WO2010017119A1 - Reusable analyte sensing system and methods - Google Patents

Reusable analyte sensing system and methods Download PDF

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Publication number
WO2010017119A1
WO2010017119A1 PCT/US2009/052539 US2009052539W WO2010017119A1 WO 2010017119 A1 WO2010017119 A1 WO 2010017119A1 US 2009052539 W US2009052539 W US 2009052539W WO 2010017119 A1 WO2010017119 A1 WO 2010017119A1
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sensor
analyte
example
configured
concentration
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PCT/US2009/052539
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French (fr)
Inventor
Gopikrishnan Soundararajan
Himanshu Patel
Venkata Ratnakar Vejella
Stephen M. Jaffe
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Reusense, Llc
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Priority to US8669108P priority Critical
Priority to US61/086,691 priority
Application filed by Reusense, Llc filed Critical Reusense, Llc
Publication of WO2010017119A1 publication Critical patent/WO2010017119A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electro-chemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electro-chemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28Electrolytic cell components
    • G01N27/30Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327Biochemical electrodes electrical and mechanical details of in vitro measurements
    • G01N27/3271Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood

Abstract

A reusable analyte sensor can include a low dielectric constant substrate, a conductive path, an electrode in contact with the conductive path, an analyte sensing layer in contact with the electrode, and a transport barrier layer. The sensor can be included in a reusable glucose or other analyte detection system, also including a processor circuit, communicatively coupled with the sensor and a user interface communicatively coupled with the processor circuit.

Description

REUSABLE ANALYTE SENSING SYSTEM AND METHODS

CLAIM OF PRIORITY

[0001] Benefit of priority is hereby claimed to Gopikrishnan

Soundararajan et al. U.S. Provisional Patent Application Serial Number 61/086,691, entitled REUSABLE ANALYTE SENSING SYSTEM AND METHODS RELATED THERETO, filed August 6, 2008, Attorney Docket Number 2815.001PRV, which is hereby incorporated by reference herein in its entirety, including its description of reusable analyte sensing systems and methods related thereto.

BACKGROUND [0002] The American Diabetes Association reports that over eight percent (8%) of Americans, more than 24 million people, have diabetes. According to a report by the Centers for Disease Control ("CDC"), the number represents an increase of about 3 million over two years. The CDC estimates another 57 million have blood sugar abnormalities called pre-diabetes, which puts people at increased risk for the disease.

[0003] A vital element of diabetes management is the self-monitoring of blood glucose concentration by diabetics in the home environment. Patients are often required to draw blood for sampling many times a day or to utilize a subcutaneous monitoring device. After drawing blood (e.g., pricking a finger), diabetics often place the blood sample on a disposable sensing strip for a blood glucose measurement. The disposable sensing strips have the advantage of quick response time, which refers to how fast the strip can read and report a blood glucose measurement. Such strips are limited in effectiveness by how many times a day a patient takes a reading and the significant cost in using a disposable metering apparatus.

[0004] Subcutaneous devices may allow for continuous or near- continuous blood glucose readings. Often, such implantable devices indirectly detect glucose in the interstitial fluid of a patient. Readings of glucose levels in interstitial fluid lag behind actual blood glucose amounts and are subject to interference from reactant species. Subcutaneous devices also have a long response time and may take hours to get meaningful data. Subcutaneous devices are often not covered by medical insurance and may require maintenance and a higher level of user knowledge than disposable blood glucose sensing strips.

BRIEF DESCRIPTION OF THE DRAWINGS

[0005] In the drawings, which are not necessarily drawn to scale, like numerals can describe substantially similar components throughout the several views. Like numerals having different letter suffixes can represent different instances of substantially similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.

[0006] FIG. 1 illustrates a cross-sectional view of an example of an analyte sensor. [0007] FIG. 2 illustrates a schematic view of an example of a reusable analyte detection system.

[0008] FIG. 3 illustrates a schematic view of an example of a reusable analyte detection system using a cleaning mechanism.

[0009] FIG. 4 illustrates a block diagram of an example of a method of detecting an analyte.

[0010] FIG. 5 illustrate an example of a method of forming a polymer transport barrier layer (TBL) or other polymer layer, which can include adding nanoparticles, before, during, or after polymerization.

[0011] FIG. 6 illustrates a schematic diagram of an example of an electrode configuration.

[0012] FIG. 7 is a schematic diagram showing an example of a sensor front end interface circuit.

[0013] FIG. 8 is a block diagram showing an example of a method of using a re-usable analyte detection system, such as for performing glucose monitoring in a home setting.

[0014] FIG. 9 is a schematic drawing showing an example of a mechanical configuration that includes a sensor cartridge carried within a housing. [0015] FIG. 10 shows an example in which the housing includes a capillary tube or other wicking or like fluid transport mechanism extending between the distal sensing element and the hole in the housing. [0016] FIGS. HA, HB, and HC show an example of a separate cleaning mechanism.

[0017] FIG. 12 shows an example of a rotatable circular sensor cartridge disk.

[0018] FIG. 13 shows an example of a blood glucose or other sensor assembly, which includes a housing, such as for carrying the rotatable sensor cartridge disk.

[0019] FIG. 14 is a schematic drawing showing an example of the sensor assembly, having an open hinged cover.

[0020] FIG. 15 is a schematic drawing showing an example of a separate cleaning or calibration apparatus, such as for cleaning or calibrating the sensor cartridge disk.

OVERVIEW

[0021] Embodiments relate to a reusable analyte sensor, including a substrate manufactured of a low dielectric material, an analyte sensing layer in contact with the one or more electrodes and a transport barrier layer. The sensor is reusable.

[0022] Embodiments relate to a reusable analyte detection system including one or more reusable analyte sensors, a microprocessor, in electrical contact with the one or more sensors and a user interface in electrical contact with the microprocessor.

[0023] Embodiments also relate to a method of detecting an analyte, including contacting a sensing region with a biological fluid sample, measuring an amount of analyte in the sample, displaying the amount to a user and cleaning the sensing region, sufficient to prepare the sensing region for one or more cycles of contacting.

[0024] This overview is intended to provide an overview of subject matter of the present patent application. It is not intended to provide an exclusive or exhaustive explanation of the invention. The detailed description is included to provide further information about the present patent application.

DETAILED DESCRIPTION [0025] This document describes, among other things, a reusable sensor and analyte detection system, such as for monitoring blood glucose or other biological or other substances (e.g., cholesterol, alcohol, etc.). The present systems and methods can provide the advantages of both disposable testing strips and subcutaneous monitoring devices. The present reusable sensing regions need not contact the analyte, either before or after the measurement, and can have a fast response time. Because the sensor is in use only during sampling, sensor degradation can be substantially reduced, such as when compared to a subcutaneous device. Moreover, the present sensor or sensing regions can advantageously be cleaned and reused. This can significantly reduce the cost of the system, such as when compared to disposable testing strips. [0026] FIG. 1 shows an example of a cross-sectional view 100 of an analyte sensor, such as for monitoring blood glucose or other biological or other substances. In this example, an insulating dielectric substrate 108 can include one or more electrically conductive path 112, present on the substrate 108. The conductive path 112 can make individual or shared contact with one or more electrodes 110. For example, the electrodes 110 can be located on the conductive path 112, such as on a side of the substrate 108 upon which an analyte sensing layer 106 can be placed. This permits the analyte sensing layer 106 to be in contact with the one or more electrodes 110. A side of the analyte sensing layer 106 that is located away from the electrodes 110 can be placed in contact with an optional noise reduction layer 104. The noise reduction layer 104 can include a filtration layer. If the noise reduction layer 104 is included, a transport barrier layer 102 can be in contact with a side of the noise reduction layer 104 that is away from the analyte sensing layer 106. Otherwise, the transport barrier layer 102 can be in contact with the side of the analyte sensing layer 106 that is away from the electrodes 110.

[0027] The insulating substrate 108 can be manufactured of a material that exhibits a low dielectric constant. This facilitates a short response time or measuring time of the analyte sensing. The response time of the sensor can be less than about 3 minutes, less than about 2 minutes, less than about 1 minute, less than about 30 seconds, or even less than about 5 seconds, in various examples. The low dielectric constant of the substrate 108 results in less capacitive charge storage by the substrate 108, yielding a fast response time. In some examples, the substrate 108 can have a dielectric constant value of about 9 or less, about 8 or less, about 5 to about 9, or about 3 to about 8. In some examples, the substrate 108 can be manufactured using one or any combination of alumina 96%, alumina 99.6%, silicon nitride, silicon dioxide, aluminum nitride, graphite, sapphire, or fiberglass. Some specific examples of materials of the substrate 108 can comprise or consist of one or any combination of polyester, polycarbonate composite, Accu-chek® material, Mylar® (biaxially-oriented polyethylene terephthalate (boPET)) polyester film, Teijin® Tetoron® polyester film, Teijin Teonex polyethylene naphtalate (PEN) film, Teflon (polytetrafluoroethylene (PTFE)), DuPont® Melinex® polyester film, DuPont®

Melinex ST heat-stabilized polyester film, FR-2 (Phenolic cotton paper), FR-3 (Cotton paper and epoxy), FR-4 (Woven glass and epoxy), FR-5 (Woven glass and epoxy), FR-6 (Matte glass and polyester), G-10 (Woven glass and epoxy), CEM-I (Cotton paper and epoxy), CEM-2 (Cotton paper and epoxy), CEM-3 (Woven glass and epoxy), CEM-4 (Woven glass and epoxy), or CEM-5 (Woven glass and polyester).

[0028] In some examples, the one or more electrodes 110 can include one or more working electrodes, one or more counter electrodes, one or more reference or quasi-reference electrodes, or a combination thereof. In some examples, the one or more working or counter electrodes can comprise or consist of one or any combination of platinum, iridium, palladium, palladium alloy, rhodium, gold, silver, carbon, graphite or a combination thereof. In some examples, the one or more reference electrodes can comprise or consist of one or any combination of silver and silver chloride (such as a silver/silver chloride quasi-electrode (e.g., Ag-AgCl)), a standard or reversible hydrogen electrode, a saturated calomel electrode, a hydroxide electrode, a palladium/hydrogen electrode, a copper/cuprous electrode, or a sulphate electrode. The one or more reference electrodes can be used to help filter out one or more "undesired" electrical signals, such as can result from one or more "background" chemical reactions (e.g., other than the chemical reaction of interest). Otherwise, such undesired signals could detract from a correct reading of the desired analyte level. In some examples, the analyte detection system can include multiple working electrodes. This can help permit detecting multiple different analytes, in some examples. It can also help permit comparative measuring. Such comparative measuring can include the measuring of one or more analytes with respect to one or more other analytes, or with respect to a different combination of one or more analytes. As an illustrative example, the analyte detection system can include one reference electrode, five working electrodes, and one counter electrode.

[0029] The conductive path 112 can be made with a conductive material, such as, for example, gold, platinum (e.g., a paste), palladium, rhodium solder paste, copper, or a combination thereof. [0030] In certain examples, the transport barrier layer (TBL) 102 can filter one or more substituents or otherwise control transport therethrough of one or more substances, such as one or more analytes to be detected. In certain examples, such TBL filtering can be based on one or more of substituent size, charge, affinity to water (hydrophobic/hydrophilic) or some combination thereof. In certain examples, the TBL 102 can inhibit or prevent biological fluid from directly contacting the one or more of the sensor electrodes 110, while allowing passage through the TBL 102 of one or more select substances, such as the one or more analytes to be detected. In a glucose-sensing example, the TBL 102 can control diffusion or other transport of glucose to one or more of the sensor electrodes 110 for measurement. In certain examples, the TBL 102 can comprise or consist of one or more of polyethylene, polyvinyl chloride, tetrafluoroethylene, polypropylene, cellophane, polyacrylamide, cellulose acetate, polymethyl methacrylate , hydrogel, polyurethane, cellulose acetate, polyester sulfonic acid, polyamine, polysilane, polycarbonate, cuprophane, collagen, alpha, nylon, omega-Diaminopolypropylene glycol , or a combination thereof. In an example, the TBL 102 can include both hydrophobic and hydrophilic components. The hydrophobic and hydrophilic components can be monomers that form a polymer TBL 102. The hydrophilic component can help transport the analyte through the TBL 102.

[0031] In an example, a polymer TBL 102 can be formed such as described in Allen et al. U.S. Patent No. 5,322,063, entitled HYDROPHILIC POLYURETHANE MEMBRANES FOR ELECTROCHEMICAL GLUCOSE SENSORS, filed on Oct. 4, 1991, issued on June 21, 1994, assigned-at-issue to Eli Lilly & Co., the disclosure of which is incorporated by reference herein in its entirety, including its description of forming a hydrophilic polyurethane membrane, and using such a membrane for glucose sensing. Adhesion of such a membrane onto a substrate, such as for use as TBL 102, can present some degree of difficulty.

[0032] The present inventors have recognized, among other things, that adhesion to a substrate of such a material (or one or more other polymer materials) can be improved for the TBL 102 (or another layer), such as by using nanoparticles to alter the surface structure of the polymer, such as to improve its adhesion to a substrate.

[0033] FIG. 5 shows an example of a such process for forming the TBL

102. At 500, ingredients can be provided. In an example, the ingredients for forming the polymer can include polyethylene glycol (PEG) (e.g., Molecular Weight 100 - 20,000 u), diethylene glycol (DEG), a catalyst (e.g., di butyl bis (2-ethylhexanoate) tin), or both, and the nanoparticles used to improve surface adhesion. At 502, polymerization can be initiated, such as by providing the tin catalyst to the PEG or DEG (or both) ingredients at a controlled processing temperature. The temperature profile over time of the processing can be adjusted, such as to yield a polymer with a molecular weight that is within a range between about 30 kD and about 300 kD, or to yield a polymer with different adhesive properties.

[0034] At 504, the nanoparticles can be added into the polymerization reaction, such as during an initial phase of the polymerization, or before or after the polymerization phase. This can help provide physical or chemical alteration to the polymer, such as to improve adhesion. In an example, the nanoparticles can include metal oxide nanoparticles, such as sized between about 1 nanometer and 150 nanometers, such as and preferably between about 1 nanometer and 100 nanometers, more preferably sized between about 1 nanometer and 10 nanometers. The nanoparticles can have a Brunauer-Emmett- Teller (BET) surface area that is between about 30 m2/g and about 1000 m2/g, such as preferably sized between about 40 m2/g and 600 m2/g. The size of the nanoparticles can be varied, such as based on the desired surface adhesion or other effect that is desired. Examples of the nanoparticles can include one or any combination of oxides of silicon, aluminum, titanium, magnesium, manganese, iron, cobalt, nickel, copper, zinc, or lithium, and preferably can include fumed silica, fumed alumina, or fumed titania. In certain examples, some or all of the nanoparticles can be treated, such as to modify their surface energy.

[0035] Without being bound by theory, in certain examples, the nanoparticles can change the surface structure of the polymer, giving it a certain roughness, which can help its adhesion to the substrate surface. In certain examples, the nanoparticles can act as microchannels, such as to promote or restrict the flow of one or more target substances (e.g., glucose, oxygen, water, etc.), such as based on one or more functional groups attached to the one or more target substances.

[0036] For example, without being bound by theory, if fumed silica nanoparticles (e.g., fumed silica) is dispersed in a liquid, which possesses good wetting properties with respect to the fumed silica nanoparticles, then the fumed silica nanoparticles absorb molecules from the liquid until the surface energy is minimized relative to the environment. Nanoparticles being densely covered by a molecular skin substantially similar or identical to the surrounding fluid can tend to float in the fluid medium rather independent of each other, resulting in only minor increase in viscosity or adhesion of the dispersion mixture compared to the pure liquid. As a consequence the nanoparticles can follow gravity and settle rather quickly. This can be observed with hydrophilic fumed silica in a hydrophilic fluid (e.g., such as alcohols, acetone, polar solvents, or other hydrophilic fluids). [0037] As another example, without being bound by theory, hydrophobic fumed silica, can thicken a polar fluid into a gel. In such an example, the molecules of the liquid generally cannot adsorb onto the surface of the silica. Therefore, such fumed silica nanoparticles can tend to cling to each other as close as possible in order to minimize the free energy of the nanoparticle surface. This can result in forming a substantially randomly distributed grid of solid within the fluid medium. The resulting three-dimensional solid structure can exhibit a visco-elastic property, resulting in enhanced viscosity and, depending on the concentration of the nanoparticles, can provide better adhesion of the polymer film to a substrate. The fumed silica nanoparticle network can strengthen the polymer network that interlocks with the substrate topology, and it can provide hydrophobic interaction with hydrophobic substrate constituents. [0038] Without being bound by theory, in suspension, sedimentation is inhibited, because the solid particles (e.g., the fumed silica nanoparticles and surrounding polymer molecules) are no longer free to move downwards in the gravitational field. When shearing occurs, the resistance of the fumed silica grid is overcome, and the fumed silica grid breaks into smaller domains floating along in the streaming matter. The reduction in apparent viscosity can be very large, but as the shear is reduced, the fumed silica grid quickly rearranges and the apparent viscosity rises again. This thixotropic behavior can help adhesion, such as at 506, when applying the polymer-nanoparticle mixture to a porous or other substrate, such as by brushing or spraying. [0039] The noise reduction layer 104 can be used to inhibit transport therethrough of one or more species or substances that are not of interest, such as one or more "noise" substances that could otherwise confound detection of the one or more substances of interest. In an example, the noise reduction layer 104 can include one or a combination of an ion-selective, charge- specific, or other species-selective filtration membrane to pass a species of interest, or to reject a species that could otherwise interfere with detection of a species of interest. In an example, the noise reduction layer 104 can include one or more chemicals, such as to attenuate, neutralize, or otherwise impact the noise substance, such as to reduce its impact on the detection of the substance of interest. [0040] In an illustrative example, such as the noise reduction layer 104 in blood glucose-sensing, for example, acetaminophen in the blood is a substance that can interfere with glucose-sensing. In an example, the noise reduction layer 104 can include a species -selective membrane that will pass glucose therethrough while inhibiting or rejecting acetaminophen. In an example, the noise reduction layer 104 can include a chemical substance, such as Nafion® (C7HF13O5S .C2F4), such as to reduce the effect of acetaminophen on the glucose-sensing.

[0041] The filtration layer (which can be included in the noise reduction layer 104) can provide a path through which the analyte passes before reaching the analyte sensing elements. In some examples, the path can filter a particular species, such as by way of one or more of a chemical interaction, an electrical interaction, an electrochemical interaction, an irradiative interaction, or a combination thereof. In some examples, the filtration layer can remove the target species from the analytic solution, or can reduce the target species to a desired level. In some examples, such as to avoid undesired levels of certain species in the analyte that could disrupt readings at the sensor, the filtration layer can be configured in such a way so that the unwanted species are removed or are considerably reduced, such as in one or more of quantity, concentration, or reactivity.

[0042] The filtration layer can include charge-based filtering, in some examples. For example, a charge can be attached to or otherwise associated with the filtration layer, such as in one or more of its functional groups or constituent molecules. The charge can be used such as to specifically attract or repel one or more particular species. In an example, the nature of the charge can determine the target to be filtered, and the magnitude of the charge can determine the amount of filtering.

[0043] The filtration layer can include reaction-based filtering, in some examples. For example, a reactive element such as a chemical reagent can be attached to or otherwise associated with the filtration layer. The reactive element can be selected to react with a target species. The reaction can chemically or physically alter the target species, such as so that the target species has little or no effect on the sensing output, in some examples. The nature of the chemical reagent can determine one or more of the target species for filtration, the reaction rate, or the reaction products, in some examples. The concentration of the chemical reagent can determine the amount of filtering, in some examples. [0044] The filtration layer can include size-based filtering, in some examples. For example, the filtration layer can include physical pores or the like of a desired "pore architecture", e.g., pore size or pore distribution density or the like. The pore size can determine the specific one or more analytes that pass through the filtration layer, in some examples. The density of the pores on the filter can determine the magnitude of filtering, in some examples. In an example, the pore density of a polycarbonate membrane used in the filtration layer can be between about 104 pores/cm2 and about 6-1012 pores/cm2. The pores can be made using various techniques. In some examples, a medium can be held in a mold. The medium can be curable by heat, light, pressure, or a chemical reaction (e.g., epoxies, elastomers, silicone, etc.). A pore definition structure, such as micro-needles or nanostructures can be used to define the pore architectures in the material being held by the mold. When the medium is still uncured, the definition structure can pass through the material to define the pores. After the medium has cured or otherwise stabilized, using an appropriate technique, the definition structure can be carefully pulled out of the medium. This can leave behind a solidified block with pores defined therein, by the definition structure.

[0045] In some examples, the pores can be pressure-punched or similarly formed into a solid base filter, such as by using a definition structure that includes micro-needles or nanostructures. In some examples, the pores can be created using a track ion etch, a reactive ion etch, or other etch process, such as in which the base filter material used can comprise or consist of one or more of a silver membrane, cellulose acetate, a ceramic membrane, glass fibers, a nylon membrane, a nitro cellulose mixed ester (MCE), polyester (PETE), polycarbonate(PCTE), polyethersulfone (PES) membrane, polypropelyne, polydimethylsiloxane (PDMS), or TEFLON® or other polytetrafluoroethylene (PTFE).

[0046] In an ion etch process example, such as track ion etching or reactive ion etching (RIE), a thin filter film can be exposed, such as exposed to focused, charged ionized particles. As these ions pass through the filter material, they can leave sensitized polymerized tracks, which can then be etched away using an appropriate etchant. This can leave a cylindrical columnar pore in the base filter material. The resulting pores can be used for filtration, such as for limiting or controlling the flow of glucose in a medium, which medium can include a solid, liquid, a gas, or a combination thereof. [0047] In some examples, the pore size can be controlled, such as by changing one or more different parameters in the process, such as the ionized material used, the energy with which it accelerated, the distance between the filter material and the ion source. Using this method, filters can be made such as with pore sizes ranging from about 10 nanometers to about 2 micrometers, from about 8 nanometers to about 1 micrometer, or from about 5 nanometers to about 0.5 micrometers, in some examples. Illustrative examples of porosities can include pores occupying between about 0.01% and about 50% of the surface area.

[0048] The appropriate pore size can be selected depending on what the filter is targeted to restrict. For example, to restrict or regulate flow of glucose through the filter membrane, a filter pore size that is in a range from about 10 nanometers to about 10 micrometers can be selected, such as depending on the level of restriction desired. In some examples, the regulation by the filter can also be controlled by layering filters of the same pore size, or of different pore sizes, such as to establish a desired overall filtering rate or other filtering characteristic. [0049] In some examples, the filtration can be accomplished using a combination filter, such as in which two or more of the above-mentioned or other techniques are used together, such as to provide a very specific outcome. As an illustrative example, a reaction filter can be made to react with the target species and change its size; in combination with this, a size-based filter can be used to control the flow of the altered-sized target species to the sensing electrode 110. In another illustrative example, a charge-based filter can be used to attach a certain charge to the filtration target; in combination with this, a reaction filter can be used to react with the charged target, such as to filter and restrict flow of the target to the sensing electrode 110. [0050] In some examples, the analyte sensing layer 106 can include one or more enzymes or co-enzymes. The sensing layer 106 (or one or more sensors formed using the sensing layer 106) can be configured to measure the concentration of one or more target analytes, such as a reaction product. In some examples, the sensing layer 106 can be configured to directly detect the target analyte, or to detect a substance that can be correlated to the target analyte. In some examples, the sensing layer 106 can be configured to measure a reactant or reaction product, or to measure the consumption of an enzyme or co-enzyme, for example. In a glucose detecting example, the sensing layer 106 can catalytically convert the glucose (e.g., such as by using the enzyme glucose oxidase in the presence of oxygen and water) into gluconic acid and hydrogen peroxide. In an example, the resulting hydrogen peroxide is anodically active at the electrode 110. Therefore, the hydrogen peroxide produces a resulting current that is proportional to the concentration of hydrogen peroxide in a blood sample, which, in turn, is proportional to the concentration of glucose in the blood sample upon which such catalytic conversion has been performed. Some examples of enzymes that can be used for performing a catalytic conversion (e.g., such as for glucose sensing) can include one or more of glucose oxidase, glucose dehydrogenase, hexokinase, galactose oxidase, uricase, cholesterol oxidase, alcohol oxidase, lactose oxidase, L-amino acid oxidase, D-amino acid oxidase, xanthine oxidase, ascorbic acid oxidase, or a combination thereof. [0051] FIG. 2 shows an example of a schematic view 200 of portions of a reusable analyte detection system, such as for performing external glucose monitoring, in some examples. In an example, a microprocessor 204 or other suitable circuit can be electrically or otherwise coupled to an input/output device 202, such as a keypad and display 202. The microprocessor can also be coupled to a sensor front end interface circuit 206. The microprocessor 204 can also be communicatively coupled to a calibration device such as a calibration data integrated circuit chip 208, and to an analyte detection system 216. A sensor cartridge 210 can include the calibration data chip 208 and can optionally include the sensor front end interface circuit 206. The sensor cartridge 210 can be communicatively coupled with a sensor drive mechanism or circuit 212. The sensor drive 212 can include circuitry, an electromechanical drive mechanism, or a combination thereof. A sensor position detection circuit 214 can also be in contact with the sensor cartridge 210 (e.g., when properly positioned) and communicatively coupled to the microprocessor 204. A communication interface 218 can also be communicatively coupled with the microprocessor 204. In some examples, a cleaning or calibration mechanism 302 (see FIG. 3) can be interchangeable with one or more components of the system and communicatively coupled with the microprocessor 204. [0052] A user interface can include the display and keypad or other input/output device 202, for example. The display can include a screen, such as a liquid crystal display (LCD), touch screen, or organic LED, in some examples. The display 202 can be configured to show to a user information about an analyte, such as an indication of an analyte concentration or amount. Such indication can be in one or more forms, such as in numerical form, graphical form, pictorial form, audio form etc. The user interface can also include a communication interface 218, such as to help communicate information to and from the system. In some examples, such information can include one or more of device settings, configurations, calibration, or other information. In some examples, the communication interface 218 can relay information to a local or remote external device, such as a mobile phone, laptop computer, pager, personal digital assistant (PDA), smart phone, telephone, or remote computer server, for example, such as via wired or wireless communication. [0053] One or more analyte sensors or sensing regions can be included in the cartridge 210, which can be communicatively coupled to the sensor front end interface circuit 206. A memory chip or calibration data chip 208 can be carried by or otherwise included with the sensor cartridge 210, which also includes the analyte sensors. In some examples, the memory chip or calibration data chip 208 can be rewritable (such as by including EEPROM, flash memory or other nonvolatile storage) and can store information for calibrating, tracking, improving, or otherwise affecting sensor performance. In some examples, such information can include one or a combination of factory calibration data, accuracy correction data, sensor characterization data, number of uses of the particular sensor, a maximum allowable number of uses for the particular sensor, sensor identification information, sensor cartridge identification information, patient-specific data, or information about the number of sensors per sensor cartridge 210. [0054] In some examples, the sensor drive mechanism 212 can include a mechanical or electromechanical component, such as to operate any moving parts of the system, such as one or more motors, belts, encoders, etc. In some examples, the drive mechanism 212 can control loading, unloading, positioning, electromechanical coupling, or other movement of the cartridge 210, or movement of one or more individual sensing elements or sensors. [0055] In some examples, the sensor position detection system 214 can be configured to coordinate or verify the position, movement, or replacement of the sensors or the sensor cartridge 210, such as for calibration, cleaning, or analyte sampling, for example. In some examples, the position detection system 214 or the memory chip or calibration data chip 208 can also be used to differentiate between sensors. Optical tagging, radio frequency tagging, or electrical tagging can be used, in some examples, such as to identify or differentiate between the sensors.

[0056] In some examples, one or more optical emitters or detectors are located on a side of the sensors or the sensor cartridge 210. This can include detector/emitter pairs, such as a detector located on an opposite side of the sensor cartridge 210 from an emitter. The sensor or sensor cartridge 210 can include a pattern of holes. Different sensors can be provided with different patterns of holes, in some examples. For each individual sensor, a particular combination of the holes permits emitter light to pass therethrough, such as to a detector, such as for assisting in identifying or positioning the sensor. In an example, a similar pattern electrical contacts can be used instead of (or in addition to) the holes (and light emission and detection). Such light emitters and detectors can be replaced (or combined) with electrical pathways, such as for detecting one or more of voltage, current, or frequency, such as to identify or position the sensor. In an example, a radio frequency identification (RFID) tag can be located on the sensor cartridge 210, such as for identifying the sensor cartridge 210.

[0057] FIG. 3 shows an example of the system 400 that includes the cleaning or calibration mechanism 302. In an example, the cleaning or calibration mechanism is integrated (e.g., shares the same housing) as the sensor cartridge 210. In another example, the cleaning or calibration mechanism is interchangeable with a sensor portion of the sensor cartridge 210. In an example, the cleaning component of the cleaning or calibration mechanism 302 can be used to remove unwanted or foreign species or materials from the sensors or sensor cartridge, such as contaminants or pollutants. In an example, the cleaning component of the cleaning or calibration mechanism 302 can prepare the sensor for reuse, such as for further sampling. The cleaning component of the cleaning or calibration mechanism 302 can include one or more solids, liquids, gases, or can use electromagnetic radiation to help clean the sensor. In some examples, the cleaning component of the cleaning or calibration mechanism 302 can operate mechanically, electromechanically, chemically, electrochemically, or electromagnetically. [0058] In certain examples, the calibration component of the cleaning or calibration mechanism 302 can include one or more compartments such as for housing a calibration component, such as a calibration test material, a calibration circuit, or both. This can provide information related to maintaining the accuracy of the sensors or sensing regions. In certain examples, the calibration test material can be a solid or liquid, can be organic or inorganic, and can be used to simulate various measurable limits of the analyte. In an example, the sensors can be repeatedly calibrated, such as on a systematic schedule, or in response to one or more conjunctive, disjunctive, weighted or other pre-selected conditions (e.g., following cleaning). [0059] In an example, the sensor cartridge 210 can pass each sensor through the cleaning and calibration mechanism 302. The cleaning media or calibration media can be held statically, such as in respective compartments through which the sensor elements can pass. The cleaning media or calibration media can be packaged in cartridges or packs and occasionally replaced, such as after a certain number of uses by the user. The cleaning or calibration mechanism can use one or a combination of contact cleaning, ultrasonic cleaning, chemical cleaning, or optical cleaning, in some examples. The calibration can be performed as triggered by the microprocessor, such as based on a specified condition. [0060] FIG. 4 shows a diagram 400 of an example of a method of detecting an analyte. In this example, at 402, a sensing region can be contacted, such as by a substance (e.g., blood or another substance) in which a concentration of the analyte (e.g., glucose or another analyte) is to be determined. At 404, an amount of the analyte of interest can then be measured. At 406, information from the measurement can be displayed or provided to a local or remote user or automated process. At 408, the sensing region can be cleaned, such as in preparation for further sampling and measuring. [0061] At 402, in certain examples, contacting the sensing region can include depositing a biological sample, such as blood, onto a sensing region or sensor, such as upon the TBL 102 of FIG. 1. In an example, this can involve using a blood collection device, such as a lancet, to take a blood sample, which can then be deposited upon the sensing region or sensor of the device. In certain examples, the sample can be collected mechanically, electromechanically, or some combination thereof. The sample can be acquired using a needle device, syringe or other suction device, lancet device, or with a device using wicking action or capillary action, for example. A detection circuit can then be used to directly or indirectly detect the presence of an analyte. [0062] At 404, analyte measuring can be performed, in various examples, in less than about 3 minutes, less than about 2 minutes, less than about 1 minute, less than about 30 seconds, or less than about 5 seconds. The measuring can include determining the amount of one or more analytes directly or indirectly, such as by measuring a concentration of a substance that can then be correlated to the concentration of the analyte of interest. A measuring or sensing circuit can be signaled by the detection circuit, such as to trigger a measurement.

[0063] At 408, before optionally cleaning, another sensing region can be optionally contacted, an analyte measured, and information about the result displayed. In this way, the optional cleaning can include concurrently cleaning more than one sensing region or sensor, for example, which were used in different analyte measurements.

[0064] The acts of contacting the sensing region at 402, measuring at

404, displaying at 406, and cleaning at 408 can be repeated, such as by using the same re-usable sensor cartridge. In some examples, this allows such repeating about 5 or more times, about 10 or more times, about 25 or more times, or about 50 or more times, or about 5000 or more times (e.g., in an example in which the

5000 or more times are carried out over a relatively short time duration, such as about 3 days, in an illustrative example). This allows re-use of the sensor of FIG. 1.

[0065] Calibrating can occur before, during, or after any of the above mentioned acts at 402, 404, 406, or 408. The calibrating can involve measuring a test sample with one or more sensors, and comparing to the result to a specified value for the test sample. The difference between the measured value and the specified value can be used as an calibration offset to apply to later (calibrated) measurements. In certain examples, the calibration can involve measuring multiple test samples (e.g., of different concentrations of a test analyte) and using the results to perform a linear or non- linear calibration of later measurements using the calibration data.

[0066] FIG. 6 shows a schematic diagram of an example of a configuration of various electrodes 110. In this illustrative example, the electrodes 110 can include a working electrode 610, a counter electrode 612, and a reference electrode 608, which, together, can be used for measuring a concentration a desired analyte. For example, in a glucose-sensing application, the working electrode 610, the counter electrode 612, and the reference electrode 608 can be used to detect anodically active hydrogen peroxide (which is correlative to glucose concentration when the glucose has been catalytically converted to gluconic acid and hydrogen peroxide by glucose oxidase enzyme in the sensing layer 106). The resulting charge will generate a current that is proportional to the hydrogen peroxide concentration, and therefore, proportional to the glucose concentration. The working electrode 610, the counter electrode 612, and the reference electrode 608 are electrically connected to the sensor front end interface circuit 206 for detecting the resulting electrical signal, and performing signal processing that determines the glucose concentration for communication to a local or remote user or automated process. [0067] In the example of FIG. 6, the configuration of various electrodes

110 can also include status electrodes 606, which can be located on the surface upon which a liquid sample (e.g., blood) is to be placed. In an example, the working electrode 610, the counter electrode 612, and the reference electrode 608 can be located between the status electrodes 606. The status electrodes 606 can form part of an impedance sensor, which can detect a change in impedance (e.g., resistance or capacitance) when conductive blood spans the region between the status electrodes 606. This detected change in impedance can provide information that can be used to ensure that the liquid sample (e.g., blood) is present at the working electrode 610, the counter electrode 612, and the reference electrode 608. Therefore, the detected change in impedance can be used as a timing signal to trigger a glucose measurement by the sensor front end interface circuit 206 using the working electrode 610, the counter electrode 612, and the reference electrode 608, such as after an appropriate delay (e.g., to allow the catalytic conversion by the enzyme, or to account for one or more other system response delay factors).

[0068] FIG. 7 is a schematic diagram showing an example of a sensor front end interface circuit 206, such as can be communicatively coupled to a microprocessor 204, and to one or more working electrodes 610, one or more counter electrodes 612, and one or more reference electrodes 608. In an example, the sensor front end interface circuit 206 can include a sensor potentiostat circuit 702, a current-to-voltage converter circuit 704, an analog-to- digital converter circuit 706, and a digital-to-analog converter circuit 708. In an example, the sensor potentiostat circuit 702 can be configured to drive one or more working electrodes 610 with a specified voltage difference (e.g., such as between about 0 Volts and about 2.0 Volts) from the voltage at one or more reference electrodes 608. In an example, the sensor potentiostat circuit 702 can be configured to drive one or more working electrodes 610 with a specified voltage difference from the voltage at one or more reference electrodes 608, where the driven voltage difference is at least slightly less than a reduction/oxidation (redox) potential of an unwanted "noise" species, which could otherwise interfere with detection of the desired analyte of interest. In an illustrative blood glucose testing example, if the blood sample to be tested includes both glucose and an unwanted "noise" species such as acetaminophen, the specified driven voltage can be maintained at less than the redox potential for the acetaminophen, such that the electrochemical reaction is representative of the glucose concentration, and not adversely affected by an electrochemical reaction involving the acetaminophen. [0069] The one or more counter electrodes 612 can be configured to

"float," such that they can attain whatever voltage is needed to provide a current that counters the current (e.g., such as between about 0 microampere to about 1 microampere) at the one or more working electrodes 610, in an example. For example, the current at the one or more working electrodes 610 can include electrons flowing into the one or more working electrodes 610, such as resulting from the electrochemical reaction at the one or more working electrodes 610, such as occurring during analyte detection of hydrogen peroxide occurring at the one or more working electrodes 610 during glucose sensing, in an example. The current sensed between the working and reference electrodes can be mirrored or otherwise provided to the current-to-voltage converter circuit 704. The current- to-voltage converter circuit 704 can be configured to convert the current into a voltage, and can output the resulting voltage to an input of the analog-to-digital converter circuit 706. The analog-to-digital converter circuit 706 can be configured to convert its input voltage to a digital value. The analog-to-digital converter circuit 706 can output the digital value to a data input bus of the microprocessor 204, to which it is communicatively coupled. The microprocessor 204 can be configured to use this digitized sensed information, such as to calculate and provide an analyte concentration reading. In an example, the microprocessor 204 can similarly use such information during a calibration operation. In an illustrative example, the calibration operation can include providing two different samples of two different (e.g., low and high) known analyte concentrations. The resulting measurements can be used to form one or more linear or non-linear calibration correction factors (e.g., offset, slope, etc.), which can then be applied to later (e.g., non-calibration) measurements, such as to provide a calibrated output reading for such later measurements. In an illustrative glucose sensing calibration example, a first calibration fluid corresponding to a glucose concentration of 40 mg/dL can be used, and a second calibration fluid corresponding to a glucose concentration of 400 mg/dL can be used. In another illustrative example, a first calibration fluid corresponding to a glucose concentration of 100 mg/dL can be used, and a second calibration fluid corresponding 300 mg/dL can be used. In other examples, other concentrations can be used for performing the calibration. [0070] In an example, the microprocessor 204 can output one or more control parameters to an input bus of the digital-to-analog converter 708. In an example, the digital-to-analog converter 708 can convert an input digital parameter into an output voltage or other signal level that can be provide to the sensor potentiostat circuit 702, such as for helping control its operation during an analyte reading or calibration operation.

[0071] FIG. 8 is a block diagram showing an example of a method 800 of using a re-usable analyte detection system, such as for performing glucose monitoring in a home setting. At 802, in this example, a re-usable glucose sensing device can be turned-on, such as by a user engaging a switch. At 804, a glucose sensing element can be automatically or manually moved to a desired sensing position for performing the glucose sensing, such as from a designated storage position. [0072] At 806, the glucose-sensor device can be checked to prepare for making a glucose measurement. In an example, this checking can involve checking whether the sensor element has been properly positioned, such as by interrogating a sensor position detection circuit, such as the sensor position detection circuit 214. In an example, this checking can involve checking a sensor identification, such as by interrogating the calibration data integrated circuit chip 208, an RFID tag, or the like. The sensor identification information can be used to determine whether the sensor is the correct type for performing the glucose measurement. In an example, this checking can also include interrogating the calibration data integrated circuit chip 208 to determine whether the number of previous uses (e.g., measurements) of the sensor cartridge 210 is less than a maximum number of allowable uses, such that the sensor cartridge 210 still has at least one available remaining use for performing another measurement. At this time, or alternatively after the glucose measurement, the calibration data integrated circuit chip 208 can be rewritten to increment the number of uses to reflect the additional measurement that will be (or has been) performed. In an example, the checking at 804 can involve determining whether the sensor cartridge 210 has been properly calibrated and, if not, calibrating the sensor cartridge 210. If the sensor cartridge 210 cannot be properly calibrated, then a corresponding calibration error condition can be generated, and the glucose measurement can be inhibited, such as by issuing an alert to the user, in an example. In an example, the checking at 804 can involve determining whether the sensor cartridge 210 has been properly cleaned since the last measurement or, if applicable, within a specified number of previous measurements, or within a specified maximum period of time between cleanings (which can, if desired, allow multiple measurements per cleaning), or a specified conjunctive, disjunctive, weighted, or other combination of these or other conditions. In an example, data about such cleaning can be stored on the calibration data integrated circuit chip 208, such as in conjunction with an episode of cleaning.

[0073] At 808, if the checking at 806 indicates that it is OK to proceed, then process flow continues at 810, otherwise an error or other message is communicated at 812, and process flow continues elsewhere, such as to 814. [0074] At 810, the user can be prompted to place an analyte sample (e.g., blood, bodily fluid, organic or inorganic fluid or solid such as alcohol, aldehide, hydrocarbon, etc.) at a desired location such as at the sensing element. In an example, this can involve using the display portion of an input/output device 202 to display a prompt indicating that the user should place a blood sample at a sensing element on the sensor cartridge 210 for a glucose measurement. [0075] At 816, a determination can be made as to whether the sample is present at the sensing element on the sensor cartridge 210. In an example, this can involve performing an impedance detection between status electrodes 606 that straddle the measurement electrodes, such as to detect a drop in impedance when blood is present, as described above. [0076] At 816, if the analyte sample is determined to be present, the process flow continues at 818, otherwise process flow returns to 810. At 818, one or more measurement parameters can be optionally applied to the measurement. In an example, this can include applying one or more calibration parameters to be used in the measurement. [0077] At 820, the measurement can be performed. In an example, this can include determining glucose concentration in a blood sample, such as by measuring a current generated that is proportional to the hydrogen peroxide concentration, and therefore, proportional to the glucose concentration, where the hydrogen peroxide has been formed by catalytic conversion such as described above.

[0078] At 822, the measurement result can be computed and communicated to a local or remote user or automated process. In an example, this can involve applying an offset or other specified linear or non-linear calibration factor to a measured result.

[0079] At 824, the sensing element can be moved away from the sensing position. As described above, storage between intermittent uses can help prolong life of the sensor, such as compared to a continuous or near-continuous sensing application. In an example, this movement can be automatic, such as in response to completion of the measurement. In an example, this movement can be user-initiated, but machine-assisted, such as by a motor. In an example, this movement can be manual, such as by the user applying a force, such as to the sensing element or an actuator. [0080] At 826, the sensing element can be cleaned. In an example, this cleaning can be carried out during or in conjunction with the movement or storage of the sensing element, such as by passing the sensing element through a cleaning region or chamber. [0081] At 814, the sensing element can be stored, and the device can be turned off. Process flow can then return to 802.

[0082] FIG. 9 is a schematic drawing showing an example of a mechanical configuration that can include a sensor cartridge 210 carried within a housing 902. In this example the housing 902 can include an opening 904. The sensor cartridge 210 can ride on a track 906 that allows longitudinal re- positioning of the sensor cartridge 210 within the housing 902. This can allow a distal-most sensor element IOOA to be extended out of the opening 904 in the housing 902 (such as for receiving a blood sample or other sample to be analyzed), and retracted back into the housing 902. The extension and retraction can be user-actuated, such as by depressing a spring-loaded button 908 that can be located on a proximal end of the housing 902, and that can be attached to or otherwise associated with the sensor cartridge 210. In this example, the sensor cartridge 210 can include a plurality of sensing elements 100A-J. The sensing elements 100A-J can ride on a conveyor belt 910 that can allow the sensing elements 100A-J to be repositioned. Such repositioning can occur after a specified number of one or more uses, after a specified time, or other specified conjunctive, disjunctive, weighted or other combination of specified conditions, such as explained above. In an illustrative example, each sensing element 100 can be used once, then repositioned, until each sensing element has been used once, after which the belt 910 can be removed and placed into a cleaning apparatus for cleaning the sensing elements 100 on the belt 910. In another illustrative example, each sensing element 100 can be used until a calibration condition (or one or more other test conditions) is met, then repositioned. In an example, the belt 910 can be driven by a gear, wheel, or other sensor drive mechanism 912, which can be used for repositioning the sensing elements 100 by driving the belt 910.

[0083] In an example, a memory or calibration data integrated circuit 208 can be provided on the sensor cartridge 210, such as can be shared between the plurality of the sensing elements 100A-J. In an example, a memory or calibration data integrated circuit 208 can also be provided on the belt 910. Because the belt 910 is moving, the memory or calibration circuit 208 located on the sensor cartridge 210 may, in certain examples, not always be electrically connected to the sensing elements 100A-J. However, by providing electrical traces on the belt 910, such as individual traces from each of the sensing elements 100A-J to the memory or calibration circuit 208 that is located on the belt 910, an electrical connection can be maintained between the sensing elements 100A-J and the memory or calibration circuit 208 that is located on the belt 910. Data from the memory or calibration circuit 208 that is located on the belt 910 can be transferred to the memory or calibration circuit 208 that is located on the sensor cartridge 210, such as when the belt is positioned, with respect to contacts on the sensor cartridge 210, to make such an electrical connection. In an example, the memory or calibration circuit 208 on the sensor cartridge 210 can be omitted, and the memory or calibration circuit 208 on the belt 910 can be used exclusively to provide such function.

[0084] In an example, the belt 910 can be keyed or otherwise configured such that the belt 910 can only be mounted on the sensor cartridge 210 in a particular position, such as in which electrical contact is made between the belt 910 and the sensor cartridge 210, allowing information to be communicated between the memory or calibration circuit 208 that is located on the sensor cartridge 210 and the memory or calibration circuit 208 that is located on the belt 910. This can allow information to be written to the memory or calibration circuit 208 that is located on the belt 910, for example. In this example, after the belt 910 has been repeatedly advanced, such that all of the sensing elements 100A-J have been used, the belt 910 can return to the position that allows electrical communication between the memory or calibration circuit 208 that is located on the belt 910, and the memory or calibration circuit 208 that is located on the sensing cartridge 210. This can allow information to be automatically written back from the memory or calibration circuit 208 on the belt 910 to the memory or calibration circuit 210 that is located on the sensing cartridge 210. The belt 910 can then be removed, such as for cleaning the sensing elements 100 A- J on the belt, in an example. [0085] In an example, a microprocessor 204 can be provided within the housing 902, either integrated with or separate from the sensor cartridge 210. An output of the microprocessor 204 can be connected to an input of a display 914, which can be either integrated with or separate from the sensor cartridge 210. In an example, a portion of the housing 902 can be substantially clear, such that the display 914 can be read by a user, such as to obtain information about the determined glucose or other analyte concentration measured for a particular blood or other sample. In an example, the housing 902 can include a universal serial bus (USB) port 916, or other wired or wireless connection, such as to permit data transfer from the housing 902 to another local or remote device. [0086] FIG. 10 shows an example in which the housing 902 includes a capillary tube 1002 or other wicking or other fluid transport mechanism extending between the distal sensing element IOOA and the hole 904 in the housing 902. This permits blood or another fluid sample to be drawn into or otherwise transported to the housing 902 and transported to the distal sensing element IOOA. This technique can be used to avoid moving the sensor cartridge 210 to extend and retract the distal sensing element IOOA into and out of the opening 904. [0087] FIGS. 11A-11C show an example of a separate cleaning mechanism 1100, such as for cleaning the sensing elements 100, such as by removing the belt 910 from the housing 902, and inserting the belt 910 into a housing 1102 of the separate cleaning mechanism 1100. In the example shown in the side cross-sectional view of FIG. HA, the housing 1102 comprises calibration fluid reservoirs 1104A-B, a sensing element chamber 1106, and an electronics chamber 1108. In an example, the belt 910 carrying the sensing elements 100 can be placed into the sensing element chamber 1106, such as for cleaning, rinsing, or calibration. [0088] In this example, the calibration fluid reservoirs 1104 A-B and the sensing element chamber 1106 can carry a fluid. In an example, the calibration fluid reservoirs 1104A-B can carry different respective calibration fluids, such as can be introduced through respective fill ports 1110A-B and removed through respective drain ports 1112A-B. In an example, the sensing element chamber 1106 can carry a cleaning fluid, such as can be introduced through or removed from one or more ports 1114. In an example, the belt 910 can be placed within the sensing element chamber 1106, such that its sensing elements 100 can be cleaned by the cleaning fluid in the sensing element chamber 1106. In an example, the cleaning fluid is pumped into the sensing element chamber 1106 for performing the cleaning. An on-board cleaning fluid pump can be provided for this. In a blood glucose concentration measurement application, residual blood on the sensing elements 100 can be cleaned using a cleaning fluid that can include Trypsin, which can help remove or otherwise clean blood or proteins from the sensing elements 100. After such cleaning has been performed, the cleaning fluid can be pumped out of the sensing element chamber 1106, such as by the on-board cleaning fluid pump. Then, a buffering solution, such as phosphorus-buffered saline (PBS) solution can be pumped into the sensing element chamber 1106, such as for rinsing residual cleaning fluid from the sensing elements 100. An on-board buffer fluid pump can be provided for this. After rinsing, the buffer solution can be pumped out of the sensing element chamber 1106, such as by using the on-board buffer fluid pump. [0089] In an example, a stepper motor or other drive mechanism 1114 can be programmably controlled to drive the belt 910, such as to advance the position of the sensing elements 110. In an example, this can be accomplished by using the drive mechanism 1114 to rotate a spindle 1116 that extends from the electronics chamber 1108 into the sensing element chamber 1106. In an example, the rotatable spindle 1116 can directly or indirectly engage the belt 910 upon which the sensing elements 100 can be located. The belt 910 can be driven to move the sensing elements 100, such as to calibrate such sensing elements 100. The calibration can occur after the sensing elements 100 have been cleaned and rinsed, and the cleaning fluid and the buffer fluid have each been pumped out of the sensing element chamber 1106. [0090] FIGS. 11B-11C show top views of the apparatus shown in FIG.

HA, but in two different operating positions. In the example of FIG. HB, the end sensing elements 100 can be positioned away from their respective adjacent end calibration fluid reservoirs 1104A-B. However, in the example of FIG. HC, the end sensing elements 100 can be extended into their respective adjacent end calibration fluid reservoirs 1104A-B, such as through respective push-activated valves in the walls of the adjacent calibration fluid reservoirs 1104 A-B. In an example, such push-activated valves can operate similar to an infusion port, and can include a push- activated aperture and an O-ring seal. [0091] In an example, the extension and retraction of the end-most sensing elements 100 into and out of the push- activated valves of the calibration reservoirs can be actuated by an eccentric-shaped cam 1118 and spacers 1120A- B. In an example, the cam 1118 can be engaged and rotated by the spindle 1116, such as to push out and allow retraction of the spacers 1120A-B, which, in turn, extends and retracts the end-most sensing elements 100. In an example, the belt 910 can be elastic enough to accommodate this extension and to provide biasing for the retraction. In an example, the spindle 1116 can be configured to selectively engage either a drive mechanism for the belt 910 or the cam 1118, such as by providing multiple gears and translating the spindle 1116 longitudinally to select between driving the belt 910 or the cam 1118. In another example, different spindles 1116 can be used to independently drive the belt 910 and the cam 1118 separately. [0092] In an example, the calibration fluid reservoirs 1104, the cam

1118, the spacers 1120A-B can be omitted, and a simpler system can be constructed by cycling the cleaning fluid, the rinsing fluid, and the calibration fluids through the sensing element chamber 1106. For example, first, the Trypsin or other cleaning fluid can be pumped or otherwise introduced into the sensing element chamber 1106 to clean blood or other substances away from the sensing elements 100. Then, the cleaning fluid can be pumped out or otherwise removed from the sensing element chamber 1106. Then, the PBS or other rinsing fluid can be pumped in or otherwise introduced into the sensing element chamber 1106, such as to rinse away any residual cleaning fluid. Then, the rinsing fluid can be pumped out or otherwise removed from the sensing element chamber 1106. Then, a first calibration fluid can be pumped in or otherwise introduced into the sensing element chamber 1106, and each of the sensing elements 100 can acquire calibration data with the first calibration fluid present. Then, the first calibration fluid can be pumped out or otherwise removed from the sensing element chamber 1106. Then, the rinsing fluid can be pumped or otherwise introduced into the sensing element chamber 1106, such as to rinse away any of the residual first calibration fluid. Then the rinsing fluid can be pumped out or otherwise removed from the sensing element chamber 1106. Then, a second calibration fluid can be pumped in or otherwise introduced into the sensing element chamber 1106, and each of the sensing elements 100 can acquire calibration data with the second calibration fluid present. Then, the second calibration fluid can be pumped out or otherwise removed from the sensing element chamber 1106. Then, the rinsing fluid can be pumped or otherwise introduced into the sensing element chamber 1106, such as to rinse away any of the residual second calibration fluid. Each of the sensing elements can then be calibrated using the calibration data that was acquired when the first and second calibration fluids were present.

[0093] FIG. 12 shows an example of a rotatable circular sensor cartridge disk 1200. In this example, the sensor cartridge disk 1200 includes a plurality of sensing elements 100 distributed about the outer circumferential periphery of the sensor cartridge disk 1200. Although FIG. 12 shows an example that includes four sensing elements 100, this is for illustration only; more or fewer sensing elements 100 can be included. Each sensing element 100 can include a corresponding designated pattern of holes 1202 through the sensor cartridge disk 1200, through which light can be passed by a corresponding light emitter 1203, located on a first side of the sensor cartridge disk 1200, and detected by a corresponding light detector 1205, located on an opposing second side of the sensor cartridge disk 1200. The pattern can be used as an identification tag, comprising the holes 1202 providing binary data, such as for identifying the particular sensing element 100. This can help ensure that the sensing element 100 corresponds to an expected sensing element, such as based on the identification information. In an example, the sensing electrodes 1201 (e.g., working, reference, counter, status) of the sensing element 100 can be located on a first side of the sensor cartridge disk 1200. Electronics, or electrical contacts to which electronics can be coupled, can optionally be located on a second side of the sensor cartridge disk 1200, such as opposite from the first side of the sensor cartridge disk 1200. In an example, such electronics can include a sensor calibration data or other memory integrated circuit 208. In an example, vias 1204 can extend through the sensor cartridge disk 1200, such as between respective electrodes on the first side of the sensor cartridge disk 1200 and corresponding electrical contacts on the second side of the sensor cartridge disk 1200. In an example, the vias 1204 and the sensor cartridge disk 1200 can be configured such as shown and described with respect to FIGS. 5A-5F. In the example of FIG. 12, the sensor cartridge disk 1200 can include a center hole

1220, such as for receiving a spindle or other rotational drive mechanism. In an example, the center hole 1220 can be geared or keyed, such as to engage the rotational drive mechanism. The rotational drive mechanism can be used to rotate the sensor cartridge disk 1200, such as to advance individual sensing elements 100, e.g., one at a time, into a particular sensing location at which the blood glucose or other sample testing can be carried out, or for cleaning, or calibration, or for another desired purpose.

[0094] FIG. 13 shows an example of a blood glucose or other sensor assembly 1300, which includes a housing 1302, such as for carrying the rotatable sensor cartridge disk 1200. In an example, the housing 1302 can include a circular or other face portion 1304 and a body portion 1306 extending therefrom. In an example, the face portion 1304 can include a measurement output data display 1308, such as the circular display window shown in the center of the face portion 1304. In this example, the circular display 1308 window can be an LCD or other display, which, in FIG. 13 is shown as displaying a blood glucose concentration of 126 mg/dL. In an example, the face portion 1304 can also include a text display window 1310, such as for displaying one or more messages to the user, if needed. In an example, the body portion 1306 can include a user input device, such as one or more buttons 1312 for scrolling through a menu (e.g., displayed in the text display window 1310) or for selecting a displayed element of the menu. In the example shown in FIG. 13, the buttons 1312 can include directional arrows and a center "select" button, such as for allowing a user to manipulate the menu. In an example, the face portion 1304 can include an opening 1314, such as for exposing a particular sensing element 100 of the plurality of sensing elements 100 that can be distributed about the peripheral circumference of the sensor cartridge disk 1200. This allows the user to place a drop of blood (or other substance to be analyzed) onto the exposed sensing element 100, such as for glucose or other testing. In an example, the sensor cartridge disk 1200 automatically rotates after each measurement (or before each measurement, if desired).

[0095] FIG. 14 is a schematic drawing showing an example of the sensor assembly 1300, having opened a hinged cover 1402 portion of the face portion 1304 of the housing 1302, such that the rotatable sensor cartridge disk 1200 can be seen inside. In an example, the cover 1402 is affixed to a base 1404 portion of the face portion 1304, such as by a hinge 1406. In an example, a spindle 1408 can be used to rotate the sensor cartridge disk 1200. The cover 1402 can include the display 1308. The cover 1402 can also include the emitters 1203, such as for use in determining sensor positioning or identification using the holes 1202 in the sensor cartridge disk 1200 and underlying detectors 1205, such as described above. Electrical connections can be made between components on the cover 1402 and electronics in the housing 1302 or body portion 1306, such as via flex circuitry extending within or along the hinge 1406. [0096] FIG. 15 is a schematic drawing showing an example of a separate cleaning or calibration apparatus 1500, such as for cleaning or calibrating the sensor cartridge disk 1200. After all the sensing elements 100 on the sensor cartridge disk 1200 have been used, the sensor cartridge disk 1200 can be removed from the sensor assembly 1300 and placed into the cleaning or calibration apparatus 1500, such as shown in FIG. 15 (side view of the sensor cartridge disk 1200), in which the rotatable sensor cartridge disk 1200 has been placed upon the rotatable horizontal spindle 1502. The spindle 1502 can ride up and down (e.g., as shown in FIG. 15) upon a post 1504, and can be longitudinally translated left- to-right (e.g., as shown in FIG. 15), such as by respective corresponding actuators. In an example, the cleaning and calibration apparatus can include a linear arrangement of reservoirs, such as a cleaning solution reservoir 1506, a buffer solution reservoir 1508, a first calibration fluid reservoir 1510, and a second calibration fluid reservoir 1512. The sensor cartridge disk 1200 can be rotated upon the spindle 1502, such as to selectively sequentially expose the different sensing elements 100 to the fluid in a particular reservoir. The sensor cartridge disk 1200 can be raised and partially lowered into a particular reservoir, such as by actuating the post 1504. The sensor cartridge disk 1200 can be moved from reservoir-to-reservoir, such as by actuating lateral translation of the spindle 1502. In this way, the sensor cartridge disk 1200 can sequentially expose various sensing elements 100 to cleaning by a cleaning fluid in the cleaning solution reservoir 1506, then to rinsing by the buffer solution in the buffer solution reservoir 1508, then to calibration using a first calibration fluid in the first calibration fluid reservoir 1510, then to calibration using a second calibration fluid in the second calibration fluid reservoir 1512. The assembly 1500 can also include a cartridge cleaning mechanism 1514, such as to provide ultrasonic cleaning or rinsing (e.g., by inducing cavitation, agitation, or the like). [0097] In an example, the system can be simplified by using a common reservoir for staged introduction of the cleaning fluid, then the rinsing fluid, then the first calibration fluid, then the rinsing fluid, then the second calibration fluid, and then the rinsing fluid, such as similarly described above with respect to the simplified example using the belt 910. [0098] Although the above description particularly emphasized use of a low dielectric constant substrate for reducing the response time of performing the analyte measurement, one or more other techniques of reducing response time can be used, either additionally or alternatively. The response time of the analyte measurement can be affected by the diffusion or other transport of the analyte of interest to the sensing electrode 110, such as through the various sensor layers, such as the TBL 102, the noise reduction layer 104, or any filtration layer such as may be included in the noise reduction layer 104 or elsewhere.

[0099] In an example, such transport of the analyte of interest can be expedited, such as by applying an electric field or a physical force (e.g., to the sample), such as to urge the analyte of interest toward the sensing electrode 110, such as to reduce response time. In an example, such transport can be expedited by providing mechanical vibration, ultrasonic vibration, microwave vibration, or other vibration or agitation, such as to encourage diffusion or other transport of the analyte of interest toward the sensing electrode 110, such as to reduce response time. In an example, such transport can be expedited by applying a positive or vacuum pressure, such as to encourage transport of the analyte of interest toward the sensing electrode. In another example, such transport can be expedited by using one or more microfluidic channels, such as to transport the analyte of interest toward the sensing electrode, which can optionally use a microfluidic or other pump, such as for assisting such transport. [00100] In an illustrative example, each sensor element 100 can be reused for at least five blood glucose or other analyte measurements, and the sensor element 100 can be cleaned between such measurements. In an example, the sensor cartridge 210 includes at least seven sensing elements 100, such that each sensing element can be used one day per week, and then the sensor cartridge 210 (including all seven of the sensing elements 100) can be cleaned weekly. Because each sensing element can be used for at least five blood glucose measurements, the sensor cartridge can be used for at least a month (up to five weeks, or a total of 35 glucose measurements), with weekly cleanings, and then disposed of or returned to the manufacturer to be refurbished or recycled.

Additional Notes: The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention can be practiced. These embodiments are also referred to herein as "examples." Such examples can include elements in addition to those shown and described. However, the present inventors also contemplate examples in which only those elements shown and described are provided.

All publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference. In the event of inconsistent usages between this document and those documents so incorporated by reference, the usage in the incorporated reference(s) should be considered supplementary to that of this document; for irreconcilable inconsistencies, the usage in this document controls.

In this document, the terms "a" or "an" are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of "at least one" or "one or more." In this document, the term "or" is used to refer to a nonexclusive or, such that "A or B" includes "A but not B," "B but not A," and "A and B," unless otherwise indicated. In the appended claims, the terms "including" and "in which" are used as the plain-English equivalents of the respective terms "comprising" and "wherein." Also, in the following claims, the terms "including" and "comprising" are open-ended, that is, a system, device, article, or process that includes elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms "first," "second," and "third," etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.

Method examples described herein can be machine or computer- implemented at least in part. Some examples can include a computer-readable medium or machine-readable medium encoded with instructions operable to configure an electronic device to perform methods as described in the above examples. An implementation of such methods can include code, such as microcode, assembly language code, a higher-level language code, or the like. Such code can include computer readable instructions for performing various methods. The code may form portions of computer program products. Further, the code may be tangibly stored on one or more volatile or non-volatile computer-readable media during execution or at other times. These computer- readable media may include, but are not limited to, hard disks, removable magnetic disks, removable optical disks (e.g., compact disks and digital video disks), magnetic cassettes, memory cards or sticks, random access memories (RAMs), read only memories (ROMs), and the like. The above description is intended to be illustrative, and not restrictive.

For example, the above-described examples (or one or more aspects thereof) may be used in combination with each other. Other embodiments can be used, such as by one of ordinary skill in the art upon reviewing the above description. The Abstract is provided to comply with 37 C.F.R. §1.72(b), to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Also, in the above Detailed Description, various features may be grouped together to streamline the disclosure. This should not be interpreted as intending that an unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter may lie in less than all features of a particular disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate embodiment. The scope of the invention should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

CLAIMSWhat is claimed is:
1. An apparatus comprising: a reusable analyte sensor, comprising: an exposed surface, configured to receive a bolus of a substance from which a concentration of an analyte is to be determined; an electrode; an analyte sensing layer, in contact with the electrode, the analyte sensing layer configured to produce at the electrode a charge indicative of a concentration of the analyte; and wherein the sensor is reusable such that it is capable of receiving multiple separate boluses, comprising at least 5 boluses, over a period of time and capable of determining the concentration of the analyte in the multiple boluses.
2. The apparatus of claim 1, wherein the reusable analyte sensor comprises: a substrate, comprising a dielectric constant of less than 9; an electrically conductive path of the substrate; wherein the electrode is in contact with the conductive path; and a transport barrier layer, located between the analyte sensing layer and the exposed surface, the transport barrier layer configured to permit transport of the analyte across the transport barrier layer, wherein the transport barrier layer comprises a composite material including a polymer and nanoparticles incorporated into the polymer.
3. The apparatus of any of claims 1 or 2, comprising a noise reduction layer positioned between the analyte sensing layer and the exposed surface, the noise reduction layer configured to inhibit transport of a substance other than the analyte across the noise reduction layer.
4. The apparatus of any of claims 1 through 3, further comprising an ion- etched filtration layer positioned between the analyte sensing layer and the exposed surface, the ion-etched filtration layer configured to pass glucose therethrough.
5. The apparatus of any of claims 1 through 4, wherein the electrode comprises a working electrode, a counter electrode, and a reference electrode.
6. The apparatus of any of claims 1 through 5, wherein the analyte sensing layer comprises an enzyme configured to convert glucose received in the bolus of the substance into a byproduct, and wherein the electrode is configured to measure a concentration of the glucose received in the bolus of the substance by measuring a current indicative of a concentration of the byproduct.
7. The apparatus of claim 6, wherein the analyte sensing layer comprises an enzyme configured to convert glucose received in the bolus of the substance into gluconic acid and hydrogen peroxide, and wherein the electrode comprises a working electrode, a counter electrode, and a reference electrode configured to measure a concentration of the glucose received in the bolus of the substance by measuring a current indicative of a concentration of the hydrogen peroxide.
8. The apparatus of any of claims 6 or 7, wherein the enzyme comprises glucose oxidase.
9. The apparatus of any of claims 1 through 8, comprising a transport barrier layer including polyester with fumed silica nanoparticles incorporated into the polyester.
10. The apparatus of any of claims 1 through 9, comprising: a processor circuit, communicatively coupled to the sensor to receive information determined from a current of the electrode, and to determine, in response thereto, a concentration of the analyte in the bolus of the substance, the processor further configured to determine a reusability status of the sensor indicative of whether the sensor is capable of further reuse; and a user interface, communicatively coupled to the processor circuit, the user interface configured to provide to a user, in response to information provided by the processor circuit, an indication of the concentration of the analyte in the bolus of the substance.
11. The apparatus of claim 10, comprising a sensor cartridge, carrying the sensor, the sensor cartridge configured to be user-attachable and user-detachable from a housing comprising the user interface.
12. The apparatus of claim 11, wherein the sensor cartridge comprises a plurality of the sensors arranged to be interchangeably positionable for receiving boluses of the substance, and comprising an actuator configured to position the sensors.
13. The apparatus of claim 12, wherein a number of the sensors included in the sensor cartridge multiplied by a number of usable boluses per sensor exceeds 30.
14. The apparatus of any of claims 1 through 13, comprising a cleaning mechanism, configured to permit cleaning of the exposed surface of the sensor.
15. The apparatus of any of claims 1 through 14, further comprising a calibration circuit, configured to permit calibration of the sensor for determining the concentration of the analyte.
16. The apparatus of any of claims 1 through 15, further comprising a communication circuit, configured for communicating, from the apparatus to elsewhere, information about the concentration of the analyte.
17. A method of detecting an analyte, comprising: receiving a biological fluid sample contacting a reusable analyte sensor that it is configured for receiving multiple separate boluses, comprising at least 5 boluses, over a period of time and configured for determining the concentration of the analyte in the multiple boluses; measuring an amount of an analyte in the sample; and providing information about the amount to a user or automated process.
18. The method of claim 17, comprising: cleaning the sensor, sufficient to prepare the sensor for another cycle of using the same sensor for receiving the biological fluid sample, measuring the amount, and providing information about the amount.
19. The method of any of claims 17 through 18, wherein the measuring occurs in less than about 3 minutes.
20. The method of any of claims 17 through 19, wherein the measuring occurs in less than about 30 seconds.
21. The method of any of claims 17 through 20, wherein the measuring occurs in less than about 5 seconds.
22. The method of any of claims 17 through 21, further comprising before cleaning, contacting a second sensor with a biological fluid sample.
23. The method of any of claims 17 through 22, wherein cleaning the sensing region comprises cleaning more than one sensor.
24. The method of any of claims 17 through 23, wherein contacting, measuring, displaying and cleaning are repeated 50 or more times using the same sensor.
25. The method of any of claims 17 through 24, wherein contacting, measuring, displaying and cleaning are repeated 5000 or more times using the same sensor.
26. The method of any of claims 17 through 25, wherein measuring an amount of analyte in the sample comprises measuring an amount corresponding to a glucose concentration.
27. The method of claim 26, comprising converting glucose in the sample to gluconic acid and hydrogen peroxide using a glucose oxidase enzyme, and wherein measuring the amount corresponding to the glucose concentration comprises detecting a concentration of the hydrogen peroxide.
28. The method of any of claims 17 through 27, comprising receiving the biological fluid sample via a layer comprising a polymer and nanoparticles.
29. The method of any of claims 17 through 28, comprising interchangeably positioning multiple sensors for receiving multiple separate boluses of the biological fluid sample.
30. The method of any of claims 17 through 29, comprising calibrating the sensor before measuring the amount of the analyte in the sample.
31. The method of claim 30, comprising cleaning the sensor before the calibrating.
PCT/US2009/052539 2008-08-06 2009-08-03 Reusable analyte sensing system and methods WO2010017119A1 (en)

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Citations (4)

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Publication number Priority date Publication date Assignee Title
WO2005121355A1 (en) * 2004-06-04 2005-12-22 Medtronic Minimed, Inc. Analyte sensors and methods for making and using them
US20060076236A1 (en) * 2003-11-13 2006-04-13 Rajiv Shah Fabrication of multi-sensor arrays
US20070135698A1 (en) * 2005-12-13 2007-06-14 Rajiv Shah Biosensors and methods for making and using them
US20070227907A1 (en) * 2006-04-04 2007-10-04 Rajiv Shah Methods and materials for controlling the electrochemistry of analyte sensors

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060076236A1 (en) * 2003-11-13 2006-04-13 Rajiv Shah Fabrication of multi-sensor arrays
WO2005121355A1 (en) * 2004-06-04 2005-12-22 Medtronic Minimed, Inc. Analyte sensors and methods for making and using them
US20070135698A1 (en) * 2005-12-13 2007-06-14 Rajiv Shah Biosensors and methods for making and using them
US20070227907A1 (en) * 2006-04-04 2007-10-04 Rajiv Shah Methods and materials for controlling the electrochemistry of analyte sensors

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