USRE36268E - Method and apparatus for amperometric diagnostic analysis - Google Patents

Method and apparatus for amperometric diagnostic analysis Download PDF

Info

Publication number
USRE36268E
USRE36268E US08679312 US67931296A USRE36268E US RE36268 E USRE36268 E US RE36268E US 08679312 US08679312 US 08679312 US 67931296 A US67931296 A US 67931296A US RE36268 E USRE36268 E US RE36268E
Authority
US
Grant status
Grant
Patent type
Prior art keywords
sample
cell
cholesterol
blood
glucose
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US08679312
Inventor
Neil J. Szuminsky
Joseph Jordan, deceased
Paul A. Pottgen
Jonathan L. Talbott
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Roche Diabetes Care Inc
Original Assignee
Roche Diagnostics Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Grant date
Family has litigation

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001Enzyme electrodes
    • C12Q1/004Enzyme electrodes mediator-assisted

Abstract

The present invention relates to a novel method and apparatus for the amperometric determination of an analyte, and in particular, to an apparatus for amperometric analysis utilizing a novel disposable electroanalytical cell for the quantitative determination of biologically important compounds from body fluids.

Description

The present application .Iadd.is a continuation of Ser. No. 08/176,863 filed Dec. 30, 1993, now abandoned; which is a Re-issue of Ser. No. 07/745,544 filed Aug. 15, 1991, now U.S. Pat. No. 5,108,564 which .Iaddend.is a division of application Ser. No. 07/322,598, filed Mar. 13, 1989, which is a continuation-in-part of our earlier filed application, U.S. Ser. No. 168,295, filed Mar. 15, 1988.Iadd., now abandoned.Iaddend..

FIELD OF THE INVENTION

The present invention relates to a disposable electroanalytical cell and a method and apparatus for quantitatively determining the presence of biologically important compounds such as glucose; TSH; T4; hormones such as HCG; cardiac glycosides such as Digoxin; antiarrhythmics such as Lidocaine; antiepileptics such as phenobarbital; antibiotics such as Gentamicin; cholesterol; non-therapeutic drugs and the like from body fluids.

Although the present invention has broad applications, for purposes of illustration of the invention specific emphasis will be placed upon its application in quantitatively determining the presence of two biologically important compounds--glucose and cholesterol.

WITH RESPECT TO GLUCOSE

Diabetes, and specifically diabetes mellitus, is a metabolic disease characterized by deficient insulin production by the pancreas which results in abnormal levels of blood glucose. Although this disease afflicts only approximately 4% of the population in the United States, it is the third leading cause of death following heart disease and cancer. With proper maintenance of the patient's blood sugar through daily injections of insulin, and strict control of dietary intake, the prognosis for diabetics is excellent. However, the blood glucose levels must be closely followed in the patient either by clinical laboratory analysis or by daily analyses which the patient can conduct using relatively simple, non-technical, methods.

At the present, current technology for monitoring blood glucose is based upon visual or instrumental determination of color change produced by enzymatic reactions on a dry reagent pad on a small plastic strip. These colorimetric methods which utilize the natural oxidant of glucose to gluconic acid, specifically oxygen, are based upon the reactions:

B-D-Glucose+O.sub.2 +H.sub.2 O→D-Gluconic Acid+H.sub.2 O.sub.2

H.sub.2 O.sub.2 +Reagent-H.sub.2 O+color.
WITH RESPECT TO CHOLESTEROL

Current technology for the determination of cholesterol is also based upon similar methods. In the case of cholesterol, the methods presently used are based upon the generalized reactions:

Cholesterol+H.sub.2 O+O.sub.2 →Cholestenone+H.sub.2 O.sub.2

H.sub.2 O.sub.2 +Reagent→H.sub.2 O+color.

In all present techniques, Dioxygen is the only direct oxidant used with the enzyme cholesterol oxidase for the determination of both free and total cholesterol. Using conventional test methods, oxygen must diffuse into the sensor solution during use from the surrounding air in order to provide sufficient reagent for a complete reaction with the analyte cholesterol in undiluted serum and whole blood specimens.

In both instances, the presence of the substance is determined by quantifying, either colorometrically or otherwise, the presence of hydrogen peroxide. The present methods of detection may include direct measurement of the hydrogen peroxide produced by either spectroscopic or electrochemical means and indirect methods in which the hydrogen peroxide is reacted with various dyes, in the presence of the enzyme peroxidase, to produce a color that is monitored.

While relatively easy to use, these tests require consistent user technique in order to yield reproducible results. For example, these tests require the removal of blood from a reagent pad at specified and critical time intervals. After the time interval, excess blood must be removed by washing and blotting, or by blotting alone, since the color measurement is taken at the top surface of the reagent pad. Color development is either read immediately or after a specified time interval.

These steps are dependent upon good and consistent operating technique requiring strict attention to timing. Moreover, even utilizing good operating technique, colorimetric methods for determining glucose, for example, have been shown to have poor precision and accuracy, particularly in the hypoglycemic range. Furthermore, instruments used for the quantitative colorimetric measurement vary widely in their calibration methods: some provide no user calibration while others provide secondary standards.

Because of the general lack of precision and standardization of the various methods and apparatus presently available to test for biologically important compounds in body fluids, some physicians are hesitant to use such equipment for monitoring levels or dosage. They are particularly hesitant in recommending such methods for use by the patients themselves. Accordingly, it is desirable to have a method and apparatus which will permit not only physician but patient self-testing of such compounds with greater reliability.

The present invention addresses the concerns of the physician by providing enzymatic amperometry methods and apparatus for monitoring compounds within whole blood, serum, and other body fluids. Enzymatic amperometry provides several advantages for controlling or eliminating operator dependant techniques as well as providing a greater linear dynamic range. A system based on this type of method could address the concerns of the physician hesitant to recommend self-testing for his patients.

Enzymatic amperometry methods have been applied to the laboratory based measurement of a number of analytes including glucose, blood urea nitrogen, and lactate. Traditionally the electrodes in these systems consist of bulk metal wires, cylinders or disks imbedded in an insulating material. The fabrication process results in individualistic characteristics for each electrode necessitating calibration of each sensor. These electrodes are also too costly for disposable use, necessitating meticulous attention to electrode maintenance for continued reliable use. This maintenance is not likely to be performed properly by untrained personnel (such as patients), therefore to be successful, an enzyme amperometry method intended for self-testing (or non-traditional site testing) must be based on a disposable sensor that can be produced in a manner that allows it to give reproducible output from sensor to sensor and at a cost well below that of traditional electrodes.

The present invention address these requirements by providing miniaturized disposable electroanalytic sample cells for precise micro-aliquote sampling, a self-contained, automatic means for measuring the electrochemical reduction of the sample, and a method for using the cell and apparatus according to the present invention.

The disposable cells according to the present invention are preferably laminated layers of metallized plastic and nonconducting material. The metallized layers provide the working and reference electrodes, the areas of which are reproducibly defined by the lamination process. An opening through these layers is designed to provide the sample-containing area or cell for the precise measurement of the sample. The insertion of the cell into the apparatus according to the present invention, automatically initiates the measurement cycle.

To better understand the process of measurement, a presently preferred embodiment of the invention is described which involves a two-step reaction sequence utilizing a chemical oxidation step using other oxidants than oxygen, and an electro-chemical reduction step suitable for quantifying the reaction production of the first step. One advantage to utilizing an oxidant other than dioxygen for the direct determination of an analyte is that they may be prepositioned in the sensor in a large excess of the analyte and thus ensure that the oxidant is not the limiting reagent (with dioxygen, there is normally insufficient oxidant initially present in the sensor solution for a quantitative conversion of the analyte).

In the oxidation reaction, a sample containing glucose, for example, is converted to gluconic acid and a reduction product of the oxidant. This chemical oxidation reaction has been found to precede to completion in the presence of an enzyme, glucose oxidase, which is highly specific for the substrate B-D-glucose, and catalyzes oxidations with single and double electron acceptors. It has been found, however, that the oxidation process does not proceed beyond the formation of gluconic acid, thus making this reaction particularly suited for the electrochemical measurement of glucose.

In a presently preferred embodiment, oxidations with one electron acceptor using ferricyanide, ferricinium, cobalt (III) . .orthophenantroline.!. .Iadd.orthophenanthroline.Iaddend., and cobalt (III) dipyridyl are preferred. Benzoquinone is a two electron acceptor which also provides excellent electro-oxidation characteristics for amperometric quantitation.

Amperometric determination of glucose, for example, in accordance with the present invention utilizes Cottrell current micro-chronoamperometry in which glucose plus an oxidized electron acceptor produces gluconic acid and a reduced acceptor. This determination involves a preceding chemical oxidation step catalyzed by a bi-substrate bi-product enzymatic mechanism as will become apparent throughout this specification.

In this method of quantification, the measurement of a diffusion controlled current at an accurately specified time (e.g. 20, 30, or 50 seconds, for example) after the instant of application of a potential has the applicable equation for amperometry at a controlled potential (E=constant) of: ##EQU1## where i denotes current, nF is the number of coulombs per mole, A. .D.!. is the area of the electrode.Iadd., .Iaddend.D is the diffusion coefficient of the reduced form of the reagent, t is the preset time at which the current is measured, and C is the concentration of the metabolite. Measurements by the method according to the present invention of the current due to the reoxidation of the acceptors were found to be proportional to the glucose concentration in the sample.

The method and apparatus of the . .prevent.!. .Iadd.present .Iaddend.invention permit, in preferred embodiments, direct measurements of blood glucose, cholesterol and the like. Furthermore, the sample cell according to the . .prevent.!. .Iadd.present .Iaddend.invention, provides the testing of controlled volumes of blood without premeasuring. Insertion of the sample cell into the apparatus thus permits automatic functioning and timing of the reaction allowing for patient self-testing with a very high degree of precision and accuracy.

One of many of the presently preferred embodiments of the invention for use in measuring B-D glucose is described in detail to better understand the nature and scope of the invention. In particular, the method and apparatus according to this embodiment are designed to provide clinical self-monitoring of blood glucose levels by a diabetic patient. The sample cell of the invention is used to control the sampling volume and reaction media and acts as the electrochemical sensor. In this described embodiment, benzoquinone is used as the electron acceptor.

The basic chemical binary reaction utilized by the method according to the present invention is:

B-D-glucose+Benzoquinone+H.sub.2 O→Gluconic Acid+Hydroquinone

Hydroquinone→benzoquinone+2e-+2H+.

The first reaction is an oxidation reaction which proceeds to completion in the presence of the enzyme glucose oxidase. Electrochemical oxidation takes place in the second part of the reaction and provides the means for quantifying the amount of hydroquinone produced in the oxidation reaction. This holds true whether catalytic oxidation is conducted with two-electron acceptors or one electron acceptors such as ferricyanide (wherein the redox couple would be Fe(CN)6 -3 /Fe(CN)6 -4), ferricinium, cobalt III . .orthophenantroline.!. .Iadd.orthophenanthroline .Iaddend.and cobalt (III) dipyridyl.

Catalytic oxidation by glucose oxidase is highly specific for B-D-glucose, but is nonselective as to the oxidant. It has now been discovered that the preferred oxidants described above have sufficiently positive potentials to convert substantially all of the B-D-glucose to gluconic acid. Furthermore, this system provides a means by which amounts as small a 1 mg of glucose (in the preferred embodiment) to 1000 mg of glucose can be measured per deciliter of sample--results which have not previously been obtained using other glucose self-testing systems.

The sensors containing the chemistry to perform the desired determination, constructed in accordance with the present invention, are used with a portable meter for self-testing systems. In use the sensor is inserted into the meter which turns the meter on and initiates a wait for the application of the sample. The meter recognizes sample application by the sudden charging current flow that occurs when the electrodes and the overlaying reagent layer are initially wetted by the sample fluid. Once the sample application is detected, the meter begins the reaction incubation step (the length of which is chemistry dependent) to allow the enzymatic reaction to reach completion. This period is on the order of 15 to 90 seconds for glucose, with incubation times of 20 to 45 seconds preferred. Following the incubation period, the instrument then imposes a known potential across the electrodes and measures the current at specific time points during the Cottrell current decay. Current measurements can be made in the range of 2 to 30 seconds following potential application with measurement times of 10 to 20 seconds preferred. These current values are then used to calculate the analyte concentration which is then displayed. The meter will then wait for either the user to remove the sensor or for a predetermined period before shutting itself down.

The present invention provides for a measurement system that eliminates several of the critical operator dependant variables that adversely affect the accuracy and reliability and provides for a greater dynamic range than other self-testing systems.

These and other advantages of the present invention will become apparent from a perusal of the following detailed description of one embodiment presently preferred for measuring glucose and another for measuring cholesterol which is to be taken in conjunction with the accompanying drawings in which like numerals indicate like components and in which:

FIG. 1 is an exploded view of a portable testing apparatus according to the present invention;

FIG. 2 is a plan view of the sampling cell of the present invention;

FIG. 3 is an exploded view of the sample cell shown in FIG. 2;

FIG. 4 is an exploded view of another embodiment of a sample cell according to the invention;

FIG. 5 is a plan view of the cell shown in FIG. 4;

FIG. 6 is still another embodiment of a sample cell;

FIG. 7 is a graph showing current as a function of glucose concentration;

FIG. 8 is a graphical presentation of Cottrell current as a function of glucose concentration; and

FIG. 9 is a presently preferred circuit diagram of an electrical circuit for use in the apparatus shown in FIG. 1.

FIG. 10 is a preferred embodiment of the electrochemical cell.

With specific reference to FIG. 1, a portable electrochemical testing apparatus 10 is shown for use in patient self-testing, such as, for example, for blood glucose levels. Apparatus 10 comprises a front and back housing 11 and 12, respectively, a front panel 13 and a circuit board 15. Front panel 13 includes graphic display panels 16 for providing information and instructions to the patient, and direct read-out of the test results. While a start button 18 is provided to initiate an analysis, it is preferred that the system being operation when a sample cell 20 (FIG. 2) is inserted into the window 19 of the apparatus.

With reference to FIGS. 2 and 3.Iadd., .Iaddend.sample cell 20 is a metallized plastic substrate having a specifically-sized opening 21 which defines a volumetric well 21, when the cell is assembled, for containing a reagent pad and the blood to be analyzed. Cell 20 comprises a first substrate 22 and a second substrate 23 which may be preferably made from styrene or other substantially non-conducting plastic. Positioned on second substrate 23 is reference electrode 24. Reference electrode 24 may be preferably manufactured, for example, by vapor depositing the electrode onto a substrate made from a material such as the polyimide Kapton. In the preferred embodiment, reference electrode 24 is a silver-silver chloride electrode. This electrode can be produced by . .first.!. depositing a silver .Iadd.chloride .Iaddend.layer on a silver . .chloride.!. layer by either chemical or electrochemical means before the substrate is used to construct the cells. The silver chloride layer may even be generated in-situ on a silver electrode when the reagent layer contains certain of the oxidants, such as ferricyanide, and chloride as shown in the following reactions:

Ag+Ox→ag.sup.+ +Red

Ag.sup.+ +Cl.sup.- →AgCl.

Alternatively the silver-silver chloride electrode can be produced by depositing a layer of silver oxide (by reactive sputtering) onto the silver film. The silver oxide layer is then converted in-situ at the time of testing to silver chloride according to the reaction:

Ag.sub.2 O+H.sub.2 O+2Cl.sup.- →2AgCl+2(OH).sup.-

when the sensor is wetted by the sample fluid and reconstitutes the chloride containing reagent layer. The silver electrode is thus coated with a layer containing silver chloride.

The reference electrode may also be of the type generally known as a "pseudo" reference electrode which relies upon the large excess of the oxidizing species to establish a known potential at a noble metal electrode. In a preferred embodiment, two electrodes of the same noble metal are used, however one is generally of greater surface area and is used as the reference electrode. The large excess of the oxidized species and the larger surface area of the reference resists a shift of the potential of the reference electrode.

Indicator or working electrode 26 can be either a strip of platinum, gold, or palladium metallized plastic positioned on reference electrode 24 or alternately the working electrode 26 and the reference electrode may be manufactured as a coplanar unit with electrode 26 being sandwiched between coplanar electrode 24 material. Preferable, sample cell 20 is prepared by sandwiching or laminating the electrodes between the substrate to form a composite unit.

As shown in FIG. 2, first substrate 22 is of a slightly shorter length so as to expose an end portion 27 of electrodes 24 and 26 and allow for electrical contact with the testing circuit contained in the apparatus. In this embodiment, after a sample has been positioned within well 21, cell 20 is pushed into window 19 of the front panel to initiate testing. In this embodiment, a reagent may be applied to well 21, or, preferably, a pad of dry reagent is positioned therein and a sample (drop) of blood is placed into the well 21 containing the reagent.

Referring to FIGS. 4-6, alternative embodiments of sample cell 20 are shown. In FIG. 4, sample cell 120 is shown having first 122 and second 123 substrates. Reference electrode 124 and working electrode 126 are laminated between substrates 122 and 123. Opening 121 is dimensioned to contain the sample for testing. End 130 (FIG. 5) is designed to be inserted into the apparatus, and electrical contact is made with the respective electrodes through cut-outs 131 and 132 on the cell. Reference electrode 124 also includes cut out 133 to permit electrical contact with working electrode 126.

In FIG. 6, working electrode 226 is folded, thereby providing increased surface area around opening 221, to achieve increased sensitivity or specificity. In this case, reference electrode 224 is positioned beneath working electrode 226. Working electrode includes cut out 234 to permit electrical contact with reference electrode 224 through cut out 231 in substrate 222. End 230 of substrate 222 also includes cut out 232 to permit electrical contact with working electrode 226.

Referring to FIGS. 1 and 2, the sample cell according to the present invention is positioned through window 19 (FIG. 1) to initiate the testing procedure. Once inserted, a potential is applied at portion 27 (FIG. 2) of the sample cell across electrodes 24 and 26 to detect the presence of the sample. Once the sample's presence is detected, the potential is removed and the incubation period initiated. Optionally during this period, a vibrator means 31 (FIG. 1) may be activated to provide agitation of the reagents in order to enhance dissolution (an incubation period of 20 to 45 seconds is conveniently used for the determination of glucose and no vibration is normally required). An electrical potential is next applied at portion 27 of the sample cell to electrodes 24 and 26 and the current through the sample is measured and displayed on display 16.

. .The.!. .Iadd.To .Iaddend.fully take advantage of the above apparatus, the needed chemistry for the sell testing systems is incorporated into a dry reagent layer that is positioned onto the disposable cell creating a complete sensor for the intended analyte. The disposable electrochemical cell is constructed by the lamination of metallized plastics and nonconducting materials in such a way that there is a precisely defined working electrode area. The reagent layer is either directly coated onto the cell or preferably incorporated (coated) into a supporting matrix such as filter paper, membrane filter, woven fabric or non-woven fabric, which is then placed into the cell. When a supporting matrix is used, it pore size and void volume can be adjusted to provide the desired precision and mechanical support. In general, membrane filters or nonwoven fabrics provide the best materials for the reagent layer support. Pore sizes of 0.45 to 50 μm and void volumes of 50-90% are appropriate. The coating formulation generally includes a binder such as gelatin, carrageenan, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, etc., that acts to delay the dissolution of the reagents until the reagent layer has adsorbed most of the fluid from the sample. The concentration of the binder is generally on the order of 0.1 to 10% with 1-4% preferred.

The reagent layer imbibes a fixed amount of the sample fluid when it is applied to the surface of the layer thus eliminating any need for premeasurement of sample volume. Furthermore, by virtue of measuring current flow rather than reflected light, there is no need to remove the blood from the surface of the reagent layer prior to measurement as there is with reflectance spectroscopy systems. While the fluid sample could be applied directly to the surface of the reagent layer, to facilitate spread of blood across the entire surface of the reagent layer the sensor preferably includes a dispersing spreading or wicking layer. This layer, generally a non-woven fabric or adsorbant paper, is positioned over the reagent layer and acts to rapidly distribute the blood over the reagent layer. In some applications this dispersing layer could incorporate additional reagents.

For glucose determination, cells utilizing the coplanar design were constructed having the reagent layer containing the following formulations:

______________________________________Glucose oxidase   600        u/mlPotassium Ferricyanide             0.4MPhosphate Buffer  0.1MPotassium Chloride             0.5MGelatin           2.0        g/dl______________________________________

This was produced by coating a membrane filter with a solution of the above composition and air drying. The reagent layer was then cut into strips that just fit the window opening of the cells and these strips were place over the electrodes exposed within the windows. A wicking layer of a non-woven rayon fabric was then placed over this reagent layer and held in place with an overlay tape.

In order to prove the application of the technology according to the present invention, a large number of examples were run in aqueous solution at 25° C. The electrolyte consisted of a phosphate buffer of pH 6.8 which was about 0.1 molar total phosphate and 0.5M potassium chloride reagent. The potentials are referenced to a normal hydrogen electrode (NHE). In these tests it was found that any potential between approximately +0.8 and 1.2 volt (vs NHE) is suitable for the quantification of hydroquinone when benzoquinone is used as the oxidant. The limiting currents are proportional to hydroquinone concentrations in the range between 0.0001M and 0.050M.

Determination of glucose by Cottrell current (it) microchronoamperometry with the present method is created in the reaction of hydroquinone to benzoquinone. Cottrell currents decay with time in accordance with the equation:

i.sub.r t1/2=const

where t denotes time.

The main difference between these two techniques consists of applying the appropriate controlled potential after the glucose-benzoquinone reaction is complete and correlating glucose concentrations with Cottrell currents measured at a fixed time thereafter. The current-time readout is shown in FIG. 8. Proportionality between glucose concentrations and Cottrell currents (recorded at t=30 seconds after the application of potential) is shown in FIG. 7.

It should be noted that Cottrell chronoamperometry of metabolites needs the dual safeguards of enzymatic catalysis and controlled potential electrolysis. Gluconic acid yields of 99.9+ percent were attained in the presence of glucose oxidase. Concomitantly, equivalent amounts of benzoquinone were reduced to hydroquinone, which was conveniently quantitated in quiescent solutions, at stationary palladium thin film anodes or sample cells.

The results of these many tests demonstrates the microchronoamperometric methodology of the present invention and its practicality for glucose self-monitoring by diabetics.

In a presently preferred embodiment of the invention utilizing ferrocyanide, a number of tests were run showing certain improved operating capabilities.

Referring to FIG. 9, a schematic diagram of a preferred circuit 15 for use in the apparatus 10 is shown. Circuit 15 includes a microprocessor and LCD panel 16. The working and reference electrodes on the sample cell 20 make contact at contacts W (working electrode) and R (reference electrode), respectively. Voltage reference 41 is connected to battery 42 through analogue power switch 43. Current from the electrodes W and R is converted to a voltage by op amp 45. That voltage is converted into a digital signal (frequency) by and voltage to frequency converter 46 electrically connected to the microprocessor 48. The microprocessor 48 controls the timing of the signals. Measurement of current flow is converted by microprocessor 48 to equivalent glucose, cholesterol or other substance concentrations. Other circuits within the skills of a practiced engineer can obviously be utilized to obtain the advantages of the present invention.

With regard to FIG. 10, cell 400 consists of coplanar working 426 and reference 424 electrodes laminated between an upper 422 and lower 423 nonconducting material. Lamination is on an adhesive layer 425. The upper material 422 includes a die cut opening 428 which, along with the width of the working electrode material defines the working electrode area and provides (with an overlapping reagent layer not depicted) the sampling port of the cell. At one end of cell 400 is an open area 427 similar to end position 27 of FIG. 2.

The efficiency of using the apparatus according to the present invention to provide a means for in-home self testing by patients such as diabetics (in the preferred embodiment) can be seen in the following table in which the technology according to the present invention is compared to four commercially available units. As will be seen, the present invention is simpler, and in this instance simplicity breeds consistency in results.

______________________________________GLUCOSE SYSTEM COMPARISONS                                   Present                                   Inven-Steps      1        2       3     4     tion______________________________________Turn Instrument On      X        X       X     X     XCalibrate Instrument      X        XFinger Puncture      X        X       X     X     XApply Blood      X        X       X     X     XInitiate Timing      X        X       XSequenceBlot       X        X       XInsert Strip to Read      X        X       X     XRead Results      X        X       X     X     XTotal Steps Per      8        8       7     5     4TestingDetection System      RS*      RS      RS    RS    Polaro-                                   graphicRange (mg/dl)      10-400   40-400  25-450                             40-400                                   0-1000CV**Hypoglycemic      15%      15%                 5%Euglycemic 10%      10%                 3%Hyperglycemic      5%       5%                  2%Correlation      0.921    0.862               0.95______________________________________ *RS--Reflectance Spectroscopy **Coefficient of variation

With specific regard to the determination of cholesterol utilizing the present invention, the generalized chemistry may be depicted as: ##STR1## where the enzymes cholesterol esterase (CE) and cholesterol oxidase (CO) catalyze reactions 1 and 2 respectively and CO permits electron transfer with a variety of electroactive couples (Ox and Red). Reaction 2 is novel in that electron acceptors other than dioxygen may be used to oxidize cholesterol in the presence of the enzyme cholesterol oxidase. Reaction 1 is well known to those in the field and is necessary for the determination of total cholesterol (free cholesterol and cholesterol esters). Reaction 3 is an electro-oxidation process for probing and quantitating the cholesterol.

Utilizing alternative oxidants according to the present invention, the specific reactions become: ##STR2##

Cholesterol oxidase (CO) from a variety of sources will catalyze electron transfer from cholesterol to a variety of the oxidants including benzoquinone, benzoquinone derivatives such as methylbenzoquinone, ethylbenzoquinone, chlorobenzoquinone, ortho-benzoquinone (oxidized form of catechol), benzoquinonesulfonate, and potassium ferricyanide. It is also anticipated that the enzyme will allow electron transfer with other alternate oxidants. As indicated in Reaction 3, the reduced product can then be monitored amperometrically for the quantitative determination of cholesterol.

Sources of the enzyme catalyzing the oxidation of cholesterol with alternate oxidants include CO from Nocardia, Streptomyces, Schizophyllum, Pseudomonas, and Brevibacterium; experimental conditions under which it is able to rapidly catalyze the oxidation of cholesterol by benzoquinone or any of the other oxidants depend somewhat upon the source of the enzyme. For example, CO from Streptomyces rapidly catalyzes substrate oxidation with benzoquinone in phosphate buffer in the presence of any of a variety of the surfactants including octylgluconopyranoside and CHAPSO; the same reaction under identical conditions with CO from either Brevibacterium or Nocardia is slower. However, both Nocardia and Brevibacterium sources are active catalysts for cholesterol oxidation by alternate oxidants under other conditions.

The oxidant also plays a role in which the enzyme is most active. For example, cholesterol oxidase from Nocardia rapidly catalyzes substrate oxidation with benzoquinone in 0.2 molar TRIS buffer and 3 g/dL CHAPSO but is slower with ferricyanide under identical conditions; the Brevibacterium source of the enzyme is relatively inactive with ferricyanide in TRIS buffer with a variety of surfactants but when benzoquinone is used as the oxidant the reaction is very fast. Alternatively, the Schizophyllum source of the enzyme CO rapidly catalyzes the oxidation of cholesterol in phosphate buffer with either ferricyanide or benzoquinone and with a variety of surfactants as activators.

As indicated, cholesterol oxidase will catalyze the oxidation of cholesterol by ferricyanide. Additional examples where CO catalyzes cholesterol oxidation by ferricyanide include a Nocardia source in TRIS buffer with a variety of surfactants including sodium deoxycholate, sodium taurodeoxycholate, CHAPS, Thesit, and CHAPSO. Furthermore, CO from Nocardia will also catalyze substrate oxidation with ferricyanide in phosphate buffer with sodium dioctylsulfosuccinate, sodium deoxycholate, sodium taurodeoxycholate, and Triton X-100. The buffer concentration is from 0.1 to 0.4 molar. Surfactant concentration for maximum activity of the oxidase enzyme varies with each detergent. For example, with deoxycholate or taurodeoxycholate, the enzyme in 0.2M TRIS is most active with detergent in the range from 20 to 90 millimolar. However, enzyme catalytic activity is observed up to . .an.!. .Iadd.and .Iaddend.through a 10% concentration. With octyl-gluconopyranoside, the maximum activity of the enzyme with the oxidant ferricyanide occurs at a detergent concentration of approximately 1.2%; however, the enzyme still maintains activity at higher and lower concentrations of the surfactant.

Both esterase and CO require a surfactant for high activity. Specific surfactants include sodium deoxycholate, sodium taurodeoxycholate, sodium glycodeoxycholate, CHAPS (3-(3-chlolamidopropyl)dimethylammonio-1-propanesulfonate), CHAPSO (3-(3-chlolamidopropyl)dimethylammonio-2-hydroxy-1-propanesulfonate), octyl-gluconopyranoside, octylthio-gluconopyranoside, nonyl-gluconopyranoside, dodecyl-gluconopyranoside, Triton X-100, Dioctyl sulfosuccinate, Thesit (Hydroxypolyethoxydodecane), and lecithin (phosphatidylcholine). Buffers acceptable for this reaction to occur with the enzyme include phosphate, TRIS, MOPS, MES, HEPES, Tricine, Bicine, ACES, CAPS, and TAPS. An alternate generallized reaction scheme for the measurement of cholesterol in serum and other biological fluids is given ##STR3## where Ox, and Red2 function as an electron mediator couple between the cholesterol and the electroactive couple Ox2 /Red2. In this case Ox1 and Red1 need not be electroactive because they do not have to participate in the electrooxidation process (Reaction 6). However, from both a thermodynamic and kinetic perspective, this couple with the assistance of the enzyme cholesterol oxidase must be able to accept electrons from cholesterol and relay them to the electroactive couple (Ox2 /Red2). Specific examples of this chemistry include

EXAMPLE 1 ##STR4## Scheme II is beneficial when the rate of reaction of cholesterol with the electroactive oxidant as in Scheme I is so slow that it precludes its use in a practical sensor. As mentioned above, Scheme II is also beneficial when the electron mediator itself (Ox1 /Red1) is either not electroactive or exhibits poor electrochemistry under conditions of the enzyme chemistry. It is under these conditions that Scheme II is particularly applicable. Other electron mediators (Ox1 /Red1) between cholesterol and ferricyanide for use in Scheme II may be possible including phenazine ethosulfate, phenazine methosulfate, tetramethylbenzidine, derivatives of benzoquinone, naphthoquinone and naphthoquinone derivatives, anthraquinone and anthraquinone derivatives, catechol, phenylenediamine, . .tetramethylphenenediamine.!. .Iadd.tetramethylphenylenediamine.Iaddend., and other derivatives of phenylenediamine.

Furthermore, while it is understood that the oxidized form of the electron relay accepts electrons from cholesterol, in the sensor either the oxidized or the reduced form of the mediator may be incorporated provided it reacts rapidly with both cholesterol and ferricyanide. If the reduced form is sufficiently stable and the oxidized form is not, then reductant, may be incorporated into the sensor in relatively small quantity (in comparison with the analyte to be determined) and still provide the electron relay. However, this causes a corresponding background signal that must be accounted for. The reductant, must also be isolated from ferricyanide in the sensor by incorporation into a separate reagent layer.

Several formulations of the above chemistries encompassing both Schemes I and II have been prepare as dry films on membranes. These membranes are positioned in the sensor which can then be used for the determination of cholesterol. A preferred formulation of the reagents involving Scheme II consists of the following

Cholesterol Esterase @400 Units/mL

Cholesterol Oxidase from Streptomyces @200 Units/mL

0.05 molar Potassium Ferricyanide

0.5 molar Potassium Chloride

0.2 molar Phosphate, pH 6.9

3 g/dL CHAPSO

2 g/dL gelatin

and 0.0001 molar hydroquinone (in the spreading or wicking layer).

The concentractions provided are . .that.!. .Iadd.those .Iaddend.of the solutions which are coated onto porous supports, filter paper or membranes; . .these.!. .Iadd.those .Iaddend.concentrations are reestablished when the membrane imbibes the serum or whole blood specimen. For cholesterol determinations large pore sizes in the filter support are .Iadd.more .Iaddend.necessary than that used for glucose. This is because the cholesterol resides in the serum in large lipoproteins (chylomicrons. ...!. .Iadd., .Iaddend.LDL, VLDL, and HDL) which must penetrate the various layers of the sensor until they reach the reagents. The surfactants to the major extent break these natural micelles up into smaller micelles providing a greater total surface . .are.!. .Iadd.area .Iaddend.on which the enzymes catalyze the reaction. Due to the instability of benzoquinone.Iadd., .Iaddend.a small quantity of hydroquinone, which is more stable by nature of its lower vapor pressure, is incorporated into the sensor to assist electron mediation between cholesterol and ferricyanide. Upon introduction of the serum specimen into the sensor.Iadd., .Iaddend.the hydroquinone is oxidized to benzoquinone; the benzoquinone is then free to pick up electrons from the substrate and cycle them to ferricyanide. Under these conditions the rate of the reaction of cholesterol with a small quantity of benzoquinone is more rapid than that with a large excess of ferricyanide.

An alternate and preferred formulation of reagents utilizing Scheme II that may be incorporated into the reagent layer of the sensor is:

Cholesterol Oxidase from Streptomyces @200 Units/mL

Lipase from Candida @500 Units/mL

3 g/dL CHAPSO

0.2 molar TRIS, pH 7.5

0.05 molar Potassium Ferricyanide

0.5 molar Potassium Chloride

0.05 molar MgCl2

2 g/dL gelatin

and 0.001 molar hydroquinone (in the spreading layer).

The magnesium salt in this formulation increases stability of the esterase enzyme in the phosphate-free reagent layer; Lipase assists the break up of the lipoproteins. With these dry reagent layers incorporated into the sensor and using the evaluation methodology as described, the following results were obtained.

______________________________________Serum Cholesterol, mg %            Average Current, uA______________________________________91               19.3182              27.2309              38.5______________________________________

These results demonstrate the quantitative response of the sensor to serum cholesterol levels.

Alternate and preferred embodiment of the sensor utilizing Scheme I is provided by reagent compositions:

Cholesterol Esterase @400 Units/mL

Cholesterol Oxidase from Nocardia @200 Units/mL

1 g/dL Triton X-100

0.1 molar TRIS buffer, pH 8.6

0.2 molar Potassium Ferricyanide

0.5 molar Potassium Chloride

0.02 molar MgCl2

2 g/dL gelatin

OR

Cholesterol Esterase @200 Units/mL

Cholesterol Oxidase from Streptomyces @200 Units/mL

0.06 molar Sodium deoxycholate

0.1 molar TRIS buffer, pH 8.6

0.2 molar Potassium Ferricyanide

0.5 molar Potassium Chloride

2 g/dL gelatin.

Thus, while we have illustrated and described the preferred embodiment of my invention, it is to be understood that this invention is capable of variation and modification, and we therefore do not wish or intend to be limited to the precise terms set forth, but desire and intend to avail ourselves of such changes and alterations which may be made for adapting the invention of the present invention to various usages and conditions. Accordingly, such changes and alterations are properly intended to be within the full range of equivalents, and therefore within the purview, of the following claims. The terms and expressions which have been employed in the foregoing specifications are used therein as terms of description and not of limitation, and thus there is no intention, in the use of such terms and expressions, of excluding equivalents of the features shown and described or portions thereof, it being recognized that the scope of the invention is defined and limited only by the claims which follow.

Having thus described our invention and the manner and process of making and using it in such full, clear, concise, and exact terms so as to enable any person skilled in the art to which it pertains, or to with which it is most nearly connected, to make and use the same.

Claims (15)

We claim:
1. A method of measuring the amount of a selected compound in body fluids comprising,
a) providing a measuring cell having at least a first and second electrode and said cell containing an oxidant and a buffer,
b) placing a sample of fluid to be tested in said cell,
c) reconstituting said oxidant and buffer with said sample fluid to generate a predetermined reaction,
d) allowing said reaction to proceed substantially to completion,
e) applying a potential across said electrodes and sample, and
f) measuring the resulting Cottrell current to determine the concentration of said selected compound present in said sample.
2. A method as set forth in claim 1, wherein the compound is selected from the group consisting of glucose, cholesterol, TSH, T4, hormones, antiarrhythmics, antiepileptics and nontherapeutic drugs.
3. A method as set forth in claim 1, wherein the oxidant is a material selected from the group consisting of benzoquinone, ferricyanide, ferricinium, .Iadd.orthophenanthroline .Iaddend.and Cobalt (III) dipyridyl.
4. The method as set forth in claim 1 including providing
as said first electrode a working electrode and as said second electrode a reference electrode.
5. The method of claim 1 including also providing in said cell . .and.!. .Iadd.an .Iaddend.enzyme as a catalyst and said enzyme is an oxidoreductase.
6. The method of claim 1 including selecting said buffer from the group consisting of phosphate, TRIS, MOPS, MES, HEPES, Tricine, Bicine, ACES, CAPS and TAPS. . .7. A method for measuring the amount of glucose in blood, comprising
a) providing a measuring cell having at least a first and second electrode and said cell containing an oxidant, a buffer and an enzyme,
b) placing a blood sample to be tested in said cell,
c) reconstituting said oxidant, buffer and enzyme with said blood sample to generate a predetermined reaction,
d) essentially immediately applying a potential across said electrodes and blood sample, and
e) measuring the resultant Cottrell current when the reaction has proceeded to completion to determine the concentration of said glucose present in
blood sample..!.. .8. The method of claim 7 including selecting said oxidant from the group consisting of benzoquinone, ferricyanide, ferricinium, Cobalt (III) orthophenantroline, and Cobalt (III) dipyridyl..!.. .9. The method of claim 7 including providing as said first electrode a working electrode and said second electrode a reference electrode..!.. .10. The method of claim 7 including adding as said enzyme,
glucose oxydase..!.11. The method of claim 1 wherein .Iadd.the sample of fluid is blood and .Iaddend.in step b) said placing of the blood sample to be tested in the cell generates a current and initiates a timing sequence, and wherein the reaction of step d) is allowed to proceed with an open circuit between said first and second . .electrode.!. .Iadd.electrodes.Iaddend.. .Iadd.12. A method of measuring the amount of an analyte in a blood sample, comprising:
a) adding the blood sample to an electrochemical cell that includes an electron transfer agent that will react in a reaction involving the analyte, thereby forming a detectable species;
b) incubating the reaction involving analyte and electron transfer agent in an open circuit until the reaction has substantially completed;
c) applying a sufficient potential difference between the electrodes of the electrochemical cell, after the incubation step, to readily transfer at least one electron between the detectable species and one of the electrodes, thereby resulting in a Cottrell current;
d) measuring the Cottrell current; and
e) correlating the measured Cottrell current to the amount of analyte in
the blood sample..Iaddend..Iadd.13. The method of claim 12, wherein adding the blood sample to the electrochemical cell causes a sudden charging current, which automatically initiates incubation step b) performed under open circuit..Iaddend..Iadd.14. The method of claim 13, wherein the Cottrell current is measured at a preset time following the incubation step..Iaddend..Iadd.15. The method of claim 12, wherein the electrochemical cell further includes a catalyst in sufficient amount to catalyze the reaction involving the analyte and the electron transfer agent..Iaddend..Iadd.16. The method of claim 15, wherein the catalyst is an enzyme..Iaddend..Iadd.17. The method of claim 16, wherein the analyte is glucose and the enzyme is glucose oxidase..Iaddend..Iadd.18. The method of claim 12, wherein the electron transfer agent is included in a reagent layer that is coated directly onto the electrochemical cell or is incorporated into a supporting matrix that is placed into the electrochemical cell..Iaddend..Iadd.19. The method of claim 18, wherein the supporting matrix is filter paper, membrane filter, woven fabric, or nonwoven fabric..Iaddend..Iadd.20. The method of claim 18, wherein the reagent layer further includes a binder..Iaddend..Iadd.21. The method of claim 20, wherein the binder is gelatin, carrageenan, methylcellulose, polyvinyl alcohol, or polyvinylpyrrolidone..Iaddend..Iadd.22. The method of claim 21, wherein a dispersing, spreading, or wicking layer overlays the reagent layer..Iaddend..Iadd.23. The method of claim 18, wherein adding the blood sample to the electrochemical cell causes a sudden charging current, which automatically initiates incubation step b) performed under open circuit..Iaddend..Iadd.24. The method of claim 23, wherein the Cottrell current is measured at a preset time following the incubation step..Iaddend..Iadd.25. The method of claim 24, wherein the reagent layer further includes an enzyme catalyst in sufficient amount to catalyze the reaction involving the analyte and the electron transfer
agent..Iaddend..Iadd.26. The method of claim 25, wherein the analyte is glucose in a concentration from about 1 milligram glucose per deciliter of blood sample to about 1000 milligrams glucose per deciliter of blood sample, and the fluid sample is blood..Iaddend..Iadd.27. The method of claim 26, wherein the electron transfer agent is ferricyanide, ferricinium, cobalt (III) orthophenanthroline, cobalt (III) dipyridyl, or benzoquinone..Iaddend..Iadd.28. The method of claim 12, wherein the analyte is glucose, TSH, T4, a hormone, a cardiac glycoside, an antiarrhythmic, an antiepileptic, an antibiotic, cholesterol, or a non-therapeutic drug..Iaddend..Iadd.29. The method of claim 25, wherein the analyte is glucose in a concentration from about 1 milligram glucose per deciliter of blood sample to about 1000 milligrams glucose per deciliter of blood sample, the incubation period is from about 15 seconds to about 160 seconds, and current measurements are made in the range from about 2 seconds to about 30 seconds following the incubation step..Iaddend..Iadd.30. A method of measuring the amount of an analyte in a blood sample, comprising:
a) adding the blood sample to an electrochemical cell that includes
an electron transfer agent,
a first catalyst in sufficient amount to catalyze a first reaction involving the analyte, and
a second catalyst in sufficient amount to catalyze a second reaction involving a product of the first reaction and the electron transfer agent, thereby forming a detectable species;
b) incubating the first and second reactions in an open circuit until the reactions have substantially completed;
c) applying a sufficient potential difference between electrodes of the electrochemical cell, after the incubation step, to readily transfer at least one electron between the detectable species and one of the electrodes, thereby resulting in a Cottrell current;
d) measuring the Cottrell current; and
e) correlating the measured Cottrell current to the amount of analyte in
the blood sample..Iaddend..Iadd.31. The method of claim 30, wherein adding the blood sample to the electrochemical cell causes a sudden charging current, which automatically initiates incubation step b) performed under open circuit..Iaddend..Iadd.32. The method of claim 31, wherein the Cottrell current is measured at a preset time following the incubation step..Iaddend..Iadd.33. A method of measuring the amount of cholesterol in a blood sample, comprising:
a) adding the blood sample to an electrochemical cell that includes
an electron transfer agent,
cholesterol esterase in sufficient amount to catalyze the hydrolysis of cholesterol esters in the blood sample, thereby forming cholesterol,
cholesterol oxidase in sufficient amount to catalyze a reaction involving cholesterol and the electron transfer agent, thereby forming a detectable species;
b) incubating the reactions of step a) in an open circuit until those reactions have substantially completed;
c) applying a sufficient potential difference between electrodes of the electrochemical cell, after the incubation step, to readily transfer at least one electron between the detectable species and one of the electrodes, thereby resulting in a Cottrell current;
d) measuring the Cottrell current; and
e) correlating the measured Cottrell current to the amount of cholesterol in the blood sample..Iaddend..Iadd.34. The method of claim 33, wherein adding the blood sample to the electrochemical cell causes a sudden charging current, which automatically initiates incubation step b) performed under open circuit..Iaddend..Iadd.35. The method of claim 34, wherein the Cottrell current is measured at a preset time following the incubation step..Iaddend..Iadd.36. The method of claim 35, wherein the electron transfer agent is ferricyanide or
benzoquinone..Iaddend..Iadd. A method of measuring the amount of an analyte in a blood sample, comprising:
a) adding the blood sample to an electrochemical cell that includes
first and second electron transfer agents,
a first catalyst in sufficient amount to catalyze a first reaction involving the analyte,
a second catalyst in sufficient amount to catalyze a second reaction involving a product of the first reaction and the first electron transfer agent, thereby forming an intermediate species that reacts with the second electron transfer agent, thereby forming a detectable species;
b) incubating the reactions of step a) in an open circuit until those reactions have substantially completed;
c) applying a sufficient potential difference between electrodes of the electrochemical cell, after the incubation step, to readily transfer at least one electron between the detectable species and one of the electrodes, thereby resulting in a Cottrell current;
d) measuring the Cottrell current; and
e) correlating the measured Cottrell current to the amount of analyte in the blood sample..Iaddend..Iadd.38. A method of measuring the amount of cholesterol in a blood sample, comprising:
a) adding the blood sample to an electrochemical cell that includes
first and second electron transfer agents,
cholesterol esterase in sufficient amount to catalyze the hydrolysis of cholesterol esters in the blood sample, thereby forming cholesterol,
cholesterol oxidase in sufficient amount to catalyze a reaction involving cholesterol and the first electron transfer agent, thereby forming an intermediate species that reacts with the second electron transfer agent, thereby forming a detectable species;
b) incubating the reactions of step a) in an open circuit until those reactions have substantially completed;
c) applying a sufficient potential difference between the electrodes of the electrochemical cell, after the incubation step, to readily transfer at least one electron between the detectable species and one of the electrodes, thereby resulting in a Cottrell current;
d) measuring the Cottrell current; and
e) correlating the measured Cottrell current to the amount of cholesterol
in the blood sample..Iaddend..Iadd.39. The method of claim 38, wherein adding the blood sample to the electrochemical cell causes a sudden charging current, which automatically initiates incubation step b) performed under open circuit..Iaddend..Iadd.40. The method of claim 39, wherein the Cottrell current is measured at a preset time following the incubation step..Iaddend..Iadd.41. The method of claim 40, wherein the first electron transfer agent is benzoquinone, phenazine ethosulfate, phenazine methosulfate, tetramethylbenzidine, a derivative of benzoquinone, naphthoquinone, a derivative of naphthoquinone, anthraquinone, a derivative of anthraquinone, catechol, phenylenediamine, tetramethylphenylenediamine, or a derivative of phenylenediamine..Iaddend..Iadd.42. The method of claim 41, wherein the
second electron transfer agent is ferricyanide..Iaddend..Iadd.43. A method for measuring the amount of a selected compound in a blood sample, comprising:
providing a measuring cell having at least first and second electrodes for contact with the blood sample introduced into the cell,
applying a potential to the electrodes to detect the presence of the blood sample in the cell,
placing the blood sample into the cell,
removing the potential to the electrodes after the blood sample is detected in the cell,
selectively oxidizing the compound in the blood sample with an oxidized electron acceptor to produce an oxidized form of the selected compound and a reduced electron acceptor, and
re-applying a potential across the cell electrodes after the selective oxidation of the compound in the blood sample has substantially completed and measuring the resulting Cottrell current, said current being proportional to the concentration of the reduced electron acceptor and the selected compound in the blood sample..Iaddend..Iadd.44. The method of claim 43, wherein placing the fluid sample into the measuring cell causes a sudden charging current, which automatically initiates removal of the potential from the electrodes and performance of the selective oxidation of the selected compound under open circuit..Iaddend..Iadd.45. The method of claim 44, wherein the Cottrell current is measured at the preset time after re-application of a potential across the measuring cell electrodes..Iaddend..Iadd.46. The method of claim 47, wherein placing the volume of blood into the measuring cell causes a sudden charging current, which automatically initiates removal of the potential across the electrodes and performance of the oxidation of glucose in the blood under
open circuit..Iaddend..Iadd.47. A method for measuring the amount of glucose in blood, comprising:
providing a measuring cell with at least first and second electrodes for contact with blood introduced into the cell,
applying a potential across the electrodes,
placing a volume of blood into the cell,
removing the potential across the electrodes after the volume of blood is placed into the measuring cell,
oxidizing the glucose in the blood with an oxidized electron acceptor in the presence of glucose oxidase to produce gluconic acid and a reduced electron acceptor,
re-applying a potential across the measuring cell electrodes after the oxidation of glucose has substantially completed, and
measuring the Cottrell current through the cell, the Cottrell current being proportional to the glucose concentration in the blood..Iaddend..Iadd.48. The method of claim 46, wherein the Cottrell current is measured at a preset time after re-application of a potential across the measuring cell electrodes..Iaddend.
US08679312 1988-03-15 1996-07-12 Method and apparatus for amperometric diagnostic analysis Expired - Lifetime USRE36268E (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US16829588 true 1988-03-15 1988-03-15
US07322598 US5128015A (en) 1988-03-15 1989-03-13 Method and apparatus for amperometric diagnostic analysis
US07745544 US5108564A (en) 1988-03-15 1991-08-15 Method and apparatus for amperometric diagnostic analysis
US17686393 true 1993-12-30 1993-12-30
US08679312 USRE36268E (en) 1988-03-15 1996-07-12 Method and apparatus for amperometric diagnostic analysis

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US08679312 USRE36268E (en) 1988-03-15 1996-07-12 Method and apparatus for amperometric diagnostic analysis

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
US07745544 Reissue US5108564A (en) 1988-03-15 1991-08-15 Method and apparatus for amperometric diagnostic analysis
US17686393 Continuation 1993-12-30 1993-12-30

Publications (1)

Publication Number Publication Date
USRE36268E true USRE36268E (en) 1999-08-17

Family

ID=27496781

Family Applications (1)

Application Number Title Priority Date Filing Date
US08679312 Expired - Lifetime USRE36268E (en) 1988-03-15 1996-07-12 Method and apparatus for amperometric diagnostic analysis

Country Status (1)

Country Link
US (1) USRE36268E (en)

Cited By (100)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20010045355A1 (en) * 2000-03-09 2001-11-29 Clinical Analysis Corporation Medical diagnostic system
US6572745B2 (en) 2001-03-23 2003-06-03 Virotek, L.L.C. Electrochemical sensor and method thereof
US6576102B1 (en) 2001-03-23 2003-06-10 Virotek, L.L.C. Electrochemical sensor and method thereof
US20040079652A1 (en) * 2002-08-27 2004-04-29 Bayer Healthcare Llc Methods of determining glucose concentration in whole blood samples
US20040094432A1 (en) * 2002-04-25 2004-05-20 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US20040138588A1 (en) * 2002-11-06 2004-07-15 Saikley Charles R Automatic biological analyte testing meter with integrated lancing device and methods of use
US20040182703A1 (en) * 2002-04-25 2004-09-23 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US20040253367A1 (en) * 2003-06-12 2004-12-16 Wogoman Frank W. Sensor format and construction method for capillary-filled diagnostic sensors
US20050045476A1 (en) * 2002-04-25 2005-03-03 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US20050147811A1 (en) * 2002-12-17 2005-07-07 Richard Baron Adhesive articles which contain at least one hydrophilic or hydrophobic layer, method for making and uses for same
US20050164329A1 (en) * 2002-05-17 2005-07-28 Wallace-Davis Emma N.K. Analyte measurement
US20050194265A1 (en) * 2004-03-03 2005-09-08 Apex Biotechnology Corp. Method for reducing measuring bias in amperometric biosensors
US20060108218A1 (en) * 2001-03-05 2006-05-25 Clinical Analysis Corporation Test cell for use with medical diagnostic instrument
US20060148096A1 (en) * 2002-11-05 2006-07-06 Jina Arvind N Assay device, system and method
US7208071B2 (en) 2000-11-01 2007-04-24 Rosemount Analytical Inc. Amperometric sensor for low level dissolved oxygen with self-depleting sensor design
US20080112852A1 (en) * 2002-04-25 2008-05-15 Neel Gary T Test Strips and System for Measuring Analyte Levels in a Fluid Sample
US20090090623A1 (en) * 2007-05-21 2009-04-09 Delta Electronics, Inc. Biosensor having integrated heating element and electrode with metallic catalyst
US20090093735A1 (en) * 2006-03-29 2009-04-09 Stephan Korner Test unit and test system for analyzing body fluids
US20090145775A1 (en) * 2007-12-10 2009-06-11 Bayer Healthcare Llc Reagents and methods for detecting analytes
US7648468B2 (en) 2002-04-19 2010-01-19 Pelikon Technologies, Inc. Method and apparatus for penetrating tissue
US20100012049A1 (en) * 2006-04-12 2010-01-21 Jms Co., Ltd Cavitation heating system and method
US7666149B2 (en) 1997-12-04 2010-02-23 Peliken Technologies, Inc. Cassette of lancet cartridges for sampling blood
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7682318B2 (en) 2001-06-12 2010-03-23 Pelikan Technologies, Inc. Blood sampling apparatus and method
US7699791B2 (en) 2001-06-12 2010-04-20 Pelikan Technologies, Inc. Method and apparatus for improving success rate of blood yield from a fingerstick
US7708701B2 (en) 2002-04-19 2010-05-04 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device
US7717863B2 (en) 2002-04-19 2010-05-18 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7731729B2 (en) 2002-04-19 2010-06-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7749174B2 (en) 2001-06-12 2010-07-06 Pelikan Technologies, Inc. Method and apparatus for lancet launching device intergrated onto a blood-sampling cartridge
US7766846B2 (en) 2008-01-28 2010-08-03 Roche Diagnostics Operations, Inc. Rapid blood expression and sampling
EP2213231A1 (en) 2009-01-30 2010-08-04 Roche Diagnostics GmbH Integrated body fluid meter and lancing device
US7780631B2 (en) 1998-03-30 2010-08-24 Pelikan Technologies, Inc. Apparatus and method for penetration with shaft having a sensor for sensing penetration depth
US7822454B1 (en) 2005-01-03 2010-10-26 Pelikan Technologies, Inc. Fluid sampling device with improved analyte detecting member configuration
US7819822B2 (en) 2004-03-06 2010-10-26 Roche Diagnostics Operations, Inc. Body fluid sampling device
US7833171B2 (en) 2002-04-19 2010-11-16 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7850621B2 (en) 2003-06-06 2010-12-14 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US7850622B2 (en) 2001-06-12 2010-12-14 Pelikan Technologies, Inc. Tissue penetration device
US7862520B2 (en) 2002-04-19 2011-01-04 Pelikan Technologies, Inc. Body fluid sampling module with a continuous compression tissue interface surface
US7862696B2 (en) 2006-09-22 2011-01-04 Bayer Healthcare Llc Biosensor system having enhanced stability and hematocrit performance
WO2011000527A2 (en) 2009-06-29 2011-01-06 Roche Diagnostics Gmbh Modular diabetes management systems
US7874994B2 (en) 2002-04-19 2011-01-25 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7892183B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US7892185B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US7901365B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
WO2011029567A1 (en) 2009-09-09 2011-03-17 Roche Diagnostics Gmbh Storage containers for test elements
US7909778B2 (en) 2002-04-19 2011-03-22 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7909777B2 (en) 2002-04-19 2011-03-22 Pelikan Technologies, Inc Method and apparatus for penetrating tissue
US7914465B2 (en) 2002-04-19 2011-03-29 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
EP2339337A2 (en) 2009-12-23 2011-06-29 Roche Diagnostics GmbH System for reading analyte test elements and for other uses
US7976476B2 (en) 2002-04-19 2011-07-12 Pelikan Technologies, Inc. Device and method for variable speed lancet
US7988645B2 (en) 2001-06-12 2011-08-02 Pelikan Technologies, Inc. Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties
WO2011092010A1 (en) 2010-01-29 2011-08-04 Roche Diagnostics Gmbh Electrode arrangements for biosensors
US8000762B2 (en) 2004-03-06 2011-08-16 Roche Diagnostics Operations, Inc. Body fluid sampling device
US8007656B2 (en) 2003-10-24 2011-08-30 Bayer Healthcare Llc Enzymatic electrochemical biosensor
US8007446B2 (en) 2002-04-19 2011-08-30 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8026104B2 (en) 2006-10-24 2011-09-27 Bayer Healthcare Llc Transient decay amperometry
US8079960B2 (en) 2002-04-19 2011-12-20 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
WO2012072251A1 (en) 2010-12-02 2012-06-07 Roche Diagnostics Gmbh Test element ejection mechanism for a meter
US8197421B2 (en) 2002-04-19 2012-06-12 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
WO2012084194A1 (en) 2010-12-22 2012-06-28 Roche Diagnostics Gmbh Systems and methods to compensate for sources of error during electrochemical testing
US8221334B2 (en) 2002-04-19 2012-07-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8262614B2 (en) 2003-05-30 2012-09-11 Pelikan Technologies, Inc. Method and apparatus for fluid injection
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US8282576B2 (en) 2003-09-29 2012-10-09 Sanofi-Aventis Deutschland Gmbh Method and apparatus for an improved sample capture device
US8337421B2 (en) 2001-06-12 2012-12-25 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8360992B2 (en) 2002-04-19 2013-01-29 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8404100B2 (en) 2005-09-30 2013-03-26 Bayer Healthcare Llc Gated voltammetry
US8425757B2 (en) 2005-07-20 2013-04-23 Bayer Healthcare Llc Gated amperometry
US8435190B2 (en) 2002-04-19 2013-05-07 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
WO2013079177A1 (en) 2011-11-28 2013-06-06 Roche Diagnostics Gmbh Insert component for storage container for biosensor test elements
US8556829B2 (en) 2002-04-19 2013-10-15 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8574895B2 (en) 2002-12-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
US8641644B2 (en) 2000-11-21 2014-02-04 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US8652831B2 (en) 2004-12-30 2014-02-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte measurement test time
US8668656B2 (en) 2003-12-31 2014-03-11 Sanofi-Aventis Deutschland Gmbh Method and apparatus for improving fluidic flow and sample capture
US8696880B2 (en) 2004-02-06 2014-04-15 Bayer Healthcare Llc Oxidizable species as an internal reference for biosensors and method of use
US8702624B2 (en) 2006-09-29 2014-04-22 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US8721671B2 (en) 2001-06-12 2014-05-13 Sanofi-Aventis Deutschland Gmbh Electric lancet actuator
US8784335B2 (en) 2002-04-19 2014-07-22 Sanofi-Aventis Deutschland Gmbh Body fluid sampling device with a capacitive sensor
US8828203B2 (en) 2004-05-20 2014-09-09 Sanofi-Aventis Deutschland Gmbh Printable hydrogels for biosensors
WO2014140172A1 (en) 2013-03-15 2014-09-18 Roche Diagnostics Gmbh Methods of failsafing electrochemical measurements of an analyte as well as devices, apparatuses and systems incorporating the same
WO2014140177A2 (en) 2013-03-15 2014-09-18 Roche Diagnostics Gmbh Methods of detecting high antioxidant levels during electrochemical measurements and failsafing an analyte concentration therefrom as well as devices, apparatuses and systems incorporting the same
WO2014140164A1 (en) 2013-03-15 2014-09-18 Roche Diagnostics Gmbh Methods of using information from recovery pulses in electrochemical analyte measurements as well as devices, apparatuses and systems incorporating the same
US8965476B2 (en) 2010-04-16 2015-02-24 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
WO2014025415A3 (en) * 2012-08-08 2015-06-18 Scanadu Incorporated Quantitative colormetric analysis of biological analytes in an automatically calibrated environment
US9144401B2 (en) 2003-06-11 2015-09-29 Sanofi-Aventis Deutschland Gmbh Low pain penetrating member
US9226699B2 (en) 2002-04-19 2016-01-05 Sanofi-Aventis Deutschland Gmbh Body fluid sampling module with a continuous compression tissue interface surface
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US9285323B2 (en) 2012-08-08 2016-03-15 Scanadu Incorporated Quantifying color changes of chemical test pads induced concentrations of biological analytes under different lighting conditions
US9314194B2 (en) 2002-04-19 2016-04-19 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US9351680B2 (en) 2003-10-14 2016-05-31 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a variable user interface
US9375169B2 (en) 2009-01-30 2016-06-28 Sanofi-Aventis Deutschland Gmbh Cam drive for managing disposable penetrating member actions with a single motor and motor and control system
US9386944B2 (en) 2008-04-11 2016-07-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte detecting device
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US9528941B2 (en) 2012-08-08 2016-12-27 Scanadu Incorporated Method and apparatus for determining analyte concentration by quantifying and interpreting color information captured in a continuous or periodic manner
US9775553B2 (en) 2004-06-03 2017-10-03 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
US9795747B2 (en) 2010-06-02 2017-10-24 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US9820684B2 (en) 2004-06-03 2017-11-21 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
US9863811B2 (en) 2014-08-15 2018-01-09 Scanadu Incorporated Precision luxmeter methods for digital cameras to quantify colors in uncontrolled lighting environments

Citations (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3838033A (en) * 1971-09-09 1974-09-24 Hoffmann La Roche Enzyme electrode
US3925183A (en) * 1972-06-16 1975-12-09 Energetics Science Gas detecting and quantitative measuring device
US4005002A (en) * 1973-08-06 1977-01-25 Hoffmann-La Roche Inc. Apparatus for measuring substrate concentrations
US4169779A (en) * 1978-12-26 1979-10-02 Catalyst Research Corporation Electrochemical cell for the detection of hydrogen sulfide
JPS5510584A (en) * 1978-07-10 1980-01-25 Matsushita Electric Ind Co Ltd Enzyme electrode and its manufacture
US4217196A (en) * 1978-05-30 1980-08-12 Albert Huch Dish-electrode concentration meter with detachable transducer
US4224125A (en) * 1977-09-28 1980-09-23 Matsushita Electric Industrial Co., Ltd. Enzyme electrode
US4225410A (en) * 1978-12-04 1980-09-30 Technicon Instruments Corporation Integrated array of electrochemical sensors
US4321123A (en) * 1978-04-21 1982-03-23 Matsushita Electric Industrial Co., Ltd. Coenzyme immobilized electrode
JPS5798853A (en) * 1980-12-12 1982-06-19 Matsushita Electric Ind Co Ltd Enzyme electrode
US4392933A (en) * 1978-10-31 1983-07-12 Matsushita Electric Industrial Co., Ltd. Electrochemical measuring apparatus comprising enzyme electrode
US4407959A (en) * 1980-10-29 1983-10-04 Fuji Electric Co., Ltd. Blood sugar analyzing apparatus
US4420564A (en) * 1980-11-21 1983-12-13 Fuji Electric Company, Ltd. Blood sugar analyzer having fixed enzyme membrane sensor
US4431507A (en) * 1981-01-14 1984-02-14 Matsushita Electric Industrial Co., Ltd. Enzyme electrode
JPS59166852A (en) * 1983-03-11 1984-09-20 Matsushita Electric Ind Co Ltd Biosensor
EP0136362A1 (en) * 1983-03-11 1985-04-10 Matsushita Electric Industrial Co., Ltd. Biosensor
GB2154003A (en) * 1983-12-16 1985-08-29 Genetics Int Inc Diagnostic aid
JPS60173459A (en) * 1984-02-20 1985-09-06 Matsushita Electric Ind Co Ltd Biosensor
JPS60173457A (en) * 1984-02-20 1985-09-06 Matsushita Electric Ind Co Ltd Biosensor
JPS60173458A (en) * 1984-02-20 1985-09-06 Matsushita Electric Ind Co Ltd Biosensor
US4545382A (en) * 1981-10-23 1985-10-08 Genetics International, Inc. Sensor for components of a liquid mixture
JPS60211350A (en) * 1984-04-06 1985-10-23 Matsushita Electric Ind Co Ltd Biosensor
US4579643A (en) * 1983-11-18 1986-04-01 Ngk Insulators, Ltd. Electrochemical device
JPS6190050A (en) * 1984-10-09 1986-05-08 Matsushita Electric Ind Co Ltd Production of chip for biosensor
JPS6191558A (en) * 1984-10-12 1986-05-09 Matsushita Electric Ind Co Ltd Biosensor
WO1986004926A1 (en) * 1985-02-21 1986-08-28 Genetics International Inc. Assay for degradable substrates by electrochemical detection of redox species
JPS61294356A (en) * 1985-06-21 1986-12-25 Matsushita Electric Ind Co Ltd Biosensor
EP0206218A2 (en) * 1985-06-28 1986-12-30 Miles Inc. Electrode for electrochemical sensors
WO1986007632A1 (en) * 1985-06-21 1986-12-31 Matsushita Electric Industrial Co., Ltd. Biosensor and method of manufacturing same
US4654197A (en) * 1983-10-18 1987-03-31 Aktiebolaget Leo Cuvette for sampling and analysis
US4655901A (en) * 1983-08-09 1987-04-07 Ngk Insulators, Ltd. Oxygen sensor element
JPS62156553A (en) * 1985-12-27 1987-07-11 Daikin Ind Ltd Concentration measuring instrument
US4682602A (en) * 1981-05-07 1987-07-28 Ottosensor Corporation Probe for medical application
EP0230786A1 (en) * 1985-12-24 1987-08-05 MediSense, Inc. Assay for cholesterol and derivatives thereof
EP0241309A2 (en) * 1986-04-10 1987-10-14 MediSense, Inc. Measurement of electroactive species in solution
US4711245A (en) * 1983-05-05 1987-12-08 Genetics International, Inc. Sensor for components of a liquid mixture
JPS633249A (en) * 1986-06-23 1988-01-08 Matsushita Electric Ind Co Ltd Biosensor
EP0255291A1 (en) * 1986-07-23 1988-02-03 Unilever Plc Method and apparatus for electrochemical measurements
JPS6358149A (en) * 1986-08-28 1988-03-12 Matsushita Electric Ind Co Ltd Biosensor
JPS63128252A (en) * 1986-11-18 1988-05-31 Matsushita Electric Ind Co Ltd Biosensor
US4758323A (en) * 1983-05-05 1988-07-19 Genetics International, Inc. Assay systems using more than one enzyme
US4796014A (en) * 1987-03-24 1989-01-03 Chia Jack T Device for detecting urine in diapers
US4810633A (en) * 1984-06-04 1989-03-07 Miles Inc. Enzymatic ethanol test
US4820399A (en) * 1984-08-31 1989-04-11 Shimadzu Corporation Enzyme electrodes
US4820636A (en) * 1985-02-21 1989-04-11 Medisense, Inc. Electrochemical assay for cis-diols
US4830959A (en) * 1985-11-11 1989-05-16 Medisense, Inc. Electrochemical enzymic assay procedures
US4836904A (en) * 1985-03-28 1989-06-06 Medisense, Inc. Graphite electrode with modified surface
US4894137A (en) * 1986-09-12 1990-01-16 Omron Tateisi Electronics Co. Enzyme electrode
EP0170375B1 (en) * 1984-06-13 1990-05-16 Unilever Plc Devices for use in chemical test procedures
US4927516A (en) * 1986-06-27 1990-05-22 Terumo Kabushiki Kaisha Enzyme sensor
US4935105A (en) * 1987-02-24 1990-06-19 Imperial Chemical Industries Plc Methods of operating enzyme electrode sensors
US4935106A (en) * 1985-11-15 1990-06-19 Smithkline Diagnostics, Inc. Ion selective/enzymatic electrode medical analyzer device and method of use
US4948727A (en) * 1984-10-12 1990-08-14 Medisense, Inc. Chemical sensor
US4952300A (en) * 1987-03-19 1990-08-28 Howard Diamond Multiparameter analytical electrode structure and method of measurement
US4959305A (en) * 1986-06-18 1990-09-25 Miles Inc. Reversible immobilization of assay reagents in a multizone test device
US4970145A (en) * 1986-05-27 1990-11-13 Cambridge Life Sciences Plc Immobilized enzyme electrodes
US4995402A (en) * 1988-10-12 1991-02-26 Thorne, Smith, Astill Technologies, Inc. Medical droplet whole blood and like monitoring
US5030310A (en) * 1985-06-28 1991-07-09 Miles Inc. Electrode for electrochemical sensors
US5049487A (en) * 1986-08-13 1991-09-17 Lifescan, Inc. Automated initiation of timing of reflectance readings
US5140393A (en) * 1985-10-08 1992-08-18 Sharp Kabushiki Kaisha Sensor device
US5141868A (en) * 1984-06-13 1992-08-25 Internationale Octrooi Maatschappij "Octropa" Bv Device for use in chemical test procedures
US5171689A (en) * 1984-11-08 1992-12-15 Matsushita Electric Industrial Co., Ltd. Solid state bio-sensor
EP0786361A1 (en) * 1996-01-26 1997-07-30 COMPAGNIE GENERALE DES ETABLISSEMENTS MICHELIN-MICHELIN & CIE Method for processing signals in a tyre monitoring system of a running vehicle
EP0785901A1 (en) * 1994-10-14 1997-07-30 Ier Cartridge and roller for a consumable ribbon, receiving apparatus, and rotational roller coupling method
EP1251371A1 (en) * 2000-01-27 2002-10-23 IDEMITSU PETROCHEMICAL CO. Ltd. Light guide plates and process for producing the same
EP1279581A1 (en) * 2001-07-16 2003-01-29 Siemens Aktiengesellschaft External train length measuring device
EP1363621A1 (en) * 2000-11-30 2003-11-26 Teva Pharmaceutical Industries Ltd. Novel crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
JP5510584B2 (en) 2013-04-24 2014-06-04 富士通株式会社 Communication apparatus and communication system according to a multicarrier transmission scheme
JP5798853B2 (en) 2006-01-16 2015-10-21 セイコーインスツル株式会社 The method of manufacturing the near-field light generating element

Patent Citations (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3838033A (en) * 1971-09-09 1974-09-24 Hoffmann La Roche Enzyme electrode
US3925183A (en) * 1972-06-16 1975-12-09 Energetics Science Gas detecting and quantitative measuring device
US4005002A (en) * 1973-08-06 1977-01-25 Hoffmann-La Roche Inc. Apparatus for measuring substrate concentrations
US4224125A (en) * 1977-09-28 1980-09-23 Matsushita Electric Industrial Co., Ltd. Enzyme electrode
US4321123A (en) * 1978-04-21 1982-03-23 Matsushita Electric Industrial Co., Ltd. Coenzyme immobilized electrode
US4217196A (en) * 1978-05-30 1980-08-12 Albert Huch Dish-electrode concentration meter with detachable transducer
JPS5510584A (en) * 1978-07-10 1980-01-25 Matsushita Electric Ind Co Ltd Enzyme electrode and its manufacture
US4392933A (en) * 1978-10-31 1983-07-12 Matsushita Electric Industrial Co., Ltd. Electrochemical measuring apparatus comprising enzyme electrode
US4225410A (en) * 1978-12-04 1980-09-30 Technicon Instruments Corporation Integrated array of electrochemical sensors
US4169779A (en) * 1978-12-26 1979-10-02 Catalyst Research Corporation Electrochemical cell for the detection of hydrogen sulfide
US4407959A (en) * 1980-10-29 1983-10-04 Fuji Electric Co., Ltd. Blood sugar analyzing apparatus
US4420564A (en) * 1980-11-21 1983-12-13 Fuji Electric Company, Ltd. Blood sugar analyzer having fixed enzyme membrane sensor
JPS5798853A (en) * 1980-12-12 1982-06-19 Matsushita Electric Ind Co Ltd Enzyme electrode
US4431507A (en) * 1981-01-14 1984-02-14 Matsushita Electric Industrial Co., Ltd. Enzyme electrode
US4682602A (en) * 1981-05-07 1987-07-28 Ottosensor Corporation Probe for medical application
US4545382A (en) * 1981-10-23 1985-10-08 Genetics International, Inc. Sensor for components of a liquid mixture
EP0136362A1 (en) * 1983-03-11 1985-04-10 Matsushita Electric Industrial Co., Ltd. Biosensor
JPS59166852A (en) * 1983-03-11 1984-09-20 Matsushita Electric Ind Co Ltd Biosensor
US4758323A (en) * 1983-05-05 1988-07-19 Genetics International, Inc. Assay systems using more than one enzyme
US4711245A (en) * 1983-05-05 1987-12-08 Genetics International, Inc. Sensor for components of a liquid mixture
US4655901A (en) * 1983-08-09 1987-04-07 Ngk Insulators, Ltd. Oxygen sensor element
US4654197A (en) * 1983-10-18 1987-03-31 Aktiebolaget Leo Cuvette for sampling and analysis
US4579643A (en) * 1983-11-18 1986-04-01 Ngk Insulators, Ltd. Electrochemical device
GB2154003A (en) * 1983-12-16 1985-08-29 Genetics Int Inc Diagnostic aid
JPS60173457A (en) * 1984-02-20 1985-09-06 Matsushita Electric Ind Co Ltd Biosensor
JPS60173459A (en) * 1984-02-20 1985-09-06 Matsushita Electric Ind Co Ltd Biosensor
JPS60173458A (en) * 1984-02-20 1985-09-06 Matsushita Electric Ind Co Ltd Biosensor
JPS60211350A (en) * 1984-04-06 1985-10-23 Matsushita Electric Ind Co Ltd Biosensor
US4810633A (en) * 1984-06-04 1989-03-07 Miles Inc. Enzymatic ethanol test
US5141868A (en) * 1984-06-13 1992-08-25 Internationale Octrooi Maatschappij "Octropa" Bv Device for use in chemical test procedures
EP0170375B1 (en) * 1984-06-13 1990-05-16 Unilever Plc Devices for use in chemical test procedures
US4820399A (en) * 1984-08-31 1989-04-11 Shimadzu Corporation Enzyme electrodes
EP0177743B1 (en) * 1984-08-31 1991-11-06 Shimadzu Corporation Enzyme electrodes
JPS6190050A (en) * 1984-10-09 1986-05-08 Matsushita Electric Ind Co Ltd Production of chip for biosensor
US4948727A (en) * 1984-10-12 1990-08-14 Medisense, Inc. Chemical sensor
JPS6191558A (en) * 1984-10-12 1986-05-09 Matsushita Electric Ind Co Ltd Biosensor
US5171689A (en) * 1984-11-08 1992-12-15 Matsushita Electric Industrial Co., Ltd. Solid state bio-sensor
WO1986004926A1 (en) * 1985-02-21 1986-08-28 Genetics International Inc. Assay for degradable substrates by electrochemical detection of redox species
US4820636A (en) * 1985-02-21 1989-04-11 Medisense, Inc. Electrochemical assay for cis-diols
US4836904A (en) * 1985-03-28 1989-06-06 Medisense, Inc. Graphite electrode with modified surface
JPS61294356A (en) * 1985-06-21 1986-12-25 Matsushita Electric Ind Co Ltd Biosensor
EP0230472A1 (en) * 1985-06-21 1987-08-05 Matsushita Electric Industrial Co., Ltd. Biosensor and method of manufacturing same
WO1986007632A1 (en) * 1985-06-21 1986-12-31 Matsushita Electric Industrial Co., Ltd. Biosensor and method of manufacturing same
US4897173A (en) * 1985-06-21 1990-01-30 Matsushita Electric Industrial Co., Ltd. Biosensor and method for making the same
US4938860A (en) * 1985-06-28 1990-07-03 Miles Inc. Electrode for electrochemical sensors
EP0206218A2 (en) * 1985-06-28 1986-12-30 Miles Inc. Electrode for electrochemical sensors
US5030310A (en) * 1985-06-28 1991-07-09 Miles Inc. Electrode for electrochemical sensors
US5140393A (en) * 1985-10-08 1992-08-18 Sharp Kabushiki Kaisha Sensor device
US4830959A (en) * 1985-11-11 1989-05-16 Medisense, Inc. Electrochemical enzymic assay procedures
US4935106A (en) * 1985-11-15 1990-06-19 Smithkline Diagnostics, Inc. Ion selective/enzymatic electrode medical analyzer device and method of use
EP0230786A1 (en) * 1985-12-24 1987-08-05 MediSense, Inc. Assay for cholesterol and derivatives thereof
JPS62156553A (en) * 1985-12-27 1987-07-11 Daikin Ind Ltd Concentration measuring instrument
EP0241309A2 (en) * 1986-04-10 1987-10-14 MediSense, Inc. Measurement of electroactive species in solution
US4970145A (en) * 1986-05-27 1990-11-13 Cambridge Life Sciences Plc Immobilized enzyme electrodes
US4959305A (en) * 1986-06-18 1990-09-25 Miles Inc. Reversible immobilization of assay reagents in a multizone test device
JPS633249A (en) * 1986-06-23 1988-01-08 Matsushita Electric Ind Co Ltd Biosensor
US4927516A (en) * 1986-06-27 1990-05-22 Terumo Kabushiki Kaisha Enzyme sensor
EP0255291A1 (en) * 1986-07-23 1988-02-03 Unilever Plc Method and apparatus for electrochemical measurements
US5049487A (en) * 1986-08-13 1991-09-17 Lifescan, Inc. Automated initiation of timing of reflectance readings
JPS6358149A (en) * 1986-08-28 1988-03-12 Matsushita Electric Ind Co Ltd Biosensor
US4894137A (en) * 1986-09-12 1990-01-16 Omron Tateisi Electronics Co. Enzyme electrode
JPS63128252A (en) * 1986-11-18 1988-05-31 Matsushita Electric Ind Co Ltd Biosensor
US4935105A (en) * 1987-02-24 1990-06-19 Imperial Chemical Industries Plc Methods of operating enzyme electrode sensors
US4952300A (en) * 1987-03-19 1990-08-28 Howard Diamond Multiparameter analytical electrode structure and method of measurement
US4796014A (en) * 1987-03-24 1989-01-03 Chia Jack T Device for detecting urine in diapers
US4995402A (en) * 1988-10-12 1991-02-26 Thorne, Smith, Astill Technologies, Inc. Medical droplet whole blood and like monitoring
EP0785901A1 (en) * 1994-10-14 1997-07-30 Ier Cartridge and roller for a consumable ribbon, receiving apparatus, and rotational roller coupling method
EP0786361A1 (en) * 1996-01-26 1997-07-30 COMPAGNIE GENERALE DES ETABLISSEMENTS MICHELIN-MICHELIN & CIE Method for processing signals in a tyre monitoring system of a running vehicle
EP1251371A1 (en) * 2000-01-27 2002-10-23 IDEMITSU PETROCHEMICAL CO. Ltd. Light guide plates and process for producing the same
EP1363621A1 (en) * 2000-11-30 2003-11-26 Teva Pharmaceutical Industries Ltd. Novel crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms
EP1279581A1 (en) * 2001-07-16 2003-01-29 Siemens Aktiengesellschaft External train length measuring device
JP5798853B2 (en) 2006-01-16 2015-10-21 セイコーインスツル株式会社 The method of manufacturing the near-field light generating element
JP5510584B2 (en) 2013-04-24 2014-06-04 富士通株式会社 Communication apparatus and communication system according to a multicarrier transmission scheme

Non-Patent Citations (15)

* Cited by examiner, † Cited by third party
Title
Biochemica Information; pp. 18, 19, 27 and 28 (J. Keesey, ed., Boehringer Mannheim Biochemicals, 1987) no month available. *
Laboratory Techniques in Electroanalytical Chemistry; pp. 51 64 and 124 (Kissinger and Heineman, eds., 1984) no month available. *
Laboratory Techniques in Electroanalytical Chemistry; pp. 51-64 and 124 (Kissinger and Heineman, eds., 1984) no month available.
Myland, Janice C. and Oldham, Keith B.; "Membrane-Covered Oxygen Sensors: An Exact Treatment of the Switch-on Transient"; Aug. 1984; pp. 1815-1823; J. Electrochem. Soc.
Myland, Janice C. and Oldham, Keith B.; Membrane Covered Oxygen Sensors: An Exact Treatment of the Switch on Transient ; Aug. 1984; pp. 1815 1823; J. Electrochem. Soc. *
Talbott et al.; "A New Microchemical Approach to Amperometric Analysis", Feb. 1988, vol. 37, pp. 5-12, Microchemical Journal.
Talbott et al.; A New Microchemical Approach to Amperometric Analysis , Feb. 1988, vol. 37, pp. 5 12, Microchemical Journal. *
Talbott, Jonathan Lee; "Enzymatic Amperometry of Glucose"; 1988; Pennsylvania State University (Thesis for Doctor of Philosophy in Chemistry) no month available.
Talbott, Jonathan Lee; Enzymatic Amperometry of Glucose ; 1988; Pennsylvania State University (Thesis for Doctor of Philosophy in Chemistry) no month available. *
Tokuda, Koichi; "Measurement of Current--Potential Curves"; 1986; pp. 471-475; Denki Kagaku (English Translation Included) no month available.
Tokuda, Koichi; Measurement of Current Potential Curves ; 1986; pp. 471 475; Denki Kagaku (English Translation Included) no month available. *
Van Nostrand Reinhold Encyclopedia of Chemistry; pp. 149 150 (4th edition 1984) no month available. *
Van Nostrand Reinhold Encyclopedia of Chemistry; pp. 149-150 (4th edition 1984) no month available.
Williams et al.; "Electrochemical--Enzymatic Analysis of Blood Glucose and Lactate"; Jan. 1970; pp. 118-121; Analytical Chemistry.
Williams et al.; Electrochemical Enzymatic Analysis of Blood Glucose and Lactate ; Jan. 1970; pp. 118 121; Analytical Chemistry. *

Cited By (202)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7666149B2 (en) 1997-12-04 2010-02-23 Peliken Technologies, Inc. Cassette of lancet cartridges for sampling blood
US7780631B2 (en) 1998-03-30 2010-08-24 Pelikan Technologies, Inc. Apparatus and method for penetration with shaft having a sensor for sensing penetration depth
US8439872B2 (en) 1998-03-30 2013-05-14 Sanofi-Aventis Deutschland Gmbh Apparatus and method for penetration with shaft having a sensor for sensing penetration depth
US20010045355A1 (en) * 2000-03-09 2001-11-29 Clinical Analysis Corporation Medical diagnostic system
US7041206B2 (en) 2000-03-09 2006-05-09 Clinical Analysis Corporation Medical diagnostic system
US7208071B2 (en) 2000-11-01 2007-04-24 Rosemount Analytical Inc. Amperometric sensor for low level dissolved oxygen with self-depleting sensor design
US8641644B2 (en) 2000-11-21 2014-02-04 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US20060108218A1 (en) * 2001-03-05 2006-05-25 Clinical Analysis Corporation Test cell for use with medical diagnostic instrument
US20050067737A1 (en) * 2001-03-23 2005-03-31 Craig Rappin Method of making sensor
US6572745B2 (en) 2001-03-23 2003-06-03 Virotek, L.L.C. Electrochemical sensor and method thereof
US6576102B1 (en) 2001-03-23 2003-06-10 Virotek, L.L.C. Electrochemical sensor and method thereof
US7682318B2 (en) 2001-06-12 2010-03-23 Pelikan Technologies, Inc. Blood sampling apparatus and method
US8123700B2 (en) 2001-06-12 2012-02-28 Pelikan Technologies, Inc. Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge
US8016774B2 (en) 2001-06-12 2011-09-13 Pelikan Technologies, Inc. Tissue penetration device
US9694144B2 (en) 2001-06-12 2017-07-04 Sanofi-Aventis Deutschland Gmbh Sampling module device and method
US8337421B2 (en) 2001-06-12 2012-12-25 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8622930B2 (en) 2001-06-12 2014-01-07 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8282577B2 (en) 2001-06-12 2012-10-09 Sanofi-Aventis Deutschland Gmbh Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge
US7988645B2 (en) 2001-06-12 2011-08-02 Pelikan Technologies, Inc. Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties
US9802007B2 (en) 2001-06-12 2017-10-31 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US8360991B2 (en) 2001-06-12 2013-01-29 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8206319B2 (en) 2001-06-12 2012-06-26 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7981055B2 (en) 2001-06-12 2011-07-19 Pelikan Technologies, Inc. Tissue penetration device
US8641643B2 (en) 2001-06-12 2014-02-04 Sanofi-Aventis Deutschland Gmbh Sampling module device and method
US8206317B2 (en) 2001-06-12 2012-06-26 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8211037B2 (en) 2001-06-12 2012-07-03 Pelikan Technologies, Inc. Tissue penetration device
US7909775B2 (en) 2001-06-12 2011-03-22 Pelikan Technologies, Inc. Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8679033B2 (en) 2001-06-12 2014-03-25 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8721671B2 (en) 2001-06-12 2014-05-13 Sanofi-Aventis Deutschland Gmbh Electric lancet actuator
US9937298B2 (en) 2001-06-12 2018-04-10 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7850622B2 (en) 2001-06-12 2010-12-14 Pelikan Technologies, Inc. Tissue penetration device
US8216154B2 (en) 2001-06-12 2012-07-10 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8845550B2 (en) 2001-06-12 2014-09-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7749174B2 (en) 2001-06-12 2010-07-06 Pelikan Technologies, Inc. Method and apparatus for lancet launching device intergrated onto a blood-sampling cartridge
US8382683B2 (en) 2001-06-12 2013-02-26 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7699791B2 (en) 2001-06-12 2010-04-20 Pelikan Technologies, Inc. Method and apparatus for improving success rate of blood yield from a fingerstick
US9560993B2 (en) 2001-11-21 2017-02-07 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US8382682B2 (en) 2002-04-19 2013-02-26 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7708701B2 (en) 2002-04-19 2010-05-04 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device
US7713214B2 (en) 2002-04-19 2010-05-11 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with optical analyte sensing
US9089294B2 (en) 2002-04-19 2015-07-28 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US7731729B2 (en) 2002-04-19 2010-06-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9186468B2 (en) 2002-04-19 2015-11-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9072842B2 (en) 2002-04-19 2015-07-07 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8905945B2 (en) 2002-04-19 2014-12-09 Dominique M. Freeman Method and apparatus for penetrating tissue
US7648468B2 (en) 2002-04-19 2010-01-19 Pelikon Technologies, Inc. Method and apparatus for penetrating tissue
US9226699B2 (en) 2002-04-19 2016-01-05 Sanofi-Aventis Deutschland Gmbh Body fluid sampling module with a continuous compression tissue interface surface
US8845549B2 (en) 2002-04-19 2014-09-30 Sanofi-Aventis Deutschland Gmbh Method for penetrating tissue
US8430828B2 (en) 2002-04-19 2013-04-30 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a multi-use body fluid sampling device with sterility barrier release
US8808201B2 (en) 2002-04-19 2014-08-19 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for penetrating tissue
US7833171B2 (en) 2002-04-19 2010-11-16 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8784335B2 (en) 2002-04-19 2014-07-22 Sanofi-Aventis Deutschland Gmbh Body fluid sampling device with a capacitive sensor
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US7862520B2 (en) 2002-04-19 2011-01-04 Pelikan Technologies, Inc. Body fluid sampling module with a continuous compression tissue interface surface
US9314194B2 (en) 2002-04-19 2016-04-19 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8690796B2 (en) 2002-04-19 2014-04-08 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7875047B2 (en) 2002-04-19 2011-01-25 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with sterility barrier release
US7874994B2 (en) 2002-04-19 2011-01-25 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7892183B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US7892185B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US7901365B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9339612B2 (en) 2002-04-19 2016-05-17 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7909778B2 (en) 2002-04-19 2011-03-22 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7909777B2 (en) 2002-04-19 2011-03-22 Pelikan Technologies, Inc Method and apparatus for penetrating tissue
US8556829B2 (en) 2002-04-19 2013-10-15 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7914465B2 (en) 2002-04-19 2011-03-29 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7938787B2 (en) 2002-04-19 2011-05-10 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7717863B2 (en) 2002-04-19 2010-05-18 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9498160B2 (en) 2002-04-19 2016-11-22 Sanofi-Aventis Deutschland Gmbh Method for penetrating tissue
US7976476B2 (en) 2002-04-19 2011-07-12 Pelikan Technologies, Inc. Device and method for variable speed lancet
US7981056B2 (en) 2002-04-19 2011-07-19 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US8414503B2 (en) 2002-04-19 2013-04-09 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US7988644B2 (en) 2002-04-19 2011-08-02 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with sterility barrier release
US8636673B2 (en) 2002-04-19 2014-01-28 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8403864B2 (en) 2002-04-19 2013-03-26 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8579831B2 (en) 2002-04-19 2013-11-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8007446B2 (en) 2002-04-19 2011-08-30 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9724021B2 (en) 2002-04-19 2017-08-08 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8562545B2 (en) 2002-04-19 2013-10-22 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8062231B2 (en) 2002-04-19 2011-11-22 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8496601B2 (en) 2002-04-19 2013-07-30 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US8079960B2 (en) 2002-04-19 2011-12-20 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
US9795334B2 (en) 2002-04-19 2017-10-24 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8157748B2 (en) 2002-04-19 2012-04-17 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
US8491500B2 (en) 2002-04-19 2013-07-23 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US8360992B2 (en) 2002-04-19 2013-01-29 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8197423B2 (en) 2002-04-19 2012-06-12 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8197421B2 (en) 2002-04-19 2012-06-12 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8202231B2 (en) 2002-04-19 2012-06-19 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9839386B2 (en) 2002-04-19 2017-12-12 Sanofi-Aventis Deustschland Gmbh Body fluid sampling device with capacitive sensor
US8388551B2 (en) 2002-04-19 2013-03-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus for multi-use body fluid sampling device with sterility barrier release
US8435190B2 (en) 2002-04-19 2013-05-07 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8366637B2 (en) 2002-04-19 2013-02-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8372016B2 (en) 2002-04-19 2013-02-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling and analyte sensing
US9907502B2 (en) 2002-04-19 2018-03-06 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8235915B2 (en) 2002-04-19 2012-08-07 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8221334B2 (en) 2002-04-19 2012-07-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US20080112852A1 (en) * 2002-04-25 2008-05-15 Neel Gary T Test Strips and System for Measuring Analyte Levels in a Fluid Sample
US7160251B2 (en) 2002-04-25 2007-01-09 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US6964871B2 (en) 2002-04-25 2005-11-15 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US6959247B2 (en) 2002-04-25 2005-10-25 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US6953693B2 (en) 2002-04-25 2005-10-11 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US6946299B2 (en) 2002-04-25 2005-09-20 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US20050045476A1 (en) * 2002-04-25 2005-03-03 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US20040182703A1 (en) * 2002-04-25 2004-09-23 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US20040104131A1 (en) * 2002-04-25 2004-06-03 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US6743635B2 (en) 2002-04-25 2004-06-01 Home Diagnostics, Inc. System and methods for blood glucose sensing
US20040094432A1 (en) * 2002-04-25 2004-05-20 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US7819161B2 (en) 2002-04-25 2010-10-26 Nipro Diagnostics, Inc. Systems and methods for blood glucose sensing
US20070089987A1 (en) * 2002-04-25 2007-04-26 Home Diagnostics, Inc. Systems and methods for blood glucose sensing
US20050164329A1 (en) * 2002-05-17 2005-07-28 Wallace-Davis Emma N.K. Analyte measurement
US7534583B2 (en) 2002-05-17 2009-05-19 Oxford Biosencors Limited Analyte measurement
US20040079652A1 (en) * 2002-08-27 2004-04-29 Bayer Healthcare Llc Methods of determining glucose concentration in whole blood samples
US20100190268A1 (en) * 2002-11-05 2010-07-29 Abbott Diabetes Care Inc. Assay Device, System and Method
US20060148096A1 (en) * 2002-11-05 2006-07-06 Jina Arvind N Assay device, system and method
US7670853B2 (en) 2002-11-05 2010-03-02 Abbott Diabetes Care Inc. Assay device, system and method
US20040138588A1 (en) * 2002-11-06 2004-07-15 Saikley Charles R Automatic biological analyte testing meter with integrated lancing device and methods of use
US9060727B2 (en) 2002-11-06 2015-06-23 Abbott Diabetes Care Inc. Automatic biological analyte testing meter with integrated lancing device and methods of use
US7572237B2 (en) 2002-11-06 2009-08-11 Abbott Diabetes Care Inc. Automatic biological analyte testing meter with integrated lancing device and methods of use
US8079961B2 (en) 2002-11-06 2011-12-20 Abbott Diabetes Care Inc. Automatic biological analyte testing meter with integrated lancing device and methods of use
US20050147811A1 (en) * 2002-12-17 2005-07-07 Richard Baron Adhesive articles which contain at least one hydrophilic or hydrophobic layer, method for making and uses for same
US7175897B2 (en) 2002-12-17 2007-02-13 Avery Dennison Corporation Adhesive articles which contain at least one hydrophilic or hydrophobic layer, method for making and uses for same
US9034639B2 (en) 2002-12-30 2015-05-19 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
US8574895B2 (en) 2002-12-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
US8262614B2 (en) 2003-05-30 2012-09-11 Pelikan Technologies, Inc. Method and apparatus for fluid injection
US8251921B2 (en) 2003-06-06 2012-08-28 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling and analyte sensing
US7850621B2 (en) 2003-06-06 2010-12-14 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US9144401B2 (en) 2003-06-11 2015-09-29 Sanofi-Aventis Deutschland Gmbh Low pain penetrating member
US7544277B2 (en) * 2003-06-12 2009-06-09 Bayer Healthcare, Llc Electrochemical test sensors
US20040253367A1 (en) * 2003-06-12 2004-12-16 Wogoman Frank W. Sensor format and construction method for capillary-filled diagnostic sensors
US8282576B2 (en) 2003-09-29 2012-10-09 Sanofi-Aventis Deutschland Gmbh Method and apparatus for an improved sample capture device
US8945910B2 (en) 2003-09-29 2015-02-03 Sanofi-Aventis Deutschland Gmbh Method and apparatus for an improved sample capture device
US9351680B2 (en) 2003-10-14 2016-05-31 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a variable user interface
US9803228B2 (en) 2003-10-24 2017-10-31 Ascensia Diabetes Care Holdings Ag Electrochemical sensor strip
US8007656B2 (en) 2003-10-24 2011-08-30 Bayer Healthcare Llc Enzymatic electrochemical biosensor
US8691073B2 (en) 2003-10-24 2014-04-08 Bayer Healthcare Llc Enzymatic electrochemical biosensor
US9157111B2 (en) 2003-10-24 2015-10-13 Bayer Healthcare Llc Method of making an electrochemical sensor strip
US8296918B2 (en) 2003-12-31 2012-10-30 Sanofi-Aventis Deutschland Gmbh Method of manufacturing a fluid sampling device with improved analyte detecting member configuration
US9561000B2 (en) 2003-12-31 2017-02-07 Sanofi-Aventis Deutschland Gmbh Method and apparatus for improving fluidic flow and sample capture
US8668656B2 (en) 2003-12-31 2014-03-11 Sanofi-Aventis Deutschland Gmbh Method and apparatus for improving fluidic flow and sample capture
US8696880B2 (en) 2004-02-06 2014-04-15 Bayer Healthcare Llc Oxidizable species as an internal reference for biosensors and method of use
US9410917B2 (en) 2004-02-06 2016-08-09 Ascensia Diabetes Care Holdings Ag Method of using a biosensor
US20050194265A1 (en) * 2004-03-03 2005-09-08 Apex Biotechnology Corp. Method for reducing measuring bias in amperometric biosensors
EP2727531A2 (en) 2004-03-06 2014-05-07 Roche Diagnostics GmbH Body fluid sampling device
US8369918B2 (en) 2004-03-06 2013-02-05 Roche Diagnostics Operations, Inc. Body fluid sampling device
US7819822B2 (en) 2004-03-06 2010-10-26 Roche Diagnostics Operations, Inc. Body fluid sampling device
US8814808B2 (en) 2004-03-06 2014-08-26 Roche Diagnostics Operations, Inc. Body fluid sampling device
US9022952B2 (en) 2004-03-06 2015-05-05 Roche Diagnostics Operations, Inc. Body fluid sampling device
US8000762B2 (en) 2004-03-06 2011-08-16 Roche Diagnostics Operations, Inc. Body fluid sampling device
EP2705792A1 (en) 2004-03-06 2014-03-12 F. Hoffmann-La Roche AG Body fluid sampling device
US8162854B2 (en) 2004-03-06 2012-04-24 Roche Diagnostics Operations, Inc. Body fluid sampling device
US9261476B2 (en) 2004-05-20 2016-02-16 Sanofi Sa Printable hydrogel for biosensors
US8828203B2 (en) 2004-05-20 2014-09-09 Sanofi-Aventis Deutschland Gmbh Printable hydrogels for biosensors
US9820684B2 (en) 2004-06-03 2017-11-21 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
US9775553B2 (en) 2004-06-03 2017-10-03 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
US8652831B2 (en) 2004-12-30 2014-02-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte measurement test time
US7822454B1 (en) 2005-01-03 2010-10-26 Pelikan Technologies, Inc. Fluid sampling device with improved analyte detecting member configuration
US8425757B2 (en) 2005-07-20 2013-04-23 Bayer Healthcare Llc Gated amperometry
US8877035B2 (en) 2005-07-20 2014-11-04 Bayer Healthcare Llc Gated amperometry methods
US8647489B2 (en) 2005-09-30 2014-02-11 Bayer Healthcare Llc Gated voltammetry devices
US8404100B2 (en) 2005-09-30 2013-03-26 Bayer Healthcare Llc Gated voltammetry
US9835582B2 (en) 2005-09-30 2017-12-05 Ascensia Diabetes Care Holdings Ag Devices using gated voltammetry methods
US9110013B2 (en) 2005-09-30 2015-08-18 Bayer Healthcare Llc Gated voltammetry methods
US20090093735A1 (en) * 2006-03-29 2009-04-09 Stephan Korner Test unit and test system for analyzing body fluids
US20100012049A1 (en) * 2006-04-12 2010-01-21 Jms Co., Ltd Cavitation heating system and method
US8728299B2 (en) 2006-09-22 2014-05-20 Bayer Healthcare Llc Biosensor performance increasing methods having enhanced stability and hematocrit performance
US8702965B2 (en) 2006-09-22 2014-04-22 Bayer Healthcare Llc Biosensor methods having enhanced stability and hematocrit performance
US9459229B2 (en) 2006-09-22 2016-10-04 Ascenia Diabetes Care Holdings AG Electrochemical test sensor
US9239312B2 (en) 2006-09-22 2016-01-19 Bayer Healthcare Llc Methods of determining analyte concentration having enhanced stability and hematocrit performance
US20110115504A1 (en) * 2006-09-22 2011-05-19 Bayer Healthcare Llc Biosensor Methods Having Enhanced Stability and Hematocrit Performance
US7862696B2 (en) 2006-09-22 2011-01-04 Bayer Healthcare Llc Biosensor system having enhanced stability and hematocrit performance
US8702624B2 (en) 2006-09-29 2014-04-22 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US9005527B2 (en) 2006-10-24 2015-04-14 Bayer Healthcare Llc Transient decay amperometry biosensors
US8026104B2 (en) 2006-10-24 2011-09-27 Bayer Healthcare Llc Transient decay amperometry
US8470604B2 (en) 2006-10-24 2013-06-25 Bayer Healthcare Llc Transient decay amperometry
US20090090623A1 (en) * 2007-05-21 2009-04-09 Delta Electronics, Inc. Biosensor having integrated heating element and electrode with metallic catalyst
US20090145775A1 (en) * 2007-12-10 2009-06-11 Bayer Healthcare Llc Reagents and methods for detecting analytes
US7766846B2 (en) 2008-01-28 2010-08-03 Roche Diagnostics Operations, Inc. Rapid blood expression and sampling
US9386944B2 (en) 2008-04-11 2016-07-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte detecting device
US9375169B2 (en) 2009-01-30 2016-06-28 Sanofi-Aventis Deutschland Gmbh Cam drive for managing disposable penetrating member actions with a single motor and motor and control system
EP2213231A1 (en) 2009-01-30 2010-08-04 Roche Diagnostics GmbH Integrated body fluid meter and lancing device
WO2011000527A2 (en) 2009-06-29 2011-01-06 Roche Diagnostics Gmbh Modular diabetes management systems
WO2011029567A1 (en) 2009-09-09 2011-03-17 Roche Diagnostics Gmbh Storage containers for test elements
EP2339337A2 (en) 2009-12-23 2011-06-29 Roche Diagnostics GmbH System for reading analyte test elements and for other uses
WO2011092010A1 (en) 2010-01-29 2011-08-04 Roche Diagnostics Gmbh Electrode arrangements for biosensors
US8965476B2 (en) 2010-04-16 2015-02-24 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US9795747B2 (en) 2010-06-02 2017-10-24 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
WO2012072251A1 (en) 2010-12-02 2012-06-07 Roche Diagnostics Gmbh Test element ejection mechanism for a meter
WO2012084194A1 (en) 2010-12-22 2012-06-28 Roche Diagnostics Gmbh Systems and methods to compensate for sources of error during electrochemical testing
WO2013079177A1 (en) 2011-11-28 2013-06-06 Roche Diagnostics Gmbh Insert component for storage container for biosensor test elements
WO2014025415A3 (en) * 2012-08-08 2015-06-18 Scanadu Incorporated Quantitative colormetric analysis of biological analytes in an automatically calibrated environment
US9528941B2 (en) 2012-08-08 2016-12-27 Scanadu Incorporated Method and apparatus for determining analyte concentration by quantifying and interpreting color information captured in a continuous or periodic manner
US9311520B2 (en) 2012-08-08 2016-04-12 Scanadu Incorporated Method and apparatus for performing and quantifying color changes induced by specific concentrations of biological analytes in an automatically calibrated environment
US9285323B2 (en) 2012-08-08 2016-03-15 Scanadu Incorporated Quantifying color changes of chemical test pads induced concentrations of biological analytes under different lighting conditions
WO2014140172A1 (en) 2013-03-15 2014-09-18 Roche Diagnostics Gmbh Methods of failsafing electrochemical measurements of an analyte as well as devices, apparatuses and systems incorporating the same
WO2014140177A2 (en) 2013-03-15 2014-09-18 Roche Diagnostics Gmbh Methods of detecting high antioxidant levels during electrochemical measurements and failsafing an analyte concentration therefrom as well as devices, apparatuses and systems incorporting the same
WO2014140164A1 (en) 2013-03-15 2014-09-18 Roche Diagnostics Gmbh Methods of using information from recovery pulses in electrochemical analyte measurements as well as devices, apparatuses and systems incorporating the same
US9863811B2 (en) 2014-08-15 2018-01-09 Scanadu Incorporated Precision luxmeter methods for digital cameras to quantify colors in uncontrolled lighting environments

Similar Documents

Publication Publication Date Title
US7604722B2 (en) Electrochemical cell
US7276146B2 (en) Electrodes, methods, apparatuses comprising micro-electrode arrays
Hönes et al. The technology behind glucose meters: test strips
EP0537761B1 (en) A biosensor and a method for measuring a concentration of a substrate in a sample
Sprules et al. Evaluation of a new disposable screen‐printed sensor strip for the measurement of NADH and its modification to produce a lactate biosensor employing microliter volumes
US7498132B2 (en) Electrochemical test strip kit for analyte determination
US7276147B2 (en) Method for determining the concentration of an analyte in a liquid sample using small volume samples and fast test times
US6565738B1 (en) Diagnostic test for the measurement of analyte in abiological fluid
EP0255291B1 (en) Method and apparatus for electrochemical measurements
US6878251B2 (en) Heated electrochemical cell
US6878262B2 (en) Analytical element and measuring device and substrate quantification method using the same
US4356074A (en) Substrate specific galactose oxidase enzyme electrodes
US5695947A (en) Amperometric cholesterol biosensor
US6416641B1 (en) Biosensor
US6475360B1 (en) Heated electrochemical cell
US6210907B1 (en) Measuring device with electrodes fabricated on porous membrane substrate in whole
US6893552B1 (en) Microsensors for glucose and insulin monitoring
US20060231396A1 (en) Thin analyzing device
EP0795748B1 (en) Biosensor and method for quantitating biochemical substrate using the same
US6033866A (en) Highly sensitive amperometric bi-mediator-based glucose biosensor
US20050247562A1 (en) Determination method for automatically identifying analyte liquid and standard solution for biosensor
US6287451B1 (en) Disposable sensor and method of making
US20080173552A1 (en) Gated Amperometry
US20070193882A1 (en) Electrochemical test strip for multi-functional biosensor
US5066372A (en) Unitary multiple electrode sensor

Legal Events

Date Code Title Description
AS Assignment

Owner name: ROCHE DIAGNOSTICS CORPORATION, INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BOEHRINGER MANNHEIM CORPORATION;REEL/FRAME:009730/0414

Effective date: 19981211

FPAY Fee payment

Year of fee payment: 8

FPAY Fee payment

Year of fee payment: 12

AS Assignment

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC.,INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC.,INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS CORPORATION;REEL/FRAME:015215/0061

Effective date: 20040101

AS Assignment

Owner name: CORANGE INTERNATIONAL LIMITED (UNDIVIDED 1/2 INTER

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS OPERATIONS, INC.;REEL/FRAME:015756/0677

Effective date: 20040423

AS Assignment

Owner name: ROCHE OPERATIONS LTD., BERMUDA

Free format text: CHANGE OF NAME;ASSIGNOR:CORANGE INTERNATIONAL LIMITED;REEL/FRAME:022634/0371

Effective date: 20080715

Owner name: ROCHE OPERATIONS LTD., BERMUDA

Free format text: CHANGE OF NAME;ASSIGNOR:CORANGE INTERNATIONAL LIMITED;REEL/FRAME:022634/0371

Effective date: 20080715

Owner name: ROCHE OPERATIONS LTD., BERMUDA

Free format text: CHANGE OF NAME;ASSIGNOR:CORANGE INTERNATIONAL LIMITED;REEL/FRAME:022634/0371

Effective date: 20080715

Owner name: ROCHE OPERATIONS LTD., BERMUDA

Free format text: CHANGE OF NAME;ASSIGNOR:CORANGE INTERNATIONAL LIMITED;REEL/FRAME:022634/0371

Effective date: 20080715

Owner name: ROCHE OPERATIONS LTD.,BERMUDA

Free format text: CHANGE OF NAME;ASSIGNOR:CORANGE INTERNATIONAL LIMITED;REEL/FRAME:022634/0371

Effective date: 20080715

Owner name: ROCHE OPERATIONS LTD., BERMUDA

Free format text: CHANGE OF NAME;ASSIGNOR:CORANGE INTERNATIONAL LIMITED;REEL/FRAME:022634/0371

Effective date: 20080715

Owner name: ROCHE OPERATIONS LTD., BERMUDA

Free format text: CHANGE OF NAME;ASSIGNOR:CORANGE INTERNATIONAL LIMITED;REEL/FRAME:022634/0371

Effective date: 20080715

Owner name: ROCHE OPERATIONS LTD., BERMUDA

Free format text: CHANGE OF NAME;ASSIGNOR:CORANGE INTERNATIONAL LIMITED;REEL/FRAME:022634/0371

Effective date: 20080715

AS Assignment

Owner name: BOEHRINGER MANNHEIM CORPORATION,INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:TALL OAK VENTURES;REEL/FRAME:023892/0975

Effective date: 19921013

AS Assignment

Owner name: ROCHE DIABETES CARE, INC., INDIANA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS OPERATIONS, INC.;REEL/FRAME:036008/0670

Effective date: 20150302