The present disclosure relates to structures, functions, and fabrication methods for a biosensor.
Blood analyte measurement systems typically comprise an analyte test meter that is configured to receive a biosensor, usually in the form of a test strip. A user may obtain a small sample of blood typically by a fingertip skin prick and then may apply the sample to the test strip to begin a blood analyte assay. Because many of these systems are portable, and testing can be completed in a short amount of time, patients are able to use such devices in the normal course of their daily lives without significant interruption to their personal routines. A person with diabetes may measure their blood glucose levels several times a day as a part of a self management process to ensure glycemic control of their blood glucose within a target range.
Analyte detection assays find use in a variety of applications, including clinical laboratory testing, home testing, etc., where the results of such testing play a prominent role in diagnosis and management in a variety of disease conditions. Analytes of interest include glucose for diabetes management, cholesterol, and the like. In response to this growing importance of analyte detection, a variety of analyte detection protocols and devices for both clinical and home use have been developed.
One type of method that is employed for analyte detection is an electrochemical method. In such methods, a blood sample is placed into a sample-receiving chamber in an electrochemical cell that includes two electrodes, e.g., a counter and working electrode, and a redox reagent. The analyte is allowed to react with the redox reagent to form an oxidizable (or reducible) substance in an amount corresponding to the blood analyte concentration. The quantity or concentration of the oxidizable (or reducible) substance present is then estimated electrochemically by applying a voltage signal via the electrodes and measuring an electrical response which is related to the amount of analyte present in the initial sample.
The electrochemical cell is typically present on a test strip which is configured to electrically connect the cell to an analyte measurement device. While current test strips are effective, the size of the test strips can directly impact the manufacturing costs. While it is desirable to provide test strips having a size that facilitates handling of the strip, increases in size will tend to increase manufacturing costs where there is an increased amount of material used to form the strip. Moreover, increasing the size of the test strip tends to decrease the quantity of strips produced per batch, thereby further increasing manufacturing costs. Accordingly, there is a need for improved electrochemical test strip fabrication methods and structures to reduce material and manufacturing costs. Embodiments disclosed herein generally provide a co-facial test strip and method of manufacturing that minimize costs, and provides outside facing electrical contact areas for easy access by a hand held analyte measurement device such as a blood glucose test meter. The contact areas present completely accessible full strip width top and bottom layer electrodes to the meter. This allows for greater tolerances in the strip port connector of the meter and a simpler meter design because only one connection per side is required.
These and other embodiments, features and advantages will become apparent to those skilled in the art when taken with reference to the following more detailed description of various exemplary embodiments of the invention in conjunction with the accompanying drawings that are first briefly described.
The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate presently preferred embodiments of the invention, and, together with the general description given above and the detailed description given below, serve to explain features of the invention (wherein like numerals represent like elements).
Certain exemplary test strip embodiments will now be described to provide an overall understanding of the principles of the structure, function, manufacture, and use of the test strips and methods of fabrication disclosed herein. One or more examples of these embodiments are illustrated in the accompanying drawings. Those skilled in the art will understand that the devices and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments and that the scope of the present disclosure is defined solely by the claims. The features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Such modifications and variations are intended to be included within the scope of the present disclosure.
As used herein, the terms “patient” or “user” refer to any human or animal subject and are not intended to limit the systems or methods to human use, although use of the subject invention in a human patient represents a preferred embodiment.
The term “sample” means a volume of a liquid, solution or suspension, intended to be subjected to qualitative or quantitative determination of any of its properties, such as the presence or absence of a component, the concentration of a component, e.g., an analyte, etc. The embodiments of the present invention are applicable to human and animal samples of whole blood. Typical samples in the context of the present invention as described herein include blood, plasma, red blood cells, serum and suspensions thereof.
The term “about” as used in connection with a numerical value throughout the description and claims denotes an interval of accuracy, familiar and acceptable to a person skilled in the art. The interval governing this term is preferably ±10%. Unless specified, the terms described above are not intended to narrow the scope of the invention as described herein and according to the claims. The terms “top” and “base” as used herein are intended to serve as a reference for illustration purposes only, and that the actual position of the portions of the test strip will depend on its orientation.
The present invention generally provides an electrochemical biosensor, or test strip, having electrodes that communicate with an analyte measurement system or device. The biosensor is particularly advantageous as it offers a relatively small size, while providing a large surface area for ease of handling. The smaller size of the electrochemical biosensor may reduce manufacturing costs, as less material is required to manufacture it.
The test strip 100 can have various configurations, but it is typically in the form of rigid, semi-rigid, or flexible layers 104-105, and flexible layers 106-107, having sufficient structural integrity to allow handling and connection to an analyte measurement system or device, as will be discussed in further detail below. The test strip layers 104-107 may be formed from various materials, including plastic, polyester, or other materials. The material of the layers 104-107, typically is one that is insulating (non-conductive) and may be inert and/or electrochemically non-functional, where they do not readily corrode over time nor chemically react with a sample applied to the sample chamber 113 of the test strip 100. The top electrode 101 includes a flexible insulating layer 106 and a flexible conductive material, or layer, 102 disposed on an inwardly facing surface thereof (facing the electrode 109). The base electrode 109 also includes a flexible insulating layer 107 and a flexible conductive material, or layer, 110 disposed on an inwardly facing surface thereof (facing electrode 101). The conductive layers should be resistant to corrosion wherein their conductivity does not change during storage of the test strip 100.
In the embodiment shown in
The top and base electrodes 101, 109 include a substantially insulating and inert substrate, 106, 107, respectively, and have a conductive material disposed on one surface thereof 102, 110, respectively, to facilitate communication between the electrodes 101, 109 and an analyte measurement system or device. The top and base electrodes 101, 109 and the conductive material disposed thereon also each comprise a generally elongated, rectangular, planar shape. The electrically conducting layers 102, 110 may be formed from any conductive material, including inexpensive materials, such as aluminum, carbon, graphene, graphite, silver ink, tin oxide, indium oxide, copper, nickel, chromium and alloys thereof, and combinations thereof (e.g., indium doped tin oxide) and may be deposited, adhered, or coated on the insulating layers 106, 107. However, precious metals that are conductive, such as palladium, platinum, indium tin oxide or gold, can optionally be used. The conductive layer may be deposited onto the insulating layers 106, 107 by various processes, such as sputtering, electroless plating, thermal evaporation and screen printing. In one exemplary embodiment, the reagent-free electrode, e.g., the top electrode 101, is a sputtered gold electrode, and the electrode containing the reagent 108, e.g., the base electrode 109, is a sputtered palladium electrode. As discussed in further detail below, in use one of the electrodes can function as a working electrode and the other electrode can function as the counter/reference electrode. The electrically conducting layers may be disposed on the entire inward facing surfaces of the top and base electrodes 101, 109, or they may terminate at a distance (e.g., 1 mm) from the edges of the electrodes 101, 109 but the particular locations of the electrically conducting layers 102, 110, should be configured to electrically couple the electrochemical cell of the sample chamber 113 to an analyte measurement system or device.
In one exemplary embodiment, the entire portion or a substantial portion of the inwardly facing surfaces of the top and base electrodes 101, 109 are coated with the electrically conducting layers 102, 110 at a preselected thickness. When the electrochemical test strip is assembled, as shown in
To maintain electrical separation between the top and base conductive layers 102, 110, the test strip 100 may further include a spacer layer, comprising proximal and distal spacers 104, 105, which may also be double-sided adhesive spacers for securing to one another the top and base electrodes 101, 109, in a spaced relationship. The spacers 104, 105 can function to maintain the top and base electrodes 101, 109 at a distance apart from one another, thereby preventing electrical contact between the co-facial top and base conducting layers 102, 110. The spacers 104, 105 may be formed from a variety of materials, including rigid, semi-rigid, or flexible material with adhesive properties, or the spacers 104, 105 can include a separate adhesive applied thereon to attach the spacers 104, 105 to the inside surfaces of electrodes 101, 109. The spacer material may have a small coefficient of thermal expansion such that the spacers do not adversely affect the volume of the sample chamber 113. The spacers 104, 105 may have a width that can be substantially equal to a width Wt (
The top and base electrodes 101, 109 may be configured in any suitable configuration in an opposed spaced apart relationship for receiving a sample. The illustrated reagent film 108 may be disposed on either of the top or base electrodes 101, 109 between the spacers 104, 105 and within the chamber 113 for coming into physical contact, and reacting, with an analyte in a sample applied thereto. Alternatively, the reagent layer can be disposed on multiple faces of the sample chamber 113. A person skilled in the art will appreciate that the electrochemical test strip 100, in particular the electrochemical cell formed thereby, may have a variety of configurations, including having other electrode configurations, such as co-planar electrodes. The reagent layer 108 can be formed from various materials, including various mediators and/or enzymes. Suitable mediators include, by way of non-limiting example, ferricyanide, ferrocene, ferrocene derivatives, osmium bipyridyl complexes, and quinone derivatives. Suitable enzymes include, by way of non-limiting example, glucose oxidase, glucose dehydrogenase (GDH) based onpyrroloquinoline quinone (PQQ) co-factor, GDH based on nicotinamide adenine dinucleotide co-factor, and FAD-based GDH. One exemplary reagent formulation, which would be suitable for making the reagent layer 108, is described in U.S. Pat. No. 7,291,256, entitled “Method of Manufacturing a Sterilized and Calibrated Test strip-Based Medical Device,” the entirety of which is hereby incorporated as if fully set forth herein by reference. The reagent layer 108 can be formed using various processes, such as slot coating, dispensing from the end of a tube, ink jetting, and screen printing. While not discussed in detail, a person skilled in the art will also appreciate that the various electrochemical modules disclosed herein can also contain a buffer, a wetting agent, and/or a stabilizer for the biochemical component.
As described above, the spacers 104, 105 and the electrodes 101, 109 generally define a space or gap, also referred to as a window, therebetween which forms an electrochemical cavity or sample chamber 113 for receiving a sample. In particular, the top and base electrodes 101, 109 define the top and bottom of the sample chamber 113 and the spacers 104, 105 define the sides of the sample chamber 113. The gap between the spacers 104, 105 will result in an opening or inlet extending into the sample chamber 113 at both ends. The sample can thus be applied through either opening. In one exemplary embodiment, the volume of the sample chamber can range from about 0.1 microliters to about 5 microliters, preferably about 0.2 microliters to about 3 microliters, and more preferably about 0.2 microliters to about 0.4 microliter. To provide the small volume, the gap between the spacers 104, 105 have an area ranging from about 0.005 cm2 to about 0.2 cm2, preferably about 0.0075 cm2 to about 0.15 cm2, and more preferably about 0.01 cm2 to about 0.08 cm2, and the thickness of the spacers 104, 105 can range from about 1 micron to 500 microns, and more preferably about 10 microns to 400 microns, and more preferably about 40 microns to 200 microns, and even more preferably about 50 microns to 150 microns. As will be appreciated by those skilled in the art, the volume of the sample chamber 113, the area of the gap between the spacers 104, 105, and the distance between the electrodes 101, 109 can vary significantly.
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After formation of the web 301 with reagent layer 408, and spacers 404, 405 assembled thereon, the bi-laminate web structure formed thereby may be cut according to the cutting pattern 304, 305 (
It should be noted that the fabrication steps just described may be modified in various combinations as is well known to those skilled in the art. For example, the steps just described for forming the electrodes 101, 109 may have a variety of configurations and sequences and are considered to be within the scope of the present disclosure. In another exemplary embodiment, the reagent layer may be applied, as necessary, to the top electrode instead of the base electrode. One advantage of the fabrication steps just described is that the method makes use of an interlocking, or tessellated, electrode web design that, when cut, forms electrode components, or completed test strips, without wasting fabrication materials.
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While the invention has been described in terms of particular variations and illustrative figures, those of ordinary skill in the art will recognize that the invention is not limited to the variations or figures described. In addition, where methods and steps described above indicate certain events occurring in certain order, those of ordinary skill in the art will recognize that the ordering of certain steps may be modified and that such modifications are in accordance with the variations of the invention. Additionally, certain of the steps may be performed concurrently in a parallel process when possible, as well as performed sequentially as described above. Therefore, to the extent there are variations of the invention, which are within the spirit of the disclosure or equivalent to the inventions found in the claims, it is the intent that this patent will cover those variations as well.