Integrated lancing and measurement device and analyte measuring methods

• US 6,607,658 B1
• Filed: 11/15/2000
• Issued: 08/19/2003
• Est. Priority Date: 02/06/1997
• Status: Expired due to Term

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Therasense Incorporated (Abbott Laboratories Incorporated)
• Inventors: Heller, Adam, Say, James, Vreeke, Mark S., Feldman, Benjamin J.
• Primary Examiner(s): Nguyen, Nam
• Assistant Examiner(s): Noguerola, Alex
• Application Number:
  US09/714,360
• Time in Patent Office: 1,007 Days
• Field of Search: 204/403.14, 204/403.11, 204/403.1, 205/777.5, 205/789, 205/792, 600/347
• US Class Current: 205/777.5
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157 disposable multilayered or laminated electrodes G01N27/307; details of handling chemical test elements G01N33/4875
• CPC Class Codes: A61B 5/1411 by percutaneous method, e.g. by lancet
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150358 Strips for collecting blood, e.g. absorbent optical reagent test strips G01N21/8483; chemical reagent test strips G01N33/4875, G01N33/52
• CPC Class Codes: A61B 5/150412 Pointed piercing elements, e.g. needles, lancets for piercing the skin blade-like piercing elements A61B5/150442
• CPC Class Codes: A61B 5/150503 Single-ended needles hollow piercing element tip design A61B5/150396, needle sets for catheters A61M25/06, needles for bringing media into the body A61M5/32
• CPC Class Codes: A61B 5/15105 Purely manual piercing, i.e. the user pierces the skin without the assistance of any driving means or driving devices
• CPC Class Codes: A61B 5/15113 Manually triggered, i.e. the triggering requires a deliberate action by the user such as pressing a drive button
• CPC Class Codes: A61B 5/15144 comprising driving means, e.g. a spring, for retracting the piercing unit into the housing
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 2333/904 acting on CHOH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
• 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 33/5438 : Electrodes

Abstract

A sensor designed to determine the amount and concentration of analyte in a sample having a volume of less than about 1 μL. The sensor has a working electrode coated with a non-leachable redox mediator. The redox mediator acts as an electron transfer agent between the analyte and the electrode. In addition, a second electron transfer agent, such as an enzyme, can be added to facilitate the electrooxidation or electroreduction of the analyte. The redox mediator is typically a redox compound bound to a polymer. The preferred redox mediators are air-oxidizable.

The amount of analyte can be determined by coulometry. One particular coulometric technique includes the measurement of the current between the working electrode and a counter or reference electrode at two or more times. The charge passed by this current to or from the analyte is correlated with the amount of analyte in the sample. Other electrochemical detection methods, such as amperometric, voltammetric, and potentiometric techniques, can also be used.

The invention can be used to determine the concentration of a biomolecule, such as glucose or lactate, in a biological fluid, such as blood or serum. An enzyme capable of catalyzing the electrooxidation or electroreduction of the biomolecule is provided as a second electron transfer agent.

Claims

1. A device for determining the concentration of glucose in blood from a patient, comprising:

a piercing member adapted to pierce and retract from a site on the patient to cause blood to flow therefrom;

a sensor positioned adjacent to the site on the patient and adapted to receive the blood flowing from the site to generate an electrical signal indicative of the concentration of glucose in the blood, the sensor comprising

a working electrode comprising a glucose-responsive enzyme and a redox mediator, and

a counter electrode,

wherein the working and counter electrodes are each positioned to contact a sample in a measurement zone having a volume of less than about 1 μ

l; and

a glucose monitor operatively connected to the sensor and adapted to measure the signal generated by the sensor,

wherein the sensor is adapted so that a signal generated by electrolysis of a buffer solution with 10 mM glucose is at least about nine times greater than a signal generated by electrolysis of a buffer solution with no glucose by the sensor.

2. The device of claim 1, wherein the sensor and the piercing member form an integrated unit.

3. The device of claim 2, wherein the sensor is detachable from the integrated unit.

4. The device of claim 1, wherein the measurement zone volume is no more than about 0.5 μ

l.

5. The device of claim 1, wherein the glucose monitor is adapted to measure the signal amperometrically.

6. The device of claim 1, wherein the glucose monitor is adapted to measure the signal coulometrically.

7. The device of claim 1, wherein the sensor is in the shape of a strip.

8. The device of claim 1, wherein the sensor includes a sorbent material for transporting blood to contact the working and counter electrodes.

9. The device of claim 8, wherein the sorbent material is contained in the measurement zone.

10. The device of claim 1, wherein the glucose-responsive enzyme is a glucose oxidase.

11. The device of claim 1, further comprising a vacuum producing means for assisting blood flow toward the sensor.

12. The device of claim 11, wherein the vacuum producing means comprises a vacuum pump.

13. The device of claim 1, wherein the piercing member is a lancet.

14. The device of claim 1, wherein the working electrode is on a first substrate and the counter electrode is on a second substrate.

15. The device of claim 1, wherein the piercing member and the glucose monitor are integrated components of a single device.

16. The device of claim 1, wherein the sensor further comprises a third electrode.

17. A method for determining the blood glucose concentration in a patient, the method comprising the steps of:

(a) providing the device of claim 1;

(b) piercing a skin site on the patient with the piercing member of the device to cause blood to flow from the site to the sensor; and

(c) measuring the signal generated by the sensor using the glucose monitor.

18. The method of claim 17, further comprising, after step and before step (c), (b′

) generating a vacuum at the site on the patient.

19. The method of claim 18, wherein step (b′

) is carried out before step (b).

20. The method of claim 17, wherein step (c) is carried out amperometrically.

21. The method of claim 17, wherein step (c) is carried out coulometrically.

22. A method for determining the concentration of glucose in blood from a site on a patient, comprising the steps of:

(a) providing a sensor operatively connected to a glucose monitor, the sensor comprising

a working electrode comprising a glucose-responsive enzyme and a redox mediator, and

a counter electrode,

wherein the working and counter electrodes are each positioned to contact a sample in a measurement zone having a volume of less than about 1 μ

l, and

further wherein the sensor is adapted so that a signal generated by electrolysis of a buffer solution with 10 mM glucose is at least nine times greater than a signal generated by electrolysis of a buffer solution with no glucose by the sensor;

(b) positioning the sensor adjacent to the site;

(c) using a piercing member to pierce the site in order to cause blood to flow from the site to the sensor and thereby causing the sensor to generate a signal indicative of the concentration of glucose in the blood; and

(d) measuring the signal generated by the sensor using the glucose monitor.

23. The method of claim 22, wherein the site is located on an arm of the patient.

24. The method of claim 22, wherein the sensor and the piercing member form an integrated unit.

25. The method of claim 22, wherein the measurement zone volume is no more than about 0.5 μ

l.

26. The method of claim 22, wherein step (d) is carried out amperometrically.

27. The method of claim 22, wherein step (d) is carried out coulometrically.

28. The method of claim 22, wherein step (c) comprises using a sorbent material to transport blood to contact the working and counter electrodes.

29. The method of claim 22, wherein the sorbent material is contained in the measurement zone.

30. The method of claim 22, wherein the glucose-responsive enzyme is a glucose oxidase.

31. The method of claim 22, further comprising, after step (b) and no later than step (c), (b′

) producing a vacuum around the site.

32. The method of claim 22, wherein the piercing member comprises a lancet.

33. The method of claim 22, wherein the working electrode is on a first substrate and the counter electrode is on a second substrate.

34. The method of claim 22, wherein the sensor, the piercing member and the glucose monitor are integrated as a single device.

35. The method of claim 22, wherein the sensor further comprises a third electrode.

36. A method for determining the concentration of glucose in blood from a site on a patient'"'"'s arm, comprising the steps of:

(a) providing a sensor operatively connected to a glucose monitor, the sensor comprising

a working electrode comprising a glucose-responsive enzyme and a redox mediator, and

a counter electrode,

wherein the working and counter electrodes are each positioned to contact a sample in a measurement zone having a volume of less than about 1 μ

l, and

further wherein the sensor is adapted so that a signal generated by electrolysis of a buffer solution with 10 mM glucose is at least nine times greater than a signal generated by electrolysis of a buffer solution with no glucose by the sensor;

(b) positioning the sensor adjacent to the site;

(c) producing a vacuum around the site;

(d) using a piercing member to pierce the site in order to cause blood to flow from the site to the sensor and thereby causing the sensor to generate a signal indicative of the concentration of glucose in the blood; and

(e) measuring the signal generated by the sensor using the glucose monitor.

37. A device for deter mining the concentration of glucose in blood from a patient, comprising:

a piercing member adapted to pierce and retract from a site on the patient to cause blood to flow therefrom;

a sensor positioned adjacent to the site on the patient and adapted to receive the blood flowing from the site to generate an electrical signal indicative of the concentration of glucose in the blood, the sensor comprising

a working electrode comprising a glucose-responsive enzyme and a redox mediator,

a counter electrode, and

a sorbent material for transporting blood to contact the working and counter electrodes,

wherein the working and counter electrodes are each positioned to contact a sample in a measurement zone having a volume of less than about 1 μ

l; and

a glucose monitor operatively connected to the sensor and adapted to measure the signal generated by the sensor.

38. The device of claim 37, wherein the sorbent material is contained in the measurement zone.

39. A device for determining the concentration of glucose in blood from a patient, comprising:

a piercing member adapted to pierce and retract from a site on the patient to cause blood to flow therefrom;

a sensor positioned adjacent to the site on the patient and adapted to receive the blood flowing from the site to generate an electrical signal indicative of the concentration of glucose in the blood, the sensor comprising

a working electrode comprising a glucose-responsive enzyme and a redox mediator, and

a counter electrode,

wherein the working electrode is on a first substrate, the counter electrode is on a second substrate, and the working and counter electrodes are each positioned to contact a sample in a measurement zone having a volume of less than about 1 μ

l; and

a glucose monitor operatively connected to the sensor and adapted to measure the signal generated by the sensor.

40. A method for determining the blood glucose concentration in a patient, the method comprising the steps of:

(a) providing a device for determining the concentration of glucose in blood from a patient, the device comprising;

a piercing member adapted to pierce and retract from a site on the patient to cause blood to flow therefrom;

a sensor positioned adjacent to the site on the patient and adapted to receive the blood flowing from the site to generate an electrical signal indicative of the concentration of glucose in the blood, the sensor comprising

a working electrode comprising a glucose-responsive enzyme and a redox mediator, and

a counter electrode,

wherein the working and counter electrodes are each positioned to contact a sample in a measurement zone having a volume of less than about 1 μ

l; and

a glucose monitor operatively connected to the sensor and adapted to measure the signal generated by the sensor;

(b′

) generating a vacuum at the site on the patient, after step (a);

(b) piercing a skin site on the patient with the piercing member of the device to cause blood to flow from the site to the sensor, after step (b′

); and

(c) measuring the signal generated by the sensor using the glucose monitor.

41. A method for determining the concentration of glucose in blood from a site on a patient, comprising the steps of:

(a) providing a sensor operatively connected to a glucose monitor, the sensor comprising

a working electrode comprising a glucose-responsive enzyme and a redox mediator, and

a counter electrode,

wherein the working and counter electrodes are each positioned to contact a sample in a measurement zone having a volume of less than about 1 μ

l;

(b) positioning the sensor adjacent to the site;

(c) using a piercing member to pierce the site in order to cause blood to flow from the site via a sorbent material to the sensor so as to transport blood to contact the working and counter electrodes and thereby causing the sensor to generate a signal indicative of the concentration of glucose in the blood; and

(d) measuring the signal generated by the sensor using the glucose monitor.

42. The method of claim 41, wherein the sorbent material is contained in the measurement zone.

43. A method for determining the concentration of glucose in blood from a site on a patient, comprising the steps of:

(a) providing a sensor operatively connected to a glucose monitor, the sensor comprising

a working electrode comprising a glucose-responsive enzyme and a redox mediator, and

a counter electrode,

wherein the working electrode is on a first substrate, the counter electrode is on a second substrate, and the working and counter electrodes are each positioned to contact a sample in a measurement zone having a volume of less than about 1 μ

l;

(b) positioning the sensor adjacent to the site;

(c) using a piercing member to pierce the site in order to cause blood to flow from the site to the sensor and thereby causing the sensor to generate a signal indicative of the concentration of glucose in the blood; and

(d) measuring the signal generated by the sensor using the glucose monitor.