Patent Application
20080006530
The preferred embodiments of the present invention are illustrated in
Turning now to
Base layer 20 has a conductive layer 21 on which are delineated four conductive paths 22, 24, 26, and 28. It should be understood that the conductive paths in any of the embodiments disclosed herein may be made from any non-corroding metal. Carbon deposits such as for example carbon paste or carbon ink may also be used as the conduit paths, all as is well known by those of ordinary skill in the art.
The conductive paths 22, 24, 26, and 28 may be formed by scribing or scoring conductive layer 21, or by silk-screening conductive paths 22, 24, 26, and 28 onto base layer 20. Scribing or scoring of conductive layer 21 may be done by mechanically scribing the conductive layer 21 sufficiently to create the independent conductive paths 22, 24, 26, and 28. The preferred scribing or scoring method of the present invention is done by using a carbon dioxide laser, a YAG laser or an eximer laser. Conductive layer 21 may be made of any electrically conductive material such as, for example, gold, tin oxide/gold, palladium, other noble metals or their oxides, or carbon film compositions. The preferred electrically conductive material is gold or tin oxide/gold. A usable material for base layer 20 is a tin oxide/gold polyester film (Cat. No. FM-1) or a gold polyester film (Cat. No. FM-2) sold by Courtaulds Performance Films, Canoga Park, Calif.
Electrode forming layer 30 has two or more electrode forming openings. In this preferred embodiment, electrode forming layer 30 has four electrode forming openings 32, 34, 36, and 38. Electrode forming opening 32 exposes a portion of conductive path 22, electrode forming opening 34 exposes a portion of conductive path 24, electrode forming opening 36 exposes a portion of conductive path 26, and electrode forming opening 38 exposes a portion of conductive path 28. Each of the openings form electrode forming wells when electrode forming layer is disposed onto base layer 20. Electrode forming layer 30 also includes a flow terminating mechanism 39. In this embodiment, flow terminating mechanism 39 is a flow terminating opening 39a that creates a recess/opening in one wall of sample chamber 17 (preferably in the wall opposite vent opening 52) when assembled into sensor strip 10. Flow terminating opening 39a is a critical aspect of the present invention that causes sensor strip 10 to provide more accurate measurements. Flow terminating opening 39a, when incorporated into sensor strip 10, is always the opening/recess on electrode forming layer 30 that is the furthest downstream from sample inlet 18. Electrode forming layer 30 also includes an optional notch 31 at fluid sampling end 14 to facilitate loading of the fluid sample into sample chamber 17. The preferred shape is a half circle, which is located approximately in the middle of the channel entrance. The preferred size is 0.028 in. (0.71 mm) in diameter.
Electrode forming layer 30 is made of a plastic material, preferably a medical grade, one-sided, adhesive tape available from Adhesive Research, Inc., of Glen Rock, Pa. Acceptable thicknesses of the tape for use in the present invention are in the range of about 0.001 in. (0.025 mm) to about 0.005 in. (0.13 mm). One such tape, Arcare® 7815 (about 0.0025 in. (0.063 mm)), is preferred due to its ease of handling and good performance. It should be understood that the use of a tape is not required. Electrode forming layer 30 may be made from a plastic sheet and may be coated with a pressure sensitive adhesive, a photopolymer, ultrasonically-bonded to base layer 20, or silk-screened onto the base layer 20 to achieve the same results as using the polyester tape mentioned.
The four electrode forming openings 32, 34, 36, and 38 define four electrode areas that can be any combination of working electrodes, reference electrodes, and/or other interference compensating electrodes. Each electrode area holds chemical reagents specific for the type of electrode desired. The chemical reagents for the working electrode areas are typically a mixture of enzymes and redox mediators with optional polymers, surfactants, and buffers. Examples of usable reagents are disclosed in U.S. Pat. Nos. 6,258,229; 6,287,451; 6,837,976; 6,942,770, which are incorporated herein by reference. A reference reagent matrix may be loaded in at least one electrode area forming a reference electrode.
Typically, the reference electrode area must be loaded with a redox reagent or mediator to make the reference electrode function when using the preferred conductive coating material. The reference reagent matrix preferably contains either oxidized or a mixture of an oxidized and reduced form of redox mediators, at least one binder, a surfactant and an optional antioxidant (if a reduced form of redox mediator is used) and a bulking agent. In the alternative, the reference electrode could be also loaded with a Ag/AgCl layer (e.g. by applying Ag/AgCl ink or by sputter-coating a Ag or Ag/AgCl layer) or other reference electrode materials that do not require a redox mediator to function properly.
The size of the electrode forming openings is preferred to be made as small as possible in order to make the sample chamber of the sensor as short as possible while still being capable of holding sufficient chemical reagent to function properly. The preferred shape of the electrode forming openings is round and has a preferred diameter of about 0.03 in. (0.76 mm). The four electrode forming openings 32, 34, 36, and 38 illustrated in
The positional arrangement of the working electrode and the reference electrode in the channel is also not critical for obtaining usable results from the sensor. The position of the flow terminating opening/recess 39a, however, is critical. As disclosed above, it is important that flow terminating opening/recess 39a is the last (i.e. downstream) opening/recess in sample chamber 17 and that it is formed within the wall and across the entire width of the wall in sample chamber 17 in which it is located.
The working electrode and the reference electrode are each in electrical contact with separate conductive paths. The separate conductive paths terminate and are exposed for making an electrical connection to a reading device at electrical contact end 16 of laminated body 12.
Spacer layer 40 has a U-shaped cutout or slot 42 located at the fluid sampling end 14. The length of cutout 42 is such that when spacer layer 40 is laminated to electrode forming layer 30, the electrode areas and the flow terminating opening/recess 39a are within the space defined by cutout 42. Spacer layer 40 is made of a plastic material, preferably a medical grade, double-sided, pressure sensitive adhesive tape available from Adhesive Research, Inc., of Glen Rock, Pa. Acceptable thicknesses of the tape for use in the present invention are in the range of about 0.001 in. (0.025 mm) to about 0.010 in. (0.25 mm). One such tape is Arcare® 7840 (about 0.0035 in. (0.089 mm)). U-shaped cutout 42 can be made with a laser or by die-cutting. The preferred method is to die-cut the cutout. The preferred size of the U-shaped cutout is about 0.05 in. wide (1.27 mm) and about 0.0035 in. thick (0.089 mm). The length is dependent on the number of working, reference and other electrodes incorporated into sensor strip 10.
Cover layer 50, which is laminated to spacer layer 40, has vent opening 52 spaced from the fluid sampling end 14 of sensor strip 10 to insure that fluid sample in the sample chamber 17 will completely cover all the electrode areas. Vent opening 52 is positioned in cover layer 50 so that it will align somewhat with U-shaped cutout 42. Preferably, vent opening 52 will expose a portion of and partially overlay the base of the U-shaped cutout 42. The preferable shape of vent hole 52 is a rectangle with dimensions of about 0.08 in. (2 mm) by about 0.035 in. (0.9 mm). Preferably, the top layer also has an optional notch 54 at fluid sampling end 14 to facilitate loading of the fluid sample into sample chamber 17. The preferred shape is a half circle, which is located approximately in the middle of the channel entrance. The preferred size is 0.028 in. (0.71 mm) in diameter. The preferred material for cover layer 50 is a polyester film. In order to facilitate the capillary action, it is desirable for the polyester film to have a highly hydrophilic surface that faces the capillary channel. Transparency films (Cat. No. PP2200 or PP2500) from 3M are the preferred material used as the cover layer in the present invention.
Laminated body 12 has a base layer 20, a electrode forming layer 30, a spacer layer 40 with a U-shaped cutout 42, and a cover layer 50 with an optional inlet notch 54. Base layer 20 has a conductive layer 21 on which is delineated a plurality of conductive paths 22, 24, 26, and 28. Electrode forming layer 30 has two or more electrode forming openings. In this embodiment, like the previous embodiment, electrode forming layer 30 has four electrode forming openings 32, 34, 36, and 38, and an optional notch 31.
Unlike the previous embodiment, this embodiment does not have a flow terminating opening/recess. Flow control is accomplished in this embodiment by a hydrophobic layer 39b on electrode forming layer 30 or by making electrode forming layer 30 using a hydrophobic material. The important aspect of the present invention is that the portion of electrode forming layer 30 lying within sample chamber 17 is made hydrophobic over its entire length. Maintaining this portion of sample chamber 17 hydrophobic reduces the momentum of the sample fluid as it enters sample chamber 17 by capillary action. The reduced momentum caused by making the electrode forming layer hydrophobic allows edge 51 of vent opening 52 to prevent sample creep by stopping the sample fluid completely.
In sensor strips having a hydrophilic or somewhat less hydrophobic sample chamber 17, it was found that the sample fluid would in some instances continue to creep along the sample chamber wall opposite vent opening 52 past the first edge 51 of vent opening 52.
Sample movement arising from this creeping of the sample fluid that occurs during the measurement reading time of sensor strip 10 introduces error in the measurement.
Making of the Sensor Strip
Assembly of the various embodiments of the present invention is relatively straightforward. Generally, the base layer and electrode forming layer are laminated to each other followed by dispensing the appropriate reagent mixture(s) into each of the electrode forming openings. After drying the reagent mixture, the spacer layer is laminated onto the electrode forming layer and the cover layer is then laminated onto the spacer layer.
More particularly, a piece of a gold polyester film is cut to shape as illustrated in
A piece of one-sided adhesive tape is then cut to size and shape, forming electrode forming layer 30 so that it will cover a major portion of conductive layer 21 of base layer 20 except for exposing a small electrical contact area illustrated in
The flow terminating mechanism 39 and the electrode forming openings are incorporated into electrode forming layer 30. In the embodiment where flow terminating mechanism 39 is a flow terminating opening/recess 39a, flow terminating opening/recess 39a and the two or more circular openings such as those illustrated in
Electrode forming layer 30 is then attached to base layer 20 in such a way as to define the two or more electrode wells. Approximately 0.05 to 0.09 μL of the appropriate reagent mixture (or mixtures) is dispensed into respectively appropriate electrode areas. After the addition of the reagents, the reagents are dried. Drying of the reagents can occur within a temperature range of about room temperature to about 80° C. The length of time required to dry the reagents is dependent on the temperature at which the drying process is performed.
After drying, a piece of double-sided tape available from Adhesive Research is fashioned into spacer layer 40 containing U-shaped channel 42. Spacer layer 40 is then layered onto electrode forming layer 30. As mentioned earlier, spacer layer 40 serves as a spacer and defines the size of the sample chamber 17.
A piece of a transparency film (Cat. No. PP2200 or PP2500 available from 3M) is fashioned into top layer/cover layer 50. A rectangular vent opening 52 is made using the laser previously mentioned or by means of a die-punch. Vent opening 52 is located approximately 0.180 in. (4.57 mm) from sample inlet 18. Cover layer 50 is aligned and layered onto spacer layer 40 to complete the assembly of sensor 10, as illustrated in
Those skilled in the art, however, will recognize that a sensor strip incorporating the flow terminating mechanism of the present invention may be utilized in sensor strips based on amperometric, coulometric, potentiometric, voltammetric, and other electrochemical techniques as well as optical techniques for determining the concentration of an analyte in a sample.
The following examples illustrate the unique features of the present invention. All three examples used the same aqueous control samples. Control 1 is a low level control containing a glucose concentration of 60±15 mg/dL. Control 2 is a normal level control containing a glucose concentration of 120±25 mg/dL. Control 3 is a high level control containing a glucose concentration of 300±35 mg/dL. The meter used to make the measurements in the examples is a prototype glucose meter based on amperometry and made by Nova Biomedical Corporation, Waltham, Mass.
Control samples with different glucose concentrations were tested with the glucose measuring strips manufactured by Nova Biomedical Corporation and having the laminated structure disclosed in the preferred embodiment and connected to the prototype meter. These strips did not have any flow terminating mechanism within the sample chamber. Table 1 shows the data obtained using the single use glucose measuring sensor strips at each of three control levels of glucose. A total of 20 measurements were made for each control sample.
As shown in Table 1, the coefficients of variation for the three control groups were 15.1, 9.1 and 11.2, respectively.
Control samples with different glucose concentrations were tested with modified glucose strips manufactured by Nova Biomedical Corporation. The modified strips had the laminated structure disclosed in the preferred embodiment and further incorporated a hydrophobic coating 39b as the flow terminating mechanism 39 illustrated in
As shown in Table 2, the coefficients of variation for the three control groups were 3.5, 3.4 and 3.1, respectively. When compared to the unmodified sensor strips, it was found that the sensor strips having the hydrophobic coating as the flow terminating mechanism had less error in the measurements (i.e. better C.V.) and were more consistent than the unmodified strips.
Control samples with different glucose concentrations were tested with modified glucose strips manufactured by Nova Biomedical Corporation. The modified strips had the laminated structure disclosed in the preferred embodiment and incorporated a flow terminating recess 39a in the electrode forming layer 20 as the flow terminating mechanism 39 illustrated in
As shown in Table 3, the coefficients of variation for the three control groups were 2.6, 2.2 and 1.8, respectively. As illustrated in Table 3, the coefficients of variation are improved compared to the coefficients of variation resulting from the use of a hydrophobic coating 39b as the flow terminating mechanism 39 and is significantly improved compared to the coefficients of variation for the sensor strips having no flow terminating mechanism. The flow terminating mechanism 39 used in Example 3 provided measurement values having the least amount of error in the measurements (i.e. best C.V.) and were the most consistent.
Although the preferred embodiments of the present invention have been described herein, the above description is merely illustrative. Further modification of the invention herein disclosed will occur to those skilled in the respective arts and all such modifications are deemed to be within the scope of the invention as defined by the appended claims.
