negative pressure is particularly important for applications outside laboratory environments, such as in emergency vehicles, care facilities or the home environment.
  • this is also a great advantage in the hospital environment. For example, if the test is performed directly on the patient's bed and the result is thus immediately available.
  • a further possibility for a quasi-automatic blood filling of the sample vessel filled with microspheres is to form the geometry and / or inner surface quality of the container such that a blood sample is drawn into the sample vessel by capillary action without additional negative pressure generated at the moment of filling.
  • Such purely capillary force driven filling is made possible due to the very small sample volumes required.
  • the blood sample may be drawn into the sample vessel by microfluidic techniques.
  • FIG. 1 shows a schematic structure of a device according to the invention
  • Fig. 2 (a) to (e) is a sequence of schematic illustrations illustrating the operation of the
  • Fig. 4 shows the time course of the coagulation between successive
  • Figures 5 (a) to (d) are bar graphs for coagulation times versus various doses of argatroban for the method of the invention ( Figure 5 (d)) and for three conventional test methods ( Figures 5 (a) to (c)). , and
  • FIG. 6 shows a diagram showing the coagulation time as a function of a heparin dose in five volunteers
  • Fig. 7 is a graph showing the coagulation time versus dose of the platelet aggregation inhibitor abciximab. DESCRIPTION OF THE PREFERRED EMBODIMENT
  • the device 10 includes a receptacle 12 for receiving a sample vessel 14.
  • the recording is located on a device 16 for generating surface acoustic waves, which are sometimes referred to in the German literature as SAW (surface acoustic waves).
  • the device 16 comprises a piezoelectric chip 18, on the upper side of which comb-like electrode arrangements (not shown) are formed, each having a plurality of parallel fingers arranged in an intermeshing manner.
  • the electrode assemblies (not shown) are connected via a line 20 to an AC power source, more specifically to a frequency generator 22.
  • the fluorescence microscope 24 includes a light source (not shown) for exciting the fluorescence of microspheres contained in the sample vessel 14 (not shown in FIG. 1) and imaging optics (not shown) adapted to image an image of the fluorescent microspheres onto an image sensor , Both the fluorescence microscope 24 and the frequency generator 22 are connected via data lines 26 to a control device 28.
  • Microspheres are known to the person skilled in the art. They are commercially available in various designs with the desired physicochemical properties, such as diameter, fluorescence wavelengths, and surface chemistry. For further details, see the reviews "Microspheres for Biomedical Applications: Preparation of Reactive and Labeled Microspheres” by Reza Arshady, Biomaterials 1993; 14 (1): 5-15 and “Polymer microbeads in immunology” by Vetvicka et al. , Biomaterials. 1987 Sep; 8 (5): 341-5.
  • FIG. 2 (a) shows the empty sample vessel 14 in a schematic representation.
  • FIG. 2 (b) shows the sample vessel 14 filled with a blood sample 30 containing biocompatible fluorescent microspheres 32.
  • Such fluorescent microspheres 32 are known from chemical and biological analysis. In the illustrated embodiment, they consist of a biocompatible material and have a diameter of about 1 ⁇ .
  • acoustic surface waves are generated and coupled into the sample liquid, as shown in Fig. 2 (d) is shown schematically.
  • the surface acoustic waves coupled into the sample liquid act like a "nano-earthquake” and lead to a vigorous mixing of the blood sample 30, and simultaneously to a rapid movement of the fluorescent microspheres 32, which is shown schematically in Fig. 2 (d).
  • This movement can be monitored by means of the fluorescence microscope 24 (see Fig. 1) .
  • the fluorescence microscope 24 contains not only an imaging optics but also an image sensor which receives digital images which are transmitted through the data line 26 to the control device 28.
  • the controller 28 performs a correlation analysis on successive images of the fluorescence microscope 24 at regular time intervals. It turned out that no special software had to be developed for this correlation analysis, but that even the use of a publicly accessible standard software, namely the plug-in "CorrelationJ” of the software "ImageJ” gave very good results.
  • Fig. 3 shows the time course of the correlation between successive images, which resulted with the structure of Fig. 1 in blood samples from seven different subjects. The output parameter of the program representing the correlation was normalized to 100%, which corresponds to the case of greatest similarity or stoppage of the sample.
  • the coagulation times of the subjects spread in a range of about 80 s around a mean value of just over 200 s. This variability is due to the fact that the coagulation ability of the blood and thus the coagulation time measured with the device of the invention also varies in healthy volunteers.
  • Fig. 4 also shows the time course of the correlation, but for one and the same blood sample to which different amounts of an anticoagulant, in this case argatroban, have been added.
  • an anticoagulant in this case argatroban
  • the anticoagulant effect of the argatroban becomes directly visible through an extension of the coagulation time.
  • the device 10 of the invention allows to check the effect of an anticoagulant directly in whole blood. According to the result, the dose can then be adjusted, for example.
  • Figure 5 shows comparative measurements of coagulation times as determined by different established methods ( Figures 5 (a) to (c)) and by the apparatus and method of the invention ( Figure 5 (d)).
  • the APPT Figure 5 (a)) measures the time required for thrombus formation after addition of phospholipids and coagulation accelerators (such as kaolin, silica, or the like) in the recalcified platelet-poor plasma.
  • phospholipids and coagulation accelerators such as kaolin, silica, or the like
  • Fig. 5 shows that the method of the invention provides a characteristic monotonic relationship between coagulation time and drug dose in a manner similar to established, but much more sophisticated, procedures that can only be performed by trained personnel, so that the method of the invention as well as the established methods for the determination adequate doses is suitable.
  • the method ECAT ( Figure 5 (b)) can no longer be used for a dose of 4000 ng / ml argatroban, therefore the corresponding value in the bar graph has been omitted.
  • coagulation times in the illustrated embodiment of the invention take somewhat longer than in the established methods ATTP, ECAT and PICT, in which coagulation accelerators such as phospholipids, kaolin etc. are used.
  • coagulation accelerators such as phospholipids, kaolin etc.
  • similar coagulation accelerators may also be used in the apparatus and method of the invention, thereby also reducing measurement times.
  • FIG. 6 shows the coagulation times for untreated blood and four different doses of heparin. The measurement was based on values from five subjects. Again, one recognizes the characteristic dependence of the coagulation time on the dose, so that the device and method of the invention is ideally suited to the setting of the appropriate dose.
  • the device of the invention shows particular advantages outside of a laboratory environment. Characteristic of the device and method of the invention is that the blood is not in any way needs to be pretreated, but that simply the existing whole blood can be used, of which already a lot of only 5 ⁇ sufficient.
  • the appropriate dosage is already factory manufacturer TIG by the size of the sample vessel 14, which has been shown only schematically in Fig. 1 and 2, and a predosed provision of Recalcrancesreagenz 34 (eg., Calcium chloride) plus any coagulation accelerator achieved.
  • Recalceuticsreagenz 34 eg., Calcium chloride
  • the device of the invention can also be easily integrated into existing device landscapes, for example via a docking station.
  • the sample vessel 14 is already prefilled with a suitable amount of fluorescent microspheres 32.
  • the sample vessel 24 may already be prefilled with the recalcification reagent 34 at an appropriate dose.
  • recalcification reagent 34 could also be provided in predosed containers (not shown). The user then only has to completely fill up the pre-filled sample vessel 14 with blood, place it in the receptacle 12 of the device 10 and start the analysis program, for example, by simply pressing a button. The controller 28 then outputs the coagulation time.
  • the controller 28 may of course also output other information related to the measured coagulation time, for example, a low coagulant warning, as would be beneficial in emergency medicine, for example, or a specific dose suggestion to a patient who is taking anticoagulant medication on a permanent basis Use the device 10 in home use to monitor its dose.
  • the device and method of the invention can be used to quantitatively evaluate the efficacy of anticoagulant drugs such as argatroban and heparin. These drugs are agents that inhibit plasmatic coagulation. Further experiments of the inventors show, however, that with the method and the device of the invention, the mode of action of platelet aggregation inhibitors is observable or measurable. Platelet aggregation inhibitors are used, for example, before heart surgery and for short-term cardiac infarction prophylaxis.
  • abciximab is a Fab fragment of a monoclonal antibody that inhibits the binding of the glycoprotein IIb / IIIa receptors on the surface of platelets and therefore blocks the binding sites for fibrinogen and other adhesion molecules.
  • abciximab is a Fab fragment of a monoclonal antibody that inhibits the binding of the glycoprotein IIb / IIIa receptors on the surface of platelets and therefore blocks the binding sites for fibrinogen and other adhesion molecules.
  • the coagulation time is only information that can be obtained from the analysis of the images, but that the time course of the movement of the microspheres also discloses further information about the hydrodynamic state of the blood sample, for example the time course of the viscosity etc.
  • anticoagulants in the true sense refer to substances that influence the coagulation factors of blood plasma
  • coagulation may also be delayed by so-called platelet aggregation inhibitors acting on the platelets.
  • abciximab is a Fab fragment of a monoclonal antibody that inhibits binding to the glycoprotein IIb / IIIa receptors on the surface of the platelet.
  • FIG. 7 shows measurement data of the coagulation time without adding abciximab, with an addition of 4 mg / ml and with an addition of 40 mg / ml abciximab.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Ecology (AREA)
  • Medical Informatics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Optics & Photonics (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Abstract

La présente invention a pour objet un dispositif et un procédé pour la détermination du temps de coagulation du sang. Des ondes de surface sont injectées dans un échantillon de sang (30) qui contient des microsphères fluorescentes (32). La fluorescence des microsphères est excitée et les mouvements des microsphères sont surveillés optiquement. Le moment de la coagulation peut être déterminé à l'aide du ralentissement ou de l'arrêt du mouvement des microsphères.
EP12713609.1A 2011-04-11 2012-04-11 Dispositif et procédé pour la détermination du temps de coagulation du sang Withdrawn EP2697644A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102011001952A DE102011001952B8 (de) 2011-04-11 2011-04-11 Vorrichtung und Verfahren zur Bestimmung der Koagulationszeit von Blut
PCT/EP2012/001575 WO2012139752A1 (fr) 2011-04-11 2012-04-11 Dispositif et procédé pour la détermination du temps de coagulation du sang

Publications (1)

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EP2697644A1 true EP2697644A1 (fr) 2014-02-19

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US (1) US20140064595A1 (fr)
EP (1) EP2697644A1 (fr)
DE (1) DE102011001952B8 (fr)
WO (1) WO2012139752A1 (fr)

Families Citing this family (3)

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Publication number Priority date Publication date Assignee Title
EP2975383A1 (fr) * 2014-07-14 2016-01-20 Johann Wolfgang Goethe-Universität, Frankfurt am Main Procédé et dispositif pour analyser un milieu fluide tel qu'un échantillon de sang
WO2021012075A1 (fr) * 2019-07-19 2021-01-28 Medtrum Technologies Inc. Dispositif de perfusion de médicament intégré
CN112924491B (zh) * 2021-01-27 2022-08-19 江苏科技大学 一种血凝检测装置及其检测方法

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5469497A (en) * 1977-11-12 1979-06-04 Kyoto Daiichi Kagaku Kk Method and device for measuring blood solidification time
JPH0726965B2 (ja) 1988-01-14 1995-03-29 ノボ‐ノルディスク アクティーゼルスカブ 血液試料の凝固時間の測定装置
TW221493B (fr) * 1990-07-10 1994-03-01 Cardiovascular Diagnostics Inc
DE4237449C1 (de) 1992-11-06 1994-06-16 Heinrich Amelung Gmbh Herstell Probenaufnahmeeinrichtung für die Blutgerinnungsmessung
US5302348A (en) 1992-12-10 1994-04-12 Itc Corporation Blood coagulation time test apparatus and method
US5378431A (en) * 1993-06-14 1995-01-03 Becton, Dickinson And Company Dual pathway clotting enhancer for blood collection tube
US5567596A (en) * 1994-12-29 1996-10-22 Research Foundation Of State University Of New York Rapid assay of activators and inhibitors of clotting
DE19850803A1 (de) * 1998-11-04 2000-05-11 Bosch Gmbh Robert Sensoranordnung und ein Verfahren zur Ermittlung der Dichte und der Viskosität einer Flüssigkeit
US6451610B1 (en) * 1999-04-14 2002-09-17 International Technidyne Corporation Method and apparatus for coagulation based assays
GB2399876B (en) * 2003-03-27 2005-12-21 Michael Catt Method of investigating a blood sample
EP1771724A1 (fr) * 2004-07-29 2007-04-11 MNT Innovations Pty Ltd Capteur biologique saw
US9068977B2 (en) * 2007-03-09 2015-06-30 The Regents Of The University Of Michigan Non-linear rotation rates of remotely driven particles and uses thereof
DE102008026009B4 (de) 2008-05-29 2010-09-16 Leibniz-Institut Für Festkörper- Und Werkstoffforschung Dresden E.V. Verfahren zur Bestimmung der Viskosität und Elastizität von viskoelastischen Medien
FR2943789B1 (fr) * 2009-03-26 2013-07-26 Commissariat Energie Atomique Procede et dispositif pour la caracterisation de la dynamique de coagulation ou sedimentation d'un fluide tel que le sang ou le plasma sanguin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DARREN W BRANCH ET AL: "Active Mixing in Microchannels using Surface Acoustic Wave Streaming on Lithium Niobate", SCITECH CONNECT, 1 November 2005 (2005-11-01), pages 1 - 25, XP055407549, Retrieved from the Internet <URL:http://prod.sandia.gov/techlib/access-control.cgi/2005/057036.pdf> [retrieved on 20170918] *

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DE102011001952B4 (de) 2012-12-06
WO2012139752A1 (fr) 2012-10-18
US20140064595A1 (en) 2014-03-06
DE102011001952B8 (de) 2012-12-20
DE102011001952A1 (de) 2012-10-11

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