WO2003077761A1

WO2003077761A1 - Blood analyzer

Info

Publication number: WO2003077761A1
Application number: PCT/JP2003/003247
Authority: WO
Inventors: Shunji Egawa
Original assignee: Citizen Watch Co., Ltd.
Priority date: 2002-03-18
Filing date: 2003-03-18
Publication date: 2003-09-25
Also published as: JP2005253478A

Abstract

A blood analyzer for measuring blood hemoglobin concentrations serving as indications in diagnosing diabetes or controlling blood glucose level. From characteristic curves showing the molar absorption coefficient ratios of three hemoglobin components including HbAlc-O2, Hb-O2 and Hb-CO, the wavelength at which the absorbance ratio of each component attains a peak or the wavelength at which the absorbance ratio of each component attains the maximum level is selected. Then the composition ratio of the hemoglobin components is calculated based on the molar absorption coefficients of the hemoglobin components at these wavelengths and the absorbances of a biological tissue at these wavelengths. Thus, the concentrations of the hemoglobin components are indicated non-invasively.

Description

Description Hematology analyzer Technical field

The present invention relates to a blood analyzer for non-invasively measuring a specific component in blood, particularly, hemoglobin in blood. Background art

Conventionally, hemoglobin, particularly hemoglobin A 1c in a state of being bound to blood glucose, has been clinically used as an index for diagnosing diabetes and knowing the state of glycemic control. Hemoglobin binds to glucose according to the glucose concentration in the blood. This is an irreversible reaction with a slow reaction time. Since the life span of red blood cells is about 120 days, hemoglobin A 1c reflects the average blood glucose level in the past month or two.

Methods for analyzing hemoglobin A1c include high performance liquid chromatography (HPLC) and immunoassay. For example, as a commercially available hemoglobin Alc analyzer for the HP LC method, there is a Tosoh automatic glycohemoglobin analyzer HLC-723G7 (medical device license number 35BZ0019). An ADAMS Master-DM-3310 (medical device approval number 2100BZZ 00391) is an example of an immunoassay hemoglobin Alc analyzer.

These hemoglobin A1c analyzers collect venous blood from patients and examine whole blood. Such a method of testing caused pain and discomfort to the patient during blood collection. In addition, since blood cannot be collected without doctors, nurses, and laboratory technicians, and because the equipment is large and expensive, it is used for medical examinations for diabetes and medical examinations in hospitals, etc. It could not be used easily. Further, as an apparatus for inspecting the blood components without blood sampling, analysis contents are different is Parusuokishime coater to measure oxygen saturation of arterial blood (hereinafter abbreviated as "Sp_〇 _2".). An example of such a pulse oximeter is disclosed in Japanese Patent Publication No. 53-26437 as an optical blood measuring device. This optical blood measurement According to the measurement device, the change in transmitted light due to the pulsation of the blood flow is measured in two wavelength bands of 630 nm and 900 nm, and the ratio of these two changes, that is, the ratio of the absorption coefficient, is determined. and calculates the Sp_〇 ₂ of arterial blood. In this optical blood measuring apparatus, the component ratio of the two components of O carboxymethyl hemoglobin (H -0 ₂₎ the de O carboxymethyl hemoglobin (hereinafter abbreviated as "Hb".), Measured at two wavelengths 630 nm and 900 nm It was done.

In general, the pulse O carboxymethyl meters is for obtaining the component ratio of only 2 components of Hb-0 ₂ and Hb, the presence of local ports carboxymethyl hemoglobin combined with carbon monoxide (Hb-C 〇) was ignored. This is because the presence of Hb-CO caused negligible errors in clinical settings, such as during and after surgery, in intensive care units, and during emergency transport. However, the need for high-precision measurement results has made it possible to consider Hb_CO as the analysis target.

As an example, in Japanese Unexamined Japanese Patent Publication No. 5-two hundred twenty-eight thousand one hundred twenty-nine, apparatus which can measure the respective percentage of Hb-0 ₂ and Hb and Hb-CO in arterial blood is disclosed. According to this device, in three of the light source of 660 nm, 750 nm, 940 nm , Hb- 0 2 and in addition to Hb, Hb-calculate the three component ratios of CO, S of arterial blood p0 ₂ Can be requested.

However, although the above-described conventional techniques can calculate Hb-CO, they all determine the Sp 比₂ , which is the component ratio of oxyhemoglobin Hb in arterial blood, and are used to diagnose diabetes and control glycemic control. Hemoglobin A 1 c (HbAl c — 0 ₂ ) could not be directly obtained as an indicator of the state of.

Figure 8 is a commercially available pulse O carboxymethyl meter one shows the results obtained indirectly to Mog Robin A 1 c from S p0 _2. The light source for this device is a light emitting diode with 660 ηm and 940 nm. The subjects of the measurement experiment were 5 diabetic patients and 22 normal subjects, a total of 27 cases.The total was categorized into 16 cases of non-smokers who did not smoke and 11 cases of smokers who smoked. did. The Parusuokishime Isseki one display value S p0 _2, in order to convert hemoglobin A 1 c corresponding value, and the processing of 100- S P_〇 _2. For example, if Sp_〇 ₂ 92%, hemoglobin A 1 c corresponding value is set to 8%. The result of the measurement experiment was The number of cases (frequency) is shown.

In the non-smoker group, hemoglobin A 1c equivalent was high only in diabetic patients and low in normal subjects. In the smoker group as well, diabetic patients showed high levels, but normal subjects showed high levels. Thus, in the case of a smoker, there is a risk that hemoglobin A 1c may be measured as a high value, and that a conventional pulse oximeter cannot accurately determine hemoglobin A 1c. It was revealed.

Accordingly, an object of the present invention is to provide a blood analyzer capable of non-invasively analyzing the concentration of glycated hemoglobin in blood used as various diagnostic and medical indicators. Disclosure of the invention

The blood analyzer of the present invention, when measuring the concentration of a specific component from among blood components using light having a plurality of different wavelengths, measuring at least Darico's hemoglobin as the specific component. Specifically, it is characterized by measuring hemoglobin A1c. The wavelength of at least one of the plurality of lights is set to a wavelength at which the absorbance ratio of dalicohaemoglobin is maximized.

According to the present invention, a specific component in blood, for example, glycohemoglobin can be measured by non-invasive method, and thus, the risk of infection due to blood collection can be eliminated. In addition, since the blood analyzer has a simple configuration and can be miniaturized, an inexpensive blood analyzer can be realized, and a patient can easily perform a test at home. Further, the blood analyzer of the present invention is characterized in that, in addition to the glycohemoglobin, oxyhemoglobin and carboxyhemoglobin are measured as the specific components. The light of a plurality of different wavelengths is set to a wavelength near the maximum value of the absorbance ratio of carboxyhemoglobin and the maximum value of the absorbance ratio of oxyhemoglobin.

Furthermore, in the blood analyzer of the present invention, the molar extinction coefficient of the daricohemoglobin, the molar extinction coefficient of the oxyhemoglobin, and the molar extinction coefficient of the lipoxyhemoglobin are respectively k1, k2, and k3. At this time, among the lights of the plurality of different wavelengths, the first wavelength is set in a region of k3>kl> k2, and the second wavelength is set to kl≥ The region is set in the region of k 3> k 2, and the third wavelength is set in the region of k 1 k 2 k 3.

According to the present invention, in addition to glycohemoglobin, oxyhemoglobin and carboxyhemoglobin can be directly measured in a non-invasive manner. In other words, in an analyzer that cannot measure the carboxyhemoglobin component, the measurement results are in a state in which carboxyhemoglobin is included in either dalicohemoglobin or oxyhemoglobin, so there is a point that accuracy is required. However, the present invention does not cause such a problem.

Further, according to the present invention, the concentrations of glycohemoglobin, oxyhemoglobin, and lipoxyhemoglobin are measured based on the maximum value of the absorbance ratio and the wavelength near the maximum value of the absorbance ratio, so that accurate measurement can be performed. The result can be obtained. No :! The wavelengths of ~ 3 are preferably wavelengths of 600 ~: L000nm, and specifically, the first wavelength is a wavelength of 65 ~ 780nm, and the second wavelength is Preferably, the wavelength is between 600 and 600 nm, and the third wavelength is between 850 and 00 nm.

Incidentally, glycohemoglobin is sometimes is sometimes used to agree to hemoglobin A le (H b A lc -〇 _2), to be precise, in particular hemoglobin having a glycated hemoglobin caries Chino specific chemical structure A 1 c. Many types of glycohemoglobin are known in addition to hemoglobin A1'c. On the other hand, the present invention can be used not only for analysis of hemoglobin A1c but also for other types of analysis of glycohemoglobin. Therefore, in this specification, the term "glycated hemoglobin" refers to a broad concept including hemoglobin Alc as well as other types. BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is an external view of a blood analyzer according to an embodiment of the present invention, wherein (a) is a front view and (b) is a side view.

FIG. 2 is a mounting view of the blood analyzer according to the embodiment of the present invention.

FIG. 3 is a cross-sectional view showing a sensor unit structure of the blood analyzer according to the embodiment of the present invention. FIG. 4 is a block diagram of the blood analyzer according to the embodiment of the present invention.

Figure 5 is hemoglobin A le (H b A lc- 0 2), O carboxymethyl hemoglobin (H b - 0 _2), absorbance showing the change of the molar extinction coefficient at the wavelength of the local port carboxymethyl hemoglobin (H b-CO) It is a characteristic curve.

6 is a characteristic curve showing the percentage of the molar absorption coefficient at each wavelength of H b A lc-〇 _2, H b-〇 _2, H b-CO.

FIG. 7 is an external view of a blood analyzer according to another embodiment of the present invention.

FIG. 8 shows the results of measurements performed using a conventional pulse oximeter. BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

1) and (b) are external views of a blood analyzer according to one embodiment of the present invention. This blood analyzer is a blood analyzer for examining the proportions of various hemoglobins contained in red blood cells in blood.

The blood analyzer 10 is provided with an insertion hole 11 for inserting a measurement site on a side surface, and has a substantially cylindrical shape so that a subject's finger can be inserted. In addition, a switch 12 for turning on the power and starting an analysis and a display 13 for displaying an analysis result are provided on the front. The display 13 displays hemoglobin Ale, which is an indicator of blood sugar control.

Next, a method of using the blood analyzer of the present embodiment will be described with reference to FIG. Insert a finger into the insertion hole 11 of the blood analyzer 10. To use a standard finger, insert the third finger (middle finger) of the right hand into the insertion hole 11 and support the blood analyzer 10 lightly with the second finger (index finger) and fourth finger (ring finger) on both sides. Turn your palm up. This is the standard mounting posture during measurement. In this case, the living tissue 1 to be measured is the third finger of the right hand. When switch 12 is pressed with another finger, for example, the first finger (thumb) in this position, the power is turned on and the analysis is started.

The analysis result can be easily read because the display 13 is facing upward. Here, the living tissue 1 to be inserted into the insertion hole 11 is the third finger of the right hand, but the present invention is not limited to this finger, and other fingers can be similarly measured. In addition, all fingers and toes can be measured. By changing the shape of the insertion hole 11 of the blood analyzer, it is possible to measure the hemoglobin A 1c with the earlobe or nose as a measurement target.

Next, a sensor unit structure of the blood analyzer of the present embodiment will be described with reference to FIG.

The insertion hole 11 is formed by a substantially cylindrical holder 27 having a closed end. The living tissue 1, which is a finger, is inserted into the tip of the holder 27 so as to abut it. The holder 27 is provided with a light receiving filter 26 at a portion where a finger pad touches, and a diffusion plate 25 is provided on the opposite side of the light receiving filter 26. The diffusion plate 25 is formed by molding a transparent polystyrene (PS) resin or an acrylic (PMMA) resin. Light emitting elements 21, 22, and 23 are arranged close to the outside of the diffusion plate 25.

The light-emitting elements 21, 22, and 23 are chip-type light-emitting diodes having peak emission wavelengths of λ1, λ2, and λ3, respectively. Light-emitting elements 21, 22, and 23 are arranged close to each other, but cannot emit light from the same position. Therefore, a diffusion plate 25 is provided in order to minimize an error caused by a difference in the position of the light emitting elements 21, 22, 23. By providing the diffusion plate 25, the point light emitted by the chip-type light emitting diode is converted into the surface light emitted by the diffusion plate 25, and the effect of the light path difference between the light emitting elements 21, 22, and 23 is eliminated. .

Here, the light emitting elements 21, 22, and 23 are light emitting diodes, but laser diodes having excellent wavelength selectivity may be used.

The light receiving filter 26 receives only the light transmitted through the living tissue 1 from the light of the wavelengths λ 1, λ 2, and λ 3 respectively emitted from the light emitting elements 21, 22, and 23. That is, the light receiving filter 26 is an optical filter for attenuating fluorescent lights and sunlight, and reduces the influence of extraneous light leaking from the gap between the input hole 11 and the living tissue 1. In addition, the light receiving filter 26 also has a dustproof effect, so that cleaning can be easily performed.

The light receiving element 24 is disposed outside the light receiving filter 26. The light receiving element 24 is a photodiode that receives light having wavelengths of λ 1, λ 2, and λ 3.

The circuit board 30 mounts the light receiving element 24 and also mounts each unit (not shown) such as an arithmetic unit described later. The calculation means obtains a change in photocurrent due to pulsation at each wavelength, and further calculates hemoglobin A1c. Its calculation The result is displayed by the display 13 connected to the circuit board 30.

Next, a block diagram of the blood analyzer of this embodiment will be described with reference to FIG. There are a first light emitting element 21, a second light emitting element 22, and a third light emitting element 23 which emit light of the first wavelength λ1, the second wavelength λ2, and the third wavelength λ3, respectively. Are turned on sequentially in response to the output of the light emitting drive circuit 31. Light from these light emitting elements 21, 22, and 23 is applied to the finger as the living tissue 1. The irradiated light is absorbed by various hemoglobins of the living tissue 1, but is also scattered by red blood cells. The transmitted light is received by the light receiving elements 24 arranged facing each other with the living tissue 1 interposed therebetween. Here, the emission wavelengths λΐ, λ2, and λ3 are in a relationship of λ1 and λ2 <ぇ 3, and are set to, for example, 630 nm, 680 nm, and 940 nm, respectively.

The light receiving element 24 receives the light emitted from the light emitting elements 21, 22, and 23, which is attenuated by passing through the living tissue 1 to have transmitted light amounts I1, 12, and I3. The amplifier 32 converts the photocurrent of the light receiving element 24 into a voltage, and amplifies the voltage. The transmitted light amounts I1, 12, and I3 at each wavelength include a pulsation component corresponding to a pulsation.

In the multiplexer (MPX) .33, the output signal of the amplifier 32 is divided for each of the wavelengths λΐ, λ2, and λ3, and supplied to the band-pass filters (BPF) 34, 35, and 36. The BPFs 34, 35, and 36 remove high-frequency noise components contained in each signal, and further reduce the pulsating components of transmitted light at the respective wavelengths λ1, λ2, λ3 in the biological tissue 1. It outputs a corresponding amplitude signal, that is, a finger plethysmogram. The pulsation extraction means (DET) 37, 38, 39 detects and extracts a signal corresponding to the amplitude value of the pulsation component of living tissue 1 for each wavelength from each output signal from the BPFs 34, 35, 36 ing. These detection signals correspond to the pulsatile components ΔΑ1, ΔΑ2, and ΔΑ3 of the transmitted light at the respective wavelengths; 1, λ • 2, λ3 in the biological tissue 1, and are analog / digital converted data. . The output signals ΔΑΙ, ΔΑ2, ΔΑ3 of the DETs 37, 38, 39 are supplied to the calculating means 40, and the component ratios of various hemoglobins to all hemoglobins are calculated. Then, the display means 41 displays the component ratio of hemoglobin A 1c as the calculation result.

Next, the calculation of the hemoglobin component ratio calculated by the calculating means 40 will be described. From the molar extinction coefficient of various hemoglobins and the absorbance of the living tissue 1, the component ratio of various hemoglobins, which are absorption components, is calculated by mathematical conversion.

Here, the molar extinction coefficient £ _U is the value of various hemoglobins j (where j = 1 is HbA 1 c _0 ₂ ,: | = 2 is 1 ^ 13-0 ₂ , at wavelength λ i (i = 1, 2, 3), j = 3 is the molar extinction coefficient of Hb-CO), which can be known as obtained from experiments and the like.

X is HbAl c-〇 _2, y is Hb-0 _2, z is the concentration (concentration in unit volume) of the Hb-CO.

k is a proportional constant representing the optical path length due to the blood vessel.

& Also, the absorbance by the biological tissue 1 at the wavelength 1 (i = 1, 2, 3), the absorbing component mainly HbA 1 c-〇 _2, due to various hemoglobin Hb-0 _2, H b-CO is there.

According to Lambert-Beer's law, the simultaneous equations (1), (2) and (3) are derived.

k (ε χ + ε _r y + ε ₁₃ z) = a ₁ 1 k (ε 21 ^X + ^ε 22 ^ + 23 *) (2) k (£ ₃₁ x + _e32 y + e ₃₃ z) = a ₃ (3) If this simultaneous ternary linear equation is expressed by a cubic determinant, it becomes the following equation (4).

This is called HbA 1 c--o ₂ , Hb-〇 ₂

Solving the equations gives equations (5), (6) and (7), respectively. ^a i ^£ 12 ^£ 13

ε 22 ^£ 23

1 ³ 3 ^£ 32 ^ε 33

X—

k ^£ 11 ^£ 12 ^S 13

^£ 22 ^£ 23

^£ 31 ^£ 32 ^ε 33

³ 1 ^ε 22 ^ε 33 ⁺³ 2 ^£ 13 ^£ 32 ⁺³ 3 ^£ 12 ^£ 23 ^_3 1 ^£ 23 ^£ 32 ^α 2 ^£ 12 ^£ 33 ^1-3 3 ^£ 13 ^£ 22

33, + ε

13 21 32 32 11 ^'11 ^-23 ^c 32 12 ^ε 21 ^£ ₃₃ per ^£ 13 ^ε 22 ^ε ;

"(Five)

^{^{^{^{3 1 £ 23 £ 31 +3 2}}}} £ 11 ε 33 +3 3 £ 13 £ 21 one ^{^{^{^{3 1 £ 21 £ 33- 3 2}}}} S 13 ^ 31 3 3 S 11 £ 23 y =

k (s S ₂₂ ε ₃₃ ^{+ ε} 12 ^ε 23 ^ε 31 ^{+ £} 13 ^£ 21 ^£ 32 ~ ^£ 11 ^£ 23 ^£ 32 ^S 12 ^£ 21 ^ε 33— ^£ 13 ^£ 22 ^£ 31)

…… (6)

³ 1 ^£ 21 ^£ 32 ⁺³ 2 ^ε 12 ^ε 3 ^α 3 ^£ 11 ^ 22 ^α 1 ^£ 22 ^£ 31 ° 2 ^£ 11 ^£ 32 ^& 3 ^£ 12 ^£ 21 k ( ^ε 11 ^ε 22 ^£ 33+ ^ε 12 ^ε 23 ^£ 31+ ^£ 13 ^£ 21 ^£ 32— ^ 11 ^£ 23 ^£ 32 per ^£ 12 ^£ 21 ^£ 33 per ^S 13 ^S 22 ^£ 31)

…… (7) Here, the component ratio X of HbA 1 c—O _{2 is} the ratio of the concentration of Hb A 1 c— 濃度_{2 to} the concentration of total hemoglobin, and is given by equation (8). Similarly, Hb 〇 _second component ratio Y, and Hb-CO component ratio Ζ of each (9) and (10).

X

X =

x + y + z

ai ( ^ε 22 ^ε 33- ^ε 23 ^£ 32) 2 ( ^£ 13 ^£ 32 one ^£ 12 ^£ 33 ³ 3 ゝ^£ 12 “23 one ^£ 13 ^£ 22)

ε ₂₁ , ε ₃₂ ~ ε ε ₂₂ゝ₃₃ ~ ε ₃₁ ) + ε ₂₃ (ε ₃₁ -ε

+ a ₂ {ε ε ₃₃ ~ ε ₃₂ ) ⁺ ε ₁₂ (ε ₃ Factory ε ₃₃ ) + ε ₁₃ (ε ₃₂ -ε ₃₁ )}

(8) y

Y =

x + y + z

ai ( ^£ 23 ^ε 31— ^ε 21 ^£ 33) ^{+ a} 2 ( ^ε 11 ^ε 33- ^ε 13 ^ε 3l) ^{+ a} 3 ( ^ε 13 ^ε 21— ^ε 11 ^ε 23)

a ^ S ₂₁ (ε ^ε 33) + ^ε 22 ( ^ε 33— ^Ε 31) + ^£ 23 ( ^ε 31- ^ε 32 + ^a J ^£ “ ^(Ε 33- ^£ 32) + ^£ ₁₂ ( ^ε 31— ^£ 33 ^{) + £} 13 ^(ε 32— ^ε ₃₁ ))

+ a ₃ {ε "(ε ₂₂ -ε ₂₃ ) + ε ₁₂ (ε ₂₃ -ε ₂₁ ) + ε ₁₃ (ε ₂₁ — ε ₂₂ )}

'(9) x + y + z

ai ( ^ε 21 ^ε 32- ^ε 22 ^£ 3i) ^{+ a} 2 ( ^£ 12 ^£ ^{31- £} 11 ^ε 32) + ( ^£ 11 ^ε 22- ^ε 12 ^£ 21)

ai ( ^ε 21 32- ^ε 33) + ^£ 22 ( ⁵ 33— ^ε 31) + ^ε 23 ( ^ε 31- ^ε 32

+ a ₂ {ε "(ε ₃₃ -ε ₃₂ ) + ε ₁₂ (ε ₃₁ ~ ε ₃₃ ) + ε ε ₃₂ -ε ₃₁ ) 1

+ a ₃ {ε "(ε ₂₂ -ε ₂₃ ) + ε ₁₂ (ε ₂₃ -ε ₂₁ ) + _{ε ε ε 22} )}

…… (10) Note that the proportionality constant k has been eliminated from the component ratios X Υ の of various hemoglobins. This indicates that the optical path length due to the blood vessel can be solved even if it is unknown.

Also, ε _u has been described as a molar extinction coefficient, but if the concentrations of various hemoglobins are unknown, they can be treated as absorbance under the same concentration conditions. At this time, the dimensions change, but the basic idea is the same.

So far, the mathematical transformation from molar extinction coefficient at the wavelength of HbAl c-〇 ₂ Hb-〇 ₂ Hb-CO, has been described to be able to calculate the component ratio. However, in absorption spectroscopy using light absorption, it is necessary to devise a method for setting the emission wavelength in order to improve measurement accuracy and simplify calculations. Basically, set a specific wavelength that is characteristic of the molar extinction coefficient of each hemoglobin component.

The absorption spectrum used in the absorption analysis will be described. The electron spectrum derived from the electronic transition has a large absorption spectrum in the ultraviolet-visible region. However, at wavelengths less than 600 ηm, it is difficult to detect transmitted light because the absorption by hemoglobin is strong and the transmitted light through living tissue is reduced. In addition, the vibration spectrum derived from molecular vibration has an absorption spectrum in the near infrared region, but the absorption itself is small. In particular, at wavelengths above 1000 nm, analysis is difficult because the absorption by hemoglobin is small and the absorption by water molecules is large.

Therefore, the emission wavelengths 1 λ2 and λ3 are visible from 600 nm to 1000 nm. Set from light and near-infrared light. Furthermore, when setting the emission wavelength by focusing on the difference in molar extinction coefficient, it is advisable to set it from the visible light region where the electronic spectrum appears, that is, from 600 nm to 780 nm.

_{Here, HbAl c- 0 2, Hb- 0} 2, and the change of the molar absorption light coefficient at each wavelength H b _ CO and by connexion measured spectrophotometer. Fig. 5 shows the measured P and light characteristic curves. In addition, in order to clearly understand the difference in the molar extinction coefficient of each type of hemoglobin at each wavelength, FIG. 6 shows the characteristic curves in which the ratio of the molar extinction coefficient of each type of hemoglobin is P and the light intensity ratio.

A method for setting the wavelengths λ 1, λ 2 and λ 3 in the blood analyzer according to the present embodiment will be described with reference to FIG.

The vertical axis is the molar extinction coefficient of each hemoglobin component, and the horizontal axis is the wavelength.

The first k 1 molar extinction coefficient of HbAl c- 0 ₂ is a component, the molar extinction coefficient k 2 of the Hb-0 ₂ which is the second component is the third component Hb- C_〇 molar absorption Let the coefficient be k3.

As the first wavelength λ 波長, a wavelength having a large difference in molar extinction coefficient between various hemoglobins is selected. According to FIG. 5, there is a large difference in the molar extinction coefficient near the wavelength of 630 nm. In 650 nm region from 600 nm, when arranged in descending order of molar extinction coefficients, Hb -CO, HbAl c-〇 _2, Hb_〇 ₂ that is, a k 3> k 1> k 2 . The first wavelength λ 1 is set from the range from 600 nm to 650 nm. For example, if the emission wavelength λ1 is designed to be 63 O nm and an orange light-emitting diode is used, it is advantageous in terms of cost and delivery time in parts procurement.

The second wavelength λ 2 is set from a region different from the molar extinction coefficient ratio at the previously set wavelength λ 1. According to FIG. 5, in the region from 650 nm to 780 nm, when the molar extinction coefficient is arranged in descending order, HbAl c—O ₂ , Hb—CO, Hb—O ₂ , and HbAl c—O ₂ and Hb—CO It turns out that it is reversed. That is, kl≥k3> k2. The second wavelength λ 2 is set from the range of 650 nm to 780 nm. For example, if the emission wavelength λ 2 is 680 nm and a red emission diode is used, it is advantageous in terms of cost and delivery time in parts procurement. Of course, if 660 nm or 700 nm red light-emitting diodes can be easily procured, the design may be made using them. The third wavelength λ 3 is set from a region different from the ratio of the molar extinction coefficient at the wavelengths 1 and λ 2 set previously. In the 1000 nm region _{850n m, Hb Al e- 0 2} , Hb- 0 2, Hb- difference in molar extinction coefficient of CO is little. That is, kl = k 2 = k 3. This isosbestic characteristic shows a characteristic different from the ratio of the molar extinction coefficient at the wavelengths λΐ and λ 2. The third wavelength λ 3 is set from the range of 850 nm to 1000 nm. For example, if a design is made to use a 940 nm infrared light emitting diode, which is often used for optical communication using infrared light with an emission wavelength of λ3, it is advantageous in terms of cost and delivery time in parts procurement.

As described above, by appropriately selecting the wavelength of the light emitting element serving as the light source, the component ratio of hemoglobin can be accurately calculated.

In addition, by selecting the wavelength of the light-emitting diode from the light-emitting diodes having a large supply amount, it is possible to design a more easily procured and inexpensive product.

By the way, it is known that an optical analyzer can reduce the error when measured at an absorption band (singular point) peculiar to a substance. For example, HbAl c- 0 ₂ shown in FIG. 5, the wavelength one molar extinction coefficient graph Hb-CO, and HbAl c-〇 ₂ curve arrows and Moriaga One in which point (position of the wavelength λ ΐ), Hb — The point where the CO curve rises slightly (the wavelength λ 2 position) is the singular point. However, as shown in FIG. 5, HbAl c-〇 _2, Hb-wavelength of CO - difficult to find the singular point in the molar extinction coefficient graphs. For this reason, when determining the wavelength of a light-emitting element by the method based on Fig. 5, it is difficult to determine the wavelength that is most suitable for measurement, and the set wavelength may deviate from the best wavelength, thereby reducing measurement accuracy. there were.

Accordingly, the present invention is, HbA 1 c- 0 ₂ shown in FIG. 6, Hb-0 _2, Hb-CO based on the wavelength one molar absorbance ratio, locate the wavelength of the absorbance ratio is maximum, measurement results definitive in this wavelength From the analysis.

Based on FIG. 6, a method of setting the wavelengths λ1, λ2, λ3 having the maximum absorbance ratio will be specifically described. The method of setting the wavelengths λΐ, λ2, and 3 is a method of obtaining the ratio of the molar extinction coefficient of various hemoglobins, that is, the absorbance ratio.

The absorbance ratio on the vertical axis in FIG. 6 is the ratio of the molar extinction coefficient of various hemoglobins, kj / (k1 + k2 + k3). The horizontal axis is the wavelength.

First, focusing on the third component, Hb—CO, the P and luminous intensity ratio are k 3 / (k 1 + k 2 + k 3). Here, it can be seen that the maximum of the absorbance ratio of Hb—CO is in the wavelength range from 600 nm to 650 nm. Therefore, the first wavelength 1 may be set from this wavelength region. In particular, it can be seen that it is almost maximum around 630 nm. This is because the absorption band of Hb—CO is in this region.

Next, focusing on HbAl c-〇 ₂ is a first component, the maximum of the absorbance ratio of HbAl C_〇 _2, it can be seen that from wavelength 650 nm to 780 nm region. Therefore, the second wavelength λ 2 may be set from this wavelength region. In particular, it can be seen that it is almost maximum around 680 nm. This is because there is an absorption band of Hb A 1 c—〇 ₂ in this region.

Further, paying attention to Hb-〇 ₂ is a second component, in the region of 100 0 nm wavelength 850 nm, Cal Kotogawa absorbance ratio of Hb-0 ₂ becomes maximum or maximum. Therefore, the third wavelength λ 3 is set from this region. As described above, the wavelengths λ, λ2, and λ3 are set from the wavelengths at which the absorbance ratio of various hemoglobins is maximum or the absorbance ratio is maximum.

As described above, when the analysis is performed by irradiating an emission wavelength at which the absorbance ratio is maximum or the absorbance ratio is maximum, it is possible to obtain a highly accurate analysis result.

The maximum of the absorbance ratio may be obtained from the absorbance obtained by an experiment.

Furthermore, the calculation can be simplified by selecting the isosbestic point for the emission wavelength. Although the third wavelength is already choose isosbestic point, the second wavelength may be chosen isosbestic point of the near with 650 nm HbAl c-〇 ₂ and Hb-CO. Showed calculation formula of Mo-globin to glycolide in (8), HbAl c-〇 ₂ wavelength λ 3, Hb- 0 _2, as isosbestic point of Hb-CO, and ε 31 = ε 32 = ε33 . Further, if the wavelength λ 2 is set as an equal absorption point of HbAl c−〇 ₂ and Hb—CO and ε21 = ε23, the equation (11) is obtained, and the calculation can be simplified. χ = ³ 1 ( ^£ 22 ⁸ 33 ^ ^ 21 ^£ 32) ^{+ a} 2 ( ^£ 11 ^ε 32— ^ε 11 ^£ 33 ^{/ + a} 3 ( ^£ 11 ^£ 23— ^£ 11 ^£ 22)

21 22) ( ^ε 31- ^ε 33 The relationship between the component ratio (%) of hemoglobin A 1 c (HbAl c- 0 ₂ ) in blood and the average blood glucose level (mg / dl) is as shown in the following table. , by the above method, when obtaining the component ratio of HbA 1 c- 0 _2, it can therefore be found even an average blood glucose level.

Therefore, as the concentration of the blood component in the present invention, a mass percent concentration such as a component ratio (%) of various hemoglobins in blood and a substance amount in a fixed volume such as an average blood sugar level (mg / d1) are determined. be able to.

In addition, both the component ratio and the blood glucose level can be displayed on the display unit of the blood analyzer, and in some cases, only the average blood glucose level can be displayed.

FIG. 7 is an external view of a blood analyzer according to another embodiment of the present invention. The difference between the blood analyzer of this embodiment and the blood analyzer shown in FIG.

In addition to displaying glycohemoglobin in Fig. 3, it also indicates the component ratio of carboxyhemoglobin Hb-CO. This Hb—CO often binds to the carbon monoxide contained in tobacco smoke and can be used as an indicator of smoker health care. In particular, for patients with emphysema with reduced pulmonary function, Hb_C〇 can also be a cause of shortness of breath, and is therefore an important indicator of health care. Industrial applicability

Diabetes must be patient on diet and exercise. It needs to remain strong and dedicated to treatment. If you can easily measure glycohemoglobin at home at home, you can maintain your willingness to bring it close to normal. In other words, the non-invasive and inexpensive blood analyzer according to the present invention is a useful self-care means that not only can perform measurement without pain but also can improve treatment consciousness for diabetic patients. And it can prevent complications such as neuropathy, retinopathy and nephropathy. Furthermore, if the self-measurement of glycated hemoglobin is measured not only for diabetic patients but also for healthy adults, it will help prevent diabetes.

Claims

The scope of the claims

1. A blood analyzer that measures the concentration of a specific component in blood components using light of different wavelengths.

A blood analyzer, wherein at least the concentration of glycohemoglobin is measured as the specific component.

2. The blood analyzer according to claim 1, wherein said glycated hemoglobin is hemoglobin Alc.

3. The blood analyzer according to claim 1, wherein a wavelength of at least one of the plurality of lights is set to a wavelength at which the absorbance ratio of glycated hemoglobin is a maximum value.

4. The blood analyzer according to any one of claims 1 to 3, wherein, as the specific component, in addition to the glycohemoglobin, human hemoglobin and carboxyhemoglobin are included.

5. The blood analyzer according to claim 4, wherein the light of the plurality of different wavelengths is set to a wavelength near a maximum value or a maximum value of the absorbance ratio of the plurality of specific components.

6. When the molar absorption coefficient of the glycohemoglobin, the molar absorption coefficient of the oxyhemoglobin, and the molar absorption coefficient of the carboxyhemoglobin are k1, k2, and k3, respectively, The first wavelength is set in the region of k3> kl> k2, the second wavelength is set in the region of k1≥k3> k2, and the third wavelength is set in kl ^ k2k3 6. The blood analyzer according to claim 4, wherein the blood analyzer is set in a region of the blood analyzer.

7. The first to third wavelengths are wavelengths of 600 to 1000 nm. 7. The blood analyzer according to claim 6, wherein:

8. The blood analyzer according to claim 6, wherein the first wavelength is a wavelength of 650 to 780 nm.

9. The blood analyzer according to claim 6, wherein the second wavelength is a wavelength of 600 to 650 nm.

10. The blood analyzer according to claim 6, wherein the third wavelength is a wavelength of 850 to 1,000 nm.