WO2009107936A2 - Blood glucose measuring system - Google Patents
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- WO2009107936A2 WO2009107936A2 PCT/KR2009/000578 KR2009000578W WO2009107936A2 WO 2009107936 A2 WO2009107936 A2 WO 2009107936A2 KR 2009000578 W KR2009000578 W KR 2009000578W WO 2009107936 A2 WO2009107936 A2 WO 2009107936A2
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1486—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1486—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
- A61B5/14865—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
Definitions
- the present invention provides a blood glucose measuring system including an electrode portion including an ion selective electrode contacting or being inserted in the skin, a signal measuring portion electrically connected to the electrode of the electrode portion, and a monitoring portion connected to the signal measuring portion.
- Diabetes is a disease in which glucose is accumulated in the blood of the body due to insufficient secretion of insulin or poor sensitivity of cells to insulin. Moreover, diabetes may cause complications including cardiovascular diseases such as atherosclerosis, hypertension, cerebrovascular infarction, renal diseases such as diabetic nephrosis, ophthalmologic diseases such as diabetic retinisis or cataracts, skin diseases such as pyoderma or gangrene, and oral diseases such as gingival blennorrhea.
- cardiovascular diseases such as atherosclerosis, hypertension, cerebrovascular infarction
- renal diseases such as diabetic nephrosis
- ophthalmologic diseases such as diabetic retinisis or cataracts
- skin diseases such as pyoderma or gangrene
- oral diseases such as gingival blennorrhea.
- gingival blennorrhea As socioeconomical development progresses, the diabetic population is increasing dramatically due to dietary excess, lack of exercise, and
- Diabetic patients are encouraged to monitor their blood glucose level regularly, typically at empty stomach (acceptable maximum 140 mg/dL) and 2 hours (acceptable maximum 200 mg/dL) after meals, to manage their blood glucose.
- blood glucose level varies dramatically over the course of a day depending on many conditions such as the overall condition of the body, types and quantity of the diet, age, presence of associated complications, stress level, and other accompanying diseases, and therefore testing and managing their blood glucose level is a very important factor for diabetes patients in maintaining their health and preventing associated complications.
- a diabetes patient needs to manage one's own blood glucose level by measuring one's blood glucose level several times a day, regardless of the time and place.
- An invasive method is a method of drawing blood directly from the skin before blood glucose analysis, then measuring the blood glucose level using the drawn blood.
- the method of measuring the blood glucose level using the conventional invasive method involves an inconvenient and uncomfortable process of drawing blood through the skin before analyzing the blood glucose level, which thus restricts regular use.
- a reverse iontophoresis method is typically involved.
- a calibration involving a blood sample is needed every time.
- a glucose level monitoring system which does not require a repetitive calibration by drawing blood, can be simply manufactured, and which can be miniaturized is needed, so as to measure blood glucose levels without being restricted to time and place.
- the present invention provides a blood glucose measuring system which does not require drawing of blood for a calibration of blood glucose level every time, thereby reducing inconvenience and discomfort.
- the present invention provides a blood glucose level measuring system including an electrode portion including an ion selective electrode which contacts or is inserted in the skin, a signal measuring portion electrically connected to the electrode portion, and a monitoring portion connected to the signal measuring portion.
- the electrode portion includes a nano-sized, multiporous platinum-based working electrode inserted into the skin, a reference electrode, a counter electrode, and the ion selective electrode.
- the electrode portion includes an ion conductive medium contacting the skin, and a working electrode, at least one extraction electrode, a reference electrode, a counter electrode, and an ion selective electrode, wherein the electrodes are disposed on the opposite side of a skin-contacting side of the ion conductive medium.
- the blood glucose measuring system including the ion selective electrode measures a non-glucose reference material using the ion selective electrode or the like, without an initial drawing of blood at least one time in order to calibrate a measured signal (current or wavelength) into blood glucose, and calibrating the measured signal (current or wavelength) into blood glucose using its correlation with glucose obtained by the measurement.
- Body fluid includes ions such as Na + , K + and materials such as urea.
- these materials are used as the reference material for measuring the glucose level.
- the reference materials are extracted simultaneously when the glucose is extracted through the ion conductive medium.
- the ion selective electrode with respect to the reference material is installed in the blood glucose measuring system of the present invention, and thus the extracted reference material may be measured by potentiometry.
- the correlation may be entered into the blood glucose measuring system through a one-time measurement. Therefore, the concentration of the extracted reference material can be measured simultaneously with the extraction of glucose, and the concentration of the glucose can be calculated using the correlation.
- the glucose level can be calculated through the correlation between the glucose and the reference material without calibration by continuous drawing of blood.
- the reference electrode of the ion selective electrode may be a Ag/AgCl-based extraction electrode. Therefore, by using the Ag/AgCl-based extraction electrode conventionally used in blood glucose measuring devices as the reference electrode of the ion selective electrode, installation of a separate reference electrode is not required, and the system can be miniaturized, and manufactured more easily and economically.
- the ion selective electrode is an electrode measuring, by selectively drawing particular ions using an ion selective membrane, the potential of the membrane surface.
- the reference material is Na + ions or K + ions
- measurements can be made by directly using selective membranes for Na + ions or K + ions, respectively.
- the reference material is a non-ionic material such as urea
- measurement for urea can be made using an ion selective membrane for NH 4 + ions.
- Ion selective electrodes are manufactured by mixing an ion selective material that is selective towards a specific ion, and a support (such as PVC and PU), dissolving the mixture in an organic solvent, and applying and then drying the solution on a conventional electrode.
- a support such as PVC and PU
- Materials selective for specific ions, as well as the method of manufacturing ion selective electrodes using such materials, are well known to one of ordinary skill in the art.
- Na + selective membrane used for a Na + selective electrode is manufactured by mixing 49.5 mg of PU (polyurethane) and 16.5 mg of PVC (polyvinyl chloride), and mixing 2 mg of a Na + selective material 4-tert-butylcalix[4]arene-tetraacetic acid tetraethyl ester, 0.2 mg of KTpCIPB (potassium tetrakis(4-chlorophenyl)borate), and 132 mg of DOA (dioctyl adipic acid).
- PU polyurethane
- PVC polyvinyl chloride
- DOA dioctyl adipic acid
- a K + selective membrane used for a K + selective electrode is manufactured by mixing 66 mg of PU/PVC (PU 49.5 mg/PVC 16.5 mg), 2 mg of a K + selective material valinomycin, and 132 mg of DOA.
- a NH 4 + selective membrane used for a NH 4 + selective electrode is manufactured by mixing 66 mg of PU/PVC (PU 49.5 mg/PVC 16.5 mg), 2 mg of an NH 4 + ion selective material nonactin, and 132 mg of DOA.
- the manufactured ion selective membranes are respectively attached to a planar electrode made of PET, and then dried to complete the manufacture of ion selective electrodes. Contents of all materials used in manufacturing the ion selective electrodes may be modified.
- a reference material with respect to glucose being extracted may be Na + ion or urea.
- Urea may be measured by measuring a potential difference of CO 2 or NH 4 + produced by urease reaction using a CO 2 gas sensor or a NH 4 + selective electrode.
- a CO 2 gas sensor has a very complex electrode structure, and thus is not suitable for installation in a miniaturized blood glucose measuring system.
- a pH change by CO 2 permeation is measured, there is a time delay in responding.
- both CO 2 and NH 4 + are acidic, the CO 2 gas sensor and the NH 4 + selective electrode are affected by the pH of the sample.
- Na + ions are included in large amounts in body fluid and are maintained at a constant concentration within the body fluid, Na + ions can be used as a reference material.
- the Na + ions may be measured with a Na + selective electrode using an ion potential difference measurement method, and the Na + selective electrode may be used without any pretreatment process, and can be applied directly to the electrode portion of the blood glucose measuring system, thus enabling miniaturization of the blood glucose measuring system and making it pH-resistant. Therefore, the Na + ion selective electrode is particularly preferable in the blood glucose measuring system of the present invention.
- FIG. 2 illustrates electrochemical sensitivity of a Na + selective membrane toward Na + ions used in the present invention.
- w hen electrochemical sensitivity of a Na + selective membrane was investigated, the Na + selective membrane showed high selectivity towards Na + compared to K + , NH 4 + , Mg 2+ or Ca 2+ , and had a high sensitivity within the concentration range of 10 -5 to10 -1 M for Na + ions.
- a conventional extraction electrode can be used as a reference electrode with respect to a Na + selective electrode in a blood glucose measuring system. Specifically, in the blood glucose measuring system having a structure of an electrode portion as illustrated in FIG. 1, electrochemical sensitivity towards Na + when a Ag/AgCl-based extraction electrode and the Na + selective electrode were combined (FIG. 4), and electrochemical sensitivity towards Na + when a conventionally used reference electrode (Orion double junction Ag/AgCl electrode (model 90-02)) and the Na + selective electrode according to the present invention were combined (FIG. 3) were compared. As a result, the same characteristics of electrochemical sensitivity were exhibited towards Na + (refer to FIGS. 3 and 4). Therefore, an extraction electrode used in conventional blood glucose measuring apparatuses may be used as the reference electrode of the Na + selective electrode in the blood glucose measuring system of the present invention.
- FIGS. 6A, 6B, and 6C illustrates a correlation between the glucose extracted and Na + ions extracted .
- the concentration of glucose increased in proportion to the concentration of Na + ions.
- the ion selective electrode of the blood glucose measuring system of the present invention may be disposed in one of a first extraction electrode portion including a working electrode, a counter electrode, a reference electrode, and a first extraction electrode, and a second extraction electrode portion including a second extraction electrode.
- a first extraction electrode has a partly cut ring shape, wraps around the working electrode, is disposed on an ion conductive medium (not shown) on the opposite side of a side contacting the skin
- the second extraction electrode which has a partly cut ring shape, is disposed on the ion conductive medium on the opposite side of the side in contact with the skin
- the first extraction electrode and the second extraction electrode are separated from each other
- the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith, and the reference electrode and the counter electrode are positioned in line at the cut part of the first extraction electrode
- the ion selective electrode is disposed on the inside of the ring-shape of the second extraction electrode (Refer to FIG. 1).
- the first extraction electrode has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin
- the second extraction electrode has a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin
- the first extraction electrode and the second extraction electrode are separated from each other
- the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith
- the reference electrode and the counter electrode are positioned in parallel, on the cut part of the first extraction electrode
- the ion selective electrode is disposed on the inside of the ring shape of the second extraction electrode.
- the first extraction electrode has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin
- the second extraction electrode has a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin
- the reference electrode and the counter electrode are positioned such that each wraps around one half of the perimeter of the first extraction electrode, and the ion selective electrode is disposed on the inside of the ring shape of the second extraction electrode.
- the first extraction electrode has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin
- the second extraction electrode has a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin
- the first extraction electrode and the second extraction electrode are separated from each other
- the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith
- the reference electrode wraps around the first extraction electrode from the part to which the counter electrode does not extend
- the ion selective electrode is disposed on the inside of the ring shape of the second extraction electrode.
- the first extraction electrode has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin
- the second extraction electrode has a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode, the ion selective electrode and the reference electrodes wrap around the first extraction electrode together, without being in contact with one another.
- FIG. 1 is an electrode portion of a blood glucose measuring system according to one of the above-described embodiments of the present invention .
- the blood glucose measuring system includes a first extraction electrode 1 of the extraction electrodes that has a partly cut ring shape, wraps around a working electrode 3, and is disposed on an ion conductive medium (not shown) at an opposite side of a side contacting the skin, and a second extraction electrode 2 among the extraction electrodes is a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, wherein the first extraction electrode 1 and the second extraction electrode 2 are separated from each other, and the counter electrode 4 wraps around the first extraction electrode 1, and is electrically connected to the working electrode 3 so as to be conductive therewith, and the reference electrode 5 and the counter electrode 4 are positioned in line at the cut part of the first extraction electrode 1, and the ion selective electrode 6 is disposed inside of the ring-shape of the second extraction electrode 2.
- the blood glucose measurement system includes an ion selective electrode, thereby allowing measurement of a reference material within a body fluid by using a method of potential difference measurement with high electrochemical sensitivity. Moreover, glucose and the reference material are extracted using such a system to calculate a correlation therebetween, measuring the concentration of the reference material being extracted along with the glucose. The concentration of glucose is then calculated using the correlation between the glucose and the reference material, and thus the system enables measurement of blood glucose without calibration by continuous drawing of blood, but by calibration of the calculated concentration of glucose using the correlation between the glucose and the reference material.
- the blood glucose measuring system uses an extraction electrode, conventionally used in blood glucose measuring devices, as a reference electrode of the ion selective electrode, therefore not requiring a separate reference electrode, such that the blood glucose measuring system can be miniaturized and manufactured more easily and economically.
- FIG. 1 is a diagram illustrating an electrode system of a blood glucose measuring system, according to an embodiment of the present invention
- FIG. 2 is a diagram illustrating electrochemical sensitivity of a Na + selective membrane toward Na + ions used in the present invention
- FIG. 3 is a diagram illustrating electrochemical sensitivity of a Na + selective electrode of a blood glucose measuring system according to the present invention toward Na + ions using a conventionally used Ag/AgCl reference electrode, and electrochemical sensitivity of the Ag/AgCl-based extraction electrode to be used as the reference electrode toward Cl - ions;
- FIG. 4 is a diagram illustrating electrochemical sensitivity of a Na + selective electrode toward Na + ions when a Ag/AgCl-based extraction electrode was used as the reference electrode, of the blood glucose measurement system according to the present invention
- FIG. 5 is a diagram illustrating a Franz cell structure used in Experimental Example 3.
- FIG. 6A to 6C are diagrams illustrating a correlation between the glucose extracted and Na + ions extracted, when the extraction current densities are 0.1 mA/cm 2 , 0.3 mA/cm 2 , and 0.5 mA/cm 2 , respectively.
- a membrane composing material PU/PVC(PU 49.5mg/PVC 16.5mg), 2 mg of a Na + ion selective material 4-tert-butylcalix[4]arene-tetraacetic acid tetraethyl ester, 0.2 mg of KTpCIPB (potassium tetrakis(4-chlorophenyl)borate), and 132 mg of DOA (dioctyl adipic acid) were dissolved in 800 ⁇ l of a solvent THF to prepare a membrane composing solution, which was either formed in its original form or was thinly applied to a surface of a PET-based solid planar electrode using an Air Fluid Dispensor (1000XL; EFD Inc,. East Buffalo, RI, USA). Then the membrane was dried for approximately 4 days in air to manufacture a Na + selective electrode.
- An Orion double junction Ag/AgCl electrode (model 90-02), that is, a PET-based planar solid electrode, was used as an external reference electrode .
- a base electrolyte solution (0.01 M Tris-H 2 SO 4 , pH 7.0)
- concentrations of Na + ions were altered (10 -6 ⁇ 10 -1 M) in 100-second intervals and the potential difference was measured.
- the potential difference between the reference electrode and a working electrode was measured using a data acquisition system, in which measured data is input to a high impedance input 16-channel analog-to-digital converter of a Multi pH/Ion Meter KST101B (Kosentech, Korea), and is stored in a PC-compatible computer. The results are shown in FIG. 2.
- the Na + selective electrode manufactured in the Manufacturing Example according to the present invention had a high selectivity toward Na + ions, and had high electrochemical sensitivity to Na + ions at a Na + ion concentration of 10 -5 -10 -1 M.
- a blood glucose measuring system having an electrode portion described with reference to FIG. 1 was manufactured, and the electrochemical sensitivity of the Na + selective electrode to Na + ions and electrochemical sensitivity of a Ag/AgCl-based extraction electrode that is to be used as a reference electrode with respect to Cl - were investigated.
- the reference electrode used was an Orion double junction Ag/AgCl electrode (model 90-02). Since the Ag/AgCl-based extraction electrode exhibits electrochemical sensitivity to Cl - , the base electrolyte solution (0.01 M Tris-H 2 SO 4 , pH 7.0) used previously was replaced with a base electrolyte solution containing 10 mM or more of Cl - , and electrochemical sensitivity was investigated for Na + and Cl - respectively. The results are shown in FIG. 3.
- the Na + selective electrode of the present invention had high electrochemical sensitivity to Na + ions at a Na + concentration of 10 -5 -10 -1 M, while sensitivity to Cl - of the Ag/AgCl-based extraction electrode used as the reference electrode was barely detectable up to 10 -2 M.
- the Ag/AgCl-based extraction electrode was suitable as a reference electrode.
- a blood glucose measuring system having an electrode portion described with reference to FIG. 1 was manufactured, and the electrochemical sensitivity of the Na + selective electrode was investigated when a Ag/AgCl-based extraction electrode was used as the reference electrode. The results are shown in FIG. 4.
- the electrochemical sensitivity of the Na + selective electrode to Na + ions when the Ag/AgCl-based extraction electrode was used as the reference electrode exhibited the same characteristics as the electrochemical sensitivity of the Na + selective electrode to Na + ions when a conventional reference electrode was used.
- Glucose and Na + ions extracted via the skin with respect to extraction current density and time change were quantified, and the correlation between the glucose concentration and the Na + ion concentration were investigated.
- the extraction current was within a range applied in a mimic system using a skin of an animal carcass.
- FIG. 5 is a diagram illustrating a Franz cell structure used in Experimental Example 4.
- the Franz cell was designed so as to practically have the same conditions as an extraction condition of body fluid by reverse-ion osmosis, by arranging the electrodes on an outer surface of the skin.
- a skin tissue of a hairless mouse was used.
- the lower part of the Franz cell was filled with a solution of 0.05 M Tris-HCl, pH 7.4/0.1 M NaCl/0.01 M glucose, and the skin tissue was carefully covered so as not to produce air bubbles, and the upper part of the Franz cell was raised and fixed.
- 1.5 ml of a solution of 0.05 M Tris-HCl, pH 7.4 was added to an area of extraction to which ( - ) potential was to be applied, and 1.5 ml of a mixture solution of 0.05 M Tris-HCl, pH 7.4/0.1 M NaCl was added to an area of extraction to which (+) potential was to be applied.
- the Ag/AgCl-based extraction electrode was installed in the cell in order to apply an extraction current.
- a conducting wire was connected to the extraction electrode, and the extraction densities of the current applied (0.1 mA/cm 2 , 0.3 mA/cm 2 and 0.5 mA/cm 2 ) and the extraction times (1 hour, 3 hours, and 5 hours) were controlled using a constant current supplier (RCP-2000 ⁇ , Young-Nam Instruments, Korea).
- RCP-2000 ⁇ Young-Nam Instruments, Korea
- the concentrations of the extracted glucose and Na + ions increase in proportion, with respect to time of extraction at the same extraction current density.
- FIGS. 6A 0.1 mA/cm 2
- 6B 0.3 mA/cm 2
- 6C 0.5 mA/cm 2
- the correlation had low linearity (R) at an extraction current density of 0.1 mA/cm 2 or less, but had high linearity (R) at extraction current densities of 0.3 mA/cm 2 and 0.5 mA/cm 2 .
Abstract
Provided is a blood glucose measuring system including an electrode portion including an ion selective electrode which is contacting or inserted in the skin, a signal measuring portion electrically connected to the electrode of the electrode portion, and a monitoring portion connected to the signal measuring portion.
Description
The present invention provides a blood glucose measuring system including an electrode portion including an ion selective electrode contacting or being inserted in the skin, a signal measuring portion electrically connected to the electrode of the electrode portion, and a monitoring portion connected to the signal measuring portion.
Diabetes is a disease in which glucose is accumulated in the blood of the body due to insufficient secretion of insulin or poor sensitivity of cells to insulin. Moreover, diabetes may cause complications including cardiovascular diseases such as atherosclerosis, hypertension, cerebrovascular infarction, renal diseases such as diabetic nephrosis, ophthalmologic diseases such as diabetic retinisis or cataracts, skin diseases such as pyoderma or gangrene, and oral diseases such as gingival blennorrhea. As socioeconomical development progresses, the diabetic population is increasing dramatically due to dietary excess, lack of exercise, and increase in stress. For developed countries, 5 to 10% of the total population is estimated to be diabetic, and 50% of them are found to be unaware of their diabetic condition. However, despite the seriousness of the situation, diabetic patients generally believe that measurement of blood glucose level must be taken with a blood sample, discouraging them from measuring their blood glucose level willingly.
Diabetic patients are encouraged to monitor their blood glucose level regularly, typically at empty stomach (acceptable maximum 140 mg/dL) and 2 hours (acceptable maximum 200 mg/dL) after meals, to manage their blood glucose. Besides this, blood glucose level varies dramatically over the course of a day depending on many conditions such as the overall condition of the body, types and quantity of the diet, age, presence of associated complications, stress level, and other accompanying diseases, and therefore testing and managing their blood glucose level is a very important factor for diabetes patients in maintaining their health and preventing associated complications. To this end, a diabetes patient needs to manage one's own blood glucose level by measuring one's blood glucose level several times a day, regardless of the time and place.
Conventionally, diabetes patients have measured blood glucose levels by an invasive method. An invasive method is a method of drawing blood directly from the skin before blood glucose analysis, then measuring the blood glucose level using the drawn blood. However, the method of measuring the blood glucose level using the conventional invasive method involves an inconvenient and uncomfortable process of drawing blood through the skin before analyzing the blood glucose level, which thus restricts regular use. Moreover, if a non-invasive method which does not draw blood is used, a reverse iontophoresis method is typically involved. However, in order to obtain the blood glucose level using such method, a calibration involving a blood sample is needed every time.
Therefore, a glucose level monitoring system which does not require a repetitive calibration by drawing blood, can be simply manufactured, and which can be miniaturized is needed, so as to measure blood glucose levels without being restricted to time and place.
The present invention provides a blood glucose measuring system which does not require drawing of blood for a calibration of blood glucose level every time, thereby reducing inconvenience and discomfort.
Hereinafter, the present invention will be described more fully with reference to the accompanying drawings, in which preferred embodiments of the invention are shown.
The present invention provides a blood glucose level measuring system including an electrode portion including an ion selective electrode which contacts or is inserted in the skin, a signal measuring portion electrically connected to the electrode portion, and a monitoring portion connected to the signal measuring portion.
The electrode portion includes a nano-sized, multiporous platinum-based working electrode inserted into the skin, a reference electrode, a counter electrode, and the ion selective electrode.
Moreover, the electrode portion includes an ion conductive medium contacting the skin, and a working electrode, at least one extraction electrode, a reference electrode, a counter electrode, and an ion selective electrode, wherein the electrodes are disposed on the opposite side of a skin-contacting side of the ion conductive medium.
The blood glucose measuring system including the ion selective electrode measures a non-glucose reference material using the ion selective electrode or the like, without an initial drawing of blood at least one time in order to calibrate a measured signal (current or wavelength) into blood glucose, and calibrating the measured signal (current or wavelength) into blood glucose using its correlation with glucose obtained by the measurement.
Body fluid includes ions such as Na+, K+ and materials such as urea. In the blood glucose measuring system of the present invention, these materials are used as the reference material for measuring the glucose level. In the blood glucose measuring system of the present invention, the reference materials are extracted simultaneously when the glucose is extracted through the ion conductive medium. The ion selective electrode with respect to the reference material is installed in the blood glucose measuring system of the present invention, and thus the extracted reference material may be measured by potentiometry. There is a set correlation between the concentrations of the extracted glucose and the extracted reference material. The correlation may be entered into the blood glucose measuring system through a one-time measurement. Therefore, the concentration of the extracted reference material can be measured simultaneously with the extraction of glucose, and the concentration of the glucose can be calculated using the correlation. Thereby, according to the present invention, the glucose level can be calculated through the correlation between the glucose and the reference material without calibration by continuous drawing of blood.
According to the present invention, the reference electrode of the ion selective electrode may be a Ag/AgCl-based extraction electrode. Therefore, by using the Ag/AgCl-based extraction electrode conventionally used in blood glucose measuring devices as the reference electrode of the ion selective electrode, installation of a separate reference electrode is not required, and the system can be miniaturized, and manufactured more easily and economically.
The ion selective electrode is an electrode measuring, by selectively drawing particular ions using an ion selective membrane, the potential of the membrane surface. If the reference material is Na+ ions or K+ ions, measurements can be made by directly using selective membranes for Na+ ions or K+ ions, respectively. In addition, in the case where the reference material is a non-ionic material such as urea, because urea produces NH4
+ ion through a reaction with urease, measurement for urea can be made using an ion selective membrane for NH4
+ ions.
Ion selective electrodes are manufactured by mixing an ion selective material that is selective towards a specific ion, and a support (such as PVC and PU), dissolving the mixture in an organic solvent, and applying and then drying the solution on a conventional electrode. Materials selective for specific ions, as well as the method of manufacturing ion selective electrodes using such materials, are well known to one of ordinary skill in the art. As an example, Na+ selective membrane used for a Na+ selective electrode is manufactured by mixing 49.5 mg of PU (polyurethane) and 16.5 mg of PVC (polyvinyl chloride), and mixing 2 mg of a Na+ selective material 4-tert-butylcalix[4]arene-tetraacetic acid tetraethyl ester, 0.2 mg of KTpCIPB (potassium tetrakis(4-chlorophenyl)borate), and 132 mg of DOA (dioctyl adipic acid). A K+ selective membrane used for a K+ selective electrode is manufactured by mixing 66 mg of PU/PVC (PU 49.5 mg/PVC 16.5 mg), 2 mg of a K+ selective material valinomycin, and 132 mg of DOA. A NH4
+ selective membrane used for a NH4
+ selective electrode is manufactured by mixing 66 mg of PU/PVC (PU 49.5 mg/PVC 16.5 mg), 2 mg of an NH4
+ ion selective material nonactin, and 132 mg of DOA. The manufactured ion selective membranes are respectively attached to a planar electrode made of PET, and then dried to complete the manufacture of ion selective electrodes. Contents of all materials used in manufacturing the ion selective electrodes may be modified.
A reference material with respect to glucose being extracted may be Na+ ion or urea. Urea may be measured by measuring a potential difference of CO2 or NH4
+ produced by urease reaction using a CO2 gas sensor or a NH4
+ selective electrode. However, a CO2gas sensor has a very complex electrode structure, and thus is not suitable for installation in a miniaturized blood glucose measuring system. Moreover, if a pH change by CO2 permeation is measured, there is a time delay in responding. Also, because both CO2 and NH4
+ are acidic, the CO2 gas sensor and the NH4
+ selective electrode are affected by the pH of the sample. However, since Na+ ions are included in large amounts in body fluid and are maintained at a constant concentration within the body fluid, Na+ ions can be used as a reference material. In addition, the Na+ ions may be measured with a Na+ selective electrode using an ion potential difference measurement method, and the Na+ selective electrode may be used without any pretreatment process, and can be applied directly to the electrode portion of the blood glucose measuring system, thus enabling miniaturization of the blood glucose measuring system and making it pH-resistant. Therefore, the Na+ ion selective electrode is particularly preferable in the blood glucose measuring system of the present invention.
A key example of an ion selective membrane is a Na+ selective membrane. FIG. 2 illustrates electrochemical sensitivity of a Na+ selective membrane toward Na+ ions used in the present invention. Referring to FIG. 2, w hen electrochemical sensitivity of a Na+ selective membrane was investigated, the Na+ selective membrane showed high selectivity towards Na+ compared to K + , NH4
+, Mg2+ or Ca2+, and had a high sensitivity within the concentration range of 10-5 to10-1 M for Na+ ions.
Whether or not a conventional extraction electrode can be used as a reference electrode with respect to a Na+ selective electrode in a blood glucose measuring system has been investigated. Specifically, in the blood glucose measuring system having a structure of an electrode portion as illustrated in FIG. 1, electrochemical sensitivity towards Na+ when a Ag/AgCl-based extraction electrode and the Na+ selective electrode were combined (FIG. 4), and electrochemical sensitivity towards Na+ when a conventionally used reference electrode (Orion double junction Ag/AgCl electrode (model 90-02)) and the Na+ selective electrode according to the present invention were combined (FIG. 3) were compared. As a result, the same characteristics of electrochemical sensitivity were exhibited towards Na+ (refer to FIGS. 3 and 4). Therefore, an extraction electrode used in conventional blood glucose measuring apparatuses may be used as the reference electrode of the Na+ selective electrode in the blood glucose measuring system of the present invention.
A constant correlation was exhibited between the concentration of glucose and the concentration of Na+, extracted via the ion conductive medium in the blood glucose measuring system of the present invention. Specifically, glucose and Na+ ions were extracted using the blood glucose measuring system of the present invention, while changing the current density of extraction and the extraction time, and the concentrations thereof were quantified respectively. FIGS. 6A, 6B, and 6C illustrates a correlation between the glucose extracted and Na+ ions extracted . Referring to FIGS. 6A, 6B, and 6C, at a current density of 0.3 mA/cm2 or greater, the concentration of glucose increased in proportion to the concentration of Na+ ions. In particular, at an extraction current density of 0.3 - 0.5 mA/cm2, there was a linearity (R) of 0.995 or greater between the concentration of the extracted glucose and the concentration of the extracted Na+.
The ion selective electrode of the blood glucose measuring system of the present invention may be disposed in one of a first extraction electrode portion including a working electrode, a counter electrode, a reference electrode, and a first extraction electrode, and a second extraction electrode portion including a second extraction electrode.
According to an embodiment of the present invention, in which the Ion selective electrode is disposed in the second extraction electrode portion, a first extraction electrode has a partly cut ring shape, wraps around the working electrode, is disposed on an ion conductive medium (not shown) on the opposite side of a side contacting the skin, and the second extraction electrode, which has a partly cut ring shape, is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith, and the reference electrode and the counter electrode are positioned in line at the cut part of the first extraction electrode, and the ion selective electrode is disposed on the inside of the ring-shape of the second extraction electrode (Refer to FIG. 1).
According to another embodiment of the present invention, if the ion selective electrode is disposed in the second extraction electrode portion , the first extraction electrode has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, and the second extraction electrode has a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith, the reference electrode and the counter electrode are positioned in parallel, on the cut part of the first extraction electrode, and the ion selective electrode is disposed on the inside of the ring shape of the second extraction electrode.
According to another embodiment of the present invention, if the ion selective electrode is disposed in the second extraction electrode portion , the first extraction electrode has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, and the second extraction electrode has a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith, the reference electrode and the counter electrode are positioned such that each wraps around one half of the perimeter of the first extraction electrode, and the ion selective electrode is disposed on the inside of the ring shape of the second extraction electrode.
According to another embodiment of the present invention, if the ion selective electrode is disposed in the second extraction electrode portion, the first extraction electrode has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, and the second extraction electrode, has a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith, the reference electrode wraps around the first extraction electrode from the part to which the counter electrode does not extend, and the ion selective electrode is disposed on the inside of the ring shape of the second extraction electrode.
According to another embodiment of the present invention, if the ion selective electrode is disposed in the second extraction electrode portion, the first extraction electrode has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, and the second extraction electrode has a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode, the ion selective electrode and the reference electrodes wrap around the first extraction electrode together, without being in contact with one another.
FIG. 1 is an electrode portion of a blood glucose measuring system according to one of the above-described embodiments of the present invention .
Referring to FIG. 1, the blood glucose measuring system according to the current embodiment includes a first extraction electrode 1 of the extraction electrodes that has a partly cut ring shape, wraps around a working electrode 3, and is disposed on an ion conductive medium (not shown) at an opposite side of a side contacting the skin, and a second extraction electrode 2 among the extraction electrodes is a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, wherein the first extraction electrode 1 and the second extraction electrode 2 are separated from each other, and the counter electrode 4 wraps around the first extraction electrode 1, and is electrically connected to the working electrode 3 so as to be conductive therewith, and the reference electrode 5 and the counter electrode 4 are positioned in line at the cut part of the first extraction electrode 1, and the ion selective electrode 6 is disposed inside of the ring-shape of the second extraction electrode 2.
The blood glucose measurement system according to the present invention includes an ion selective electrode, thereby allowing measurement of a reference material within a body fluid by using a method of potential difference measurement with high electrochemical sensitivity. Moreover, glucose and the reference material are extracted using such a system to calculate a correlation therebetween, measuring the concentration of the reference material being extracted along with the glucose. The concentration of glucose is then calculated using the correlation between the glucose and the reference material, and thus the system enables measurement of blood glucose without calibration by continuous drawing of blood, but by calibration of the calculated concentration of glucose using the correlation between the glucose and the reference material. Furthermore, the blood glucose measuring system according to the present invention uses an extraction electrode, conventionally used in blood glucose measuring devices, as a reference electrode of the ion selective electrode, therefore not requiring a separate reference electrode, such that the blood glucose measuring system can be miniaturized and manufactured more easily and economically.
The above and other features and advantages of the present invention will become more apparent by describing in detail exemplary embodiments thereof with reference to the attached drawings in which:
FIG. 1 is a diagram illustrating an electrode system of a blood glucose measuring system, according to an embodiment of the present invention;
FIG. 2 is a diagram illustrating electrochemical sensitivity of a Na+ selective membrane toward Na+ ions used in the present invention;
FIG. 3 is a diagram illustrating electrochemical sensitivity of a Na+ selective electrode of a blood glucose measuring system according to the present invention toward Na+ ions using a conventionally used Ag/AgCl reference electrode, and electrochemical sensitivity of the Ag/AgCl-based extraction electrode to be used as the reference electrode toward Cl- ions;
FIG. 4 is a diagram illustrating electrochemical sensitivity of a Na+ selective electrode toward Na+ ions when a Ag/AgCl-based extraction electrode was used as the reference electrode, of the blood glucose measurement system according to the present invention;
FIG. 5 is a diagram illustrating a Franz cell structure used in Experimental Example 3;
FIG. 6A to 6C are diagrams illustrating a correlation between the glucose extracted and Na+ ions extracted, when the extraction current densities are 0.1 mA/cm2, 0.3 mA/cm2, and 0.5 mA/cm2, respectively.
The present invention will now be described in more detail with reference to the following examples. However, these examples are for illustrative purposes only and are not intended to limit the scope of the invention.
<Examples>
Manufacturing Example: Manufacture of Na
+
Selective Membrane Electrode
66 mg of a membrane composing material PU/PVC(PU 49.5mg/PVC 16.5mg), 2 mg of a Na+ ion selective material 4-tert-butylcalix[4]arene-tetraacetic acid tetraethyl ester, 0.2 mg of KTpCIPB (potassium tetrakis(4-chlorophenyl)borate), and 132 mg of DOA (dioctyl adipic acid) were dissolved in 800 ㎕ of a solvent THF to prepare a membrane composing solution, which was either formed in its original form or was thinly applied to a surface of a PET-based solid planar electrode using an Air Fluid Dispensor (1000XL; EFD Inc,. East Providence, RI, USA). Then the membrane was dried for approximately 4 days in air to manufacture a Na+ selective electrode.
Experimental Example 1: Investigation of Electrochemical Sensitivity of Na
+
Selective Electrode
Electrochemical sensitivity toward Na+ ions of the Na+ selective electrode manufactured in Example 1 was investigated.
An Orion double junction Ag/AgCl electrode (model 90-02), that is, a PET-based planar solid electrode, was used as an external reference electrode . In a base electrolyte solution (0.01 M Tris-H2SO4, pH 7.0), concentrations of Na+ ions were altered (10-6~ 10-1 M) in 100-second intervals and the potential difference was measured. The potential difference between the reference electrode and a working electrode was measured using a data acquisition system, in which measured data is input to a high impedance input 16-channel analog-to-digital converter of a Multi pH/Ion Meter KST101B (Kosentech, Korea), and is stored in a PC-compatible computer. The results are shown in FIG. 2.
Referring to FIG. 2, the Na+ selective electrode manufactured in the Manufacturing Example according to the present invention had a high selectivity toward Na+ ions, and had high electrochemical sensitivity to Na+ ions at a Na+ ion concentration of 10-5 -10 -1 M.
Experimental Example 2: Investigation of Electrochemical Sensitivity of Na
+
Selective Electrode to Na
+
ions and Electrochemical Sensitivity of a Ag/AgCl-based Extraction Electrode that is to be used as Reference Electrode toward Cl
-
, in the Blood Glucose Measuring System
A blood glucose measuring system having an electrode portion described with reference to FIG. 1 was manufactured, and the electrochemical sensitivity of the Na+ selective electrode to Na+ ions and electrochemical sensitivity of a Ag/AgCl-based extraction electrode that is to be used as a reference electrode with respect to Cl- were investigated. The reference electrode used was an Orion double junction Ag/AgCl electrode (model 90-02). Since the Ag/AgCl-based extraction electrode exhibits electrochemical sensitivity to Cl-, the base electrolyte solution (0.01 M Tris-H2SO4, pH 7.0) used previously was replaced with a base electrolyte solution containing 10 mM or more of Cl-, and electrochemical sensitivity was investigated for Na+ and Cl- respectively. The results are shown in FIG. 3.
Referring to FIG. 3, the Na+ selective electrode of the present invention had high electrochemical sensitivity to Na+ ions at a Na+ concentration of 10-5-10-1 M, while sensitivity to Cl- of the Ag/AgCl-based extraction electrode used as the reference electrode was barely detectable up to 10-2 M. Thus, the Ag/AgCl-based extraction electrode was suitable as a reference electrode.
Experimental Example 3: Investigation of Electrochemical Sensitivity of Na
+
Selective Electrode when Ag/AgCl-based Extraction Electrode was used as Reference Electrode within the Blood Glucose Measuring System
A blood glucose measuring system having an electrode portion described with reference to FIG. 1 was manufactured, and the electrochemical sensitivity of the Na+ selective electrode was investigated when a Ag/AgCl-based extraction electrode was used as the reference electrode. The results are shown in FIG. 4.
Referring to FIG. 4, the electrochemical sensitivity of the Na+ selective electrode to Na+ ions when the Ag/AgCl-based extraction electrode was used as the reference electrode, exhibited the same characteristics as the electrochemical sensitivity of the Na+ selective electrode to Na+ ions when a conventional reference electrode was used.
Experimental Example 4: Correlation between Glucose and Na
+
ions Extracted with Respect to Extraction Current Density and Time Change
Glucose and Na+ ions extracted via the skin with respect to extraction current density and time change were quantified, and the correlation between the glucose concentration and the Na+ ion concentration were investigated. The extraction current was within a range applied in a mimic system using a skin of an animal carcass.
1. Design and Preparation of Extraction Cell
FIG. 5 is a diagram illustrating a Franz cell structure used in Experimental Example 4. Referring to FIG. 5, the Franz cell was designed so as to practically have the same conditions as an extraction condition of body fluid by reverse-ion osmosis, by arranging the electrodes on an outer surface of the skin. A skin tissue of a hairless mouse was used.
2. Extraction Experiment
The lower part of the Franz cell was filled with a solution of 0.05 M Tris-HCl, pH 7.4/0.1 M NaCl/0.01 M glucose, and the skin tissue was carefully covered so as not to produce air bubbles, and the upper part of the Franz cell was raised and fixed. On the Franz cell, 1.5 ml of a solution of 0.05 M Tris-HCl, pH 7.4 was added to an area of extraction to which ( - ) potential was to be applied, and 1.5 ml of a mixture solution of 0.05 M Tris-HCl, pH 7.4/0.1 M NaCl was added to an area of extraction to which (+) potential was to be applied. The Ag/AgCl-based extraction electrode was installed in the cell in order to apply an extraction current.
A conducting wire was connected to the extraction electrode, and the extraction densities of the current applied (0.1 mA/cm2, 0.3 mA/cm2 and 0.5 mA/cm2) and the extraction times (1 hour, 3 hours, and 5 hours) were controlled using a constant current supplier (RCP-2000 μ, Young-Nam Instruments, Korea). Once the extraction ended, the solution of the upper part where the (-) potential was applied was drawn and fractionated to quantify the concentrations of the glucose and the Na+ ions extracted.
3. Quantitative Analysis of Extracted Glucose and Na+ Ions
A Bio-LC (DX-2500 System, DIONEX, USA) was used for analyzing the extracted glucose. An ICP-Mass (iCAP 6300 Duo, Thermo Electron, USA) was used for analyzing the extracted Na+ Ions. The quantitative analysis results of the extracted glucose and Na+ ions are shown in Table 1 below.
Table 1
As shown in Table 1, the concentrations of the extracted glucose and Na+ ions increase in proportion, with respect to time of extraction at the same extraction current density. Using the results in Table 1, correlations between glucose and Na+ ions with respect to extraction current density are shown in FIGS. 6A (0.1 mA/cm2), 6B (0.3 mA/cm2) and 6C (0.5 mA/cm2). Referring to FIGS. 6A, 6B, and 6C, the correlation had low linearity (R) at an extraction current density of 0.1 mA/cm2 or less, but had high linearity (R) at extraction current densities of 0.3 mA/cm2 and 0.5 mA/cm2. There was a correlation of Y = aX + b (a is 45.67-49.77, b is 28.15-40.29 between the concentration of glucose (X) (ppm) and the concentration Na+ ions (Y)(ppm) when the extraction c urrent density was 0.3 - 0.5 mA/cm2. Specifically, in the case where the extraction c urrent density was 0.3 mA/cm2, there was a correlation of Y=49.77X + 40.29 between the glucose (X) and the Na+ ions (Y). Moreover, in the case where the extraction current density was 0.5 mA/cm2, there was a correlation of Y=45.67X + 28.15. Using the correlations, concentrations of glucose calculated with specific concentrations of Na+ ions are presented in Table 2 below.
Table 2
Referring to Table 2, it can be seen that the glucose concentration calculated increased fivefold as the concentration of Na+ ions increased fivefold, at the extraction current densities of 0.3 mA/cm2 and 0.5 mA/cm2.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the following claims.
Claims (16)
- A blood glucose measuring system comprising an electrode portion comprising an ion selective electrode contacting or inserted in the skin, a signal measuring portion electrically connected to the electrode portion, and a monitoring portion connected to the signal measuring portion.
- The system of claim 1, wherein the electrode portion comprises a nanosized multiporous platinum-based working electrode inserted in the skin, a reference electrode, a counter electrode and an ion selective electrode.
- The system of claim 1, wherein the electrode portion comprises an ion conductive medium contacting the skin, and a working electrode, at least one extraction electrode, a reference electrode, a counter electrode, and an ion selective electrode, wherein the electrodes are disposed on the opposite side of a skin-contacting side of the ion conductive medium.
- The system of claim 1, wherein the ion selective electrode is one of a Na+ ion, K+ ion, or NH4 + ion selective electrode.
- The system of claim 1 or 3, wherein there is a correlation between a concentration of glucose and a concentration of extracted ions at a current density of 0.3 mA/cm2 or greater.
- The system of claim 5, wherein the current density is 0.3 to 0.5 mA/cm2.
- The system of claim 6, wherein the correlation between a concentration of glucose (X) (ppm) and a concentration of extracted ions (Y) (ppm) is Y = aX + b (a is 45.67 - 49.77, and b is 28.15 - 40.29), when the current density is 0.3 to 0.5 mA/cm2.
- The system of claim 1 or 3, wherein a reference electrode of the ion selective electrode is the extraction electrode.
- The system of claim 1 or 3, wherein the ion selective electrode is disposed in a first extraction electrode portion, comprising a working electrode, a first extraction electrode, a reference electrode, and a counter electrode.
- The system of claim 1 or 3, wherein the ion selective electrode is disposed in a second extraction electrode portion which comprises a second extraction electrode.
- The system of claim 1 or 3, wherein the first extraction electrode among the extraction electrodes has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive medium on the opposite side of a side in contact with the skin, and the second extraction electrode among the extraction electrodes is a partly cut ring shape, and is disposed on the ion conductive medium on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith, and the reference electrode and the counter electrode are positioned in line at the cut part of the first extraction electrode, and the ion selective electrode is disposed on the inside of the ring-shape of the second extraction electrode.
- The system of claim 1 or 3, wherein the first extraction electrode among the extraction electrodes has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive media on the opposite side of the side in contact with the skin, and the second extraction electrode among the extraction electrodes has a partly cut ring shape, and is disposed on the ion conductive media on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith, the reference electrode and the counter electrode are positioned in parallel at the cut part of the first extraction electrode, and the ion selective electrode is disposed on the inside of the ring shape of the second extraction electrode.
- The system of claim 1 or 3, wherein the first extraction electrode among the extraction electrodes has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive media on the opposite side of the side in contact with the skin, and the second extraction electrode among the extraction electrodes has a partly cut ring shape, and is disposed on the ion conductive media on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith, the reference electrode and the counter electrode are positioned such that each wraps around one half of the perimeter of the first extraction electrode, and the ion selective electrode is disposed on the inside of the ring shape of the second extraction electrode.
- The system of claim 1 or 3, wherein the first extraction electrode among the extraction electrodes has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive media on the opposite side of the side in contact with the skin, and the second extraction electrode among the extraction electrodes has a partly cut ring shape, and is disposed on the ion conductive media on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode wraps around the first extraction electrode, and is electrically connected to the working electrode so as to be conductive therewith, the reference electrode wraps around the first extraction electrode from the part to where the counter electrode does not extend, and the ion selective electrode is disposed on the inside of the ring shape of the second extraction electrode.
- The system of claim 1 or 3, wherein the first extraction electrode among the extraction electrodes has a partly cut ring shape, wraps around the working electrode, and is disposed on the ion conductive media on the opposite side of the side in contact with the skin, and the second extraction electrode among the extraction electrodes has a partly cut ring shape, and is disposed on the ion conductive media on the opposite side of the side in contact with the skin, wherein the first extraction electrode and the second extraction electrode are separated from each other, and the counter electrode, the ion selective electrode and the reference electrodes wrap around the first extraction electrode together, without being in contact with one another.
- A method of measuring a blood glucose level using the system according to any one of claims 1 though 7, without calibrating by drawing blood.
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KR1020080017785A KR20090092506A (en) | 2008-02-27 | 2008-02-27 | Glucose measuring system |
KR10-2008-0017785 | 2008-02-27 |
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KR20060082852A (en) * | 2003-08-15 | 2006-07-19 | 애니머스 테크놀로지스 엘엘씨 | Microprocessors, devices, and methods for use in monitoring of physiological analytes |
SG146630A1 (en) * | 2003-09-03 | 2008-10-30 | Life Patch International Inc | Personal diagnostic devices and related methods |
US7914460B2 (en) * | 2006-08-15 | 2011-03-29 | University Of Florida Research Foundation, Inc. | Condensate glucose analyzer |
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2008
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KR20090092506A (en) | 2009-09-01 |
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