JP2002085385A - Method and apparatus for measuring blood sugar value - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method and apparatus capable of taking accurate measurements of blood sugar values without sampling blood. SOLUTION: The apparatus includes a laser beam applying portion for applying a laser beam of a single wavelength into a living body from the outside of the body through the skin; a Raman analysis portion for measuring the amounts of Schiff base type glycohemoglobin oxides in blood through Raman spectroscopy by selecting only a Raman scattered portion whose strength varies in synchronism with the pulse waves of the living body, from the laser beam applied and passed through the living body in a laser beam application process; a converting portion for converting the amounts of Schiff based glycohemoglobin oxides measured by the Raman analysis portion into a blood sugar value on the basis of a criteria which was used to select only the portion of the beam whose strength varies in synchronism with the pulse waves of the living body; and a display portion for visibly displaying the blood sugar value provided by the converting portion.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a blood glucose level measuring method and a blood glucose level measuring apparatus capable of measuring a blood glucose level without collecting blood.

[0002]

2. Description of the Related Art Diabetes is determined by measuring glucose concentration in blood, that is, blood sugar level. Conventionally, as a measurement of blood sugar level, a glucose oxidase method utilizing the decomposition of glucose by glucose oxidase from collected blood, a simple colorimetric method using a test paper containing a coloring reagent, and the like are generally performed. I was

[0003]

However, the above method is
Blood must be collected to measure blood glucose.
For this reason, a great burden is imposed on the blood-collecting person, such as causing pain to the blood-collecting person, disturbing disinfection of the blood-collecting needle used for blood collection, and having a problem with the safety of the blood-collecting person. Had to be forced. From the above,
Although a method and an apparatus for measuring a blood glucose level without performing blood collection have been proposed, an accurate blood glucose level cannot be obtained by a conventional blood glucose measurement method without performing blood collection.

[0004] In view of such circumstances, an object of the present invention is to provide a blood sugar level measuring method and apparatus capable of accurately measuring a blood sugar level without performing blood sampling.

[0005]

In order to achieve the above object, a blood sugar level measuring method according to the present invention has a blood sugar level measuring method according to claim 1 of the present invention (hereinafter referred to as "measurement of claim 1"). Method)) is a laser irradiation step of irradiating a single-wavelength laser from the outside of the living body to the inside of the living body through the skin, and a method in which the laser irradiated by the laser irradiation step passes through the inside of the living body. A light-receiving step of receiving at least light including Raman scattered light, and among the Raman scattered light received in the light-receiving step, selecting only a part whose intensity fluctuates in synchronization with a pulse wave of a living body, A Raman analysis step of measuring the amount of oxidized glycohemoglobin of Schiff base type in blood by performing Raman spectroscopy analysis of the selected Raman scattered light was adopted.

[0006] In the above configuration, the wavelength of the laser irradiated in the laser irradiation step is not particularly limited as long as oxyhemoglobin in the blood can be specified, but the blood glucose measurement method according to claim 2 of the present invention. (Hereinafter, it is described only as “the measuring method of claim 2”).
It is preferable that the laser irradiated in the laser irradiation step is excitation light (absorbed light of oxyhemoglobin) that excites absorption of wavelength in the oxyhemoglobin molecule. That is, when the laser which is the laser irradiation step is the absorption light of oxyhemoglobin, by irradiating the laser, the resonance Raman spectrum in the reaction product of oxyhemoglobin or oxyhemoglobin is selectively excited from the blood components. It will be. Therefore, when performing Raman spectroscopic analysis, noise due to other substances in the living body can be removed, and only the amount of oxidized glycohemoglobin of the Schiff base type can be selectively measured.

[0007] Here, the excitation light for exciting the Schiff base type glycated hemoglobin refers to light having an absorption wavelength of iron oxide of hemoglobin, specifically, 570 nm to 580 nm.
Refers to the wavelength of nm. At this time, the light source of the laser is not particularly limited. For example, a semiconductor laser or a light emitting diode (LED) is preferably used. That is, a semiconductor laser or a light emitting diode (LE)
When D) or the like is used as a light source,
It is possible to improve energy efficiency, reduce the size and weight of the device, make it portable, and improve the S / N ratio.

[0008] The Raman scattered light in the above-mentioned structure is the scattered light that is shifted to a longer wavelength side than the wavelength of the laser in the light passing through the living body when the laser is irradiated into the living body. Refers to light. The Raman scattered light has such a property that when a laser is irradiated on an object, a characteristic unique to each object appears. Raman spectroscopy refers to an analysis technique for performing spectroscopic analysis of the characteristics of the Raman scattered light to specify an object.

Next, the oxidized glycohemoglobin of the Schiff base type will be described. First, blood contains hemoglobin called "hemoglobin" contained in red blood cells of blood. Hemoglobin has a role of transporting oxygen to the whole body in the body, and reacts with glucose in the blood as shown by the following chemical formula in the blood to generate Schiff base glycohemoglobin (I) and Amadori glycohemoglobin (I).
Glycohemoglobin in the form of I).

[0010]

[Formula 1]

In the above formula, when hemoglobin reacts with glucose, first, an unstable reactant, Schiff base glycohemoglobin (I), is formed, and thereafter, Schiff base glycohemoglobin (I) undergoes Amadori transfer. After that, it becomes Amadori-type glycohemoglobin (II) which is a stable reactant. At this time, the production reaction in which Schiff base glycohemoglobin (I) is produced from hemoglobin and glucose is a reversible reaction, and the production reaction in which Amadori glycohemoglobin (II) is produced from Schiff base glycohemoglobin (I). Is an irreversible reaction.

As described above, there are two kinds of reactants as glycohemoglobin, but Schiff bases (-HC = N
Containing (-) is glycohemoglobin (I) of the Schiff base type. Most of hemoglobin is present as oxidized hemoglobin in arteries of living organisms. Therefore, oxidized glycohemoglobin of the Schiff base type can perform Raman spectroscopy more easily than that of (non-oxidized) glycohemoglobin of the Schiff base type.

[0013] Further, the blood glucose level measuring apparatus according to claim 3 of the present invention (hereinafter, referred to only as "apparatus of claim 3").
A laser irradiation unit that irradiates a laser of a single wavelength into the living body through the skin from outside the living body, and at least the Raman scattered light is included in the light emitted from the laser irradiated in the laser irradiation step through the living body. A light receiving unit that receives light and, from among the Raman scattered lights received in the light receiving step, select only a part whose intensity fluctuates in synchronization with a pulse wave of a living body, and select the selected Raman scattered light. Raman spectroscopic analysis to measure the amount of oxidized glycated hemoglobin of Schiff base type in blood, and the amount of oxidized glycated hemoglobin of Schiff base type measured by the Raman analysis unit is synchronized with the pulse wave of the living body. And a table for displaying the blood glucose level converted by the conversion unit in a visually recognizable manner. And a configuration in which a part.

In the above configuration, the living body part to be irradiated with the laser from the laser irradiation part is not particularly limited as long as a blood vessel passes through the inside thereof. For example, it is preferable to target a fingertip or an earlobe. That is,
In this way, the measuring device can be downsized,
There is no exaggeration when performing measurements. Further, the light receiving section is not particularly limited, and includes, for example, those using an electric coupling device (CCD) and those using an infrared light receiving element.

The Raman analyzer is not particularly limited as long as it can perform Raman spectroscopy, and examples thereof include a Raman analyzer of a prism type, a diffraction type, a Fourier type, and the like.

The processing means of the conversion unit is not particularly limited, but includes, for example, beat processing, digitization processing, processing using a CPU, and the like. The display unit may be a digital display using a light emitting diode (LED) or a liquid crystal (LCD) or an analog display as long as it can recognize the blood sugar level. It may be used and is not particularly limited.

[0017]

Embodiments of the present invention will be described below in detail with reference to the drawings. FIG. 1 is a perspective view showing one embodiment of a blood sugar level measuring device (hereinafter, referred to simply as “measuring device”) according to the present invention. FIG. 2 is similar to FIG.
FIG. 2 is a schematic diagram for explaining a mechanism of the measuring device 1 shown in FIG.

As shown in FIGS. 1 (a) and 1 (b), the measuring device 1 has a cylindrical shape, a finger insertion portion 11 for inserting a fingertip F, a display portion 12 for displaying a blood glucose level, and the like. It has. The finger insertion unit 11 is formed of a hollow portion of the measurement device 1 having a cylindrical shape, and the display unit 12 displays a blood glucose level in mg / d.
Digital display is performed in units of L.

Next, the mechanism of the measuring device 1 that can measure the blood glucose level by simply inserting the fingertip F into the finger insertion section 11 will be described. As shown in FIG. 2, the measurement device 1 includes a laser irradiation unit 2, a light receiving unit 3, a Raman analysis unit 4, a conversion unit 5, a finger insertion unit 11, and a display unit 12.

The laser irradiation unit 2 is not shown,
It has a light source that emits a laser, and a filter for extracting a laser of a single wavelength from the laser beam. As shown in FIG. 2, as shown in FIG. Single wavelength laser L
Is illuminated.

The laser L irradiated into the fingertip F described above
Is transmitted light O after passing through the fingertip F. The transmitted light O is
Rayleigh scattered light R2 having exactly the same wavelength as the laser L irradiated into the fingertip F, and Raman scattered light R1 having a wavelength shifted to a longer wavelength side than the wavelength of the laser L are provided.

The light receiving section 3 receives all of the above-mentioned transmitted light O, that is, receives both the Raman scattered light R1 and the Rayleigh scattered light R2. Although not shown, the light receiving section 3 includes a light collecting means (lens) and an optical filter. Therefore, the light receiving unit 3
Is configured to separate the Raman scattered light R1 and the Rayleigh scattered light R2 by an optical filter, send the Raman scattered light R1 to the Raman analysis unit 4, and send the Rayleigh scattered light R2 to the Rayleigh analysis unit 6.

The Raman analysis unit 4 includes the filter 41 shown in FIG. 4, and the intensity of the Raman scattered light R1 sent from the light receiving unit 3 fluctuates in synchronization with the pulse wave of the living body. The Raman scattered light R11, which is the portion where the light is emitted, is selected, Raman spectroscopic analysis is performed, the amount of glycated hemoglobin is measured, and the measurement data D1 is sent to the converter 5.

The conversion unit 5 converts the measurement data D1 of glycated hemoglobin measured by the Raman analysis unit 4 on the display unit 12 based on the normalized data D3 sent from the Rayleigh analysis unit 6. (Unit: mg / dL) The conversion data D2 is converted and sent to the display unit. Similar to the Raman analysis unit 4, the Rayleigh analysis unit 6 obtains the ratio of the portion where the intensity fluctuates in synchronization with the pulse wave from the Rayleigh scattered light R2 separated by the light receiving unit 3, and based on this ratio, The standardized data D3 is created and sent to the conversion unit 5.

As described above, the measuring device 1 does not simply analyze the Raman scattered light R1 but performs the measurement data D1 analyzed by the Raman analysis unit 4 on the basis of the normalized data D3 obtained by the Rayleigh analysis unit 6. Since it is displayed after being converted to be standardized, the blood glucose level can be measured in a standardized state despite individual differences such as the diameter of the fingertip F and the thickness of the blood vessel. is there.

In the above description of the measuring apparatus 1, the laser irradiation unit 2, the Raman analysis unit 4, the conversion unit 5, the Rayleigh analysis unit 6, and the display unit 12 use a power source as a power source. Description is omitted. Of course, the power source may be an alternating current (AC) power source or a direct current (DC) power source, and even if a power source such as a battery that emphasizes portability is used, it is taken in through an outlet or the like. However, a commercial power supply may be used.

Next, a method for measuring a blood sugar level using the blood sugar level measuring apparatus 1 according to the present invention will be described. First, as shown in FIGS. 1A and 1B, a subject who wants to measure a blood glucose level has a finger insertion portion 1 of a measuring device 1.
1 to insert the fingertip F. A power switch (not shown) of the measuring device 1 is turned on, and as shown in FIG. 2, a laser L having a wavelength of 580 nm, which is a wavelength for exciting oxyhemoglobin, is emitted from the laser irradiation unit 2 as a single wavelength laser. Irradiate fingertip F.

The laser beam L applied to the fingertip F becomes passing light O emitted from the fingertip F by passing or reflecting the fingertip F. The transmitted light O is received by the light receiving unit 3 and is also separated into Raman scattered light R1 and Rayleigh scattered light R2. The Raman scattered light R1 is sent to the Raman analysis unit 4, and the Rayleigh scattered light R2 is converted into the Rayleigh scattered light. Sent to 6.

As for the Raman scattered light R 1 sent to the Raman analysis unit 4, only the Raman scattered light R 11 whose intensity fluctuates in synchronization with the pulse wave of the living body is selected by the Raman analysis unit 4. Spectroscopic analysis is performed. The amount of oxidized hemoglobin (I) of Schiff base type shown in Table 1 is measured by the Raman spectroscopy. The measurement data D1 of Schiff base oxyhemoglobin (I) measured by the Raman analysis unit 4 is sent to the conversion unit 5.

On the other hand, as for the Rayleigh scattered light R2 sent to the Rayleigh analyzer 6, the ratio of the Rayleigh scattered light (not shown) whose intensity fluctuates in synchronization with the pulse wave of the living body is obtained. Normalized data D3 is created based on the ratio.
The normalized data D3 is sent to the conversion unit 5. The converter 5 converts the measurement data D1 and the standardized data D
3 and converts the converted data D2, which is the standardized blood glucose level data, and sends the converted data D2 to the display unit 12.

The display unit 12 displays the blood glucose level of the subject on the basis of the conversion data D2 converted by the conversion unit 5 in units of mg / mg.
Display in dL. As described above, the measuring device 1
Since the subject who has inserted the fingertip F into the finger insertion section 11 can check his / her own blood sugar level just by looking at the numerical value displayed on the display section 12 without performing blood sampling. is there.

Next, the principle of the above method will be described.
First, in the above measurement method, the wavelength of the laser L irradiated from the laser irradiation unit 2 was set to 580 nm.
This is because the vicinity of 580 nm is the excitation wavelength of oxyhemoglobin.

Oxygenated hemoglobin is a combination of hemoglobin and oxygen, and is contained at a high ratio in arterial blood, which supplies oxygen to the whole body. The measurement method of the present invention measures oxidized hemoglobin at 580 nm to excite oxyhemoglobin in order to measure oxidized glycated hemoglobin of a Schiff base type in a portion of which the intensity fluctuates in synchronization with a pulse wave of a living body, that is, an artery by Raman spectroscopy. Wavelength laser at fingertip F
When irradiation is performed, the effect of substances other than oxyhemoglobin on arterial blood in a living body is reduced, and a more accurate analysis can be performed.

In the above-mentioned measuring method, the Raman analysis unit 4 detects the Raman scattered light R
The reason why only the arterial blood portion is selected from the components in the living body from among 1, ie, only the Raman scattered light R11 is selected to perform Raman spectroscopic analysis is to remove analysis noise due to other components as much as possible.

That is, the Raman scattered light R is in a state as shown in FIG. That is, the Raman scattered light R
Has a shape in which a pulse wave H is superimposed on a certain component d. Here, the constant component d refers to components of various cells forming the fingertip F or components such as venous blood components. In addition,
The output of the light receiving unit shown on the vertical axis in FIG. 3 is a value obtained by electrically converting the passing light O received by the light receiving unit 3 by the light receiving unit 3, and the unit is a digital or analog processing of current or voltage. It is represented by processing. That is, the Raman analysis unit 4 removes the Raman scattered light R2 corresponding to the constant component d by the filter 41 and analyzes only the Raman scattered light R11 corresponding to the pulse wave H, thereby performing Raman spectroscopic analysis of only arterial blood. It does.

The reason why the Rayleigh analyzer 6 creates the normalized data D3 based on the ratio of the portion of the Rayleigh scattered light R2 whose intensity fluctuates in synchronization with the pulse wave is based on the diameter of the fingertip F. This is because it is possible to derive a standardized blood sugar level irrespective of different biological factors such as the size of blood vessels and blood vessels. When the standardized data D3 is created, that is, in order to correct and normalize individual differences in the biological elements of the subject, instead of the Rayleigh analysis unit 6 or in addition to the Rayleigh analysis unit 6, The following processing may be performed. One or more lights having a wavelength different from the laser L as excitation light (light in a band that is not relatively absorbed)
The fingertip F is irradiated so as to have the same optical path as the laser L, and the standardized data D3 is determined by performing arithmetic processing including the same processing as the processing of the Rayleigh scattered light R2 by the Rayleigh analyzer 6.

The above-mentioned normalized data D3 does not need to be created if the spatial region in the living body where Raman scattering occurs is constant. However, since the spatial region in a living body varies from person to person, it is necessary to standardize it. Therefore, not only in the Raman scattered light R1 but also in the Rayleigh scattered light R2, the ratio of the portion where the intensity fluctuates in synchronization with the pulse wave is calculated, the pulse wave component is calculated, and the measurement data D1 analyzed by the Raman analysis unit 4 is obtained. The standardization is performed.

The Raman analyzer 4 measures the Schiff base-type oxidized glycohemoglobin (I) (see the following formula) generated by the reaction between oxyhemoglobin and glucose. This is because the main wavelength shift of oxidized glycohemoglobin (I) of the Schiff base type by Raman spectroscopy is several tens nm under this excitation light.
This is because the influence of molecules on other biological components is reduced.

[0039]

Embedded image This is because, as shown in the above chemical formula, the formation reaction in which Schiff base-type oxidized glycohemoglobin (I) is generated from oxyhemoglobin and glucose is a reversible reaction, and the reaction rate is high. The state changes. This shift in the equilibrium state depends on the amount of glucose in the blood. Therefore, it can be said that the amount of oxidized glycohemoglobin (I) of the Schiff base type is proportional to the amount of glucose in the blood. This is because the blood sugar level can be determined by measuring the amount of the basic oxidized glycated hemoglobin (I).

Further, the oxidized glycohemoglobin (I) of the Schiff base type has a feature that it contains a Schiff base (in this case, HC = N-). That is, when focusing on the Schiff base itself, it is known that when Raman spectroscopy is performed, a unique characteristic appears at a shift wave number of 1600 to 1700 cm ^-1 (excitation wavelength +54 nm to +57 nm). Therefore, the blood sugar level can be easily derived by measuring the amount of the oxidized glycohemoglobin (I) of the Schiff base type also from the characteristic characteristic of the Schiff base appearing in the Raman spectroscopic analysis.

As described above, the blood sugar level measuring method according to the present invention can easily measure the blood sugar level without collecting blood. In addition, the measuring method and measuring device of the blood glucose level according to the present invention are not limited to the above embodiment. For example, the measuring device 1 in the above embodiment is
The fingertip F is inserted into the finger insertion portion 11 to perform the measurement. For example, as shown in FIG. 5, a form such as the measuring device 10 that inserts the wrist and measures the blood glucose level You can do it.

[0042]

As described above, the blood glucose measuring method and the measuring apparatus according to the present invention are configured as described above, and therefore, by performing the present measuring method, an accurate blood glucose level can be obtained without collecting blood. be able to.

[Brief description of the drawings]

FIG. 1 is a perspective view showing one embodiment of a blood sugar level measuring device according to the present invention.

FIG. 2 is an explanatory diagram for explaining the operation of the apparatus in FIG. 1;

FIG. 3 is a graph showing Raman scattered light synchronized with a pulse wave.

FIG. 4 is an explanatory diagram showing a filter of a Raman analysis unit.

FIG. 5 is a perspective view showing another embodiment of the blood sugar level measuring device according to the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 (Blood glucose level) measuring device 10 (Blood glucose level) measuring device 12 Display part 2 Laser irradiation part 3 Light receiving part 4 Raman analysis part 5 Conversion part

Claims (3)

[Claims] 1. A laser irradiation step of irradiating a laser of a single wavelength into the living body from outside the living body through the skin, and at least Raman scattering is performed by using the laser irradiated by the laser irradiation step from light passing through the inside of the living body. A light-receiving step of receiving light including light, and, from the Raman scattered light received in the light-receiving step, selecting only a portion whose intensity fluctuates in synchronization with a pulse wave of a living body, and selecting the selected Raman A Raman analysis step of measuring the amount of oxidized glycated hemoglobin of Schiff base type in blood by Raman spectroscopy analysis of scattered light. 2. The laser irradiation in the laser irradiation step,
The method for measuring a blood glucose level according to claim 1, wherein the excitation light is excitation light for exciting absorption of a wavelength in the oxyhemoglobin molecule. 3. A laser irradiator for irradiating a single-wavelength laser from the outside of the living body to the inside of the living body through the skin, and at least Raman scattering from the light emitted from the laser irradiated in the laser irradiation step through the living body. A light receiving unit for receiving light including light, and from the Raman scattered light received in the light receiving step, selecting only a portion whose intensity fluctuates in synchronization with a pulse wave of a living body, and selecting the selected Raman Raman spectroscopic analysis of the scattered light to measure the amount of oxidized glycohemoglobin of the Schiff base type in blood, and the amount of the oxidized glycated hemoglobin of the Schiff base type measured by the Raman analysis unit is determined by measuring the pulse wave of the living body. A conversion unit for converting only the part whose intensity fluctuates in synchronization with the blood glucose level based on the selected criterion, and the blood glucose level converted by the conversion unit to be displayed visually. Measuring device of the blood glucose values and a display unit for.