Small volume in vitro analyte sensor

• US 7,909,984 B2
• Filed: 02/07/2008
• Issued: 03/22/2011
• Est. Priority Date: 02/06/1997
• Status: Expired due to Fees

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Say, James, Heller, Adam, Vreeke, Mark S., Feldman, Benjamin J.
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US12/027,805
• Publication Number:
  US 20080277291A1
• Time in Patent Office: 1,139 Days
• Field of Search: 20440301-40315, 205/777.5, 205/778, 205/792
• US Class Current: 205/792
• 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. An integrated piercing and sensing device for determining the concentration of analyte in a biological fluid from a patient, comprising:

a sensor element adapted to be positioned adjacent to a site on the patient from which a biological fluid is to be collected to receive the biological fluid flowing from the site into a boundary area having a volume of less than about 1 μ

L;

a piercing element adapted to pierce a site on a patient to cause biological fluid to flow therefrom, the piercing element being movable in a parallel manner relative to said sensor element and comprising a piercing end on the same face of said device as said sensor element; and

an analyte measurement element operatively connected to said sensor element and adapted to measure the signal generated by said sensor element.

2. The device according to claim 1, wherein said analyte is glucose from diabetic patients or lactate from critical care patients.

3. The device according to claim 1, wherein said biological fluid is blood from the patient.

4. The device according to claim 1, wherein said biological fluid comprises blood.

5. The device according to claim 1, wherein said piercing element is adapted to pierce and retract from the site on the patient to cause blood to flow therefrom.

6. The device according to claim 1, wherein said piercing element includes a lancet.

7. The device according to claim 1, wherein said piercing element includes a spring.

8. The device according to claim 1, wherein said site on the patient is located in a region not heavily supplied with near-surface capillary vessels on an arm or thigh of the patient.

9. The device according to claim 1, wherein said site on the patient is a region on an arm of the patient.

10. The device according to claim 9, wherein said region of the arm of the patient is the left anterior, right anterior or left dorsal region of the forearm.

11. The device according to claim 1, wherein said analyte measurement element utilizes potentiometric, amperometric, voltammetric, and other electrochemical techniques to determine the concentration of the analyte in the sample.

12. The device according to claim 1, wherein said sensor element is an optical sensor.

13. The device according to claim 12, wherein said optical sensor utilizes absorption, transmission, reflection, or fluorescence measurements to determine the concentration of the analyte in the sample.

14. The device according to claim 1, wherein said sensor element is an electrochemical sensor.

15. The device according to claim 14, wherein said sensor element is a disposable electrochemical glucose sensor strip.

16. The device according to claim 1, wherein said sensor element is a disposable measurement strip.

17. The device according to claim 1, wherein said sensor element is in the shape of a strip.

18. The device according to claim 1, wherein said sensor element comprises two electrodes disposed in a coplanar.

19. The device according to claim 1, wherein said wherein said boundary area receives a volume of from about 0.1 μ

L to about 1 μ

L of biological fluid.

20. The device according to claim 1, wherein said sensor element comprises two electrodes disposed as facing electrodes.

21. The device according to claim 1, wherein said sensor element is detachable from the integrated unit.

22. The device according to claim 1, wherein said biological fluid flows directly from the pierced site into said boundary area without displacement of the sensor element.

23. The device according to claim 1, wherein said analyte measurement element includes a reader.

24. The device according to claim 1, wherein said sensor element comprises a working electrode and a counter electrode, wherein said working electrode comprises a glucose-responsive enzyme and a redox mediator, and wherein said working electrode and said counter electrode are each positioned to contact said biological fluid in said boundary area.

25. The device according to claim 24, wherein said working electrode is on a first substrate and said counter electrode is on a second substrate.

26. An integrated piercing and sensing device for determining the concentration of glucose in blood from a patient, comprising:

a sensor element adapted to be positioned adjacent to a site on the patient from which blood is to be collected to receive the blood flowing from the site, wherein said sensor element comprises a working electrode and a counter electrode, wherein said working electrode comprises a glucose-responsive enzyme and a redox mediator and wherein said working electrode and said counter electrode are facing electrodes and are each positioned to contact blood in a boundary area receiving a volume of less than about 1 μ

L to generate an electrical signal indicative of the concentration of glucose in the blood;

a piercing element adapted to pierce and retract from the site on the patient to cause blood to flow therefrom, said piercing element being movable in a parallel manner relative to said sensor element and comprising a piercing end on the same face of the device as said sensor element; and

an analyte measurement element operatively connected to said sensor and adapted to measure the signal generated by said sensor.

27. A sample acquisition and analyte measuring device for determining the concentration of an analyte in a biological fluid of a patient, the apparatus comprising:

an analyte sensor element comprising a boundary area and an opening for transport of a biological fluid into said boundary area, said analyte sensor element being configured and arranged for determining the concentration of analyte in a biological fluid using an undiluted sample of biological fluid having a volume of less than about 1 μ

L , disposed thereof;

a piercing member configured and arranged to pierce a site on the patient and then withdraw from said site to cause a flow of biological fluid from said site, the piercing element being movable in a parallel manner relative to said analyte sensor element and comprising a piercing end on the same face of the device as the opening of said analyte sensor element; and

an analyte measurement element operatively connected to said sensor element and adapted to measure the signal generated by said sensor element.

28. A method for determining a concentration of an analyte in a biological fluid from a patient, the method comprising the steps of:

piercing a site on the patient with a piercing element of an integrated piercing and sensing device to cause said biological fluid to flow from the site, wherein the integrated piercing and sensing device comprises the piercing element, a sensor element, and an analyte measurement element, the piercing element being movable in a parallel manner relative to said sensor element and comprising a piercing end on the same face of the device as said sensor element, and the sensor element being operatively connected to the analyte measurement element and being adapted to be positioned adjacent to the site on the patient from which a biological fluid is to be collected to receive the biological fluid into a boundary area receiving a volume of less than about 1 μ

L to generate an electrical signal indicative of the concentration of analyte in said biological fluid;

positioning said sensor element adjacent to said site on the patient such that said sensor element receives biological fluid flowing from said site; and

measuring the signal generated by said sensor element using said analyte measurement element to determine the concentration of the analyte.

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

piercing a site on the patient with a piercing element of an integrated piercing and sensing device to cause blood to flow from the site, wherein the integrated piercing and sensing device comprises the piercing element, a sensor element, and an analyte measurement element, the piercing element being movable in a parallel manner relative to the sensor element and comprising a piercing end on the same face of the device as said sensor element, and the sensor element being operatively connected to the analyte measurement element and comprising a working electrode and a counter electrode, wherein said working electrode comprises a glucose-responsive enzyme and a redox mediator and wherein said working electrode and said counter electrode are facing electrodes and are each positioned to contact blood in a boundary area receiving a volume of less than about 1 μ

L to generate an electrical signal indicative of the concentration of glucose in blood;

positioning said sensor element adjacent to said site on the patient such that said sensor element receives blood flowing from said site;

measuring the signal generated by said sensor element using said analyte measurement element to determine the concentration of glucose.

30. A method for determining a concentration of an analyte in a biological fluid from a patient, the method comprising the steps of:

piercing a site on the patient with a piercing element of a sample acquisition and analyte measuring device to cause biological fluid to flow from the site, wherein the sample acquisition and analyte measuring device comprises the piercing element, an analyte sensor element, and an analyte measurement element, the piercing element comprising a piercing end and being movable in a parallel manner relative to the analyte sensor element, and the analyte sensor element being operatively connected to said analyte measurement element and comprising a boundary area and an opening for transport of biological fluid into said boundary area that is on the same face of the device as the piercing end of said piercing element, wherein the analyte sensor element is configured and arranged for determining the concentration of analyte in a biological fluid using an undiluted sample of biological fluid having a volume of less than about 1 μ

L disposed thereof;

positioning the opening of the sensor element adjacent to the site on the patient; and

measuring the signal generated by the sensor element using the analyte measurement element to determine the concentration of the analyte.