Small Volume In Vitro Analyte Sensor

• US 20090078586A1
• Filed: 02/07/2008
• Published: 03/26/2009
• 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 8,114,270 B2
• Time in Patent Office: Days
• US Class Current: 205/777.500
• 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

1-132. -132. (canceled)

133. A biosensor for determining the concentration of an analyte, comprising:

at least two plates, wherein at least one of said plates form at least one boundary area wherein a biological fluid is analyzed;

a plurality of electrodes, wherein said electrodes are associated with at least one of said plates, wherein said plurality of electrodes includes at least two working electrodes and at least one reference electrode, counter electrode and/or counter-reference electrode;

a tip fill region associated with said boundary area for the transport of a biological fluid; and

a reagent layer including an enzyme-based composition, wherein said reagent layer is associated with at least one of said working electrodes.

134. The biosensor according to claim 133, wherein enzyme-based composition comprises glucose oxidase.

135. The biosensor according to claim 133, wherein said reagent layer includes a mediator selected from the group consisting of ferricyanide and ferrocyanide.

136. The biosensor according to claim 133, wherein any of said electrodes are constructed of materials selected from the group consisting of gold, platinum, ruthenium dioxide, palladium, and other non-corroding materials.

137. The biosensor according to claim 133, wherein any of said electrodes are constructed of carbon or carbon-like materials.

138. The biosensor according to claim 133, wherein at least one of said plates is at least partially transparent or translucent transparent.

139. The biosensor according to claim 133, further comprising at least one of said plates being a spacer located at least partially between said plates.

140. The biosensor according to claim 133, further comprising an opening downstream of said reagent layer.

141. The biosensor according to claim 133, wherein said reference electrode is upstream of said at least one of said working electrodes.

142. The biosensor according to claim 133, wherein said counter electrode is upstream of said at least one of said working electrodes.

143. The biosensor according to claim 133, wherein said counter/reference electrode is upstream of said at least one of said working electrodes.

144. The biosensor according to claim 133, wherein said biosensor receives a volume of biological fluid of no more than 1.0 μ

L.

145. The biosensor according to claim 133, wherein said biosensor receives a volume of biological fluid from about 0.1 μ

L to about 1.0 μ

L.

146. The biosensor according to claim 133, wherein said biosensor includes at least one tab or at least one electrode extension having a contact region for connection with external electronics.

147. The biosensor according to claim 139, wherein said spacer is an adhesive which ensures that said biological fluid remains within said boundary area.

148. The biosensor according to claim 139, wherein said spacer covers at least a portion of said reagent layer.

149. The biosensor according to claim 133, further includes structures which prevent or substantially reduce the diffusional loss of said mediators.

150. A method of using a biosensor, comprising:

providing at least two plates, wherein at least one of said plates includes forming a boundary area to house a biological fluid;

forming at least two electrodes on at least one plate which are not in electrical contact with each other, wherein at least two electrodes are working electrodes and one electrode is at least one of a reference electrode, counter or counter/reference electrode, wherein said at least one reference electrode, counter or said counter/reference electrode is upstream of at least one of said working electrodes;

forming at least one reagent layer is associated with at least one of said working electrodes;

applying a biological fluid to said boundary area;

detecting said biological fluid in said boundary area;

measuring said biological fluid in said boundary area; and

providing an actual concentration of said analyte in said biological fluid.

151. The method according to claim 150, wherein at least one of any of said reference electrode, counter electrode, or counter/reference electrode is upstream of at least one of said working electrode.

152. A biosensor for determining the concentration of an analyte, comprising:

at least two plates, wherein at least one of said plates form at least one boundary area wherein a biological fluid is analyzed, wherein said boundary area receives a volume of biological fluid no greater than 1.5 μ

L;

a plurality of electrodes, wherein said electrodes are associated with at least one of said plates, wherein said plurality of electrodes includes at least two working electrodes and at least one reference electrode, counter electrode and/or counter-reference electrode is upstream of said at least one of said working electrodes;

a tip fill region associated with said boundary area for the transport of a biological fluid; and

a reagent layer including an enzyme-based composition including glucose oxidase and ferricyanide, wherein said reagent layer is associated with at least one of said working electrodes.

153. The biosensor according to claim 152, wherein said biosensor receives a volume of biological fluid of no more than 1.0 μ

L.