Method for quality assurance of a biosensor test strip

Field of the invention The present invention relates to apparatus for use in measuring signals, such as those associated with analyte concentrations (such as blood glucose) in a biological fluid, as well as related to interference factors (such as hematocrit and temperature in the case of glucose in blood ) and analyte concentration signals. The invention more particularly relates to a system for providing a quality test strip to a biological sensor.

Background of the Invention [0002] Measuring the concentration of a substance in biological fluids is an important tool for diagnosing and treating a variety of medical conditions. For example, the measurement of glucose in body fluids such as blood is crucial in the effective treatment of diabetes.

[0003] Diabetic therapy usually involves two types of insulin treatment: basal and auxiliary. Basic insulin means insulin administered continuously, e.g. released over time, and often taken before going to sleep. Insulin supplementary treatment includes additional doses of faster-acting insulin to regulate blood glucose fluctuations caused by various factors, including the metabolism of sugars and carbohydrates. Correct regulation of blood glucose fluctuations requires careful measurement of blood glucose. Failure to do so can cause extreme complications, including blindness and loss of circulation in the limbs, which ultimately deprives the diabetic of the ability to use the fingers, hands, feet, etc.

[0004] Many methods are known for determining the concentration of analytes in blood samples, such as for example glucose. Such methods typically fall into one of two categories: optical methods and electrochemical methods. Optical methods include essentially spectroscopy to observe changes in the liquid spectrum caused by the analyte concentration, typically in association with a reagent that, in combination with ananite, gives a known color. Electrochemical methods are basically based on the correlation between current (amperometry), potential (potentiometry) or accumulated charge (coulometry), as well as analyte concentration, typically in combination with a reagent that generates charge carriers when combined with an analyte. For example, US Patent Nos. 4,233,029 to Columbus, US 4,22,5,410 to Pace, US 4,323,536 to Columbus, US 4 008 448 to Muggli, US 4 654 197 to Lilja et al., US 5 108 564 to Szuminsky et al., US 5 120 420 to Nankai et al., US 5 128 015 to Szuminsky et al. , US 5 243 516 to White, US 5 437 999 to Diebold et al., US 5 288 636 to Pollmann et al., US 5 628 890 to Carter et al., US 5 682 884 to Hill et al., US 5 727 548 to Hill et al., US 5 997 817 to Crismore et al., US 6 004 441 to Fujiwara et al., US 4 919 770 to Priedel, et al. also US 6 054 039 to Shieh, as well as WO 99/32881. The biosensor for testing is typically a disposable test strip, which has a reagent on it that is chemically reacted with the appropriate analyte in the biological fluid. This test strip is adapted to the test meter in such a way

[0005] Fig. 1 schematically illustrates a single-use disposable test strip of a biosensor, indicated generally by the designation 10 (see, for example, patents

US4 999 582 and US 5 438 271, whose rights have been transferred to the same licensee as in 1

ΕΡ 2 325 629 Β1 of the current application). This test strip 10 is formed on a non-conductive substrate 12 on which conductive regions 14, 16 are formed. Chemical reagent 18 is applied to conductive regions 14, 16 at one end of test strip 10. Reagent 18 will react with the corresponding analyte in the biological sample at a method that can be detected when voltage is applied between the measuring electrodes 14a and 16a.

[0006] The test strip 10 thus has a reaction zone 20 comprising measuring electrodes 14a, 16a, in direct contact with the sample containing the analyte whose concentration in the sample is to be determined. In an amperometric or coulometric electrochemical measurement system, the measuring electrodes 14a, 16a in the reaction zone 20 are coupled to an electronic circuit (typically in a test meter (not shown) to which the test strip 10 is inserted, as is well known in the art), which brings the electrical potential to the measuring 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.

[0007] The test meter comes into contact with the test strip 10 at the contact fields 14b, 16b in the contact zone 22 of the test strip 10. The contact zone 22 is located at a slight distance from the measuring zone 20, usually (but not always) at the opposite end of the test strip 10. The conducting paths 14c, 16c couple the contact fields 14b, 16b in the contact zone 22 with the respective measuring electrodes 14a, 16a in the reaction zone 20.

[0008] Especially for biosensors 10 in which the electrodes, paths and contact pads are contained in electrically conductive thin films (e.g. precious metals, carbon coating and silver plating with a paste, as part of non-limiting examples), resistance of conductive paths 14c, 16c, which connect the contact zone 22 with the reaction zone 20, may be several hundred ohms or more. This parasitic resistance causes a decrease in potential along the paths 14c, 16c, in such a way that the potential present on the measuring electrodes 14a, 16a in the reaction zone 20 is significantly smaller than the potential applied by the test meter to the contact areas 14b, 16b of the test strip 10 in the zone 22. Due to the impedance of the reaction, occurring within the reaction zone 20 may be of the order of magnitude of parasitic resistance in paths 14c, 16c, the measured signal may have a significant displacement due to the decrease in lR (current x resistance) induced by the paths. If this offset changes for different strips, noise is added to the measurement result. Furthermore, physical damage to the test strip 10, such as seizing, cracks, scratches, chemical degradation, etc., may occur during manufacture, transport, storage and / or incorrect handling by the user. These defects can cause damage to the conducting areas 14, 16 to the point where they give extremely high resistance or even an open circuit. Such an increase in path resistance may prevent the test meter from performing an accurate test. the measured signal may have a significant displacement due to the lR (current x resistance) induced by the path. If this offset changes for different strips, noise is added to the measurement result. Furthermore, physical damage to the test strip 10, such as seizing, cracks, scratches, chemical degradation, etc., may occur during manufacture, transport, storage and / or incorrect handling by the user. These defects can cause damage to the conducting areas 14, 16 to the point where they give extremely high resistance or even an open circuit. Such an increase in path resistance may prevent the test meter from performing an accurate test. the measured signal may have a significant displacement due to the lR (current x resistance) induced by the path. If this offset changes for different strips, noise is added to the measurement result. Furthermore, physical damage to the test strip 10, such as seizing, cracks, scratches, chemical degradation, etc., may occur during manufacture, transport, storage and / or incorrect handling by the user. These defects can cause damage to the conducting areas 14, 16 to the point where they give extremely high resistance or even an open circuit. Such an increase in path resistance may prevent the test meter from performing an accurate test. If this offset changes for different strips, noise is added to the measurement result. Furthermore, physical damage to the test strip 10, such as seizing, cracks, scratches, chemical degradation, etc., may occur during manufacture, transport, storage and / or incorrect handling by the user. These defects can cause damage to the conducting areas 14, 16 to the point where they give extremely high resistance or even an open circuit. Such an increase in path resistance may prevent the test meter from performing an accurate test. If this offset changes for different strips, noise is added to the measurement result. Furthermore, physical damage to the test strip 10, such as seizing, cracks, scratches, chemical degradation, etc., may occur during manufacture, transport, storage and / or incorrect handling by the user. These defects can cause damage to the conducting areas 14, 16 to the point where they give extremely high resistance or even an open circuit. Such an increase in path resistance may prevent the test meter from performing an accurate test. may appear during manufacture, transport, storage and / or incorrect handling by the user. These defects can cause damage to the conducting areas 14, 16 to the point where they give extremely high resistance or even an open circuit. Such an increase in path resistance may prevent the test meter from performing an accurate test. may appear during manufacture, transport, storage and / or incorrect handling by the user. These defects can cause damage to the conducting areas 14, 16 to the point where they give extremely high resistance or even an open circuit. Such an increase in path resistance may prevent the test meter from performing an accurate test.

[0009] WO 2004/005908 describes a system in which a voltage is applied to one of the electrodes, a voltage is measured at the same electrode, and then the voltage applied to the electrode is regulated until the voltage measured at the electrode reaches the desired electrode voltage. .

[0010] Thus, a system and method is needed that allows confirming the integrity of the test strip paths, for measuring the parasitic resistance of the test strips, and also for controlling the level of potential actually applied to the test strip measuring electrodes in the reaction zone. The present invention relates to the fulfillment of these needs.

ΕΡ 2,325,629 Β1

Summary of the Invention [0011] The present invention relates to methods for calculating the parasitic impedance of at least the path of a biosensor test strip according to claim 1. 1 and 3, and methods of using a biosensor meter to perform the same according to claim 1; 5 and 8.

Brief Description of the Drawings [0012] The invention will be further described only by way of example, with reference to the figures of the attached drawing, in which:

Fig. 1 is a schematic elevational view of a typical prior art test strip for use when measuring the concentration of a corresponding analyte in a biological fluid.

Fig. 2 is a schematic top view of a test strip.

Fig. 3 is a diagram of an embodiment of the electronic test circuit for use with the test strip according to Fig. 2.

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

Fig. 5 is a view of the ablative apparatus.

Fig. 6 is a view of the laser ablation apparatus according to Fig. 5 showing a second bezel.

Fig. 7 is a view of the ablative apparatus.

Fig. 8 is a schematic top view of a test strip for use in the present invention. Fig. 9 is a diagram of an embodiment of the electronic test circuit for use with the test strip according to Fig. 8.

Fig. 10 is a diagram of an embodiment of the electronic test circuit for use with the test strip according to Fig. 8.

Detailed Description of Preferred Embodiments [0013] For presenting and understanding the basic features of the invention, reference will now be made to the embodiment illustrated in the drawings, and particular terms will be used to describe this embodiment. It is understood, however, that this is not intended to limit the scope of the invention. Changes and modifications in the apparatus illustrated herein, as well as further applications of the basic features of the invention as illustrated, which are obvious to those skilled in the art to which the invention belongs, have been considered and protected. More specifically, although the invention has been discussed with reference to a blood glucose meter, consideration is given to the possibility of using the invention with devices for measuring other analytes and other types of samples.

[0014] Although the methods of the invention may be used with test strips having a large variety of designs and a large variety of construction techniques and processes, the first solution of the electrochemical test strip according to the invention is schematically shown in Fig. 2, and generally designated as 200. Test strip parts 200, which are substantially identical to parts of the test strip 10, have been designated by like numerals. Referring to Fig. 2, the test strip 200 includes a bottom substrate 12 formed of an opaque piece of polyester having a thickness of 350 μm (such as Melinex 329 available from Du-Pont) coated on its upper surface with a conductive 50 nm thick gold layer (e.g. for example by sputtering or steam deposition, in ra3

ΕΡ 2 325 629 Β1 of non-limiting example). The electrodes, the paths connecting them and their contact areas are arranged according to the pattern in the conductive layer in the laser ablation process. This laser ablation process is performed using an excimer laser that passes through a chrome-covered quartz mask. The pattern of the mask causes that parts of the laser field will be reflected by it, while other parts of the field will pass through it, creating a pattern on the gold, which is evaporated in places where it comes into contact with the laser light. The laser ablation process is described in more detail below. For example, the working electrode 214a, the counter electrode 216a, and the sensor counterpart 224a can be made as shown and connected to the respective measuring contact pads 214b, 216b and 224b via respective paths 214c, 216c and 224c. These contact pads 214b, 216b and 224b provide a conducting area on the test strip 200 for contacting the test switch connector (not shown) when the test strip 200 is inserted into the test meter as known in the art.

[0015] Figs. 2 and 3 illustrate a schematic electric circuit that is not covered by this invention and is only presented for explanation purposes and which is an improvement over prior art test strips by allowing the parasitic slope lR of the counter-electron line of the test strip to be compensated. It will be understood that the test strip 200 of Fig. 2 is substantially identical to the prior art test strip 10 of Fig. 1, with the exception of adding the sensor counterpart 224a, the contact pad 224b, and the track 224c. The use of iinii 224 sensor counter-electrode enables the test meter (as described below) to compensate for the parasitic resistance between contact piles 216b, 224b. It is noted that the embodiment of Fig. 2 when used with the circuit according to Fig. 3, only compensates for a drop! -R on the side of the counter-electrode of the test strip 200. The parasitic resistance on the working side of the starter strip 200 can not be detected using this circuit, however it can be replicated on the working electrode side, if needed, as will be understood by specialists in this field based on the present disclosure. There are ways to compensate for the parasitic resistance of both the working electrode and the test strip counter electrodes below. The sensor counter electrode line according to Fig. 2 thus allows the test sensor to compensate for any decrease in the potential of the parasitic resistance in the counter electrode line 216, as explained in more detail with reference to Fig. 3. The parasitic resistance on the working side of the starting strip 200 can not be detected using this circuit, although it can be replicated on the working electrode side, if needed, as will be understood by those skilled in the art from the present disclosure. There are ways to compensate for the parasitic resistance of both the working electrode and the test strip counter electrodes below. The sensor counter electrode line according to Fig. 2 thus allows the test sensor to compensate for any decrease in the potential of the parasitic resistance in the counter electrode line 216, as explained in more detail with reference to Fig. 3. The parasitic resistance on the working side of the starting strip 200 can not be detected using this circuit, although it can be replicated on the working electrode side, if needed, as will be understood by those skilled in the art from the present disclosure. There are ways to compensate for the parasitic resistance of both the working electrode and the test strip counter electrodes below. The sensor counter electrode line according to Fig. 2 thus allows the test sensor to compensate for any decrease in the potential of the parasitic resistance in the counter electrode line 216, as explained in more detail with reference to Fig. 3. however, it can be replicated on the side of the working electrode, if needed, as will be understood by those skilled in the art from the present disclosure. There are ways to compensate for the parasitic resistance of both the working electrode and the test strip counter electrodes below. The sensor counter electrode line according to Fig. 2 thus allows the test sensor to compensate for any decrease in the potential of the parasitic resistance in the counter electrode line 216, as explained in more detail with reference to Fig. 3. however, it can be replicated on the side of the working electrode, if needed, as will be understood by those skilled in the art from the present disclosure. There are ways to compensate for the parasitic resistance of both the working electrode and the test strip counter electrodes below. The sensor counter electrode line according to Fig. 2 thus allows the test sensor to compensate for any decrease in the potential of the parasitic resistance in the counter electrode line 216, as explained in more detail with reference to Fig. 3. There are ways to compensate for the parasitic resistance of both the working electrode and the test strip counter electrodes below. The sensor counter electrode line according to Fig. 2 thus allows the test sensor to compensate for any decrease in the potential of the parasitic resistance in the counter electrode line 216, as explained in more detail with reference to Fig. 3. There are ways to compensate for the parasitic resistance of both the working electrode and the test strip counter electrodes below. The sensor counter electrode line according to Fig. 2 thus allows the test sensor to compensate for any decrease in the potential of the parasitic resistance in the counter electrode line 216, as explained in more detail with reference to Fig. 3.

[0016] Referring now to Fig. 3, an electrical circuit diagram for the electrode compensation circuit t (indicated generally by the sign 300) is shown encapsulated within the test meter. As indicated, the circuit is coupled to the contact 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, the voltage potential is applied to the counter contact contact zone 216b, which will generate a current flow between the counter electrode 216a and the working electrode 214a that is proportional to the amount of the analyte present in the biological sample applied to the reagent 18.

ΕΡ 2 325 629 wi1 wi via a suitable output device 316, such as a liquid crystal display (LCD) screen.

[0017] Microprocessor 314 also sends a digital signal indicating the voltage potential to be applied to contact-oriented contact arrester 216b. This digital signal is converted into an analog voltage signal by a digital-to-analog (D / A) converter 318. An analogue output from D / A 318 is routed to the first operational input of the amplifier 320. The second input of the operational amplifier 320 is coupled to the contact pad 224b sensor overload. The output from the operational amplifier 320 is coupled to the contact contact field 216b of the intrusions. [0018] The operational amplifier 320 is connected in a voltage follower configuration in which the amplifier will regulate its output signal (within its physical limits), until the voltage appearing at its second input will be equal to the desired voltage appearing at its first input. The second input of the operational amplifier 320 is a high impedance input, and therefore no current flows substantially in line 224 of the sensor overload. Because there is no current there, no parasitic resistance in the sensor overlapping line 224 will cause a drop in potential, whereas the voltage appearing at the second input of the operational amplifier 320 is substantially the same as the voltage at the counter-electrode sensor 224a, which is in turn, basically the same as the voltage appearing on the counter electrode 216a due to their close physical proximity. The working amplifier 320 thus operates that it changes the potential of the voltage acting on the contact contact field 216b of the overloads until the actual voltage potential appearing on the counter electrode 216a (as reverse on the sensor overload line 224) is equal to the voltage potential demanded by the microprocessor 314. The operating amplifier 320 automatically compensates any potential drop caused by the parasitic resistance in the path 216c of the intrusions, as well as the potential occurring at the counter-electrode 216a is the desired potential. Calculation of the concentration of the analyte in the biological sample based on the current generated by the working electrode is therefore made more accurately, because the voltage that generated the current is in fact the same voltage requested by the microprocessor 314.

[0019] A variety of methods are available for preparing test strips having a plurality of electrodes, such as carbon-paper printing, silver-stamp sieve printing, milling of metallized plastic, electroplating, chemical coating, and photochemical etching, as a non-limiting example. One of the preferred methods for preparing a test strip having additional sensor electrode lines, as described, is the use of laser ablation techniques. Examples of the use of these techniques for the preparation of electrodes for biosensors are described in U.S. Serial No. US 09/866 030, entitled "Biosensors with Laser Ablation Eiectrodes with a Continuous Coverlay Channel", filed May 25, 2001, and currently US Patent No. 7,473. 398, because it allows the precise production of conductive areas having extremely small element sizes in a repetitive manner. Laser ablation za5 because it allows the precise production of conductive areas having extremely small element sizes in a repetitive manner. Laser ablation za5

ΕΡ 2 325 629 Β 1 means for adding additional sensor lines according to the present invention in the test strip without increasing the size of the test strip.

[0020] It is desirable in the present invention to provide a precise positioning of the electrical components relative to each other and to the entire biological sensor. The relative arrangement of the components is obtained at least in part by the use of a broad laser ablation field that is provided by a masking device or other device that has a precise pattern for electrical components. This enables precise positioning of adjacent edges, which is further improved by strict tolerances of edge smoothness, Fig. 4 illustrates a straight lineand a biological sensor 401, suitable for illustrating the laser ablation process of the present invention, comprising a substrate 402 having conductive material 403 formed thereon, designing electrode arrangements comprising a first electrode set 404 and a second electrode set 405, and corresponding paths 406, 407 and contact contact pads 408, 409. It should be noted that the biological sensor 401 is used herein to illustrate a laser ablation process that is not illustrated as including the detection lines of the present invention. The conductive material 403 may contain pure metals or alloys and other materials that are metallic conductors. preferably, the conductive material is absorptive at the laser wavelength used to form the electrodes and with a thickness that allows fast and precise 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 or metal compounds of these elements. Preferably, the conductive material includes metals precious or alloys or their oxides. Most preferably, the conductive material comprises gold, palladium, aluminum, titanium, platinum, TO and chromium. The thickness of the conductive material is in the range of about 10 nm to 80 nm, more preferably 30 nm to 70 nm, and most preferably 50 nm. It should be understood

[0022] Although not illustrated, it should be understood that the resulting pattern of conductive material may be coated or galvanized with additional metal layers. For example, the conductive material may be copper, which is then subjected to laser ablation to an electrode pattern; and later this copper can be coated with a titanium / tungsten layer and then with a gold layer to create the desired electrodes. Preferably, a single layer of conductive material is used which rests on the substrate 402. Although not essential, it is possible to improve the adhesion of the conductive material to the substrate, as is well known in the art, by applying dressing or auxiliary layers such as chromium, nickel or titanium. In preferred embodiments,

[0023] The biological sensor 401 is, as illustrated, manufactured using the two apparatuses 10, 10 'shown in Figs. 5, 6 and 7, respectively. It is important to bear in mind that, unless otherwise described, the apparatus 410, 410 'work in a similar way. Referring first to FIG. 5, the biosensor 401 is generated by feeding a web of web 420 having an 80 nm laminated gold layer that is about 40 mm wide to a typical wide area laser ablation apparatus 410. This apparatus 410 includes a laser source 411 that generates a beam of 412 laser light, a chromed quartz 414 mask, and 416 optical array. It should be understood that, however,

ΕΡ 2 325 629 Β 1 optical system 416 here is a single lens, the optical system 416 is preferably several different lenses that cooperate, causing light 412 to take a predetermined shape. [0024] A non-limiting example of a suitable ablation apparatus 410 {Fig. 5-6) is a customized MicrolineLaser 200-4 laser system, commercially available from LPKF Laser Electronic GmbH, from Garbsen, Germany, which includes the LPX-400, LPX-300 or LPX-200 laser system, available commercially from Lambda Physik AG, from Góttingen, Germany, as well as a chrome-coated quartz mask, available commercially from the International Phototool Company, of Colorado Springs, Co.

[0025] For the MicrolineLaser 200-4 laser system (Figures 5-6), the laser source 411 is a KrX-UV LPX-200 laser. It is to be understood, however, that UV lasers having a higher wavelength may be used in accordance with this disclosure. Laser source 411 operates at 248 nm, with a pulse energy of 600 mJ and a pulse repetition frequency of 50 Hz. The intensity of the laser beam 412 can be freely adjusted between 3% and 92% by a dielectric beam suppressor (not shown). The beam profile is 27 x15 mm² (0.62 square inches) and pulse duration 25 ns. The system on the mask 414 is designed homogeneously by the optical beam extender, the homogenizer, and the field lens (not shown). The operation of the homogenizer was determined by measuring the energy profile. The imaging physics 416 carries the mask structure 414 to the web 420. The imaging ratio is 2: 1, on the one hand to allow the removal of a large area, and on the other hand to maintain the energy density below the ablation point of the chromed bezel. Although 2: 1 imaging is illustrated herein, it should be understood that according to this disclosure any number of alternative ratios is possible, depending on the desired design requirements. The web 420 moves as shown by the arrow 425,

[0026] The positioning of the mask 414, the movement of the web 420, as well as the laser energy are computer controlled. As shown in Fig. 5, the faser beam 412 is directed to a web 420 intended for ablation. Light 412 passing through transparent areas or windows 418 in mask 414 causes metal ablation from web 420. Chrome-coated areas 424 of mask 414 block laser light 412 and prevent ablation in these areas, resulting in a metallized structure on the surface 420. Referring now to Fig. 6, the complete structure of the electrical components may require additional ablation steps through the second bezel 414 '. It should be understood 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. Moreover, it should be borne in mind that according to this disclosure, instead of numerous masks, you can create multiple boxes on the same mask.

[0027] More specifically, the second non-limiting example of a suitable ablative apparatus 410 '(Fig. 7) is a customized laser system commercially available from LPKF Laser Electronic GmbH, from Garbsen, Germany, in which the Lambda STEEL laser system is used (laser an energy-stable excimer) commercially available from Lambda Physik AG, from Góttingen, Germany, as well as a chrome-coated quartz mask, commercially available from the International Phototool Company, of Colorado Springs, Co. This laser system has pulsed energy of up to 1000 mJ at a wavelength of 308 nm. Moreover, this laser system has a frequency of 100 Hz. Apparatus 410 'can be formed for the production of biosensors with two phases as shown in Figs. 5 and 6, but preferably its

ΕΡ2 325 629 Β1

The optical system enables the creation of a pattern having a surface area of ​​10x40 mm in a single pass 25 ns.

Without being bound by any particular theory, it can be concluded that a laser pulse or beam 412 passing through the mask 414, 414 ', 414 "is absorbed in less than 1 pm of the surface 402 on the web 420. The photons of the beam 412 have sufficient energy, to cause photodissociation and rapid disruption of chemical bonds at the interface between metal and polymer It is thought that this rapid disruption of the chemical bond causes a sudden increase in pressure within the absorption region and forces the material (metal film 403) to be ejected from the polymer substrate surface. that the pulse durations are about 20-25 nanoseconds, the interaction with the material occurs very quickly, and thermal damage to the edges of the conductive material 403 and surrounding structures is minimized.The resulting edges of the electrical components have a high edge quality and precise positioning as contemplated in the present invention.

[0029] The ffu tion energy used to remove or ablate metals from the web 420 depends on the material from which the web 420 is formed, adheres the metal foil to the substrate material, the thickness of the metal foil, and optionally a process used to place the film on the substrate, i.e. application and steam deposition. The levels of fluency for gold on KALADEX® are in the range of about 50 to about 90 mJ / cm²on a polyimide of about 100 to about 120 mJ / cm²while on MELINEX® about 60 to about 120 mJ / cm². It should be understood that according to this disclosure, other fluent materials may have adequate fluence levels lower or higher than those mentioned above.

[0030] The making of the pattern in regions of the web 420 is achieved by using the masks 414, 414 '. Each mask 414, 414 'according to the illustration comprises a masking box 422 containing a precise two-dimensional illustration of a predetermined portion of the electrode components patterns to be made. Fig. 5 illustrates a masking field 422 including contact pads and a portion of tracks. As shown in Fig. 6, the second bezel 414 'comprises a second corresponding portion of the tracks and electrode patterns including fingers. As previously described, it is believed that according to this disclosure depending on the size of the area to be ablated, the mask 414 can include a full illustration of the electrode patterns (Fig. 7), or parts of patterns different from those illustrated in Figs. 5 and 6. Preferably . it is contemplated that in one aspect of the present invention, the entire pattern of electrical components on the test strip is simultaneously subjected to laser ablation, i.e. the wide field covers the entire size of the test strip (Fig. 7). In an alternative concept, as illustrated in Figs. 5 and 6, parts of the entire biosensor are sequentially performed.

Although masking 414 will be discussed below, it should be understood that, unless otherwise indicated, this discussion will also apply to masks 414 ', 414. "Referring to Fig. 5, areas of the chromed-protected masking field 424 will block projecting the laser beam 412 onto the web 420. The transparent areas or windows 418 in the masking field 422 allow the laser beam 412 to pass through the mask 414 and impact on predetermined regions of the web 420. As shown in Figure 5, the transparent area 418 of the masking field 422 corresponds areas of web 420 from which the conductive material 403 is to be removed.

[0032] Moreover, the masking field 422 has the length shown by the line 430 and the width shown by the line 432. Given the imaging ratio of 2: 1 for LPX- 200,

ΕΡ 2 325 629 Β1, it is understood that the length of the mask 430 is twice the length of 434 of the obtained pattern, while the width 432 of the mask is twice the width 436 of the obtained pattern on the ribbon 420. The optical method 416 reduces the size of the laser beam 412 which strikes the web 420. It should be understood that the relative dimensions of the masking field 422 and the pattern obtained in this way may vary within the scope of this disclosure. The mask 414 '(Fig. 6) is used to complement the two-dimensional illustration of electrical components.

[0033] Still referring to Fig. 5, a laser source 411 in the form of an excimer laser sends a beam 412 that passes through a chromium-plated quartz bezel 414. The masking field 422 causes the parts of the laser beam 412 to be reflected while the other parts of the beam are to pass, they form a pattern on the gold foil where the laser beam 412 strikes. It should be understood that the web 420 may be stationary with respect to the apparatus 410 or may continuously move on the roller apparatus 410. Accordingly, , the non-limiting translational speeds of the web 420 may be from about 0 m / min to about 100 m / min, more preferably about 30 m / min to about 60 m / min. Keep in mind that

[0034] When a pattern from the mask 414 is formed on the web 420, the web is rewound and fed again through the apparatus 410 with the mask 414 '(Fig. 6). It should be understood that, alternatively, the laser apparatus 410 may be arranged in series in accordance with this disclosure. Thus, through the use of the masks 414, 414 ', pattern areas of the web 420 can be patterned using repetitive step steps, including a plurality of camouflaging boxes 422 in the same masking area to allow economical production of complex electrode patterns and other electrical components on the base substrate. , the precise edges of the electrode components and the removal of larger amounts of metal foil from the substrate material.

[0035] The test strip and perimeter illustrated in Figs. 8 and 9 is an improvement over the prior art by providing compensation for the lR fall in both the working electrode wires and the intrusions on the test strip. Referring now to Fig. 8, a schematic example of the test strip configuration according to the present invention is shown schematically, indicated generally at 800. This test strip 800 includes a bottom substrate 12 coated on its upper surface with a conductive 50 nm gold layer (e.g. by sputtering or steam deposition). , as a non-limiting example). The electrodes, liaison paths and contact pads are then mapped in the conductive layer via a laser ablation process as described above. For example, working electrode 814a, working sensor electrode 826a, counter-electrode 216a, and sensing counter electrode 224a can be formed as shown and coupled to corresponding measuring contact pads 814b, 826b, 216b and 224b via respective paths 814c, 826c, 216c and 224c. These contact contact pads 814b, 826b, 216b and 224b provide a conducting area on the test strip 800 to be in contact with the contact connector in the test meter (not shown) as soon as the test strip 800 is inserted into the test meter.

[0036] It will be understood that the test strip 800 of Fig. 8 is substantially identical to the test strip 200 of Fig. 2, with the exception of adding a working sensor electrode 826a, contact pad 826b, and track 826c. The use of the operating sensor line 826 allows the test meter

ΕΡ2 325 629 Β1 compensating for any drop in lR caused by the resistance of the contact of the contacts to the contact contact pads 814b and 216b, and also the compensation of path resistance 814c and 216c.

[0037] Now referring to Fig. 9, there is shown an electrical circuit diagram as 900) located inside a test meter. As indicated, this circuit is coupled to the contact 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 contact contact pad 216b of the counter electrodes, which will cause current to flow between the counter electrode 216a and the working electrode 814a which is proportional to the amount of the analyte present in the biological sample applied to the reagent. The working electrode 814a is transferred via the electrode path 814c to the contacting field 814b of the working electrode and supplied to the current-voltage amplifier 310.

[0038] Microprocessor 314 also sends a digital signal indicating the voltage potential to be applied to the contact pad contact zone 216b. This digital signal is converted into an analog voltage signal by the D / A converter 318 (reference voltage source). An analog D / A converter output 318 is applied to the first operational input of the amplifier 320. The second input of the operational amplifier 320 is coupled to the output of the operational amplifier 910. The operational amplifier 910 is connected to a differential amplifier configuration using an amplifier. The first input of the operational amplifier 910 is coupled to the contact contact pad 826b of the sensor electrode, while the second input of the operational amplifier 910 is coupled to the contact pad contact area 224b of the sensor counter-electrode. The output of the operational amplifier 320 is coupled to the contact contact pad 216b of the counter electrode. When the test strip (800) containing the biosensor is coupled to the test meter, the first input of the operational amplifier 910 is operatively coupled to the sensor electrode path 826c, while the second input is operatively coupled to the sensor countersensor path 224c. The output of the operational amplifier is operatively coupled to the counter electrode path. A working amplifier 910 in this configuration works as a differential amplifier. When the test strip (800) containing the biosensor is coupled to the test meter, the first input of the operational amplifier 910 is operatively coupled to the sensor electrode path 826c, while the second input is operatively coupled to the sensor countersensor path 224c. The output of the operational amplifier is operatively coupled to the counter electrode path. A working amplifier 910 in this configuration works as a differential amplifier. When the test strip (800) containing the biosensor is coupled to the test meter, the first input of the operational amplifier 910 is operatively coupled to the sensor electrode path 826c, while the second input is operatively coupled to the sensor countersensor path 224c. The output of the operational amplifier is operatively coupled to the counter electrode path. A working amplifier 910 in this configuration works as a differential amplifier.

[0039] The operational amplifier 320 is connected in a voltage follower configuration in which the amplifier will adapt its output (within the physical limits of operation) until the voltage appearing at its second input will be equal to the desired voltage appearing at its first input. Both inputs of this operational amplifier 910 are high impedance inputs, and therefore no current is substantially in line 224 of the sensor counter electrode or in the sensor electrode working line 826. Due to the fact that virtually no current flows, no parasitic resistance in the sensor counter electrode 224 or sensor electrode working line 826 will cause a drop in potential, and the voltage appearing at the inputs of the amplifier 910 is substantially the same as the voltage on the measuring cell (i.e. on the counter electrode 216a and the working electrode 814a). Due to the fact that the operational amplifier 910 is connected in the differential amplifier configuration, its output represents the voltage on the measuring cell.

[0040] The operational amplifier 320 will thus function such that it will change the parameters of its output (i.e., the potential of voltage on contact contact field 216b of the counter electrode) until the actual voltage potential appearing on the measuring cell will be equal to the potential of the voltage demanded. by the microprocessor 314. The operational amplifier 320 automatically compensates for any potential drop caused by the parasitic resistance in the counter electrode path 216c, the counter electrode contact 216b, the electrode working path 814c and the electrode working contact 814b, and thus the potential appearing on the measuring cell is a desired potential. Calculation of the concentration of the analyte in the biological sample on the basis of the current generated by the working electrode is therefore more accurate.

[0041] Fig. 10, in conjunction with Fig. 8, illustrates a third embodiment of the present invention that improves prior art by providing 1R fall compensation for both electrode and counter electrode working lines, and ensuring that both the electrode and counter electrode working lines will not be higher than a predetermined threshold to ensure that the test meter is suitable for compensating Iow drops. Referring now to Fig. 10, there is shown an electrical circuit diagram according to a third embodiment of the electrode compensation circuit (indicated generally as 1000) located inside the test meter. This electrode compensation circuit 1000 operates with the test strip 800 according to Fig. 8. As indicated, this circuit is coupled to the contact 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 contact contact area of ​​the electrode contact point 216b, which generates a current flow between the counter electrode 216a and the working electrode 814a which is proportional to the analyte present in the biological sample applied to the reagent 18. The current coming from the working electrode 814a is transmitted to the contacting working contact pad 814b via the electrode work path 814c and supplied to the voltage amplifier 310. The output from this current-voltage amplifier 310 is connected to the input of the amplifier 1002, which is configured as a buffer having a unit gain when the switch 1004 is in the closed position. The voltage of the analog output of the amplifier 1002 is converted to a digital signal by the converter A / D 312. This digital signal is then processed by the microprocessor 314 according to a previously stored program to determine the concentration of the analyte in the biological sample applied to the test strip 800. This concentration is displayed to the user via an output device 316 having an LCD display.

[0042] Microprocessor 314 also sends a digital signal indicating the voltage potential to be acted on the counter contact pad contact area 216b. This digital signal is converted into an analog voltage signal by the D / A converter 318. An analog D / A converter output 318 is applied to an operational input of the amplifier 320, which is configured as a voltage follower when the switch 1006 is in the position shown. The output of the operational amplifier 320 is coupled to the contact contact pad 216b of the counter electrode, which allows measuring the sample of the biological fluid applied to the reagent 18. Furthermore, when the switches 1006, 1008 and 1010 are positioned as illustrated in Fig. 10, the circuit is configured as shown in FIG. FIG.

9.

ΕΡ 2 325 629 Β1 [0043] In order to measure the size of the parasitic resistance in the line 216, the overloads, switch 1008 is placed in the position shown in Fig. 10, and the switch 1006 is placed in the opposite position to that shown in Fig. 10, with the switch 1010 is closed. The operational amplifier 320 therefore acts as a unit-amplified buffer and acts on the contact potential of the contact field 216b by means of known resistivity Rnom. This resistance causes the currents detected by the current-voltage amplifier 310 to be connected to the sensor overlapping line 216, coupled now to the current detection line via the switch 1010. The current-voltage amplifier 310 is fed to the microprocessor 314 via the converter A / D 312. Because of the fact that the Rnom value is known, the microprocessor 314 can calculate the value of any parasitic resistance in the sensor overload line 224 and the intrusion line 216. This value of parasitic resistance can be compared to a predetermined threshold stored in the test meter to determine if there has been physical failure of the test strip 800 or whether there is an accumulation of non-conductive material on the contact pads to such an extent that the test strip 800 can not be reliably used to perform the test. In such situations, the test meter can be programmed to inform the user about the need to insert another test strip into the test meter before performing the test. microprocessor 314 can calculate the value of any parasitic resistance in line 224 of the sensor overload and line 216 of the intrusions. This value of parasitic resistance can be compared to a predetermined threshold stored in the test meter to determine if there has been physical failure of the test strip 800 or whether there is an accumulation of non-conductive material on the contact pads to such an extent that the test strip 800 can not be reliably used to perform the test. In such situations, the test meter can be programmed to inform the user about the need to insert another test strip into the test meter before performing the test. microprocessor 314 can calculate the value of any parasitic resistance in line 224 of the sensor overload and line 216 of the intrusions. This value of parasitic resistance can be compared to a predetermined threshold stored in the test meter to determine if there has been physical failure of the test strip 800 or whether there is an accumulation of non-conductive material on the contact pads to such an extent that the test strip 800 can not be reliably used to perform the test. In such situations, the test meter can be programmed to inform the user about the need to insert another test strip into the test meter before performing the test.

In order to measure the parasitic resistance in the working electrode line 8, the switches 1006 and 1008 are set in a position opposite to that shown in Fig. 10, while the switch 1010 is open. The operating amplifier 320 therefore acts as a unit amplifier buffer and operates with a voltage potential on the contact contact pad 826b of the sensor electrode by known resistance Rnom. This resistance causes the current to flow in the sensor electrode working line 826 and the electrode working line 814, which is detected by the current-voltage amplifier 310. The output of the current-voltage amplifier 310 is fed to the microprocessor 314 via the A / D converter 312. Because of this, that the value of Rnom is known, microprocessor 314 can calculate the value of any parasitic resistance in line 826 of the working sensor electrode and electrode working line 814. This value of parasitic resistance can be compared with a predetermined threshold stored in the test meter to determine if there has been physical failure of the test strip 800 or whether there is an accumulation of non-conductive material on the contact pads to such an extent that the test strip 800 can not be a reliable method used to perform the test. In such situations, the test meter can be programmed to inform the user that a test strip should be inserted into the test meter before the test is performed. This value of parasitic resistance can be compared with a predetermined threshold stored in the test meter to determine if there has been physical failure of the test strip 800 or whether there is an accumulation of non-conductive material on the contact pads to such an extent that the test strip 800 can not be a reliable method used to perform the test. In such situations, the test meter can be programmed to inform the user that a test strip should be inserted into the test meter before the test is performed. This value of parasitic resistance can be compared with a predetermined threshold stored in the test meter to determine if there has been physical failure of the test strip 800 or whether there is an accumulation of non-conductive material on the contact pads to such an extent that the test strip 800 can not be a reliable method used to perform the test. In such situations, the test meter can be programmed to inform the user that a test strip should be inserted into the test meter before the test is performed. that test strip 800 can not be reliably used to perform the test. In such situations, the test meter can be programmed to inform the user that a test strip should be inserted into the test meter before the test is performed. that test strip 800 can not be reliably used to perform the test. In such situations, the test meter can be programmed to inform the user that a test strip should be inserted into the test meter before the test is performed.