This application claims the benefit of U.S. Provisional Application Ser. No. 60/521,555, filed May 21, 2004, which is incorporated herein by reference.
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OF THE INVENTION
This invention relates to electrochemical cells and methods of making electrochemical cells for detecting the presence of, measuring the amount of, and/or monitoring the level of one or more components in a liquid sample. The cells perform an electrochemical measurement by evaluating an electrochemical parameter (i.e., potential, current, resistance, etc) between two or more electrodes which are in contact with a sample. Electrode sensors typically include a working electrode and either a counter or a reference/counter (“reference”) electrode.
While use may be made of this invention in the chemical industry, especially where complex mixtures are encountered (e.g. in food chemistry or biochemical engineering) it is of particular value in biological investigation and control techniques. More particularly, it lends itself to animal or human medicine, and in particular to in vitro measuring or monitoring of components in body fluids. For convenience, the invention will be described with reference to one such procedure, the determination of glucose within a human.
In order to effectuate a measurement of glucose in a human, a sample of blood is drawn from a test subject and the sample mixed with a reagent typically comprising an enzyme and a redox mediator. The chemistry used in such a measuring device is typically:
where GODox is the enzyme glucose oxidase in its oxidized state, and GODred is the enzyme in a reduced state. Ferricyanide ([Fe(CN)6]3−) is the oxidized mediator which oxidizes GODred so it can oxidize further glucose molecules. Ferrocyanide ([Fe(CN)6]4−) is the reduced form of the mediator which transfers electrons to an electrode (thereby regenerating ferricyanide). Thus, the generation of ferrocyanide (measured electrochemically) indicates the concentration of glucose in the sample. Other enzymes, such as glucose dehydrogenase, have also been used.
Because glucose monitoring for diabetics is preferably done several times a day, and because each test using conventional apparatus for home use requires a finger stick to obtain blood or interstitial fluid, the developmental pressure has been towards apparatus with ever increasing convenience to the user and lower cost. As a result, electrochemical cells with small sample test volumes have been disclosed. See, for example U.S. Pat. Nos. 6,576,101; 6,551,494; 6,129,823 and 5,437,999. As the size of the sample cell becomes smaller, however, the percentage change in electrode area and cell volume resulting from a small error in manufacturing tolerance becomes greater. This is significant because the magnitude of the signal may depend on the electrode area and cell volume. Thus, stricter manufacturing controls may be required in order to achieve the necessary precision in cell size, but these stricter controls are not compatible with the goal of reduced cost.
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OF THE INVENTION
In a first aspect, the present invention provides a simple method for producing electrochemical cells that is particularly applicable to the manufacture of cells with small and consistent sample volumes and electrode areas. The resulting electrochemical cell comprises opposing first and second electrodes separated by an electrically resistive sheet. The method comprises the steps of:
(a) forming a first bound opening in an electrically resistive sheet thereby forming a punched electrically resistive sheet;
(b) adhering the punched electrically resistive sheet to a first electrically conductive sheet thereby forming a combined sheet, wherein a first portion of a conductive surface of the first electrically conductive sheet is exposed through the first bound opening, and a second portion of the conductive surface of the electrically conductive sheet is exposed either through a second bound opening in the electrically resistive sheet or as an extension beyond an edge of the electrically resistive sheet;
(c) punching a notching opening through the electrically resistive sheet and the first electrically conductive sheet of the combined sheet, wherein the notching opening intersects the first bound opening in the electrically resistive sheet thereby transforming the first bound opening into a notch in the electrically resistive sheet, and punching a first contact area opening through the second exposed portion of the electrically conductive sheet visible to form a first electrical contact, thereby forming a punched combined sheet;
(d) punching a second electrically conductive sheet with a punch or punches to form an electrically conductive sheet having a notching opening corresponding to that of the punched combined sheet and a second contact area in the second electrically conductive sheet, thereby forming an opposite electrode sheet;
(e) adhering the opposite electrode sheet to the electrically resistive sheet portion of the punched combined sheet with an electrically conductive surface facing the electrically resistive sheet, said opposite electrode sheet being adhered such that the notching opening corresponding to the notching opening in the combined sheet is aligned with the notching opening in the combined sheet, and the second contact area is aligned with the second bound opening, thereby forming an electrochemical sheet, and
(f) cleaving the electrochemical sheet thereby forming a spent electrochemical sheet and a free electrochemical cell having a sample space for receiving a sample defined by the first and second conductive sheets and the notch in the electrically resistive sheet, and first and second contact areas in electrically-conductive contact with electrode portions of the first and second conductive sheets exposed in the sample space for connection of said first and second electrode portions with a meter.
If appropriate for the test strip being made, reagent can be added during the construction of the test strip as described above.
In a preferred embodiment, both ends of the first major open area are cut in step (c) to form a sample space that is open at both ends, and defined on the sides. One opening of the sample space is at the outer edge of the sample-collection tip of the device and the other opening adjoins a hole formed near the tip of the device.
The method of the invention provides numerous advantages over prior art methods for the construction of electrochemical cells. First, the method utilizes only a limited number of sheets of material that can be the same size, and significantly larger than the cells as finally made. Second, the method of the invention does not require any printing or lithography techniques to define the sample space volume and the electrode area or to form the electrode leads and connections. Third, because the significant dimensions of the device can be defined by die cutting or similar punching operations, both the accuracy and precision of the manufacturing process is good using macroscopic processes. This allows the manufacture of electrochemical cells that operate with very small sample volumes, without substantial increase in manufacturing expense. Fourth, electrochemical cells made using the method of the invention have reduced electrode “edge” effects which reduce the accuracy of the cell. Thus, the method of the present invention provides a cost effective and therefore disposable (single use) electrochemical cell that demonstrates remarkable accuracy in measurements while requiring only a minimal amount of sample.
Practicing this method results in an electrochemical cell of simple construction. Thus, in a further aspect of the invention, there is provided an electrochemical cell having a sample-receiving end and a connector end comprising, in sequence:
(a) a first substrate, having an unpatterned layer of conductive material applied to a first surface thereof;
(b) an electrically-resistive middle layer, and
(c) a second substrate, having an unpatterned layer of conductive material applied to a first surface thereof;
wherein the first surface of the first substrate and the first surface of the second substrate are adhered to the electrically resistive middle layer;
wherein the cell has a hole disposed near the sample receiving end, but spaced away from the free edge of the cell, said hole passing through the first substrate, the electrically resistive middle layer, and the second substrate,
wherein the cell has a sample space, said sample space passing through electrically resistive middle layer and being bounded on opposing sides by the unpatterned conductive materials of the first substrate and the unpatterned conductive material of the second substrate and said sample space extending from the free edge of the cell to the hole and being open at both ends. Where appropriate to the cell being made, the electrochemical cell may also include a reagent in the sample space.