Method for performing coagulation assays accurately, rapidly and simply, using dry chemical reagents and paramagnetic particles
First Claim
1. In a coagulation assay comprising combining a coagulation assay reagent and a whole blood sample or plasma sample and obtaining a coagulation assay measurement, the improvement comprising adding to a dry coagulation assay reagent containing magnetic particles distributed substantially homogeneously therethrough, arranged in a substantially flattened format, and under the influence of an oscillating magnetic field or moving permanent magnetic field, or both, a whole blood sample or a plasma sample thereby substantially simultaneously initiating movement of said magnetic particles and the coagulation assay measurement and monitoring movement of said magnetic particles to obtain said assay measurement.
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Accused Products
Abstract
A method and apparatus for the measurement of clot formation times, clot dissolution times, or clotting parameters is disclosed. This method performs these measurements by monitoring movement of magnetic particles incorporated in the sample being assayed, where the movement is induced by a magnetic field.
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Citations
59 Claims
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1. In a coagulation assay comprising combining a coagulation assay reagent and a whole blood sample or plasma sample and obtaining a coagulation assay measurement, the improvement comprising adding to a dry coagulation assay reagent containing magnetic particles distributed substantially homogeneously therethrough, arranged in a substantially flattened format, and under the influence of an oscillating magnetic field or moving permanent magnetic field, or both, a whole blood sample or a plasma sample thereby substantially simultaneously initiating movement of said magnetic particles and the coagulation assay measurement and monitoring movement of said magnetic particles to obtain said assay measurement.
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2. A method for performing a clot lysis assay measurement on a whole blood or plasma sample fibrinolytically active containing a component of the blood coagulation cascade system, comprising:
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(i) adding a measured amount of said sample to a dry reagent arranged in a substantially flattened configuration and containing a fibrin clot from whole blood or plasma and magnetic particles distributed substantially homogeneously throughout said clot, thereby substantially simultaneously initiating the assay measurement, wherein said reagent containing magnetic particles is subjected to (ia) an oscillating magnetic field or (ib) a moving permanent magnetic field or (ic) a combination of an oscillating magnetic field and a stationary permanent magnetic field; and (ii) obtaining said assay measurement by monitoring the movement of said magnetic particles induced by (ia), (ib) or (ic).
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3. A method for performing a clot lysis assay measurement, comprising:
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(i) contacting a whole blood or plasma sample and a dry composition arranged in a substantially flattened configuration and containing at least one whole blood or plasma clot producing reagent and magnetic particles distributed substantially homogeneously throughout said composition to obtain a clot containing magnetic particles;
then(ii) adding a whole blood or plasma clot lysis assay reagent to said clot, thereby substantially simultaneously initiating said clot lysis assay measurement, and optically monitoring movement in said magnetic particles induced by (ia) an oscillating magnetic field or (ib) a moving permanent magnetic field or (ic) a combination of an oscillating magnetic field and a stationary permanent magnetic field, to obtain said clot lysis assay measurement.
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- 4. A method for performing a clot lysis assay measurement, comprising:
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5. contacting a whole blood or plasma sample and a dry composition arranged in a substantially flattened configuration, containing at least one whole blood or plasma clot producing reagent and magnetic particles distributed substantially homogeneously therethrough, and being subjected to (a) an oscillating magnetic field or (b) a moving permanent magnetic field or (c) a combination of an oscillating magnetic field and a stationary permanent magnetic field, thereby substantially simultaneously initiating movement of said magnetic particles and said clot lysis assay measurement and obtaining the formation of a clot containing magnetic particles, and subsequently allowing lysis of said clot to proceed, thereby obtaining said clot lysis assay measurement by monitoring movement of said magnetic particles.
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7. A method for performing a clot lysis assay measurement on a whole blood or plasma sample containing a fibrinolytically active component of the blood coagulation cascade system, comprising:
contacting a whole blood or plasma sample and a fibrin clot arranged in a substantially flattened configuration and containing magnetic particles distributed substantially homogeneously therethrough, said clot being subjected to (a) an oscillating magnetic field or (b) a moving permanent magnetic field or (c) a combination of an oscillating magnetic field and a stationary permanent magnetic field, thereby substantially simultaneously initiating movement of said magnetic particles and the clot lysis assay measurement, and obtaining the clot assay measurement by monitoring movement of said magnetic particles.
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9. A method for performing a coagulation assay on a whole blood or plasma sample, comprising:
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(i) adding a first, whole blood or plasma, component of the assay to a second component of the assay, wherein said second component comprises a dry coagulation assay reagent arranged in a substantially flattened configuration and containing magnetic particles distributed substantially homogeneously therethrough, and wherein said second is subjected to (ia) an oscillating magnetic field or (ib) a moving permanent magnetic field or (ic) a combination of an oscillating magnetic field and a stationary permanent magnetic field, whereby said adding of said first component to said second component substantially simultaneously initiates movement of said magnetic particles and the coagulation assay measurement; and (ii) monitoring movement induced in said magnetic particles by (ia) or (ib) or (ic) to obtain said coagulation assay measurement. - View Dependent Claims (11, 12, 13, 14, 15, 17, 19)
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23. An element for performing a liquid sample assay, said element comprising therein a channel structure defining a sample well and a reaction volume in fluid communication with each other, wherein said reaction volume contains at least one dry assay reagent arranged in a substantially flattened configuration and containing magnetic particles distributed substantially homogeneously therethrough, and wherein said reaction volume is defined by an upper surface having attached thereto a reflectance layer comprising a semipermeable matrix, said channel structure having a geometry causing the liquid sample, when placed in said sample well, to be drawn into and filling said reaction volume via capillary action, after said reaction volume is filled said liquid sample remains stationary.
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32. A method for performing a coagulation assay measurement, comprising:
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(i) adding a whole blood or plasma sample to the sample well of an element comprising; a channel structure defining a sample well and a reaction volume in fluid communication with each other, wherein said reaction volume is defined by an upper surface having attached thereto a reflectance layer, comprising a semipermeable matrix wherein said reaction volume contains a measured amount of at least one dry coagulation assay reagent arranged in a substantially flattened configuration and containing magnetic particles distributed substantially homogeneously therethrough, wherein a specific volume of said sample is drawn into said reaction volume by capillary action and contacts, together with said semipermeable layer, said reagent to thereby substantially simultaneously initiate said coagulation assay measurement; and (ii) performing said coagulation assay measurement by measurement the reflectance of said semipermeable layer. - View Dependent Claims (34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 48, 50, 52, 53, 54, 56, 57, 58)
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33. A dry coagulation assay reagent comprising magnetic particles distributed substantially homogeneously therethrough wherein said reagent is selected from the group consisting of:
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(1) one member selected from the group consisting of prothrombin time reagents and (ii) prothrombin time reagents and calcium salts; (2) partial thromboplastin time reagents with calcium chloride; (3) partial thromboplastin time reagents with calcium chloride and clot formation activators; (4) thrombin or a snake venom with thrombotic activity; (5) fibrin, or plasminogen and fibrin; (6) plasminogen activator assay reagents containing (i) plasminogen and (ii) either fibrin, a snake venom with thrombotic activity, or thrombin; (7) plasminogen assay reagents containing (i) a plasminogen activator and (ii) either fibrin, a snake venom with thrombotic activity, or thrombin; (8) natural and synthetic plasminogen activators; (9) α
-2-antiplasmin assay reagents containing fibrin and plasmin; and(10) combinations thereof.
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47. A kit for performing a coagulation assay, comprising, in one or more containers, a permanent magnet, a timing means, and an element containing at least one dry coagulation assay reagent arranged in a substantially flattened format and containing magnetic particles distributed substantially homogeneously therethrough.
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49. A system for performing a coagulation assay measurement, comprising:
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(i) an instrument with a means for temperature control, a means for producing an oscillating magnetic field or for moving a permanent magnetic field, an illuminating means, and a photometric monitoring means; and (ii) an element for performing said coagulation assay, said element comprising a channel structure defining a sample well and reaction volume in fluid communication with each other, said channel structure having a geometry causing a liquid sample placed in said sample well to be drawn into and filling said reaction volume via capillary action, said reaction volume comprising at least one dry coagulation assay reagent arranged in a substantially flattened configuration and containing magnetic particles distributed substantially homogeneously therethrough. - View Dependent Claims (51)
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55. A system for performing a coagulation assay, comprising:
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(i) a reaction element comprising (1) a sample well for receiving a liquid sample and (2) a reaction chamber containing a dry coagulation assay reagent arranged in a substantially flattened configuration and in which is embedded, substantially homogeneously therethrough, magnetic particles; (ii) said sample well and said reaction chamber being in fluid communication through a transport zone of geometry such that a volume of liquid sample placed in said sample well and corresponding to the volume of said reaction chamber is transported from said sample well to said reaction chamber simultaneously; (iii) means for optically monitoring said reaction chamber; (iv) means for subjecting said reaction chamber to an oscillating magnetic field; (v) whereby, when said sample is introduced into said reaction chamber, said dry coagulation assay reagent is solubilized and said magnetic particles are thereby freed to move in an oscillating pattern induced by said oscillating magnetic field, thus providing a measurement of the kinetics of said coagulation assay corresponding to changes in the degree of said magnetic particles movement relative to said oscillating magnetic field.
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59. A method for performing a coagulation assay, comprising:
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(i) subjecting to an oscillating magnetic field a reaction element bearing (1) a sample well for receiving a whole blood or plasma sample and (2) a reaction chamber containing a dry coagulation assay reagent arranged in a substantially flattened format and in which is embedded, substantially homogeneously therethrough, magnetic particles, said sample well and reaction chamber being in fluid communication through a transport zone of geometry such that a volume of sample placed in said sample well and corresponding to the volume of said reaction chamber is transported from said sample well to said reaction chamber simultaneously; (ii) adding a whole blood or plasma sample susceptible to coagulation to said sample well whereby at least a part of said sample is introduced simultaneously to said reaction chamber, said reagent is solubilized and said particles are freed to move in an oscillating pattern induced by said oscillating magnetic field; and (iii) optically monitoring said reaction chamber to measure kinetics for the coagulation assay corresponding to changes in the degree of said particle movement relative to said magnetic field.
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Specification