Small Volume In Vitro Analyte Sensor

• US 20080277291A1
• Filed: 02/07/2008
• Published: 11/13/2008
• Est. Priority Date: 02/06/1997
• Status: Active Grant

• 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.
• Granted Patent: US 7,909,984 B2
• Time in Patent Office: Days
• 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

1-139. -139. (canceled)

140. A system for determining the concentration of analyte in a biological fluid from a patient, comprising:

at least one substrate associated with at least one transducer;

a piercing member adapted to pierce 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 into a boundary area having a volume of less than about 1 μ

L; and

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

141. The system according to claim 140, wherein said analyte is glucose from diabetic patients or lactate from critical care patients.

142. The system according to claim 140, wherein said biological fluid is blood from the patient.

143. The system according to claim 140, wherein said biological fluid comprises blood.

144. The system according to claim 140, wherein said piercing member is adapted to pierce and retract from the site on the patient to cause blood to flow therefrom.

145. The system according to claim 140, wherein said piercing member includes a lancet.

146. The system according to claim 140, wherein said piercing member also includes a spring.

147. The system according to claim 140, 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.

148. The system according to claim 140, wherein said site on the patient is located on an arm of the patient.

149. The system according to claim 140, wherein said region of the arm of the patient is the left anterior, right anterior or left dorsal region of the forearm.

150. The system according to claim 140, wherein said sensor utilizes potentiometric, amperometric, voltammetric, and other electrochemical techniques to determine the concentration of the analyte in the sample.

151. The system according to claim 140, wherein said sensor is an optical sensor.

152. The system according to claim 151, wherein said optical sensor utilizes absorption, transmission, reflection, or fluorescence measurements to determine the concentration of the analyte in the sample.

153. The system according to claim 140, wherein said sensor is an electrochemical sensor.

154. The system according to claim 140, wherein said sensor is a disposable electrochemical glucose sensor strip.

155. The system according to claim 140, wherein said sensor is a disposable measurement strip.

156. The system according to claim 140, wherein said sensor is in the shape of a strip.

157. The system according to claim 140, wherein said boundary area receives a volume of less than about 1 μ

L of biological fluid.

158. The system according to claim 140, wherein said wherein said boundary area receives a volume of from about 0.1 μ

L to about 1 μ

L of biological fluid.

159. The system according to claim 140, wherein said sensor and the piercing member form an integrated unit in the system/apparatus.

160. The system according to claim 140, wherein said sensor is detachable from the integrated unit.

161. The system according to claim 140, wherein said patient is pierced with the piercing member, biological fluid flows directly from the pierced site into boundary area without displacement of the sensor.

162. The system according to claim 140, wherein said piercing member and the analyte measurement device are integrated components of the system/apparatus.

163. The system according to claim 162, wherein said analyte measurement device includes a reader.

164. The system according to claim 140, wherein said transducer includes a working electrode comprising a glucose-responsive enzyme and a redox mediator, and a counter electrode, wherein said working electrodes and said counter electrodes are each positioned to contact the biological fluid in said boundary area receiving a volume of less than about 1 μ

L.

165. The system according to claim 140, wherein said transducer includes at least one working electrode is on a first substrate and at least one counter electrode is on a second substrate, and said working electrodes and said counter electrodes are each positioned to contact the biological fluid in a boundary area receiving a volume of less than about 1 μ

L.

166. A system 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 said biological fluid to said boundary area receiving a volume of less than about 1 μ

L; and

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

167. An apparatus for determining the concentration of an analyte in a biological fluid of a patient, the apparatus comprising:

a piercing member configured and arranged to pierce a site on the patient and then withdraw from the site to cause a flow of biological fluid from the site;

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

L disposed thereof; and

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

168. 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 member to cause said biological fluid to flow from the site;

positioning a sensor operatively connected to an analyte measurement device adjacent to the site on the patient with the sensor adapted to receive the biological fluid flowing from the site into 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 said biological fluid; and

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

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

piercing a site on the patient with a piercing member to cause biological fluid to flow from the site;

collecting said biological fluid having a volume of about 1 μ

L or less flowing from the site;

filling said boundary area of a sensor with at least a portion of said biological fluid;

holding said biological fluid within at least a portion of said boundary area; and

determining the concentration of the analyte.

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

creating an unassisted flow of said biological fluid from a site on the patient by piercing the site with a piercing member;

transporting a portion of said biological fluid into an analyte sensor configured and arranged to determine the concentration of the analyte from said biological fluid of a volume of about 1 μ

L or less;

holding at least a portion of said biological fluid within said boundary area of the analyte sensor; and

determining the concentration of the analyte in said biological fluid from the portion of the biological fluid transported into the analyte sensor.