JP2009233253A - Blood sugar measuring apparatus and method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a blood sugar measuring apparatus and method capable of highly accurately measuring a blood-sugar level. <P>SOLUTION: This blood sugar measuring apparatus is provided with: a light emitting element 25 that emits a second light λ<SB>2</SB>with at least one absorption waveform specific to a pigment generated by a reaction, and a first light λ<SB>1</SB>with at least one absorption waveform specific to hemoglobin in blood specimen, to test paper; a light receiving element 26 that receives a reflected light of the light emitted by the light emitting element 25; a CPU 41 that calculates a reflectance R<SB>1</SB>of the light with absorption waveform of hemoglobin based on the receiving light intensity of the light receiving element 26 and a reflectance R<SB>2</SB>of the light with absorption waveform of the pigment, based on the intensity of the received light of the light receiving element 26; a storage section 42 that stores a first calibration curve group indicating a relationship between a hematocrit value (Ht) and the reflectance R<SB>1</SB>for every blood-sugar level, and a second calibration curve group indicating a relationship between the blood-sugar value (G) and the reflectance R<SB>2</SB>for every plurality of hematocrit values (Ht); and a blood-sugar value calculation section that substitutes the reflectance R<SB>1</SB>and the reflectance R<SB>2</SB>calculated by the CPU 41 for the first calibration curve group and the second calibration curve group to calculate the blood-sugar value (G). <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a blood glucose measurement device and a blood glucose measurement method.

  For prevention and treatment of diabetes, it is important to know blood glucose level.

As a technique for optically measuring a blood glucose level from collected blood, a glucose concentration quantification method as shown in Patent Document 1 below is known. The quantification method disclosed in Patent Document 1 uses a multilayer analytical element containing a coloring composition, and uses red light of a red blood cell dye using light of one wavelength defined within a range of 500 to 590 nm. On the other hand, while measuring the concentration, the color density of the blood sample is measured using light of one wavelength determined within the range of the shorter wavelength side region than 500 nm or the longer wavelength side region than 590 nm. According to the quantification method of such a configuration, the glucose concentration can be quantified while correcting the glucose value obtained from the color concentration using the hematocrit value obtained from the red concentration.
JP 2000-262298 A

  However, in the above quantification method, the measurement accuracy of the hematocrit value obtained using light of one wavelength defined within the range of 500 to 590 nm is insufficient, so the glucose concentration cannot be accurately quantified. There is a problem.

  The present invention has been made to solve the above-described problems. Accordingly, an object of the present invention is to provide a blood glucose measurement device and a blood glucose measurement method capable of accurately measuring a blood glucose level.

The blood glucose measurement device of the present invention is a blood glucose measurement device for measuring a blood glucose level using a test paper containing a coloring reagent that reacts with glucose in a blood sample, and at least one absorption wavelength specific to hemoglobin in the blood sample And at least one light emitting element that irradiates the test paper with light having at least one absorption wavelength specific to the dye generated by the reaction, and reflected light of the light emitted by the light emitting element. Reflection for calculating a reflectance R ₁ of light having an absorption wavelength of the hemoglobin and a reflectance R ₂ of light having an absorption wavelength of the dye, based on at least one light receiving element that receives light and the received light intensity of the light receiving element. a rate calculating unit, for each blood glucose level, a first calibration line group showing the relationship between the hematocrit value and the reflectivity R _1, for each hematocrit value, a second calibration showing a relationship between blood glucose and a reflectance R ₂ The blood glucose level by substituting the reflectance R ₁ and the reflectance R ₂ calculated by the storage unit storing the line group and the reflectance calculating unit into the first calibration curve group and the second calibration curve group Or calculating the hematocrit value by substituting the reflectance R ₁ and the reflectance R ₂ calculated by the reflectance calculation unit into the first calibration curve group and the second calibration curve group. And a blood sugar level calculating unit that calculates the blood sugar level by using the blood sugar level.

The blood glucose measurement method of the present invention is a method for measuring a blood glucose level using a test paper containing a coloring reagent that reacts with glucose in a blood sample, and is light having at least one absorption wavelength specific to hemoglobin in the blood sample. Irradiating the test paper with light having at least one absorption wavelength specific to the dye produced by the reaction, receiving reflected light of the irradiated light, and receiving the light Based on the intensity, a step of calculating a reflectance R ₁ of light having an absorption wavelength of the hemoglobin and a reflectance R ₂ of light having an absorption wavelength of the dye, a hematocrit value and a reflectance R ₁ for each blood glucose level, The calculated reflectance R ₁ and reflectance R ₂ are substituted into the first calibration curve group indicating the relationship between the blood glucose level and the reflectance R ₂ for each hematocrit value. To calculate the blood sugar level, Other includes a step of calculating the blood sugar level is calculated hematocrit value by using the hematocrit value.

  According to the blood glucose measurement device of the present invention, the blood glucose level is calculated by substituting the reflectance of light of two wavelengths into the first calibration curve group and the second calibration curve group stored in advance. Compared to the case where the blood glucose level is calculated based on the reflectance of light having a wavelength, the blood glucose level can be measured more accurately.

  According to the blood glucose measurement method of the present invention, the blood glucose level is calculated by substituting the reflectance of light of two wavelengths into the first calibration curve group and the second calibration curve group stored in advance. Compared to the case where the blood glucose level is calculated based on the reflectance of light having a wavelength, the blood glucose level can be measured more accurately.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 1 is a perspective view showing a schematic configuration of a blood glucose measurement device according to an embodiment of the present invention, and FIG. 2 is a partial cross-sectional view of the blood glucose measurement device shown in FIG.

  As shown in FIG. 1, the blood glucose measurement device 10 according to the present embodiment includes a measurement device main body 20 and a chip 30 attached to the measurement device main body 20. Hereinafter, the chip 30 and the measurement apparatus main body 20 will be described in this order.

(Chip)
The chip 30 holds a blood sample. As shown in FIGS. 1 and 2, the chip 30 includes a holder 31 provided with a thin tube portion 31 a and a test paper 32 fixed inside the holder 31.

  The capillary tube portion 31a introduces a blood sample into the holder 31 from the tip opening by capillary action. The blood sample introduced through the thin tube portion 31 a is absorbed by the test paper 32 inside the holder 31. The test paper 32 is composed of a sheet-like porous substrate, and the test paper 32 is impregnated with a coloring reagent that reacts with glucose and exhibits a color reaction. According to such a configuration, the blood sample introduced into the holder 31 through the narrow tube portion 31a causes a color reaction on the test paper 32 impregnated with the coloring reagent.

  Examples of the material of the test paper 32 include polyesters, polyamides, polyolefins, polysulfones, and celluloses. Examples of the coloring reagent include glucose oxidase (GOD), peroxidase (POD), 4-aminoantipyrine, N-ethyl-N- (2-hydroxy-3-sulfopropyl) -m-toluidine sodium (TOOS). Is mentioned.

(Measurement device body)
The measuring device main body 20 measures the blood sugar level of the blood sample held on the chip 30. As shown in FIG. 1, the measurement device main body 20 of the present embodiment controls the photometry unit 21 and a photometry unit 21 that measures the intensity of reflected light by irradiating a blood sample with two lights having different wavelengths. A control unit (not shown) that performs various calculations on the photometric value data acquired by the photometric unit 21. The photometry unit 21 is provided at the tip of the outer case 22. The control unit is housed inside the outer case 22 together with a power source and the like. A detailed description of the control unit will be described later. On the surface of the outer case 22, a display unit 23 and various switches 24 for displaying blood glucose level measurement results and the like are provided.

As shown in FIG. 2, the photometric unit 21 of the present embodiment receives a light emitting element 25 that emits _two lights λ ₁ and λ ₂ having different wavelengths, and a light receiving element that receives reflected light of the _two lights λ ₁ and λ _2. And an element 26. The light emitting element 25 and the light receiving element 26 are accommodated in a holder 27.

The light emitting element 25 has at least one absorption wavelength (for example, 545 nm) specific to hemoglobin (hereinafter referred to as first light) λ ₁ and at least one specific to a dye generated as a result of a color reaction of a blood sample. Irradiation is performed with light (hereinafter referred to as second light) λ ₂ having an absorption wavelength (for example, 630 nm). The light-emitting element 25 of the present embodiment is a two-wavelength light-emitting diode, which is controlled by the control unit, and is a first light λ _{1 having} an absorption wavelength specific to hemoglobin or a second light λ having an absorption wavelength specific to a dye. ₂ is irradiated. The first and second lights λ ₁ and λ ₂ emitted from the light emitting element 25 of the present embodiment are pulsed light having a cycle of about 0.5 to 3.0 msec and a light emission time of one pulse of 0. It is set to about 05 to 0.3 msec. The first and second lights λ ₁ and λ ₂ emitted from the light emitting element 25 are reflected by the test paper 32. In this embodiment, a two-wavelength light emitting diode is used as the first and second light emitting means, but two one-wavelength light emitting diodes may be provided.

The light receiving element 26 receives the first and second lights λ ₁ and λ ₂ reflected by the test paper 32, and absorbs the absorbance of the blood sample, that is, the first and second lights λ ₁ and λ ₂ of the blood sample. The reflectance is measured.

The light receiving element 26 of the present embodiment is a photodiode that receives the first light λ ₁ and the second light λ ₂ reflected by the test paper 32 and outputs these intensities as photometric value data. To do.

  FIG. 3 is a block diagram showing a schematic configuration of the blood glucose measurement device shown in FIG.

  As described above, the blood glucose measurement device 10 of the present embodiment includes the photometry unit 21 and the control unit 40. Light emission of the light emitting element 25 of the photometry unit 21 is controlled by the control unit 40, and photometric value data from the light receiving element 26 of the photometry unit 21 is input to the control unit 40 via the A / D converter 28. The control unit 40 is electrically connected to an input unit 29 corresponding to the display unit 23 and various switches 24 on the surface of the outer case 22.

  As shown in FIG. 3, the control unit 40 of the present embodiment includes a CPU 41 and a storage unit 42. The storage unit 42 is electrically connected to the CPU 41.

The CPU 41 performs various calculations on the photometric value data for the _two lights λ ₁ and λ _{2 having} different wavelengths. The CPU 41 of the present embodiment calculates the reflectances R ₁ and R ₂ of the blood sample with respect to the _two lights λ ₁ and λ _{2 having} different wavelengths from the photometric value data of the light receiving element 26. The CPU 41 functions as a reflectance calculation unit and a blood sugar level calculation unit.

Here, as a reflectance calculation unit, the CPU 41 serves as a reflectance R ₁ for light having an absorption wavelength specific to hemoglobin and a reflectance R _{2 for} light having an absorption wavelength specific to the dye, based on the received light intensity of the light receiving element 26. And calculate. Further, the CPU 41 substitutes the reflectance R ₁ and the reflectance R ₂ calculated by the reflectance calculator as the blood glucose level calculator into the first calibration curve group and the second calibration curve group described later, and calculates the blood glucose level. calculate. Specific processing of the CPU 41 will be described later.

The storage unit 42 stores a first calibration curve group and a second calibration curve group. The first calibration line group, for each blood glucose level, a relational expression between the hematocrit value and the reflectivity R _1, the second calibration line group, for each hematocrit value, in relation to the blood glucose level and the reflectance R ₂ is there. The first calibration curve group and the second calibration curve group may be stored as a group of coefficients (first coefficient group, second coefficient group) of each relational expression. In addition, the storage unit 42 stores a blood sugar level calculation program.

In the blood glucose measurement device 10 of the present embodiment configured as described above, the first light λ ₁ having a specific absorption wavelength is irradiated to hemoglobin, and the reflectance R ₁ of the first light λ ₁ from the blood sample is measured. Is done. Next, the second light λ ₂ having a specific absorption wavelength is irradiated to the pigment generated by the color reaction of the blood sample, and the reflectance R ₂ of the second light λ ₂ from the blood sample is measured. Next, the blood glucose level of the blood sample is calculated using the two measured reflectances R ₁ and R ₂ . Hereinafter, the flow of blood sugar level measurement by the CPU 41 will be described with reference to FIGS.

  FIG. 4 is a flowchart for explaining component measurement processing in the blood glucose measurement device shown in FIG.

In the blood glucose level measurement processing in the present embodiment, first, before spotting blood, the reference value of the first light λ _{1 having} an absorption wavelength specific to hemoglobin and the reference value of the second light λ _{2 having} an absorption wavelength specific to the dye In this case, the first light λ ₁ and the second light λ ₂ are alternately emitted in a time-division manner and are irradiated onto the test paper 32. In order to detect that the blood sample has been absorbed by the test paper 32 and a color reaction has occurred, the second light λ ₂ having the absorption wavelength of the dye is used. After the color is detected, only the first light lambda ₁ second light lambda ₂ is stopped is used once (step S101). In the blood glucose level measuring device 10 of the present embodiment, while the blood sample is absorbed into the test paper 32 from one side of the test paper 32, the first light lambda ₁ and the second light lambda ₂ will test paper The test paper 32 is irradiated from the other surface side of 32.

The first light λ ₁ is reflected by the test paper 32 and received by the light receiving element 26 (step S102). The light intensity of the received first light λ1 is reduced by the light absorption action of hemoglobin in the blood sample. This intensity signal is temporarily stored in the storage unit 42.

The CPU 41 calculates the reflectance R ₁ of the received intensity signal of the first light λ ₁ (step S103). Here, the reflectance R ₁ is for the reflected light intensity signal obtained while reflecting the test paper 32 which does not hold a blood by projecting the first light lambda _1, the first light lambda ₁ of which has been received in step S102 It is the ratio of the intensity signal. The intensity signal of the reflected light when the first light λ ₁ is projected onto the test paper 32 in a state where no blood is held is measured in advance and stored in the storage unit 42.

Next, in place of the first light λ ₁ having the absorption wavelength of hemoglobin, the second light λ ₂ having the absorption wavelength of the dye generated by the color reaction of the blood sample is irradiated (step S104). In the present embodiment, the two-wavelength light emitting element 25 emits the second light λ ₂ having an absorption wavelength specific to the dye, instead of the first light λ ₁ having an absorption wavelength specific to hemoglobin. The second light λ ₂ is reflected by the test paper 32 and received by the light receiving element 26 (step S105). The light intensity of the received second light λ ₂ is reduced by the light absorption action of the dye in the blood sample. This intensity signal is temporarily stored in the storage unit 42.

The CPU 41 calculates the reflectance R ₂ of the intensity signal of the received second light λ ₂ (step S106). Here, the reflectance R _2, the relative reflected light intensity signal obtained while reflecting the test paper 32 which does not hold a blood by projecting the second light lambda _2, the second light lambda ₂ that has been received in step S105 It is the ratio of the intensity signal. The intensity signal of the reflected light when the second light λ ₂ is projected onto the test paper 32 in a state where no blood is held is measured in advance and stored in the storage unit 42.

CPU41, using the calculated reflectance _{R 1} and _{R 2,} and calculates the blood glucose level (step S107).

  A detailed flow of blood glucose level calculation in step S107 will be described. Here, for blood glucose level calculation, as a preliminary preparation, the above-mentioned first calibration curve group (first coefficient group) and second calibration curve group (second coefficient group) are calculated and stored in the storage unit 42 in advance. It is necessary to keep. Therefore, in the following, first, a process of preparing the first calibration curve group and the second calibration curve group will be described as advance preparation. Next, the process until the blood glucose level is actually calculated using the first and second calibration curve groups will be described.

(Advance preparation)
FIG. 5 is a data table for storing a data set of blood glucose level (G) and variables x and y when the hematocrit value (Ht) is fixed.

  As a preliminary preparation, data is accumulated in the data table shown in FIG. 5, and the accumulated data is analyzed to create a second calibration curve group indicating the correlation between the blood glucose level and the variable y. Before describing data accumulation, the structure of a data table will be described first.

(Advance preparation-data accumulation)
In FIG. 5, “Ht” indicates a hematocrit value, and a numerical difference in the hematocrit value is indicated by a subscript h (1 to m) on the right side. The hematocrit value is a numerical value indicating the proportion of the volume of blood cells in the blood and correlates with the amount of hemoglobin. “G” indicates a blood glucose level, and a numerical difference in the blood glucose level is indicated by the subscript g (1 to n) on the right side. “X” is a variable corresponding to the reflectance R ₁ of the first light λ ₁ , and “y” is a variable corresponding to the reflectance R ₂ of the second light λ ₂ . x and y are, for example, operations described later, such as 1 / R ₁ , 1 / R ₂ or the logarithm thereof, (1-R ₁ ) / 2R ₁ , (1-R ₂ ) / 2R ₂ , respectively. Is a numeric value that has been converted to facilitate approximation. Since this variable conversion is general, a description thereof will be omitted.

In this manner, in FIG. 5, n blood glucose levels (G), x, and y data sets can be stored for m hematocrit values from Ht _{1 to} Ht _m , respectively. That is, for x and y, m × n data sets can be stored.

The data set stored in the data table of FIG. 5 is completed by an experiment using a blood sample whose blood glucose level (G) and hematocrit level (Ht) are known. By measuring the reflectance R ₁ , R ₂ of the blood sample with the blood glucose measurement device 10 described above, x and y are obtained and stored in the data table as a data set.

(Preliminary preparation-creation of calibration curve group)
The completed data table is extracted for each row, and the data series (G _g , y _g ) _h (g = 1, 2... N h = 1, 2... M) at each hematocrit value (Ht) is extracted. The

  From this data series, the blood glucose level (G) is approximated to an appropriate function representing the variable (y). As the function, a polynomial of y or a spline function is used. When the polynomial of y is applied, only the number of Ht, that is, m relational expressions are created.

In the above equation (1), _h G (y) means a function at the time of the h-th hematocrit value (Ht) in FIG. n _G means the degree of the polynomial, and it is necessary to satisfy n _G ≦ n−1. _h b _j means a coefficient of the j-th order term in the relational expression at the h-th hematocrit value (Ht) in FIG.

The coefficient _h b _j can be obtained by the method of least squares. The function J to be minimized is weighted in the sense of reducing the relative error, and is defined as the following equation (2). In some cases, the error can be reduced.

As described above, the coefficient group _h b _j (j = 0, 1... N _G ) (h = 1, 2... M) that approximates the blood glucose level (G) with the variable (y) is determined for each hematocrit value (Ht). Hereinafter, this coefficient group is referred to as a second coefficient group. Even when the spline function is used, a coefficient group is obtained in the same manner.

  A group of relational expressions that approximate the blood glucose level (G) with the variable (y), that is, the second calibration curve group is as follows.

  FIG. 6 is a schematic diagram showing a relational expression that approximates the blood glucose level (G) with the variable (y) for each hematocrit value (Ht).

  FIG. 6 shows the function G of the variable (y) for each h = 1, 2... m-th hematocrit value (Ht). Although only h = 3 is shown in the figure, all the functions up to the m-th are included in the (y, Ht, G) space.

Next, a relational expression that approximates the hematocrit value (Ht) with the variable (x) is determined for each blood glucose level (G) by the same procedure as described above. Therefore, first, the data table of FIG. 5 is retrieved for each column, data series _{(Ht h, x h)} for each blood glucose (G) g (h = 1,2 ... m g = 1,2 ... n ) Is extracted.

  From this data series, the hematocrit value (Ht) is approximated to an appropriate function representing the variable (x). When the polynomial of x is applied, the number of relational expressions corresponding to the number of G, that is, n, is created.

In the above formula (4), _g Ht (x) means a function at the time of the g-th blood glucose level (G) in FIG. n _Ht means the degree of the polynomial and satisfies n _Ht ≦ m−1. _g a _j means a coefficient of the j-th order term in the relational expression at the g-th blood glucose level (G) in FIG.

The coefficient _g a _j can be obtained by the least square method or the like, similarly to the above and _h b _j .

As described above, the coefficient group _g a _j (j = 0, 1... N _Ht ) (g = 1, 2... N) that approximates the hematocrit value (Ht) with the variable (x) is determined for each blood glucose level (G). This coefficient group _g a _j is hereinafter referred to as a first coefficient group. Even when the spline function is used, a coefficient group is obtained in the same manner.

  A group of relational expressions that approximate the hematocrit value (Ht) with the variable (x), that is, the first calibration curve group is as follows.

  FIG. 7 is a schematic diagram showing a relational expression that approximates the hematocrit value (Ht) with the variable (x) for each blood glucose level (G).

  FIG. 7 shows the function Ht of the variable (y) for each of g = 1, 2,... nth blood glucose level (G). Although only g = 3 is shown in the figure, in practice, all the functions up to the nth are included in the (x, G, Ht) space. As shown in FIGS. 6 and 7, each space includes three variables.

  In the above preparation, considering actual experimental procedures, it may be difficult to align blood glucose levels (G) at different hematocrit levels (Ht). In this case, an expression in which the blood glucose level (G) is approximated by a polynomial of the variable (x), for example, the following expression (6) is created.

From this equation, it is possible to generate data x in which blood glucose levels (G) are aligned at each hematocrit value (Ht). In this way, the first coefficient group _g a _j (j = 0, 1... N _Ht ) (h = 1, 2... M) that approximates the hematocrit value (Ht) with the variable (x) for each blood glucose level (G). ) May be obtained.

  Thus, the first coefficient group and the second coefficient group prepared in advance are stored in the storage unit 42 together with the above formulas (1) and (4), and the preliminary preparation is completed.

(Blood glucose level calculation)
FIG. 8 is a flowchart showing the flow of the blood sugar level calculating step. 9 is a diagram illustrating a state where the space illustrated in FIG. 7 is cut out by a plane of x = x ^* , and FIG. 10 is a diagram illustrating a state where the space illustrated in FIG. 6 is cut out by a plane of y = y ^* .

First, the CPU 41 converts the reflectances R ₁ and R ₂ measured in steps S103 and S106 of FIG. 4 into x ^* and y ^* (step S201). x ^* and y ^* are obtained by converting the reflectances R ₁ and R ₂ in the above-described “preparation-data accumulation”.

Subsequently, the CPU 41 substitutes the obtained x ^* into the above equation (5) (step S202). Thereby, the system in which the first calibration curve group is shown, that is, the system expressed by the coefficient group 1 is cut off in the (Ht, G) plane of x = x ^* as shown in FIG.

The CPU 41 defines an interpolation function Ht = g (G) using the blood glucose level (G) as a variable based on the intersection sequence between the (Ht, G) plane and the first calibration curve group (step S203). The interpolation function is a curve shown on the (Ht, G) plane of x = x ^* in FIG. For example, Newton's polynomial or Lagrange's polynomial is suitable as the interpolation function, but it may be in the form of a function that can be easily defined from a point sequence. When applying Lagrangian polynomials, the interpolation function is expressed as:

Here, _mg is not as good as possible, but is suppressed to such an extent that the interpolation function does not vibrate.

The CPU 41 substitutes the obtained y ^* into the above equation (3) (step S204). The system in which the second calibration curve group is shown, that is, the system represented by the coefficient group 2 is cut off in the (G, Ht) plane of y = y ^* as shown in FIG.

The CPU 41 defines an interpolation function G = h (Ht) using the hematocrit value (Ht) as a variable based on the intersection sequence between the (G, Ht) plane and the second calibration curve group (step S205). The interpolation function is a curve shown on the (G, Ht) plane where y = y ^* in FIG. For example, when applying a Lagrangian polynomial, the interpolation function is expressed as follows.

Here, m _h is not as good as possible, but is suppressed to such an extent that the interpolation function does not vibrate. In equation (8), for example, the hematocrit value (Ht) when h = 1 = 20%, the hematocrit value (Ht) when h = 2 = 40%, and the hematocrit value (Ht) when H = 3 = 60%. In this case, since the hematocrit value (Ht) = (20, 40, 60) is given at equal intervals, the calculation can be simplified by normalizing these to (-1, 0, 1).

As described above, by substituting x = x ^* and y = y ^* , two expressions having only the hematocrit value (Ht) and the blood glucose level (G) are defined.

The CPU 41 solves the above equations (7) and (8) simultaneously (step S206). This is to obtain the intersection of the curve shown on the (Ht, G) plane of x = x ^* in FIG. 9 and the curve shown on the (G, Ht) plane of y = y ^{* in} FIG. means.

  When the CPU 41 does not obtain a solution in a positive form by modifying the simultaneous equations, the CPU 41 can obtain a solution by using a numerical release of a widely known nonlinear equation such as a sandwich method or a Newton method. For example, the following sequential solution can be applied.

Ht is obtained from the k-th estimated value G ^{(k) of} G by Expression (7).

An error Y between the calculated value G and the estimated value G ^(k) obtained by substituting this into the equation (8) is obtained.

G ⁽⁰⁾ and G ⁽¹⁾ corresponding to k = 0 and ¹ are determined in advance. For this purpose, for example, G ⁽⁰⁾ = 40 mg / dl and G ⁽¹⁾ = 300 mg / dl, as long as Equation (7) is not negative.

(Example)
Next, an example of the blood glucose measurement method will be described.

<1. Measurement of variables x and y>
FIG. 11 is a diagram showing variables x and y obtained by measuring blood whose blood glucose level is known.

First, blood with a known hematocrit value (Ht) and blood glucose level (G) was prepared and measured by the blood glucose measurement device 10. At this time, the first light λ ₁ had a wavelength of 545 nm and was used for measuring the amount of reflected light after 5 seconds from the start of coloring. The second light λ ₂ had a wavelength of 630 nm and was used for measurement of the amount of reflected light 10 seconds after the start of coloring. The obtained reflectivities R ₁ and R ₂ of the first and second light λ ₁ and λ ₂ were converted into x = 256 / R ₁ and y = 256 / R ₂ , respectively. For the known hematocrit value (Ht) and blood glucose level (G), the measured variables (x) and (y) are as shown in FIG.

<2. Determination of first and second coefficient groups>
12 is a graph showing the relationship between the hematocrit value (Ht) and the variable (x), FIG. 13 is a diagram showing the first coefficient group, and FIG. 14 is the relationship between the blood glucose level (G) and the variable (y). FIG. 15 is a diagram showing the second coefficient group.

In formula (1) and formula (4), n _G = n _Ht = 2 was set. Then, the relational expression (first calibration curve group) between each hematocrit value (Ht) and variable (x) when the blood glucose level (G) is G = 45, 100, 400 mg / dl by the above-described method is obtained. It was. The obtained relational expression is as shown in FIG. The first coefficient group _g a _j (j = 0, 1, 2) (g = 45, 100, 400) of this relational expression is also obtained at the same time. The obtained first coefficient group is as shown in FIG.

When the hematocrit value (Ht) was Ht = 20, 40, 60%, the relational expression between each blood glucose level (G) and the variable (y) was obtained. The obtained relational expression (second calibration curve group) is as shown in FIG. The second coefficient group _h b _j (j = 0, 1, 2) (h = 20, 40, 60) of this relational expression is also obtained at the same time. The obtained second coefficient group is as shown in FIG.

<3. Calculation of blood glucose level and hematocrit level>
FIG. 16 shows the calibration results.

Assuming that the blood glucose level and the hematocrit value are unknown, the blood glucose level and the hematocrit value are calculated using the variables x and y shown in FIG. 11 and the first coefficient group and the second coefficient group shown in FIGS. Calculated. Specifically, the values of x and y in FIG. 11 are substituted into the relational expressions of the first coefficient group and the second coefficient group, respectively, and the variables are only the blood sugar level (G) and the hematocrit value (Ht). A formula was made, and blood glucose level (G) was calculated according to formulas (7) to (13). Here, in the convergence determination of Expression (13), ε _G = ε _Y = 10 ⁻⁴ . The number of iterations for solving the simultaneous equations was 3 to 7 times. The calculation result is as shown in FIG.

<4. Evaluation>
In FIG. 16, the values of the known hematocrit value (Ht) and blood glucose level (G) are shown in the “sample” column. In the column “Calculated value of G”, the blood glucose level (G) is calculated by assuming that the blood glucose level (G) and the hematocrit level (Ht) are unknown. In the column “G (reference value)”, the blood glucose level (G) is calculated on the assumption that the blood glucose level (G) is unknown but the hematocrit level (Ht) is known. In the calculation of the blood glucose level (G) here, the relational expression of the corresponding hematocrit value (Ht) is selected in FIG. 14, and the variable (y) is substituted. Thereby, the blood glucose level (G) was specified without solving the simultaneous equations. In the column of “calculated value of Ht”, an error between the calculated hematocrit value (Ht) and the actual value is shown.

  The “relative error” column in the “calculated value of G” column indicates a relative error from the value of “G (reference value)”. Here, the value of the calculated blood glucose level (G) is compared with the value of the blood glucose level (G) calculated on the assumption that only the hematocrit value (Ht) is known. For the following reason. That is, since the blood glucose measurement device 10 itself also has an error, by comparing the values calculated using the measurement values x and y, the device error can be reduced and the accuracy of the measurement method can be evaluated. . When compared with the value of the known blood glucose level (G), up to the device error, it will appear as a numerical value as an error in the measurement method.

  As a result of the measurement as described above, the calculated value in which both the hematocrit value (Ht) and the blood glucose level (G) are unknown has an average relative error of 0.2% from the calculated value in which the hematocrit value (Ht) is known. Met. The maximum error was 0.8%. The error of the hematocrit value (Ht) was 0.7% on average and 2.0% at maximum.

(Comparative example)
FIG. 17 is a diagram illustrating polynomial coefficients used in the comparative example, and FIG. 18 is a diagram illustrating a calculation result of the blood glucose level (G) in the comparative example.

In the comparative example, blood having a known hematocrit value (Ht) and blood glucose level (G) is measured by the blood glucose measuring device 10 and the variables x and y are calculated from the reflectances R ₁ and R ₂ as in the above example. did. Thereafter, unlike the example, the blood glucose level (G) was obtained by curved surface approximation using the variables x and y. The relational expression for approximating the blood glucose level (G) by polynomials of variables x and y is as follows.

  The order was a quadratic expression similar to that of the example for comparison.

  The coefficient e obtained by the least square method is as shown in FIG. The blood glucose level (G) calculated using the obtained coefficient is as shown in FIG. The relative error of blood glucose level (G) calculated with actual blood was 2.6% on average, and the maximum error was 8.6%.

(Discussion)
FIG. 19 is a diagram illustrating a state in which an approximate expression of blood glucose level (G) on the xy plane and measured values (x, y) in the example are plotted, and FIG. 20 illustrates blood glucose on the xy plane in the comparative example. It is a figure which shows a mode that the approximate expression of value (G) and the measured value (x, y) were plotted.

  The above example and a comparative example are compared. In the examples, the error of blood glucose level (G) was 0.2% on average and 0.8% at maximum. On the other hand, in the comparative example, the error of the blood glucose level (G) was 2.6% on average and 8.6% at maximum. From this, it can be seen that the error is one digit worse in the comparative example.

  Further, referring to FIG. 19, in the example, it can be seen that each measured value (x, y) is substantially in agreement with the approximate expression. On the other hand, referring to FIG. 20, in the comparative example, it can be seen that the measured values (x, y) deviate from the approximate expression, particularly in the case of a high blood glucose level. Also in this point, it can be said that the blood glucose level (G) can be calculated more accurately in the example. 19 and 20, the plot indicated by 403 is a plot of the x and y values when the blood glucose level (G) = 402, 403, 404 mg / dl.

  From the comparison between the above example and the comparative example, it can be seen that the blood glucose level can be obtained more accurately by using the calculation method of the example. That is, as in the embodiment, first, four variables (blood glucose level (G), hematocrit value (Ht), x, y) are set, and the first and second calibration curve groups (first and second coefficient groups) are set. ) Are determined as three variables (Ht, G, y or G, Ht, x), and further, by substituting x and y into the first and second calibration curve groups, two variables (Ht, It can be seen that an accurate blood glucose level (G) can be obtained by calculating the blood glucose level (G) as a simultaneous equation of G).

(effect)
As described above, according to the blood glucose measurement device and the method thereof according to the present embodiment, the reflectances R ₁ and R ₂ of the two wavelengths of light λ ₁ and λ ₂ are stored in the storage unit 42 in advance. Since the blood glucose level (G) is calculated by substituting it into the calibration curve group and the second calibration curve group, the blood glucose level (G) is calculated more accurately than when calculating the blood glucose level (G) based on the reflectance of light of one wavelength. Blood glucose level can be measured.

  In addition, as can be seen from the comparison with the comparative example, the blood glucose level can be measured more accurately than in the case of approximation as a curved surface using the reflectance of light of two wavelengths.

  Moreover, since the blood glucose measuring device 10 has the display part 23, the measured blood glucose level can be seen on the spot.

  In the present embodiment, the hematocrit value can be calculated simultaneously with the calculation of the blood glucose level by providing two equations consisting of two variables (Ht, G) simultaneously. That is, the CPU 41 can calculate the hematocrit value of the blood sample using the first calibration curve group and the second calibration curve group stored in the storage unit 42. Here, using the calculated hematocrit value, the blood glucose level may be calculated by a conventionally used hematocrit correction method, for example, a correction method using a table method or the like. In other words, the hematocrit value can be accurately calculated by the method used in the present embodiment, and the blood glucose level can be obtained by applying the hematocrit value to another blood glucose level calculation method.

1 is a perspective view showing a schematic configuration of a blood glucose measurement device according to an embodiment of the present invention. It is a fragmentary sectional view of the blood glucose measuring device shown in FIG. It is a block diagram which shows schematic structure of the blood glucose measuring device shown in FIG. It is a flowchart for demonstrating the component measurement process in the blood glucose measuring device shown in FIG. It is a data table which stores a data set of a blood glucose level (G) and variables x and y when the hematocrit value (Ht) is fixed. It is the schematic which shows the relational expression which approximates a blood glucose level (G) by the variable (y) for every hematocrit value (Ht). It is the schematic which shows the relational expression which approximates a hematocrit value (Ht) with the variable (x) for every blood glucose level (G). It is a flowchart which shows the flow of a blood glucose level calculation process. It is a figure which shows a mode that the space shown in FIG. 7 is cut out by the plane of x = x ^* . It is a figure which shows a mode that the space shown in FIG. 6 is cut out by the plane of y = y ^* . It is a figure which shows the variables x and y obtained by measuring the blood whose blood glucose level is known. It is a graph which shows the relationship between a hematocrit value (Ht) and a variable (x). It is a figure which shows a 1st coefficient group. It is a graph which shows the relationship between a blood glucose level (G) and a variable (y). It is a figure which shows a 2nd coefficient group. It is a figure which shows a calibration result. It is a figure which shows the coefficient of the polynomial used by a comparative example. It is a figure which shows the calculation result of the blood glucose level (G) in a comparative example. It is a figure which shows a mode that the approximate expression of the blood glucose level (G) in the xy plane in an Example, and the measured value (x, y) were plotted. It is a figure which shows a mode that the approximate expression of the blood glucose level (G) in the xy plane in a comparative example and the measured value (x, y) were plotted.

Explanation of symbols

10 blood glucose measuring device,
20 measuring device body,
21 Metering unit,
22 exterior case,
23 display section,
24 Various switches,
25 light emitting element,
26 light receiving element,
27 holder,
28 transducer,
29 Input section,
30 chips,
31 holder,
31a capillary section,
32 test paper,
40 control unit,
41 CPU,
42 storage unit,
G blood sugar level,
Ht hematocrit value,
R ₁ , R ₂ reflectivity,
x, y variables,
λ ₁ first light,
λ ₂ second light,
_g a _j first coefficient,
_h b _j second coefficient.

Claims (7)

A blood glucose measuring device for measuring a blood glucose level using a test paper containing a coloring reagent that reacts with glucose in a blood sample,
At least one light emitting element that irradiates the test paper with light having at least one absorption wavelength specific to hemoglobin in the blood sample and light having at least one absorption wavelength specific to the dye generated by the reaction; ,
At least one light receiving element that receives reflected light of the light emitted by the light emitting element;
A reflectance calculation unit that calculates a reflectance R ₁ of light having an absorption wavelength of the hemoglobin and a reflectance R ₂ of light having an absorption wavelength of the dye based on the light reception intensity of the light receiving element;
Per blood sugar level, and stores the first calibration line group showing the relationship between the hematocrit value and the reflectivity R _1, for each hematocrit, and a second calibration line group showing the relationship between blood glucose and a reflectance R ₂ A storage unit,
The blood glucose level is calculated by substituting the reflectance R ₁ and the reflectance R ₂ calculated by the reflectance calculator into the first calibration curve group and the second calibration curve group, or the reflectance calculation unit A blood glucose level calculating unit for substituting the reflectance R ₁ and the reflectance R ₂ calculated in step ₁ into the first calibration curve group and the second calibration curve group to obtain a hematocrit value and calculating a blood glucose level using the hematocrit value; ,
A blood glucose measuring device. The blood glucose level calculation unit includes a relational expression between the blood glucose level and the hematocrit value obtained by substituting the reflectance R ₁ into the first calibration curve group, and the reflectance R in the second calibration curve group. The blood glucose measuring device according to claim 1, wherein the blood glucose level is calculated by simultaneously combining the blood glucose level obtained by substituting ₂ and the relational expression between the hematocrit level. Wherein the storage unit, as the first coefficient group of the formula representing the hematocrit value in the reflectivity R _1, stores the first calibration line group, the second coefficient group of the formula which represents the blood glucose level in the reflectance R ₂ The blood glucose measurement device according to claim 1, wherein the second calibration curve group is stored.   The blood glucose measurement device according to any one of claims 1 to 3, further comprising a display unit that displays the calculated blood glucose level. A method for measuring a blood glucose level using a test paper containing a coloring reagent that reacts with glucose in a blood sample,
Irradiating the test paper with at least one absorption wavelength light specific to hemoglobin in a blood sample and at least one absorption wavelength light specific to the dye produced by the reaction;
Receiving reflected light of the irradiated light;
Calculating a reflectance R ₁ of light having an absorption wavelength of the hemoglobin and a reflectance R ₂ of light having an absorption wavelength of the dye based on the received light intensity of the light;
A first calibration line group showing the relationship between the hematocrit value for each blood glucose level and the reflectivity R _1, and a second calibration line group showing the relationship between the blood glucose level for each hematocrit value and the reflectance R _2, calculated above Substituting the reflectance R ₁ and the reflectance R ₂ to calculate a blood glucose level, or calculating a hematocrit value and calculating the blood glucose level using the hematocrit value;
A method for measuring blood glucose. The step of calculating the blood sugar level, the blood sugar value obtained by substituting the reflectance R ₁ to the first calibration line group and the relationship between the hematocrit value, the reflection on the second calibration line group by simultaneous and relationship of said blood glucose level obtained by substituting the rate R ₂ and the hematocrit, blood glucose measurement method of claim 5, wherein calculating the blood sugar level.   The blood glucose measurement method according to claim 5 or 6, further comprising a step of displaying the calculated blood glucose level.

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