Systems, Devices, and Methods for Improving Accuracy of Biosensors Using Fill Time

• US 20110155585A1
• 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., Chatelier, Ronald C.
• Granted Patent: US 8,101,065 B2
• Time in Patent Office: Days
• US Class Current: 205/777.5
• CPC Class Codes: C12Q 1/006 for glucose
• 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 27/416 Systems G01N27/27 takes precedence

Abstract

Methods for determining a concentration of an analyte in a sample, and the devices and systems used in conjunction with the same, are provided herein. In one exemplary embodiment of a method for determining a concentration of an analyte in a sample, a sample including an analyte is provided in a sample analyzing device having a working and a counter electrode. An electric potential is applied between the electrodes and a fill time of the sample into the device is calculated. A concentration of the analyte in view of fill time can then be determined. Systems and devices that take advantage of the fill time to make analyte concentration determinations are also provided.

Claims

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

introducing a sample including an analyte into an electrochemical cell of a sample analyzing device, the electrochemical cell having a working electrode and a counter electrode;

determining a fill time of the sample;

calculating a prepulse time in view of at least the fill time;

applying an electric potential between the working electrode and the counter electrode for a length of time equal to the prepulse time; and

determining a concentration of the analyte.

2. The method of claim 1, wherein determining a fill time of the sample comprises:

applying an electric potential between the working electrode and the counter electrode as the sample is introduced;

measuring cell current as a function of time; and

determining a current drop time based on cell current as a function of time, wherein the current drop time corresponds to the fill time of the sample.

3. The method of claim 2, wherein determining a current drop time is achieved by calculating the maximum negative value of the change in measured cell current over time.

4. The method of claim 2, wherein measuring cell current as a function of time comprises:

performing current measurements approximately every 2 milliseconds; and

calculating and storing an average current based on the current measurements approximately every 10 milliseconds.

5. The method of claim 1, further comprising:

determining a level of haematocrit in the sample in view of the fill time of the sample.

6. The method of claim 5, wherein determining a concentration of the analyte comprises calculating the concentration of the analyte in view of the determined level of haematocrit.

7. The method of claim 1, wherein the sample analyzing device comprises a glucose sensor.

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

9. The method of claim 1, wherein the sample comprises blood.

10. The method of claim 9, wherein the blood comprises whole blood.

11. An electrochemical system, comprising:

an electrochemical cell having a lower electrode and an upper electrode;

a meter connected to the electrochemical cell so that the meter applies a potential between the lower electrode and the upper electrode of the electrochemical cell; and

a control unit connected to the meter so that the control unit determines a fill time of a sample introduced into the electrochemical cell and uses the fill time to calculate a concentration of an analyte in the sample.

12. The electrochemical system of claim 11, further comprising a heating element configured to heat at least a portion of the electrochemical cell.

13. The electrochemical system of claim 11, wherein the electrochemical cell comprises an immunosensor.

14. The electrochemical system of claim 13, 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 an electrochemical 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.

15. The electrochemical system of claim 14, wherein the first sealing component comprises a hydrophilic adhesive tape.

16. The electrochemical system of claim 14, wherein at least one of the immunosensor, the meter, and the control unit include a configuration to measure a temperature of the sample.

17. The electrochemical system of claim 14, wherein the analyte comprises C-reactive protein.

18. The electrochemical system of claim 11, wherein the sample comprises blood.

19. The electrochemical system of claim 18, wherein the blood comprises whole blood.

20. A method for measuring a blood sample, comprising:

providing;

an immunosensor having two electrodes; and

a meter connected to the immunosensor so that the meter applies a potential between the two electrodes of the immunosensor;

introducing a blood sample including an antigen into the immunosensor;

applying an electric potential between the two electrodes;

calculating a fill time of the blood sample; and

determining a concentration of the antigen in view of the fill time.

21. The method of claim 20, wherein the immunosensor further comprises:

a reaction chamber and a detection chamber formed in a separator disposed between the two electrodes;

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

a vent at least partially formed in the separator and the two electrodes, spaced a distance apart from the reaction chamber, and overlapping at least a portion of the detection chamber;

the method further comprising;

providing;

an antibody-enzyme conjugate in a first buffer and magnetic beads linked to an antigen in a second buffer in the reaction chamber;

ferricyanide, glucose, and a mediator in a dilute acid in the detection chamber;

a first seal over a first side of the vent that forms a wall of the fill chamber; and

a second seal over a second side of the vent,

wherein at least a portion of the blood sample moves from the fill chamber to the reaction chamber when introducing a blood sample into the immunosensor;

opening the vent after a pre-determined time by piercing at least one of the first and second seals, thereby allowing portions of the blood sample containing the antibody-enzyme conjugate that is not bound to the magnetic beads to move to the detection chamber;

catalyzing oxidation of the glucose in the detection chamber, which results in the formation of ferrocyanide;

electrochemically detecting a current from the ferrocyanide; and

determining a concentration of the antigen in the blood sample in view of the signal detected.

22. The method of claim 20, wherein calculating a fill time further comprises:

applying an electric potential between the working electrode and the counter electrode as the sample is introduced;

measuring cell current as a function of time; and

determining a current drop time based on cell current as a function of time,

wherein the current drop time corresponds to the fill time of the sample.

23. The method of claim 20, further comprising

determining a level of haematocrit in the sample in view of the fill time of the sample, wherein determining the concentration of the antigen is performed in view of the determined level of haematocrit.

24. The method of claim 20, wherein the antigen comprises C-reactive protein.

25. The method of claim 20, further comprising:

measuring a temperature of the blood sample.