Method and device for measuring blood coagulation or lysis by viscosity changes

• US 6,046,051 A
• Filed: 06/27/1997
• Issued: 04/04/2000
• Est. Priority Date: 06/27/1997
• Status: Expired due to Term

• Current Assignee: Alere San Diego Incorporated (Abbott Laboratories)
• Original Assignee: Hemosense Incorporated (Abbott Laboratories)
• Inventors: Jina, Arvind N.
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US08/884,027
• Time in Patent Office: 1,012 Days
• Field of Search: 436/69, 422/56, 422/58, 422/82.01, 422/82.02, 422/73, 73/54.01, 73/54.02, 600/369
• US Class Current: 436/69
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/56
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors

Abstract

The present invention provides a single-use electronic device and test card for use therein which performs a coagulation or lysis assay of a blood sample. The device includes a housing having an exterior surface and defining an interior area and means for receiving the sample through the housing into the interior space. A non-porous substrate is positioned within the interior space for receiving the sample thereon. A reagent accelerates the coagulation of the sample and is positioned on the substrate and in contact with the sample. Optionally, an electroactive species may also be reacted with the sample. The device also includes means for measuring the viscosity of the sample and generating an electrical signal which correlates to a curve of the coagulation/lysis assay. Processing means positioned within the interior space is connected to the measuring means for receiving and converting the electrical signal into a digital output corresponding to the coagulation/lysis assay using assay calibration information stored therein. Display means visually displays the digital output external to the housing and is connected to the processing means. A method of determining the coagulation or lysis of a sample provides for accelerating the coagulation of the sample by chemically reacting the sample with at least one reagent on the substrate to produce a detectable change in the viscosity of the sample which correlates with the state of coagulation or lysis of the sample and measuring the viscosity of the sample and generating an electrical signal which correlates to a curve of the coagulation/lysis assay.

Claims

1. A single-use electronic device for performing a coagulation or lysis assay of a blood sample, the device comprising:

a housing having an exterior surface and defining an interior area;

means for receiving the blood sample through the housing into the interior area;

a non-porous substrate positioned within the interior area for receiving the blood sample thereon;

a reagent for accelerating the coagulation of the blood sample positioned on the substrate and in contact with the blood sample;

an electroactive species positioned on the substrate and in contact with the blood sample;

means for measuring the viscosity of the blood sample and generating an electrical signal which correlates to a curve of a coagulation or lysis assay;

processing means being positioned within the interior area and connected to the measuring means for receiving and converting the electrical signal into a digital output corresponding to the coagulation or lysis assay using assay calibration information stored in the processing means; and

display means for visually displaying the digital output external to the housing, the display means being connected to the processing means.

2. The device of claim 1 wherein the measuring means includes:

means for generating a signal of predetermined frequency, the generating means being positioned within the interior area;

a plurality of electrodes being positioned on the substrate and contacting the blood sample, the electrodes connecting to the generating means for passing the signal into the blood sample, the electrodes generating an electrical signal corresponding to the conductivity/resistivity of the blood sample.

3. The device of claim 1 wherein the measuring means includes:

means for generating a signal of predetermined frequency, the generating means being positioned within the interior area;

a plurality of electrodes being positioned on the substrate and contacting the blood sample, the electrodes connecting to the generating means for passing the signal into the blood sample, the electrodes generating an electrical signal corresponding to the diffusion coefficient of the electroactive species.

4. The device of claim 1 wherein the electroactive species is selected from the group consisting of ferricyanide, ferrocyanide, cadmium chloride, and methylviologen.

5. The device of claim 1 wherein the device further includes a heater being positioned within the interior area and in thermal contact with the substrate so that the substrate can be warmed to a pre-determined temperature upon receiving the blood sample.

6. The device of claim 1 wherein the processing means further calibrates the electrical signal to a reference standard using the stored assay calibration information.

7. The device of claim 1 wherein the processing means further receives the ambient temperature of the assay device from a sensor within the housing and adjusts assay results using the stored assay calibration information.

8. The device of claim 1 wherein the assay calibration information stored in the processing means determines results for at least one of assays selected from the group consisting of a Prothrombin Time, an Activated Partial Thromboplastin Time, platelet aggregation, and fibrinogen.

9. A test card for an electronic device which generates a signal having a pre-determined frequency and determines a curve of a coagulation or lysis assay of a blood sample, the test card comprising:

a non-porous substrate defining a surface for receiving the blood sample;

an electroactive species positioned on the substrate and in contact with the blood sample;

a reagent initially immobilized on the surface for contact with the blood sample; and

a plurality of electrodes being positioned on the substrate and contacting the blood sample, the electrodes adapted to receive and pass the signal into the blood sample, the electrodes generating an electrical signal corresponding to the viscosity of the blood sample which correlates to the curve of the coagulation or lysis assay.

10. The test card of claim 9 wherein the electrical signal generated by the electrodes measures the conductivity/resistivity of the blood sample.

11. The test card of claim 9 wherein the electrical signal generated by the electrodes measures the diffusion coefficient of the electroactive species.

12. The test card of claim 9 wherein the electroactive species is selected from the group consisting of ferricyanide, ferrocyanide, cadmium chloride, and methylviologen.

13. A method of determining the coagulation or lysis of a blood sample, the steps of the method comprising:

introducing the blood sample to a sample receptor site on a substrate and contacting an electroactive species positioned on the substrate with the blood sample;

accelerating coagulation of the blood sample by chemically reacting the blood sample with at least one reagent on the substrate to produce a detectable change in the viscosity of the blood sample which correlates with a state of coagulation or lysis of the blood sample;

measuring the viscosity of the blood sample and generating an electrical signal which correlates to a curve of a coagulation or lysis assay; and

processing the electrical signal into a digital output corresponding to the coagulation or lysis assay using assay calibration information.

14. The method of claim 13 wherein the method includes the step of displaying the digital output.

15. The method of claim 13 wherein the measuring step includes:

generating a signal of predetermined frequency;

contacting a plurality of electrodes with the blood sample;

passing the signal of predetermined frequency through the electrodes into the blood sample; and

generating the electrical signal with the electrodes corresponding to the conductivity/resistivity of the blood sample.

16. The method of claim 13 wherein the measuring step includes:

generating a signal of predetermined frequency;

contacting a plurality of electrodes with the blood sample;

passing the signal of predetermined frequency through the electrodes into the blood sample; and

generating the electrical signal with the electrodes corresponding to the diffusion coefficient of the electroactive species.

17. The method of claim 13 wherein the method includes calibrating the electrical signal to a reference standard using the assay calibration information to determine results for at least one of assays selected from the group consisting of a Prothrombin Time, an Activated Partial Thromboplastin Time, platelet aggregation, and fibrinogen.