WO2012060483A1

WO2012060483A1 - Biosensor strip and strip reader

Info

Publication number: WO2012060483A1
Application number: PCT/KR2010/007660
Authority: WO
Inventors: Jungsun Han; Gueisam Lim
Original assignee: Lg Electronics Inc.
Priority date: 2010-11-02
Filing date: 2010-11-02
Publication date: 2012-05-10

Abstract

Disclosed is a biosensor strip in accordance with one exemplary embodiment, the biosensor strip including a first membrane chemically reacting with a bio sample, a second membrane located below the first membrane and configured to generate an electric signal by a chemical reaction with the bio sample, electrodes configured to transfer the generated electric signal to a strip reader by coming in contact with the second membrane, and a separator interposed between the first membrane and the second membrane, and configured to control an amount of the bio sample flowing from the first membrane to the second membrane.

Description

BIOSENSOR STRIP AND STRIP READER

The present disclosure relates to an analysis strip for analyzing causes of diseases within body fluids for a diagnosis of patients, and a strip reader.

In general, diagnosis of a state of health for patients is achieved by a mechanism of analyzing a patient’s bio sample, for example, body fluids to measure an amount or concentration of a substance (hereinafter, referred to as an indicative substance (marker, indicator )) related to diseases existing within the body fluids or the state of the patient’s health such as pregnancy. Here, the measurement for the indicative substance is performed through a biochemical reaction, such as an oxidation-reduction reaction with respect to an indicator within body fluids taken from a patient. Hence, quantitative or qualitative analysis for an analysis substance existing within a bio sample is important both in a chemical aspect and in a clinical aspect. For instance, representative examples include measurement of a blood sugar level within blood for diabetic patients, measurement of cholesterol causing various adult diseases, and the like.

For such measurement or examination, reagents or equipment, for which professional knowledge is required, have been used. Accordingly, much expenses have been incurred and much time has been taken. Furthermore, the diagnosis has been made only by going to the hospital, which has resulted in a variety of restrictions to patients.

In recent time, a point-of-care test (POCT), which overcomes the drawbacks of the examinations is on the rise. The POCT is a test for diagnosing a patient within a short time by immediately taking and analyzing body fluids directly at a place where the patient is. The POCT is a simplified method, so it has various advantages, such as a patient’s self-diagnosis, reduction of additional expenses and time and the like. Consequently, the POCT is being widely used.

The POCT has been enabled by development of a biosensor. The biosensors may be divided into an electrochemical type, an optic (LED, PD) type or a fluorescent type.

In the meantime, an electrochemical biosensor using enzyme activities is used for measuring a specific substance present within a bio sample (hereinafter, referred to as ‘specimen’), for example, used in a clinical chemical test for measuring glucose, uric acid, protein, DNA and cyclose.

Among others, a biosensor for measuring a concentration of glucose within blood has been concerned the most by several hundreds of diabetic patients and patients having potential for suffering from diabetes.

In order to prevent diabetes and diabetic complications, a quantity of glucose within blood should be accurately measured and the concentration of glucose within blood should be controlled to be maintained at a constant level. Hence, there is a need of accurate, continuous, periodical measurement of blood sugar.

For the continuous, periodical measurement of blood sugar, it is needed to develop a measurement system, which satisfies some conditions, such as minimization of blood requirements for measurement, reduction of analysis time, simplification of measurement mechanism and the like, and is simplified in size and light in weight for high portability.

Consequently, demands on a strip type biosensor and a strip reader are increasing.

An electrochemical biosensor of various types of biosensors for measurement of blood sugar (or blood glucose) may be produced in a form of enzyme electrode, which includes oxidase having glucose as a matrix, for example, glucose oxidase, and an electron transfer mediator, which serves to transfer electrons generated by oxidation-reduction reaction between glucose and enzyme within blood to the electrode surface. Glucose oxidase, glucose dehydrogenase and the like are used as the oxidase. Ferrocene, ferrocene-derivative, potassium ferricyanide, quinone, quinone-derivative, metal-compound and the like are widely used as the electron transfer mediator.

The electron transfer mediator (reduction state) is diffused up to an electrode surface of a strip. Here, a current, which is generated by applying an oxidation potential of the electron transfer mediator in the reduction state at a surface of a working electrode, is measured so as to measure a concentration of blood sugar.

The electrochemical biosensor may reduce the influence of oxygen and be capable of using a sample without any pre-treatment even if the sample is opaque.

However, those strip type biosensors, which have been developed so far, can be used for only one kind of measurement. Hence, for performing various kinds of measurements, a user should be equipped with various types of strips, resulting in user’s inconvenience. Furthermore, upon preparing the various types of strips, it is difficult to discriminate each type of strip, thereby causing a user to be in trouble upon performing a measurement that the user wants.

Therefore, one exemplary embodiment of the present disclosure is to address the problems, and more particularly, to perform various types of measurements.

To achieve these and other advantages and in accordance with one exemplary embodiment, there is provided a biosensor strip, including a biosensor strip including a first membrane chemically reacting with a bio sample, a second membrane located below the first membrane and configured to generate an electric signal using a chemical reaction with the bio sample, electrodes by being in contact with the second membrane and configured to transfer the generated electric signal to a strip reader, and a separator interposed between the first membrane and the second membrane, and configured to control an amount of the bio sample flowing from the first membrane to the second membrane.

The first membrane may filter off particles larger than a predetermined size from the bio sample. The biosensor strip may further include a third membrane located below the second membrane and configured to generate an electric signal by a chemical reaction with the bio sample, and electrodes being in contact with the third membrane and configured to transfer the electric signal to the strip reader.

The second membrane may be provided in plurality, and the plurality of second membranes may be arranged in a lengthwise direction of the first membrane.

Meanwhile, the separator may be made of polyethylene. Also, the separator may include a plurality of holes for allowing the bio sample to move into the second membrane. The separator may filter off particles larger than a predetermined size from the bio sample.

To achieve the aspect, in accordance with one exemplary embodiment, there is provided a biosensor including a biosensor strip provided with a first membrane chemically reacting with a bio sample, a second membrane located below the first membrane and configured to generate an electric signal using a chemical reaction with the bio sample, electrodes being in contact with the second membrane and configured to transfer the generated electric signal to a strip reader, and a separator interposed between the first membrane and the second membrane, and configured to control an amount of the bio sample flowing from the first membrane to the second membrane, and a strip reader provided with an insertion unit in which the biosensor strip is inserted, a connector contactable with the electrodes, and a measurement unit configured to perform measurements of the bio sample according to the electric signal from the electrodes.

The strip reader may include a light emitting element for emitting light to a lower surface of the second membrane, and a light receiving element for receiving reflected light.

In accordance with a strip and a strip reader according to one exemplary embodiment, various types of measurements can be simultaneously performed at one time. Also, according to the strip, the user does not have to be equipped with various types of strips, resulting in reduction of user’s inconvenience and giving gains in a financial aspect.

FIG. 1 is an exemplary view of a biosensor strip reader in accordance with one exemplary embodiment;

FIG. 2 is an exemplary view showing a configuration of the strip reader shown in FIG. 1;

FIG. 3 is a detailed exemplary view of the biosensor strip shown in FIG. 1;

FIG. 4 is an exemplary view showing a structure of the strip shown in FIG. 3 in accordance with one exemplary embodiment;

FIG. 5 is an exemplary view showing a structure of the strip shown in FIG. 3 in accordance with another exemplary embodiment;

FIG. 6 is an exemplary view showing a structure of the strip shown in FIG. 3 in accordance with another exemplary embodiment; and

FIG. 7 is an exemplary view showing a structure of the strip shown in FIG. 3 in accordance with another exemplary embodiment.

Technical terms used in this specification are used to merely illustrate specific embodiments, and should be understood that they are not intended to limit the present disclosure. As far as not being defined differently, all terms used herein including technical or scientific terms may have the same meaning as those generally understood by an ordinary person skilled in the art to which the present disclosure belongs to, and should not be construed in an excessively comprehensive meaning or an excessively restricted meaning. In addition, if a technical term used in the description of the present disclosure is an erroneous term that fails to clearly express the idea of the present disclosure, it should be replaced by a technical term that can be properly understood by the skilled person in the art. In addition, general terms used in the description of the present disclosure should be construed according to definitions in dictionaries or according to its front or rear context, and should not be construed to have an excessively restrained meaning.

A singular representation may include a plural representation as far as it represents a definitely different meaning from the context. Terms ‘include’ or ‘has’ used herein should be understood that they are intended to indicate an existence of several components or several steps, disclosed in the specification, and it may also be understood that part of the components or steps may not be included or additional components or steps may further be included.

It will be understood that, although the terms first, second, etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, a first element could be termed a second element, and, similarly, a second element could be termed a first element, without departing from the scope of the present disclosure.

Exemplary embodiments of the present disclosure will be described below in detail with reference to the accompanying drawings, where those components are rendered the same reference number that are the same or are in correspondence, regardless of the figure number, and redundant explanations are omitted.

In describing the exemplary embodiments, if a detailed explanation for a related known function or construction is considered to unnecessarily divert the gist of the present disclosure, such explanation has been omitted. The accompanying drawings are used to help easily understood the technical idea of the present disclosure and it should be understood that the idea of the present disclosure is not limited by the accompanying drawings.

FIG. 1 is an exemplary view showing a biosensor strip reader in accordance with one embodiment, FIG. 2 is an exemplary view showing a configuration of the strip reader shown in FIG. 1, and FIG. 3 is a detailed exemplary view of the biosensor strip shown in FIG. 1.

Referring to FIGS. 1 and 2, a strip reader 200 according to one exemplary embodiment may perform a component measurement (for example, measurement of blood sugar) of a specimen by virtue of a biosensor strip 100, and display the measurement result on a display unit.

The strip reader 200 may externally include an insertion unit in which the biosensor strip 100 is inserted, a display unit and an audio generator.

The strip reader 200, as shown in FIG. 2, may internally include a connector 210 present within the insertion unit and connected to an electrode unit of the biosensor strip 100, and a measurement unit 220 configured to perform component measurements. Also, the strip reader 200 may include a display unit 230, an audio generator 240, a memory 250 and a controller 260.

The measurement unit 220 may include an electron measurement performing unit for performing an electronic measurement by receiving an electric signal sent from the electrode unit of the strip via the connector 210, and an optical measurement performing unit for performing an optical or fluorescent measurement. The optical measurement performing unit may include a light emitting element (for example, light emitting diode (LED)) and a light receiving element (for example, photo diode (PD)).

The light emitting element may include at least one light emitting diode (e.g., LEDs) all integrated within a narrow space. The light emitting diodes may emit, for example, red, blue and green colored light, or white, red, blue and green colored light. Alternatively, the light emitting diode may emit infrared rays.

The controller 260 may display a numerical value measured by the measurement unit on the display unit 230. The controller 260 may also generate a sound (audio signal) via the audio generator 240 when the strip 100 is completely inserted into the insertion unit, and generate another sound when the measurement is completed.

In the meantime, as shown in FIG. 3 with dotted lines, a reaction unit 120, which generates an electric signal through a chemical reaction or a physical variation, may be present on one surface of the biosensor strip 100. The electrode unit 110 for transferring the electric signal may be formed on one surface of the biosensor strip 100.

Although not shown, an accommodation portion for accommodating a bio sample (specimen), for example, serum, body fluids or the like, may be formed in one surface of the biosensor strip 100. Also, a specimen inlet may be formed at a lower side of the accommodation portion. The specimen inlet may allow the specimen to be fast introduced into the reaction unit 120.

Meanwhile, in the fabrication of electrodes for the electrochemical biosensor strip, precious metals (e.g., gold, palladium, platinum and the like) and carbon are generally used as an electrode material. The precious metals and the carbon have high electrical conductivities, are rarely denatured and facilitate signal acquisition. The electrode material may be coated in various manners, for example, screen printing, sputtering, plating and the like, upon forming electrodes on an insulation substrate, such as a plastic film.

FIG. 4 is an exemplary view showing a structure of the strip shown in FIG. 3 in accordance with one exemplary embodiment.

As shown in FIG. 4, the reaction unit of the biosensor strip 100 may be formed by stacking two or more thin films, for example, membranes.

Electrodes may be interposed between the two membranes. The upper first membrane may be configured to filter off a bio sample (specimen), for example, whole blood. That is, the upper first membrane may filter off a substance composed of large particles, such as red blood corpuscles, from the whole blood. The lower second membrane may physically or chemically react with the specimen and generate an electric signal to transmit to the electrodes.

For example, a principle of measuring blood sugar may be described as follows.

GOx-FADH₂+ Electron transfer mediator (oxidation state) → GOx-FAD + Electron transfer mediator (reduction state)

In the chemical equation 1, GOx denotes glucose oxidase, GOx-FAD and GOx-FADH2 respectively denote an oxidation state and a reduction state of flavin adenine dinucleotide (FAD), an active portion of the glucose oxidase.

The electrochemical biosensor may utilize, as the electron transfer mediator, ferrocene, ferrocene derivatives, quinones, quinone derivatives, transition metal-containing organic or inorganic substances (hexamine ruthenium, osmium-containing polymers, potassium ferricyanide, etc), organic conducting salts, electron transfer organic substances, such as viologen, and the like.

Hereinafter, description will be given of a principle of blood sugar measurement in the biosensor.

Glucose is oxidized into gluconate by a catalysis of glucose oxidase. Here, FAD as an active portion of the glucose oxidase is reduced into FADH2. The reduced FADH2 is then oxidized into FAD and the electron transfer mediator is reduced, through oxidation-reduction reaction between FAD and the electron transfer mediator. The electron transfer mediator in the reduction state is diffused up to the surfaces of the electrons. Here, a current, which is generated by applying an oxidation potential of the electron transfer mediator in the reduction state at surfaces of working electrons, is measured, thereby measuring a concentration of blood sugar.

The first or second membrane includes a reaction reagent layer. The reaction reagent layer may include oxidase, such as glucose oxidase, lactate oxidase and the like, an electron transfer mediator, water-soluble polymers, such as cellulose acetate, polyvinyl alcohol, polypyrrole and the like, fatty acid having 4~20 carbon in number as reagents for reduction of hematocrit effect, and oleophilic quaternary ammonium.

Meanwhile, a reaction layer, which reacts with light emitted from the light emitting element may be provided below the second membrane. The light emitting element, as aforementioned, may emit red, blue and/or green colored light. Here, a reaction mechanism with the light will be described as follows.

First, a reaction mechanism between glucose and light will be expressed according to Chemical Equation 2.

A reaction mechanism between cholesterol and light will be expressed according to Chemical Equation 3.

A reaction mechanism between triglyceride and light will be expressed according to Chemical Equation 4.

A reaction mechanism between alanine aminotransferase and light will be expressed according to Chemical Equation 5.

A reaction mechanism between aspartate aminotransferase and light will be expressed according to Chemical Equation 6.

Meanwhile, a reaction color may depend on chromogen, but a representative dye type of λmax(nm) value will be described as follows.

Table 1

When light emitted from the light emitting element is reflected by the second membrane, the light receiving element may read out a level of color change from the reflected light.

FIG. 5 is an exemplary view showing a structure of the strip shown in FIG. 3 in accordance with another exemplary embodiment.

As shown in FIG. 5, a separator may be formed between the two membranes.

The separator may be made of polyethylene. The separator may prevent a reagent of the upper first membrane, which is melted by whole blood, from being introduced into the second membrane. Also, the separator may perform filtering of large particles from the whole blood. To this end, the separator may include a plurality of fine holes.

Briefly explaining operations through such structure, if a bio sample, for example, whole blood is injected into the upper first membrane, relatively large particles, such as red blood corpuscles, are filtered out of the whole blood, and small particles flow downwardly. Slightly larger particles of the small particles are filtered off by the separator again, and minute particles flow to the second membrane via the separator. The minute particles make a physical or chemical reaction.

For instance, as shown in the lower side of FIG. 5, the electrodes may measure glucose, cholesterols, CK-MB and the like, and the second membrane may measure TC, TG, HDL, AST, ALT and the like.

FIG. 6 is an exemplary view showing a structure of the strip shown in FIG. 3 in accordance with another exemplary embodiment.

As shown in FIG. 6, a plurality of second membranes may be provided.

In detail, a plurality of electrode pairs are present below the first membrane, and the second membrane may be present below each electrode pair. In addition, a separator may be disposed between an electrode pair and the lower second membrane.

When whole blood is injected into the first membrane, the whole blood is widely spread over an area of the first membrane and flows through the first membrane. The whole blood flowed through the first membrane then passes through the second membrane.

Here, pressure is applied onto the first membrane to render the first membrane contacted by the electrodes, whereby the whole blood can easily flows into the second membrane.

As shown in FIG. 7, a plurality membranes may be arranged in a perpendicular direction. Here, each membrane may be provided with holes which allow movement of blood to a lower membrane. Also, the separator may be interposed between the membranes.

The present disclosure has been explained with reference to the embodiments which are merely exemplary. It will be apparent to those skilled in the art that various modifications and equivalent other embodiments can be made in the present disclosure without departing from the spirit or scope of the invention. Also, it will be understood that the present disclosure can be implemented by selectively combining the aforementioned embodiment(s) entirely or partially. Thus, it is intended that the present disclosure cover modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.

Claims

A biosensor strip comprising:

a first membrane chemically reacting with a bio sample;

a second membrane located below the first membrane and configured to generate an electric signal using a chemical reaction with the bio sample;

electrodes being contact with the second membrane and configured to transfer the generated electric signal to a strip reader ; and

a separator interposed between the first membrane and the second membrane, and configured to control an amount of the bio sample flowing from the first membrane to the second membrane.
The biosensor strip of claim 1, wherein the first membrane filters off particles larger than a predetermined size from the bio sample.
The biosensor strip of claim 1, further comprising:

a third membrane located below the second membrane and configured to generate an electric signal using a chemical reaction with the bio sample; and

electrodes being contact with the third membrane and configured to transfer the electric signal to the strip reader.
The biosensor strip of claim 1, wherein the second membrane is provided in plurality, the plurality of second membranes being arranged in a lengthwise direction of the first membrane.
The biosensor strip of claim 1, wherein the separator is made of polyethylene.
The biosensor strip of claim 1, wherein the separator comprises a plurality of holes for allowing the bio sample to move into the second membrane.
The biosensor strip of claim 1, wherein the separator filters off particles larger than a predetermined size from the bio sample.
A biosensor comprising:

a biosensor strip provided with a first membrane chemically reacting with a bio sample, a second membrane located below the first membrane and configured to generate an electric signal using a chemical reaction with the bio sample, electrodes being contact with the second membrane and configured to transfer the generated electric signal to a strip reader, and a separator interposed between the first membrane and the second membrane and configured to control an amount of the bio sample flowing from the first membrane to the second membrane; and

a strip reader provided with an insertion unit in which the biosensor strip is inserted, a connector contactable with the electrodes, and a measurement unit configured to perform measurements of the bio sample according to the electric signal from the electrodes.
The biosensor of claim 8, wherein the strip reader comprises a light emitting unit for emitting light to a lower surface of the second membrane, and a light receiving unit for receiving reflected light.
The biosensor of claim 8, wherein the first membrane filters off particles larger than a predetermined size from the bio sample.
The biosensor of claim 8, wherein the strip further comprises:

a third membrane located below the second membrane and configured to generate an electric signal by a chemical reaction with the bio sample; and

electrodes being contact with the third membrane and configured to transfer the electric signal to the strip reader.
The biosensor of claim 8, wherein the second membrane is provided in plurality, the plurality of second membranes being arranged in a lengthwise direction of the first membrane.
The biosensor of claim 7, wherein the separator is made of polyethylene.