JP4706028B2 - Blood glucose level measuring apparatus and method - Google Patents

Description

  The present invention relates to a blood glucose level measuring apparatus and method, and more particularly, to a blood glucose level measuring apparatus and method that can measure a blood glucose level non-invasively using a circular dichroism spectrum.

  Various non-invasive blood sugar level measuring devices have been proposed by many research institutions and companies. The proposed devices are mainly devices that use optical measurement methods, including near-infrared spectroscopy (including transmission, reflection, and multiple scattering methods), Raman spectroscopy using visible light, and optical rotation. A spectroscopic method, a method using a refractive index (interference method, scattering intensity method), a fluorescence method, or the like is known.

As an apparatus using near-infrared light, a living body measurement site is irradiated with three near-infrared lights having different wavelengths from a light source, and the transmission intensities of the three lights transmitted through the living body are detected at the same time. An apparatus is known that calculates a second-order absorbance value of near-infrared light from a site to be measured from the intensity, and calculates a blood glucose level in the living body based on calibration curve data from the fluctuation range of the second-order absorbance value ( Patent Document 1)
JP 2000-189404 A

  However, since the conventional blood glucose level measurement device uses visible light or near infrared light, it distinguishes glucose from other substances that show the same permeability as glucose for visible light or near infrared light. Since it is difficult to do this, there is a problem that sufficient measurement accuracy cannot be obtained.

  In order to solve the above problems, the present invention has a characteristic wavelength of glucose concentration in the ultraviolet region, and a vinegar pectin of the characteristic wavelength is unique to glucose not found in other substances, and has a characteristic wavelength peak. An object of the present invention is to provide a blood sugar level measuring apparatus that can measure a blood sugar level with high accuracy, and has been made paying attention to the fact that the position and the peak intensity have a correlation with the glucose concentration.

  In order to achieve the above object, a blood glucose level measuring apparatus according to the present invention comprises a light source for irradiating light in the ultraviolet wavelength region, and two types of circularly polarized light having rotation directions opposite to each other. Obtained from the circularly polarized light converting means for conversion, the detecting means for detecting the absorption spectrum of two kinds of transmitted circularly polarized light that has been converted by the circularly polarized light converting means and transmitted through the subject, and the absorption spectrum detected by the detecting means A calculation means for calculating a blood sugar level based on an intensity corresponding to a difference spectrum obtained from an absorption spectrum of transmitted circularly polarized light transmitted through a subject having a normal blood sugar level. It is composed.

  Moreover, the blood glucose level measuring method of the present invention irradiates a subject by converting light irradiated from a light source that irradiates light in an ultraviolet wavelength region into two types of circularly polarized light having mutually opposite rotation directions, The intensity of the difference spectrum obtained from the absorption spectra of the two types of transmitted circularly polarized light that has passed through the subject, and a plurality of difference spectra obtained from the absorption spectrum of the transmitted circularly polarized light that has passed through the subject having a normal blood glucose level The blood glucose level is calculated based on the intensity corresponding to the peak.

  In the present invention, since the peak position and the peak relative intensity in the characteristic wavelength spectrum in the ultraviolet region are used, the glucose concentration corresponding to the blood glucose level can be directly detected without much influence from the attenuation effect in the subject. Ultraviolet light is more sensitive than visible or near-infrared light for measuring glucose concentration, and is an intensity measurement at the characteristic wavelength of glucose, so other fats, proteins similar to glucose, or Since it can distinguish and measure from an electrolyte, a highly accurate measurement can be performed.

  In the present invention, the blood glucose level can also be measured using the intensity of the characteristic wavelength peak of the difference spectrum itself, but since the peak position of the characteristic wavelength of the difference spectrum has a correlation with the glucose concentration, the blood glucose level is It is effective to calculate

  Further, the characteristic wavelength peak corresponding to glucose in the difference spectrum is preferably a wavelength in the vicinity of 180 nm to 185 nm.

  As described above, according to the present invention, since the blood glucose level is measured by paying attention to the fact that the characteristic wavelength of the glucose concentration exists in the ultraviolet region, the blood glucose level can be accurately measured. Is obtained.

It is a block diagram which shows embodiment of this invention. It is a diagram which shows the relationship between the wavelength of the circular dichroism spectrum of the aqueous solution from which glucose concentration differs, and a molecular ellipticity. In Example 1, it is a diagram which shows the peak position of CD spectrum, and the glucose concentration dependence of the intensity | strength. 3 is a flowchart illustrating a routine for calculating a blood glucose level in the first embodiment. In Example 2, it is a diagram which shows the peak position and intensity | strength of CD spectrum of optically active molecules other than glucose. 9 is a flowchart showing a routine for calculating a blood sugar level in the second embodiment.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In the present embodiment, as shown in FIG. 1, an ultraviolet light source 10 that emits light in a wavelength region of 160 to 200 nm, for example, is provided as light in the ultraviolet wavelength region. On the light emitting side of the ultraviolet light source 10, incident light in the ultraviolet wavelength region is converted into two types of circularly polarized light having rotation directions opposite to each other according to two applied voltages having different magnitudes. A Pockels cell 12 that is a circular polarization conversion optical device is disposed.

  The Pockels cell 12 is connected to a drive circuit 14 for applying a voltage to the Pockels cell.

  Instead of the Pockels cell, an element that applies distortion to quartz based on the principle of the piezoelectric effect and generates circularly polarized light by the distortion may be used.

  A subject 16 is disposed on the circularly polarized light emission side of the Pockels cell 12. As a subject, a part of a thin skin layer of a living body such as a finger or earlobe of a human hand is assumed. The subject may be an intercellular fluid, gingival crevicular fluid, urine, or the like extracted non-invasively from the human body.

  A spectroscope 18 for detecting an absorption spectrum of transmitted light is disposed on the light transmission side of the subject 16. A computer 20 is connected to the spectroscope 18, and a calibration curve (calibration curve data) indicating the relationship between the glucose concentration, the peak position of the characteristic wavelength, and the peak intensity ratio is stored in advance in the computer 20. A program for calculating a blood glucose level from the absorption spectrum detected by the spectroscope 18 and the stored calibration curve is stored.

Next, the calibration curve stored in the computer 20 will be described. It should be noted that in the present invention, several embodiments that differ depending on the contents of the calibration curve stored in the computer 20 can be considered. Hereinafter, as Example 1, a case where the calibration curve shown in FIG. 2 is used will be described.
FIG. 2 shows the absorption spectra of two types of transmitted circularly polarized light that are transmitted through the subject by converting light of wavelength 175 to 500 nm into left and right circularly polarized light and irradiating the subject with four types of aqueous solutions having different glucose concentrations. The experimental result which computed the molecular ellipticity of the difference spectrum (Circular Dichroism: Circular Dichroism) of the absorption spectrum in the case of detecting is shown. The experiment was performed on aqueous solutions having glucose concentrations of 121 mg / dl, 242 mg / dl, 485 mg / dl, and 970 mg / dl.

  As understood from FIG. 2, the peak value of the difference spectrum, that is, the circular dichroism spectrum is shifted to the longer wavelength side as the glucose concentration increases from 121 mg / dl to 970 mg / dl. The spectral height near the peak also increases as the glucose concentration increases.

  FIG. 3 is a graph showing the dependence of the peak position of the CD spectrum on the glucose concentration and its intensity on the glucose concentration. As can be seen from FIG. 3, the position of the peak wavelength and the CD intensity are monotonic functions with respect to the glucose concentration. Therefore, the glucose concentration in the blood can be quantitatively calculated from the position and intensity of the peak wavelength obtained by measuring the CD spectrum in the blood.

  Next, a blood glucose level measurement routine executed according to a program stored in the computer will be described with reference to the flowchart shown in FIG.

  In a state in which light in the ultraviolet wavelength region is emitted from the ultraviolet light source 10, the drive circuit 14 is controlled so that right polarized light and left polarized light are alternately emitted from the Pockels cell in step 100, and a voltage is applied to the Pockels cell. As a result, the right polarized light and the left polarized light are alternately irradiated on the subject, and the transmitted right polarized light and the transmitted left polarized light transmitted through the subject are alternately incident on the spectroscope 18. Each absorption spectrum of polarized light is detected alternately.

  In step 102, the absorption spectrum detected by the spectroscope 18 is captured by A / D conversion (analog / digital conversion). In step 104, a difference spectrum representing the difference between the absorption spectrum of the transmission right polarization and the absorption spectrum of the transmission left polarization is calculated. In step 106, the molecular ellipticity at each wavelength is calculated based on the difference spectrum.

  In step 108, the peak position of the spectrum caused by glucose in the wavelength region of a wavelength of 200 nm or less is obtained from the measured value of the CD spectrum. In step 112, the blood glucose level is calculated from the peak position and the calibration curve in FIG.

  Next, Example 2 will be described. In Example 2, components from albumin, globulin, and ascorbic acid, which are major optically active molecules other than glucose present in blood, are fitted and separated from the total spectrum, and the CD intensity and glucose of each of these major optically active molecules are determined. The glucose concentration is quantitatively determined from the relative intensity to the CD intensity.

  Specifically, as can be seen from FIG. 5, the peak position of the CD spectrum of the optically active molecule other than glucose exists at a position different from the peak position of glucose.

  In general, albumin, globulin and ascorbic acid are known to show constant values over time.

  Therefore, it is possible to quantitatively determine the glucose concentration at any time by measuring the relative intensity of albumin, globulin and ascorbic acid CD intensity and glucose CD intensity.

  Next, a blood glucose level measurement routine executed in accordance with a program stored in the computer in the second embodiment will be described with reference to the flowchart shown in FIG.

The processing in steps 200, 202, 204, and 206 in the flowchart in FIG. 6 is the same as the processing in steps 100, 102, 104, and 106 in the flowchart in FIG.
Unlike Example 1 of FIG. 4, in step 208, the CD spectrum is fitted and separated into glucose, albumin, globulin, and ascorbic acid spectra, and the CD intensity by each component is obtained. In step 212, the CD intensity by the glucose component is obtained. Then, the blood glucose level is calculated from the ratio of the CD intensities of albumin, globulin and ascorbic acid and the calibration curve of FIG.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Ultraviolet light source 12 Pockels cell 14 Drive circuit 16 Subject 18 Spectrometer 20 Computer

Claims (4)

A light source that emits light in the ultraviolet wavelength region;
Circularly polarized light conversion means for converting light emitted from the light source into two types of circularly polarized light having rotation directions opposite to each other;
Detecting means for detecting absorption spectra of two kinds of transmitted circularly polarized light converted by the circularly polarized light converting means and transmitted through the subject;
Calculation means for calculating a blood glucose level based on the intensity of the peak of the difference spectrum obtained from the absorption spectrum detected by the detection means and the relationship between the wavelength of the peak and the glucose concentration;
A blood glucose level measuring device including The blood glucose level measuring apparatus according to claim 1, wherein a wavelength corresponding to the peak wavelength is 180 nm to 190 nm. Emits light in the ultraviolet wavelength region,
The emitted light is converted into two types of circularly polarized light having rotation directions opposite to each other,
Detecting the absorption spectrum of the two types of circularly polarized light that has been converted and transmitted through the subject;
Calculating the blood glucose level based on the intensity of the peak of the difference spectrum obtained from the detected absorption spectrum and the relationship between the wavelength of the peak and the glucose concentration;
Blood glucose measurement method.   The blood sugar level measuring method according to claim 3, wherein a wavelength corresponding to the peak wavelength is 180 nm to 190 nm.

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