Working lines for biosensors

Abstract

Disclosed is a working wire for a biosensor. The working wire comprises: a substrate comprising a cobalt-chromium (Co-Cr) alloy or a nitinol alloy; a platinum layer disposed on the substrate and comprising platinum; and a membrane layer applied on the platinum layer and comprising a biofilm.

Description

[0001] Related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 021,212, filed May 7, 2020, and entitled “Working Electrode for a Continuous Biological Sensor,” which is hereby incorporated by reference in its entirety. Background Art

[0003] Medical patients with illnesses or conditions often need to measure and report their biological conditions. For example, if a patient has diabetes, it is important for them to have an accurate understanding of the glucose level in their blood. Traditionally, diabetics monitor their glucose levels by pricking their finger with a small spear, allowing a drop of blood to form, and then dipping a test strip into the blood. The test strip with the blood sample is positioned in a handheld monitor, which analyzes the blood and visually reports the glucose level measured in the patient's blood sample. Based on the glucose level, the patient may need to lower or raise their glucose level. This requires making important decisions about which foods to consume or how much insulin to inject into their bloodstream. While it is beneficial for patients to check their glucose levels multiple times a day, many are unable to adequately monitor their glucose levels due to the pain and inconvenience. As a result, patients may consume foods improperly or inject too much or too little insulin. Either way, the patient's quality of life decreases and the chance of permanent damage to their health and well-being increases. Diabetes is a devastating disease that, if not properly controlled, can lead to serious physical symptoms such as kidney failure, skin ulcers, eye bleeding, blindness, pain, and sometimes amputation.

[0004] Glucose monitoring is a complex process, and it is known that the glucose level in the blood can increase or decrease significantly rapidly due to several reasons. Therefore, a single glucose measurement only provides a snapshot of the instantaneous glucose level in the patient. This single measurement provides very little information about the change in the patient's use of glucose over time or the patient's response to a specific dose of insulin. Patients who follow a strict blood strip test schedule may make wrong decisions in diet, exercise, and insulin injections because the blood strip test is only a snapshot of time. Of course, this can be exacerbated when the patient's condition is not quite consistent with the execution strip test. In order to give the patient a more comprehensive understanding of its diabetic condition and obtain better treatment results, continuous glucose monitoring is used.

[0005] Monitoring glucose levels in the body is crucial for people with diabetes. Continuous glucose monitoring devices measure glucose in a patient's body multiple times a day from tissue fluid sampled from an area just under the skin. Continuous glucose monitoring devices typically involve a small housing in which the electronics are located, and the housing is adhered to the patient's skin and worn for a certain period of time. A small needle within the continuous glucose monitoring device delivers a subcutaneous sensor, which is typically electrochemical. It should be understood that continuous glucose monitoring can be performed at different intervals, depending on the needs of the patient. For example, some continuous glucose monitoring devices can be programmed to take multiple readings per minute, while in other cases, the continuous glucose monitoring device can be programmed to take readings every hour or so. It should be understood that the continuous glucose monitoring device can sense and report measurements at different intervals.

[0006] Electrochemical glucose sensors are typically part of a continuous glucose monitoring device and operate by using electrodes that typically detect an amperometric signal caused by the oxidation of an enzyme during the conversion of glucose into gluconolactone in the patient's body. The amperometric signal can then be correlated to the glucose concentration. A two-electrode (also called a bipolar) design uses a working electrode and a reference electrode, where the reference electrode provides a reference and the working electrode is biased relative to the reference. The reference electrode essentially completes the flow of electrons in the electrochemical circuit. A three-electrode (or tripole) design has a working electrode, a reference electrode, and a counter electrode. The counter electrode replenishes ion losses at the reference electrode and is part of the ionic circuit.

[0007] Monitoring devices can track and analyze glucose readings taken by sensors, such as by scanning the sensors with custom receivers or by transmitting signals to smartphones or other devices with associated software applications. These are called continuous glucose monitoring systems. Software features already included in continuous glucose monitoring systems include viewing glucose levels over time, indicating glucose trends, and alerting patients to high and low glucose levels.

[0008] Unfortunately, the cost of using a continuous glucose monitoring system can be expensive for many patients who could benefit greatly from its use. As generally described above, a continuous glucose monitor has two main components. First, a housing encloses the electronics, processor, memory, wireless communication, and power supply. The housing is typically reusable and can be reused over an extended period of time (such as several months). The housing is then connected to or communicates with a disposable sensor that has been subcutaneously inserted into the patient. This sensor must sometimes be replaced once every three days or at least every other week. Therefore, the cost of purchasing new disposable sensors brings a significant financial burden to patients and insurance companies. Because of this, a large number of patients who could benefit from continuous glucose monitoring cannot use such systems and are forced to rely on less reliable blood test strips—finger pricking—monitoring. Therefore, there is a significant need on the market for low-cost sensors for continuous glucose monitoring systems. By reducing the cost of continuous monitoring, more patients can benefit from the enhanced therapeutic effects of improved quality of life and continuous monitoring.

[0009] Conventional continuous glucose monitoring systems typically use a working wire that utilizes a tantalum core onto which a thin layer of platinum is deposited. Tantalum is a relatively hard material and can therefore be pressed into the skin without bending. Furthermore, it is inexpensive compared to platinum, which makes economical working wires possible. However, tantalum has the disadvantage of permanently deforming when placed under stress. For example, if tantalum is wound onto a reel or roller, even a short section of tantalum wire will retain some of the roller's curvature when unwound. In another example, if the tantalum wire bends during insertion into the skin, the bend will be permanent, and the working wire will need to be disposed of. Summary of the Invention

[0010] Disclosed is a working line for a biosensor, comprising: a substrate comprising a cobalt-chromium (Co-Cr) alloy; a platinum layer disposed on the substrate, the platinum layer comprising platinum; and a membrane layer applied on the platinum layer, the membrane layer comprising a biofilm.

[0011] Disclosed is a working line for a biosensor, comprising: a substrate comprising a nitinol alloy; a platinum layer deposited on the substrate, the platinum layer comprising platinum; and a membrane layer applied on the platinum layer, the membrane layer comprising a biofilm.

[0012] A method for manufacturing a working wire for a biosensor is disclosed. The method includes receiving a substrate in a coiled position. The substrate comprises a cobalt-chromium (Co-Cr) alloy or a nitinol alloy. Unwinding the substrate from the coiled position and allowing the substrate to transition from the coiled position to a linear position. The substrate is divided into lengths suitable for the working wire. A platinum layer is disposed on the substrate, and the platinum layer comprises platinum. A membrane layer is applied over the platinum layer, and the membrane layer comprises a biofilm. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Each of the aspects and embodiments of the invention described herein can be used alone or in combination with each other.The aspects and embodiments will now be described with reference to the accompanying drawings.

[0014] Figure 1A 、 Figure 1B 、 Figure 2A and Figure 2B is a cross-sectional view of a working line for a biosensor according to some embodiments.

[0015] Figure 3 and Figure 4 is a flow chart of a method for fabricating a working line for a biosensor, according to some embodiments. DETAILED DESCRIPTION

[0016] Biosensors (such as electrochemical glucose sensors) are used in continuous glucose monitoring devices and systems. The sensor typically detects the concentration of an analyte in a patient's body by measuring the concentration or ion flow in the blood or other body fluids. It should be understood that the sensor may include a plurality of working wires, a plurality of reference electrodes, and a counter electrode that are constructed and arranged for sensing. Typically, the working electrode including the working wire is constructed to meet three basic requirements. First, it must be strong enough to withstand insertion under the patient's skin and then withstand vibration, tremor, and movement during use. Second, it needs to be flexible, but straight and strong enough to follow the desired path into the skin and allow some movement after insertion to make the patient feel comfortable. Third, it needs to provide electrical properties to support consistent and accurate sensing. In addition, it is highly desirable that the working electrode and working wire can be easily and efficiently manufactured according to precise medical standards.

[0017] Embodiments disclosed herein relate to cost-effective biosensors for use in continuous glucose monitoring devices and systems. The embodiments reduce the cost of manufacturing the working wire of the working electrode, as well as provide excellent straightness, flexibility, durability, and strength of the working wire of the working electrode. In addition, the working wire of the working electrode is flexible enough to allow the patient to feel comfortable and move, but straight and rigid to enable accurate insertion along the desired insertion path without deformation. Although the embodiments have been discussed primarily with respect to use in continuous glucose monitoring devices and systems, it will be understood that there are many other uses for biosensing that would benefit from reduced-cost sensors and working wires for working electrodes.

[0018] The embodiments disclosed herein enable cost-effective manufacturing of working wires with excellent mechanical strength and flexibility, ultimately increasing patient safety, comfort, and utility of the biosensor. Furthermore, the working wire of the working electrode is constructed from materials known to be safe for the human body. This also allows for the use of alternative sensor geometries and different forms of sensor fabrication.

[0019] In some embodiments, the working wire comprises a Co-Cr alloy instead of tantalum. Tantalum is widely used in the industry for working wires. Co-Cr alloys are known to be dense, ductile, very hard, easy to manufacture, highly conductive to heat and electricity, and resistant to corrosion. However, Co-Cr alloys are more expensive than tantalum and therefore have not been used in this context before. In other embodiments, the working wire comprises "Nitinol" instead of tantalum. Nitinol alloy is an alloy comprising nickel and titanium and is known to be dense, ductile, very hard, easy to manufacture, highly conductive to heat and electricity, and resistant to corrosion. Nitinol alloy is most commonly available in alloys having approximately 55% (by weight) nickel and approximately 60% nickel. Nitinol is electrically active outside the body and cannot survive in the human body uncoated. If placed under the skin and an electrical current is applied, Nitinol will corrode the wire and structurally degrade the wire. Nitinol can be coated to prevent electroactive corrosion, but providing such a coating increases manufacturing cost and complexity and therefore has not been used before.

[0020] In the present disclosure, Co-Cr alloy is used to refer to alloys containing only cobalt (Co) and chromium (Cr). Nitinol alloy is used to refer to alloys containing only nickel and titanium. In some embodiments, the Co-Cr alloy or Nitinol alloy may also include other additives or elements. For example, depending on the specific requirements of the application, the Co-Cr alloy may be further alloyed with nickel, molybdenum or magnesium. It should be understood that other additives or elements may be added. In a specific application, the Co-Cr alloy wire or Nitinol alloy wire may be made into a straight linear position and then treated, for example, by annealing. The Co-Cr alloy wire or Nitinol alloy wire may be wound onto a reel or roller for storage, distribution and use in an automated manufacturing machine. When unwinding, the Co-Cr alloy wire or Nitinol alloy wire may automatically return to its original straight shape, or in some embodiments, a process may be applied to the Co-Cr alloy wire or Nitinol alloy wire to help transform the wire from the wound position to its original shape or linear position. For example, the Co-Cr alloy wire or Nitinol alloy wire may be heated, cooled, subjected to air flow, or other processes to return the Co-Cr alloy wire or Nitinol alloy wire to its original straight shape. The Co-Cr alloy wire or Nitinol alloy wire can then be cut into appropriate lengths as needed for the working wire and, despite having been previously wound onto a reel, will still exhibit the straightness required for use as a working wire for a biosensor.

[0021] The Co-Cr alloy substrate or Nitinol alloy substrate (i.e., the wire used as the core for the biosensor) is strong enough to support insertion into the human body while having the flexibility and patient comfort required for insertion. The Co-Cr alloy substrate or Nitinol alloy substrate may include a platinum layer that has been formed using a draw-fill-tube (DFT) process, deposition, or electroplating. In the DFT process, the metal core comprises a Co-Cr alloy or Nitinol alloy, and the outer tube consists of platinum. The Co-Cr alloy is stretched as the core and the platinum as the tube, or the Nitinol alloy is stretched as the core and the platinum as the tube until the desired wire diameter is obtained. In this way, a slender wire is formed of a Co-Cr alloy core or a Nitinol alloy core and a platinum coating. Alternatively, if a thinner platinum layer is required, the Co-Cr alloy or Nitinol alloy can be formed into an elongated wire and then coated with platinum using a deposition or electroplating process. Typically, the platinum layer has a thickness in the range of 20 microns to 100 microns, but typically in the range of 25-40 microns.

[0022] In embodiments where the substrate comprises a Nitinol alloy, a protective layer may be applied between the Nitinol alloy and the platinum, since the Nitinol alloy is electrically active. The protective layer may comprise nickel or gold. To complete the biosensor, one or more film layers may be applied or deposited over the platinum. The total thickness of the working wire, including the Cr-Co alloy or Nitinol alloy, the protective layer (if necessary), the platinum layer, and the film layer, may be in the range of 0.0025 inches to 0.005 inches. In some embodiments, the working wire may be 0.0033 inches thick.

[0023] In some applications, further strength and flexibility can be obtained by having a Co-Cr alloy substrate or a Nitinol alloy substrate with a titanium core. Typically, the titanium core will have the same cross-sectional shape as the alloy substrate, but with a smaller diameter. It should be understood that in order to support specific applications and depending on the availability of materials, titanium can have other relationships with the alloy substrate shape. Titanium is a transition metal that is known to be lightweight and has low density and excellent strength. It is also highly corrosion resistant. Titanium can be used in its elemental form, but is typically used in alloy form with aluminum, vanadium, molybdenum or iron. It should be understood that titanium alloys can be used to support specific applications.

[0024] In one specific example, a titanium alloy commonly referred to as Ti-6Al-4V is used as the core in a Co-Cr alloy substrate or a Nitinol alloy substrate. Ti-6Al-4V has a particularly high strength-to-weight ratio and excellent corrosion resistance. In addition, it has been widely used in human implants and prostheses, resulting in a firmly established safety record. Embodiments include using a titanium-vanadium alloy as the core in a Co-Cr alloy substrate or a Nitinol alloy substrate.

[0025] Co-Cr alloys and Nitinol alloys can exhibit a shape memory effect, whereby the alloy "remembers" its original shape (such as a straight position, a linear position) and can be temporarily deformed, but then returns to its original shape when the deforming load is released. This means that a straight Co-Cr alloy wire or Nitinol alloy wire can be made and processed, and then wound onto rolls for simple and economical transportation. Thereafter, the Co-Cr alloy wire or Nitinol alloy wire can be unwound, and the wire will return to its original straight state. In some embodiments, the Co-Cr alloy wire or Nitinol alloy wire will naturally return to its original state, and in other embodiments, a process can be applied to the wire in order to return to its original state. For example, application of heating, cooling, air flow or other temperature cycles can be implemented.

[0026] The Co-Cr alloy wire or Nitinol alloy wire can be cut into the desired length for the working wire, such as by cutting. In this way, the working wire can be constructed to be straight, durable, strong, flexible, and possess superior electrical and sensitivity properties. These excellent properties allow the working wire of the working electrode to be reliably and safely inserted into the patient's body, improving patient comfort and enabling efficient positioning of the resulting biosensor.

[0027] Figure 1A is a cross-sectional view of a working wire for a biosensor according to some embodiments. As shown, the working wire 100 is an elongated wire with a circular cross-section. It should be understood that the working wire 100 may have other cross-sectional shapes, such as square, rectangular, triangular or other geometric shapes. It should be further understood that the working wire 100 may take other forms, such as a plate or a strip. The working wire 100 has a substrate 111 comprising a cobalt-chromium (Co-Cr) alloy and platinum. The Co-Cr alloy is in the form of a substrate or wire (such as a Co-Cr alloy wire 113). The Co-Cr alloy is a cost-effective alloy that is known to be dense, ductile, very hard, easy to manufacture, highly thermally and electrically conductive and well-known for its corrosion resistance. Therefore, the Co-Cr alloy provides an excellent substrate for the working wire 100. The platinum layer 115 comprising platinum is a thin platinum coating deposited or applied on the Co-Cr alloy wire 113. The application may include using a draw-fill-tube (DFT) process, or using chemical deposition or electroplating to deposit the platinum layer.

[0028] The DFT process allows for the matching of dissimilar materials to provide a variety of properties within a single wire system. Most commonly, an inner core of a composite material provides strength, while an outer sheath material is used to provide conductivity. DFT involves inserting a metal core into an outer tube and then stretching and annealing the combination. The DFT process was developed to combine the strength and biocompatibility of implant alloys with the properties of other materials. It will be appreciated that other processes may be used instead to apply the platinum layer 115 to the Co-Cr alloy wire 113. The platinum layer 115 may have a thickness ranging from 20 microns to 100 microns, but it will be appreciated that other thicknesses may be used.

[0029] Working wire 100 includes a membrane layer 118 disposed on a platinum layer 115 of substrate 111. In this example, membrane layer 118 is shown as three layers, and it should be understood that membrane layer 118 can have more or fewer layers. Membrane layer 118 is a biofilm, and therefore, the application of biofilms is well known in the art and will not be discussed in detail. Briefly, the biofilm is polyurethane-based and provides enzyme stability in the implant as well as diffusion control of known metabolites (i.e., glucose).

[0030] To be used as the working line 100, the distal end of the working line 100 may be sharpened or lubricated to facilitate insertion into the patient. For example, the distal end of the working line 100 or the end of the working line 100 may be formed into a pointed form. In one embodiment, the Co-Cr alloy wire 113 may be selected to have a diameter and strength that allows it to pierce the patient's skin and be inserted into the working line 100 without the use of a disposable insertion needle. This not only reduces costs but also simplifies the insertion process for the patient. Due to its desired flexibility, strength, and straightness, the working line 100 can be reliably inserted along the desired insertion path while still allowing the patient to feel comfortable and move. In addition, the Co-Cr alloy wire 113 can be successfully straightened after being in a wound position, such as on a reel, thereby avoiding buckling or bending when it is inserted into the patient's skin. This improved straightness can also improve functionality and efficiency in manufacturing, for example, by enabling precise coating of the working line.

[0031] The working wire 100 can be formed to a certain thickness to support the specific needs of the application and can be formed according to the physical properties of the specific Co-Cr alloy used. The working wire 100 can have a thickness or overall diameter in the range of 0.0025 inches to 0.005 inches, which has proven to be effective. That is, the working wire and its associated reference wire are sized to be insertable using a standard 25 or 26 gauge needle and therefore must be assembled into the needle body. It should be understood that other wire diameters can be used to support other needle gauges. In some embodiments, the working wire 100 can have a thickness of 0.0033 inches. It should be understood that other thicknesses can be used.

[0032] Figure 1B is a cross-sectional view of a working wire for a biosensor according to some embodiments. Working wire 120 is shown in cross-section. In this example, working wire 120 is an elongated wire having a circular cross-section. It should be understood that other cross-sections, such as square, rectangular, triangular, or other geometric shapes, may be used. It should further be understood that working wire 120 may take other forms, such as a plate or ribbon.

[0033] The working wire 120 has a substrate 121 comprising a Nitinol alloy, platinum, and a protective layer. The Nitinol alloy is in the form of a substrate or a wire (such as a Nitinol alloy wire 123). Nitinol alloy is an alloy comprising nickel and titanium, and typically these two elements are present in approximately equal atomic percentages. In some embodiments, the Nitinol alloy comprises 55% nickel (by weight) or 60% nickel. Nitinol alloy is a cost-effective alloy that is known to be dense, ductile, very hard, easy to manufacture, and highly thermally and electrically conductive. The alloy is known for its corrosion resistance. Therefore, Nitinol alloy provides an excellent substrate for the working wire 120.

[0034] Since Nitinol is electrically active, a protective layer 122 is applied to the Nitinol wire 123 of the substrate 121. The protective layer 122 can be, for example, a thin layer of nickel or gold having a thickness in the range of 3 microns to 55 microns. In some embodiments, the nickel layer or gold layer has a thickness of 3-5 microns. It will be appreciated that other materials may be used. The Nitinol wire 123 may then have a platinum layer 125 deposited or applied over the protective layer 122, the platinum layer 125 comprising platinum. This may be a thin platinum coating and may be applied using a draw-fill-tube (DFT) process, or by depositing the platinum layer using chemical deposition or electroplating. For example, the protective layer 122 may be located between the Nitinol wire 123 and the platinum layer 125. It will be appreciated that other processes may be used instead to apply the platinum layer 125 to the Nitinol wire 123. The platinum layer 125 may have a thickness in the range of 20 microns to 100 microns, although it will be appreciated that other thicknesses may be used.

[0035] The working line 120 includes a membrane layer 128 disposed on a platinum layer 125 of a substrate 121. In this example, the membrane layer 128 is shown as three layers, and it should be understood that the membrane layer 128 can have more or fewer layers. The membrane layer 128 is as shown in FIG. Figure 1A The disclosed biofilms.

[0036] To be used as the working wire 120, the distal end of the working wire 120 may be sharpened or lubricated to facilitate insertion into the patient. For example, the distal end of the working wire 120 or the end of the working wire 120 may be formed into a pointed form. In one embodiment, the nitinol wire 123 may be selected to have a diameter and strength such that it can pierce the patient's skin and can be inserted into the working wire 120 without the use of a disposable insertion needle. This not only reduces costs but also simplifies the insertion process for the patient. Due to its desirable flexibility, strength, and straightness, the working wire 120 can be reliably inserted along the desired insertion path while still allowing the patient to feel comfortable and move. In addition, the nitinol wire 123 can be successfully straightened after being in a wound position, such as on a spool, thereby avoiding buckling or bending when inserted into the patient's skin. This improved straightness can also improve functionality and efficiency in manufacturing, for example, by enabling precise dipping of the working wire.

[0037] The working wire 120 can be formed to a certain thickness to support the specific needs of the application and can be formed according to the physical properties of the specific Nitinol alloy used. The working wire 120 can have a thickness in the range of 0.0025 inches to 0.005 inches, which has proven effective. That is, the working wire and its associated reference wire are sized to be insertable using a standard 25 or 26 gauge needle and therefore must be assembled into the needle body. It should be understood that other wire diameters can be used to support other needle gauges. In some embodiments, the working wire 120 can have a thickness of 0.0033 inches. It should be understood that other thicknesses can be used.

[0038] Figure 2A FIG2 is a cross-sectional view of a working wire 200 for a biosensor according to some embodiments. As shown, working wire 200 is an elongated wire having a circular cross-section. It should be understood that working wire 200 may have other cross-sectional shapes, such as square, rectangular, triangular, or other geometric shapes. It should further be understood that working wire 200 may take other forms, such as a sheet or ribbon.

[0039] The working line 200 has a substrate 211 comprising a Co-Cr alloy, titanium and platinum. Figure 2A In the example of FIG. 2 , substrate 211 comprises a Co-Cr alloy wire 213 having a core 217 that is a different material than the Co-Cr alloy wire. Core 217 may comprise titanium, which forms the elongated Co-Cr alloy / core wire 213. Co-Cr alloy and titanium are cost-effective materials known to be strong, easy to manufacture, and corrosion-resistant. Therefore, Co-Cr alloy / core wire 213 provides an excellent substrate 211 for working wire 200. A platinum layer 215 comprising platinum may be deposited or applied to Co-Cr alloy / core wire 213 to form a thin platinum coating. This may be accomplished, for example, using a chemical deposition or electroplating process. It should be understood that other processes may be used to apply platinum layer 215 to Co-Cr alloy / core wire 213.

[0040] The working line 200 includes a membrane layer 218 disposed on a platinum layer 215. Figure 1A and Figure 1B , the membrane layer 218 is shown as three layers, and it should be understood that the membrane layer 218 can have more or fewer layers. As described herein, the membrane layer 218 is as described in reference Figure 1A and Figure 1B The disclosed biofilms.

[0041] like Figure 2AAs shown, core 217 has the same cross-sectional shape as substrate 211, but has a smaller diameter of 25 microns to 100 microns. It should be understood that core 217 may have other shapes, depending on material availability and specific process requirements. In some embodiments, the cross-sectional shape of core 217 may be different from the cross-sectional shape of substrate 211. In a specific example, core 217 comprises Ti-6Al-4V, which is sometimes referred to as TC4, Ti64 or ASTM Grade 5 and is a titanium alloy. Ti-6Al-4V is known to have excellent weight to strength ratio and corrosion resistance, and has been thoroughly tested and approved for use in the human body. It should be understood that other titanium alloys may be used. Titanium can be used in its elemental form, but can also be used in alloy form with aluminum, vanadium, molybdenum or iron. It should be understood that many titanium alloys can be used to support specific applications. For example, titanium alloys using vanadium also show desirable weight to strength ratio and corrosion resistance. The use of a titanium core or titanium alloy core advantageously improves flexibility to allow patient comfort and movement, and provides additional straightness to enable accurate positioning of the working wire during insertion. In this way, the working wire can be reliably and comfortably positioned within the patient.

[0042] Figure 2B FIG2 is a cross-sectional view of a working wire 220 for a biosensor according to some embodiments. As shown, working wire 220 is an elongated wire having a circular cross-section. It should be understood that working wire 220 may have other cross-sectional shapes, such as square, rectangular, triangular, or other geometric shapes. It should further be understood that working wire 220 may take other forms, such as a sheet or ribbon.

[0043] The working wire 220 has a substrate 221 comprising Nitinol, titanium, platinum and a protective layer. Figure 2B In the example of , the substrate 221 comprises a nitinol alloy wire having a core 227 that is a different material than the wire. The core 227 may comprise titanium, which forms an elongated nitinol alloy / core wire 223. Nitinol alloy and titanium are cost-effective materials known to be strong, easy to manufacture, and corrosion-resistant. Therefore, the nitinol alloy / core wire 223 provides an excellent substrate 221 for the working wire 220. A thin platinum coating may be deposited or applied to the nitinol alloy / core wire 223 to form a platinum layer 225. This may be accomplished, for example, using an electroplating process. It should be understood that other processes may be used instead to apply the platinum layer 225 to the nitinol alloy / core wire 223.

[0044] The working line 220 includes a membrane layer 228 disposed on a platinum layer 225. Figure 1A and Figure 1B , membrane layer 228 is shown as three optional layers, and it is understood that membrane layer 228 can have more or fewer layers. As described herein, membrane layer 228 is a biological membrane.

[0045] like Figure 2B As shown, core 227 has the same cross-sectional shape as substrate 221, but with a smaller diameter. It should be understood that core 227 may have other shapes, depending on material availability and specific process requirements. In some embodiments, the cross-sectional shape of core 227 may differ from that of substrate 221. In one specific example, core 227 comprises Ti-6Al-4V, sometimes referred to as TC4, Ti64, or ASTM Grade 5, and is a titanium alloy. Ti-6Al-4V is known to have an excellent weight-to-strength ratio and corrosion resistance, and has been thoroughly tested and approved for use in the human body. It should be understood that other titanium alloys may be used. Titanium can be used in its elemental form, but can also be used in alloys with aluminum, vanadium, molybdenum, or iron. It should be understood that many titanium alloys are available to support specific applications. For example, titanium alloys using vanadium also exhibit desirable weight-to-strength ratios and corrosion resistance. The use of a titanium core or titanium alloy core advantageously improves flexibility to facilitate patient comfort and movement, and provides additional straightness to enable accurate positioning of the working wire during insertion. In this way, the working line can be securely and comfortably positioned within the patient.

[0046] Figure 3 FIG3 is a flow chart of a method 300 for manufacturing a working wire for a biosensor, according to some embodiments. At block 302, an alloy substrate material is selected. For example, the alloy substrate material may be elemental Co-Cr or a Co-Cr alloy without additives, and may also include nickel, molybdenum, or manganese. In another embodiment, the alloy substrate may be a Nitinol alloy. It will be appreciated that other additives or elements may be used as needed for specific applications.

[0047] In some cases, the alloy substrate selected in block 302 may have a core made of a different material than the substrate material, thereby having a Figure 2A and Figure 2B The alloy / core shown. Optionally, as indicated by the dashed box, at box 304, the core can include titanium, a titanium alloy, or in a specific example, Ti-6Al-4V. By using a titanium or titanium-based core with an alloy substrate, the working wire can have excellent strength properties at a lower overall weight and exhibit the ability to maintain a straight insertion path when inserted into a patient.

[0048] At block 305, the alloy or alloy / core can then be formed into an elongated wire. In some embodiments, it can be formed into other shapes, such as a ribbon or sheet. The alloy or alloy / core elongated wire can have a circular cross-sectional shape. It should be understood that other cross-sectional shapes can be used, such as square, rectangular, triangular, hexagonal, or other geometric shapes.

[0049] In embodiments of a Nitinol alloy substrate, a protective layer, such as an electroactive protective layer, may be applied to the Nitinol alloy at block 306. The protective layer may comprise nickel or gold. This block is optional, depending on the material of the substrate.

[0050] At box 307, a platinum layer is applied to the alloy wire or alloy / core wire. In embodiments of the Nitinol alloy substrate, a protective layer may be located between the Nitinol alloy substrate and the platinum layer. In some embodiments, the platinum layer is formed using a DFT process. In this way, a core of the selected alloy and an outer tube of platinum are stretched until the desired thickness is achieved. In some embodiments, the platinum layer may be applied to the alloy or alloy / core wire using an electroplating process or chemical deposition. The electroplating or deposition process allows for precise control of the thickness of the platinum layer. It is preferred that the platinum be layered or deposited directly onto the alloy or alloy / core wire, but in some cases, for example, it may be desirable to have an intermediate layer, such as when Nitinol alloy is selected as the substrate and a protective layer is applied. It should be understood that other processes may be used to apply the platinum to the alloy or alloy / core wire.

[0051] At block 308, after platinum has been applied to the substrate, the working wire is processed by applying a biofilm layer or layers to provide the electrochemical process required to operate as a biosensor. The working wire is then associated with a reference electrode, and in some cases, a protective coating may be added to the working wire. In this way, the biosensor can be manufactured for use, for example, with a continuous glucose monitoring device.

[0052] Figure 4 4 is a flow chart of a method 400 for manufacturing a working line for a biosensor according to some embodiments. It should be understood that the frames represent only the main steps of the manufacturing process, and those skilled in the art will appreciate that additional processes and details may be needed to manufacture or produce the working line. At frame 402, a substrate is received in a winding position such as on a reel, and the substrate will be processed into the working line. The reel can have a typical arrangement and include two discs rotatably supported in a coaxially spaced relationship from each other and a hub positioned between the discs for winding the substrate thereon.

[0053] As described herein, the substrate may be Co-Cr, a Co-Cr alloy, a Co-Cr alloy with a core (alloy / core), a Nitinol alloy, or a Nitinol alloy with a core (alloy / core). The substrate may be formed in one of several possible cross-sections, such as round, square, rectangular, trapezoidal, oblong, or other geometric shapes. When originally manufactured, the substrate may have been produced in a straight linear position and then heat treated or annealed so that it retains a memory shape. In order to facilitate easy distribution and automated manufacturing processes, the substrate may be wound onto a reel. It will be understood that the reel of substrate may be received without a platinum layer, or the substrate may already have a platinum layer. In the case of using a Nitinol alloy, a protective layer of gold or nickel may be provided between the Nitinol alloy and the platinum layer, for example.

[0054] Once received in the manufacturing facility of the work line, at frame 404, the substrate is unwound or unfolded from the winding position on the reel. This can be a manual process or an automated process by a machine. At frame 406, the substrate is allowed to transition from the winding position to a linear position so that the substrate returns to its original straight shape. This eliminates any circular deformation caused by being in the winding position or rolled-up position on the reel. In some embodiments, the substrate can automatically return to its original straight shape when it is unfolded. In other embodiments, additional processes (such as applying a thermal cycle to the substrate) can be used to assist or accelerate the transition of the substrate to the linear position. The thermal cycle can include: exposing the substrate to a temperature higher than the ambient temperature, such as heating; exposing the substrate to a temperature lower than the ambient temperature, such as cooling; or moving ambient air around the substrate, such as an air flow. In some embodiments, other processes can be used to assist the transition of the substrate to its original straight linear state.

[0055] At block 407, the substrate is divided into lengths suitable for the working wire. The lengths suitable for the working wire can be determined based on the dimensions required to support further manufacturing of the working wire and are typically between 10 mm and 40 mm. It should be understood that these usable lengths can be the lengths of a single working wire, or can be sized to support multiple working wires and can include additional lengths to support the manufacturing process. Furthermore, it should be understood that when the substrate is in a linear position, with a manageable, suitable length, further manufacturing processes, such as dip coating and electroplating, can be performed more efficiently, more accurately, and more consistently than when the substrate has bends, kinks, or other deformations as a result of the coiled position. Optionally, the tip of one end of the substrate can be shaped or sharpened or made into a pointed shape so that the finished working wire can be inserted under the patient's skin without the need for a needle. It should be understood that this step of sharpening or providing a sharpening point on the substrate can occur at an alternative step in the manufacturing process.

[0056] At block 408, a platinum layer is provided on the substrate. The platinum layer comprises platinum. In some embodiments, the platinum layer is formed using a DFT process. In some embodiments, the platinum layer is deposited or electroplated onto the substrate. In some embodiments, the substrate is received in block 402 without a platinum layer, and the providing includes applying a platinum layer to the substrate before receiving the substrate in the winding position. Thus, in some embodiments, if the substrate is initially manufactured with a platinum layer, block 408 is optional after block 407. It will be appreciated that platinum may be applied at other steps in the process, such as before separation at block 407.

[0057] A biofilm is deposited over the platinum layer at block 409. One skilled in the art will appreciate that other layers and materials may be deposited on the substrate to form the working line.

[0058] Although this specification has been described in detail with respect to specific embodiments of the present invention, it will be appreciated that those skilled in the art, upon gaining an understanding of the foregoing, will readily appreciate alternatives, variations, and equivalents to these embodiments. These and other modifications and variations of the present invention may be practiced by those skilled in the art without departing from the scope of the present invention, which is more particularly set forth in the appended claims. Furthermore, those skilled in the art will appreciate that the foregoing description is by way of example only and is not intended to limit the present invention.

Claims

1. A working line for a continuous glucose monitoring sensor, comprising: A substrate for a working wire of a continuous glucose monitoring sensor made of a cobalt-chromium (Co-Cr) alloy, wherein the substrate is manufactured into a shape having an original straight linear position and is heat-treated or annealed to exhibit a shape memory effect; a platinum layer disposed on the substrate, the platinum layer comprising platinum; and A membrane layer, the membrane layer being applied over the platinum layer, the membrane layer comprising a biofilm; The thickness of the working wire is in the range of 0.0025 inches to 0.005 inches. 2 . The working wire of claim 1 , wherein the substrate further comprises a core comprising titanium, a titanium alloy, or a vanadium alloy.

3. The work wire of claim 1, wherein the substrate further comprises a core comprising Ti-6Al-4V.

4. The working wire of claim 1, wherein the substrate is an elongated wire having a circular cross-section.

5. The working line according to claim 1, wherein: The thickness of the platinum layer is in the range of 20 micrometers to 100 micrometers.

6. The working line of claim 1, wherein the platinum of the platinum layer is applied to the substrate by a drawn filled tube (DFT) process.

7. The working line of claim 1, wherein the platinum of the platinum layer is deposited using chemical deposition or electroplating.

8. The working line of claim 1, wherein the membrane layer is polyurethane based.

9. The working line according to claim 1, wherein the membrane layer is used for continuous glucose monitoring.

10. The working wire of claim 1, wherein the distal end of the working wire is formed into a pointed structure.

11. The working line of claim 1 , wherein the working line naturally transitions from a wound position to a shape of an original straight linear position.

12. The work wire of claim 1, wherein the substrate returns to the shape of the original straight linear position when the deforming load is released.

13. A method of manufacturing a working line for a continuous glucose monitoring sensor, comprising: receiving a substrate in a coiled position, the substrate being made of a cobalt-chromium (Co—Cr) alloy, wherein the substrate is fabricated into a shape having an original straight linear position and is heat treated or annealed to exhibit a shape memory effect; unwinding the substrate from the winding position; a shape that allows the substrate to naturally transition from the coiled position to an original straight linear position; dividing the substrate into lengths suitable for the working line; providing a platinum layer on the substrate, the platinum layer comprising platinum; and applying a membrane layer over the platinum layer, the membrane layer comprising a biofilm; The thickness of the working wire is in the range of 0.0025 inches to 0.005 inches.

14. The method of claim 13, wherein said providing comprises: The platinum layer is applied to the substrate prior to receiving the substrate in the winding position.

15. The method of claim 14, wherein applying comprises: The platinum layer is deposited using a draw-fill-tube (DFT) process, or using electroless deposition or electroplating.

16. The method of claim 13, wherein the providing comprises: After receiving the substrate and before applying the membrane layer, the platinum layer is applied to the substrate.

17. The method of claim 13, wherein the substrate returns to the original straight linear shape when the deforming load is released.

18. The method of claim 13, wherein the substrate further comprises a core comprising titanium, a titanium alloy, or a vanadium alloy.

19. The method of claim 13, wherein the substrate further comprises a core, the core comprising Ti-6Al-4V.

20. The method of claim 13, wherein: The thickness of the platinum layer is in the range of 20 micrometers to 100 micrometers.

21. The method of claim 13, wherein the allowing further comprises: A thermal cycle is applied to the substrate to transition the substrate from the wound position to the linear position, wherein the thermal cycle comprises applying a temperature above ambient temperature, applying a temperature below ambient temperature, or moving ambient air around the substrate.

Images