Patent Application
20080035478
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the invention and together with the description, serve to explain the principles of the invention.
Reference will now be made in detail to the exemplary embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.
In accordance with an exemplary embodiment, a biosensor manufacturing method is described. Many industries have a commercial need to monitor the concentration of particular constituents in a fluid. The oil refining industry, wineries, and the dairy industry are examples of industries where fluid testing is routine. In the health care field, people such as diabetics, for example, need to monitor various constituents within their bodily fluids using biosensors. A number of systems are available that allow people to test a body fluid (e.g. blood, urine, or saliva), to conveniently monitor the level of a particular fluid constituent, such as, for example, cholesterol, proteins or glucose.
A biosensor may include a test strip, which can be disposable, that may facilitate the detection of a particular constituent of a body fluid. The test strip can include a proximal end, a distal end, and at least one electrode. The proximal end of the test strip may include a sample chamber for receiving a body fluid to be tested. The sample chamber can be dimensioned and configured to draw a fluid sample into the sample chamber via capillary action. Electrodes positioned within the sample chamber may contact the fluid sample. The distal end of the test strip may be configured to operatively connect the test strip to a meter that may determine the concentration of the body fluid constituent. For example, the distal end of the test strip may include a plurality of electrical contacts configured to provide electrical connections between the electrodes within the sample chamber and the meter. The ends of the test strip may also include a visual and/or tactile distinguishable section, such as, for example, a taper, in order to make it easier for the user to operatively connect the test strip to the meter or apply a body fluid to the sample chamber.
Electrodes positioned within the sample chamber may include a working electrode, a counter electrode, and a fill-detect electrode. A reagent layer can be disposed in the sample chamber and may cover at least a portion of the working electrode, which can also be disposed at least partially in the sample chamber. The reagent layer can include, for example, an enzyme, such as glucose oxidase or glucose dehydrogenase, and a mediator, such as potassium ferricyanide or ruthenium hexamine, to facilitate the detection of glucose in blood. It is contemplated that other reagents and/or other mediators can be used to facilitate detection of glucose and other constituents in blood and other body fluids. The reagent layer can also include other components, such as buffering materials (e.g., potassium phosphate), polymeric binders (e.g., hydroxypropyl-methyl-cellulose, sodium alginate, microcrystalline cellulose, polyethylene oxide, hydroxyethylcellulose, and/or polyvinyl alcohol), and surfactants (e.g., Triton X-100 or Surfynol 485).
The present disclosure provides a method for producing a diagnostic test strip 10, as shown in
As shown in
Test meter 200, 208 may be selected from a variety of suitable test meter types. For example, as shown in
With reference to the drawings,
Test strip 10 is depicted in
In one embodiment, at least one electrode is partially housed within a sample chamber to allow contact with a fluid to be tested. For example,
As shown in
According to the exemplary embodiment of
Layered on top of base layer 18 and conductive components 20 is a spacer layer 64. Spacer layer 64 may include an electrically insulating material such as polyester. Spacer layer 64 can cover portions of working electrode 22, counter electrode 24, fill-detect anode 28, fill-detect cathode 30, and conductive regions 40-46. In the exemplary embodiment of
A cover 72 may be provided. As shown in
Slot 52, together with base layer 18 and cover 72, may define sample chamber 88 in test strip 10, which receives a fluid sample, such as a blood sample, for measurement in the exemplary embodiment. A proximal end 68 of slot 52 can define a first opening in sample chamber 88, through which the fluid sample is introduced. At distal end 70 of slot 52, break 84 can define a second opening in sample chamber 88, for venting sample chamber 88 as a fluid sample enters sample chamber 88. Slot 52 may be dimensioned such that a blood sample applied to its proximal end 68 is drawn into and held in sample chamber 88 by capillary action, with break 84 venting sample chamber 88 through an opening 86, as the fluid sample enters. Moreover, slot 52 may be dimensioned so that the volume of fluid sample that enters sample chamber 88 by capillary action is about 1 micro-liter or less.
Test strip 10 may include one or more reagent layers 90 disposed in sample chamber 88. In the exemplary embodiment, reagent layer 90 contacts a partially exposed portion 54 of working electrode 22. It is also contemplated that reagent layer 90 may or may not contact exposed portion 56 of counter electrode 24. Reagent layer 90 may include chemical components to enable the level of glucose or other analyte in the body fluid, such as a blood sample, to be determined electro-chemically. For example, reagent layer 90 can include an enzyme specific for glucose, such as glucose oxidase or glucose dehydrogenase, and a mediator, such as potassium ferricyanide or ruthenium hexamine. Reagent layer 90 can also include other components, such as buffering materials (e.g., potassium phosphate), polymeric binders (e.g., hydroxypropyl-methyl-cellulose, sodium alginate, microcrystalline cellulose, polyethylene oxide, hydroxyethylcellulose, and/or polyvinyl alcohol), and surfactants (e.g., Triton X-100 or Surfynol 485).
An example of the way in which chemical components of reagent layer 90 may react with glucose in the blood is described next. The glucose oxidase initiates a reaction that oxidizes glucose to gluconic acid and reduces the ferricyanide to ferrocyanide. When an appropriate voltage is applied to working electrode 22, relative to counter electrode 24, the ferrocyanide is oxidized to ferricyanide, thereby generating a current that is related to the glucose concentration in the blood sample.
As depicted in
Test strip 10 can be sized for easy handling. For example, test strip 10 may measure approximately 27 mm long (i.e., from proximal end 12 to distal end 14) and about 9 mm wide. According to the exemplary embodiment, base layer 18 may be a polyester material about 0.35 mm thick and spacer layer 64 may be about 0.127 mm thick and cover portions of working electrode 22. Adhesive layer 78 may include a polyacrylic or other adhesive and have a thickness of about 0.013 mm. Cover 72 may be composed of an electrically insulating material, such as polyester, and can have a thickness of about 0.1 mm. Sample chamber 88 can be dimensioned so that the volume of fluid sample held is about 1 micro-liter or less. For example, slot 52 can have a length (i.e., from proximal end 12 to distal end 70) of about 3.6 mm, a width of about 1.52 mm, and a height (which can be substantially defined by the thickness of spacer layer 64) of about 0.10 mm. The dimensions of test strip 10 for suitable use can be readily determined by one of ordinary skill in the art. For example, a meter with automated test strip handling may utilize a test strip smaller than 9 mm wide.
Although
A plurality of feature sets 80 may be formed on base layer 118, wherein each feature set 80 may include a plurality of conductive components 120, such as, for example, an electrode, a conductive region and an electrode contact. Feature sets 80 may include any suitable conductive or semi-conductive material. In some embodiments, feature sets 80 can be formed using lift-off lithography or shadow masking, as described in commonly-assigned, copending non-provisional U.S. patent application Ser. No. 11/476,702 “Method of Manufacturing a Diagnostic Test Strip”, filed Jun. 29, 2006, the disclosure of which is hereby incorporated herein by reference in its entirety. It is also contemplated that feature sets 80 may be formed by direct writing, laser ablation, sputtering, screen printing, contact printing or any suitable manufacturing method. One exemplary process is direct writing of electrodes as described in commonly-assigned, copending provisional patent application No. 60/716,120 “Biosensor with Direct Written Electrode”, filed Sep. 13, 2005, the disclosure of which is hereby incorporated herein by reference in its entirety. Another exemplary process is screen printing as described in commonly-assigned, U.S. Pat. No. 6,743,635 “System and methods for blood glucose sensing,” filed Nov. 1, 2002, the disclosure of which is hereby incorporated herein by reference in its entirety.
Following the formation of one or more feature sets 80 on base layer 118, various layers may be added to base layer 118 and feature sets 80 to form a laminate structure as shown in
As shown in
As shown in
Increasing a surface area of base layer 118 may offer several advantages over existing planar designs. For example, an increased surface area of base layer 118 will increase an area available for deposition of conductive components 20 and/or reagent layer 90. Increasing an electrode surface area may permit enhanced detection of an electrochemical reaction, such as, for example, as described above for glucose detection. Specifically, conductive components 20 formed on surface texture 400 will have a greater surface area than conductive components 20 formed on a planar base layer 118 without surface texture 400. The increased surface area may enhance signal detection by providing an electrode with a larger surface area to detect a current generated by an electrochemical reaction. Further, by increasing the surface area of one or more conductive components 20, test strip size may be reduced while retaining appropriate signal detection, requiring smaller quantities of materials and/or smaller volumes of body fluid. In addition, an increased surface area may permit improved adhesion between adjacent layers.
Surface texture 400 may include any surface profile or geometry that functions to increases a surface area of a generally planar substrate. For example, surface texture 400 may include one or more protrusions extending from a generally planar substrate. In addition, surface texture 400 may include one or more indentations extending into a generally planar substrate. As shown in
In some embodiments, surface texture 400 may include one or more surface features 410 configured to increase an area of a generally planar substrate. Surface feature 410 may include any structure configured to increase the surface area of a generally planar substrate. For example, surface features 410 may include one or more protrusions from base layer 118 and/or indentations into base layer 118 as described above.
Surface features 410 may be any suitable shape or size. For example, surface feature 410 may include a corrugation, a prism, a box-like, a needle, or any other shape that increases a surface area of a generally planar surface. Surface features 410 may also include indentations formed into a surface of a generally planar surface. For example, surface features 410 may include one or more dimples etched into a generally planar surface. In some embodiments, surface texture 400 may include one or more surface features 410 of different and/or similar shape.
Surface features 410 may be any suitable size, such as, for example, approximately 200 micro-meters wide and approximately 100 micro-meters high. In some embodiments, surface features 410 may have a dimension in a range of 100 micrometers to 1 nanometer, wherein the dimension may include a height, width, or depth of surface feature 410. Surface texture 400 may include one or more surface features 410 of different and/or similar size.
In some embodiments, surface features 410 may include smaller structures (not shown) to further increase the surface area of surface features 410. Such smaller structures, termed secondary surface features, may be formed on any suitable location on surface features 410. Surface features 410 may include one or more secondary surface features, wherein the secondary surface features may be of similar and/or different size, shape or spatial distribution. For example, a plurality of secondary surface features may form an array on surface feature 410.
Surface texture 400 may include any suitable spatial distribution of surface features 410 on base layer 118. For example, a plurality of surface features 410 may be arranged to form an array, as shown in
In some embodiments, surface texture 400 may be formed in select regions of base layer 118. For example, surface texture 400 may be formed at proximal end 112 of base layer 118 surrounding. It is also contemplated that surface texture 400 may be formed in select regions of test strip 10, such as, for example exposed portion of working electrode 54 and/or exposed portion of counter electrode 56, as shown in
Surface texture 400 may be formed on a generally planar substrate using any suitable method. For example, surface features 410 may be formed on base layer 118 using a microreplication process. Such a process may include exposing base layer 118 to heat and/or pressure and then contacting base layer 118 with a suitable tool or die to form surface features 410. Other processes may include thermoforming, traditional embossing, injection molding, plasma etching, and other process to add, transform, or remove material from base layer 118 to form surface texture 400. For example, surface texture 400 may be formed on a substrate by exposure to extreme ultra-violet radiation. It is also contemplated that surface texture 400 may be formed using any suitable type of mold, such as, for example, a rulable mold or a non-rulable mold. Such a mold may be manufactured using any suitable process. For example, a mold may be manufactured as described in U.S. Pat. No. 6,010,609 “Method of making a microprism master mold,” published Jan. 4, 2000, the disclosure of which is hereby incorporated herein by reference in its entirety.
In some embodiments, surface texture 400 may be formed by a deposition process. For example, particles of may be deposited on base layer 118 to more one or more surface features 410. Specifically, surface texture 400 may be formed by sputtering nanoparticles, nanotubes or colloids on any suitably prepared planar substrate. Such a process may form an irregular surface of similar and/or different sized micro- and/or nano-structures.
Surface texture 400 may be formed at any stage during the formation and/or processing of reel 100. For example, reel 100 may be formed with one or more surface features 410 In other embodiments, surface texture 400 may be formed on reel 100 during the test strip manufacturing process. Specifically, surface texture 400 may be formed before, during, or after deposition of conductive components 20 on base layer 118.
Following formation of surface texture 500, substrate 518 was patterned with a photoresist (not shown). A layer of gold conductive material was then sputtered onto the photoresist patterned substrate. The photoresist was subsequently removed to reveal a plurality of conductive components 520 formed on base layer 518. Conductive components 520 include a working electrode 522, a fill-detect anode 528, and a counter electrode conductive region 542 shown as light shaded regions on surface texture 500. The surface area of conductive components 520 is increased approximately 40% relative to conductive components formed on a generally planar substrate. The gap between working electrode 522 and fill-detect anode 528 is approximately 1000 microns.
As depicted in the exemplary embodiment shown in
Test strip 310 may also include one or more coding regions (not shown), configured to provide coding information on test strip 310. For example, coding regions may include a discrete set of contacting pads as described in commonly-assigned, copending patent application Ser. No. 11/181,778, filed Jul. 15, 2005, entitled “DIAGNOSTIC STRIP CODING SYSTEM AND RELATED METHODS OF USE”, (Attorney Docket 06882-0147), the disclosures of which is hereby incorporated herein by reference in its entirety. The discrete pattern formed by a set of contacting pads may include conducting and non-conducting regions designed to be readable by test meter to identify data particular to the test strip.
Following the formation of feature set 380 on base layer 318, spacer layer 364 can be applied to conductive components 320 and base layer 318, as illustrated in
Alternatively, spacer layer 364 could be applied in other ways. For example, spacer layer 64 can be injection molded onto base layer 318 and conductive components 320. Spacer layer 64 could also be built up on base layer 318 and conductive components 320 by screen-printing successive layers of a dielectric material to an appropriate thickness, e.g., about 0.005 inches. An exemplary dielectric material comprises a mixture of silicone and acrylic compounds, such as the “Membrane Switch Composition 5018” available from E.I. DuPont de Nemours & Co., Wilmington, Del. Other materials also could be used, however.
Reagent layer 390 (not shown) can then be applied to each test strip structure after forming spacer layer 364. In an exemplary approach, reagent layer 390 may be applied by dispensing an aqueous composition onto exposed portion 354 of working electrode 322 and letting it dry to form reagent layer 390. It is also contemplated that reagent layer 390 may or may not contact exposed portion 356 of counter electrode 324. An exemplary aqueous composition has a pH of about 7.5 and contains 175 mM ruthenium hexamine, 75 mM potassium phosphate, 0.35% METHOCEL water-soluble cellulose ether, 0.08% TRITON X-100 nonionic surfactant, 5000 u/mL glucose dehydrogenase, 5% sucrose, and 0.05% SILWET L-7608 silicone surfactant. Alternatively, other methods, such as screen-printing, spray deposition, piezo and ink jet printing, can be used to apply the composition used to form reagent layer 390.
Cover 372 (not shown) can then be attached to spacer layer 364, where cover 372 is constructed to cover slot 352, as previously described with respect to
Preferred embodiments of the present invention have been described above. Those skilled in the art will understand, however, that changes and modifications may be made to these embodiments without departing from the true scope and spirit of the invention, which is defined by the claims.
This application claims priority to U.S. Provisional Patent Application No. 60/836,935 filed on Aug. 11, 2006, the contents of which are incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 60836935 | Aug 2006 | US |
