BACKGROUND

The present disclosure relates to metal alloys; electrodes, for example, physical vapor deposited components for electrodes such as those found in biosensors; and methods for creating a biosensor. In particular, the biosensors have one or more electrodes made from a non-noble metal alloy, such as a nickel (Ni) based alloy in combination with elements such as aluminum (Al), gold (Au), chromium (Cr), copper (Cu), molybdenum (Mo), palladium (Pd), ruthenium (Ru), tantalum (Ta), or titanium (Ti), having desired mechanical and electrical properties, and will be described with particular reference thereto. However, it is to be appreciated that the present disclosure is also amenable to other like applications.

Biosensors can be used in several applications, such as for measuring the amount of an analyte (e.g., glucose) in a biological fluid (e.g., blood). Blood glucose monitoring is a valuable tool in the management of diabetes. Diabetes is a disease in which the body is unable to control tightly the level of blood glucose, which is the most important and primary fuel of the body. This is due to either the pancreas not producing enough insulin, or to the cells of the body not responding properly to the insulin produced. Patients with diabetes are encouraged to monitor their glucose levels to prevent hyperglycemia, as well as other long-term complications such as heart disease, stroke, kidney failure, foot ulcers, and eye damage. A glucose biosensor is an analytical device for detecting the analyte, glucose, in the blood. Although glucose biosensors have been devised based on potentiometry, amperometry, and colorimetry, to date most commercially available biosensors are amperometric biosensors. These biosensors use a redox enzyme (e.g., glutathione peroxidases (GPX), nitric oxide synthase (eNOS, iNOS, and nNOS), peroxiredoxins, super oxide dismutases (SOD), thioredoxins (Trx), and the like), as the biological component responsible for the selective recognition of the analyte of interest (e.g., glucose).

A biosensor of this type is a relatively small strip of laminated plastic that can be exposed to a biological sample such as blood. An important feature of the biosensor is that it is disposable and only used one time. The strip acts as a substrate for a reaction chamber and two electrodes, a reference electrode and a working electrode, which are connected to the reaction chamber. The glucose biosensor contains a reagent layer that is attached to the working electrode. The reagent layer includes the selective recognition component (i.e., the redox enzyme) as well as electron mediators.

An electron mediator is an artificial electron transferring agent that helps shuttle electrons from the redox enzyme to the electrode surface. The mediator does this by reacting with the reduced enzyme and then diffusing to the electrode surface. Examples of mediators include vinyl ferrocene (VFc) initiated by 2,2r-azobisisobutyronitrile (AIBN), osmium complexes, quinone, ferricyanide, methylene blue, 2,6-dichloroindophenol, thionine, gallocyanine, indophenol, combinations thereof, and the like.

The biological fluid sample is introduced into the reaction chamber of the glucose biosensor and the biosensor is connected to a measuring device such as a meter for analysis using the biosensor's electrodes. The analyte (glucose) in the sample undergoes a reduction/oxidation reaction at the working electrode (where the redox enzyme is located) while the measuring device applies a biasing potential signal through the electrodes of the biosensor. The redox reaction produces an output signal in response to the biasing potential signal. The output signal usually is an electronic signal, such as potential or current, which is measured and correlated with the concentration of the analyte in the biological fluid sample.

Electrodes in such biosensors are typically made from expensive precious metals, such as silver, gold, palladium, or platinum. It would be desirable to develop new alloys that can be used as electrodes in a biosensor that have additional advantages when used with specific enzyme/mediator systems. It would also be desirable if such alloys did not include precious metals, which are costly.

BRIEF DESCRIPTION

The present disclosure relates to biosensors having electrodes formed from a metal alloy, such as a nickel-based alloy. A reagent is disposed on the electrode, the reagent comprising specific combinations of an enzyme and an electron mediator. The resulting electrode has physical and/or electrical properties that are advantageous when used with the reagent. These properties can include thinness, safety during reaction with the redox reagent, electrical conductivity, and reactivity with the redox reagent. While most of this disclosure relates to electrodes used as biosensor components, it is contemplated that the electrodes can be used in other end-use applications as well. As a result, any disclosure herein related to electrodes used in biosensors is intended to incorporate herein applicability to all electrodes that this technology could reasonably be applied to by one of ordinary skill in the art.

Disclosed in various embodiments are metal alloys comprising nickel in combination with at least one additional alloying element. It is contemplated that the nickel-containing alloy may be a binary, ternary, or quaternary alloy. The alloy may contain from about 20 atomic percent (at %) to about 95 at % nickel; about 55 atomic percent (at %) to about 95 at % nickel; about 55 at % to about 65 at % nickel; from about 55 at % to about 60 at %; about 55 at % to about 75 at % nickel; from about 60 at % to about 70 at %; about 65 at % to about 85 at % nickel; from about 70 at % to about 80 at %; about 75 at % to about 95 at % nickel; from about 80 at % to about 90 at %; or about 85 at % to about 95 at % nickel. This is on the basis of the alloy totaling 100 at %.

The additional alloying element(s) are, in particular embodiments, selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium. The alloy may contain nickel in combination with about 5 at % to about 45 at % of the additional alloying element(s), including; about 35 at % to about 45 at %; from about 25 at % to about 45 at %; from about 30 at % to about 40 at %; about 15 at % to about 35 at %; from about 20 at % to about 30 at %; about 5 at % to about 25 at %; from about 10 at % to about 20 at %; or about 5 at % to about 15 at %; or from about 0 at % to about 10 at % of the additional alloying element(s). In particular embodiments when the nickel-based alloy is a ternary alloy, the weight ratio of the first alloying element to the second alloying element may be from about 1:1: to about 2:1.

In one set of embodiments, the nickel-based alloy comprises from about 55 at % to about 95 at % nickel. In particular embodiments, the alloy is a binary alloy and comprises from about 5 at % to about 45 at % of the first alloying element, and the first alloying element is selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium. In other particular embodiments, the alloy is a ternary alloy and consists essentially of about 55 at % to about 95 at % nickel; the first alloying element; and a second alloying element; wherein the first alloying element and the second alloying element are each selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium, and together the first alloying element and the second alloying element comprise from about 5 at % to about 45 at % of the alloy.

In another set of embodiments, the alloy comprises from about 55 at % to about 65 at % nickel. In particular embodiments, the alloy is a binary alloy and comprises from about 35 at % to about 45 at % of the first alloying element, and the first alloying element is selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium. In other embodiments, the alloy is a ternary alloy and consists essentially of about 55 at % to about 65 at % nickel; the first alloying element; and a second alloying element, wherein the first alloying element and the second alloying element are each selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium, and together the first alloying element and the second alloying element comprise from about 35 at % to about 45 at % of the alloy.

In yet another set of embodiments, the alloy comprises from about 55 at % to about 75 at % nickel. In specific embodiments, the alloy is a binary alloy and comprises from about 25 at % to about 45 at % of the first alloying element, and the first alloying element is selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium. In other specific embodiments, the alloy is a ternary alloy and consists essentially of about 55 at % to about 75 at % nickel; the first alloying element; and a second alloying element, wherein the first alloying element and the second alloying element are each selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium, and together the first alloying element and the second alloying element comprise from about 25 at % to about 45 at % of the alloy.

In a different set of embodiments, the alloy comprises from about 65 at % to about 85 at % nickel. In particular embodiments, the alloy is a binary alloy and comprises from about 15 at % to about 35 at % of the first alloying element, and the first alloying element is selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium. In other particular embodiments, the alloy is a ternary alloy and consists essentially of about 65 at % to about 85 at % nickel; the first alloying element; and a second alloying element; wherein the first alloying element and the second alloying element are each selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium, and together the first alloying element and the second alloying element comprise from about 15 at % to about 35 at % of the alloy.

In a further set of embodiments, the alloy comprises from about 75 at % to about 95 at % nickel. In particular embodiments, the alloy is a binary alloy and comprises from about 5 at % to about 25 at % of the first alloying element, and the first alloying element is selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium. In other particular embodiments, the alloy is a ternary alloy and consists essentially of about 75 at % to about 95 at % nickel; the first alloying element; and a second alloying element, wherein the first alloying element and the second alloying element are each selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium, and together the first alloying element and the second alloying element comprise from about 5 at % to about 25 at % of the alloy.

In other embodiments, the alloy comprises from about 85 at % to about 95 at % nickel. In some specific embodiments, the alloy is a binary alloy and comprises from about 5 at % to about 15 at % of the first alloying element, and the first alloying element is selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium. In other specific embodiments, the alloy is a ternary alloy and consists essentially of about 85 at % to about 95 at % nickel; the first alloying element; and a second alloying element; wherein the first alloying element and the second alloying element are each selected from the group consisting of aluminum, gold, chromium, copper, molybdenum, palladium, ruthenium, tantalum, and titanium, and together the first alloying element and the second alloying element comprise from about 5 at % to about 15 at % of the alloy.

In a different set of embodiments, the alloy comprises from about 20 at % to about 95 at % nickel. In more specific embodiments, the alloy is a binary alloy and comprises from about 5 at % to about 80 at % of the first alloying element, and the first alloying element is selected from the group consisting of aluminum, ruthenium, tantalum, and titanium. In other specific embodiments, the alloy is a ternary alloy and consists essentially of about 20 at % to about 95 at % nickel; the first alloying element; and a second alloying element; wherein the first alloying element and the second alloying element are each selected from the group consisting of aluminum, ruthenium, tantalum, and titanium, and together the first alloying element and the second alloying element comprise from about 5 at % to about 80 at % of the alloy.

In some further embodiments, the alloy is a binary alloy consisting essentially of (a) about 55 at % to about 95 at % nickel and (b) about 5 at % to about 45 at % of either aluminum, chromium, or ruthenium.

In other further embodiments, the alloy is a binary alloy consisting essentially of (a) about 55 at % to about 95 at % nickel and (b) about 5 at % to about 45 at % of either aluminum, copper, chromium, tantalum, or titanium.

In still other embodiments, the alloy is a binary alloy consisting essentially of (a) about 55 at % to about 95 at % nickel and (b) about 5 at % to about 45 at % of aluminum, chromium, or titanium.

In some particular embodiments, the alloy is a binary alloy consisting essentially of (a) about 45 at % to about 95 at % nickel and (b) about 5 at % to about 55 at % of ruthenium.

In yet other embodiments, the alloy is a ternary alloy consisting essentially of (a) about 20 at % to about 55 at % nickel, (b) about 20 at % to about 30 at % titanium, and (c) about 20 at % to about 30 at % tantalum.

In more different embodiments, the alloy is a ternary alloy consisting essentially of (a) about 20 at % to about 55 at % nickel, (b) about 20 at % to about 30 at % aluminum, and (c) about 20 at % to about 30 at % ruthenium.

In additional particular embodiments when the nickel-based alloy is a ternary alloy, the alloy comprises (a) nickel and (b) either aluminum, ruthenium, tantalum, or titanium. These ternary alloys may comprise from about 20 at % to about 95 at % nickel, the remainder aluminum, ruthenium, tantalum, or titanium.

In some particular embodiments, the alloy is a binary alloy of (a) nickel and (b) either aluminum, chromium, or ruthenium. These binary alloys may comprise about 55 at % to about 95 at % nickel, remainder aluminum, chromium, or ruthenium.

In some particular embodiments, the alloy is a binary alloy of (a) nickel and (b) either aluminum, copper, chromium, tantalum, or titanium. These binary alloys may comprise about 55 at % to about 95 at % nickel, remainder aluminum, copper, chromium, tantalum, or titanium.

In some other particular embodiments, the alloy is a ternary alloy combining about 20 at % to about 55 at % nickel with about 20 at % to about 30 at % titanium and about 20 at % to about 30 at % tantalum.

In some other particular embodiments, the alloy is a ternary alloy combining about 20 at % to about 55 at % nickel with about 20 at % to about 30 at % aluminum and about 20 at % to about 30 at % ruthenium.

In some particular embodiments, the alloy is a binary alloy of (a) nickel and (b) either aluminum, chromium, or titanium. These binary alloys may comprise about 55 at % to about 95 at % nickel, remainder aluminum, chromium, or titanium.

In some particular embodiments, the alloy is a binary alloy of (a) nickel and (b) ruthenium. These binary alloys may comprise about 45 at % to about 95 at % nickel, remainder ruthenium.

Also disclosed herein are biosensors, electrodes, and articles comprising such alloys.

Also disclosed in various embodiments are methods of creating a biosensor, comprising: forming a first electrode from a nickel-based alloy on a surface of a substrate. The nickel-based alloys can include any of the aforementioned alloys. The biosensor can be used to measure an analyte in a biological fluid.

The methods can further comprise forming the first electrode by co-sputtering.

The methods can additionally comprise forming a reaction chamber in the substrate, the reaction chamber contacting the first electrode. In addition, a reagent layer can be formed on the first electrode to form a working electrode.

The methods contemplate that the first electrode operates as a reference electrode, and further comprise forming a second electrode on the substrate from the binary nickel-based alloy, and placing a reagent layer on the second electrode to form a working electrode.

These and other non-limiting characteristics of the disclosure are more particularly disclosed below.

