Patent Application
20230375495
This application generally relates to the field of biosensors and more specifically to a test strip, as well as a related method for manufacturing a test strip having one or more spaced electrically conductive material layers. Cofacial electrodes locally formed at one end of the test strip are made from a precious metal with the remainder of the electrically conductive layer(s) of the test strip being made from another electrically conductive material that is configured to enable electrical connection between the cofacial electrodes and a test meter.
Biosensors are known in the field of diabetes management, such as test strips, onto which a blood sample can be deposited. One end of the test strip is inserted into a test meter that applies at least one predetermined voltage to two or more electrodes formed on the test strip. The electrodes are made from a precious metal, such as gold or palladium, in addition to at least one reagent layer that is applied to one of the electrodes. Upon application of the at least one predetermined voltage, electrochemical reactions are created wherein the resulting current can be measured in order to provide a determination of the concentration of blood glucose in the blood sample.
The inclusion of precious metals significantly impacts cost in the manufacture of the above described test strips. Accordingly, there is a prevailing need in the field to reduce the amount of precious metals used in the manufacture of biosensors, such as those described above, but without impacting functionality or overall performance.
Therefore and according to an aspect of the present invention, there is provided a biosensor comprising a first base member and a second base member, the first and second base members being made from an insulative material that face one another in a spaced and parallel relationship. At least one electrically conductive layer is deposited onto a facing surface of each of the first and second base members and more specifically at a first conductive region and a second conductive region adjacent the first conductive region. According to at least one version, the first conductive region includes a deposited layer of a first electrically conductive material and the second conductive region includes at least a second electrically conductive material different from the first electrically conductive material, the first electrically conductive material being a precious metal and wherein the first conductive regions form cofacial electrodes of the biosensor.
According to at least one embodiment, the precious metal disposed in the first conductive region of the biosensor can be at least one of gold and palladium. Alternatively, other precious metals from the group consisting of platinum, iridium, osmium, rhenium, ruthenium, and rhodium can be used to form the cofacial electrodes. The second conductive material can be made from any suitable electrically conductive material including, but not limited to silver, copper, nickel, chromium and/or alloys thereof wherein the first and second conductive regions are electrically coupled to one another. According to one version, the first conductive region is defined by a single deposited layer of the precious metal. In another version, the first conductive region is defined by a first deposited layer made from the second electrically conductive material and a second deposited layer made from the precious metal that is applied onto the first deposited layer.
Preferably, the precious metal layer overlaps with a portion of the non-precious layer. The biosensor can further include a spacer or spacer layer, made from plastic or other insulative material, which is introduced between the electrically conductive material layers. The spacer layer includes a gap or spacing serving as a functional area in which electrochemical reaction take place in the presence of blood or other bodily fluid introduced into the biosensor. The biosensor further includes contact pads defined in the second electrically conductive regions that are connectable to a test meter configured to deliver at least one test voltage to the electrodes of the biosensor.
The base members facing one another in the biosensor can be a substrate or a film made from an electrically inert material. The precious metal layer can be applied by any suitable deposition process including physical vapor deposition (PVD) or chemical vapor deposition (CVD) processes. According to at least one embodiment, the precious metal layer is deposited with the second conductive region being masked in relation to the first conductive region. The second conductive metal layer(s) can also be applied by means of any suitable deposition process.
According to another aspect, there is provided a method for manufacturing a biosensor, the method comprising:
In at least one version, the second electrically conductive material is applied to the entire surface of each base member and then the first conductive material is deposited onto the second conductive material, but only in the first conductive region of the biosensor.
In another version, the first electrically conductive material can be deposited on the first conductive regions of each base member and the second electrically conductive material can be deposited on the second conductive regions. Preferably, a seam or other overlap is provided between the precious and non-precious material layers in order maintain electrical connectivity between the defined electrodes and a test meter.
According to the present invention, non-precious metals can be incorporated in combination with precious metals into a biosensor and more specifically an electrochemically-based test strip having cofacial electrodes using a mask during the deposition process in order to apply a well-defined layer of precious metal to cover at least the working area (that is, the area of the test strip in which a heterogeneous electrochemical reaction takes place) of the test strip. Advantageously, this design allows for the separation of two functions of the test strip, namely, the transmission of an electrical signal which is performed by the non-precious metal or alloy and the surface chemistry reactions, which are performed on the precious metal portion of the substrate layers.
An advantage provided is that existing precious metal layers can be used in combination with non-precious metal materials for use within a test strip production line without impacting overall performance. Accordingly, significant cost savings can be realized in terms of manufacturing the biosensor.
Another advantage is that by using a precious metal stripe in combination with a non-precious metal or alloy layer, the chemistry of the test strip is unchanged in terms of interaction with the existing precious metal surface.
Considerations such as surface energy, reagent adhesion, surface oxidation and adsorption of contaminants to the electrode surface are all substantially unchanged from prior known test strip designs.
In addition, the control of non-precious metal or alloy layer thickness according to the presently described method allows for resistance values to be tailored to match those of the precious metals, thereby providing a conductive pathway or bridge for electrical signal transmission with a resistance equivalent to that of the precious metals (e.g., palladium and gold).
Furthermore, the use of non-precious metal or alloys, having a greater hardness than that of precious metals, particularly gold, improves robustness of the electrical contacts of the test strip with the connectors of the test meter.
These and other features and advantages will be readily apparent from the following Detailed Description, which should be read in conjunction with the accompanying drawings.
The following describes several embodiments of biosensors used for determining at least one analyte of interest (e.g., blood glucose), as well as a related method for manufacturing a biosensor. More specifically, each of the herein described biosensors and related manufacturing method(s) relate to a test strip having one or more facing (cofacial) electrodes defining an electrochemical cell in which electrical potentials are driven in the presence of an enzyme or other reagent applied to at least one of the electrodes to create electrochemical reactions in the presence of a bodily fluid sample (e.g., whole blood). It will be understood, however, that the presently disclosed invention can be used, in principle, with any type of electrochemical cell having spaced apart cofacial electrodes and a reagent layer. For example, an electrochemical cell can be in the form of a test strip. In one aspect, the test strip may include two opposing electrodes separated by a thin spacer layer, defining a sample-receiving chamber or zone in which a reagent layer is positioned on one of the opposing electrodes. One skilled in the art will appreciate that other types of test strips, including those with configurations having more than two facing electrodes, may also be used in accordance with the methods described herein.
In addition, a number of terms are used throughout the following description to provide a suitable frame of reference with regard to the accompanying drawings. These terms, which include “first”, “second”, “distal”, proximal”, “above”, “below”, “top”, “bottom” and the like are not intended to overly narrow the intended scope of the present invention, except where so specifically indicated. Additionally, the accompanying drawings are intended to adequately depict salient features of the present invention. Accordingly, the drawings are not necessarily to scale and should not be used for scalar purposes.
For purposes of background,
Sandwiched between the upper and lower precious metal layers is a spacer layer 60, which is also made from a suitable plastic. The spacer layer 60 includes a cut-out region 68 adjacent the distal end 80 of the test strip 62 that provides a predetermined spacing or gap between the metallized film layers and cooperates to form the sample receiving chamber 61. A reagent layer 72 which includes an enzyme/mediator is deposited onto a portion of the surface of the metallized palladium layer at the distal end 80 of the test strip 62, forming cofacial electrodes of the test strip 62 separated by the spacer layer 60 extending through the spacing 68. The test strip 62 further includes one or more electrode connection points or contact pads 67 formed at the proximal end 82 of the test strip 10 wherein the gold and palladium layers define electrodes in a working area of the test strip and electrode track connections to the contact pads 67, as shown in
The applied metallized film layers commonly provide upper and lower cofacial electrodes 166, 164, connection tracks 76, 78, and contact pads 67, 63, where the connection tracks 76, 78 of each metallized film layer electrically connects the electrodes 166, 164 to the contact pad 63, 67, as shown in
The sample-receiving chamber 61 is defined by the first electrode 166, the second electrode 164, and the spaced gap or cutout area 68 formed in the spacer 60 near the distal end 80 of the test strip 62, as shown in
The sample-receiving chamber 61 of this described test strip 62 has a small volume in the range of from about 0.1 microliters to about 5 microliters, about 0.2 microliters to about 3 microliters, or, preferably, about 0.3 microliters to about 1 microliter. To provide the small sample volume, the cutout 154 has an area ranging from about 0.01 cm2 to about 0.2 cm2, about 0.02 cm2 to about 0.15 cm2, or, preferably, about 0.03 cm2 to about 0.08 cm2. In addition, the formed electrodes 166, 164 are spaced apart in the range of about 1 micron to about 500 microns, preferably between about 10 microns and about 400 microns, and more preferably between about 40 microns and about 200 microns. The relatively close spacing of the electrodes 166, 164 also allows redox cycling to occur, where oxidized mediator generated at the first electrode can diffuse to the second electrode to become reduced, and subsequently diffuse back to the first electrode to become oxidized again.
For the reagent layer 60, examples of suitable mediators include ferricyanide, ferrocene, ferrocene derivatives, osmium bipyridyl complexes, and quinone derivatives. Examples of suitable enzymes include glucose oxidase, glucose dehydrogenase (GDH) using a pyrroloquinoline quinone (PQQ) co-factor, GDH using a nicotinamide adenine dinucleotide (NAD) co-factor, and GDH using a flavin adenine dinucleotide (FAD) co-factor [E.C.1.1.99.10].
In terms of operability, either the gold layer or the palladium layer can perform the function of a working electrode of the test strip 62, depending on the magnitude and/or polarity of an applied test voltage from a test meter coupled to the test strip 62. The working electrode may measure a limiting test current that is proportional to the reduced mediator concentration. For example, if the current limiting species is a reduced mediator (e.g., ferrocyanide), then it can be oxidized at the first electrode 166 as long as the test voltage is sufficiently more positive than the redox mediator potential with respect to the second electrode 164. In such a situation, the first electrode 166 performs the function of the working electrode and the second electrode 164 performs the function of a counter/reference electrode.
Similarly, if the test voltage is sufficiently more negative than the redox mediator potential, then the reduced mediator can be oxidized at the second electrode 164 as a limiting current. In such a situation, the second electrode 164 performs the function of the working electrode and the first electrode 166 performs the function of the counter/reference electrode.
Initially, performing an analysis using the herein described test strip 62 includes introducing a quantity of a fluid sample into the sample-receiving chamber 61 via one of the ports 70. The port 70 and/or the sample-receiving chamber 61 are configured such that capillary action causes the fluid sample to fill the sample-receiving chamber 61. The first electrode 166 and/or second electrode 164 may be coated with a hydrophilic reagent to promote the capillarity of the sample-receiving chamber 61.
The test meter 100 is configured to apply a test voltage and/or a current between the first contact pad 67 and the second contact pad 63. Once the test meter 100 recognizes that the test strip 62 has been inserted, the test meter 100 turns on and initiates a fluid detection mode. In one embodiment, the fluid detection mode causes the test meter 100 to attempt to apply a voltage such that a constant current of about 0.5 microampere would flow between the first electrode 166 and the second electrode 164. Because the test strip 62 is initially dry, the test meter 100 measures a relatively large voltage, which can be limited by the maximum voltage that the test meter 100 is capable of supplying. When the fluid sample bridges the gap between the first electrode 166 and the second electrode 164 during the dosing process, the test meter 100 will measure a decrease in applied voltage and when it is below a predetermined threshold will cause the test meter 100 to automatically initiate a glucose test sequence.
In the version herein described in this background, the test meter 100 can perform a glucose test by applying a plurality of test voltages for a number of prescribed intervals, as shown in
Once the glucose assay has been initiated, the test meter 100 may apply a first test voltage V1 (e.g., about −20 mV as shown in
The first time interval T1 may be sufficiently long so that the sample-receiving chamber 61 can fully fill with sample and also so that the reagent layer 72 can at least partially dissolve or solvate. The reagent layer 160 has an area larger than the area of the formed electrode in which a portion of the spacer layer 150 can overlap and contact the reagent layer 160. In one aspect, the first test voltage V1 may be a relatively low value so that a relatively small amount of a reduction or oxidation current is measured. Typically, a relatively small amount of current is observed during the first time interval T1 compared to the second and third time intervals T2 and T3. For example, when using ferricyanide and/or ferrocyanide as the mediator, the first test voltage V1 can range from about −100 mV to about −1 mV, preferably range from about −50 mV to about −5 mV, and most preferably range from about −30 mV to about −10 mV.
After applying the first test voltage V1, the test meter 100 applies a second test voltage V2 between the first electrode 166 and the second electrode 164 (e.g., about −0.3 Volts as shown in
The second time interval T2 should be sufficiently long so that the rate of generation of reduced mediator (e.g., ferrocyanide) can be monitored based on the magnitude of a limiting oxidation current. Reduced mediator is generated by enzymatic reactions with the reagent layer 72. During the second time interval T2, a limiting amount of reduced mediator is oxidized at the second electrode 164 and a non-limiting amount of oxidized mediator is reduced at the first electrode 166 to form a concentration gradient between the first electrode 166 and the second electrode 164. Additional details relating to the manufacture and testing of the test strip 62 are described in U.S. Pat. Nos. 8,529,751 and 8,449,740, the entire contents of each being herein incorporated by reference.
With the preceding background,
According to a first embodiment shown in
According to this first embodiment and adjacent the distal end 410 of the test strip 400, a second electrically conductive material layer 470 is deposited directly onto a portion of the first electrically conductive layer 460 of each of the upper and lower base members 404, 408. As shown in
According to another embodiment and with reference to
Where differences in resistances exist (for example when using an alloy with a higher resistance than that of a precious metal) sputtered layer thicknesses may be increased or decreased for either the precious metal or the non-precious metal layer to alter and match electrical conductivity between the two layers to ensure that conductivity of the non-precious metal or alloy layer is not signal limiting. For example the thickness of the precious metal layer 470 of
It should be understood that other variations and modifications are possible. With reference to
In each of the embodiments described herein, the locally applied or deposited precious metal layers 470, 470A, for each test strip define respective cofacial electrodes that are separated by the cut out area 428 of the spacer layer 420 at the working area of the test strip. The overlapping portions of the non-precious material layers 460, 460A define electrode connection tracks that extend to contact pads provided at the opposing (proximal) end 414 of the test strip, thereby enabling connection to a test meter as previously discussed at
It will be understood that only a number of exemplary embodiments have been described herein and a number of variations and modifications embodying the inventive concepts will be readily apparent to a person of ordinary skill reading this application and in accordance with the following appended claims.
