Systems, Devices, and Methods for Measuring Whole Blood Hematocrit Based on Initial Fill Velocity

• US 20110155584A1
• Filed: 12/30/2009
• Published: 06/30/2011
• Est. Priority Date: 12/30/2009
• Status: Active Grant

• Current Assignee: Cilag Gmbh International (Johnson & Johnson)
• Original Assignee: Lifescan Incorporated (Duv Holding Corporation)
• Inventors: Hodges, Alastair M., Raineri, Linda, Chatelier, Ronald C., Rylatt, Dennis
• Granted Patent: US 8,877,034 B2
• Time in Patent Office: Days
• US Class Current: 205/777.5
• CPC Class Codes: G01N 2333/4737 C-reactive protein
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 27/48 using polarography, i.e. measuring changes in current under a slowly-varying voltage
• CPC Class Codes: G01N 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G01N 33/80 involving blood groups or blood types or red blood cells white blood cells G01N33/56972

Abstract

Methods for determining the hematocrit of a blood sample, and devices and systems used in conjunction with the same. The hematocrit value can be determined on its own, and further, it can be further used to determine a concentration of an analyte in a sample. In one exemplary embodiment of a method for determining the hematocrit value in a blood sample, a volume of blood is provided in a sample analyzing device having a working and a counter electrode. An electric potential is applied between the electrodes and an initial fill velocity of the sample into the device is calculated. The hematocrit of the blood, as well as a concentration of an analyte in view of the initial fill velocity can then be determined. Systems and devices that take advantage of the use of an initial fill velocity to determine hematocrit levels and make analyte concentration determinations are also provided.

Claims

1. A method for determining a hematocrit value of a whole blood sample, the method comprising:

providing a sample of whole blood to a sample analyzing device having a capillary space;

measuring an initial fill velocity of the sample in at least a portion of the capillary space; and

determining a hematocrit value of the sample from the initial fill velocity.

2. The method of claim 1, wherein measuring an initial fill velocity of the sample further comprises:

applying an electrical potential;

measuring an electrical current; and

determining an initial current flow.

3. The method of claim 2, wherein measuring an initial fill velocity further comprises:

performing current measurements approximately every 10 milliseconds for at least approximately 50 milliseconds; and

calculating an average current based on the current measurements.

4. The method of claim 1, wherein measuring an initial fill velocity of the sample further comprises detecting an optical signal.

5. The method of claim 1, wherein measuring an initial fill velocity of the sample occurs directly after the sample enters the capillary space.

6. The method of claim 1, wherein measuring an initial fill velocity of the sample occurs after the sample crosses into a region of the capillary space of the sample analyzing device where a detection signal is generated.

7. The method of claim 1, further comprising at least one of measuring a temperature of the sample or inferring a temperature of the sample.

8. The method of claim 1, wherein the sample analyzing device is an immunosensor.

9. The method of claim 1, wherein the sample includes an analyte, the method further comprising:

calculating a concentration of the analyte in view of the determined hematocrit value.

10. The method of claim 9, further comprising:

applying an electric potential;

measuring an initial current after applying the electric potential; and

reversing the electric potential.

11. The method of claim 10, further comprising measuring a change in current over a period of time following reversing the electric potential, wherein calculating a concentration of the analyte further comprises calculating the concentration of the analyte in view of the change in current over the period of time.

12. The method of claim 10, further comprising at least one of measuring a temperature of the sample or inferring a temperature of the sample.

13. The method of claim 12, further comprising measuring a change in current over a period of time after reversing the electric potential, wherein calculating a concentration of the analyte further comprises calculating the concentration of the analyte in view of the change in current over the period of time and the temperature of the sample.

14. A method for determining a concentration of an analyte in a sample, the method comprising:

providing a sample including an analyte to a sample analyzing device having a working electrode and a counter electrode;

applying an electric potential between the working electrode and the counter electrode;

determining an initial fill velocity of the sample; and

calculating a concentration of the analyte in view of the initial fill velocity.

15. The method of claim 14, wherein determining an initial fill velocity further comprises:

measuring an initial current after applying the electric potential;

determining a level of hematocrit in the sample; and

reversing the electric potential between the working electrode and the counter electrode.

16. The method of claim 15, wherein calculating the concentration of the analyte further comprises computing the concentration based on the determined level of hematocrit.

17. The method of claim 16, further comprising measuring a change in current over a period of time following reversing the electric potential, wherein calculating a concentration of the analyte further comprises calculating the concentration of the analyte in view of the change in current over the period of time.

18. The method of claim 16, wherein the sample comprises whole blood, the method further comprising at least one of measuring a temperature of the whole blood or inferring a temperature of the whole blood.

19. The method of claim 14, wherein determining an initial fill velocity further comprises determining a rate of change in an optical signal to calculate the initial fill velocity.

20. The method of claim 14, wherein determining an initial fill velocity further comprises determining an initial current flow to determine the initial fill velocity.

21. The method of claim 20, wherein determining an initial current flow further comprises:

performing current measurements approximately every 10 milliseconds for at least approximately 50 milliseconds; and

calculating an average current based on the current measurements.

22. The method of claim 14, wherein determining an initial fill velocity further comprises determining an initial fill velocity directly after the sample enters a capillary space of the sample analyzing device.

23. The method of claim 14, wherein determining an initial fill velocity further comprises determining an initial fill velocity after the sample crosses into a region of a capillary space of the sample analyzing device where a detection signal is generated.

24. The method of claim 14, wherein the sample analyzing device comprises an immunosensor.

25. The method of claim 18, further comprising measuring a change in current over a period of time after reversing the electric potential, wherein calculating a concentration of the analyte further comprises calculating the concentration of the analyte in view of the change in current over the period of time.

26. An electrochemical system, comprising:

an immunosensor having a lower electrode and an upper electrode;

a meter configured to apply a potential between the lower electrode and the upper electrode of the immunosensor; and

a control unit connected to the meter so that the control unit measures an initial fill velocity of a sample introduced into the immunosensor and uses the initial fill velocity to calculate at least one of a value of hematocrit of the sample when the sample is blood and a concentration of an analyte in the sample.

27. The electrochemical system of claim 26, further comprising a heating element configured to heat at least a portion of the immunosensor.

28. The electrochemical system of claim 26, wherein the immunosensor further comprises:

a first liquid reagent comprising an antibody conjugated to an enzyme in a buffer, the first liquid reagent being striped on the lower electrode and dried;

a second liquid reagent comprising ferricyanide, a substrate for the enzyme, and a mediator in a dilute acid solution, the second liquid reagent being striped on the lower electrode and dried;

magnetic beads conjugated to an antigen, the magnetic beads being striped on the upper electrode and dried thereon;

a separator disposed between the lower and upper electrodes;

a reaction chamber formed in the separator and having the first reagent and the magnetic beads conjugated to the antigen disposed therein;

a detection chamber formed in the separator and having the second reagent disposed therein;

a fill chamber formed at least partially in the separator and one of the lower and upper electrodes, spaced a distance apart from the detection chamber, and overlapping at least a portion of the reaction chamber;

a vent formed at least partially in each of the separator, the lower electrode, and the upper electrode, spaced a distance apart from the reaction chamber, and overlapping at least a portion of the detection chamber;

a first sealing component having an incorporated anticoagulant coupled to one of the lower and upper electrodes, disposed over the vent, and configured to form a wall of the fill chamber and seal the vent; and

a second sealing component coupled to the other of the lower and upper electrodes, disposed over the vent, and configured to seal the vent.

29. The electrochemical system of claim 28, wherein the first sealing component comprises a hydrophilic adhesive tape.

30. The electrochemical system of claim 28, wherein the control unit further comprises an optical signal detector configured to measure a rate of change in an optical signal to measure the initial fill velocity of the sample.

31. The electrochemical system of claim 28, wherein the control unit further comprises a current flow detector configured to measure an initial current flow to measure the initial fill velocity.

32. The electrochemical system of claim 28, wherein the control unit includes a configuration to measure the initial fill velocity of the sample directly after the sample enters a capillary space of the immunosensor.

33. The electrochemical system of claim 28, wherein the control unit includes a configuration to measure an initial fill velocity of the sample after the sample crosses into a region of a capillary space of the immunosensor where a detection signal is generated.

34. The electrochemical system of claim 28, wherein at least one of the immunosensor, the meter, and the control unit are configured to perform at least one of the following functions:

measure a temperature of the sample or infer a temperature of the sample.