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

• US 6,060,323 A
• Filed: 11/19/1998
• Issued: 05/09/2000
• 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:
  US09/195,842
• Time in Patent Office: 537 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 device for performing a coagulation or lysis assay of a sample, the device comprising:

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

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

a non-porous substrate positioned within the interior area for receiving the sample thereon and retaining the sample in a particular position on the substrate;

a reagent positioned in the housing and in contact with the sample for accelerating the coagulation of the sample;

means for continuously measuring a value of an electrical property of the sample itself while in the particular position on the substrate 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 device; 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 sample in the particular position, the electrodes connecting to the generating means for passing the signal into the sample, the electrodes generating an electrical signal corresponding to the conductivity/resistivity of the sample.

3. 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 sample.

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

5. 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.

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

7. A device for performing a coagulation or lysis assay of a sample, the device comprising:

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

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

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

a reagent positioned in the housing and in contact with the sample for accelerating the coagulation of the sample;

means for continuously measuring the viscosity of only the sample while being held in a particular position during the assay and generating an electrical signal which correlates to a curve of a coagulation or lysis assay, the substrate retaining the sample in continuous, direct contact with the measuring means;

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 device; and

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

8. The device of claim 7 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 sample, the electrodes connecting to the generating means for passing the signal into the sample, the electrodes generating an electrical signal corresponding to the conductivity/resistivity of the sample.

9. The device of claim 7 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 sample.

10. The device of claim 7 wherein the processing means further calibrates the electrical signal to a reference standard using the stored assay calibration information.

11. The device of claim 7 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.

12. The device of claim 7 wherein the assay calibration information stored in the device determines results for at least one of assays selected from the group consisting of a Prothrombin Time, an Activated Clotting Time, an Activated Partial Thromboplastin Time, platelet aggregation, and fibrinogen.

13. A device for performing a coagulation or lysis assay of a sample, the device comprising:

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

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

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

a reagent positioned in the housing and in contact with the sample for accelerating the coagulation of the sample;

means for measuring a value of the electrolytic conductance of the sample itself 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 generating a digital output corresponding to the coagulation or lysis assay using assay calibration information stored in the device; and

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

14. The device of claim 13 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 sample, the electrodes connecting to the generating means for passing the signal into the sample, the electrodes generating an electrical signal corresponding to the electrical conductance of the sample, the processing means receiving and converting the electrical signal into the digital output.

15. The device of claim 14 wherein the processing means further calibrates the electrical signal to a reference standard using the stored assay calibration information.

16. The device of claim 13 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 sample.

17. The device of claim 13 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.

18. The device of claim 13 wherein the assay calibration information stored in the device determines results for at least one of assays selected from the group consisting of a Prothrombin Time, an Activated Clotting Time, an Activated Partial Thromboplastin Time, platelet aggregation, and fibrinogen.

19. 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 sample, the test card comprising:

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

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

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

20. The test card of claim 19 wherein the electrical signal generated by the electrodes measures the conductivity/resistivity of the sample.

21. The test card of claim 19 wherein the electrodes are in direct contact with the sample.

22. 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 sample, the test card comprising:

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

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

means for continuously measuring a value of an electrical property of the sample itself by receiving the predetermined frequency and generating an electrical signal which correlates to a curve of the coagulation or lysis assay.

23. The test card of claim 22 wherein the measuring means includes measuring the electrolytic conductance of the sample.

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

retaining the sample in a particular position on a substrate;

accelerating 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 a state of coagulation or lysis of the sample;

continuously measuring the viscosity of the sample in the particular position and generating an electrical signal which correlates to a curve of the coagulation or lysis of the sample; and

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

25. The method of claim 24 wherein the method includes the step of displaying the output.

26. The method of claim 24 wherein the measuring step includes:

generating a signal of predetermined frequency;

contacting a plurality of electrodes with the sample;

passing the signal through the electrodes into the sample; and

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

27. The method of claim 24 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 Clotting Time, an Activated Partial Thromboplastin Time, platelet aggregation, and fibrinogen.

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

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

continuously measuring a value of an electrical property of the sample itself and generating an electrical signal which correlates to a curve of the coagulation or lysis of the sample by continuously contacting a plurality of electrodes directly with the sample and passing a signal of predetermined frequency through the electrodes into the sample to generate an electrical signal; and

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

29. The method of claim 28 wherein the method includes the step of displaying the digital output.

30. The method of claim 28 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 Clotting Time, an Activated Partial Thromboplastin Time, platelet aggregation, and fibrinogen.

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

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

measuring the viscosity of the sample by electrolytic conductance which correlates to the coagulation or lysis and generating an output using assay calibration information.

32. The method of claim 31 wherein the method includes the step of displaying the output.

33. The method of claim 31 wherein the method includes calibrating the output 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 Clotting Time, an Activated Partial Thromboplastin Time, platelet aggregation, and fibrinogen.