Novel electrode design for biosensor

ES 2 644 041 T3

DESCRIPTION

New electrode design for biosensor

TECHNICAL FIELD

Reference is made to an apparatus for use in measuring signals such as those related to concentrations of an analyte (such as blood glucose) in a biological fluid, as well as those related to interferents (such as hematocrit and temperature in the case of glucose) to analyte concentration signals. It relates more particularly to the system and method for quality assurance of a biosensor test strip.

BACKGROUND OF THE INVENTION

Measuring the concentration of substances in biological fluids is an important tool for the diagnosis and treatment of many medical conditions. For example, measuring glucose in body fluids, such as blood, is crucial for the effective treatment of diabetes.

Diabetic therapy typically involves two types of insulin treatment: basal, and mealtime. Basal insulin refers to sustained-release insulin, for example, long-term, often taken before bedtime. Meal-based insulin therapy provides additional doses of faster-acting insulin to regulate fluctuations in blood glucose caused by a variety of factors, including the metabolism of sugars and carbohydrates. Proper regulation of blood glucose fluctuations requires an accurate measurement of blood glucose concentration. Failure to do so can lead to extreme complications, such as blindness and loss of circulation to the extremities, which can ultimately deprive the diabetic of the use of their fingers, hands, feet, etc.

Multiple methods are known to determine the concentration of analytes in a blood sample, such as, for example, glucose. Such methods typically fall into one of two categories: optical methods and electrochemical methods. Optical methods generally involve spectroscopy to observe the spectrum shift in the fluid caused by the concentration of the analyte, typically in conjunction with a reagent that produces a known color when combined with the analyte. Electrochemical methods are generally based on the correlation between a current (Amperometry), a potential (Potentiometry) or accumulated charge (Coulometry) and the concentration of the analyte, typically in conjunction with a reagent that produces charge carriers when combined with the analyte. . See, for example, US Patent Nos. 4,233,029 to Columbus, 4,225,410 to Pace, 4,323,536 to Columbus, 4,008,448 to Muggli, 4,654,197 to Lilja et al., 5,108,564 to Szuminsky et al., 5,120,420 to Nankai et al., 5,128,015 to Szuminsky et al. 5 243,516 to White, 5,437,999 to Diebold et al., 5,288,636 to Pollmann et al., 5,628,890 to Carter et al., 5,682,884 to Hill et al., 5,727,548 to Hill et al., 5,997 .817 to Crismore et al., 6,004,441 to Fujiwara et al., 4,919,770 to Priedel, et al., And 6,054,039 to Shieh. The biosensor for conducting the assays is typically a disposable test strip that has a reagent on it that chemically reacts with the analyte of interest in the biological fluid. The test strip attaches to an unavailable test meter so that the test meter can measure the reaction between the analyte and the reagent in order to determine and display the analyte concentration to the user.

US 2004 / 0251131A1 describes a biosensor including a working electrode, a counter electrode opposite the working electrode, a working electrode terminal and a working electrode reference terminal connected to the working electrode by wires and a terminal of counter electrode connected to the counter electrode by a wire. By employing a structure with at least three electrodes, it is possible to test a target substance without being influenced by the line resistance on the side of the working electrode.

Figure 1 schematically illustrates a typical prior art disposable biosensor test strip, generally indicated at 10 (see, for example, US Patent Nos. 4,999,582 and 5,438,271, assigned to the same assignee as the present application). The test strip 10 is formed on a non-conductive substrate 12, on which the conductive areas 14, 16 are formed. A chemical reagent 18 is applied over the conductive areas 14, 16 at one end of the test strip 10. Reagent 18 will react with the analyte of interest in the biological sample in a manner that can be detected when a voltage potential is applied between the measurement electrodes 14a and 16a.

Therefore, the test strip 10 has a reaction zone 20 containing the measurement electrodes 14a, 16a that come into direct contact with a sample containing an analyte for which the concentration in the sample is to be determined. In an amperometric or coulometric electrochemical measurement system, the measurement electrodes 14a, 16a in the reaction zone 20 are coupled to electronic circuits (typically in a test meter (not shown) into which the test strip 10 is inserted, as is well known in the art) that supplies an electrical potential to the measurement electrodes and measures the response of the electrochemical sensor to this potential (eg, current, impedance, charge, etc.). This response is proportional to the concentration of the analyte.

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The test counter comes into contact with the test strip 10 at the contact pads 14b, 16b in a contact area 22 of the test strip 10. Contact zone 22 is located somewhat remotely from measurement zone 20, usually (but not always) at the opposite end of test strip 10. Conductive tracks 14c, 16c couple contact pads 14b, 16b in contact zone 22 to respective measurement electrodes 14a, 16a in reaction zone 20.

Especially for biosensors 10 where the electrodes, tracks and contact pads are made up of electrically conductive thin films (e.g. noble metals, carbon ink and silver paste as non-limiting examples), the resistivity of the conductive tracks 14c, 16c connecting the contact zone 22 to the reaction zone 20 can be several hundred Ohms or more. This parasitic resistance causes a potential drop along the length of the tracks 14c, 16c, so that the potential presented to the measurement electrodes 14a, 16a in the reaction zone 20 is considerably less than the potential applied by the test meter to the contact pads 14b, 16b of the test strip 10 in the contact zone 22. Since the impedance of the reaction taking place within the reaction zone 20 can be within an order of magnitude of the parasitic resistance of the tracks 14c, 16c, the signal being measured can have a significant offset due to the IR drop. (current x resistance) induced by the tracks. If this offset varies from test strip to test strip, noise will be added to the measurement result.

In addition, physical damage may occur to the test strip 10, such as abrasion, cracks, scratches, chemical degradation, etc. during the manufacture, transport, storage and / or incorrect handling of the user. These defects can damage the conductive areas 14, 16 to the point where they present extremely high resistance or even an open circuit. Such increases in track resistance can prevent the test meter from performing an accurate test.

SUMMARY OF THE INVENTION

A test strip for measuring a signal of interest in a biological fluid when the test strip is coupled to an appropriate test meter, wherein the test strip and test meter include structures for verifying the integrity of the test tracks. test strip, the parasitic resistance of the test strip tracks and to provide an offset in the voltage applied to the test strip to account for resistive parasitic losses in the test strip tracks. Additionally, conductive tracks are placed to ensure structural interrogation of all electrodes and tracks present on the test strip.

BRIEF DESCRIPTION OF THE DRAWINGS

The following description and examples illustrate some embodiments that are not part of the claimed invention.

FIG. 1 is a schematic plan view of a typical prior art test strip for use in measuring the concentration of an analyte of interest in a biological fluid.

FIG 2 is a schematic plan view of a first embodiment of a test strip in accordance with the specification.

FIG 3 is a schematic diagram of a first embodiment of an electronic test circuit for use with the first embodiment of the test strip of FIG. two.

FIG. 4 is an enlarged assembly view of a typical second test strip for use in measuring the concentration of an analyte of interest in a biological fluid.

FIG 5 illustrates a view of an ablation apparatus suitable for use with the present invention.

FIG 6 is a view of the laser ablation apparatus of FIG. 5 showing a second mask.

FIG 7 is a view of an ablation apparatus suitable for use with the present invention.

FIG 8 is a schematic plan view of a second embodiment of the test strip in accordance with the specification.

FIG 9 is a schematic diagram of a second embodiment electronic test circuit for use with the second embodiment of the test strip of FIG. 8.

FIG. 10 is a schematic diagram of a third embodiment electronic test circuit for use with the second embodiment of the test strip of FIG. 8.

FIG. 11 is a schematic plan view of a third embodiment of a test strip.

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FIG 12 is a schematic plan view of a fourth embodiment of a test strip.

DETAILED DESCRIPTION OF THE SELECTED FORMS OF REALIZATION

In order to promote an understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the drawings, and specific language will be used to describe said embodiment. However, it will be understood that no limitation of the scope of the invention is intended. Alterations and modifications to the illustrated device and other applications of the principles of the invention as illustrated therein are desired to be protected, as would normally be the case for one of ordinary skill in the art contemplating the invention. In particular, although the invention is discussed in terms of a blood glucose meter, it is contemplated that the invention may be used with devices for measuring other analytes and other types of samples. Such alternative embodiments require certain adaptations to the embodiments discussed herein that would be obvious to those skilled in the art.

Although the system and method of the specification can be used with test strips that have a wide variety of designs and are manufactured with a wide variety of construction techniques and procedures, it is schematically illustrated in FIG. 2 an electrochemical test strip of the first embodiment of the specification and is generally indicated at 200. Portions of test strip 200 that are substantially identical to those of test strip 10 are marked with similar reference designators. Referring to FIG. 2, the test strip 200 comprises a lower substrate 12 formed from an opaque piece of 350 µm thick polyester (such as Melinex 329 available from DuPont) coated on its upper surface with a 50 nm conductive gold layer. (for example, by way of non-limiting example). The electrodes, the connecting tracks, and the contact pads therefor are then patterned into the conductive layer, for example, by a laser ablation process. One embodiment of a laser ablation procedure is performed by means of an excimer laser that passes through a mask of chromium on quartz. The mask pattern defined by the chromium causes parts of the laser field to reflect while other parts of the field are allowed to pass through the quartz, creating a pattern in the gold that evaporates when it comes in contact with the laser light. The laser ablation procedure is described in more detail below. For example, working electrodes 214a, counter 216a, and detection counter 224a may be formed as shown and coupled to respective measurement contact pads 214b, 216b, and 224b via respective tracks 214c, 216c, and 224c. These contact pads 214b, 216b, and 224b provide a conductive area on the test strip 200 to contact a test meter connection contact (not shown) once the test strip 200 is inserted into the test meter. proof, as is well known in the art.

FIGs. 2 and 3 illustrate an embodiment of the specification that improves prior art test strip designs by allowing compensation for parasitic IR drop on the test strip counter electrode line.

It will be appreciated that the test strip 200 of FIG. 2 is substantially identical to the prior art test strip 10 of FIG. 1, except for the addition of the detection counter electrode 224a, contact pad 224b, and track 224c. The provision of counter detector line 224 allows the test meter (as described later in this document) to compensate for parasitic resistance between contact pads 216b, 224b. Note that the embodiment of FIG. 2 when used with the circuit of FIG. 3 only compensates for the IR drop on the counter electrode side of the test strip 200. The parasitic resistance on the working electrode side of the test strip 200 cannot be detected using this circuitry, although it could be replicated on the working electrode side if desired, as will be apparent to those skilled in the art with reference. to the present description. Here are other methods to compensate for parasitic drag on both the working sides and the counters of the test strip. The detection counting line of FIG. 2 therefore allows the test meter to compensate for any drop in parasitic resistance potential on counter line 216, as explained in more detail with respect to FIG. 3.

Referring now to FIG. 3, a schematic electrical circuit diagram of an electrode compensation circuit of the first embodiment (indicated generally at 300) housed within the test meter is shown. As indicated, the circuit engages the contact pads 214b, 216b, and 224b when the test strip 200 is inserted into the test meter. As will be appreciated by those skilled in the art, a voltage potential will be applied to the contact pad 216b of the counter electrode, which will produce a current between the counter electrode 216a and the working electrode 214a that is proportional to the amount of analyte present. in the biological applied to reagent 18. The current from the working electrode 214a is transmitted to the contact pad of the working electrode 214b via the working electrode track 214c and is provided to a current-to-voltage amplifier 310. The analog output voltage from amplifier 310 is converted to a digital signal by analog-to-digital (A / D) converter 312. This digital signal is then processed by microprocessor 314 in accordance with a previously stored program to determine the concentration of analyte within the biological sample applied to test strip 200. This concentration is displayed to the user by means of an output device 316 appropriate, such as a liquid crystal display (LCD) screen.

The microprocessor 314 also generates a digital signal indicative of the voltage potential to be applied to the contact pad 216b of the counter electrode. This digital signal is converted to an analog voltage signal by means of a 318 digital-to-analog (A / D) converter. The analog output of A / D 318 is applied to a

ES 2 644 041 T3 first input of an operational amplifier 320. A second input of operational amplifier 320 is coupled to contact pad 224b of the detection counter electrode. The output of the operational amplifier 320 is coupled to the contact pad 216b of the counter electrode.

The op amp 320 is wired in a voltage follower configuration, in which the amplifier will adjust its output (within its physical operating limits) until the voltage appearing at its second input equals the commanded voltage appearing at its first entry. The second input of operational amplifier 320 is a high impedance input, therefore, substantially no current flows on meter line 224. Since there is substantially no current flowing, any parasitic resistance in counter line 224 will not cause a potential drop and the voltage appearing at the second input of op amp 320 is substantially the same as the voltage at sensing counter electrode 224a, which in turn, it is substantially the same as the voltage appearing at the counter electrode 216a due to its close physical proximity. The op amp 320 therefore acts to vary the voltage potential applied to the counter electrode contact pad 216b until the actual voltage potential appearing at the counter electrode 216a (as fed back on the counter line 224) is equal to the voltage potential commanded by the microprocessor 314. The operational amplifier 320 then automatically compensates for any potential drop caused by parasitic resistance in the counter electrode track 216c, and the potential appearing at the counter electrode 216a is the desired potential. The calculation of the analyte concentration in the biological sample from the current produced by the working electrode is therefore made more precise, since the voltage produced by the current is in fact the same voltage commanded by the microprocessor 314 . Without compensation for parasitic resistance, provided by circuit 300, microprocessor 314 would analyze the resulting current under the wrong assumption that the commanded voltage was actually applied to counter electrode 216a.

Many methods for preparing test strips having multiple electrodes are available, such as carbon ink printing, silver-paste silk printing, metallized plastic scribing, electroplating, chemical plating, and photochemical etching, by way of non-limiting example. One method of preparing a test strip having additional electrode detection lines as described in the present invention is through the use of laser ablation techniques. Examples of the use of these techniques in the preparation of electrodes for biosensors are described in United States Patent US2002192115 and in United States Patent US6662439. Laser ablation is useful in preparing test strips to specification because it allows conductive areas that have extremely small feature sizes to be precisely manufactured in a repeatable manner. Laser ablation provides a means to add the extra sense lines of the specification to a test strip without increasing the size of the test strip.

It is desirable to provide precise placement of electrical components to each other and to the overall biosensor. In one embodiment, the relative placement of components is achieved, at least in part, through the use of wide-field laser ablation that is performed through a mask or other device that has a precise pattern for the electrical components. This allows for precise positioning of adjacent edges, which is enhanced by close tolerances for edge smoothness.

Figure 4 illustrates a simple biosensor 401 useful to illustrate the specification's laser ablation process, which includes a substrate 402 having a conductive material 403 that defines electrode systems comprising a first set 404 of electrodes and a second set. 405 of corresponding electrodes and tracks 406, 407 and contact pads 408, 409, respectively. Note that biosensor 401 is used herein for purposes of illustrating the laser ablation process, and is not shown as incorporating the sense lines of the specification. Conductive material 403 may contain pure metals or alloys, or other materials, that are metallic conductors. In some embodiments, the conductive material is absorbent at the wavelength of the laser used to form the electrodes and of a thickness capable of fast and accurate processing. Non-limiting examples include aluminum, carbon, copper, chromium, gold, indium tin oxide (ITO), palladium, platinum, silver, tin / gold oxide, titanium, mixtures thereof, and metal alloys or compounds of these elements. In some embodiments, the conductive material includes noble metals or alloys or their oxides.

Other embodiments use conductive materials such as gold, palladium, aluminum, titanium, platinum, ITO, and chromium. The conductive material has a thickness of about 10 nm to 80 nm. Some embodiments use thicknesses ranges between 30 nm and 70 nm, others use thicknesses at 50 nm. It will be appreciated that the thickness of the conductive material depends on the transmissive property of the material and other factors related to the use of the biosensor.

Although not illustrated, it is appreciated that the resulting molded conductive material can be coated or plated with additional metallic layers. For example, the conductive material can be copper, which will then be ablated with a laser in an electrode pattern; Subsequently, the copper can be plated with a layer of titanium / tungsten, and then a layer of gold, to form the desired electrodes. In most embodiments, a single layer of conductive material is used, resting on the base 402. Although not generally necessary, it is possible to increase the adhesion of the conductive material to the base, as is well known.

ES 2 644 041 T3 in the art, using seeds or auxiliary layers such as chrome nickel or titanium. In some embodiments, biosensor 401 has a single layer of gold, palladium, platinum, or ITO.

The biosensor 401 is illustratively manufactured using two apparatuses 10, 10 ', shown in Figures 4, 6, and 7, respectively. It will be appreciated that unless otherwise described, the apparatuses 410, 410 'function in a similar manner. Referring first to Figure 5, the biosensor 401 is manufactured by feeding a roll 420 of tape having an 80nm gold laminate, which is approximately 40mm wide, into a wide field laser ablation apparatus 410. custom fit. Apparatus 410 comprises a laser source 411 that produces a beam 412 of laser light, a chromed quartz mask 414, and optics 416. It will be appreciated that while the illustrated optics 416 is a single lens, the optics 416 can be a variety of lenses that cooperate to manufacture light 412 in a predetermined shape.

A non-limiting example of a suitable ablation apparatus 410 (Figures 5-6) is a custom MicrolineLaser 200-4 laser system commercially available from LPKF Laser Electronic GmbH, of Garbsen, Germany, incorporating an LPX-400, LPX -300 or LPX-200 commercially available from Lambda Physik AG, Gottingen, Germany and a chrome quartz mask commercially available from Infinite Graphics, Minneapolis, MN.

For the MicrolineLaser 200-4 laser system (Figures 5-6), the 411 laser source is an LPX-200 KrF-UVlaser. However, it is appreciated that higher wavelength UV lasers can be used in accordance with this disclosure. The 411 laser source operates at 248nm, with a pulse energy of 600mJ, and a pulse repetition frequency of 50 Hz. The intensity of the 412 laser beam can be infinitely adjusted between 3% and 92% by means of a dielectric beam attenuator (not shown). The beam profile is 27x15mm² (0.62 square inches) and the pulse duration is 25 ns. The arrangement on mask 414 is projected homogeneously by an optical element beam expander, a homogenizer, and a field lens (not shown). The performance of the homogenizer has been determined by measuring the energy profile. Imaging optics 416 transfers structures from mask 414 to tape 420. The imaging ratio is 2: 1 to allow a large area to be removed, on the one hand, but to keep the energy density below the ablation point of the masked chromium on the other hand. Although a 2: 1 imaging is illustrated, it is appreciated that any number of alternative ratios are possible in accordance with this description depending on the desired design requirements. Belt 420 is moved as shown by arrow 425 to allow various layout segments to be successively segregated.

The positioning of the mask 414, the movement of the tape 420, and the laser energy are controlled by computer. As shown in FIG. 5, laser beam 412 is projected onto tape 420 for ablation. The light 412 passing through the clear areas or windows 418 of the mask 414 ablates the metal of the tape 420. The chrome coated areas 424 of the mask 414 block laser light 412 and prevent ablation in those areas, resulting in a metallized structure on the tape 420 surface. Referring now to FIG. 6, a complete structure of electrical components may require additional ablation steps through a second mask 414 '. It will be appreciated that depending on the optics and size of the electrical component to be ablated, only a single ablation step or more than two ablation steps may be necessary in accordance with this disclosure. Furthermore, it is appreciated that instead of multiple masks, multiple fields can be formed in the same mask in accordance with this description.

Specifically, a second non-limiting example of a suitable ablation apparatus 410 '(Figure 7) is a commercially available custom laser system from LPKF Laser Electronic GmbH, Garbsen, Germany, incorporating an available Lambda STEEL (Stable Energy Eximer Laser) commercially from Lambda Physik AG, Gottingen, Germany and a chrome quartz mask commercially available from Infinite Graphics, Minneapolis, MN. The laser system delivers up to 1000 mJ of pulse energy at a wavelength of 308 nm. In addition, the laser system has a frequency of 100 Hz. Apparatus 410 'may be formed to produce two-pass biosensors as shown in Figures 5 and 6, but in some embodiments its optics allow the formation of a 10 x pattern. 40 mm in a single pass of 25 ns.

Although not wishing to be bound by any specific theory, it is believed that the laser pulse or beam 412 passing through the mask 414, 414 ', 414 is absorbed within less than 1 pm of the surface 402 on the tape 420. Photons in beam 412 have sufficient energy to cause photo-dissociation and rapid breaking of chemical bonds at the metal / polymer interface. This rapid breakdown of the chemical bond is believed to cause a sudden increase in pressure within the absorption region and since typical pulse durations are around 20-25 nanoseconds, interaction with the material occurs very rapidly and thermal damage to the edges of the conductive 403 material and surrounding structures is minimized The resulting edges of the electrical components have high edge quality and exact placement as contemplated in the specification .

The creep energies used to remove or ablate metals from tape 420 depend on the material from which tape 420 is formed, the adhesion of the metal film to the base material, the thickness of the metal film, and possibly the process used to place the film on the base material, that is, support and vapor deposition. The creep levels for gold in KALADEX® range from about 50 to about 90 mJ / cm² on polyimide from about 100 to about 120 mJ / cm², and about

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MELINEX® from about 60 to about 120 mJ / cm². It is understood that creep levels lower or higher than those mentioned above may be appropriate for other base materials according to the description.

Shaping of areas of the tape 420 is accomplished using masks 414, 414 '. Each mask 414, 414 'illustratively includes a mask field 422 that contains an accurate two-dimensional illustration of a predetermined portion of the electrode component patterns to be formed. Figure 5 illustrates mask field 422 including contact pads and a portion of tracks. As shown in Figure 6, the second mask 414 'contains a second corresponding portion of the fingerprints and electrode patterns that contain the fingers. As described above, it is appreciated that depending on the size of the area to be removed, the mask 414 may contain a complete illustration of the electrode patterns (Figure 7), or portions of patterns other than those illustrated in Figures 5. and 6 in accordance with this disclosure. It is contemplated that, in one aspect of the specification, the entire pattern of electrical components on the test strip is one-time laser ablation, i.e., the wide field encompasses the entire size of the test strip (Figure 7). In the alternative, and as illustrated in Figures 5 and 6, portions of the complete biosensor are successively made.

While mask 414 will be discussed later, it will be appreciated that unless otherwise noted, the discussion will apply to masks 414 ', 414' 'as well. Referring to Figure 5, the areas 424 of the mask field 422 shielded by the chrome block the projection of the laser beam 412 to the tape 420. The transparent areas or windows 418 in the mask field 422 allow the beam 412 of laser passes through mask 414 and affects predetermined areas of tape 420. As shown in FIG. 5, the free area 418 of the mask field 422 corresponds to the areas of the tape 420 from which the conductive material 403 is to be removed.

In addition, mask field 422 has a length shown by line 430 and a width as shown by line 432. Given the LPX-200's 2: 1 imaging ratio, it is appreciated that the length 30 of the mask is twice the length of a length 434 of the resulting pattern and the width 432 of the mask is twice the width of a width 436 of the resulting pattern on the tape 420. The optics 416 reduces the size of the laser beam 412 that hits the tape 420. It will be appreciated that the relative dimensions of the mask field 422 and the resulting pattern may vary in accordance with this description. The mask 414 '(Figure 6) is used to complete the two-dimensional illustration of the electrical components.

Continuing with reference to FIG. 5, in laser ablation apparatus 410, excimer laser source 411 emits beam 412, which passes through chrome-on-quartz mask 414. The mask field 422 causes parts of the laser beam 412 to be reflected while other parts of the beam are allowed to pass, creating a pattern in the gold film where it is impacted by the laser beam 412. It will be appreciated that the belt 420 may be stationary relative to the apparatus 410 or move continuously in a roll apparatus 410. Accordingly, the non-limiting speeds of movement of the belt 420 can be from about 0 m / min to about 100 m / min, and in some embodiments from about 30 m / min to about 60 m / min. It will be appreciated that the speed of movement of the tape 420 is limited only by the selected apparatus 410 and may exceed 100 m / min depending on the pulse duration of the laser source 411 in accordance with the present disclosure.

Once the mask pattern 414 has been created on tape 420, the tape is rewound and fed back through apparatus 410, with mask 414 '(Figure 6). It will be appreciated that, alternatively, the laser apparatus 410 could be placed in series in accordance with this description. Therefore, using masks 414, 414 ', large areas of tape 420 can be patterned using step-and-repeat processes involving multiple mask fields 422 in the same mask area to allow for the economical creation of intricate electrode patterns and other electrical components on a base substrate, the precise edges of the electrode components, and the removal of larger amounts of the metal film from the base material.

The second embodiment of the specification illustrated in Figs. 8 and 9 improve upon the prior art by providing IR drop compensation of both work leads and counter electrode on the test strip. Referring now to FIG. 8 a second configuration of the specification test strip, generally indicated at 800, is schematically illustrated. The test strip 800 comprises a lower substrate 12 coated on its upper surface with a 50 nm conductive gold layer (eg, by sputtering or vapor deposition, by way of non-limiting example). The electrodes, the connecting tracks, and the contact pads therefor are then patterned into the conductive layer by a laser ablation process as described above. For example, the working electrodes 814a, working sensor 826a, counter 216a, and counter sensor 224a may be formed as shown and coupled to respective measurement contact pads 814b, 826b, 216b, and 224b via the respective tracks. 814c, 826c, 216c and 4 224c. These contact pads 814b, 826b, 216b and 224b provide a conductive area on the test strip 800 to be contacted by a test meter connector contact (not shown) once the test strip 800 is inserted into the meter. test.

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It will be appreciated that the test strip 800 of FIG. 8 is substantially identical to the first embodiment of test strip 200 of FIG. 2, except for the addition of working sensor electrode 826a, contact pad 826b, and track 826c. The provision of the work sense line 826 allows the test meter to compensate for any IR drops caused by the contact resistance of the connections to the contact pads 814b and 216b, and to compensate for the track resistance of the 814c and 216c.

Referring now to FIG. 9, there is shown a schematic electrical circuit diagram of an electrode compensation circuit of the second embodiment (indicated generally at 900) housed within the test meter. As indicated, the circuit engages the contact pads 826b, 814b, 216b, and 224b when the test strip 800 is inserted into the test meter. As will be appreciated by those skilled in the art, a voltage potential will be applied to the contact pad 216b of the counter electrode, which will produce a current between the counter electrode 216a and the working electrode 814a that is proportional to the amount of analyte present. in the biological applied to reagent 18. Current from working electrode 814a is transmitted by working electrode track 814c to working electrode contact pad 814b and supplied to current-to-voltage amplifier 310. The analog output voltage from amplifier 310 is converted to a digital signal through a microprocessor 314 in accordance with a previously stored program to determine the concentration of the analyte of interest within the biological sample applied to the test strip 800. This concentration is displayed in user memory via LCD output device 316.

The microprocessor 314 also generates a digital signal indicative of the voltage potential to be applied to the contact pad 216b of the counter electrode. This digital signal is converted to an analog voltage signal by A / D 318. The analog output of A / D 318 is applied to a first input of an operational amplifier 320. A second input of operational amplifier 320 is coupled to an output of operational amplifier 910. The operational amplifier 910 is connected in a difference amplifier configuration using an instrumentation amplifier. A first input of operational amplifier 910 is coupled to contact pad 826b of the work sense electrode, while a second input of operational amplifier 910 is coupled to contact pad 224b of the reverse electrode. The output of the operational amplifier 320 is coupled to the contact pad 216b of the counter electrode.

The op amp 320 is wired in a voltage follower configuration, in which the amplifier will adjust its output (within its physical operating limits) until the voltage appearing at its second input equals the commanded voltage appearing at its first entry. Both inputs of the op amp 910 are high impedance inputs, therefore, substantially no current flows in the counter sense line 224 or the work sense line 826. Since there is substantially no current flowing, any parasitic resistance on the backlit line 224 or the work sense line 826 will not cause a potential drop and the voltage appearing across the op amp 910 inputs is substantially the same as the voltage. through the measuring cell (ie, through the counter electrode 216a and the working electrode 814a). Because the op amp 910 is wired in a difference amplifier configuration, its output represents the voltage across the measurement cell.

The op amp 320 will therefore act to vary its output (i.e., the voltage potential applied to the counter electrode contact pad 216b) until the actual voltage potential appearing across the measuring cell equals to the voltage potential commanded by the microprocessor 314. Amplifier 320 automatically compensates for any potential drop caused by parasitic resistance in track 216c of the counter electrode, contact 216b of the counter electrode, track 814c of the working electrode, and contact 814b of the working electrode, and therefore the potential appearing across the measuring cell is the desired potential. Therefore, the calculation of the analyte concentration in the biological sample from the current produced by the working electrode is more accurate.

FIG. 10, together with FIG. 8 illustrates a third embodiment of the specification that improves upon the prior art by providing IR drop compensation for the working and counter electrode lines, as well as providing verification that the resistance of both the working and electrode lines counter is not above a predetermined one to ensure that the test meter is capable of compensating for IR drops. Referring now to FIG. 10, a schematic electrical circuit diagram of a third embodiment electrode compensation circuit (indicated generally at 1000) housed within the test meter is shown. Electrode compensation circuit 1000 works with test strip 800 of FIG. 8. As indicated, the circuit engages the contact pads 826b, 814b, 216b, and 224b when the test strip 800 is inserted into the test meter. As will be appreciated by those skilled in the art, a voltage potential will be applied to the contact pad 216b of the counter electrode, which will produce a current between the counter electrode 216a and the working electrode 814a that is proportional to the amount of analyte present. in the biological applied to reagent 18. Current from working electrode 814a is transmitted to working electrode contact pad 814b via working electrode track 814c and provided to current-to-voltage amplifier 310. The output of the current-to-voltage amplifier 310 is applied to the input of the instrumentation amplifier 1002 which is configured as a snubber having unity gain when the switch 1004 is in the closed position. The analog output voltage from amplifier 1002 is converted to a digital signal by A / D 312. This digital signal is then processed by microprocessor 314

ES 2 644 041 T3 according to a previously stored program to determine the analyte concentration within the biological sample applied to the test strip 800. This concentration is displayed to the user by means of the LCD output device 316.

The microprocessor 314 also outputs a digital signal indicative of the voltage potential to be applied to the contact pad 216b of the counter electrode. This digital signal is converted to an analog voltage signal by A / D 318. The analog output of A / D 318 is applied to the input of an op amp 320 that is configured as a voltage follower when switch 1006 is in the position shown. The output of operational amplifier 320 is coupled to counter electrode contact pad 216b, which will allow measurement of a sample of biological fluid applied to reagent 18. Additionally, with switches 1006, 1008, and 1010 positioned as illustrated in FIG. . 10, the circuit is configured as shown in FIG. 9 and can be used to automatically compensate for contact and parasitic resistance as described above with respect to FIG. 9.

In order to measure the amount of parasitic resistance on the counter electrode line 216, the switch 1008 is placed in the position shown in FIG. 10, switch 1006 is positioned opposite to that shown in FIG. 10, while switch 1010 is closed. The op amp 320 thus acts as a unity gain buffer and applies a voltage potential to drive the electrode contact plate 216b through a known resistance Rnom. This resistance causes a current to flow in the counter electrode line 216 and the counter sense line 224 that is sensed by the current-voltage amplifier 310, which is now coupled to the current sense line through the switch 1010. . The output of the current-to-voltage amplifier 310 is provided to the microprocessor 314 through A / D 312. Because the value of Rnom is known, the microprocessor 314 can calculate the value of any parasitic resistance on the detector line 224. counter and counter electrode line 216. This parasitic resistance value can be compared to a predetermined threshold stored in the test meter to determine if physical damage has occurred to the test strip 800 or if there is non-conductive build-up on the contact pads to an extent such that the 800 test strip cannot be used reliably to perform a test. In such situations, the test meter can be programmed to inform the user that an alternate test strip must be inserted into the test meter before proceeding with the test.

In order to measure the amount of parasitic resistance on working electrode line 814, switches 1006 and 1008 are set to the opposite position to that shown in FIG. 10, while the switch 1010 is open. The op amp 320 therefore acts as a buffer with unity gain and applies a voltage potential to the work sense contact pad 826b through a known resistor Rnom. This resistance causes a current to flow in the work sense line 826 and the work electrode line 814 that is sensed by the current-to-voltage amplifier 310. The output of the current-to-voltage amplifier 310 is provided to the microprocessor 314 through A / D 312 Since the value of Rnom is known, the microprocessor 314 can calculate the value of any parasitic resistance on the work sense line 826 and working electrode line 814. This parasitic resistance value can be compared to a predetermined threshold stored in the test meter to determine if physical damage has occurred to the test strip 800 or if there is non-conductive build-up on the contact pads to an extent such that the strip Test 800 cannot be used reliably to perform a test. In such situations, the test meter can be programmed to inform the user that an alternate test strip must be inserted into the test meter before proceeding with the test.

FIG. 11 schematically illustrates a test strip of the third embodiment according to the specification having IR drop compensation for both the working electrode and the counter electrode as in FIG. 8. Test strip 1100 of the third embodiment comprises a lower substrate 12 coated on its upper surface with a 50 nm conductive layer (eg, by spraying or vapor deposition, by way of non-limiting example). The electrodes, the connecting tracks, and the contact pads therefor are then patterned into the conductive layer by a laser ablation process as described above. As will be readily apparent to those skilled in the art, the test strip of FIG. 11 is similar to the test strip of FIG. 8. Unlike the test strip of FIG. 8, the counter detection line 224 and the work detection line 826 do not extend into the reaction zone 20. In addition, the counter electrode 216a includes a plurality of fingers 1104 instead of just one. In other embodiments, the working electrode 814a may also include a plurality of fingers 1104. In addition, a capillary space 1102 is provided to attract the sample to the reaction zone 20 so as to cover portions of the electrodes 216a and 814a.

The design illustrated in FIG. 11 inherently includes some performance limitations. Lines AA, BB, CC, etc. are areas that cannot be interrogated to determine if there are defects in the structural integrity of electrodes 216a, 814a or fingers 1104. For example, any physical defects in these areas, such as a scratch that increases resistance to the track or completely cuts the track cannot be detected by the quality assurance checks described above. This is due to the fact that detection lines 224c, 826c join respective electrode tracks 216c, 814c at points between the test meter and line AA.

ES 2 644 041 T3

Any damage to the test strip 1100 between the AA and FF lines is therefore outside the quality assurance test circuit and will have no impact on the IR drop compensation or parasitic resistance threshold test described above. Therefore, the position of the detection lines 826, 224 prevents complete testing of the functionality of the test strip 1100 before a fluid sample is obtained and analyzed. Therefore, the final measurement of the desired characteristic of the fluid sample may be in error.

FIG. 12 illustrates a more robust test strip design to overcome the shortcomings of the design illustrated in FIG. 11. The test strip 1200 includes a work detection line 826 and a counter detector line 224 having respective points 1206, 1208 where the respective electrodes 814a, 216a intersect. The working detector line 826 and the counter detector line 224 are conductive tracks formed on the substrate 12. The distance (measured in a plane parallel to the longitudinal axis of the test strip) between the point 1206 and the power source on the test meter for the test strip 1200 is greater than or equal to the distance between any point on the part of the working electrode 814a within the reagent 18 and the power source. Similarly, the distance between point 1208 and the power source for test strip 1200 is greater than or equal to the distance between any point on the counter electrode portion 216a within reagent 18 and the power source.

The work detection line 826 and the counter detector line 224 include points 1206, 1208 at these locations allowing each point of the test strip 1200 between the power source and the fingers of the measuring electrode to be interrogated regarding to its structural integrity and parasitic resistance. As is visible from Figure 12 in combination with Figure 3, the power source is coupled to the test strip through the contact pads located in the contract zone (22). Therefore, the distance between the intersection points (1206, 1208) and the contact area (22) is greater than or equal to the distance between any point of the electrodes (814a, 216a) and the contact area (22). .

Unlike the design of FIG. 11, the design of FIG. 12 positions detection lines 224, 826 to allow interrogation of electrodes 216a, 814a and associated fingers for structural defects. If a defect is detected, it can be compensated for or it can be indicated and the test strip 1200 can be discarded and a new one can be used. This helps eliminate errors in measuring the desired characteristic of the fluid sample.