JP2012191969A - Biological information measuring apparatus - Google Patents

Abstract

A blood glucose level measuring apparatus having a blood glucose level measuring accuracy at a practical level is provided.
A biological information measuring device including a near-infrared light source, a light source-side optical fiber, a detection-side optical fiber, a near-infrared absorption spectrum measuring device, and a data analyzing device. Near-infrared light from the contact surface 131 to be contacted, the light source side optical fiber fixing part 132, the detection side optical fiber fixing part 133, and the light source side optical fiber 130 is guided to the biological information acquisition part through the gap and the biological information acquisition is performed. The biological information measurement apparatus 100 further includes a measurement attachment 130 having a light guide space 134 for guiding near-infrared light diffusely reflected at the site to the detection-side optical fiber 140 through a gap.
[Selection] Figure 1

Description

  The present invention relates to a biological information measuring device such as a blood glucose level measuring device, a blood cholesterol concentration measuring device, a blood neutral fat concentration measuring device, or a blood alcohol concentration measuring device.

  In recent years, lifestyle-related diseases such as diabetes, hypertension, hyperlipidemia, arteriosclerosis, and cancer caused by lifestyle such as diet, exercise and stress have become serious problems. In addition, it has been found that these lifestyle-related diseases are not caused by separate diseases, but are caused by obesity in which fat has accumulated in the internal organs. A state in which various diseases are likely to be caused by visceral fat obesity is called “metabolic syndrome”, and diagnostic criteria including blood glucose levels have been established and are considered as targets for treatment.

  In such a situation, in order to prevent or treat the disease, it is necessary to actually measure the blood glucose level by an individual and perform self-management. Currently, blood sampling is a common method of measurement, but it has problems such as causing pain and stress to the patient and risk of infection, so blood glucose levels can be measured non-invasively from the past. Development of measuring devices is underway (see, for example, Non-Patent Document 1 and Patent Documents 1 to 4).

  Among these, Non-Patent Document 1 describes a blood glucose level measuring device (hereinafter referred to as a conventional blood glucose level measuring device 80) using a plate prism. FIG. 16 is a diagram for explaining a conventional blood sugar level measuring apparatus 80. FIG. 16A is a diagram showing the overall configuration of the blood sugar level measuring device 80, and FIG. 16B is a diagram showing the main part of the blood sugar level measuring device 80.

  As shown in FIG. 16, a conventional blood glucose level measuring device 80 includes a light source device 810 that emits infrared light, a sample chamber 830, detection devices 850 and 852 that detect infrared light, and detection devices 850 and 852. And a data analysis device (not shown) that obtains blood sugar level information by analyzing the infrared light detected in step (b). The light source device 810, the sample chamber 830, and the detection devices 850 and 852 constitute a Fourier transform infrared spectrophotometer FTIR. The sample chamber 830 includes a plate-like prism 832 having a contact surface with which the living body LB is brought into contact, a mirror 820 for guiding near-infrared light from the light source device 810 to the plate-like prism 832, and a plate-like prism 832. And a mirror 840 for guiding the near-infrared light to the detection device 850. The plate prism 832 is made of a high refractive index substance (zinc selenide: ZnSe) that transmits infrared light.

When measuring the infrared absorption spectrum of the living body surface using the conventional blood glucose level measuring device 80, the living body LB is brought into close contact with the surface of the plate prism 832 and the infrared light made into interference light by the movable interferometer 816 is used. Light is incident on the plate prism 832 at an incident angle greater than the critical angle and guided while being repeatedly totally reflected at the interface with the living body. At this time, the evanescent light is attenuated and attenuated by the absorbing material present on the living body surface. Therefore, by measuring the intensity of infrared light that has passed through the plate prism 832 as a function of the moving distance of the movable mirror and performing Fourier transform on an interference waveform called an interferogram obtained by the detectors 850 and 852, for example, obtain an infrared absorption spectrum in the wave number range of 1500cm ^-1 ~950cm ^-1.

  When measuring a blood glucose level using the conventional blood glucose level measuring device 80, for example, an infrared absorption spectrum of the middle finger is measured according to the above procedure for a subject given a predetermined sugar load, and an invasive blood glucose level is measured. A blood glucose level is measured by a measuring instrument, a PLS regression analysis is performed using the infrared absorption spectrum as an explanatory variable, and the blood glucose level as an objective variable, and a blood glucose level calibration curve is constructed.

  FIG. 17 is a diagram for explaining a calibration curve construction result by the conventional biological information measuring device 80. FIG. 17A is a diagram showing the distribution of blood glucose level on the error grid, and FIG. 17B is a diagram showing the PLS result and the EGA result. In FIG. 17A, the horizontal axis indicates the reference blood glucose level, and the vertical axis indicates the predicted blood glucose level.

  As can be seen from FIG. 17, by using the conventional blood glucose level measuring device 80, for example, in the case of the PLS factor 8, a relatively high correlation coefficient (0.85) and a relatively low prediction error (17.4 mg / It was confirmed that a calibration curve having dl) could be prepared and that the blood glucose level could be quantitatively evaluated using this calibration curve. The correlation coefficient is a parameter that indicates the degree of correlation between the reference blood glucose level and the predicted blood glucose level, and the higher one (for example, 0.80 or more) is preferable. The prediction error is a parameter that serves as an index of the accuracy of the calibration curve, and the lower one (for example, 20 mg / dl or less) is preferable.

Non-Patent Document 1 describes a blood sugar level measuring device (hereinafter referred to as a conventional blood sugar level measuring device 90) using an optical fiber probe.
FIG. 18 is a diagram for explaining a conventional blood sugar level measuring apparatus 90.

  The conventional blood sugar level measuring device 90 measures an infrared absorption spectrum using an optical fiber probe 930 instead of the plate prism 832 in the conventional blood sugar level measuring device 80. As shown in FIG. A light source device 910 that emits external light, an optical fiber probe 930, a detection device 950 that detects infrared light, and a data analysis device (not shown) are provided. The optical fiber probe 930 has a structure in which a total reflection prism 936 made of zinc selenide (ZnSe) is arranged at the tip of a bundle type optical fiber in which seven chalcogenide fibers having a diameter of 500 μm are arranged on the light source side and twelve on the detection side. Have

When measuring the infrared absorption spectrum of the living body surface using the conventional blood sugar level measuring device 90, the total reflection prism 936 of the optical fiber probe 930 is in close contact with the living body LB, for example, 1500 cm ^{−1 to} 950 cm ^−1. The infrared absorption spectrum is measured in the wave number range.

  When measuring a blood glucose level using the conventional blood glucose level measuring device 90, for example, an infrared absorption spectrum on the back side of the earlobe is measured according to the method described above for a subject given a predetermined sugar load, and an invasive blood glucose level is measured. A blood glucose level is measured by a value measuring device, a PLS regression analysis is performed using the infrared absorption spectrum as an explanatory variable, and the blood glucose level as an objective variable, and a blood glucose level calibration curve is constructed.

  FIG. 19 is a diagram for explaining a calibration curve construction result by the conventional biological information measuring device 90. FIG. 19A is a diagram showing the distribution of blood glucose levels on the error grid, and FIG. 19B is a diagram showing PLS results and EGA results. In FIG. 19A, the horizontal axis indicates the reference blood glucose level, and the vertical axis indicates the predicted blood glucose level.

  As can be seen from FIG. 19, by using the conventional blood glucose level measuring device 90, for example, in the case of PLS factor 6, a relatively high correlation coefficient (0.82) and a relatively low prediction error (19.1 mg / It was confirmed that a calibration curve having dl) could be prepared and that the blood glucose level could be quantitatively evaluated using this calibration curve.

Junichi Fujita, Hitoshi Tamura, Wataru Kaneko, Hiroaki Ishizawa, Eiji Toba, “Development of non-invasive blood glucose level measurement sensor using infrared spectroscopy”, Electrology B, Vol. 122, No. 11, 2002

JP-A-10-325794 JP 2006-87913 A JP 2003-050200 A International Publication No. 2006/082859 Pamphlet

  However, these blood glucose level measuring devices 80 and 90 also have a problem that the blood glucose level measurement accuracy is not sufficient in practice. That is, in these blood glucose level measuring devices 80 and 90, there is a problem that the measurement accuracy (error within ± 10%) obtained by the invasive blood glucose level measuring device cannot be obtained. Moreover, the reliability which avoids the subject risk in a high blood glucose level or a low blood glucose level has not yet been sufficiently solved.

  In addition, a blood glucose level measuring apparatus using near infrared light instead of infrared light has been proposed (see, for example, Patent Documents 1 to 4). However, even in these blood glucose level measuring devices, there is a problem that the measurement accuracy (within an error of ± 10%) obtained by the invasive blood glucose level measuring device cannot be obtained in practice.

  Accordingly, the present invention has been made to solve the above-described problems, and provides a blood sugar level measuring apparatus having a blood sugar level measurement accuracy at a practical level (a blood sugar level measurement accuracy is within about 10%). With the goal.

[1] A living body information measuring device of the present invention includes a near infrared light irradiation unit that irradiates a living body with near infrared light, a detection-side light guide member that guides near infrared light diffusely reflected by the living body, Measured by a near-infrared absorption spectrum measuring device for measuring a near-infrared absorption spectrum including biological information using near-infrared light guided by the detection-side light guide member, and the near-infrared absorption spectrum measuring device. A biological information measuring device comprising a data analysis device for analyzing the near-infrared absorption spectrum to obtain biological information, wherein the biological information measuring device comprises a contact surface for contacting the living body, and the near-infrared light irradiation unit A near-infrared light irradiating part fixing part for fixing the detection-side light guiding member fixing part, and a near-infrared light from the near-infrared light irradiating part via a gap. Guiding the biological information acquisition site in the living body and And further comprising a measuring attachment and a light guiding space for guiding the near-infrared light diffused reflected by the multi-address acquisition part on the detection side light guide member through the gap.

[2] In the biological information measuring device of the present invention, the near-infrared light irradiating unit emits a near-infrared light source that emits near-infrared light and a near-infrared light emitted from the near-infrared light source. It is preferable that the light source side optical fiber which guides light from one end to the other end, and the near infrared light irradiation unit irradiates the living body with near infrared light from the other end of the light source side optical fiber.

[3] In the biological information measuring device of the present invention, the near-infrared light irradiation unit includes a near-infrared light source that emits near-infrared light, and the near-infrared light irradiation unit includes the near-infrared light source. It is also preferable to directly irradiate the living body with near infrared light.

[4] In the biological information measuring device of the present invention, the light guide member preferably comprises a detection-side optical fiber that guides near-infrared light diffusely reflected by the living body from one end to the other end.

[5] In the biological information measuring device of the present invention, the light guide member preferably includes an optical system that guides near-infrared light diffusely reflected by the living body to the near-infrared absorption spectrum measuring device.

[6] In the biological information measuring device of the present invention, the near-infrared light irradiating unit emits near-infrared light source that emits near-infrared light and near-infrared light emitted from the near-infrared light source. A light source side optical fiber that guides light from one end to the other end, and the light guide member includes a detection side optical fiber that guides near-infrared light diffusely reflected by a living body from one end to the other end, and for the measurement The attachment has a light source side optical fiber fixing part that fixes the vicinity of the other end of the light source side optical fiber as the near infrared light irradiation part fixing part, and the vicinity of one end of the detection side optical fiber as the light guide member fixing part A detection-side optical fiber fixing portion for fixing the optical fiber, and as the light guide space, guides near-infrared light from the other end of the light source-side optical fiber to a biological information acquisition site in a living body through a gap, and It is preferred to have a light guiding space for guiding the near-infrared light diffused reflected by the body information acquiring portion to one end of the detection-side optical fiber through the gap.

[7] In the biological information measuring device of the present invention, the measurement attachment includes a living body information acquisition site pressing hole with the light guide space exposed to the contact surface, and the other end of the light source side optical fiber. It is preferable that the optical axis of the optical fiber and the optical axis of the optical fiber at one end of the detection-side optical fiber intersect each other in the vicinity of the center position of the biological information acquisition site pressing hole.

[8] In the biological information measuring apparatus of the present invention, the intersection angle between the optical axis of the optical fiber at the other end of the light source side optical fiber and the optical axis of the optical fiber at one end of the detection side optical fiber is 60 ° to 120 °. It is preferable to be within the range.

[9] In the biological information measuring device of the present invention, the distance d1 from the other end of the light source side optical fiber to the central position of the biological information acquisition site pressing hole and the central position of the biological information acquisition site pressing hole It is preferable that the distance d2 from the detection side optical fiber to one end of the detection side optical fiber is in the range of 1 mm to 5 mm.

[10] In the biological information measuring apparatus of the present invention, it is preferable that the biological information acquisition site is a site located between the belly of the finger and the fingertip.

[11] In the biological information measuring apparatus of the present invention, it is preferable that the measurement attachment has a finger abdomen placement surface on which a finger abdomen is placed on one side of the contact surface.

[12] In the biological information measuring apparatus of the present invention, it is preferable that the measurement attachment has a fingertip abutting surface for abutting the fingertip against the other side of the contact portion.

[13] In the biological information measuring device of the present invention, it is preferable that the measurement attachment is made of a resin.

[14] In the biological information measuring device of the present invention, it is also preferable that the measurement attachment is made of metal.

[15] In the biological information measuring device of the present invention, the near-infrared absorption spectrum measuring device selects a diffraction grating that splits near-infrared light diffusely reflected by the living body and light that has been split by the diffraction grating. It is preferable that the MEMS near-infrared absorption spectrum measuring apparatus includes a MEMS chip that reflects light and a single photodetecting element that detects light reflected by the MEMS chip.

[16] In the biological information measurement device of the present invention, the data analysis device performs PLS regression on a near-infrared absorption spectrum in a predetermined wavelength range among the near-infrared absorption spectra measured by the near-infrared absorption spectrum measurement device. It preferably has a function of obtaining biological information by analysis by an analysis method.

[17] In the biological information measuring device of the present invention, the predetermined wavelength range preferably includes a wavelength range of 1600 nm to 2400 nm.

[18] In the biological information measuring device of the present invention, the biological information is preferably a blood glucose level.

  According to the present invention, it is possible to provide a blood sugar level measuring apparatus that has a blood sugar level measurement accuracy at a practical level (the blood sugar level measurement accuracy is within about 10%), as can be seen from the embodiments described later. It becomes.

It is a figure shown in order to demonstrate the biometric information measuring apparatus 10 which concerns on Embodiment 1. FIG. It is a figure shown in order to demonstrate the attachment 130 for a measurement. It is a figure which shows the near-infrared absorption spectrum obtained in Embodiment 1. It is a figure shown in order to demonstrate an EGA method. It is a figure shown in order to demonstrate a calibration curve construction result in Embodiment 1. It is a figure shown in order to demonstrate the calibration curve verification result in Embodiment 1. FIG. It is a figure shown in order to demonstrate the calibration curve construction result in Embodiment 2. It is a figure shown in order to demonstrate the calibration curve verification result in Embodiment 2. It is a figure shown in order to demonstrate the calibration curve construction result in Embodiment 3. It is a figure shown in order to demonstrate the calibration curve verification result in Embodiment 3. It is a side view of the measurement attachment 130a in the modification 1. It is sectional drawing of the measurement attachment 130b in the modification 2. FIG. It is sectional drawing of the measurement attachment 130c in the modification 3, and the measurement attachment 130d in the modification 4. FIG. It is sectional drawing of the measurement attachment 130e in the modification 5. FIG. It is a figure shown in order to demonstrate the biometric information measuring apparatus 12 which concerns on the modification 6. FIG. It is a figure shown in order to demonstrate the conventional biological information measuring apparatus 80. FIG. It is a figure for demonstrating the calibration curve construction result by the conventional biological information measuring device. It is a figure shown in order to demonstrate the conventional biological information measuring device 90. FIG. It is a figure shown in order to demonstrate the calibration curve construction result by the conventional biological information measuring device.

  Hereinafter, the biological information measuring apparatus of the present invention will be described in detail based on embodiments.

[Embodiment 1]
1. Configuration of Biological Information Measuring Device FIG. 1 is a diagram illustrating a biological information measuring device 10 according to the first embodiment. FIG. 2 is a view for explaining the measurement attachment 130. 2A is a side view of the measurement attachment 130, FIG. 2B is a top view of the measurement attachment 130, and FIG. 2C is a view in which the light source side optical fiber 120 and the detection side optical fiber 140 are attached. It is sectional drawing of the attachment 130 for a state measurement.

  The biological information measuring device 10 according to the first embodiment is a biological information measuring device (blood glucose level measuring device) for measuring a blood glucose level. Therefore, in the first embodiment, the biological information is a blood glucose level. As shown in FIG. 1, the biological information measuring apparatus 10 according to the first embodiment includes a near-infrared light source 110 that emits near-infrared light, and near-infrared light emitted from the near-infrared light source 110. Light source side optical fiber 120 that guides near-infrared light incident from one end to the other end and irradiates the living body, and near-infrared light incident from one end out of the near-infrared light diffusely reflected by the living body A detection-side optical fiber 140 that guides light to the end, and a near-infrared absorption spectrum measurement device 150 that measures a near-infrared absorption spectrum including biological information using near-infrared light emitted from the other end of the detection-side optical fiber 140; And a data analysis device 170 that obtains biological information by analyzing the near-infrared absorption spectrum measured by the near-infrared absorption spectrum measurement device 150. Among these, the near infrared light source 110 and the light source side optical fiber 120 constitute the near infrared light irradiation unit 100 (the near infrared light irradiation unit of the present invention). Moreover, the detection side optical fiber 140 comprises the detection side light guide member of this invention. Reference numeral 180 denotes an invasive blood sugar level measuring apparatus referred to when constructing a blood sugar level calibration curve.

  As shown in FIG. 2, the biological information measuring apparatus 10 according to the first embodiment includes a contact surface 131 that contacts a living body, a light source side optical fiber fixing unit 132 that fixes the vicinity of the other end of the light source side optical fiber 120, and a detection. The detection-side optical fiber fixing part 133 that fixes the vicinity of one end of the side optical fiber 140 and the near-infrared light from the other end of the light source-side optical fiber 120 are guided to the biological information acquisition site in the living body through the gap, and the biological information It further includes a measurement attachment 130 having a light guide space 134 for guiding near infrared light diffusely reflected at the acquisition site to one end of the detection-side optical fiber 140 through a gap.

  In the biological information measuring apparatus 10 according to the first embodiment, the measurement attachment 130 is configured such that the light guide space 134 is exposed to the contact surface 131 to form a biological information acquisition site pressing hole 135, and the other of the light source side optical fiber 120. The optical axis of the optical fiber at the end and the optical axis of the optical fiber at one end of the detection-side optical fiber 140 are configured to intersect in the vicinity of the center position of the biological information acquisition site pressing hole 135.

  In the biological information measuring apparatus 10 according to the first embodiment, the intersection angle between the optical axis of the optical fiber at the other end of the light source side optical fiber 120 and the optical axis of the optical fiber at one end of the detection side optical fiber 140 is in the range of 60 ° to 120 °. Within (for example, 90 °).

  In the biological information measuring apparatus 10 according to the first embodiment, the distance d1 from the other end of the light source side optical fiber 120 to the central position of the biological information acquisition site pressing hole 135 and the central position of the biological information acquisition site pressing hole 135. The distance d2 from the optical fiber 140 to one end of the detection-side optical fiber 140 is within a range of 1 mm to 5 mm (for example, 2.5 mm).

  In the biological information measuring apparatus 10 according to the first embodiment, the biological information acquisition site is a site located between the belly of the finger and the fingertip.

  In the biological information measuring apparatus 10 according to the first embodiment, the measurement attachment 130 has a finger abdomen mounting surface 136 on which the abdomen of the finger is mounted on one side of the contact surface 131.

  In the biological information measuring apparatus 10 according to the first embodiment, the measurement attachment 130 is made of a resin (for example, ABS resin) having excellent mechanical properties such as workability, rigidity, and hardness.

  In the biological information measuring apparatus 10 according to the first embodiment, the near-infrared absorption spectrum measuring apparatus 150 includes a diffraction grating 154 that separates near-infrared light emitted from the other end of the detection-side optical fiber 140 and a diffraction grating 154. This is a MEMS type near-infrared absorption spectrum measuring apparatus having a MEMS chip 158 that selectively reflects the dispersed light and a single InGaAs-based photodetecting element 160 that detects the light reflected by the MEMS chip 158. . In the biological information measuring apparatus 10 according to the first embodiment, a polychromix portable near-infrared spectroscopy system (LABPOD1624 / LABPOD is a trademark of Polychromix) is used as the near-infrared absorption spectrum measuring apparatus 150. A near-infrared absorption spectrum is obtained by Hadamard transform of the detected signal.

  In the biological information measurement device 10 according to the first embodiment, the data analysis device 170 performs PLS regression on a near-infrared absorption spectrum in a predetermined wavelength range among the near-infrared absorption spectra measured by the near-infrared absorption spectrum measurement device 150. It has a function of obtaining biological information by analysis by an analysis method.

  In the biological information measuring apparatus 10 according to the first embodiment, the predetermined wavelength range includes a wavelength range of 1600 nm to 2400 nm.

2. 2. Measurement of blood glucose level using biological information measuring apparatus 10-1. Measurement of blood glucose level After subjecting one subject (20-year-old male) who fasted for 12 hours to a glucose load of 75 g, the near-infrared absorption spectrum of the washed middle finger of the left hand was measured using the biological information measuring device 10. At the time of reference measurement, Spectralon (manufactured by Labsphere, reflectance in the range of 250 nm to 2500 nm) was used as a standard reflector. FIG. 3 is a diagram showing the obtained near-infrared absorption spectrum. As shown in FIG. 3, the measurement wavelength range of the near infrared absorption spectrum was a wavelength range including 1600 nm to 2400 nm, and the number of integrations was 10.

  PLS regression analysis (Partial Least Square Regression) was used for data analysis of the near infrared absorption spectrum. The near-infrared absorption spectrum obtained as described above is used as an explanatory variable, and PLS regression analysis is performed using the blood glucose level obtained by measuring with an invasive blood glucose level measuring apparatus (Antosense II manufactured by Daikin Industries) as an objective variable. A blood glucose calibration curve was constructed. The analysis wavelength range was 1600 nm to 2400 nm, and the first derivative (three points) by the Savizky-Golay method was applied as spectrum processing. Thereafter, the calibration curve was verified.

  The error grid analysis method (EGA method) is an index indicating “whether or not a blood glucose meter is clinically effective” developed by Dr. Clark at the University of Virginia. FIG. 4 is a diagram showing an error grid. In FIG. 4, the horizontal axis indicates the reference blood glucose level, and the vertical axis indicates the predicted blood glucose level. The diagonal line shows the agreement between the reference value and the predicted value.When the plot is above the diagonal line, the predicted blood glucose level is overestimated, and when the plot is below the diagonal line, the predicted blood glucose level is Indicates underestimated. In the error grid, zone A shows the region where the predicted blood glucose level is only 20% off or is low blood glucose level (<70 mg / dl) when the reference value is lower than 70 mg / dl, and zone B is above and below Indicates an area that is more than 20% above the reference blood glucose level but is undergoing benign treatment, zone C indicates an area that would overcorrect the preferred blood glucose level, and zone D is incorrect An E zone indicates an area that will make a “dangerous failure”, and an E zone indicates an “incorrect treatment” range.

  FIG. 5 is a diagram for explaining a calibration curve construction result in the first embodiment. FIG. 5A is a diagram showing blood glucose level distribution on the error grid, and FIG. 5B is a table showing PLS results and EGA results. FIG. 6 is a diagram for explaining a calibration curve verification result in the first embodiment. FIG. 6A is a diagram showing the blood glucose level distribution on the error grid, and FIG. 6B is a table showing the PLS result and the EGA result.

As can be seen from FIG. 5, in the first embodiment, even a PLS factor (3) smaller than the conventional one has a relatively high correlation coefficient (0.82) and a considerably lower prediction error (11 mg / dl) than the conventional one. ), And this can be judged as a highly significant result. Moreover, the result into which all the predicted values (79) fall into A zone (77) or B zone (2) considered clinically preferable was obtained.
As a result of the verification, as can be seen from FIG. 6, the prediction error is as large as 20 mg / dl, but all the predicted values (30) are considered to be clinically preferable A zone (26) or B zone The result of entering (4) was obtained.

  As described above, according to the biological information measuring device (blood glucose level measuring device) 10 according to the first embodiment, the blood glucose level measurement accuracy is at a practical level (the blood glucose level measurement accuracy is within about 10%). A biological information measuring device (blood glucose level measuring device) can be provided.

  In addition, according to the biological information measuring apparatus 10 according to the first embodiment, near-infrared light from the near-infrared light irradiation unit 100 is guided to a biological information acquisition site in the living body LB through a gap, and biological information acquisition is performed. Since the measurement attachment 130 having the light guide space 134 for guiding the near infrared light diffusely reflected at the site to the detection side light guide member 140 through the gap is provided, the near infrared light is irradiated to the living body. It is possible to adjust the approach distance of the near-infrared light to the living body to an appropriate value by adjusting the state of being applied to an appropriate state. As a result, it is possible to measure a near-infrared absorption spectrum having a high S / N ratio, and thus it is possible to measure a blood glucose level with higher accuracy.

  Moreover, according to the biological information measuring apparatus 10 according to the first embodiment, the near infrared light source 110 and the near infrared light emitted from the near infrared light source 110 are transmitted from one end to the other end as the near infrared light irradiation unit. And a near-infrared light irradiating unit 100 having a light source-side optical fiber 120 that guides the light, and as a detection-side light guide member, guides near-infrared light diffusely reflected by the living body LB from one end to the other end. Since the light guide member composed of the detection-side optical fiber 140 is provided, the measurement attachment most frequently used by the user can be downsized while being a high-performance and high-performance biological information measuring apparatus as a whole. It is possible to provide a biological information measuring device excellent in operability.

  Further, according to the biological information measuring apparatus 10 according to the first embodiment, the optical axis of the optical fiber at the other end of the light source side optical fiber 120 and the optical axis of the optical fiber at the one end of the detection side optical fiber 140 are used for pressing the biological information acquisition site. Since the measurement attachment configured to intersect in the vicinity of the center position of the hole 135 is provided, the near infrared light diffusely reflected by the living body can be efficiently incident on one end of the detection-side optical fiber 140. As a result, it is possible to measure a near-infrared absorption spectrum having a high S / N ratio, and thus it is possible to measure a blood glucose level with higher accuracy.

  Further, according to the biological information measuring apparatus 10 according to the first embodiment, the intersection angle between the optical axis of the optical fiber at the other end of the light source side optical fiber 120 and the optical axis of the optical fiber at one end of the detection side optical fiber 140 is 60 ° to 120 °. Since it is within the range of 0 °, the approach angle of near infrared light into the living body becomes an appropriate value, and the approach distance of near infrared light into the living body becomes an appropriate value. As a result, it is possible to measure a near-infrared absorption spectrum having a high S / N ratio, and thus it is possible to measure a blood glucose level with higher accuracy.

  In addition, according to the biological information measuring apparatus 10 according to the first embodiment, the distance d1 from the other end of the light source side optical fiber 120 to the center position of the biological information acquisition site pressing hole 135 and the biological information acquisition site pressing hole 135. Since the distance d2 from the center position to one end of the detection-side optical fiber 140 is in the range of 1 mm to 5 mm, a near-infrared absorption spectrum with a low baseline and a high S / N ratio can be measured. As a result, the blood sugar level can be measured with higher accuracy.

  In addition, according to the biological information measuring apparatus 10 according to the first embodiment, since the measurement attachment 130 in which the abdomen placement surface 136 of the finger is placed on one side of the contact surface 131 is provided, It is possible to always stably measure near-infrared light absorption spectrum at the biological information acquisition site located between the finger pad and fingertip, and to measure blood glucose level with higher accuracy. It becomes.

  Moreover, according to the biological information measuring apparatus 10 according to the first embodiment, since the measurement attachment 130 made of a resin (for example, ABS resin) having excellent mechanical properties such as workability, rigidity, and hardness is provided, it is excellent in practicality. A biological information measuring device can be provided.

  Further, according to the biological information measuring apparatus 10 according to the first embodiment, as a near infrared absorption spectrum measuring apparatus, the diffraction grating 154 that disperses the near infrared light diffusely reflected by the living body and the diffraction grating 154 are used. The MEMS type near-infrared absorption spectrum measuring apparatus 150 having the MEMS chip 158 that selectively reflects light and the single photodetecting element 160 that detects the light reflected by the MEMS chip has high performance. However, it is possible to provide a small and compact biological information measuring device.

  Moreover, according to the biological information measuring apparatus 10 according to the first embodiment, the near-infrared absorption spectrum in the predetermined wavelength range among the near-infrared absorption spectra measured by the near-infrared absorption spectrum measuring apparatus 150 is used as the data analysis apparatus. Since the data analysis device 170 having a function of obtaining biological information by analyzing by the PLS regression analysis method is provided, it is possible to calculate a regression equation using all the information of the near infrared absorption spectrum, thereby obtaining high prediction accuracy. It becomes possible.

  Moreover, according to the biological information measuring apparatus 10 according to the first embodiment, the biological information is obtained by analyzing the near-infrared absorption spectrum in the predetermined wavelength range including the wavelength range of 1600 nm to 2400 nm by the PLS regression analysis method. Compared with the case where biological information is obtained by analyzing an infrared absorption spectrum, it is possible to increase the approach distance to the living body. As a result, it is possible to measure a near-infrared absorption spectrum having a high S / N ratio, and thus it is possible to measure a blood glucose level with higher accuracy.

[Embodiment 2]
The second embodiment is the same experiment as the first embodiment except that, as a spectral process, second-order differentiation (5 points) by the Savizky-Golay method is performed to construct a blood glucose level calibration curve and to verify the blood glucose level calibration curve. Went.

  FIG. 7 is a diagram for explaining a calibration curve construction result in the second embodiment. FIG. 7A is a diagram showing the blood glucose level distribution on the error grid, and FIG. 7B is a table showing the PLS results and the EGA results. FIG. 8 is a diagram for explaining a calibration curve verification result in the second embodiment. FIG. 8A is a diagram showing the blood glucose level distribution on the error grid, and FIG. 8B is a table showing the PLS result and the EGA result.

As can be seen from FIG. 7, even in the second embodiment, even a PLS factor (4) smaller than the conventional one has a relatively high correlation coefficient (0.85) and a considerably lower prediction error (10 mg / dl) than the conventional one. ), And this can be judged as a highly significant result. Moreover, the result into which all the predicted values (79 pieces) fall into A zone (78 pieces) or B zone (one piece) considered clinically preferable was obtained.
In addition, as a result of the verification, as can be seen from FIG. 8, the prediction error has increased to 18 mg / dl, but all predicted values (30) are considered to be clinically preferable A zone (26) or B zone The result of entering (4) was obtained.

[Embodiment 3]
In the third embodiment, an experiment similar to that in the first embodiment was performed except that a near-infrared absorption spectrum was measured using an aluminum measurement attachment.

  FIG. 9 is a diagram for explaining a calibration curve construction result in the third embodiment. FIG. 9A is a diagram showing the blood glucose level distribution on the error grid, and FIG. 9B is a table showing the PLS result and the EGA result. FIG. 10 is a diagram for explaining a calibration curve verification result in the third embodiment. FIG. 10A is a diagram showing blood glucose level distribution on the error grid, and FIG. 10B is a table showing PLS results and EGA results.

As can be seen from FIG. 9, even in the third embodiment, even a PLS factor (2) smaller than the conventional one has a relatively high correlation coefficient (0.79) and a considerably lower prediction error (14 mg / dl) than the conventional one. ), And this can be judged as a highly significant result. Moreover, the result into which all the predicted values (56) enter into A zone (53) or B zone (3) considered clinically preferable was obtained.
As a result of the verification, as can be seen from FIG. 10, the prediction error is as large as 23 mg / dl, but all predicted values (17) are considered to be clinically preferable A zone (14) or B zone The result of entering (3) was obtained.

  In the third embodiment, aluminum having almost no absorption in the near infrared region is used as the material for the measurement attachment instead of the ABS resin having absorption in the near infrared region. Therefore, the PLS factor is smaller than in the case of the first embodiment. Even in the case of (2), a PLS result and an EGA result almost equivalent to those in the case of the first embodiment were obtained.

  As mentioned above, although this invention was demonstrated based on said embodiment, this invention is not limited to said embodiment. The present invention can be carried out in various modes without departing from the spirit thereof, and for example, the following modifications are possible.

(1) In the first embodiment, ABS resin is used as the material for the measurement attachment, and in the first embodiment, aluminum is used as the material for the measurement attachment. However, the present invention is not limited to this. . Resins other than ABS resin, metals other than aluminum, ceramics and other materials can be used.

(2) In the first embodiment, the measurement attachment 130 in which the abdomen placement surface 136 of the finger is formed on one side of the contact surface 131 is used as the measurement attachment. However, the present invention is limited to this. It is not a thing. FIG. 11 is a view for explaining the measurement attachment 130a in the first modification. As shown in FIG. 11, the abdomen placement surface 136 of the finger is formed on one side of the contact surface 131 and the fingertip abutting surface for abutting the fingertip on the other side of the contact surface 131 is used. Attachments can also be used. In this case, since the finger can be pressed against the measurement attachment with the fingertip abutted, the near-infrared absorption spectrum can be measured more stably, and the blood glucose level can be measured with higher accuracy. be able to.

(3) In the first embodiment, the measurement attachment 130 in which the belly placement surface 136 of the finger is formed on one side of the contact surface 131 is used as the measurement attachment. However, the present invention is limited to this. It is not a thing. FIG. 12 is a cross-sectional view of the measurement attachment 130b in the second modification. As shown in FIG. 12, a measurement attachment in which a finger belly placement surface 136 is not formed on one side of the contact surface 131 can be used. In this case, the measurement attachment can be easily pressed against various parts in the living body.

(4) In the first embodiment or the second modified example, as an attachment for measurement, the intersection angle between the optical axis of the optical fiber at the other end of the light source side optical fiber 120 and the optical axis of the optical fiber at one end of the detection side optical fiber 140 is Although the measurement attachments 130 and 130b configured to be 90 ° are used, the present invention is not limited to this. FIG. 13 is a cross-sectional view of the measurement attachment 130c in the third modification and the measurement attachment 130d in the fourth modification. As shown in FIG. 13A, a measurement attachment 130c configured such that the crossing angle is smaller than 90 ° may be used, and as shown in FIG. 13B, the crossing angle is 90 °. Alternatively, the measurement attachment 130c configured to be larger than that may be used. By adjusting the crossing angle to an appropriate angle within the range of 60 ° to 120 °, the near infrared light to the living body is adjusted to an appropriate value by adjusting the approach angle of the near infrared light to the living body. It is possible to adjust the light entry distance to an appropriate value. As a result, it is possible to measure a near-infrared absorption spectrum having a high S / N ratio, and thus it is possible to measure a blood glucose level with higher accuracy.

(5) In the first embodiment, the near infrared light irradiation unit 110 including the near infrared light source 110 that emits near infrared light and the light source side optical fiber 120 is used as the near infrared light irradiation unit. The present invention is not limited to this. FIG. 14 is a cross-sectional view of the measurement attachment 130e in Modification 5. As shown in FIG. 14, a near-infrared light irradiation unit including a near-infrared light source that emits near-infrared light can be used as the near-infrared light irradiation unit.

(6) In the first embodiment, the present invention has been described by taking the biological information measuring apparatus 10 in which the measurement attachment 130 and the near-infrared absorption spectrum measuring apparatus 150 are configured as separate bodies. However, the present invention is not limited to this. It is not limited to. FIG. 15 is a view for explaining the biological information measuring device 12 according to the sixth modification. As shown in FIG. 15, the present invention can also be applied to the biological information measuring device 12 in which the measurement attachment 130f and the near-infrared absorption spectrum measuring device 150a are integrated. In the biological information measuring device 12 according to the modified example 6, as a detection-side light guide member, an optical system (lens 142) that guides near infrared light diffusely reflected by the living body to the near infrared absorption spectrum measuring device 150a. ) Is used.

(7) In Modification 6, the lens 142 is used as an optical system that guides near-infrared light diffusely reflected by the living body to the near-infrared absorption spectrum measuring apparatus 150a as the detection-side light guide member. However, the present invention is not limited to this. An optical waveguide can also be used as the above optical system.

(8) In the above-described embodiments, the biological information measuring device of the present invention has been described by taking the blood glucose level measuring device as an example, but the present invention is not limited to this. For example, biological information measuring devices such as a blood cholesterol concentration measuring device, a blood neutral fat concentration measuring device, and a blood alcohol concentration measuring device are also included in the present invention.

DESCRIPTION OF SYMBOLS 10, 12, 80, 90 ... Blood glucose level measuring device, 100 ... Near infrared light irradiation part, 110, 810, 910 ... Light source device, 120 ... Light source side optical fiber, 130, 130a, 130b, 130c, 130d, 130e, 130f ... Measurement attachment, 131 ... Contact surface, 132 ... Light source side optical fiber fixing part, 133 ... Detection side optical fiber fixing part, 134 ... Light guiding space, 135 ... Biological information acquisition site pressing hole, 136 ... Abdomen placement of finger Surface: 137: Finger tip abutting surface, 140: Detection side optical fiber, 150: Near infrared absorption spectrum measuring device, 152: Mirror, 154: Diffraction grating, 156: Lens, 158: MEMS chip, 160: Single detection element, 170 ... Data analysis device, 180 ... Reference blood glucose level measuring device, 812 ... Infrared light source, 814,818 ... Lens, 816 Movable interferometer, 820, 840 ... mirror, 830 ... sample chamber, 832 ... plate prism, 850, 852, 950 ... detector, 930 ... optical fiber probe, 932 ... light source side optical fiber bundle, 934 ... fiber bundle, 934a ... Light source side optical fiber, 934b ... detection side optical fiber, 936 ... total reflection prism, 938 ... detection side optical fiber bundle, LB ... biological body

Claims (18)

A near-infrared light irradiation unit that irradiates a living body with near-infrared light; and
A detection-side light guide member that guides near-infrared light diffusely reflected by the living body;
A near-infrared absorption spectrum measuring apparatus for measuring a near-infrared absorption spectrum including biological information using near-infrared light guided by the detection-side light guide member;
A biological information measuring device comprising a data analysis device for analyzing the near infrared absorption spectrum measured by the near infrared absorption spectrum measuring device to obtain biological information,
The biological information measuring device includes a contact surface for contacting a living body, a near infrared light irradiation unit fixing unit for fixing the near infrared light irradiation unit, and a detection side light guide for fixing the detection side light guide member. The near-infrared light from the member fixing unit and the near-infrared light irradiation unit is guided to the biological information acquisition site in the living body through the gap, and the near-infrared light diffusely reflected by the biological information acquisition site is A biological information measuring apparatus further comprising a measurement attachment having a light guide space for guiding light to the detection-side light guide member through a gap. The biological information measuring device according to claim 1,
The near-infrared light irradiation unit includes a near-infrared light source that emits near-infrared light, and a light source-side optical fiber that guides near-infrared light emitted from the near-infrared light source from one end to the other end. Have
The near-infrared light irradiation unit irradiates a living body with near-infrared light from the other end of the light source-side optical fiber. The biological information measuring device according to claim 1,
The near-infrared light irradiator comprises a near-infrared light source that emits near-infrared light,
The near-infrared light irradiation unit directly irradiates a living body with near-infrared light from the near-infrared light source. The biological information measuring device according to any one of claims 1 to 3,
The light guide member comprises a detection-side optical fiber that guides near-infrared light diffusely reflected by a living body from one end to the other end. The biological information measuring device according to any one of claims 1 to 3,
The light guide member includes an optical system that guides near-infrared light diffusely reflected by a living body to the near-infrared absorption spectrum measuring apparatus. The biological information measuring device according to claim 1,
As the near-infrared light irradiation unit, a near-infrared light source that emits near-infrared light, and a light source-side optical fiber that guides near-infrared light emitted from the near-infrared light source from one end to the other end Prepared,
As the light guide member, provided with a detection-side optical fiber for guiding near-infrared light diffusely reflected by a living body from one end to the other end,
The measurement attachment has a light source side optical fiber fixing portion for fixing the vicinity of the other end of the light source side optical fiber as the near infrared light irradiation portion fixing portion, and the light guide member fixing portion of the detection side optical fiber as the light guide member fixing portion. A detection-side optical fiber fixing part that fixes one end vicinity, and guides near-infrared light from the other end of the light source-side optical fiber to a biological information acquisition site in a living body through a gap as the light guide space A biological information measuring apparatus comprising a light guide space for guiding near infrared light diffusely reflected at the biological information acquisition site to one end of the detection-side optical fiber through a gap. The biological information measuring device according to claim 6,
In the measurement attachment, the light guide space is exposed to the contact surface to form a biological information acquisition site pressing hole, and the optical axis of the optical fiber at the other end of the light source side optical fiber and one end of the detection side optical fiber A biological information measuring device configured to intersect with the optical axis of the optical fiber in the vicinity of the center position of the biological information acquisition site pressing hole. The biological information measuring device according to claim 7,
The biological information measuring device characterized in that the crossing angle between the optical axis of the optical fiber at the other end of the light source side optical fiber and the optical axis of the optical fiber at one end of the detection side optical fiber is in the range of 60 ° to 120 °. . In the biological information measuring device according to claim 7 or 8,
The distance d1 from the other end of the light source side optical fiber to the center position of the biological information acquisition site pressing hole and the distance d2 from the center position of the biological information acquisition site pressing hole to the one end of the detection side optical fiber are Both are in the range of 1 mm-5 mm, The biological information measuring device characterized by the above-mentioned. In the biological information measuring device according to any one of claims 1 to 9,
The biometric information measurement apparatus, wherein the biometric information acquisition part is a part located between a belly of a finger and a fingertip. The biological information measuring device according to claim 10,
The biological information measuring device according to claim 1, wherein the measurement attachment has a finger abdomen mounting surface on which a belly of a finger is mounted on one side of the contact surface. The biological information measuring device according to claim 11,
The biological information measuring device according to claim 1, wherein the measurement attachment has a fingertip abutting surface for abutting a fingertip on the other side of the contact portion. In the biological information measuring device according to any one of claims 1 to 12,
The biological information measuring device, wherein the measurement attachment is made of resin. In the biological information measuring device according to any one of claims 1 to 13,
The biological information measuring device, wherein the measurement attachment is made of metal. In the biological information measuring device according to any one of claims 1 to 14,
The near-infrared absorption spectrum measuring apparatus includes a diffraction grating that splits near-infrared light diffusely reflected by a living body, a MEMS chip that selectively reflects light dispersed by the diffraction grating, and a reflection by the MEMS chip. A biological information measuring device, which is a MEMS near-infrared absorption spectrum measuring device having a single photodetecting element for detecting the emitted light. In the biological information measuring device according to any one of claims 1 to 15,
The data analysis device has a function of obtaining biological information by analyzing a near-infrared absorption spectrum in a predetermined wavelength range among near-infrared absorption spectra measured by the near-infrared absorption spectrum measuring device by a PLS regression analysis method. The biological information measuring device characterized by the above. The biological information measuring device according to claim 16, wherein
The biological information measuring apparatus according to claim 1, wherein the predetermined wavelength range includes a wavelength range of 1600 nm to 2400 nm. The biological information measuring device according to claim 1,
The biological information measuring device, wherein the biological information is a blood glucose level.

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