Patent Publication Number: US-2005136471-A1

Title: Biosensor

Description:
FIELD OF THE INVENTION  
      The present invention is directed to a biosensor and a method of forming same. More particularly, the present invention is directed to a biosensor with connector windows that expose electrode contacts for engagement with a meter.  
     BACKGROUND AND SUMMARY OF THE INVENTION  
      Electrochemical biosensors are known. They have been used to determine the concentration of various analytes from biological samples, particularly from blood. Electrochemical biosensors are described in U.S. Pat. Nos. 5,413,690; 5,762,770; 5,798,031; and 5,997,817 the disclosure of each of which is expressly incorporated herein by reference.  
      According to the present invention a biosensor is provided. The biosensor comprises an electrode support substrate, electrodes positioned on the electrode support, each electrode including a meter-contact portion and a measurement portion, and a sensor support substrate. The sensor support substrate cooperates with the electrode support substrate to define a channel in alignment with the measurement portion of the electrodes. Additionally, the sensor support substrate includes opposite ends and at least one window. The at least one window is spaced-apart from the ends and in alignment with the meter-contact portion of at least one of the electrodes.  
      According to another aspect of the invention a method of forming a biosensor is provided. The method comprises the steps of forming electrodes on a surface of an electrode support substrate, each electrode including a meter-contact portion and a measurement portion, forming a sensor support substrate having opposite ends and at least one window spaced apart from the opposite ends, coupling the sensor support and the electrode support substrate together so that the at least one window is aligned with the meter-contact portion of the electrodes, and applying a reagent to the measurement portion of the electrodes.  
      In accordance with another aspect of the invention a biosensor is provided. The biosensor comprises an electrode support substrate, electrodes positioned on the electrode support substrate, each electrode including a meter-contact portion and a measurement portion, a sensor support substrate coupled to the electrode support substrate, the sensor support substrate including opposite ends, an opening in alignment with the measurement portion of the electrodes and at least one window spaced-apart from the ends and in alignment with the meter-contact portion of the electrodes, and a cover coupled to the sensor support substrate.  
      Additional features of the invention will become apparent to those skilled in the art upon consideration of the following detailed description of the preferred embodiment exemplifying the best mode of carrying out the invention as presently perceived. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      The detailed description particularly refers to the accompanying figures in which:  
       FIG. 1  is a perspective view of a biosensor in accordance with the present invention.  
       FIG. 2A  is an exploded view of the biosensor of  FIG. 1 .  
       FIG. 2B  is an enlarged assembled view of a portion of the biosensor of  FIG. 2  illustrating three discrete windows.  
       FIG. 3  is a view taken along lines  3 - 3  of  FIG. 1 .  
       FIG. 4  is a view taken alone lines  4 - 4  of  FIG. 1 .  
       FIG. 5  is a diagrammatic view of the method of manufacturing the biosensor of the present invention.  
       FIG. 6  is a perspective view of a biosensor in accordance with another aspect of the present invention.  
       FIG. 7  is an exploded view of the biosensor of  FIG. 6 .  
       FIG. 8  is an enlarged top diagrammatic view of a biosensor in accordance with another aspect of the present invention showing one window exposing two electrode contacts.  
       FIG. 9  is an enlarged top diagrammatic view of a biosensor of  FIG. 8  and a diagrammatic view of a corresponding meter showing the meter including two contacts for engagement with the two exposed electrode contacts of the biosensor.  
       FIG. 10  is a view similar to  FIG. 8  of a biosensor in accordance with another aspect of the present invention showing five windows exposing five electrode contacts and showing a diagrammatic view of a corresponding meter including five contacts for engagement with the five exposed electrode contacts.  
       FIG. 11  is an enlarged cross-sectional view of one window of the biosensor of  FIG. 10  and showing one meter contact sequenced in time in order to illustrate the relative positioning of the electrode contact and the meter contact during insertion of the biosensor in the meter.  
       FIG. 12  is an enlarged cross-sectional view of one window of the biosensor of  FIG. 10  and showing a diagrammatic view of a switch in accordance with another aspect of the present invention.  
       FIG. 13  is a view similar to  FIG. 8  of a biosensor in accordance with another aspect of the present invention showing four windows exposing four electrode contacts with one closed window in phantom and showing a diagrammatic view of a corresponding meter including five contacts.  
       FIG. 14  is an enlarged perspective view of a biosensor in accordance with another aspect of the present invention.  
       FIG. 15  is a view taken along lines  15 - 15  of  FIG. 14 . 
    
    
     DETAILED DESCRIPTION OF THE DRAWINGS  
      The present invention relates to a biosensor and method of manufacturing said biosensor. This biosensor of the present invention includes opposite ends and is beneficially formed to enable a user to grasp ends without touching electrode contacts, which are themselves formed to electrically connect with a meter. Biosensors of the present invention include at least one discrete window spaced-apart from the end of the biosensor. The at least one window serves as a built-in fiducial for alignment of the biosensor, enabling easy automated process control during assembly. Further, the at least one discrete window is a significant advantage for an integrated strip handling system, since each window creates a detent, providing mechanical feedback for strip mating with meter contacts. Furthermore, when biosensor includes discrete windows, strip alignment problems are eliminated enabling multiple strip configurations to be used with a single meter. That is, the discrete windows of the biosensor prevent problems associated with closely spaced electrode pads touching the wrong meter contact. Aspects of the invention are presented in  FIGS. 1-15 , which are not drawn to scale and wherein like components in the several views are numbered alike.  
      A biosensor  10  is shown in  FIGS. 1-4 . The term analyte, as used herein, refers to the molecule or compound to be quantitatively determined. Non-limiting examples of analytes include carbohydrates, proteins, such as hormones and other secreted proteins, enzymes, and cell surface proteins; glycoproteins; peptides; small molecules; polysaccharides; antibodies (including monoclonal or polyclonal Ab); nucleic acids; drugs; toxins; viruses of virus particles; portions of a cell wall; and other compounds processing epitopes. The analyte of interest preferably comprises glucose.  
      Biosensor  10  is shown in  FIG. 1  and includes opposite ends  11 ,  13 , either of which is available to be grasped by a user without contact with electrodes of the biosensor  10 . As shown in  FIG. 2A , the biosensor  10  includes an electrode support substrate  12  and an electrical conductor  14  positioned on the substrate  12 . The conductor  14  is disrupted to define electrodes  16 ,  18 ,  20 . Biosensor  10  also includes a sensor support substrate  22  positioned on the substrate  12  and a cover substrate  24  positioned on the sensor support substrate  22 . Biosensor  10  is in the form of a disposable test strip. It is appreciated however, that biosensor  10  can assume any number of forms and shapes in accordance with this disclosure.  
      Biosensor  10  is preferably produced from rolls of material. It is understood that biosensor  10  also can be constructed from individual sheets in accordance with this disclosure. When biosensors  10  are produced from rolls, the selection of materials necessitates the use of materials that are sufficiently flexible for roll processing, but which are still rigid enough to give a useful stiffness to finished biosensor  10 .  
      Referring to  FIG. 2A , the electrode support substrate  12  includes a first surface  26  facing the sensor support substrate  22  and a second surface  28 . In addition, substrate  12  has opposite first and second ends  30 ,  32  and opposite edges  34 ,  36  extending between the first and second ends  30 ,  32 . Edge  34  of substrate  12  is formed to include a generally concave-shaped notch  38 . It is appreciated that substrate  12  may be formed without a notch, or that the notch may take on any number of shapes and sizes in accordance with the present disclosure.  
      Electrode support substrate  12  is generally rectangular in shape, it is appreciated however, that support  12  may be formed in a variety of shapes and sizes in accordance with this disclosure. It is also appreciated that the substrate  12  need not necessarily extend the length of the substrate  22  as shown in  FIGS. 1 and 2 A. In fact, the substrate  12  can have a shorter length so long as it is of sufficient length to position the electrodes with a channel and windows as will be described hereafter. Substrate  12  may be constructed from a wide variety of insulative materials. Non-limiting examples of insulative materials that provide desirable electrical and structural properties include glass, ceramics, vinyl polymers, polyimides, polyesters, and styrenics. Preferably, substrate  12  is a flexible polymer, such as a polyester or polyimide. A non-limiting example of a suitable material is 5 mil (125 um) thick KALADEX®, a polyethylene naphthalate film commercially available from E.I. DuPont de Nemours, Wilmington, Del., which is coated with gold by ROWO Coating, Henbolzhelm, Germany. It is appreciated that the thickness of the support  12  can be greater or less than 5 mil (125 um) and may be suitable for a number of assembly processes (e.g., lamination, etc.).  
      Electrodes  16 ,  18 ,  20  are created or isolated from conductor  14  on first surface  26  of electrode support substrate  12 . See  FIGS. 2A and 3 . It is appreciated that electrodes  16 ,  18 ,  20  can be formed from multiple layers of same or different electrically conductive materials. Non-limiting examples of a suitable electrical conductor  14  include aluminum, carbon (such as graphite), cobalt, copper, gallium, gold, indium, iridium, iron, lead, magnesium, mercury (as an amalgam), nickel, niobium, osmium, palladium, platinum, rhenium, rhodium, selenium, silicon (such as highly doped polycrystalline silicon), silver, tantalum, tin, titanium, tungsten, uranium, vanadium, zinc, zirconium, mixtures thereof, and alloys, oxides, or metallic compounds of these elements. Preferably, electrical conductor  14  is selected from the following materials: gold, platinum, palladium, iridium, or alloys of these metals, since such noble metals and their alloys are unreactive in biological systems. Most preferably, the electrical conductor  14  is gold.  
      Electrodes  16 ,  18 ,  20  are isolated from the rest of the electrical conductor  14  by laser ablation. Techniques for forming electrodes on a surface using laser ablation are known. See, for example, U.S. patent application Ser. No. 09/411,940, titled “Laser Defined Features for Patterned Laminates and Electrodes”, the disclosure of which is expressly incorporated herein by reference. Preferably, electrodes  16 ,  18 ,  20  are created by removing the electrical conductor  14  from an area extending around the electrodes to form a gap  40  of exposed support substrate  12 . Therefore, electrodes  16 ,  18 ,  20  are isolated from the rest of the electrically-conductive material on substrate  12 . Illustratively, the gap  40  has a width of about 25 μm to about 500 μm, preferably the gap has a width of about 100 μm to about 200 μm. Alternatively, it is appreciated that electrodes  16 ,  18 ,  20  may be created by laser ablation alone on substrate  12 . It is appreciated that while laser ablation is the preferred method for forming electrodes  16 ,  18 ,  20  given its precision and sensitivity, other techniques such as lamination, screen-printing, photolithography, or contact printing may be used in accordance with this disclosure.  
      As shown in  FIG. 2A , electrodes  16 ,  18 ,  20  cooperate with one another to define an electrode array  42 . In addition, electrodes  16 ,  18 ,  20  each include a meter-contact portion  44 , a measurement portion positioned in the array  42 , and a lead  46  extending between the contact  44  and the measurement portion. Contacts  44  are spaced apart from end  32 . It is appreciated that the contacts  44  can be formed to have many lengths and can extend to end  32  or to edges  34 ,  36 , or to any number of locations on substrate  12 . Likewise, the leads  38  that extend from the array  34  can be formed to have many lengths and extend to a variety of locations on the electrode support substrate  12 . It is appreciated that the configuration of the electrode array, the number of electrodes, as well as the spacing between the electrodes may vary in accordance with this disclosure and that greater than one array may be formed as will be appreciated by one of skill in the art.  
      As described below, electrodes  16 ,  18 ,  20  are used with a reagent to determine the concentration of at least one analyte in a fluid sample. It is appreciated, however, that at least one of the electrodes may be used for purposes other than a reagent-based measurement. A non-limiting example of which includes using one set of leads (either within the reagent or on the bottom side of the sensor) to connect to a thermocouple (not shown) for temperature measurement. Alternatively, depending upon the location of the reagents on the sensor support substrate  22 , electrodes are enabled to be used as an antenna for telemetry, or to signify an expiration date, code number, analyte, etc.). It is also contemplated by the present disclosure to use the electrodes to examine a ratio of currents at one or more time points to determine if the biosensor  10  has been exposed to inappropriate temperature, humidity, interferences, etc.).  
      As shown in  FIG. 2B , the sensor support substrate  22  of biosensor  10  extends to the end  32  of substrate  12  to permit a user to grasp the end  11  of biosensor  10  without contacting the electrodes  16 ,  18 ,  20 . It is appreciated, however, that substrate  32  may extend past end  32  in accordance with this disclosure. The sensor support substrate  22  is positioned to lie between the electrode support substrate  12  and the cover substrate  24 . Referring now to  FIG. 4 , the sensor support substrate  22  cooperates with the support substrate  12  and the cover  24  to expose the electrode array  42  to a liquid sample (not shown) being applied to the biosensor  10 . Sensor support substrate  22  can be formed from any number of commercially available insulative materials. Non-limiting examples of insulative materials that provide desirable electrical and structural properties include vinyl polymers, polyimides, polyesters, and styrenics. Preferably, the sensor support substrate  22  is 10 mil (250 um) thick opaque white MELINEX® 329 plastic, a polyester commercially available from E.I. DuPont de Nemours, Wilmington, Del., which is coated with a thermoplastic resin (Griltex D 1698 E), commercially available from EMS-Chemie (North America) Inc., Sumter, S.C. It is further appreciated that sensor support substrate  22  may be formed of a double-sided adhesive tape covered by an insulative material in accordance with the disclosure, so long as it is of a sufficient thickness to create a detent about at least one window  64 , as will be described below.  
      Referring now to  FIG. 2A , the sensor support substrate  22  includes a first surface  48  and a second surface  50  facing the electrode support substrate  12 . When the sensor support substrate  22  is coupled to the substrate  12  a first end  52  of the sensor support substrate  22  is aligned with end  30 , a second end  54  is aligned with end  32 , an edge  56  is aligned with edge  34 , and an opposite edge  58  is aligned with edge  36 .  
      Further, the edge  56  is formed to include a notch  60  that is shaped so as to be aligned with notch  38  of the substrate  12 . It is appreciated that substrate  12  may be formed without a notch, or that the notch may take on any number of shapes and sizes in accordance with the present disclosure. An opening  62  extends from the notch  60  toward the edge  58 . When the sensor support substrate  22  is coupled to the substrate  12 , as shown in  FIGS. 1 and 4 , the substrates  12 ,  22  cooperate to define a channel aligned with the electrodes. Thus, upon assembly, the measurement portion of the electrodes that cooperate to form the electrode array  42  are positioned to lie in general alignment with the opening  62  and are thus positioned in the channel  78  to expose at least a portion of the electrodes  16 ,  18 ,  20  of the electrode array  42 . An interior border  80  defines the opening  62 . The width of the interior border  80  can vary in accordance with this disclosure.  
      The sensor support substrate  22  extends to the end  32  of substrate  12  and is formed to expose the electrode contacts  44  for engagement with a meter  124 . A non-limiting example of such a meter is shown diagrammatically in  FIG. 10 . Referring now to  FIG. 1 , sensor support substrate  22  includes windows  64  that extend between first and second surfaces  48 ,  50 . Each window  64  creates a detent in sensor support substrate  22  and is spaced apart from end  54 . This detent provides mechanical feedback for strip mating with meter contacts and increases the rigidity of the substrate  22 . Further, the positioning of the windows  64  enables a user to grasp the end  11  of the biosensor  10  without touching the electrode contacts  44 . Thus, the inadvertent deposit of skin oils, dirt, skin cells, etc. onto the electrical contacts  44  through simple handling of the biosensor  10  is prevented.  
      In addition, at least one window  64  may be used to perform alignment of the substrates  12  and  22 . It is also appreciated that at least one window  64  may be used to perform alignment for other manufacturing processes such as dispensing, labeling, cutting, punching, etc. Moreover, it is appreciated that windows  64  can take on a variety of shapes and sizes in accordance with the present disclosure. Illustratively, windows  64  are formed to be slightly larger than the respective contacts  44 . A non-limiting example of dimensions of suitable windows  64  when contacts have a width of about 1 mm and a length of about 2 mm, is a width of about 1.5 mm and a length of about 2.5 mm. In addition, while three windows  64  are shown, it is appreciated that biosensor  10  can be formed with greater than three windows or as few as one window in accordance with the present disclosure. Non-limiting examples of which include windows illustrated in  FIGS. 8-10 , and  13 - 15 .  
      Sensor support substrate  22  is coupled to the electrode support substrate  12  as shown in  FIG. 1 . The thermoplastic resin on surface  48  permits the substrate  22  to be heat-sealed to the conductor  14  coating substrate  12 . It is appreciated that substrates  12  and  22  may be coupled together using a wide variety of commercially available adhesives or with welding (heat or ultrasonic on portions of substrate  12  where the conductor  14  has been removed) in accordance with this disclosure. It is also appreciated that first surface  50  of substrate  22  may be printed with, for example, product labeling or instructions for use in accordance with this disclosure.  
      The cover substrate  24  is coupled to the spacer support  22  across the opening  62 . See  FIG. 1 . The cover substrate  24  of biosensor  10  includes a first surface  66  facing substrate  12 , an opposite second surface  68  and a vent  69  extending between surfaces  66 ,  68 . In addition, cover substrate  24  has opposite first and second ends  70 ,  72  and edges  74 ,  76  extending between ends  70 ,  72 . Edge  74  is preferably generally concave shape for alignment with notches  38 ,  60  of substrates  12 ,  22  respectively. It is appreciated, however, that the edge  74  may take on any number of shapes and sizes in order to be in general alignment with the shape of notches  38 ,  60 . The cover substrate  24  is formed of a flexible polymer and preferably from a polymer such as an adhesive coated polyethylene terephthalate (PET)—polyester. A non-limiting example of a suitable PET is 2 mil (50 um) thick clear PET film one side of which is coated with a hydrophilic pressure-sensitive adhesive (Product # ARcare 8877) commercially available from Adhesives Research, Inc. Glen Rock, Pa.  
      The cover substrate  24  is formed to cooperate with the sensor support substrate  22  and the support substrate  12  to define a channel  78  extending from edges  34 ,  56 ,  74  and across the electrode array  42 . The channel  78  is preferably a capillary channel that is formed to transport a fluid sample from the user to the electrode array  42 . As shown in  FIG. 4 , the channel  78  extends from edges  34 ,  56 ,  74  and is defined by the interior border  80  of the opening  62 . It is appreciated that the channel  78  can extend from any number of locations of biosensor  10  to the array  42 . It is also appreciated that channel  78  may also be formed from cooperation between only the sensor support substrate  22  and the support substrate  12 .  
      An electrochemical reagent  82  is positioned on the array  42 . The reagent  82  provides electrochemical probes for specific analytes. The choice of the specific reagent  82  depends on the specific analyte or analytes to be measured, and are well known to those of ordinary skill in the art. An example of a reagent that may be used in biosensor  10  of the present invention is a reagent for measuring glucose from a whole blood sample. A non-limiting example of a reagent for measurement of glucose in a human blood sample contains 62.2 mg polyethylene oxide (mean molecular weight of 100-900 kilo Daltons), 3.3 mg NATROSOL 244M, 41.5 mg AVICEL RC-591 F, 89.4. mg monobasic potassium phosphate, 157.9 mg dibasic potassium phosphate, 437.3 mg potassium ferricyanide, 46.0 mg sodium succinate, 148.0 mg trehalose, 2.6 mg TRITON X-100 surfactant, and 2,000 to 9,000 units of enzyme activity per gram of reagent. The enzyme is prepared as an enzyme solution from 12.5 mg coenzyme PQQ and 1.21 million units of the apoenzyme of quinoprotein glucose dehydrogenase. This reagent is further described in U.S. Pat. No. 5,997,817, the disclosure of which is expressly incorporated herein by reference.  
      Non-limiting examples of enzymes and mediators that may be used in measuring particular analytes in biosensor  10  are listed below in Table 1.  
                           TABLE 1                               Mediator           Analyte   Enzymes   (Oxidized Form)   Additional Mediator                  Glucose   Glucose   Ferricyanide               Dehydrogenase and           Diaphorase       Glucose   Glucose-   Ferricyanide           Dehydrogenase           (Quinoprotein)       Cholesterol   Cholesterol   Ferricyanide   2,6-Dimethyl-1,4-           Esterase and       Benzoquinone           Cholesterol       2,5-Dichloro-1,4-           Oxidase       Benzoquinone or Phenazine                   Ethosulfate       HDL   Cholesterol   Ferricyanide   2,6-Dimethyl-1,4-       Cholesterol   Esterase       Benzoquinone           and Cholesterol       2,5-Dichloro-1,4-           Oxidase       Benzoquinone or Phenazine                   Ethosulfate       Triglycerides   Lipoprotein Lipase,   Ferricyanide or   Phenazine Methosulfate           Glycerol Kinase,   Phenazine           and Glycerol-3-   Ethosulfate           Phosphate Oxidase       Lactate   Lactate Oxidase   Ferricyanide   2,6-Dichloro-1,4-                   Benzoquinone       Lactate   Lactate   Ferricyanide           Dehydrogenase and   Phenazine           Diaphorase   Ethosulfate, or               Phenazine               Methosulfate       Lactate   Diaphorase   Ferricyanide   Phenazine Ethosulfate, or       Dehydrogenase           Phenazine Methosulfate       Pyruvate   Pyruvate Oxidase   Ferricyanide       Alcohol   Alcohol Oxidase   Phenylenediamine       Bilirubin   Bilirubin Oxidase   1-Methoxy-               Phenazine               Methosulfate       Uric Acid   Uricase   Ferricyanide                  
 
      In some of the examples shown in Table 1, at least one additional enzyme is used as a reaction catalyst. Also, some of the examples shown in Table 1 may utilize an additional mediator, which facilitates electron transfer to the oxidized form of the mediator. The additional mediator may be provided to the reagent in lesser amount than the oxidized form of the mediator. While the above assays are described, it is contemplated that current, charge, impedance, conductance, potential, or other electrochemically indicated property of the sample might be accurately correlated to the concentration of the analyte in the sample with biosensor  10  in accordance with this disclosure.  
      A plurality of biosensors  10  are typically packaged in a vial, usually with a stopper formed to seal the vial. It is appreciated, however, that biosensors  10  may be packaged individually, or biosensors can be folded upon one another, rolled in a coil, stacked in a cassette magazine, or packed in blister packaging.  
      Biosensor  10  is used in conjunction with the following: 
          1. a power source in electrical connection with contacts  44  and capable of supplying an electrical potential difference between electrodes  16 ,  18 ,  20  sufficient to cause diffusion limited electro-oxidation of the reduced form of the mediator at the surface of the working electrode; and     2. a meter in electrical connection with contacts  44  and capable of measuring the diffusion limited current produced by oxidation of the reduced form of the mediator with the above-stated electrical potential difference is applied.        

      The meter will normally be adapted to apply an algorithm to the current measurement, whereby an analyte concentration is provided and visually displayed. Improvements in such power source, meter, and biosensor system are the subject of commonly assigned U.S. Pat. No. 4,963,814, issued Oct. 16, 1990; U.S. Pat. No. 4,999,632, issued Mar. 12, 1991; U.S. Pat. No. 4,999,582, issued Mar. 12, 1991; U.S. Pat. No. 5,243,516, issued Sep. 7, 1993; U.S. Pat. No. 5,352,351, issued Oct. 4, 1994; U.S. Pat. No. 5,366,609, issued Nov. 22, 1994; White et al., U.S. Pat. No. 5,405,511, issued Apr. 11, 1995; and White et al., U.S. Pat. No. 5,438,271, issued Aug. 1, 1995, the disclosures of each of which are expressly hereby incorporated by reference.  
      Many fluid samples may be analyzed. For example, human body fluids such as whole blood, plasma, sera, lymph, bile, urine, semen, cerebrospinal fluid, spinal fluid, lacrimal fluid and stool specimens as well as other biological fluids readily apparent to one skilled in the art may be measured. Fluid preparations of tissues can also be assayed, along with foods, fermentation products and environmental substances, which potentially contain environmental contaminants. Preferably, whole blood is assayed with this invention.  
      As shown in  FIG. 5 , biosensor  10  is manufactured using six distinct processes. In process one, a roll of sensor support substrate material  84  is fed into a window punch and web slit station  86 . In the station  86 , the windows  64  and the opening  62  are created through the sensor support substrates in the web and the web is slit to its final dimension in the station. The trim, from the edges of the web of material is removed from the material and wound into a roll  88 . Upon leaving the station  86 , the punched sensor support substrates connected to one another via a web are wound into a roll  90 .  
      In process two, a roll of metallized electrode support material  92  is fed into an ablation/washing and drying station  94 . A laser system capable of ablating support  12  is known to those of ordinary skill in the art. Non-limiting examples of which include excimer lasers, with the pattern of ablation controlled by mirrors, lenses, and masks. A non-limiting example of such a custom fit system is the LPX-300 or LPX-200 both commercially available from LPKF Laser Electronic GmbH, of Garbsen, Germany.  
      In the ablation station  94 , the metallic layer of the metallized film is ablated in a pre-determined pattern, to form a ribbon of support material with isolated electrode patterns  96 . To ablate electrodes  16 ,  18 ,  20  isolated by gaps  40  in 50 nm thick gold conductor  14 , 90 mJ/cm 2  energy is applied. It is appreciated, however, that the amount of energy required may vary from material to material, metal to metal, or thickness to thickness. If however, any seed layer or other metallic layer such as Crominium or Titanium or any other metal is used for any purpose, and then gold is put down, the total thickness of all composite metals is still preferred to be about 50 nm. It is appreciated that the total thickness may vary between about 30 and about 80 nm in accordance with this disclosure. In the ablation station  94 , the ribbon is also passed through an optional inspection system where both optical and electrical inspection can be made. The system is used for quality control in order to check for defects.  
      Next, in process three, the roll of punched sensor support substrates  90  is fed into a cutting and lamination station  98 . At the same time, the ribbon of support material with isolated electrode patterns  96  is fed into the station  98 . The thermoplastic resin coated first surface of the sensor support substrates  90  is applied to the electrode support substrate material so that the windows  64  are in general alignment with the respective contacts  44  and the openings  62  are in general alignment with the arrays  42 . It is appreciated that the windows  64  may in fact be used as a built-in fiducial for alignment the sensor support substrates  90  with the ribbon of support material. Once aligned, the web of sensor support substrates  90  is heat-sealed to the ribbon of support material  96  to form subassembly  100 .  
      In process four, the subassembly  100  is fed into a reagent dispensing station  102 . A reagent that has been compounded is fed, as shown by arrow  104 , into the dispensing station  102  where it is applied in a liquid form in multiple shots to the array  42 . It is appreciated, however, that the reagent can be applied in a single shot by a custom fit precision dispensing station available from Fluilogic Systems Oy, Espoo, Findland. Reagent application techniques are well known to one of ordinary skill in the art as described in U.S. Pat. No. 5,762,770, the disclosure of which is expressly incorporated herein by reference. It is appreciated that reagents may be applied to the array  42  in a liquid or other form and dried or semi-dried onto the array  42  in accordance with this disclosure. A reagent-coated subassembly  106  then exits the station  102 .  
      In process five, the reagent-coated subassembly  106  is fed into a second cutting and lamination station  108 . At the same time, a ribbon of cover material  110  is fed into station  108 . A liner on one side of the ribbon  110  is removed in the station  108  and rewound over guide roll  112  into a roll  114  for discard. The ribbon of cover material  110  and the subassembly  106  are aligned so that the cover material  110  lies across the electrode arrays  42  to form an assembled material  116 .  
      In process six, the assembled material  116  is fed into a sensor punch/pack station  120  where the material  116  is cut to form individual biosensors  10 . The biosensors  110  are sorted and packed into vials. Each vial is then closed with a stopper to give packaged biosensor strips as shown by arrow  122 .  
      In use, for example, a user of biosensor  10  places a finger having a blood collection incision against respective notches  38 ,  60  and edge  74  adjacent opening  62 . Capillary forces pull a liquid sample flowing from the incision into the opening  62  and through the capillary channel  78  across the reagent  82  and the array  42 . The liquid sample dissolves the reagent  82  and engages the array  42  where the electrochemical reaction takes place.  
      The user then inserts the biosensor  10  into the meter  124  (see, for example  FIG. 10 ) where an electrical connection is made between the electrode contacts  44  exposed by windows  64  and three corresponding meter contacts  126  of the meter  124 . Referring now to  FIG. 11 , a non-limiting example of a suitable meter contact  126  is illustrated. Meter contact  126  includes an electrode engagement portion  128  that is formed of an electrically conductive material and a pivot portion  130 . Each meter contact  126  is spring-loaded so that it pivots over the edge  54  of the spacer support substrate  22  when the biosensor  10  is moved into the meter  124 , as shown for example by arrow  132 , and rides across the surface  50  of said substrate. When, however, the electrode engagement portion  128  encounters a window  64 , the meter contact  126  pivots on the pivot portion  130  so that the portion  128  engages a corresponding electrode exposed by the window  64  and creates an electrically conductive connection between the exposed electrode and the contact. It is appreciated that the illustrated meter  124  includes greater than three meter contacts  126 , two of which will rest upon the second surface  50  of the spacer substrate  22  when the biosensor  10  is inserted into the meter  124 . It is appreciated that biosensor  10  may be used with a variety of meters, which may include greater or less than five meter contacts in accordance with this disclosure.  
      Moreover, it is appreciated that the biosensor  10  also may be inserted into the meter  124  at a variety of time periods including prior to the sample flowing into the opening  62 . Once the electrochemical reaction is complete, a power source (e.g., a battery) applies a potential difference between the electrodes  16 ,  18 ,  20  respectively. When the potential difference is applied, the amount of oxidized form of the mediator at the reference electrode and the potential difference must be sufficient to cause diffusion limited electro-oxidation of the reduced form of the mediator at the surface of the working electrode. The current measuring meter  124  measures the diffusion-limited current generated by the oxidation of the reduced form of the mediator at the surface of the working electrode as described above.  
      The measured current may be accurately correlated to the concentration of the analyte in sample when the following requirements are satisfied: 
          1. The rate of oxidation of the reduced form of the mediator is governed by the rate of diffusion of the reduced form of the mediator to the surface of the working electrode.     2. The current produced is limited by the oxidation of reduced form of the mediator at the surface of the working electrode.        

      It is appreciated that the meter  124  can be designed to be utilized with a number of different biosensors with a variety of different electrodes or contacts. Non-limiting examples of alternative biosensors may require temperature or hematocrit compensation, others might utilize a one, two, four, five or more electrode configuration, others might require coding or expiration information exchange with the meter, etc. Furthermore, the meter  124  may be formed to measure multiple analytes simultaneously on a single strip (e.g., glucose and fructosamine, glucose and ketones, HDL and total cholesterol, etc.). For example, the presence and location of the contacts  44  exposed through the windows  64  could readily identify such a biosensor to the meter as a glucose/ketone assay). Thus, by using different combinations of window placement on biosensor  10 , new analytes may easily be added to the meter&#39;s applications.  
      In another aspect of the invention, a biosensor  210  is provided in accordance with the present invention. Biosensor  210  is shown in  FIGS. 6-7  and includes opposite ends  211 ,  213 , either of which is available to be grasped by a user without contact with electrodes of the biosensor  210 . Biosensor  210  includes an electrode support substrate  212  that supports the electrical conductor  14  described above with reference to biosensor  10 . The conductor  14  is disrupted to define electrodes  216 ,  218 . Biosensor  210  also includes a sensor support substrate  222  positioned on the substrate  212  and a cover substrate  224  positioned on the sensor support substrate  222 . Biosensor  210  is formed in a variety of shapes and sizes and from materials similar to biosensor  10  as described above.  
      Referring to  FIG. 7 , the edge  34  of the electrode support substrate  212  is formed to include a notch  238 . It is appreciated that substrate  212  may be formed without a notch, or that the notch may take on any number of shapes and sizes in accordance with the present disclosure. Electrodes  216 ,  218  are created or isolated from conductor  14  similar to electrodes  16 ,  18 ,  20  as described above. Electrodes  216 ,  218  cooperate with one another to define an electrode array  242 . In addition, electrodes  216 ,  218  each include a contact  244  and a lead  246  extending between the contact  244  and the array  242 . Contacts  244  are spaced apart from end  32 . It is appreciated that the contacts  244  can be formed to have many lengths and can extend to end  32  or to edges  34 ,  36 , or to any number of locations on substrate  212 . Likewise, the leads  246  that extend from the array  242  can be formed to have many lengths and extend to a variety of locations on the electrode support substrate  12 . It is appreciated that the configuration of the electrode array, the number of electrodes, as well as the spacing between the electrodes may vary in accordance with this disclosure and that a greater than one array may be formed as will be appreciated by one of skill in the art.  
      Sensor support substrate  222  of biosensor  210  is positioned to lie between support substrate  212  and cover substrate  224 . Sensor support substrate  222  extends to the end  32  to permit a user to grasp the end  213  of the biosensor  210  without touching the electrodes  216 ,  218 . Moreover, the sensor support substrate  222  cooperates with the support substrate  212  and the cover  224  to expose the electrode array  242  to a liquid sample being applied to the biosensor  210 . Sensor support substrate  222  may have a variety of lengths and is formed from materials similar to substrate  22 , as described above.  
      As shown in  FIG. 7 , the edge  56  of the sensor support substrate  22  is formed to include a notch  260 . It is appreciated that substrate  212  may be formed without a notch, or that the notch may take on any number of shapes and sizes in accordance with the present disclosure. An opening  262  extends from the notch  260  toward the edge  58 . When the sensor support substrate  222  is coupled to substrate  212 , the electrode array  242  is positioned to lie in general alignment with the opening  262 , exposing at least a portion of the electrode array  242 . An interior border  280  defines the opening  262 . The width of the interior border  280  can vary in accordance with this disclosure.  
      The sensor support substrate  222  extends to the end  32  of substrate  212  and is formed to expose the electrode contacts  244  for engagement with a meter  282 , as shown for example in  FIG. 9 . Referring now to  FIGS. 7 and 9 , the sensor support substrate  222  includes discrete windows  264  that extend between first and second surfaces  48 ,  50 . Each window  264  is spaced apart from end  54  in order to enable a user to grasp the end  54  of the sensor support substrate  222  without touching the electrode contacts  244 . Thus, the inadvertent deposit of skin oils, dirt, skin cells, etc. onto the electrical contacts  244  through simple handling of the biosensor  210  is prevented. In addition, at least one window  264  may be used to perform alignment of the substrates  212  and  222 . It is also appreciated that at least one window  264  may be used to perform alignment for other manufacturing processes such as dispensing, labeling, cutting, punching, etc. Moreover, it is appreciated that windows  264  can take on a variety of shapes and sizes as described above with reference to windows  64  in accordance with the present disclosure.  
      As show in  FIG. 6 , the cover substrate  224  is coupled to the spacer support  222  and extends across the opening  262 . The edge  74  of the cover substrate  224  formed to include a notch  276 . It is appreciated that substrate  224  may be formed without a notch, or that the notch may take on any number of shapes and sizes in accordance with the present disclosure. When the cover substrate  224  is coupled to the sensor support substrate  222 , an interior border  282  is aligned with the entrance to the opening  262 . The width of the interior border  282  can vary in accordance with this disclosure.  
      Biosensor  210  is manufactured in a similar manner to biosensor  10 , except for the following differences: First, in the window punch and web slit station  86 , two windows  264  and an opening  262  that has a border  280  with corners are formed in the web of the sensor support substrate  90 . Second, in the ablation/washing and drying station  94 , two electrodes  216 ,  218  are formed on the substrate  212 . Cover material  110  is then fed into the second cutting and lamination station  108  along with the reagent-coated subassembly  106  as discussed above with reference to biosensor  10 . In addition, the ribbon of the cover material  110  and the subassembly  106  are aligned to form an assembled material  116 . The assembled material  116  is then fed into the sensor punch/pack station  120  where the material  116  is cut to form individual biosensors  210  and packed as described above with reference to biosensors  10 .  
      In use, for example, a user of biosensor  210  places a finger having a blood collection incision against array  242  exposed by opening  262 . The liquid sample flowing from the incision dissolves the reagent  82  and engages the array  42  where the electrochemical reaction takes place. Cooperation between the biosensor  210  and the meter  282  are similar to that described above with reference to biosensor  10 . Meter  282 , however, includes two meter contacts  126 . Each meter contact  126  is formed to pivot over edge  54  of the sensor support substrate  222  when the biosensor  210  is inserted into the meter  282 . These meter contacts  126  ride across the surface  50  and pivot into aligned windows  264  so that the portion  128  engages a corresponding electrode exposed by the window  264  and creates an electrically conductive connection between the exposed electrode and the contact.  
      In accordance with another aspect of the present invention, a biosensor  310  is provided and is illustrated in  FIG. 8 . The biosensor  310  is constructed and manufactured identically to biosensor  210  except its spacer support substrate  222  is formed to include one window  364 . This window  364  exposes both electrodes  216 ,  218  to a meter, such as the meter  282  illustrated in  FIG. 9 . Biosensor  310  is also used in a manner similar to biosensor  210 , except that upon insertion of the biosensor  310  into the meter  282 , the meter contacts  126  each pivot into the single window  264  for engagement with an aligned electrode to create an electrically conductive connection between the exposed electrode and the contact.  
      In accordance with another aspect of the present invention, a biosensor  410  is provided and is illustrated in  FIGS. 10-12 . As shown in  FIGS. 11 and 12 , biosensor  410  includes an electrode support substrate  412  that supports the electrical conductor  14  as described above with reference to biosensor  10 . Referring now to  FIG. 10 , the conductor  14  is disrupted to define electrodes  416 ,  418 ,  420 ,  422 ,  426 . Biosensor  410  also includes a sensor support substrate  422  positioned on the substrate  412 . Biosensor  410  may also include a cover substrate, as shown for example in  FIGS. 2 and 7 , positioned on the sensor support substrate  422 . Biosensor  410  is formed in a variety of shapes and sizes and from materials similar to biosensor  10  as described above.  
      Electrodes  416 ,  418 ,  420 ,  422 ,  426  are created or isolated from conductor  14  similar to electrodes  16 ,  18 ,  20  as described above. Each electrode  416 ,  418 ,  420 ,  422 ,  426  includes a contact  444  spaced apart from end  32  and a lead  446  extending from the contact  444 . It is appreciated that the contacts  444  can be formed to have many lengths and can extend to any number of locations on substrate  212 . Likewise, the leads  246  that extend from the contacts  444  can be formed to have many lengths and extend to a variety of locations on the electrode support substrate  412 . It is appreciated that the configuration of the electrodes may vary as discussed above with reference to biosensors  10 ,  210 ,  310 .  
      Sensor support substrate  422  of biosensor  410  extends to the end  32  of the electrode support substrate  412 . Substrate  422 , may however have a variety of lengths and be formed from materials similar to substrate  22 , as described above. In addition, the sensor support substrate  422  is formed to expose the electrode contacts  444  for engagement with the meter  124 . As shown in  FIG. 10 , the sensor support substrate  422  includes five discrete windows  464 . Windows  464  extend between first and second surfaces  48 ,  50 . Each window  264  is spaced apart from end  54 . Similar to windows  64 ,  264 , at least one window  264  may be used to perform alignment for a variety of manufacturing processes. Moreover, it is appreciated that windows  464  can take on a variety of shapes and sizes as described above with reference to windows  64  in accordance with the present disclosure.  
      Biosensor  410  is manufactured in a similar manner to biosensor  210 , except for the following differences: First, in the window punch and web slit station  86 , five windows  464  are formed in the web of the sensor support substrate  90 . Second, in the ablation/washing and drying station  94 , five electrodes  416 ,  418 ,  420 ,  424 ,  426  are formed on the substrate  412 .  
      The biosensor  410  is used in a manner similar to biosensors  10 ,  210 ,  310 . In addition, cooperation between the biosensor  410  and the meter  124  are similar to that described above with reference to biosensor  10 . Each meter contact  126  is formed to pivot over edge  54  of the sensor support substrate  422  when the biosensor  410  is inserted into the meter  124 . These meter contacts  126  ride across the surface  50  and pivot into aligned windows  464  so that the portion  128  engages a corresponding electrode exposed by the window  464  and creates an electrically conductive connection between the exposed electrode and the contact.  
      A non-limiting example of an alternative to meter contact  126  is illustrated diagrammatically in  FIG. 12 . The alternative meter contact  466  may be a mechanical switch or an optical (LED) switch. Contact  466  may be used for an automatic on/off switch, to signify which type of biosensor has been inserted into the meter, as a fail safe for the meter contact, and/or as a positive mating mechanism. It is appreciated that a variety of commercially available mechanical switches and LED switches may be used in accordance with this disclosure.  
      In use, the meter is turned on and the biosensor is inserted into the meter. It is appreciated that the user may turn on the meter, or it may turn on automatically upon insertion of the biosensor. The LED emits a light that is directed through a lens towards the biosensor. The light is reflected off of the exposed conductor  14 , through the lens, and toward the photodiode. The photodiode measures the intensity of the light that is reflected back from the conductor  14  and generates a corresponding voltage waveform. A decoder deciphers this waveform and translates it into a reading of the conductor. It is appreciated that many commercially available optical readers may be used in accordance with the present invention. Preferably, the optical reader will be a custom fit reader.  
      In addition, in accordance with another aspect of the present invention, a biosensor  510  is provided and is illustrated in  FIG. 13 . The biosensor  510  is constructed and manufactured identically to biosensor  410  except its spacer support substrate  522  is formed to include four windows  564  instead of five. Thus, one electrode, a non-limiting example of which is electrode  416 , remains covered by the spacer support substrate  522 . It is appreciated that greater than one electrode may be covered by the substrate  522 . Biosensor  510  is used in a manner similar to biosensor  410 , except that upon insertion of the biosensor  510  into the meter  124 , four meter contacts  126  pivot into corresponding windows  464  for engagement with aligned electrodes  418 ,  420 ,  424 ,  426  to create an electrically conductive connection between the exposed electrodes and the contacts. The meter contact  126  that is aligned with electrode  416  remains resting upon the second surface  50  of the spacer support substrate  522 .  
      In another aspect of the invention, a biosensor  610  is provided in accordance with the present invention. Biosensor  610  is shown in  FIGS. 14 and 15  and includes an electrode support substrate  612  that includes first and second surfaces  626 ,  628  each of which supports an electrical conductor  14  formed as described above with reference to biosensor  10 . The conductor  14  is disrupted to define electrodes  616 ,  618  on the first surface  626  and electrodes  620 ,  622  on the second surface  628 . Biosensor  610  also includes sensor support substrates  630 ,  632 . The substrate  630  extends across electrodes  616 ,  618  and the substrate  632  extends across the electrodes  620 ,  622 . Biosensor  610  may be formed in a variety of shapes and sizes and from materials similar to biosensor  10  as described above.  
      Referring to  FIG. 15 , the electrodes  616 ,  618  and the electrodes  620 ,  622  are created or isolated from conductor  14  similar to electrodes  216 ,  218  as described above with reference to biosensor  210 . Electrodes  616 ,  618  and electrodes  620 ,  622  each include a contact  644  and a lead  646  extending from the contact  644 . See  FIG. 14 . Contacts  644  are spaced apart from end  32 . It is appreciated that the contacts  644  can be formed to have many lengths and can extend to end  32  or to edges  34 ,  36 , or to any number of locations on substrates  630 ,  632 . Likewise, the leads  646  can be formed to have many lengths and extend to a variety of locations on the electrode support substrate  612 . It is appreciated that the number of electrodes as well as the spacing between the electrodes may vary in accordance with this disclosure as will be appreciated by one of skill in the art. It is also appreciated that the electrodes  616 ,  618  and the electrodes  620 ,  622  may cooperate to form a variety of electrode arrays in accordance with this disclosure.  
      Sensor support substrates  630 ,  632  of biosensor  610  each extend to the end  32  of the electrode support substrate  612 . It is appreciated, however, the relative positioning between the substrates  630 ,  632  and the electrode support substrate  612  may vary in accordance with this disclosure. Moreover, the sensor support substrates  630 ,  632  are formed from materials similar to substrate  22 , as described above. As shown in  FIG. 15 , the sensor support substrate  630  is formed to expose the contacts  644  of the electrodes  616 ,  618  for engagement with meter contacts  126 . Likewise, the sensor support substrate  632  is formed to expose the contacts  644  of the electrodes  620 ,  622  for engagement with meter contacts  126 .  
      The support substrates  630 ,  632  are formed to include discrete windows  648 ,  650  respectively. Each window  648 ,  650  extends between first and second surfaces  48 ,  50  and is spaced-apart from end  54 . It is appreciated that at least one of the windows may be used to perform alignment of the sensor support substrate  630  with the electrode support substrate  612  and the sensor support substrate  632  with the electrode support substrate  612 . It is also appreciated that at least one window may be used to perform alignment for other manufacturing processes such as dispensing, labeling, cutting, punching, etc. Moreover, it is appreciated that the windows  648 ,  650  can take on a variety of shapes and sizes as described above with reference to windows  64  in accordance with the present disclosure.  
      Biosensor  610  is manufactured in a similar manner to biosensor  10 , except for the following differences:  
      First, in the window punch and web slit station  86 , two windows  648  are formed in the web of the sensor support substrate. Likewise, either in the station  86 , or in a second slit station, two windows  650  are formed in a second web of a sensor support substrate. Second, in process two, a roll of electrode support material that is metallized on first and second surfaces  626 ,  628  is fed into an ablation/washing and drying station  94 . In the ablation station  94 , each metallic layer of the metallized film is ablated in a pre-determined pattern, to form a ribbon of support material with isolated electrode patterns on surfaces  626 ,  628 . The energy required for ablation is similar to that described above with reference to biosensor  10 .  
      Next, in process three, the first and second rolls of punched sensor support substrates are fed into a cutting and lamination station  98 . At the same time, the ribbon of support material with isolated electrode patterns is fed into the station  98 . The thermoplastic resin coated first surface of the sensor support substrates are each applied to the first and second surfaces  626 ,  628  of the electrode support substrate material so that the windows  648 ,  650  are in general alignment with the contacts  644 . It is appreciated that the windows  648 ,  650  may in fact be used as a built-in fiducial for alignment the sensor support substrates with the ribbon of support material. Once aligned, the web of sensor support substrates is heat-sealed to the ribbon of support material to form a subassembly.  
      In process four, the subassembly is fed into a first reagent dispensing station  102 . A reagent that has been compounded is fed, as shown by arrow  104 , into the dispensing station  102  where it is applied in a liquid form in multiple shots to the array on the first surface  626 . The subassembly is then fed into a second reagent dispensing station (not shown) where a second reagent that has been compounded is fed into the dispensing station where it is applied in a liquid form in multiple shots to the array on the second surface  628 . It is appreciated that the reagent can be applied in a single shot by a custom fit precision dispensing station available from Fluilogic Systems Oy, Espoo, Findland. Reagent application techniques are as described above with reference to biosensor  10 . It is appreciated that reagents may be applied to the arrays in a liquid or other form and dried or semi-dried onto the arrays in accordance with this disclosure. A reagent-coated subassembly then exits the second station.  
      In process five, the reagent-coated subassembly is fed into a second cutting and lamination station  108 . At the same time, two ribbons of cover material are fed into the station  108 . A liner on one side of each ribbon is removed in the station  108 . The ribbons of cover material and the subassembly are aligned so that one ribbon of cover material lies across a portion of the electrodes  616 ,  61   8  and that the second ribbon of cover material lies across a portion of the electrodes  620 ,  622  to form an assembled material. The assembled material is cut to form individual biosensors  610  as described above with reference to biosensor  10 .  
      Biosensor  610  is used in a manner similar to biosensor  210 . Likewise, cooperation between the biosensor  610  and a meter are similar to that described above with reference to biosensor  10 . A meter suitable for use with biosensor  610  will include meter contacts that will become aligned with windows  648 ,  650  when the biosensor  610  is inserted into the meter.  
      The processes and products described above include disposable biosensors  10 ,  210 ,  310 ,  410 ,  510 , and  610  especially for use in diagnostic devices. Also included, however, are electrochemical sensors for non-diagnostic uses, such as measuring an analyte in any biological, environmental, or other sample. As discussed above, biosensor  10  can be manufactured in a variety of shapes and sizes and be used to perform a variety of assays, non-limiting examples of which include current, charge, impedance conductance, potential or other electrochemical indicative property of the sample applied to biosensor.  
      Although the invention has been described in detail with reference to a preferred embodiment, variations and modifications exist within the scope and spirit of the invention, on as described and defined in the following claims.