US20150338369A1 - Sensor array mounted on flexible carrier - Google Patents

Abstract

A sensor apparatus is disclosed herein. The sensor apparatus includes a flexible carrier that is elongated along a length of the carrier. The sensor apparatus also includes a plurality of analysis zones carried by the carrier. The analysis zones are spaced-apart from one another along the length of the carrier. The sensor apparatus further includes first and second spaced-apart electrodes carried by the flexible carrier. The first and second electrodes have lengths that extend along the length of the carrier. At least one of the first and second electrodes includes analyte sensing chemistry. The first and second electrodes extending across and contact the plurality of analysis zones.

Description

• This application is being filed on 5 Jan. 2012, as a PCT International Patent application in the name of Pepex Biomedical, Inc., a U.S. national corporation, applicant for the designation of all countries except the US, and James L. Say, a citizen of the U.S., applicant for the designation of the US only, and claims priority to U.S. Provisional Application Ser. No. 61/430,393 filed Jan. 6, 2011, the subject matter of which is incorporated by reference in its entirety.
TECHNICAL FIELD
• The present disclosure relates generally to sensors. More particularly, the present disclosure relates to sensors for measuring bio-analyte concentrations in blood samples.
BACKGROUND
• Electrochemical bio-sensors have been developed for sensing (e.g., detecting or measuring) bio-analyte concentrations in fluid samples. For example, U.S. Pat. Nos. 5,264,105; 5,356,786; 5,262,035; 5,320,725; and 6,464,849, which are hereby incorporated by reference in their entireties, disclose wired enzyme sensors for sensing analytes, such as lactate or glucose. Wired enzyme sensors have been widely used in blood glucose monitoring systems adapted for home use by diabetics to allow blood glucose levels to be closely monitored. Other example types of blood glucose monitoring systems are disclosed by U.S. Pat. Nos. 5,575,403; 6,379,317; and 6,893,545.
SUMMARY
• One aspect of the present disclosure relates to a wired enzyme sensor system that allows for low cost manufacturing and facilitates miniaturization.
• Another aspect of the present disclosure relates to a wired enzyme sensor system conducive for continuous automated manufacturing using fiber sensor technology.
• A further aspect of the present disclosure relates to a sensor system that allows for enhanced manufacturing control to provide better accuracy and repeatability.
• Still another aspect of the present disclosure relates to a sensor system including a plurality of sample fluid analysis zones carried on an elongated, flexible dielectric carrier (e.g., a tape, sheet, film, web, layer, substrate, media etc.). The analysis zones are spaced-apart from one another along a length of the carrier and are separated from each other by gaps. Capillary flow promoting structures can be provided at each of the analysis zones for encouraging a sample fluid (e.g., blood) to flow into the analysis zone by capillary action. Two elongated electrodes extend along the length of the carrier. The electrodes each traverse the gaps between the analysis zones and contact each of the analysis zones. One of the electrodes can include a working electrode and the other of the electrodes can include a reference electrode or a counter/reference electrode. To test a fluid sample for an analyte concentration, one of the analysis zones is wetted with the fluid sample and the electrodes contacting the analysis zone are used to generate a reading indicative of the analyte concentration. After the analyte concentration has been determined and another sample is desired to be analyzed, the electrodes are severed at a location between the used analysis zone and the unused analysis zone(s) to electrically isolate the used analysis zone from the portions of the electrodes contacting the unused analysis zone(s). Thereafter, a reading can be taken at the next unused analysis zone. This process can be repeated until all of the analysis zones carried by the carrier have been used to test fluid samples.
• A variety of additional aspects will be set forth within the description that follows. The aspects can relate to individual features and to combinations of features. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the broad concepts upon which the embodiments disclosed herein are based.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a perspective view of a sensor array and flexible carrier in accordance with the principles of the present disclosure;
• FIG. 2 is a plan view of the sensor array and flexible carrier ofFIG. 1;
• FIG. 3 is a side view of the sensor array and flexible carrier ofFIG. 1;
• FIG. 4 shows a portion of a flexible carrier ofFIG. 1 with other components removed;
• FIG. 5 shows the sensor array and flexible carrier ofFIG. 1 incorporated into an analyte monitoring unit/system, the sensor array is being used to analyze a first blood sample at a first analysis zone;
• FIG. 6 shows the sensor array being used to analyze a second blood sample at a second analysis zone;
• FIG. 7 shows the sensor array being used to analyze a third blood sample at a third analysis zone;
• FIG. 8 shows the sensor array being used to analyze a fourth blood sample at a fourth analysis zone;
• FIG. 9 shows an analyte monitoring unit adapted for use with the sensor array and flexible carrier ofFIG. 1;
• FIG. 10 shows a drive gear of the analyte monitoring unit ofFIG. 9; and
• FIG. 11 shows a portion of the analyte monitoring unit ofFIG. 9 after the drive gear has been removed.
DETAILED DESCRIPTION
• Reference will now be made in detail to exemplary aspects of the present disclosure which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.
• The following definitions are provided for terms used herein:
• A “working electrode” is an electrode at which the analyte (or a second compound whose level depends on the level of the analyte) is electrooxidized or electroreduced with or without the agency of an electron transfer agent.
• A “reference electrode” is an electrode used in measuring the potential of the working electrode. The reference electrode should have a generally constant electrochemical potential as long as no current flows through it. As used herein, the term “reference electrode” includes pseudo-reference electrodes. In the context of the disclosure, the term “reference electrode” can include reference electrodes which also function as counter electrodes (i.e., a counter/reference electrode).
• A “counter electrode” refers to an electrode paired with a working electrode to form an electrochemical cell. In use, electrical current passes through the working and counter electrodes. The electrical current passing through the counter electrode is equal in magnitude and opposite in sign to the current passing through the working electrode. In the context of the disclosure, the term “counter electrode” can include counter electrodes which also function as reference electrodes (i.e., a counter/reference electrode).
• A “counter/reference electrode” is an electrode that functions as both a counter electrode and a reference electrode.
• An “electrochemical sensing system” is a system configured to detect the presence and/or measure the level of an analyte in a sample via electrochemical oxidation and reduction reactions on the sensor. These reactions are converted (e.g., transduced) to an electrical signal that can be correlated to an amount, concentration, or level of an analyte in the sample. Further details about electrochemical sensing systems, working electrodes, counter electrodes and reference electrodes can be found at U.S. Pat. No. 6,560,471, the disclosure of which is hereby incorporated herein by reference in its entirety.
• “Electrolysis” is the electrooxidation or electroreduction of a compound either directly at an electrode or via one or more electron transfer agents.
• An “electron transfer agent” is a compound that carries electrons between the analyte and the working electrode either directly or in cooperation with other electron transfer agents. One example of an electron transfer agent is a redox mediator.
• A “sensing layer” is a component of the sensor which includes constituents that facilitate the electrolysis of the analyte. The sensing layer may include constituents such as an electron transfer agent, a catalyst which catalyzes a reaction of the analyte to produce a response at the electrode, or both.
• FIGS. 1-4 illustrate asensor array20 in accordance with the principles of the present disclosure. Thesensor array20 includes a plurality of sample fluid analysis zones22a-22dcarried on an elongated, flexible dielectric carrier24 (e.g., a tape, sheet, film, web, layer, substrate, media etc.). The analysis zones are spaced-apart from one another along a length L of thecarrier24 and are separated from each other by gaps26a-26c.Twoelongated electrodes28,30 extend along the length L of thecarrier24. Theelectrodes28,30 each traverse the gaps between the analysis zones and contact each of the analysis zones. One of theelectrodes28,30 can include a working electrode and the other of theelectrodes28,30 can include a reference electrode or a counter/reference electrode.
• While, for illustration purposes, only four fluid analysis zones are shown atFIG. 1, it will be appreciated that in preferred embodiments many more than four analysis zones will be provided on each carrier. For example, in certain embodiments, at least 25, or at least 50, or at least 75, or at least 100 analysis zones can be provided on each carrier.
• Capillary flow promoting structures can be provided at each of the analysis zones for encouraging a sample fluid (blood) to flow into/across the analysis zone by capillary action. Capillary flow can be in a direction that extends across a width W of thecarrier24. As shown atFIGS. 1-3, capillaryflow promoting structures32 can be provided withinwells36 defined by thecarrier24 at each analysis zone. The capillaryflow promoting structures32 can include cast-in-place foam (e.g., open cell foam), ribbon filter media, capillary yearn or other capillary flow inducing material. The capillaryflow promoting structures32 can also include surface texturing provided on thecarrier24. The capillaryflow promoting structures32 can also include hematocrit filters.Indentations40 can be provided in the side of thecarrier24 at each of the analysis zones to provide a capillary flow director profile. Prior to use, the analysis zones are preferably dry and not electrically conductive.
• Thecarrier24 includes structures for mounting theelectrodes28,30 to the top side of thecarrier24. As shown atFIG. 4, such structures can includegrooves50 in which theelectrodes28,30 are affixed (e.g., adhesively affixed).
• As described later in the description, during use of thesensor array20 it is desirable to sever (i.e., break, disrupt, interrupt, cut) theelectrodes28,30 at the gaps. The electrodes can be mechanically severed or severed using other means such as a laser. A preferred method for severing the electrodes at the gaps is to use a punching process. To accommodate a punching process, punch holes60 are provided at each of the gaps. Theelectrodes28,30 traverse the punch holes60.
• Thecarrier24 is preferably made of a dielectric material and is preferably relatively flexible. In one embodiment, thecarrier24 can be wrapped in a cylinder having a diameter less than or equal to 3 inches without breaking. In another embodiment, thecarrier24 can be wrapped in a cylinder having a diameter less than or equal to 2 inches without breaking.
• In one embodiment, theelectrode28 is in contact with a sensing layer and functions as a working electrode and theelectrode30 can function as a reference/counter electrode. In other embodiments, separate working, reference and counter electrodes can be provided in fluid communication with the analysis zones. Theelectrodes28,30 are preferably threads, fibers, wires, or other elongated members.
• In one embodiment, the working electrode can include an elongated member that is coated or otherwise covered with a sensing layer and the reference/counter electrode can include any elongated member, such as a wire or fiber that is coated or otherwise covered with a layer, such as silver chloride. Preferably, at least a portion of each elongated member is electrically conductive. In certain embodiments, each elongated member can include a metal wire or a glassy carbon fiber. In still other embodiments, each elongated member can each have a composite structure and can include a fiber having a dielectric core surrounded by a conductive layer suitable for forming an electrode.
• A preferred composite fiber is sold under the name Resistat® by Shakespeare Conductive Fibers LLC. This composite fiber includes a composite nylon, monofilament, conductive thread material made conductive by the suffusion of about a 1 micron layer of carbonized nylon isomer onto a dielectric nylon core material. The Resistat® material is comprised of isomers of nylon to create the basic two layer composite thread. However, many other polymers are available for the construction, such as: polyethylene terephthalate, nylon 6, nylon 6,6, cellulose, polypropylene cellulose acetate, polyacrylonitrile and copolymers of polyacrylonitrile for a first component and polymers such as of polyethylene terephthalate, nylon 6, nylon 6,6, cellulose, polypropylene cellulose acetate, polyacrylonitrile and copolymers of polyacrylonitrile as constituents of a second component. Inherently conductive polymers (ICP) such as doped polyanaline or polypyrolle can be incorporated into the conductive layer along with the carbon to complete the formulation. In certain embodiments, the ICP can be used as the electrode surface alone or in conjunction with carbon. The Resistat® fiber is availability in diameters of 0.0025 to 0.016 inches, which is suitable for sensor electrodes configured in accordance with the principles of the present disclosure. Example patents disclosing composite fibers suitable for use in practicing sensor modules configured in accordance with the principles of the present disclosure include U.S. Pat. Nos. 3,823,035; 4,255,487; 4,545,835 and 4,704,311, which are hereby incorporated herein by reference in their entireties.
• The sensing layers provided at working electrodes of sensor modules configured in accordance with the principles of the present disclosure can include a sensing chemistry, such as a redox compound or mediator. The term redox compound is used herein to mean a compound that can be oxidized or reduced. Example redox compounds include transition metal complexes with organic ligands. Preferred redox compounds/mediators include osmium transition metal complexes with one or more ligands having a nitrogen containing heterocycle such as 2,2′-bipyridine. The sensing material also can include a redox enzyme. A redox enzyme is an enzyme that catalyzes an oxidation or reduction of an analyte. For example, a glucose oxidase or glucose dehydrogenase can be used when the analyte is glucose. Also, a lactate oxidase or lactate dehydrogenase fills this role when the analyte is lactate. In sensor systems, such as the one being described, these enzymes catalyze the electrolysis of an analyte by transferring electrons between the analyte and the electrode via the redox compound. Further information regarding sensing chemistry can be found at U.S. Pat. Nos. 5,264,105; 5,356,786; 5,262,035; and 5,320,725, which were previously incorporated by reference in their entireties.
• During sample analysis (e.g., blood analysis) at one of the analysis zones, a voltage can be applied through the analysis zone between theelectrodes28,30. When the potential is applied, an electrical current will flow through the fluid sample between theelectrodes28,30. The current is a result of the oxidation or reduction of an analyte, such as glucose, in the volume of fluid sample located within the analysis zone. This electrochemical reaction occurs via the electron transfer agent in the sensing layer and an optional electron transfer catalyst/enzyme in the sensing layer. By measuring the current flow generated at a given potential (e.g., with a controller described herein), the concentration of a given analyte (e.g., glucose) in the fluid sample can be determined. Those skilled in the art will recognize that current measurements can be obtained by a variety of techniques including, among other things, coulometric, potentiometric, perometric, voltometric, and other electrochemical techniques.
• Referring toFIG. 5, thesensor array20 andcarrier24 are shown incorporated as a sub-component of ananalyte monitoring unit120. Theunit120 includes a holder that houses a controller122. The housing can also include a holder that holds thesensor array20 andcarrier24. The housing can further include a drive arrangement for moving thecarrier24 to consecutively index the analysis zones to ause position80 defined by theunit120.
• In general, theunit120 includes thecontroller121, anactuator123, andinput lines125,127 extending fromcontacts128,130. The controller122 controls theactuator arrangement123 for disposable driving skin piercing members90 (e.g., needles, lancets, canulas or like structures) between the retracted and extended positions to obtain a fluid sample (e.g., a blood sample) at theuse position80. Thecontroller121 can include a microcontroller, a mechanical controller, software driven controller, a hardware driven controller, a firmware driven controller, etc. The controller can include a microprocessor that interfaces with memory.
• The input lines125,127 carry data/signals/readings (e.g., voltage values) generated between theelectrodes28,30 at a given one of the analysis zone being used during analysis of a fluid sample to thecontroller121 for analysis. Thecontroller121 converts the data/signals/reading to an analyte concentration level (e.g., a blood glucose reading) or other desired information. Thecontroller121 causes adisplay131 to indicate the processed information to the user. Other information also can be presented on thedisplay131. In one embodiment, thedisplay131 is a visual display. In other embodiments, an audio display also can be used. Additional information can be provided to theprocessor121 via a user interface129 (e.g., buttons, switches, etc.).
• In use of theunit120, thecarrier24 is indexed to align theanalysis zone22awith theuse position80 of the unit120 (seeFIG. 5). Askin piercing member90 is then loaded into the unit at theuse position80 and the person places their finger at theindentation40 corresponding to theanalysis zone22a.Theactuator123 then extends theskin piecing member90 causing a sample site at the finger in the form of a puncture wound. Blood from the sample site wets theanalysis zone22aand flows by capillary action across theanalysis zone22a.Thecontacts128,130 are placed in electrical contact with theelectrodes28,30 at thegap26a.Thecontroller121, via thelines125,127 andcontacts128,130, then causes a voltage to be applied between theelectrodes28,30 and across the wettedanalysis zone22a.Thecontroller121 then takes a reading and determines an analyte (e.g., glucose) concentration in the blood sample. Once the reading has been taken, theskin piercing member90 can be disposed of and the carrier is indexed such that theanalysis zone22band thegap26bare positioned at the use position80 (seeFIG. 6). In theuse position80, thecontacts128,130 engage theelectrodes28,30 at thegap26b.Also, thecontroller121 can actuate a punch which severs theelectrodes28,30 at thegap26asuch that the used/wettedanalysis zone22ais electrically isolated from the portions of theelectrodes28,30 traversing theunused analysis zones22b-22d.
• To analyze a second blood sample, a newskin piercing member90 is loaded into the unit and the process is repeated causing theanalysis zone22bto be wetted with the second blood sample. A voltage is then applied between theelectrodes28,30 and across theanalysis zone22band a reading is taken. Once the reading has been taken, theskin piercing member90 can be disposed of and the carrier is indexed such that theanalysis zone22cand thegap26care positioned at the use position80 (seeFIG. 7). In the use position, thecontacts128,130 engage theelectrodes28,30 at thegap26c.Also, thecontroller121 can actuate a punch which severs theelectrodes28,30 at thegap26bsuch that the used/wettedanalysis zone22bis electrically isolated from the portions of theelectrodes28,30 traversing theunused analysis zones22c-22d.
• To analyze a third blood sample, a newskin piercing member90 is loaded into the unit and the process is repeated causing theanalysis zone22cto be wetted with the third blood sample. A voltage is then applied between theelectrodes28,30 and across theanalysis zone22cand a reading is taken. Once the reading has been taken, theskin piercing member90 can be disposed of and the carrier is indexed such that theanalysis zone22dand the gap26dare positioned at the use position80 (seeFIG. 8). In the use position, thecontacts128,130 engage theelectrodes28,30 at the gap26d.Also, thecontroller121 can actuate a punch which severs theelectrodes28,30 at thegap26csuch that the used/wettedanalysis zone22cis electrically isolated from the portions of theelectrodes28,30 traversing theunused analysis zones22d.Analysis zone is then ready for use as described above. Moreover, it will be appreciated that the process can be consecutively repeated until all of the analysis zones on the carrier have been used. Thereafter, thecarrier24 can be disposed of and replaced with a like carrier having unused analysis zones.
• FIGS. 9-11 show a hand-heldanalyte monitoring unit200 that can be used with thesensor array20 andcarrier24 ofFIG. 1. Theunit200 includes amain housing202 in which a controller can be housed. Themain housing202 can also include an indexing drive. A display and a user interface can be provided on the back side of themain housing202. Themain housing202 includes a use location80 (i.e., a sampling location) defining arear receptacle204 for mounting a skin piercing member actuator. The skin piercing member actuator is adapted to extend a skin piercing member through anopening206 at theuse location80. Theunit200 also includes adrive gear210 that mounts on themain housing202 and is rotated by the indexing drive to index thecarrier24 to consecutively move unused analysis zones to theuse location80. Thedrive gear210 includes an innercylindrical surface212. Thecarrier24 is rolled/wrapped in a cylinder and secured to thecylindrical surface212. The drive gear/drive ring can be disposable and the carrier can be pre-attached to the drive gear at the manufacturing facility or elsewhere before purchase by a consumer.
• In alternative embodiments, only one of theelectrodes28,30 may be severed to isolate used/spent analysis zones from unused analysis zones. By severing at least one of theelectrodes28,30 at a gap between the used/spent analysis zone and the unused analysis zones, a voltage/potential is prevented from being applied across the used/spent analysis zone when a subsequent analysis zone is being used to analyze a fluid sample.

Claims (9)

1. A sensor apparatus comprising:

a flexible carrier that is elongated along a length of the carrier;

a plurality of analysis zones carried by the carrier, the analysis zones being spaced-apart from one another along the length of the carrier; and

first and second spaced-apart electrodes carried by the flexible carrier, the first and second electrodes having lengths that extend along the length of the carrier, at least one of the first and second electrodes including analyte sensing chemistry, the first and second electrodes extending across and contacting the plurality of analysis zones.

2. The sensor apparatus ofclaim 1, wherein the plurality of analysis zones are formed by recesses in the flexible carrier, the recesses being positioned below the first and second electrodes.

3. The sensor apparatus ofclaim 2, wherein the recesses extend across a width of the carrier.

4. The sensor apparatus ofclaim 3, wherein the plurality of analysis zones include capillary flow enhancing structures positioned within the recesses for encouraging capillary flow across the width of the carrier.

5. The sensor apparatus ofclaim 4, further comprising punch holes defined through the carrier at a location between the analysis zones, wherein the electrodes extend across the punch holes.

6. The sensor apparatus ofclaim 4, wherein the carrier includes a side surface defining indentations at each of the analysis zones.

7. The sensor apparatus ofclaim 1, wherein the carrier defines grooves in which the first and second electrodes are mounted.

8. A method for using the sensor apparatus ofclaim 1, the method comprising:

wetting a first analysis zone of the plurality of analysis zones with a first volume of sample fluid;

taking a first reading at the first analysis zone by applying a first voltage across the wetted first analysis zone and between the first and second electrodes;

wetting a second analysis zone of the plurality of analysis zones with a second volume of the sample fluid;

taking a second reading at the second analysis zone by applying a second voltage across the wetted second analysis zone and between the first and second electrodes;

preventing a voltage from being applied across the first wetted analysis zone when the second reading is being taken at the wetted second analysis zone by severing at least one of the first and second electrodes at a location between the wetted first analysis zone and the wetted second analysis zone.

9. The method ofclaim 8, wherein the analysis zones are non-conductive until the analysis zones are wetted.

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