KR20130066841A - Glycosylated hemoglobin sensor strip, glycosylated hemoglobin measurement device and method for glycosylated hemoglobin measurement - Google Patents

Abstract

PURPOSE: A glycosylated hemoglobin sensor strip, a glycosylated hemoglobin measuring device, and a glycosylated hemoglobin measuring method using the same are provided to confirm whether a sample is properly loaded or not and whether the sample is lack or not by using nano particles, which are electrochemical reaction materials, and an electrode and to obtain hematocrit without a separate test. CONSTITUTION: A glycosylated hemoglobin sensor strip(100) comprises a first strip member(200), a conjugated pad, a substrate(9), an electrode, and a second strip member(300). The first strip member includes a measuring window for measuring glycosylated hemoglobin and hemoglobin except for the glycosylated hemoglobin. The conjugated pad is arranged under the first strip member. The substrate supports the conjugated pad. The electrode is penetrate-arranged on the substrate and recognizes an electrochemical reaction by being in contact with the conjugated pad. The second strip member includes through holes and is joined to the first strip member. [Reference numerals] (AA) Flow of a specimen

Description

Glycosylated hemoglobin sensor strip and glycosylated hemoglobin measuring device and method for measuring glycated hemoglobin using the same {GLYCOSYLATED HEMOGLOBIN SENSOR STRIP

The present invention relates to a sensor strip for measuring glycated hemoglobin, an apparatus for measuring glycated hemoglobin, and a method for measuring glycated hemoglobin using the same. More specifically, a nanoparticle capable of inducing an electrochemical reaction with an electrode using an electrochemical method is described. The present invention relates to a glycated hemoglobin sensor strip, a glycated hemoglobin measuring device, and a method for measuring glycated hemoglobin using the same.

Human red blood cells contain proteins necessary for the transport of oxygen called hemoglobin. When blood sugar rises in the blood, some of the glucose in the blood is bound to hemoglobin. The hemoglobin combined with glucose (blood sugar) is called glycated hemoglobin and is also called hemoglobin A-one (HbA1c).

The normal life of red blood cells is about 120 days, and some of the red blood cells in our body are destroyed every day, and the amount of red blood cells similar to this destroyed amount is generated and maintained at a constant level. However, when glycated hemoglobin is made by combining with blood sugar, the red blood cells have a lifetime of glycated hemoglobin until decomposed.

Glucose testing is a test that checks how much sugar is in the blood every day, whereas glycated hemoglobin test reflects the average blood sugar level of 120 days.

In the case of blood glucose test, fasting blood glucose level should be fasted for at least 8 hours, and to check blood sugar level after meals, blood sampling should be done after about 2 hours, but glycated hemoglobin test is performed regardless of meal time. It has the advantage of being inspected.

On the other hand, the glycated hemoglobin test reflects a relatively long-term blood glucose level, it is used as an indicator to know whether diabetes is well managed by treatment in recent months. In other words, the treatment goal of diabetes is to maintain normal blood sugar in order to prevent complications, and frequent blood glucose measurement is necessary to determine whether diabetes management is performed well.

However, measuring blood glucose frequently is cumbersome, so if you can't measure blood glucose often, or if you don't need to measure it often, a glycated hemoglobin test can give you a relatively long-term average of blood sugar with a single measurement. It is easy to see if this is going well.

In the prior art, glycated hemoglobin has been measured using immunochromatography, which allows easy and simple measurement of blood sugar levels for a relatively long time with a single measurement. However, the glycated hemoglobin measurement had a problem of using a clinical laboratory or expensive equipment, the existing simple method of measuring glycated hemoglobin was not available immediately because of the hematocrit different from person to person, There was a problem that the exact glycated hemoglobin could not be obtained.

In addition, in the conventional chromatographic method, it is not possible to determine when the sample flows, and thus it is not possible to determine whether the sample is properly loaded on the strip and whether the amount of the sample is insufficient.

In addition, in the prior art, a method of reducing glycation hemoglobin by measuring glycated hemoglobin by subtracting hemoglobin from which hemoglobin has been removed has been performed, but it is difficult to obtain accurate glycated hemoglobin by only this method.

Accordingly, the present invention has been made to solve the above-mentioned conventional problems, and an object thereof is to provide a glycated hemoglobin sensor strip using nanoparticles and electrodes which are electrochemical reactants.

Another object of the present invention is to provide a glycated hemoglobin measuring apparatus for measuring glycated hemoglobin using the glycated hemoglobin sensor strip.

In addition, the present invention is to measure the glycated hemoglobin by using the average value of the glycated hemoglobin value and the total hemoglobin except the glycated hemoglobin except for the glycated hemoglobin and the total hemoglobin, glycated hemoglobin, and glycated hemoglobin, respectively Its purpose is to provide a method for measuring glycated hemoglobin.

In addition, an object of the present invention is to provide a method for measuring glycated hemoglobin, by correcting optically measured reflectance according to hematocrit, to obtain accurate glycated hemoglobin, regardless of the different hematocrit.

In order to achieve the above object, the present invention in the glycated hemoglobin sensor strip; A first strip member having a measurement window for measuring hemoglobin except for hemoglobin, glycated hemoglobin and glycated hemoglobin; A conjugation pad disposed below the first strip member; A substrate for supporting the conjugation pad; An electrode disposed through the substrate and contacting the conjugation pad to recognize an electrochemical reaction; And a second strip member having a through hole therein and coupled with the first strip member.

In addition, the measurement window comprises a first measurement window for measuring the total hemoglobin; A second measurement window for measuring glycated hemoglobin; And a third measurement window for measuring hemoglobin except for glycated hemoglobin.

In addition, the conjugation pad may include a first conjugation pad treated with a reagent including nanoparticles for inducing an electrochemical reaction; A second conjugation pad treated with glycated hemoglobin antibody for selective binding with the glycated hemoglobin; And a third conjugation pad treated with a secondary antibody for binding to hemoglobin except for the glycated hemoglobin.

In addition, the electrode may include a first electrode for recognizing an electrochemical reaction occurring in the first conjugation pad; The electrode may include a second electrode for recognizing an electrochemical reaction occurring in the second conjugation pad; The electrode may be configured as a third electrode for recognizing an electrochemical reaction occurring in the third conjugation pad.

In addition, glycated hemoglobin sensor strips; An electrochemical measuring unit including a recognition terminal for recognizing an electrochemical signal from an electrode of the glycated hemoglobin sensor strip; An optical measuring unit including a light receiving unit and a light emitting unit for measuring a reflectance through the measurement window; And a control unit for calculating glycated hemoglobin using measured values of the electrochemical measuring unit and the optical measuring unit.

The control unit may determine whether the sample is insufficient by measuring the loading time of the sample through the electrochemical measuring unit.

The control unit may output an error message when the sample is insufficient as a result of the determination, and measure the reflectance of hemoglobin except for glycated hemoglobin and glycated hemoglobin through the optical measuring unit when the sample is not insufficient.

In addition, the control unit is obtained by subtracting the reflectance value of the hemoglobin except the glycated hemoglobin measured in the third measurement window from the reflectance value of the total hemoglobin measured in the first measurement window and the reflectance value of the glycated hemoglobin measured in the second measurement window It is characterized by calculating the glycated hemoglobin by calculating the average value of.

The control unit may calculate a hematocrit correction factor using a loading time point of the sample measured by the electrochemical measuring unit.

The control unit may calculate the corrected glycated hemoglobin by applying the hematocrit correction factor.

The apparatus may further include a display unit for displaying the output error message and the glycated hemoglobin in which the hematocrit is corrected.

In addition, the glycated hemoglobin measurement method using the glycated hemoglobin measurement device, S1 step of measuring the reflectance of the total hemoglobin through an optical measurement in the first measurement window; S2 step of recognizing the loading time of the sample through the first electrode in the first measurement window; S3 step of recognizing the loading time of the sample through the second electrode in the second measurement window; S4 step of recognizing the loading time of the sample through the third electrode in the third measurement window; Step S5 of measuring hemoglobin reflectance excluding glycated hemoglobin and glycated hemoglobin by optical measurements in the second and third measurement windows; And a step S6 of calculating glycated hemoglobin based on the measured reflectance.

In addition, after the step S4, if the arrival time from the step S2 to the step S3 exceeds the delayed allowable time, it is determined that the amount of the sample is insufficient, and characterized in that the display of the sample lack error display on the display unit.

In addition, if the time to reach the step S4 to the step S4 after the step S4 exceeds the delay allowable time, it is determined that the amount of the sample is insufficient, characterized in that to display the sample insufficient error display on the display unit.

In addition, when the arrival time does not exceed the delayed allowable time, the hemoglobin reflectance except for glycated hemoglobin and glycated hemoglobin is measured in step S5.

In addition, the reflectance when calculating the glycated hemoglobin in step S6, the total hemoglobin reflectance measured in step S1 minus the hemoglobin reflectance except the glycated hemoglobin measured in step S5 and the glycated hemoglobin reflectance measured in step S5 It is characterized by using the average value of.

The step S6 may include calculating hematocrit according to the time taken from the step S2 to the steps S3 and S4; Calculating a hematocrit correction factor using the hematocrit; Calculating a reflectance value after correction with the hematocrit correction factor; And calculating the hematocrit-corrected glycated hemoglobin by using the reflectance value after the correction.

Accordingly, according to the glycated hemoglobin sensor strip according to the present invention, using nanoparticles and electrodes, which are electrochemical reactants, it is possible to check whether the sample is properly loaded and whether the sample is insufficient, and hematocrit can be obtained without a separate test. Will be.

In addition, according to the glycated hemoglobin measurement device according to the present invention, the hematocrit of the sample is recognized through an electrochemical reaction, thereby having the effect of correcting the effect of hematocrit.

In addition, according to the method for measuring glycated hemoglobin according to the present invention, the hematocrit obtained from the apparatus for measuring glycated hemoglobin can be accurately measured for hematocrit-corrected glycated hemoglobin, and hemoglobin except for total hemoglobin, glycated hemoglobin and glycated hemoglobin, respectively. Determination of the glycated hemoglobin value by using this, bar has the effect of reducing the error in the detection measurement.

1 is a block diagram of a glycated hemoglobin sensor strip according to an embodiment of the present invention.
2 is a measuring apparatus of a glycated hemoglobin sensor strip according to an embodiment of the present invention.
3a to 3e is an operation of the glycated hemoglobin sensor strip according to the present invention.
4 is a flowchart of a method for measuring glycated hemoglobin according to an embodiment of the present invention.

Hereinafter, with reference to the accompanying drawings will be described in detail preferred embodiments of the glycated hemoglobin sensor strip according to the present invention. In the drawings, the same reference numerals are used to designate the same or similar components throughout the drawings. In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted when it may make the subject matter of the present invention rather unclear.

1 is a block diagram of a glycated hemoglobin sensor strip according to an embodiment of the present invention. Referring to FIG. 1, the red arrow indicates the flow of the sample, and the sample is loaded into the sample pad 4 to proceed in the direction of the arrow by the absorbent pad 8.

The glycated hemoglobin sensor strip 100 of the present invention is the first strip member 200 including the first, second and third measurement windows (1, 2, 3), the sample pad (4) which is a portion to which the sample is loaded , First, second and third conjugation pads 5, 6, 7 and absorbent pads 8 for inducing the flow of the sample are arranged on the substrate 9, and electrochemical reactions on the substrate 9. First, second, and third electrodes 11, 12, and 13 for recognizing a structure are disposed through the substrate 9, and a second strip member for supporting the strip under the substrate 9. It consists of 300.

The first strip member 200 functions to protect the pads 4, 5, 6, 7 and 8 disposed on the substrate 9 and to form the glycated hemoglobin sensor strip 100. Combine with 300. The strip members 200 and 300 may use various types of materials such as plastic or reinforced plastic. In addition, a measurement window for measuring hemoglobin is included, and the measurement window may be one, or may be composed of a plurality. In FIG. 1, first, second and third measurement windows 1, 2 and 3 are included to measure each hemoglobin. Conjugation pads are arranged in correspondence with each measurement window, the number of which is determined according to the number of measurement windows.

The first measurement window 1 is for measuring the total hemoglobin of the sample and is disposed in a portion corresponding to the first conjugation pad 5. The second measurement window 2 is for measuring glycated hemoglobin and is disposed at a portion corresponding to the second conjugation pad 6. The third measurement window 3 is for measuring hemoglobin except glycated hemoglobin and is disposed at a portion corresponding to the third conjugation pad 7.

The substrate 9 may include a sample pad 4, which is a portion into which a sample is loaded, a first conjugation pad 5 disposed on the sample pad 4, and a first conjugation pad overlapping the sample pad 4. A second conjugation pad 6 disposed on the lower part of the pad 5 so as to overlap the first conjugation pad 5, and the conjugation pad 6 above the second conjugation pad 6. The third conjugation pad 7 disposed to overlap, and the absorbent pad 8 disposed to overlap with the third conjugation pad 7 on the upper part of the third conjugation pad 7 to induce the flow of a sample. And first, second and third electrodes 11, 12, 13 for recognizing an electrochemical reaction. The first, second, and third electrodes 11, 12, 13 penetrate through the substrate 9 and the second strip member 300 to recognize the recognition terminal 14 in the electrochemical measurement unit 10 shown in FIG. 2. , 15, 16).

The sample pad 4 is a portion in which the sample is loaded. When the sample is loaded, the absorbent pad 8 absorbs the sample using a hydrophilic phenomenon so that the sample is first, second, and third conjugation pads 5, 6, and the like. 7) allow it to flow through. In addition, the sample pad may also include reagents to be described later, which is to facilitate the binding of the hemoglobin and the reagent.

The first conjugation pad 5 is coated with a reagent using a colorant, a fluorescent material, and the like, and the reagent includes nanoparticles for inducing an electrochemical reaction. The nanoparticles may include any one of nanoparticles by synthesis of metals and polymers such as gold, silver, and carbon, and any type of nanoparticles may be used as long as they induce an electrochemical reaction. The glycated hemoglobin antibody may be treated in advance on the nanoparticles.

In the first conjugation pad 5 a sample is combined with the reagents and flows to the second conjugation pad 6. When combined with the reagents, the sample develops color or fluorescence, which allows the measurement of total hemoglobin.

The second conjugation pad 6 is treated with glycated hemoglobin antibody. Here, the glycated hemoglobin and glycated hemoglobin antibodies are selectively bound, and the glycated hemoglobin of the sample can be measured using this.

The third conjugation pad 7 is treated with a secondary antibody (Anti-mouse lgG) as a reaction site of hemoglobin except for glycated hemoglobin, where hemoglobin except for glycated hemoglobin is collected, and hemoglobin except glycated hemoglobin is collected. Allows you to measure.

Electrodes are placed to recognize the electrochemical reaction, and the electrodes placed vary depending on the number of measurement windows.

The first, second and third electrodes 11, 12, 13 are formed through the substrate 9, and the first electrode 11 is disposed at a position corresponding to the first conjugation pad 5. In order to recognize the electrochemical reaction generated in the first conjugation pad 5, the recognized electrochemical signal is a starting point of loading of the sample.

 The second electrode 12 is disposed at a position corresponding to the second conjugation pad 6, which is also for recognizing an electrochemical reaction occurring in the second conjugation pad 6. Is the second loading time of the sample.

  The third electrode 13 is disposed at a position corresponding to the third conjugation pad 7, which is also for recognizing an electrochemical reaction occurring in the third conjugation pad 7. Is the third loading time of the sample.

The first, second, and third electrodes 11, 12, and 13 described above are each composed of two, one is a working electrode, and the other is a counter electrode. The working electrode refers to an electrode to which an actual electrochemical reaction occurs, and when a mediator, an electron transfer material in nanoparticles, receives a voltage, electrons are generated and transferred to the electrode. The electrochemical reaction generated by the application of such a voltage determines the loading time of the sample based on the principle of obtaining the current value generated in the working electrode relatively based on the current value of the reference electrode.

In addition, the electrodes 11, 12, and 13 may be formed of one of gold, silver, carbon, copper, ITO, and Palladium. In addition, it is also possible to use a surface such as gold, silver, carbon, copper, or the like on a metal such as Inconel, Inva, Coba, molybdenum, nickel, tungsten, iron, or the like. Of these, metals such as gold, silver, copper, and carbon are preferably used as electrodes, but gold-plated electrodes are most recommended.

The second strip member 300 is coupled to the strip top plate 200 with the substrate 9 therebetween. Here, the coupling with the first strip member 200 is made through a mechanical coupling such as interference fit or a physical coupling using an adhesive.

In addition, the second strip member 300 has a through hole in a portion corresponding to the first, second and third recognition terminals 14, 15, and 16 formed in the electrochemical measurement unit 10 shown in FIG. 2. The electrodes are connected to the recognition terminals 14, 15, and 16 through the through holes.

Therefore, the glycated hemoglobin sensor strip according to an embodiment of the present invention can check whether the sample is properly loaded or not by using the electrochemical reactant nanoparticles and the electrode, and the hematocrit without a separate test. Will be available.

2 is a measuring apparatus of a glycated hemoglobin sensor strip according to an embodiment of the present invention.

An electrochemical measuring unit including a glycated hemoglobin sensor strip 100 and a recognition terminal 14, 15, and 16 for recognizing electrochemical signals generated from the electrodes 11, 12, and 13 of the glycated hemoglobin sensor strip ( 10) and an optical measuring unit 20 which obtains a reflectance by measuring the reflected light by irradiating light onto the respective conjugation pads 5, 6, and 7, and for displaying a glycated hemoglobin measurement result and an error message. The control unit 400 controls the display unit 500, the optical measuring unit 20, and the display unit 500, and performs calculations to correct the measurement result.

The electrochemical measuring unit 10 may include the first, second and third recognition terminals 14, 15, corresponding to the first, second, and third electrodes 11, 12, 13 to recognize the electrochemical signal. 16). The recognition terminals 14, 15, and 16 may protrude to form a through hole of the second strip member 300 of the glycated hemoglobin sensor strip 100, and may be connected to the electrodes 11, 12, and 13. 11, 12, and 13 may be installed through the second strip member 300, and may be configured to be in contact with the recognition terminals 14, 15, and 16.

The optical measuring unit 20 includes a light emitting unit 17 and a light receiving unit 18 and is installed around the first, second and third measuring windows 1, 2, and 3 of the glycated hemoglobin sensor strip 100. do. The light emitting unit 17 irradiates light, and any light generated such as a light emitting diode (LED), an infrared diode, a laser diode, or a halogen lamp may be used as a light source. The light receiving unit 18 receives the light sent from the light emitting unit 17. Any light receiving unit such as a photodiode PD or an avalanche photodiode APD can be used.

The light emitting unit 17 emits light onto each of the conjugation pads 5, 6, and 7, and the reflected light is measured by the light receiving unit 18. In this case, each of the conjugation pads 5, 6, and 7 has a different amount of reflected light incident on the light receiving unit 18 according to the amount of the reagent and the sample containing the coloring or fluorescent substance, and the light receiving unit 18 is incident. The reflectance can be measured according to the light amount of the reflected light.

The display unit 500 is for displaying glycated hemoglobin measurement results and error messages. The display unit 500 may include a liquid crystal display (LCD), a printer, a voice form, and the like, and may include various types of display devices.

The controller 400 controls the optical measuring unit 20, the display unit 500, and the electrochemical measuring unit 10, respectively. In addition, the calculation of calculating the hematocrit correction factor using the loading time of the sample measured by the electrochemical measuring unit 10, the calculation of calculating the glycated hemoglobin in which the hematocrit is corrected by applying the hematocrit correction factor in the control unit 400 To perform. The calculation for calculating glycated hemoglobin and the calculation of hematocrit correction factor are described in the method for measuring glycated hemoglobin which will be described later.

In addition, the controller 400 measures loading times of the samples through the first, second, and third recognition terminals 14, 15, and 16 of the electrochemical measuring unit 10, and compares them to determine whether the samples are insufficient. It also functions to judge. The determination of whether the sample is insufficient compares the time recognized by the second and third recognition terminals 15 and 16 from the time recognized by the first recognition terminal 14 with the delay allowable time described below. If the delay is larger than the allowable time, the sample is insufficient or the sample is not loaded properly, and the display unit 500 outputs a sample shortage error indication. When the delay time is smaller than that, it means that the sample is properly loaded, and the optical measurement unit 20 measures the reflectance of hemoglobin except glycated hemoglobin and glycated hemoglobin.

In addition, when measuring the glycated hemoglobin value, the reflectance value of the total hemoglobin measured in the first measurement window 1 minus the reflectance value of the hemoglobin except for the glycated hemoglobin measured in the third measurement window 3 and the second Calculation which averages the reflectance value of glycated hemoglobin measured in the measurement window 2 is performed. In addition, the controller 400 is responsible for the overall control of the glycated hemoglobin measurement device.

Therefore, the glycated hemoglobin measuring device according to the present invention has the effect of correcting the effect of hematocrit by measuring the hematocrit of the sample through an electrochemical reaction.

3a to 3e is an operation of the glycated hemoglobin sensor strip according to the present invention. 3A shows loading of a sample onto a sample pad, wherein the first conjugation pad has a reagent treated with nanoparticles containing glycated hemoglobin antibody, a second conjugation pad having a glycated hemoglobin antibody, and a third conjugation pad. In the following, the secondary antibody is treated as an example.

Figure 3b shows that the total hemoglobin binds to the nanoparticles in the first conjugation pad, where the total hemoglobin bound with the nanoparticles is first optically measured to obtain reflectance. In addition, the electrochemical signal is generated due to the bonded nanoparticles, and the electrode recognizes it so that the first recognition time of the sample can be known.

Figure 3c illustratively shows that the glycated hemoglobin antibody and the glycated hemoglobin are combined in the second conjugation pad, and here also the electrochemical signal is generated by the bound nanoparticles, the electrode recognizes the second of the sample The recognition point can be known.

3D shows that glycated hemoglobin combined with glycated hemoglobin antibody is collected in the second conjugation pad and the remaining sample is collected by binding to the secondary antibody (Anti-mouse lgG) in the third conjugation pad, which also binds Electrochemical signals are generated through the nanoparticles, and the third recognition point of the sample is recognized by recognizing the electrochemical signal.

Figure 3e shows an example after the glycated hemoglobin and hemoglobin are all captured. After the above process, the amount of hemoglobin is determined by optically measuring the reflectances in the second and third measurement windows.

Therefore, according to the present invention, the amount of glycated hemoglobin can also be obtained through the reflectance measured in the second measurement window. In addition, for a more accurate measurement value, the total hemoglobin reflectance measured in the first measurement window minus the hemoglobin reflectance except the glycated hemoglobin measured in the third measurement window and the glycated hemoglobin reflectance measured in the second measurement window Glycated hemoglobin can be obtained. In this way, more accurate quantitative analysis of glycated hemoglobin is possible.

The following table shows the experimentally obtained loading time of each electrode according to the change of hematocrit.

In Table 1, the horizontal column represents the hematocrit and the vertical column represents the electrode of the glycated hemoglobin sensor strip. When the sample has a hematocrit of 19.8%, the time when the sample reaches the first electrode 11 is the time measurement start point, and the second recognition time when the sample reaches the second electrode 12 is 4 seconds and the third time. The third recognition time reaching the electrode 13 is 28 seconds.

When the hematocrit of the sample is 61.2%, the second recognition time when reaching the second electrode 12 is 29 seconds, and the third recognition time when reaching the third electrode 13 is 87 seconds.

This is because the larger the hematocrit of the sample, the higher the viscosity, so that the flow rate of the sample is relatively different.

As such, each electrode arrival time of the sample can be checked. If this is linearized, the hematocrit of the sample can be obtained only at the second and third recognition points.

In addition, it is possible to obtain the delayed allowable time measured at each electrode from Table 1, and through this, it is possible to determine the time point at which the sample lack error is displayed. The table below illustrates this rationally.

Therefore, when the second recognition time is 30 seconds or more, or when the third recognition time is 88 seconds or more, it means that the amount of the sample is insufficient or the sample is not loaded properly. In this case, an error message can be displayed to prevent a user's measurement error, and reflectance measurement in the second and third measurement windows 2 and 3 is performed only when there is no error message, thereby making it inaccurate. One measurement can be prevented in advance.

4 is a flowchart of a method for measuring glycated hemoglobin according to an embodiment of the present invention.

Referring to Figures 2 and 4, the sample is first loaded on the sample pad (4). Then, the absorbent pad 8 moves the sample toward the first conjugation pad 5 and passes the first conjugation pad 5 including the reagent treated with the nanoparticles to which the glycated hemoglobin antibody is bound. Here, the sample and the nanoparticles are to be bonded. (S100)

Next, the control unit 400 sends a signal to the optical measuring unit 20 to measure the reflectance. The reagents include a chromophore or a fluorescent material. The reagents emit light from the light emitting unit 17 of the optical measuring unit to the first conjugation pad 5 and reflect the reflected light from the light receiving unit 18 to reflect the light. Will be measured. Here, the total hemoglobin can be measured through the measured reflectance (S110).

 Next, the electrochemical reaction by the nanoparticles is recognized by the first electrode 11 and the signal is sent to the first recognition terminal 14. Here, the measured time becomes the first recognition time of the sample. Based on this time point, the hematocrit can be obtained by comparing the next recognition time and the third recognition time, and the amount of the sample is insufficient or the sample is properly loaded. It can be confirmed whether or not. (S120)

 The hemoglobin combined with reagents then passes through the second conjugation pad 6, and the second conjugation pad 6 is treated with glycated hemoglobin antibodies, wherein the glycated hemoglobin and glycated hemoglobin antibodies of the sample are selected. It is combined to be collected. (S130)

The second electrode 12 also grasps the second recognition point of the sample on the same principle as that of the first electrode 11 (S140).

 Next, the third conjugation pad 7 is treated with a secondary antibody, and the hemoglobin other than glycated hemoglobin is collected here (S150).

The third electrode 13 also grasps the third recognition point of the sample again on the same principle as in the first electrode 11 (S160).

Next, when the time from the first recognition time to the second and the third recognition time is greater than the delayed allowable time (S170: Y), the control unit 400 compares the recognition time (S170). Sample insufficient error indication is output (S180).

When the time from the first recognition time to the second and third recognition time is smaller than the delayed allowable time (S170: N), the second light emitting unit 17 of the second and third measurement windows 2 and 3 is turned on. And irradiating light to the third conjugation pads 6 and 7 to recognize the light reflected by each light receiving unit 18 to measure the reflectance.

 The reflectance value of glycated hemoglobin may be calculated using the reflectance value measured in the second measurement window 2, but for a more accurate calculation, the third measurement window 3 may be used in the reflectance value of the total hemoglobin measured in the first measurement window 1. The average value of the value obtained by subtracting the reflectance value of the hemoglobin except for the glycated hemoglobin and measured by the second measurement window 2 is calculated by the controller 400 as the measured reflectance value.

In addition, since the reflectance value measured according to the hematocrit of the sample is different, it is somewhat inaccurate to directly obtain glycated hemoglobin using the measured reflectance. This should be further provided with a step of correcting this, Table 3 is the experimental data to obtain the glycated hemoglobin based on this by measuring the reflectance for each hematocrit.

In Table 3, the width is hematocrit and the length means glycated hemoglobin. When the hematocrit is 42.3%, the glycated hemoglobin value according to the change in reflectance is summarized by Equation 1 as follows.

When the hematocrit is 19.8%, the viscosity is thin, so the reflectance value is larger than that of the baseline 42.3%. Therefore, when compared with the reference value, when the glycated hemoglobin is 1%, the reflectance is 91%, and when the glycated hemoglobin is 13%, the reflectance is 28,7%. The reflectance values when the glycated hemoglobin was 1 to 13% were measured, respectively, and the reflectance when the hematocrit was 19.8% was subtracted from the reflectance when the hematocrit was 42.3%, and the average value of the difference was -9.8. .

When the hematocrit is 61.2%, since the viscosity is large, the reflectance value is smaller than that of the reference value of 42.3%. The reflectance values of the glycated hemoglobin were measured at 1 to 13%, respectively, and the reflectance at the hematocrit of 42.3% was subtracted from the reflectance at the hematocrit of 61.2%, indicating that the mean value was +10.2. .

As above, the average difference in reflectance is -4.8 when the hematocrit is 31,5%, and +5.0 when the hematocrit is 49.8%.

If this is expressed by linearizing it is represented by the following equation (2).

Therefore, through this hematocrit correction factor, a reflectance that can be used irrespective of the hematocrit ratio can be obtained through the control unit 400. When the corrected reflectance value is applied to Equation 2, accurate glycated hemoglobin can be obtained. (S210)

Next, the hematocrit correction factor should be multiplied by the pre-correction reflectance to obtain the post-correction reflectance. Equation 3 to obtain the reflectance after the correction is as follows (S220).

Next, the hematocrit-corrected glycated hemoglobin is calculated by using Equation 4.

If the above equation 4 is calculated and applied in the control unit 400, the accurate glycated hemoglobin level can be obtained regardless of the ratio of hematocrit in one test.

Therefore, the method of measuring glycated hemoglobin according to the present invention, by using the hematocrit obtained from the glycated hemoglobin measurement device, it is possible to measure the correct hematocrit-corrected glycated hemoglobin, and measure the hemoglobin except for total hemoglobin, glycated hemoglobin and glycated hemoglobin, respectively. And, using this to derive the value of glycated hemoglobin, there is an effect of reducing the error in the detection measurement as possible.

The foregoing description is merely illustrative of the technical idea of the present invention, and various changes and modifications may be made by those skilled in the art without departing from the essential characteristics of the present invention. Therefore, the embodiments disclosed in the present invention are intended to illustrate rather than limit the scope of the present invention, and the scope of the technical idea of the present invention is not limited by these embodiments. The scope of protection of the present invention should be interpreted by the following claims, and all technical ideas within the scope equivalent thereto should be construed as being included in the scope of the present invention.

1: first measurement window 2: second measurement window
3: third measurement window 4: sample pad
5: first conjugation pad 6: second conjugation pad
7: 3rd conjugation pad 8: absorption pad
9: substrate 10: electrochemical measurement unit
11: first electrode 12: second electrode
13: third electrode 14: first recognition terminal
15: second recognition terminal 16: third recognition terminal
17: light emitting portion 18: light receiving portion
20: optical measuring unit 100: glycated hemoglobin sensor strip
200: first strip member 300: second strip member
400: control unit 500: display unit

Claims (18)

In a glycated hemoglobin sensor strip;
A first strip member having a measurement window for measuring hemoglobin except for hemoglobin, glycated hemoglobin and glycated hemoglobin;
A conjugation pad disposed below the first strip member;
A substrate for supporting the conjugation pad;
An electrode disposed through the substrate and contacting the conjugation pad to recognize an electrochemical reaction; And
A glycosylated hemoglobin sensor strip comprising a; and a through-hole, the second strip member coupled to the first strip member. The method of claim 1,
The measurement window comprises a first measurement window for measuring the total hemoglobin;
A second measurement window for measuring glycated hemoglobin; And
A glycated hemoglobin sensor strip comprising: a third measurement window for measuring hemoglobin except glycated hemoglobin. 3. The method of claim 2,
The conjugation pad may include a first conjugation pad treated with a reagent including nanoparticles for inducing an electrochemical reaction;
A second conjugation pad treated with glycated hemoglobin antibody for selective binding with the glycated hemoglobin; And
A glycated hemoglobin sensor strip comprising a; a third conjugation pad treated with a secondary antibody for binding with hemoglobin except for glycated hemoglobin. The method of claim 3, wherein
The electrode may include a first electrode for recognizing an electrochemical reaction occurring in the first conjugation pad;
The electrode may include a second electrode for recognizing an electrochemical reaction occurring in the second conjugation pad;
The electrode is a glycated hemoglobin sensor strip, characterized in that consisting of; a third electrode for recognizing the electrochemical reaction occurring in the third conjugation pad. A glycated hemoglobin sensor strip according to any one of claims 1 to 4;
An electrochemical measuring unit including a recognition terminal for recognizing an electrochemical signal from an electrode of the glycated hemoglobin sensor strip;
An optical measuring unit including a light receiving unit and a light emitting unit for measuring a reflectance through the measurement window; And
And a control unit for calculating glycated hemoglobin by using the measured values of the electrochemical measuring unit and the optical measuring unit. The method of claim 5, further comprising:
The control unit is a glycated hemoglobin measurement device, characterized in that for determining the lack of sample by measuring the loading time of the sample through the electrochemical measuring unit. The method of claim 6, further comprising:
The control unit outputs a sample shortage error indication to the display unit when the sample is insufficient, and if the sample is not insufficient, the control unit measures the reflectance of the hemoglobin except for glycated hemoglobin and glycated hemoglobin through the optical measuring unit. Glycated hemoglobin measuring device. 8. The method of claim 7, further comprising:
The control unit subtracts the reflectance value of the hemoglobin except for the glycated hemoglobin measured in the third measurement window from the reflectance value of the total hemoglobin measured in the first measurement window and the average value of the reflectance value of the glycated hemoglobin measured in the second measurement window. Glycated hemoglobin measurement device, characterized in that for calculating the glycated hemoglobin. The method of claim 8;
The control unit is a glycated hemoglobin measurement device, characterized in that for calculating the hematocrit correction factor using the loading time of the sample measured by the electrochemical measuring unit. The method of claim 9;
The control unit is a glycated hemoglobin measurement device, characterized in that for calculating the corrected glycated hemoglobin by applying the hematocrit correction factor. The method of claim 10;
The apparatus for measuring glycated hemoglobin further comprises a display unit for displaying the outputted error message and the glycated hemoglobin corrected for the hematocrit. In the method of measuring glycated hemoglobin using the glycated hemoglobin measuring device of claim 11,
S1 step of measuring the reflectance of the total hemoglobin through the optical measurement in the first measurement window;
S2 step of recognizing the loading time of the sample through the first electrode in the first measurement window;
S3 step of recognizing the loading time of the sample through the second electrode in the second measurement window;
S4 step of recognizing the loading time of the sample through the third electrode in the third measurement window;
Step S5 of measuring hemoglobin reflectance excluding glycated hemoglobin and glycated hemoglobin by optical measurements in the second and third measurement windows; And
S6 step of calculating the glycated hemoglobin based on the measured reflectance; glycosylated hemoglobin measurement method comprising a. The method of claim 12;
After the step S4, if the reaching time from step S2 to step S3 exceeds the delayed allowable time, it is determined that the amount of the sample is insufficient, and the glycation hemoglobin measurement method characterized in that it outputs a sample insufficient error display on the display unit. The method of claim 12;
After the step S4, if the arrival time from the step S2 to the step S4 exceeds the delayed allowable time, it is determined that the amount of the sample is insufficient, and the glycation hemoglobin measurement method characterized in that it outputs a sample shortage error display on the display. The method of claim 13;
The glycated hemoglobin measurement method of measuring the hemoglobin reflectance except the glycated hemoglobin and glycated hemoglobin in the step S5 when the time to reach does not exceed the delayed allowable time. The method of claim 14;
The glycated hemoglobin measurement method of measuring the hemoglobin reflectance except the glycated hemoglobin and glycated hemoglobin in the step S5 when the time to reach does not exceed the delayed allowable time. The method of claim 12;
The reflectance at the time of calculating the glycated hemoglobin in step S6, the total hemoglobin reflectance measured in step S1 minus the hemoglobin reflectance except the glycated hemoglobin measured in step S5 and the average value of the glycated hemoglobin reflectance measured in step S5 Method for measuring glycated hemoglobin, characterized in that using. 18. The method of claim 17;
The step S6 may include calculating hematocrit according to the time taken from the step S2 to the steps S3 and S4;
Calculating a hematocrit correction factor using the hematocrit;
Calculating a reflectance value after correction with the hematocrit correction factor; And
And calculating the hematocrit-corrected glycated hemoglobin by using the reflectance value after the correction.

Images