BR122017010425B1 - METHOD OF PRODUCING AN ANALYTICAL MEASUREMENT USING A TEST STRIP - Google Patents

Abstract

The present invention relates to a method of producing a measurement of an analyte using a test strip (800) comprising a measuring cell, a counter electrode (216a), and a working electrode (814a). the method comprising the steps of receiving the test strip (800) in the biosensor device; applying stimulus to the counter electrode (216a) to produce the potential through the measuring cell; measure the potential difference developed across the measuring cell by stimulus application; and adapt the applied stimulus to the counter electrode based on the measured potential difference developed across the measuring cell.

Description

Invention Patent Descriptive Report for "METHOD OF PRODUCING AN ANALYTIC MEASUREMENT USING A TEST STRIP".

Divided from PI0510927-2, filed on June 20, 2005.

FIELD OF THE INVENTION [01] The present invention relates to an apparatus for use in measuring signals such as those related to the concentrations of an analyte (such as blood glucose) in a biological fluid as well as those related to interferents ( hematocrit and temperature in the case of blood glucose) at the analyte concentration signals. The present invention relates more particularly to a system and method for quality assurance of a biosensor test strip.

Background of the Invention [02] Measuring the concentration of substances in biological fluids is an important tool for the diagnosis and treatment of various medical conditions. For example, measuring glucose in blood fluids, such as blood, is critical to the effective treatment of diabetes.

[03] Diabetic therapy typically involves two types of insulin treatment: basal, and mealtime. Basal insulin refers to a continuous insulin, for example released over time, often before going to bed. Insulin treatment at mealtime provides additional doses of a faster acting insulin to regulate fluctuations in blood glucose caused by a variety of factors, including sugar and carbohydrate metabolism. Proper regulation of blood glucose fluctuations requires accurate measurement of blood glucose concentration. Failure to do so can produce serious complications including blindness and loss of circulation in the extremities, which may ultimately deprive the diabetic of the use of their fingers, hands, feet, etc.

[04] Multiple methods are known to determine the concentration of analytes in a blood sample, such as glucose. Said methods typically fall into one of two categories: optical methods and electrochemical methods. Optical methods generally involve spectroscopy to observe the spectrum deviation caused by analyte concentration, typically together with a reagent that produces a known coloration when combined with the analyte. Electrochemical methods are generally based on the correlation between a current (amperometry), a potential (potentiometer) or accumulated charge (coulometry) and analyte concentration, typically in conjunction with a reagent that produces charge vehicles when combined with the analyte. . See, for example, U.S. Patent Nos. 4,233,029 to Columbus, 4,225,410 to Pa-ce, 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 for Szuminsky et al., 5,243,516 for White, 5,437,999 for Diebold et al., 5,288,636 for Pollmann et al., 5,628,890 for Carter et al., 5,682,884 for Hill et al., 5,727,548 for Hill et al., 5,997,817 for Crismore et al., 6,004,441 for Fujiwara et al., 4,919,770 for Priedel, et al., and 6,054,039 for Shieh, which are incorporated herein by reference in their entirety. The biosensor for conducting the test is typically a disposable test strip provided with a reagent therein that chemically reacts with the analyte of interest in the biological fluid. The test strip is matched with a non-disposable test meter so that the test meter can measure the reaction between the analyte and the reagent to determine and display the analyte concentration to the user.

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

[06] The test strip 10 therefore has a reaction zone 20 containing the measuring electrodes 14a, 16a, which contact the sample containing the analyte for which the concentration in the sample is to be determined. In an amperometric or coulometric electrochemical measuring system, measuring electrodes 14a, 16a in reaction zone 20 are coupled to the electronic circuit (typically on a test meter (not shown) within which the test strip 10 is inserted, as is well known in the art); which provides an electrical potential to the measuring electrodes and measures the response of the electrochemical sensor to said potential (eg current, impedance, load, etc.). Said response is proportional to the concentration of the analyte.

[07] The test meter contacts the test strip 10 on the contact pads 14b, 16b in the contact zone 22 of the test strip 10. The contact zone 22 is located relatively far from the measurement zone 20 at (but not always) at the opposite end of the test strip 10. Conducting strokes 14c, 16c engage the contact pads 14b, 16b in the contact zone 22 for the respective measuring electrodes 14a, 16a in the reaction zone 20 .

[08] In particular for biosensors 10 in which the electrodes, traces and contact pads are comprised of electrically conductive thin films (eg noble metals, carbon paint, and silver paste as non-limiting examples), The resistivity of the conductive traces 14c, 16c connecting the contact zone 22 to the reaction zone 20 may be several hundred Ohms or more. Said parasitic resistance promotes a potential fall along the length of the strokes 14c, 16c, so that the potential presented to the measuring electrodes 14a, 16a in reaction zone 20 is considerably less than the potential applied by the test meter to the pads. 14b, 16b of test strip 10 in contact zone 22. Because the reaction impedance occurring within reaction zone 20 may be within an order of magnitude of the parasitic resistance of traces 14c, 16c, the signal that is The measured value may present a significant displacement due to the I - R drop (current x resistance) induced by the traces. If said offset varies from test strip to test strip, then a noise is added to the measurement result. In addition, physical damage to the test strip 10, such as abrasion, cracking, scratching, chemical degradation, etc., may occur during manufacture, transportation, storage and / or improper handling by the user. Said defects may damage conductive areas 14, 16 to the extent that they have extremely high resistance or even open circuit. Such increases in trace resistances may prevent the test meter from performing an accurate test.

[010] Thus, the system and method are necessary to allow confirmation of the integrity of the test strip strokes, to measure the parasitic resistance of the test strip strokes, and to control the potential level currently applied to the electrodes. test strip measurement in the reaction zone. The present invention is directed to meeting said needs.

SUMMARY OF THE INVENTION The present invention provides a test strip for measuring a signal of interest in a biological fluid when the test strip is matched with an appropriate test meter, where the test strip and the test meter include structures. to verify the integrity of the test strip strokes, to measure the parasitic resistance of the test strip strokes; and to provide voltage compensation applied to the test strip to compensate for parasitic resistance losses in the test strip strokes.

BRIEF DESCRIPTION OF THE DRAWINGS [012] The present invention will be further described, by way of example only, with reference to the accompanying drawings, in which: [013] Figure 1 is a plan view of a typical prior art test strip for use in measuring the concentration of an analyte of interest in a biological fluid.

Figure 2 is a schematic plan view of a first embodiment of a test strip according to the present invention.

[015] Figure 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 Figure 2.

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

Figure 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.

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

Figure 8 is a schematic plan view of a second embodiment of the test strip according to the present invention.

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

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

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS [023] In order to promote an understanding of inventive principles, reference will now be made to the embodiment illustrated in the drawings, and specific language will be used to describe that embodiment. However, it will be understood that it is not intended to limit the scope of the present invention in any way. Changes and modifications to the illustrated device, and further applications of the principles of the present invention as illustrated herein, as commonly occurring to those skilled in the art to which the invention relates are contemplated, are desired to be protected. In particular, although the present invention is discussed in terms of a blood glucose meter, it is contemplated that the present invention may be used with devices for measuring other analytes and other types of samples. Said alternative embodiments require certain adaptations to the embodiments discussed herein which would be obvious to those skilled in the art.

Although the system and method of the present invention may be used with test strips endowed with a wide variety of designs and produced with a wide variety of construction techniques and processes, a first embodiment of the electrochemistry test strip of The present invention is illustrated schematically in Figure 2, 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 designations. Referring to Figure 2, the test strip 200 comprises a bottom substrate 12 formed from a 350 pm thick opaque polyester piece (such as Melinex 329 offered by DuPont) coated on its upper surface with a layer of conductive gold of 50 nm (for example by scintillation or vapor deposition by way of a non-limiting example). Electrodes, connecting traces and contact pads are therefore then standardized on the conductive layer by a laser ablation process. The laser ablation process is performed by means of an excision laser that passes through a quartz chrome mask. The mask pattern causes parts of the laser field to be reflected while still allowing other parts of the field to pass through, creating a gold pattern which is evaporated when in contact with the laser light. The laser ablation process is described in more detail here below. For example, by working 214a, counter 216a, and perception counter 224a, electrodes may be formed as shown and coupled to respective metering pads 214b, 216b and 224b by respective traces 214c, 216c and 224c. Said contact pads 214b, 216b and 224b provide a conductive area on the test strip 200 to be contacted by a test meter connector contact (not shown) as the test strip 200 is inserted into the test meter. , as is well known in the art.

Figures 2 and 3 illustrate an embodiment of the present invention that enhances the prior art test strip configuration by allowing compensation of the parasitic 1-R drop in the test strip electrode counting 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 perception counter electrode 224a, contact pad 224b, and trace 224c. The provision of the perception counter line 224 allows the test meter (as described below) to compensate for parasitic resistance between the contact pads 216b, 224b. Note that the embodiment of figure 2 when used with the circuit of figure 3 only compensates for the 1R drop on the counter electrode side of test strip 200. Parasitic resistance on the working electrode side of test strip 200 cannot be detected. using said circuit, although it may be replicated on the working electrode side if desired, as will be apparent to those skilled in the art with reference to the present disclosure. Additional methods for compensating for parasitic resistance on both the working and counter sides of the test strip are presented here below. The perception counter line of figure 2 therefore allows the test meter to compensate for any potential drop in parasitic resistance on counter line 216, as explained in greater detail with respect to figure 3.

Referring now to Figure 3, a schematic electrical circuit diagram of a first electrode compensation circuit (generally indicated 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 is applied to the counter electrode contact pad 216b, which will produce a current between counter electrode 216a and working electrode 214a that is proportional to the amount of analyte present in the sample. The working electrode 214a current is transmitted to the working electrode contact pad 214b via the working electrode trace 214c and provided to a current amplifier for voltage 310. The analog output voltage of the amplifier 310 is converted to a digital signal by analog to digital (A / D) converter 312. Said digital signal is then processed by a microprocessor 314 according to a program previously stored to determine the concentration of the analyte within the sample. applied to the test strip 200. This concentration is displayed to the user by means of a appropriate output 316, such as a liquid crystal display (LCD). Microprocessor 314 also outputs a digital signal indicative of the voltage potential to be applied to counter electrode contact pad 216b. Said digital signal is converted to an analog voltage signal by a digital to analog (D / A) converter 318. The analog D / A output 318 is applied to a first input of an operational amplifier 320. A second input of the Operational amplifier 320 is coupled to the counter electrode contact pad 216b.

[027] Operational amplifier 320 is connected in a voltage follower configuration, in which the amplifier will adjust its output (within its physical operating limits) until the voltage appearing on its second input equals the commanded voltage. that appears on your first entry. The second input of operational amplifier 320 is a high impedance input, so substantially no current flows on the perception counter line 224. Since no current flows, any parasitic resistance on the perception counter line 224 will not cause a drop. of potential; and the voltage appearing at the second input of the operational amplifier 320 is substantially the same as the voltage at the perception counter electrode 224a, which is in turn substantially the same as the voltage appearing at the counter electrode 216a because of its physical proximity. next. Operational amplifier 320, therefore, is to vary the voltage potential applied to the counter electrode contact pad 216b until the actual voltage potential appearing on the counter electrode 216a (as fed back over the counter electrode line). 224) is equal to the voltage potential commanded by microprocessor 314. Operational amplifier 320 therefore automatically compensates for any potential drop caused by parasitic resistance in the counter electrode trace 216c, and the potential that appears on 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 produced more precisely, since the voltage that produced the current is in fact the same voltage commanded by microprocessor 314. Without compensation for voltage drops of parasitic resistance provided by circuit 300, microprocessor 315 will analyze the resulting current under the erroneous assumption that the commanded voltage has indeed been applied to counter electrode 216a.

[028] Many methods are offered for the preparation of multi-electrode test strips, such as carbon ink printing, silver paste screen printing, metallized plastic embossing, galvanizing, chemical coating, and photochemical etching, by way of example only. not limiting. A preferred method of preparing a test strip with traditional electrode perception lines as described herein is by the use of laser ablation techniques. Examples of use of such techniques in the preparation of biosensor electrodes are described in US Patent Application Serial No. 09 / 866,030, "Biosensors with Laser Ablation Electrodes with a Continuous Coverlay Channel" filed May 25, 2001, and in the application. US Patent Serial No. 09 / 411,940, entitled "Laser Defined Features for Patterned Laminates and Electrode", filed October 4, 1999, both of which are incorporated herein by reference. Laser ablation is particularly useful for the preparation of test strips in accordance with the present invention in that it enables conductive areas of extremely small characteristic sizes to be precisely manufactured in a repeatable manner. Laser ablation to the test strip without increasing the size of the test strip.

[029] It is desirable in the present invention to provide accurate placement of the electrical components with respect to each other and to the general biosensor. In a preferred embodiment, the relative placement of the components is achieved, at least in part, by the use of a wide-field laser ablation that is performed through a mask or other device that presents an accurate pattern for the electrical components. This allows precise positioning of adjacent edges, which is further increased by strict tolerances for edge smoothness.

Figure 4 illustrates a simple biosensor 401 useful for illustrating the laser ablation process of the present invention, including a substrate 402 provided with a conductive material formed thereon 403 defining electrode systems comprising a first electrode assembly. 404 and a second electrode assembly 405, and corresponding traces 406, 407, and contact pads 408, 409, respectively. Note that biosensor 401 is used herein for the purpose of illustration of the laser ablation process, and is not shown to incorporate the perception lines of the present invention. Conductive material 403 may contain pure metals or alloys, or other materials, which are metallic conductors. Preferably, the conductive material is wavelength absorbent of the laser used to form the electrodes and of a receptive thickness for fast and accurate processing. Non-limiting examples include aluminum, carbon, copper, chromium, gold, indium tin oxide (ITO), palladium, platinum, silver, tin oxide / gold, titanium, mixtures thereof, and alloys of the metal compounds of said elements. Preferably, the conductive material includes noble metals or alloys or their oxides. Preferably, the conductive material includes gold, palladium, aluminum, titanium, platinum, ITO, and chromium. The conductive material ranges in thickness from about 10 nm to about 80 nm, preferably from about 30 nm to about 70 nm, and even more preferably 50 nm. It is observed that the thickness of the conductive material depends on the transmission property of the material and other factors related to the use of the biosensor.

Although not illustrated, it is noted that the resulting standardized conductive material may be coated or laminated with additional metal layers. For example, the conductive material may be copper, which is then laser ablated, in an electrode pattern; subsequently, copper may be laminated with a titanium / tungsten layer, and then a gold layer, to form the desired electrodes. Preferably, a single layer of conductive material is used, which is at base 402. Although not generally necessary, it is possible to increase the adhesion of conductive material to the base, as is well known in the art, by using seed layers or layers. auxiliaries such as nickel chrome or titanium. In preferred embodiments, biosensor 401 has a single layer of gold, palladium, platinum or ITO.

Biosensors 401 are illustratively manufactured using two apparatuses 10, 10 ', shown in figures 5, 6 and 7, respectively. It is noted that unless otherwise described, the apparatus 410, 410 'operate in a similar manner. Referring to Figure 5, the biosensor 401 is manufactured by feeding a roll of ribbon 420 provided with an 80 nm gold laminate, which is about 40 mm wide in a plug-in wide-field laser ablation apparatus. 410. The apparatus 410 comprises a laser source 411 which produces a laser beam of light 412, a chrome-coated room mask 414, and optical elements 416. It is noted that although the illustrated optical elements 416 are a single lens, the Optical elements 416 are preferably a variety of cooperating lenses for configuring light 412 to a predetermined shape.

[033] A non-limiting example of a suitable ablation apparatus 410 (Figures 5-6) is a commercially customized 200-4 MicrolineLa-be laser system offered by LPFK Laser Electronic GmbH of Garbsen, Germany, which incorporates a system Laser-LPX-400, LPX-300 or LPX-200, commercially offered by Lamb-da Physik AG, Gottingen, Germany, and a chrome-plated quartz mask commercially offered by the International Phototool Company, Colorado Springs, Co.

[034] For the MicrolineLaser 200-4 laser system (Figures 5 - 6), the 411 laser source is an LPX-200 KrF-UV-laser. However, it is noted that higher UV wavelength lasers may be used in accordance with the present disclosure. The 411 laser source operates at 248 nm, with a pulse energy of 500 mJ, and a pulse repetition frequency of 50 Hz. The intensity of the laser beam 412 can be infinitely adjusted between 3% and 92% by a frequency attenuator. dielectric radius (not shown). The beam profile is 27 x 15 mm2 (0.62 square inch) and the pulse duration is 25 ns. The layout on mask 414 is homogeneously designed by an optical element radius expander, homogenizer and field lens (not shown). Homogenizer performance was determined by measuring the energy profile. Optical imaging elements 416 transfer the structures of the mask 414 onto tape 410. The image aspect ratio is 2: 1 to allow on the one hand a large area to be removed, and on the other hand to keep the energy density below that. ablation point of the applied chrome mask. Although a 2: 1 image is illustrated, it is observed that any number of alternative proportions is possible according to the present description depending on the desired needs. A tape 420 moves as shown by arrows 425 to allow a series of segment layout to be aborted in succession.

The positioning of the mask 414, the movement of the ribbon 420, and the laser energy are computer controlled. As shown in Fig. 5, laser beam 412 is projected onto ribbon 420 to be ablated. Light 412 passing through clear areas or windows 418 of mask 414 ablates the metal of ribbon 420. The chrome-plated areas 424 of mask 414 block laser light 412 and prevent ablation in said areas, which results in a metallic structure on the tape surface 420. Referring now to Figure 6, a complete structure of electrical components may require additional ablation steps through a second mask 414 '. It is noted that depending on the optical elements and the size of the electrical component to be blown, that only a single ablation step or more than two ablation steps may be required according to the present description. Furthermore, it is observed that instead of multiple masks, multiple fields may be formed in the same mask according to the present description.

Specifically, a second non-limiting example of a suitable ablation device 410 '(Figure 7) is a commercially available laser system offered by LPKF Laser Electronic GmbH of Garbsen, Germany, which incorporates a Lambda STEEL laser system. (Stable excision energy laser) commercially offered by Lambda Physik AG, Gottingen, Germany and a chrome-coated quartz mask commercially offered by the International Phototool Company, Colorado Springs, Co. The laser system features a pulse energy of about 1000 mJ at a wavelength of 308 nm. In addition, the laser system has a frequency of 100 Hz. The apparatus 410 'can be formed to produce two-pass biosensors as shown in figures 5 and 6, but preferably its optical elements allow the formation of a 10 x 40 pattern. mm in a single 25 ns pass.

Although not intended to adhere to a specific theory, it is believed that the pulse or laser beam 412 passing through the mask 414, 414 ', 414 "is absorbed within less than 1 μιτι of surface 402 on the surface. 420. Photons of radius 412 exhibit sufficient energy to promote photodissociation and rapid breakdown of chemical bonds at the metal / polymer interface, said rapid chemical bond breakage causing a sudden increase in pressure within the region. absorption and force the material (metal film 403) to be ejected from the base surface of the polymer Once typical pulse durations are around 20 - 25 nanoseconds, interaction with the material occurs very quickly and thermal damage to the edges of conductive material 403 and surrounding structures is minimized.The resulting edges of the electrical components feature high edge quality and precise placement. as contemplated by the present invention.

The flowing energies used to remove or ablate metals from tape 420 are dependent 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 from the process used to place the film on the base material; that is, support and vapor deposition. Creep levels for gold in KALADEX® range from about 50 mJ / cm2 to 90 mJ / cm2, polyimide at about 100 mJ / cm2 to about 120 mJ / cm2, and MELINEX® at about 60 mJ / cm2 to about 120 mJ / cm2. It is understood that creep levels lower or higher than above may be appropriate for other base materials in accordance with the present disclosure.

[039] Standardization of tape areas 420 is achieved by using masks 414, 414 '. Each mask 414, 414 'illustratively includes a mask field 422 containing 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 the strokes. As shown in Figure 6, the second mask 414 'contains a corresponding second portion of the strokes and the finger-holding electrode patterns. As previously described, it is appreciated that depending on the size of the area to be ablated, the mask 414 may contain a complete illustration of the electrode patterns (figure 7), or portions of the different patterns from those illustrated in figures 5 and 6, according to with the present description. Preferably, it is contemplated that in one aspect of the present invention, the entire pattern of electrical components on the test strip is laser ablated at one time, that is, the wide field encompasses the entire size of the test strip (Figure 7). . Alternatively, and as illustrated in Figures 5 and 6, portions of the entire biosensor are carried out successively.

Although mask 414 is discussed later here, it is appreciated that unless otherwise indicated, the discussion will apply to masks 414 ', 414 "in the same way. With reference to figure 5, the areas 424 of the field mask-protected 422 masks will block the projection of laser beam 412 to tape 420. The light areas or windows 418 in the mask 422 field allow laser beam 412 to pass through mask 414 and bump into predetermined areas of the tape. 420. As shown in Figure 5, the light area 418 of mask field 422 corresponds to the areas of tape 420 from which conductive material 403 should be removed.

In addition, mask field 422 has a length shown by line 430 and a width as shown by line 432. Considering a 2: 1 aspect ratio of the LPX-200, it is observed that mask length 30 is two times 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 ribbon 420. Optical elements 416 reduce the size of the laser beam 412 that strikes ribbon 420. It is appreciated that the relative dimensions of mask field 422 and the resulting pattern may vary according to the present disclosure. Mask 414 '(Figure 6) is used to complete the two-dimensional illustration of the electrical components.

Continuing with reference to figure 5, in laser ablation apparatus 410, excision laser source 411 emits radius 412, which passes through quartz chrome mask 414. masking field 422 causes part of the laser beam 412 is reflected while allowing other parts of the laser beam to pass through, creating a pattern in the gold film where it received the laser beam impact 412. It is observed that the tape 420 can be stationary relative to the device 410 or move continuously. thus, non-limiting coefficients of tape movement 420 may be from about 0 m / min to about 100 m / min, more preferably from about 30 m / min to about 60 m / min. m / min It is noted that the tape coefficient of motion 420 is only limited by the selected apparatus 410 and may also exceed 100 m / min depending on the pulse duration of laser source 411 according to the present disclosure.

Once the mask pattern 414 is created on tape 420, the tape is rewound and fed through the apparatus 410 once again with the mask 414 '(figure 6). It is noted that, alternatively, the laser apparatus 410 may be positioned in series according to the present disclosure. Thus, when using masks 414, 414 ', large areas of tape 420 can be patterned using step and repeat processes, which involve multiple mask fields 422 in the same mask area to enable economical creation of intricate electrode patterns and other electrical components on the base substrate; precise edges of the electrode components and the removal of larger amounts of metal film from the base material.

[044] The second embodiment of the present invention illustrated in Figures 8 and 9 improves upon the prior art by providing 1-R drop compensation of both working electrode leads and counters on the test strip. Referring now to Figure 8, a second embodiment of the test strip configuration of the present invention is shown schematically illustrated, generally indicated at 800. Test strip 800 comprises a bottom substrate 12 coated on its upper surface with a gold layer. 50 nm (eg by scintillation or vapor deposition by non-limiting example). Electrodes, connecting traces and contact pads are therefore then standardized on the conductive layer by a laser ablation process as described hereinbefore above. For example, working perception electrodes 814a, working perception 826a, counter 216a, and perception counter 224a may be formed as shown and coupled to respective metering contact pads 814b, 826b, 216b and 224b by means of their respective dashes 814c, 826c, 216c and 224c. Said contact pads 814b, 826b, 216b and 224b provide a conductive area over test strip 800 to be contacted by the test meter connection contact (not shown) as test strip 800 is inserted into the meter. of test.

It will be appreciated that the test strip 800 of figure 8 is substantially identical to the test strip of the first embodiment 200 of figure 2, except for the addition of working perception electrode 826a, contact pad 826b and trace 826c. The provision of the 826 work perception line allows the test meter to compensate for any I - R drop caused by the contact resistance of the contact pad connections 814b and 216b, and to compensate for the trace resistance of the 814c and 216c strokes. .

Referring now to Figure 9, a schematic electrical circuit diagram of a second electrode compensation circuitry (generally indicated at 900) housed within the test meter is shown. As indicated, the circuit couples 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, the voltage potential is applied to the counter electrode contact pad 216b, which will produce a current between counter electrode 216a and working electrode 814a that is proportional to the amount of analyte present in the sample. 18. The working electrode current 814a is transmitted to the working electrode trace 814c to the working electrode contact pad 814b and provided to the current amplifier for voltage 310. The analog output voltage 310 is converted to a digital signal by A / D 312. Said digital signal is then processed by microprocessor 314 according to a previously stored program to determine the concentration of analyte of interest within the biological sample applied to test strip 800. Said concentration is displayed to the user via the LCD316 output device.

Microprocessor 314 also outputs a voltage potential indicator output signal to be applied to the counter electrode contact pad 216b. Said digital signal is converted to analog voltage signal by D / A 318 (reference voltage source). Analog D / A output 318 is applied to the first input of an operational amplifier 320. A second operational amplifier input 320 is coupled to an output of operational amplifier 910. Operational amplifier 910 is connected in a different amplifier configuration using an amplifier. of instrumentation. A first input of operational amplifier 910 is coupled to the perception working electrode contact pad 826b, while the second input of operational amplifier 910 is coupled to the perception working electrode contact pad 826b, while the second input of operating amplifier 910 910 is coupled to the perception counter electrode contact pad 224b. The output of the operational amplifier 320 is coupled to the counter electrode contact pad 216b. When the biosensor test strip 800 is coupled to the test meter, a first input of the operational amplifier 910 is coupled to the perception working trace 826c and a second input is operatively coupled to the perception counter trace 224c. The output of the operational amplifier is operatively coupled to the counter electrode trace. Operational amplifier 910 in the present configuration functions as a difference amplifier.

[048] Operational amplifier 320 is connected in a voltage follower configuration, in which the amplifier will adjust its output (within physical operating limits) until the voltage appearing on its second output equals the commanded voltage that appears on your first exit. Both inputs of operational amplifier 910 are high impedance inputs, so substantially no current flows on the perception counter line 224 or the perception work line 826. Since no current flows, any parasitic resistance on the perception counter line 224 or perception line 826 will not cause a potential drop; and the voltage appearing at the inputs of operational amplifier 910 is substantially the same as the voltage across the measuring cell (i.e. through counter electrode 216a and working electrode 814a). Because the 910 operational amplifier is connected in a difference amplifier configuration, its output represents the voltage across the measuring cell.

[049] Operational amplifier 320 will therefore act to vary its output (ie, the voltage potential applied to counter electrode contact pad 216b) until the current voltage potential that appears through the measuring cell. equals the voltage potential commanded by microprocessor 314. Operational amplifier 320 therefore compensates for any potential drop caused by parasitic resistance on counter electrode trace 216c, counter electrode contact pad 216b, working electrode trace 814c, and electrode contact 814b, and therefore the potential that appears through the measuring cell is the desired potential. The calculation of the analyte concentration in the biological sample from the current produced by the working electrode is therefore more accurate produced.

Figure 10, together with Figure 8, illustrates a third embodiment of the present invention which is an improvement over the prior art by providing I - R drop compensation for both working electrode lines and for counters, as well as providing verification that the resistance of both working electrode lines such as the counters is not above a predetermined threshold to ensure that the test meter is able to compensate for I - R drops. Referring now to Figure 10, a schematic electrical circuit diagram of a third embodiment of the electrode compensation circuit (generally indicated at 1000) housed within the test meter is shown. Electrode compensation circuit 1000 works with test strip 800 of Figure 8. As indicated, the circuit couples contact pads 826b, 814b, 216b and 224b when test strip 800 is inserted into the test meter. As will be appreciated by those skilled in the art, the voltage potential is applied to the counter electrode contact pad 216b, which will produce a current between the counter electrode 216a and working electrode 814a that is proportional to the amount of analyte present in the sample. applied to the reagent 18. The current from the working electrode 814a is transmitted to the working electrode contact pad 814b by the working electrode trace 814c and provided to the voltage current amplifier 310. The output of the voltage current amplifier 310 is applied to the input of instrumentation amplifier 1002, which is configured as a buffer with a unit gain when switch 1004 is in the closed position. The analog output voltage of amplifier 1002 is converted to a digital signal by A / D 312. Said digital signal is then processed by microprocessor 314 according to a previous stored program to determine the concentration of analyte within the biological sample. applied to test strip 800. Said concentration is displayed to the user via a 316 LCD output device.

[051] Microprocessor 314 also outputs a digital signal indicating voltage potential to be applied to counter electrode contact pad 216b. Said digital signal is converted to analog voltage signal by D / A 318. Analog output of D / A 318 is applied to the input of an operational amplifier 320 which is configured as a voltage follower when switch 1006 is on. position shown. The output of the operational amplifier 320 is coupled to the counter electrode contact pad 216b, which will allow measurement of a biological fluid sample applied to reagent 18. In addition, with switches 1006, 1008 and 1010 positioned as shown in Figure 10, The circuit is configured as shown in Figure 9 and can be used to automatically compensate for parasitic and contact resistance as described hereinabove with respect to Figure 9.

In order to measure the amount of parasitic resistance on the counter electrode line 216, the key 1008 is arranged in the position shown in figure 10, the key 1006 is arranged in the opposite position to that shown in figure 10, while the key 1010 is closed. Operational amplifier 320 therefore acts as a unit gain buffer and applies a voltage potential to the counter electrode contact pad 216b through a known resistor Rn0m-A said resistor causes a flow current in the counter electrode line 216 and the perception counter line 224 which is sent by voltage current amplifier 310, which is now coupled to the perception current line via switch 1010. Output of voltage current amplifier 310 is provided to microprocessor 314 via A / D 312. Because the value of Rn0m is known, microprocessor 314 can calculate the value of any parasitic resistance at the perception counter line 224 and counter electrode line 216. Said parasitic resistance value can be compared to a threshold. stored on the test meter to determine if physical damage occurred on test strip 800 or if an Non-conductive is then present on the contact pads such that the test strip 800 cannot be reliably used to perform the test. In such a situation, the test meter may be programmed to inform the user that an alternative test strip must be inserted into the test meter before proceeding with the test.

[053] In order to measure the amount of parasitic resistance on the working electrode line 814, switches 1006 and 1008 are disposed in a position opposite to that shown in figure 10, while switch 1010 is opened. Operational amplifier 320 therefore acts as a unit gain buffer and applies the voltage potential to the perception working contact pad 826b through a known resistance Rn0m. 826 and working electrode line 814 which is perceived by voltage current amplifier 310. The output of voltage current amplifier 310 is provided to microprocessor 314 via A / D 312. Because the value Rn0m is known, microprocessor 314 can calculate the value of any parasitic resistance on the perception working line 826 and the working electrode line 814. Said parasitic resistance value can be compared to a predetermined threshold stored in the test meter to determine if the damage is present. occurred on the 800 test strip or if the nonconductive increment is present on the contact pads to an extent such that test strip 800 cannot be reliably used to perform the test. In such a situation, the test meter may be programmed to inform the user that an alternative test strip must be inserted into the test meter before proceeding with the test.

All publications, previous applications, and other documents cited herein are incorporated by reference in their entirety as if individually incorporated by reference and broadly determined.

Although the present invention has been illustrated and described in detail in the drawings and previous description, the description should be considered as illustrative and not restrictive. Only the preferred embodiment, and certain other embodiments deemed useful in further explanation of how to make use of the preferred embodiment, have been shown. All changes and modifications that are within the spirit of the invention are considered protected.

Claims (2)

Method of producing a measurement of an analyte using a test strip (800) comprising a measuring cell, a counter electrode (216a), and a working electrode (814a), the method comprising steps of receiving the test strip (800) in the biosensor device; applying stimulus to the counter electrode (216a) to produce the potential through the measuring cell; measure the potential difference developed across the measuring cell by stimulus application; and adapt the applied stimulus to the counter electrode based on the measured potential difference developed across the measuring cell. Method according to claim 1, characterized in that the test strip (800) additionally comprises a working electrode (814a); a perception working contact pad (826b) is operatively coupled to the working electrode (814a); a working electrode contact pad (814b) is operatively coupled to the working electrode (814a); a counter electrode (216a); a counter electrode contact pad (216b) is operably coupled to the counter electrode (216a); and a perception counter contact pad (224b) is operably coupled to the counter electrode (216a); the method further comprising receiving from the perception working contact pad (826b) a potential perception working contact pad (826b) from the working electrode (814a); receiving from the perception counter contact pad (224b) a potential of the perception counter contact pad (826b) from the counter electrode (216a); and comparing the perception working contact pad potential (826b) with the perception counter contact pad potential (826b) to produce potential measurement across the measuring cell.