WO2021138405A1

WO2021138405A1 - Temperature compensated biosensors and methods of manufacture and use thereof

Info

Publication number: WO2021138405A1
Application number: PCT/US2020/067442
Authority: WO
Inventors: Harvey B. Buck; Michael J. Celentano
Original assignee: Roche Diabetes Care, Inc.; F. Hoffman-La Roche Ag; Roche Diabetes Care Gmbh
Priority date: 2019-12-30
Filing date: 2020-12-30
Publication date: 2021-07-08

Abstract

An analyte test sensor strip having a heating electrode thereon, as well as a method of manufacture and a method of use. The method of manufacturing a test strip having first and second sides, a sample receiving end and a meter insertion end comprises providing a base substrate material having first and second edges. An electrode set including a heating element is formed on the base substrate material. A stripe of reagent material is applied to the base substrate material and covering at least one electrode of the electrode set with the stripe, the stripe being oriented substantially parallel to the first substrate edge. A spacing material is laminated on top of the base substrate material and provides a cavity in the spacing material such that the electrode set is received within the cavity and the cavity at least partially defines a sample receiving chamber.

Description

TEMERATURE COMPENSAETD BIOSENSORS AND METHODS OF MANUFACTURE AND USE THEREOF

FIELD OF THE INVENTION

[001] The present disclosure relates generally to an analyte test sensor for use in measuring concentrations of an analyte in a biological fluid and, more particularly, to an analyte test strip having a heating element formed thereon.

BACKGROUND

[002] Biosensors provide an analysis of a biological fluid, such as whole blood, urine, or saliva. Measuring the concentration of substances in biological fluids is an important tool for the diagnosis and treatment of many medical conditions. For example, the measurement of glucose in body fluids, such as blood, is crucial to the effective treatment of diabetes. The sample of biological fluid may be directly collected or may be a derivative of a biological fluid. Typically, biosensors have a non-disposable measurement device or test meter that is used to analyze the sample of biological fluid that is placed on the test strip.

[003] Many biosensor systems use an electrochemical enzymatic sensor which is susceptible to ambient and sample temperatures due to the temperature dependence of the electrochemical measurement process, which is diffusion dependent, and the temperature dependence of the enzymatic reaction. The difference in response of the sensor is often similar to the difference which is measured at different analyte concentrations, rendering the estimation of analyte from the sensor response inaccurate. Furthermore, small scale evaporative effects after sample application can significantly reduce the reaction temperature in short periods of time.

[004] Thus, a biosensor which is able to compensate for low temperatures and method of producing and using the biosensor are needed. SUMMARY

[005] One aspect of the present disclosure includes a method of manufacturing a test strip having first and second sides, a sample receiving end and a meter insertion end, the method comprises providing a base substrate material having first and second edges, forming an electrode set on the base substrate material, the electron set comprising a working electrode, a counter electrode and a heating electrode, the heating electrode having a resistive filament, applying a stripe of reagent material to the base substrate material and covering at least one electrode of the electrode set with the stripe, the stripe being oriented substantially parallel to the first substrate edge, laminating a spacing material on top of the base substrate material and providing a cavity in the spacing material such that the electrode set is received within the cavity and the cavity at least partially defines a sample receiving chamber, and cutting a test strip from the laminated web produced from the steps. The cutting process defining the first and second sides of the test strip, wherein the test strip comprises a reagent layer extending to the first and second sides of the test strip under the spacing layer.

[006] In at least one embodiment of the present disclosure, the step of forming the electrode set comprises removing a pre-determined pattern from a conductive layer on the base substrate material with laser ablation.

[007] In at least one embodiment of the present disclosure, the step of forming the electrode set comprises a single pass deposition of the electrode set.

[008] In at least one embodiment of the present disclosure, the resistive filament may be adjacent to the stripe of reagent, or at least partially covered by the stripe of reagent.

[009] In at least one embodiment of the present disclosure, the heating electrode is connected to the counter electrode.

[0010] In at least one embodiment of the present disclosure, the method further includes aligning and then laminating a web of covering layer material over the web of base substrate and spacing material.

[0011] In at least one embodiment of the present disclosure, the resistive filament has a resistance of about 200 to about 870 ohms.

[0012] An additional aspect of the present disclosure is directed towards a test strip.

In at least one embodiment, the test strip comprises a base substrate having a working electrode, a counter electrode, and a heating electrode formed thereon and having two opposite side edges and an end edge. The embodiment of the test strip also includes a spacing layer overlying the base substrate and having a void that at least partially defines a sample receiving chamber, a covering layer overlying the spacing layer, and a reagent layer disposed in the sample-receiving chamber and covering a portion of the base substrate and at least one of the electrodes. The reagent layer extends under the spacing layer to the two side edges of the base substrate and is sandwiched between the spacing layer and the base substrate. The heating electrode comprises a resistive filament proximal to the end edge of the base substrate. [0013] In at least one embodiment of the test strip of the present disclosure, the heating electrode is proximal to but not covered by the reagent layer.

[0014] In at least one embodiment of the test strip of the present disclosure, the heating electrode is at least partially covered by the reagent layer.

[0015] In at least one embodiment of the test strip of the present disclosure, the heating electrode is positioned in relation to an electrochemical sensor defined by the working electrode, the counter electrode and the reagent layer so as to raise the temperature at the electrochemical sensor by at least one degree Celsius when the heating element is active for at least one second.

[0016] In at least one embodiment of the test strip of the present disclosure, the heating electrode is connected to the counter electrode.

[0017] In at least one embodiment of the test strip of the present disclosure, the resistive filament has a resistance of about 200 to about 870 ohms.

[0018] An additional embodiment of the present disclosure is directed towards a method for measuring a concentration of an analyte in a sample of fluid. In at least one embodiment, the method comprises providing a test meter and providing a test strip. The test strip comprises a base substrate having a working electrode, a counter electrode, and a heating electrode formed thereon and having two opposite side edges and an end edge; a spacing layer overlying the base substrate and having a void that at least partially defines a sample-receiving chamber. Further, the covering layer overlays the spacing layer and the reagent layer is disposed in the sample-receiving chamber and covering a portion of the base substrate and at least one of the electrodes, the reagent layer extends under the spacing layer to the two side edges of the base substrate and being sandwiched between the spacing layer and the base substrate. In at least one embodiment of the method, the heating electrode comprises a resistive filament proximal to the end edge of the base substrate. The method further comprises, receiving the test strip into the test meter, connecting the working electrode, the counter electrode, and the heating electrode with the test meter; applying radiative heating to the reagent layer by applying current from the test meter to the heating electrode; and determining an attribute associated with test strip as a function of a measurement associated with at least the resistance value associated with the unique resistive path.

[0019] In at least one embodiment of a method for measuring a concentration of an analyte, the method further comprises the step of monitoring the temperature at the test strip by the test meter and initiating by the test meter the radiative heating by the heating electrode if the temperature is below a pre-determined threshold. In at least one embodiment, the predetermined threshold is 10°C or 6°C.

[0020] In at least one embodiment of a method for measuring a concentration of an analyte, the method further comprising the step of monitoring the temperature at the test strip by the test meter and initiating by the test meter the radiative heating by the heating electrode if the temperature is between 4°C and 10°C.

[0021] In at least one embodiment of a method for measuring a concentration of an analyte, wherein applying current from the test meter to the heating electrode is for a pre-set period of time. The pre-set time in at least one embodiment is between 0 and 5 seconds or between 0 and 30 seconds

[0022] In at least one embodiment of a method for measuring a concentration of an analyte, the method further comprises determining a time period for applying current from the test meter to the heating electrode using a thermistor in the test meter. In at least one embodiment, the thermistor in the test meter may be used to determine a voltage to apply from the test meter to the heating electrode.

[0023] In at least one embodiment of a method for measuring a concentration of an analyte, the method further comprises measuring a relative temperature on the test strip. The step of measuring the relative temperature in at least one embodiment comprises measuring the resistance trace of the heating electrode and converting the trace to a localized temperature.

[0024] In at least one embodiment of a method for measuring a concentration of an analyte, the step of applying radiative heat raises the localized temperature by at least 1°C, at least 2°C, at least 3°C, at least 4°C, or at least 5°C. The step of applying radiative heat in at least one embodiment raises the localized temperature by between 1°C and 5 °C, between 1°C and 10°C, or between 1°C and 20°C.

[0025] The various other features that characterize the embodiment of the disclosure are pointed out with particularity in the attached claims. For a better understanding of the disclosure, its advantages, and objectives obtained therefrom, reference should be made to the drawings and to the accompanying description, in which there is illustrated and described embodiments of the disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS [0026] The embodiments set forth in the drawings are illustrative and exemplary in nature and not intended to limit the subject matter defined by the claims. The following detailed description of the illustrative embodiments can be understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which:

[0027] FIG. 1 schematically illustrates a test strip inserted into a test meter;

[0028] FIG. 2 is an exploded view of a representative test strip;

[0029] FIG. 3 schematically illustrates a test strip for use in measuring the concentration of an analyte of interest in a biological fluid;

[0030] FIGs. 4a-c schematically illustrate at least one embodiment of a test strip with a heating filament positioned proximal to the reagent layer;

[0031] FIGs. 4d-e schematically illustrate a section of the test strip containing the reagent layer, according to at least one embodiment of the present disclosure;

[0032] FIG. 5 is a process flow diagram for a method of producing a test strip according to at least one embodiment of the present disclosure; and

[0033] FIG. 6 is a flow diagram of a representative process used to measure an analyte in a biological fluid.

DETAILED DESCRIPTION

[0034] For the purposes of promoting an understanding of the principles of the disclosure, reference will now be made to the embodiments illustrated in the drawings, and specific language will be used to describe that embodiment. It will nevertheless be understood that no limitation of the scope of the embodiments of the disclosure is intended. Alterations and modifications in the illustrated device, and further applications of the principles of the embodiments as illustrated therein, as would normally occur to one skilled in the art to which the embodiments relate are contemplated, are desired to be protected. In particular, although at least some of the embodiments of the disclosure are discussed in terms of a blood glucose meter, it is contemplated that the embodiments can be used with devices for measuring other analytes and other sample types. Such alternative embodiments may require certain adaptations to the embodiments discussed herein that would be obvious to those skilled in the art.

[0035] Embodiments of the present disclosure involve test sensors as well as methods of manufacture and use of the sensors. The sensors have incorporated a resistive filament on the same surface of the sensor as is used for enzymatic reactions and the electrochemical detection. The filament and the conductive traces to the filaments can be formed as part of the process of forming the electrodes and conductors which are used for the electrochemical process, thus incurring no or little additional cost. In at least one embodiment, the filament is located in the region of the electrochemical reaction, to most efficiently heat and/or measure the desired areas.

[0036] Referring to FIG. 1, a concentration measuring device or test meter 10 is disclosed with an analyte test sensor strip 12 mounted thereto that is used to measure the presence or concentration of an analyte in a biological fluid, such as whole blood, urine, or saliva. In this form, the test strip 12 is removably inserted into a connection terminal 14 of the test meter 10. Upon insertion of the test strip 12, the test meter 10 is configured to automatically turn on and begin the measuring process, as set forth in greater detail below. The test meter 10 includes an electronic display 16 that is used to display various types of information to the user including the test results. [0037] Referring to FIG. 2, a general test strip 12 is illustrated for background purposes and includes several components. The test strip 12 comprises a small body defining a chamber in which the sample fluid is received for testing. This sample-receiving chamber is filled with the sample fluid by suitable means, preferably by capillary action, but also optionally assisted by pressure or vacuum. The sample-receiving chamber includes electrodes and chemistry suitable for producing an electrochemical signal indicative of the analyte in the sample fluid.

[0038] In this illustrated form, the test strip 12 includes a base substrate 20, a spacing layer 22 and a covering layer 24 comprising body cover 26 and chamber cover 28. The spacing layer 22 includes a void portion 30 to provide a sample receiving chamber extending between the base substrate 20 and the covering layer 24. The base substrate 20 carries an electrode system 32 including a plurality of electrodes 34 and electrode traces 36 terminating in contact pads 38. The electrodes 34 are defined as those portions of the electrode traces 36 that are positioned within the sample-receiving chamber. A suitable reagent system 40 overlies at least a portion of the electrodes 34 within the sample-receiving chamber.

[0039] The body cover 26 and the chamber cover 28 overlying the spacing layer 22 define a slot therebetween, the slot defining a vent opening communicating with the sample receiving chamber to allow air to escape the chamber as a sample fluid enters the chamber from the edge opening or fluid receiving opening. The test strip 12 therefore includes a dosing end 42 and a meter insertion end 44. The shape of the dosing end 42 is typically distinguishable from the meter insertion end 44 so as to aid the user. The body cover 26 and chamber cover 28 are preferably secured to the spacing layer 22 by an adhesive layer 46. Further, a second adhesive layer 48 secures the spacing layer 22 to the base substrate 20. A more detailed discussion of the test strip 12 illustrated in FIG. 2 can be found in commonly owned U.S. Patent No. 7,829,023, which is hereby incorporated by reference in its entirety. [0040] Referring to FIG. 3, a more detailed image of an embodiment of a test strip 50 that is configured for use with the test meter 10 is illustrated having spacer, covering and adhesive layers removed to reveal the electrode system 32 of the test strip 50. The test strip 50 includes a non-conductive base substrate 52 having formed thereon a plurality of electrodes, traces and contact pads, as will be discussed in greater detail below. Such formation may be achieved by using any of a number of known techniques, such as screen printing, lithography, laser scribing or laser ablation. For purposes of illustration, formation using a broad field laser ablation technique is generally described herein.

[0041] Prior to formation of the electrodes, traces and contact pads, the non- conductive substrate is coated on its top surface with a conductive layer (by sputtering or vapor deposition, for example). The electrodes, traces and contact pads are then patterned in the conductive layer formed on the non-conductive substrate by a laser ablation process using a mask defining the desired design for the electrical aspects of the test strip. A more detailed discussion of the laser ablation process is set forth in commonly owned U.S. Patent No. 7,601,299, which is hereby incorporated by reference in its entirety.

[0042] The conductive layer may contain pure metals or alloys, or other materials, which are metallic conductors. The conductive material is generally absorptive at the wavelength of the laser used to form the electrodes, traces and contact pads on the non- conductive substrate 52. Non-limiting examples include aluminium, carbon, copper, chromium, gold, indium tin oxide, palladium, platinum, silver, tin oxide/gold, titanium, mixtures thereof, and alloys or metallic compounds of these elements. Various embodiments of the conductive layer may also contain bi-layers of conductors described herein. In at least one embodiment, the bi-layer comprises gold and palladium. In some embodiments, the conductive material includes noble metals or alloys or their oxides.

[0043] The test strip 50 includes a working electrode 54, a working sense trace 56, a counter electrode 58, and a counter sense trace 60 formed on the non-conductive substrate 52. The test strip 50 includes a distal end or reaction zone 62 and a proximal end or contact zone 64 extending along a longitudinal axis. As set forth in greater detail below, the test strip 50 includes a working electrode trace 54a that is used to connect the working electrode 54 to a contact pad 70. Further, the test strip 50 includes a counter electrode trace 58a that is used to connect the counter electrode 58 to a contact pad 80. As illustrated, the proximal end 64 of the test strip 50 includes a plurality of contact pads that are configured to be conductively connected with the connection terminal 14 of the test meter 10. In one form, the test meter 10 is configured to determine the type of test strip 50 inserted into the test meter 10 based on the configuration, including, e.g., any interconnection, of the contact pads. The distal end 62 of the test strip 12 includes a reagent layer 66 that covers at least a portion of the working electrode 54 and counter electrode 58.

[0044] The reagent layer 66 of the test strip 50 may comprise reagents of a chemical or biochemical nature for reacting with a target analyte to produce a detectable signal that represents the presence and/or concentration of the target analyte in a sample. The term "reagent", as used herein, is a chemical, biological or biochemical reagent for reacting with the analyte and/or the target to produce a detectable signal that represents the presence or concentration of the analyte in the sample. Suitable reagents for use in the different detection systems and methods include a variety of active components selected to determine the presence and/or concentration of various analytes, such as glucose for example. The selection of appropriate reagents is well within the skill in the art. As is well known in the art, there are numerous chemistries available for use with each of various targets. The reagents are selected with respect to the target to be assessed. For example, the reagents can include one or more enzymes, co-enzymes, and co-factors that can be selected to determine the presence of glucose in blood.

[0045] The reagent chemistry may include a variety of adjuvants to enhance the reagent properties or characteristics. For example, the chemistry may include materials to facilitate the placement of the reagent composition onto the test strip 50 and to improve its adherence to the strip 50, or for increasing the rate of hydration of the reagent composition by the sample fluid. Additionally, the reagent layer can include components selected to enhance the physical properties of the resulting dried reagent layer 66, and the uptake of a liquid test sample for analysis. Examples of adjuvant materials to be used with the reagent composition include thickeners, viscosity modulators, film formers, stabilizers, buffers, detergents, gelling agents, fillers, film openers, coloring agents, and agents endowing thixotropy.

[0046] As further illustrated in FIG. 3, a proximal end 68 of the working electrode trace 54a is connected with a working electrode measurement contact pad 70. A distal end 72 of the working electrode trace 54a is connected with the working electrode 54. A proximal end 74 of the working sense trace 56 is connected with a working sense measurement contact pad 75. As further illustrated, a distal end 76 of the working sense trace 56 is connected with the distal end 72 of the working electrode trace 54a thereby defining a working resistance loop.

[0047] In one form, the working resistance loop has a resistance value within a predetermined range of resistance values, which range corresponds to an attribute of the test strip 12. Forming the working resistance loop to have a resistance value that falls within one or another predetermined range of resistance values is within the ordinary skill in the art of forming thin conductive layers. Nevertheless, for purposes of illustration, it is known that conductive materials, such as thin layers of metals such as gold and palladium, have a characteristic sheet resistance dependent upon the thickness of the conductive layer. Sheet resistance is essentially a multiplier for calculating a predicted resistance through a path of a particular configuration (e.g. length and width) for a particular material of a particular thickness. Thus, sheet resistance and/or the configurational aspects of the conductive trace can be altered in order to achieve a desired resistance through a particular path, such as the working resistance loop.

[0048] Thus, for example, a gold layer having a thickness of 50 pm has a sheet resistance of 1.6 ohms/square. A "square" is a unitless measure of the aspect ratio of the conductive path, broken down into the number of square sheets (based on the width) that can be actually or theoretically determined in the conductive path. In one sense, the effective surface area of the conductive path is approximated as a number of squares. The number of squares that can be determined in the conductive path is multiplied by the sheet resistance to give a calculation for a predicted resistance through that conductive path.

[0049] In the context of the present disclosure, illustrative and exemplary embodiments will typically be described in the context of 50 pm thick layers of gold, thus a sheet resistance of 1.6 ohms/square. Thus, in order to manipulate the resistance along any conductive paths being described in the various contexts of this disclosure (as will be clear to persons of ordinary skill in the art), one may alter the length or width of the conductive path (thus change the number of "squares") or one may alter the thickness or material of the conductive layer (thus changing the sheet resistance) in order to increase or decrease a predicted resistance value for that particular conductive path to fall within a desired range of resistance values, wherein the range of such values is indicative of an attribute of the test strip. Determining the number of squares for a particular conductive path in a variety of patterns and configurations other than generally straight line paths is within the ordinary skill in the art and requires no further explanation here.

[0050] As will be further described, actual measured resistance values through variously identified conductive paths included in the embodiments of the present disclosure are used in various manners for purposes of indicating one or more attributes of a test strip. In this regard, it will be understood that the measured resistance values, or predetermined ranges of resistance values in which a measured resistance value lies, or ratios of the measured resistance values between different conductive paths, may correspond to a particular attribute. Which of these manners is employed for corresponding the resistance value of a conductive path to an attribute is within the discretion of the person of ordinary skill in the art.

[0051] Generally, the measured resistance value itself is useful in the event the actual, measured resistance value closely corresponds to the predicted resistance value (calculated as described above). If manufacturing tolerances are such that the measured value does not correspond well to the predicted value, then it may be advisable to predetermine a range of resistance values within which a conductive path having a certain predicted resistance value will almost certainly have a measured resistance value. In that case, the system measures the actual resistance value of a conductive path, identifies the predetermined the range within which the resistance value lies, and corresponds that identified predetermined range with the attribute of the test strip. Finally, if manufacturing tolerances are simply not conducive to accurately predicting the actual measured resistance value for a conductive path, or simply as desired, it may be useful to ratio one measured resistance value against another measured resistance value through a different conductive path, in order to determine an essentially normalized value. The normalized value may be used similarly as a measured resistance value or compared against one or more predetermined ranges of values in order to identify a corresponding attribute of the test strip. It is generally in this context of measured, predicted, and normalized resistance values that the present disclosure will be further described and understood.

[0052] For illustrative purposes only, in one form the working resistance loop has a resistance value of approximately 380.8 Ohms. (In this illustrative form, it is assumed that 50 hih thick gold is used to form the traces and contact pads and that the surface area associated with the traces and contact pads of the working resistance loop equates to approximately 238 squares. As such, the working resistance loop has a resistance value of approximately 380.8 Ohms.) In one embodiment, this resistance value is within a predetermined range, e.g. 250- 450 Ohms, and corresponds to an attribute such as the strip type, i.e. a reagent deposited on the strip that is configured for determination of glucose concentration. By way of example, a different predetermined range, e.g. 550-750 Ohms, for the resistance value of the working resistance loop may correspond to a different strip type, such as for determination of ketone concentration. As with all forms, and as described above, the resistance value of the working resistance loop as well as all resistance values disclosed herein can be adjusted by various methods, such as, for example, by adjusting the length, width, and thickness of the working sense trace 56 as well as the material from which the working sense trace 56 is manufactured. See, for example, U.S. Patent No. 7,601,299, the disclosure of which is hereby incorporated by reference herein.

[0053] A proximal end 78 of the counter electrode trace 58a is connected with a counter electrode measurement contact pad 80. A distal end 82 of the counter electrode trace 58a is connected with the counter electrode 58. In addition, a proximal end 84 of the counter sense trace 60 is connected with a counter sense measurement contact pad 86. A distal end 88 of the counter sense trace 60 is connected with the distal end 82 of the counter electrode trace 58a thereby defining a counter resistance loop. In one form, the counter resistance loop has a resistance value within a predetermined range of resistance values, which range corresponds to an attribute of the test strip 50. For illustrative purposes only, in one form the counter resistance loop has a resistance value of approximately 384 Ohms, based on a 50 pm thick layer of gold and a surface area configuration of approximately 240 squares. In one embodiment, this resistance value is within a predetermined range, e.g. 250-450 Ohms, which range corresponds to an attribute of the test strip. In other embodiments, the resistance value of the working resistance loop is ratioed with the resistance value of the counter resistance loop wherein the ratio value corresponds to an attribute of the strip, such as strip type or geographic market of distribution. [0054] As will be generally understood, designating an electrode as a "working" or

"counter" electrode is merely an indication of a particular predetermined functionality or intended use for an electrode during an electrochemical measurement method as either an anode or cathode in the presence of a particular electrical field or applied potential. Those of ordinary skill in the art will similarly understand reference to such electrodes generically as first and second measurement electrodes (and corresponding traces, sense traces, contact pads, etc.), inasmuch as such electrodes participate in the measurement of a particular analyte or target, in contrast to, for example, electrodes that may be specifically designated solely for use as dose detecting and/or sample sufficiency electrodes according to known techniques; see, for example, U.S. Patent No. 7,905,997, the disclosure of which is hereby incorporated herein by reference. In view of these understandings, the designations "working" and "counter" are used solely for contextual illustration and description, and are not intended to limit the scope of the present disclosure, whether or not recited in the claims, to a particular measurement electrode functionality.

[0055] In at least one embodiment, test strip 12 may also comprise one or more heating electrode, also referred to herein as a “resistive filament.” Exemplary embodiments of heating electrodes can be seen in FIGs. 4a-c. Heating electrode 410, may include one or more electrodes sufficient to raise the local temperature at the reagent layer 62. The border of reagent layer 62 is depicted by a dashed line. Heating electrodes 410 may be adjacent to the strip of reagent, covered by the stripe of reagent, or both. Additionally, in at least one embodiment heating electrodes 410 may be connected to heating electrode trace 420 which is then connected to heating electrode contact pad 430. Alternately, in at least one embodiment, heating electrode 410 may be connected to counter electrode 440 or working electrode 450. In at least one embodiment, working electrode 450, working electrode contact pad 455 and counter electrode contact pad 445 are also depicted.

[0056] The composition of heating electrode 410 in at least one embodiment is the same as those described for the working and counter electrodes described herein. Heating electrode 410 has the characteristic of being able to radiate heat in proximity to the reagent layer 62. The radiative heat from heating electrode 410 is substantially greater than that emitted by the other electrode traces of test strip 50. In at least one embodiment, heating electrode 410 is substantially thinner than the working electrode 450 or counter electrode 440. In at least one embodiment, the heating electrode 410 has a width of less than half that of the working electrode 450 or counter electrode 440. In at least one embodiment, the heating electrode 410 has a width of less than a third that of the working electrode 450 or counter electrode 440. In at least one embodiment, the heating electrode 410 has a width of less than one quarter that of the working electrode 450 or counter electrode 440.

[0057] Referring to FIG. 4d, an embodiment of the section of test strip 50 having reaction layer 62 is displayed. Heating element 410 in this embodiment is connected to the rear counter electrode and is covered by the reaction layer 62. Two possible edges of the reaction layer are denoted by dashed lines 64.

[0058] Referring to FIG, 4e, an additional embodiment of the section of test strip 50 having reaction layer 62 is displayed. Heating element 410 is positioned such that counter electrode 440 is between the heating electrode 410 and working electrode 450. Two possible edges of the reaction layer are denoted by dashed lines 64. Depending on the choice of edges of the reaction layer, heating element 410 is just within the reaction zone (covered by the reaction layer), or just outside the reaction zone.

[0059] Referring to FIG. 5, an embodiment of a method of manufacturing a test strip according to the present disclosure is shown. The method 500 of manufacturing a test strip 12 includes providing a base substrate material having first and second edges (step 510). On the base substrate, an electrode set is formed using one of the methods described herein (step 520). The electrode set comprising a working electrode, a counter electrode and a heating electrode, the heating electrode having a resistive filament. A stripe of an embodiment of the reagent material is then applied to the base substrate material covering at least one electrode of the electrode set (exemplary step 530). In at least one embodiment, the stripe is oriented substantially parallel to the first substrate edge. Method 500 also includes laminating a spacing material on top of the base substrate material and providing a cavity in the spacing material such that the electrode set is received within the cavity and the cavity at least partially defines a sample receiving chamber (exemplary step 540). To separate the individual test strips, the test strips are cut from the laminated web produced from method 500 (step 550). The exemplary cutting step 550 defines the first and second sides of the test strip, wherein the test strip comprises a reagent layer extending to the first and second sides of the test strip under the spacing layer. Optionally, the method may further comprise aligning and then laminating a web of covering layer material over the web of base substrate and spacing material in step 560.

[0060] According to at least one embodiment of method 500, the manufacture of an embodiment of a test strip involves the creation of a multi-layered, laminate test strip 12. As previously described, the laminate includes a base substrate 20, a spacing layer 22, and a covering layer 24. These components may be assembled in various ways. For example, the components may be assembled by use of adhesives, heat sealing, laser welding, and a variety of other suitable techniques appropriate for securing the adjacent materials. The test strips are preferably assembled in a large number on a single sheet or web (herein also described as a “laminated web”), and the strips are thereafter separated for storage and use.

[0061] The laminate test strip may be assembled sequentially by successively laying down one layer at a time. Alternatively, the test strip can be prepared by assembling and processing individual components or layers, which are then laminated together to provide the functional test strip. In one preferred form, two or more basic components of the test strip are prepared simultaneously. Then in one or a series of assembly or laminating steps, the basic components are combined to produce the test strip, which may or may not require further processing. In a preferred embodiment, the test strip is assembled from three basic components: a metallized substrate preferably with a reagent layer coated on metallic electrodes defined on the substrate, a spacing layer having a cavity preformed therein, and one or more top or cover layers.

[0062] The electrode system 32, in at least one embodiment of the method of manufacturing the test strip 500, is formed by removing a pre-determined pattern from a conductive layer on the base substrate with laser ablation. Alternately, in at least one embodiment, electrode system 32 may be formed by single pass deposition of the electrode system on the base substrate. Further, in at least one embodiment, electrode system 32 may be formed by laser scribing, screen printing or lithography.

[0063] Referring to FIG. 6, an exemplary method of measuring a concentration of an analyte in a solution is shown. The method 600 for measuring a concentration of an analyte in a sample of fluid, comprises providing a test meter (step 610) and providing an exemplary embodiment of test strip 12 as described herein (step 620). Method 600 further comprises receiving the test strip into the test meter (step 630), connecting the working electrode, the counter electrode, and the heating electrode with the test meter (step 640), applying radiative heating to the reagent layer by applying current from the test meter to the heating electrode (step 650), and determining an attribute associated with test strip as a function of a measurement associated with at least the resistance value associated with the unique resistive path (step 660).

[0064] In at least one embodiment of connecting step 640, the test strip 50 is inserted into the connection terminal 14 of the test meter 10 such that all of the contact pads of the test strip 50 are connected to contact pins within the connection terminal 14.

[0065] In at least one embodiment of heating step 650, current is applied from test meter 10 to the heating electrode of test strip 50. Following application of current to the heating electrode, the heating element emits radiative heat. Due to the proximity of the heating element to the reactive layer, the heat emitted by the heating electrode is sufficient to raise the localized temperature of the reagent layer. The heating step 650 in at least one embodiment may last for between 0 and 30 seconds, between 0 and 20 seconds, between 0 and 15 seconds, between 0 and 10 seconds, between 0 and 5 seconds, or between 1 and 5 seconds. In at least one embodiment of heating step 650, the localized temperature is raised by at least 1°C, at least 2°C, at least 3°C, at least 4°C, at least 5°C, between 1°C and 5 °C, between 1°C and 10°C, or between 1°C and 20°C. Heating step 650 may also raise the localized temperature at the reagent layer up to or above a threshold temperature. Such threshold temperature may be required to achieve a desired level of accuracy for the enzymatic assay. Such a threshold temperature may be 10°C, 15°C, 20°C, or 22°C.

[0066] Method 600, in at least one embodiment, also comprises the step of monitoring the temperature at the test strip (step 645). The results of monitoring step 645 may be used in the initiation of heating step 650. The initiation may occur in at least one instance if the monitored temperature is below a pre-set threshold, such as 10°C or 6°C, or alternately is the temperature is between 4°C and 10°C. The monitored temperature may be determined either with a thermistor in the test meter, or by measuring the resistance trace of the heating electrode and converting the trace into a localized temperature reading, since the resistance trance is correlated with temperature. The measured temperature can be used to determine the proper heating protocol, which may include heating times, voltages used, or combinations or both. Variable heating times and voltages also may be used in at least one heating protocol. Monitoring temperature may continue following heating step 650 to ensure that the desired temperature was reached and to account for and deviations when determining the analyte concentration.

[0067] For an exemplary determining step 660, working electrode 54 and counter electrode 58 remain in an open state with respect to each other (i.e. generally electrically isolated from each other) until an adequate amount of fluid, such as blood, is placed on the test strip 50. The application of an adequate amount of fluid onto the reagent layer 66 creates an electrochemical reaction that can be detected by the test meter 10.

[0068] In a general sense, the test meter 10 applies a predetermined voltage across the working electrode measurement contact pad 70 and the counter electrode measurement contact pad 80 to create a potential difference between the working electrode 54 and counter electrode 58, and then measures the resulting current flow. The magnitude and direction of the voltage is selected based on the electrochemical activation potential for an electrical measurement species to be detected which is generated from the electrochemical reaction of the reagent 66 and applied fluid. For glucose, for example, an applied potential difference typically is between about +100 mV and +550 mV when using a DC potential. When using AC potentials these can be between about +5 mV and + 100 mV RMS but can also have larger amplitude depending on the purpose for applying the AC potential. The measured amount of current flow, particularly resulting from a DC potential or sufficiently large amplitude AC potential, is indicative of the concentration of the analyte to be measured. The exact manner in which this process works is beyond the scope of the present disclosure but known to those skilled in the art. See, for example, U.S. Patent Nos. 7,727,467; 5,122,244; and 7,276,146, the disclosures of which are hereby incorporated herein by reference.

[0069] In order to compensate for the parasitic I-R (current x resistance) drop in the working electrode trace 54a and the counter electrode trace 58a, the test sensor 50 includes the working sense trace 56 and the counter sense trace 60. As set forth above, the working sense trace 56 is connected with the working electrode trace 54a at the distal end 62 of the test sensor 50 and the working sense measurement contact pad 75 at the proximal end 64 of the test sensor 50. The counter sense trace 60 is connected with the counter electrode trace 58a at the distal end 62 of the test sensor 50 and the counter sense measurement contact pad 86 at the proximal end 64 of the test sensor 50.

[0070] In one embodiment, during a test procedure a voltage potential is applied to the counter electrode measurement contact pad 80, which will produce a current between the counter electrode 58 and the working electrode 54 that is proportional to the amount of analyte present in the biological sample applied to the reagent layer 66. To ensure that the proper voltage potential is applied to the counter electrode 58, the test meter 10 includes circuitry (not shown) that ensures that a voltage potential (or absolute potential difference) applied to the counter sense trace 60 is the same as the desired voltage potential (or absolute potential difference) at the counter electrode 58. Typically, the test meter 10 will ensure that little to no current will flow through the counter sense trace 60, thereby assuring that the voltage potential seen at the counter electrode 58 corresponds to the desired voltage potential. For a more detailed discussion on the compensation functionality of the working sense trace 56 and the counter sense trace 60 reference can be made to commonly owned U.S. Patent No. 7,569,126, which is hereby incorporated by reference in its entirety.

[0071] In at least one embodiment, the heating step 650 may occur prior to the determining the analyte step 660. Alternately, the heating step 650 may occur concurrent with determining the analyte step 660, or both prior to and concurrent with determining the analyte step 660. In at least one embodiment, control of the duration of heating step 650, as well as the initiation timing (i.e. prior to or concurrent with determining step 660) and cessation of heating step 650 is controlled by test meter 10. The controlling of heating step 650 may involve determining the temperature at the test sensor, where temperature readings fall below a predetermined level triggers the initiation of heating step 650. The duration of heating step 650 may be for a predetermined time period as discussed above, or until a threshold temperature reading is achieved. In addition to duration of the heating step, test meter 10 may also apply a fixed voltage, or a fixed current, or a variable sequence to achieve the desired level of heating. In at least one embodiment, control of heating step 650 involves determining resistance measurements of the test sensor prior to initiation of heating step. In addition, resistance measurements may be taken after the heating step to predict the rise in temperature of the test sensor. Controlling of the heating step may also involve using a thermistor in the test meter 10 to determine the parameters of the heating step. In at least one embodiment, the heating electrode (or in some embodiments the resistive filament of the heating electrode) is used to measure the relative temperature based on the measured resistive trace (ohms) that varies with temperature. This can be used by itself, or in conjunction with the thermistor to determine the best parameters for the heating step.

[0072] As used herein, the term ablate should be broadly construed to mean to remove or destroy, which can be done by, for example, cutting, abrading, or vaporizing. In one form, at least a portion of the taps 120a-g shown in FIG.3 and used in coding strips (for more information see U.S. Patent No. 8,888,973, the disclosure of which is hereby incorporated by reference herein) or in the formation of the electrodes may be ablated by a laser, which can be a diode-pumped solid state laser or a fiber laser. In an illustrative form, the diode-pumped solid state laser is a 355 nanometer diode-pumped solid state laser and the fiber laser is a 1090 nanometer fiber laser.

[0073] It is noted that the terms "substantially" and "about" and “approximately” may be utilized herein to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation. These terms are also utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue .

[0074] Although embodiments of the disclosure have been described using specific terms, such description is for illustrative purposes only, and it is to be understood that changes and variations obvious to the skilled artisan are to be considered within the scope of the claims that follow and their equivalents.

[0075] Embodiments:

[0076] 1. A method of manufacturing a test strip having first and second sides, a sample receiving end and a meter insertion end, the method comprising:

[0077] a. providing a base substrate material having first and second edges; [0078] b. forming an electrode set on the base substrate material, the electron set comprising a working electrode, a counter electrode and a heating electrode, the heating electrode having a resistive filament;

[0079] c. applying a stripe of reagent material to the base substrate material and covering at least one electrode of the electrode set with the stripe, the stripe being oriented substantially parallel to the first substrate edge; and

[0080] d. laminating a spacing material on top of the base substrate material and providing a cavity in the spacing material such that the electrode set is received within the cavity and the cavity at least partially defines a sample receiving chamber,

[0081] e. cutting a test strip from the laminated web produced from steps (a)-(d), the cutting defining the first and second sides of the test strip, wherein the test strip comprises a reagent layer extending to the first and second sides of the test strip under the spacing layer.

[0082] The method of embodiment 1, wherein the step of forming the electrode set comprises removing a pre-determined pattern from a conductive layer on the base substrate material with laser ablation.

[0083] 3. The method of any previous embodiment, wherein the step of forming the electrode set comprises a single pass deposition of the electrode set.

[0084] 4. The method of any previous embodiment, wherein the resistive filament is adjacent to the stripe of reagent.

[0085] 5. The method of any previous embodiment, wherein the resistive filament is at least partially covered by the stripe of reagent.

[0086] 6. The method of any previous embodiment, wherein the heating electrode is connected to the counter electrode.

[0087] 7. The method of any previous embodiment, further comprising aligning and then laminating a web of covering layer material over the web of base substrate and spacing material.

[0088] 8. The method of any previous embodiment, wherein the resistive filament has a resistance of about 200 to about 870 ohms. [0089] 9. A test strip, comprising:

[0090] a base substrate having a working electrode, a counter electrode, and a heating electrode formed thereon and having two opposite side edges and an end edge;

[0091] a spacing layer overlying the base substrate and having a void that at least partially defines a sample-receiving chamber;

[0092] a covering layer overlying the spacing layer; and a reagent layer disposed in the sample-receiving chamber and covering a portion of the base substrate and at least one of the electrodes, the reagent layer extending under the spacing layer to the two side edges of the base substrate and being sandwiched between the spacing layer and the base substrate,

[0093] wherein the heating electrode comprises a resistive filament proximal to the end edge of the base substrate.

[0094] 10. The test strip of embodiment 9, wherein the heating electrode is proximal to but not covered by the reagent layer.

[0095] 11. The test strip of any previous embodiment, wherein the heating electrode is at least partially covered by the reagent layer.

[0096] 12. The test strip of any previous embodiment, wherein the heating electrode is positioned in relation to an electrochemical sensor defined by the working electrode, the counter electrode and the reagent layer so as to raise the temperature at the electrochemical sensor by at least one degree Celsius when the heating element is active for at least one second.

[0097] 13. The test strip of any previous embodiment, where the heating electrode is connected to the counter electrode.

[0098] 14. The test strip of any previous embodiment, wherein the resistive filament has a resistance of about 200 to about 870 ohms.

[0099] 15. A method for measuring a concentration of an analyte in a sample of fluid, comprising:

[00100] providing a test meter;

[00101] providing a test strip, the test strip comprising: [00102] a base substrate having a working electrode, a counter electrode, and a heating electrode formed thereon and having two opposite side edges and an end edge;

[00103] a spacing layer overlying the base substrate and having a void that at least partially defines a sample-receiving chamber;

[00104] a covering layer overlying the spacing layer; and a reagent layer disposed in the sample-receiving chamber and covering a portion of the base substrate and at least one of the electrodes, the reagent layer extending under the spacing layer to the two side edges of the base substrate and being sandwiched between the spacing layer and the base substrate,

[00105] wherein the heating electrode comprises a resistive filament proximal to the end edge of the base substrate.

[00106] receiving the test strip into the test meter;

[00107] connecting the working electrode, the counter electrode, and the heating electrode with the test meter;

[00108] applying radiative heating to the reagent layer by applying current from the test meter to the heating electrode; and

[00109] determining an attribute associated with test strip as a function of a measurement associated with at least the resistance value associated with the unique resistive path.

[00110] 16. The method of embodiment 15, further comprising the step of monitoring the temperature at the test strip by the test meter and initiating by the test meter the radiative heating by the heating electrode if the temperature is below a pre- determined threshold.

[00111] 17. The method of any previous embodiment, wherein the predetermined threshold is 10°C.

[00112] 18. The method of any previous embodiment, wherein the predetermined threshold is 6°C.

[00113] 19. The method of any previous embodiment, further comprising the step of monitoring the temperature at the test strip by the test meter and initiating by the test meter the radiative heating by the heating electrode if the temperature is between 4°C and 10°C.

[00114] 20. The method of any previous embodiment, wherein applying current from the test meter to the heating electrode is for a pre-set period of time.

[00115] 21. The method of any previous embodiment, wherein the pre-set period of time is between 0 and 5 seconds.

[00116] 22. The method of any previous embodiment, wherein the pre-set period of time is between 0 and 30 seconds.

[00117] 23. The method of any previous embodiment, further comprising determining using a thermistor in the test meter a time period for applying current from the test meter to the heating electrode.

[00118] 24. The method of any previous embodiment, further comprising determining using a thermistor in the test meter a voltage to apply from the test meter to the heating electrode.

[00119] 25. The method of any previous embodiment, further comprising measuring a relative temperature on the test strip.

[00120] 26. The method of embodiment 25, wherein the step of measuring the relative temperature comprises measuring the resistance trace of the heating electrode and converting the trace to a localized temperature.

[00121] 27. The method of any previous embodiment, wherein the step of applying radiative heat raises the localized temperature by at least 1°C, at least 2°C, at least 3°C, at least 4°C, or at least 5°C.

[00122] 28. The method of any previous embodiment, wherein the step of applying radiative heat raises the localized temperature by between 1°C and 5 °C, between 1°C and 10°C, or between 1°C and 20°C.

Claims

What is claimed is:

1. A method of manufacturing a test strip having first and second sides, a sample receiving end and a meter insertion end, the method comprising: a. providing a base substrate material having first and second edges; b. forming an electrode set on the base substrate material, the electron set comprising a working electrode, a counter electrode and a heating electrode, the heating electrode having a resistive filament; c. applying a stripe of reagent material to the base substrate material and covering at least one electrode of the electrode set with the stripe, the stripe being oriented substantially parallel to the first substrate edge; and d. laminating a spacing material on top of the base substrate material and providing a cavity in the spacing material such that the electrode set is received within the cavity and the cavity at least partially defines a sample receiving chamber, e. cutting a test strip from the laminated web produced from steps (a)-(d), the cutting defining the first and second sides of the test strip, wherein the test strip comprises a reagent layer extending to the first and second sides of the test strip under the spacing layer.

2. The method of claim 1, wherein the step of forming the electrode set comprises removing a pre-determined pattern from a conductive layer on the base substrate material with laser ablation.

3. The method of claim 1, wherein the step of forming the electrode set comprises a single pass deposition of the electrode set.

4. The method of claim 1, wherein the resistive filament is adjacent to the stripe of reagent.

5. The method of claim 1, wherein the resistive filament is at least partially covered by the stripe of reagent.

6. The method of claim 1, wherein the heating electrode is connected to the counter electrode.

7. The method of claim 1, further comprising aligning and then laminating a web of covering layer material over the web of base substrate and spacing material.

8 The method of claim 1, wherein the resistive filament has a resistance of about 200 to about 870 ohms.

9. A test strip, comprising: a base substrate having a working electrode, a counter electrode, and a heating electrode formed thereon and having two opposite side edges and an end edge; a spacing layer overlying the base substrate and having a void that at least partially defines a sample-receiving chamber; a covering layer overlying the spacing layer; and a reagent layer disposed in the sample-receiving chamber and covering a portion of the base substrate and at least one of the electrodes, the reagent layer extending under the spacing layer to the two side edges of the base substrate and being sandwiched between the spacing layer and the base substrate, wherein the heating electrode comprises a resistive filament proximal to the end edge of the base substrate.

10. The test strip of claim 9, wherein the heating electrode is proximal to but not covered by the reagent layer.

11. The test strip of claim 9, wherein the heating electrode is at least partially covered by the reagent layer.

12. The test strip of claim 9, wherein the heating electrode is positioned in relation to an electrochemical sensor defined by the working electrode, the counter electrode and the reagent layer so as to raise the temperature at the electrochemical sensor by at least one degree Celsius when the heating element is active for at least one second.

13. The test strip of claim 9, where the heating electrode is connected to the counter electrode.

14. The test strip of claim 9, wherein the resistive filament has a resistance of about 200 to about 870 ohms.

15. A method for measuring a concentration of an analyte in a sample of fluid, comprising: providing a test meter; providing a test strip, the test strip comprising: a base substrate having a working electrode, a counter electrode, and a heating electrode formed thereon and having two opposite side edges and an end edge; a spacing layer overlying the base substrate and having a void that at least partially defines a sample-receiving chamber; a covering layer overlying the spacing layer; and a reagent layer disposed in the sample-receiving chamber and covering a portion of the base substrate and at least one of the electrodes, the reagent layer extending under the spacing layer to the two side edges of the base substrate and being sandwiched between the spacing layer and the base substrate, wherein the heating electrode comprises a resistive filament proximal to the end edge of the base substrate. receiving the test strip into the test meter; connecting the working electrode, the counter electrode, and the heating electrode with the test meter; applying radiative heating to the reagent layer by applying current from the test meter to the heating electrode; and determining an attribute associated with test strip as a function of a measurement associated with at least the resistance value associated with the unique resistive path.

16. The method of claim 15, further comprising the step of monitoring the temperature at the test strip by the test meter and initiating by the test meter the radiative heating by the heating electrode if the temperature is below a pre-determined threshold.

17. The method of claim 16, wherein the predetermined threshold is 10°C.

18. The method of claim 16, wherein the predetermined threshold is 6°C.

19. The method of claim 15, further comprising the step of monitoring the temperature at the test strip by the test meter and initiating by the test meter the radiative heating by the heating electrode if the temperature is between 4°C and 10°C.

20. The method of claim 15, wherein applying current from the test meter to the heating electrode is for a pre-set period of time.

21. The method of claim 20, wherein the pre-set period of time is between 0 and 5 seconds.

22. The method of claim 20, wherein the pre-set period of time is between 0 and 30 seconds.

23. The method of claim 15, further comprising determining using a thermistor in the test meter a time period for applying current from the test meter to the heating electrode.

24. The method of claim 15, further comprising determining using a thermistor in the test meter a voltage to apply from the test meter to the heating electrode.

25. The method of claim 15, further comprising measuring a relative temperature on the test strip.

26. The method of claim 20, wherein the step of measuring the relative temperature comprises measuring the resistance trace of the heating electrode and converting the trace to a localized temperature.

27. The method of claim 15, wherein the step of applying radiative heat raises the localized temperature by at least 1°C, at least 2°C, at least 3°C, at least 4°C, or at least 5°C.

28. The method of claim 15, wherein the step of applying radiative heat raises the localized temperature by between 1°C and 5 °C, between 1°C and 10°C, or between 1°C and 20°C.