STRIP ELECTRODE WITH SCREEN
CROSS-REFERENCE TO RELATED
This is a request for filing a continuation application undo- 37 CFR 1.62, of prior application Ser. No. 07/888,264 filed on May 22, 1992, abandoned, by A. O. Hill et al. for STRIP ELECTRODE WITH SCREEN PRINTING; which is a continuation of U.S. Ser. No. 07/768,359, filed Sep. 30, 1991, now abandoned; which is a continuation of U.S. Ser. No. 07/634,968, filed Jan. 7, 1991, now abandoned; which is a continuation of U.S. Ser. No. 07/002,120, filed Jan. 12, 1987, now abandoned; which is a Continuation-in-Part of Ser. No. 06/607,599, filed May 7, 1984, now abandoned. The following U.S. patent applications filed May 7, 1984 and owned by applicants' assignee, Genetics International, Inc. are hereby incorporated by reference: Sensor For Components Of A Liquid Mixture (U.S. Ser. No. 607,699); Assay Techniques Utilizing Specific Binding Agents (U.S. Ser. No. 607,695); Assay Systems Using More Than One Enzyme (U.S. Ser. No. 607,698); Assay Systems Utilizing More Than One Enzyme; (U.S. Ser. No. 607,607).
BACKGROUND OF THE INVENTION
This invention relates to enzymatic sensor electrodes and their combination with reference electrodes to detect a compound in a liquid mixture.
Various electrochemical sensors are known which employ enzymes to sense the presence of a compound that serves as an enzyme substrate. As just one example, Nakamura U.S. Pat No. 4,224,125 discloses an enzyme electrode system in which an enzyme, such as glucose oxidase, is used to sense glucose. A redox compound is used to accept electrons from the enzyme. For example, at 10:21-49, Nakamura discloses (FIG. 5) press molding to the electrode a mixture of glucose oxidase cross-linked by gluteraldehyde and a fluorocarbon polymer powder together with a cation exchange resin containing potassium ferricyanide. Nakamura's electrode system (FIG. 2) consists of three electrodes: an enzyme electrode 7, a reference electrode 8, and a counter electrode 10.
In another example, Pace U.S. Pat No. 4,225,410 discloses a multi-layer enzyme sensor; for example sensor 14b (FIG. 7i>) measures levels of lactate dehydrogenase. NAD* is generated at a fourth electrode 82, and the enzymatic reaction converts it to NADH which is sensed at monitoring electrode 84 by undisclosed means. A barrier/counter electrode 80 and a reference electrode 85 are used in conjunction with monitoring electrode 84.
SUMMARY OF THE INVENTION
One aspect of the invention generally features a twoelectrode strip for releasable attachment to signal readout circuitry, forming a sensor system that detects a current representative of a compound in a liquid mixture. The strip comprises an elongated support (preferably flat) adapted for releasable attachment to the readout circuitry; a first conductor and a second conductor each extend along the support and comprise means for connection to the circuitry. An active electrode, positioned to contact the liquid mixture and the first conductor, comprises a deposit of an enzyme capable of catalyzing a reaction involving the compound. Electrons are transferred between the enzyme-catalyzed reaction and the first conductor to create the current. A
reference electrode is positioned to contact the mixture and the second conductor.
The preferred embodiment of the strip includes the following features. An electron mediator (most preferably a
5 ferrocene) is included in the active electrode deposit to effect the electron transfer. The compound being detected is glucose, and the enzyme is glucose oxidase or glucose dehydrogenase. The active electrode and the reference electrode are coatings applied to the elongated support, e.g. the
10 active electrode is formed by printing (e.g. screen printing) an ink comprising a conductive compound, the enzyme and the mediator, and the reference electrode is also formed by screen printing. The means for connecting to the readout circuit are positioned toward one end of the elongated
15 support, and the electrodes are positioned remote from that end.
In a second aspect, the invention features apparatus that includes the above-described strip and circuitry adapted to provide an electrical signal representative of the current The
20 read-out circuitry comprises an amplifier to amplify the current, a low-pass filter connected to the amplifier output, a current-to-voltage converter connected to the filter output, and a means to display a value representative of the output of the converter. The apparatus also includes means to
25 maintain a substantially constant bias voltage across the electrodes during current measurement, even without a separate voltage reference in contact with the mixture.
In a third aspect, the invention features screen printing the enzyme onto a substrate to form an enzymatic sensing
30 electrode. The ink used for screen printing includes a liquid vehicle, a suspension of conductive material, and the enzyme. Preferably, it also includes a mediator capable of transferring electrons between the enzymatic reaction and a conductor on the substrate. Also preferably, the substrate is
35 a flexible, high-dielectric polymeric substance, such as polyvinyl chloride, polyester, or polycarbonate.
The invention enables a very small, inexpensively manufactured, disposable electrode strip that provides an accurate electronic readout of the target compound. In
40 particular, the active electrode is sized to be covered by the smear of blood produced from a drop of blood (even a non-expressed drop) generated from a needle-prick at a bodily extremity, and the reference electrode is sized and spaced from the active electrode a distance such that the
45 reference electrode is covered by the same smear of blood. Other features and advantages of the invention will be apparent from the following description of the preferred embodiment.
50 DESCRIPTION OF THE PREFERRED
We first briefly describe the drawings. Drawings
FIG. 1 is a front of a strip-supported electrode configu55 ration;
FIG. 2 is a back view of the combination shown in FIG.
FIG. 3 shows an alternative strip-supported electrode; FIG. 4 shows a strip-supported electrode which is a 60 variant of FIG. 3;
FIG. 5 shows a modified connection of the strip electrode of FIGS. 3 and 4' FIG. 6 shows a further alternative supported electrode; FIG. 7 shows a combination of two electrode supports; 65 FIG. 8 shows diagrammatically the electrical performance of electrodes as described in the above Figures, with especial reference to FIGS. 6 and 7;