JP6786338B2 - Blood measuring device - Google Patents

Description

The present invention relates to a blood measuring device, and more particularly to a blood measuring device using Raman spectroscopy.

Non-invasive methods have been developed to measure the concentration of each component in blood. For example, Non-Patent Document 1 (Jingwei Shao, 6 outsiders, "In vivo Blood Glucose Quantification Using Raman Spectroscopy", PLOS ONE, October 2012, Vol. 7, No. 10, e48127) The method is disclosed. That is, a Raman spectrum is acquired by condensing a laser beam on a blood vessel in the skin, and the glucose concentration in blood is measured based on the intensity ratio of the glucose peak and the hemoglobin peak in the acquired Raman spectrum.

Further, Patent Document 1 (International Publication No. 2014/178199) discloses the following monitors. That is, the monitor is a monitor that monitors the state inside the living body from the surface of the living body, and is a probe including an observation window attached to the surface of the living body and an observation region of the surface of the living body accessed through the observation window. From each of a unit that irradiates at least a part of the laser and a plurality of observation spots that are formed intermittently so as to be dispersed in the observation area in two dimensions or continuously so as to scan the observation area. Based on the unit that detects the scattered light caused by the laser irradiation and the scattered light obtained from the plurality of observation spots, the scattered light including the information of the target portion inside the living body can be obtained from the plurality of observation spots. A spectral spectrum of at least one component is acquired from the unit that limits the first observation spot to be determined and the observation spot at or around the first observation spot, and the state inside the living body is shown based on the intensity thereof. It has a unit that outputs the first information.

Jingwei Shao, 6 outsiders, "In vivo Blood Glucose Quantification Usage Raman Spectroscopy", PLOS ONE, October 2012, Vol. 7, No. 10, e48127

International Publication No. 2014/178199

A technique capable of satisfactorily measuring blood is desired beyond the techniques described in Non-Patent Document 1 and Patent Document 1.

The present invention has been made to solve the above-mentioned problems, and an object of the present invention is to provide a blood measuring device capable of satisfactorily measuring blood.

(1) In order to solve the above problems, the blood measuring device according to a certain aspect of the present invention irradiates a living body with excitation light from a spectroscope and a light source, and emits Raman scattered light from the living body to the spectroscope. Detection that detects the spectrum of the Raman scattered light using the guiding optical system, the control unit that adjusts the irradiation position of the excitation light on the living body by the optical system, and the light of each wavelength dispersed by the spectroscope. A plurality of the spectra detected by the detector are integrated, and numerical information regarding a substance contained in the blood of the living body is measured based on the integrated result, and the control unit determines the irradiation position. The irradiation position is adjusted so that the plurality of spectra are detected while changing.

(2) Preferably, the blood measuring device further performs a determination process for determining whether or not the irradiation position is the blood vessel position of the living body based on the spectrum detected by the detector. The determination unit performs the determination process a plurality of times, and the control unit changes the irradiation position after the determination process is performed.

(3) More preferably, the blood measuring device further includes a calculation unit that integrates the plurality of spectra detected by the detector, and the calculation unit is determined not to be the blood vessel position in the determination process. The spectrum corresponding to the irradiation position is excluded from the integration target.

(4) Preferably, the time during which the excitation light is continuously irradiated to the same irradiation position is limited, and the setting of the time can be changed.

(5) In order to solve the above problems, the blood measuring device according to another aspect of the present invention irradiates a living body with excitation light from a spectroscope and a light source, and emits Raman scattered light from the living body to the spectroscope. An optical system that guides the light to the body, a control unit that adjusts the irradiation range or irradiation intensity of the excitation light to the living body by the optical system, and a detector that detects the spectrum of the Raman scattered light dispersed by the spectroscope. A plurality of the spectra detected by the detector are integrated, numerical information regarding a substance contained in the blood of the living body is measured based on the integrated result, and the control unit uses the detector to obtain the spectrum. After the detection, the irradiation range is increased and then returned to the original state, or the irradiation intensity is reduced and then returned to the original state. The detector is newly adjusted after the adjustment process is performed. The spectrum is detected.

(6) Preferably, the blood measuring device further determines whether or not the irradiation position of the excitation light on the living body is the blood vessel position of the living body based on the spectrum detected by the detector. The control unit includes a determination unit that performs the determination process, changes the irradiation position when it is determined in the determination process that it is not the blood vessel position, and determines that it is the blood vessel position in the determination process. The adjustment process is performed.

(7) More preferably, the blood measuring device further includes a calculation unit that integrates the plurality of spectra detected by the detector, and the calculation unit is determined not to be the blood vessel position in the determination process. The spectrum corresponding to the irradiation position is excluded from the integration target.

(8) Preferably, in order to detect the spectrum, the living body is irradiated with the excitation light having a predetermined size and an irradiation intensity of a predetermined size, and the irradiation range is continuously set to the predetermined size. At least one of the time and the duration of the irradiation intensity of the predetermined magnitude is limited, and the limited duration can be set and changed.

According to the present invention, blood can be measured satisfactorily.

FIG. 1 is a diagram showing a configuration of a blood measuring device according to the first embodiment of the present invention. FIG. 2 is a diagram showing an example of a blood spectrum. FIG. 3 is a flowchart defining an operation procedure when the blood measuring device according to the first embodiment of the present invention analyzes blood in a living body. FIG. 4 is a diagram showing a configuration of a blood measuring device according to a second embodiment of the present invention. FIG. 5 is a flowchart defining an operation procedure when the blood measuring device according to the second embodiment of the present invention analyzes blood in a living body. FIG. 6 is a diagram showing a configuration of a modified example of the blood measuring device according to the second embodiment of the present invention. FIG. 7 is a flowchart in which a modified example of the blood measuring device according to the second embodiment of the present invention defines an operation procedure when analyzing blood in a living body.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. The same or corresponding parts in the drawings are designated by the same reference numerals, and the description thereof will not be repeated. In addition, at least a part of the embodiments described below may be arbitrarily combined.

<First Embodiment>
[Structure of blood measuring device]
FIG. 1 is a diagram showing a configuration of a blood measuring device according to the first embodiment of the present invention.

With reference to FIG. 1, the blood measuring device 101 includes a spectroscope 1, an optical system 2, a control unit 3, a detector 4, a determination unit 5, a calculation unit 6, a processing unit 7, and a storage unit. 8, an analysis unit 9, and a light source 10 are provided. The spectroscope 1 includes a slit 1a and a diffraction grating 1b. The optical system 2 includes a collimating lens 31, a bandpass filter 32, a dichroic mirror 33, a scanning mirror 34, an objective lens 35, a bandpass filter 36, and a condenser lens 37.

The light source 10 is, for example, a light source that emits excitation light by itself, and specifically, a laser that outputs monochromatic light. The light source 10 may be an LED (Light-Emitting Diode). Further, the light source 10 may be provided outside the blood measuring device 101.

In this example, the light source 10 is, for example, a cw (continuus wave) laser, and irradiates the collimating lens 31 in the optical system 2 with laser light having a power and a wavelength of 50 mW and 785 nm, respectively, as excitation light.

The optical system 2 irradiates the living body LB with the excitation light from the light source 10 and guides the Raman scattered light from the living body LB to the spectroscope 1.

More specifically, for example, the collimating lens 31 in the optical system 2 converts the excitation light received from the light source 10 into substantially parallel light.

The bandpass filter 32 attenuates wavelength components other than the peak in the spectrum of the excitation light, that is, the strongest peak in the laser light, among the wavelength components of the excitation light from the collimating lens 31, for example.

The excitation light transmitted through the bandpass filter 32 is reflected by, for example, the dichroic mirror 33 and the scanning mirror 34, and is incident on the objective lens 35. Here, the dichroic mirror 33, for example, reflects the excitation light while transmitting the Raman scattered light described later, which has a wavelength different from that of the excitation light.

The objective lens 35 collects the excitation light reflected by the scanning mirror 34 on the living body LB, for example. In this way, the position where the excitation light is focused by the objective lens 35 is the irradiation position Ep of the excitation light on the living body LB by the optical system 2.

At the irradiation position Ep of the excitation light, a specific scattered light based on the excitation light is generated from a substance in the living body, for example, blood, fat, a component contained in the blood, or the like. This scattered light includes, for example, Raman scattered light due to Raman scattering and Rayleigh scattered light due to Rayleigh scattering.

The objective lens 35 converts, for example, scattered light spreading from the irradiation position Ep of the excitation light into substantially parallel light. The scanning mirror 34 reflects, for example, light substantially parallel from the objective lens 35.

The bandpass filter 36 attenuates the wavelength component of the peak in the spectrum of the excitation light among the wavelength components of the scattered light reflected by the scanning mirror 34 and transmitted through the dichroic mirror 33, for example.

The condenser lens 37 collects the scattered light transmitted through the bandpass filter 36 into the slit 1a in the spectroscope 1, for example.

The scattered light that has passed through the slit 1a in the spectroscope 1 is diffracted by, for example, the diffraction grating 1b and irradiated to the detector 4.

The detector 4 detects the spectrum of Raman scattered light using the light of each wave number or wavelength dispersed by the spectroscope 1. Here, the detector 4 may measure light having at least two wave numbers or wavelengths.

More specifically, when the detector 4 receives a measurement command including the exposure time Te from the processing unit 7, for example, the detector 4 accumulates the intensity of the scattered light diffracted by the diffraction grating 1b for each wavelength in the exposure time Te to obtain a spectrum. To measure. Then, the detector 4 outputs, for example, the measured spectrum to the processing unit 7.

[Task]
FIG. 2 is a diagram showing an example of a blood spectrum. In FIG. 2, the horizontal axis represents the wave number of Raman shift, and the vertical axis represents the intensity. In the measurement of the Raman spectrum, if the intensity of the detected scattered light is weak, it may be necessary to irradiate the excitation light for, for example, several tens of seconds to several minutes.

With reference to FIG. 2, for example, spectrum Sn is a spectrum of normal blood, and spectrum Sa is a spectrum of blood containing blood cells burned by excitation light.

For example, when Raman spectroscopy is used, if the excitation light is focused on the blood vessel BV in the living body LB shown in FIG. 1, the blood cells contained in the blood vessel BV may be burnt.

More specifically, the blood flow velocity vb in the blood vessel BV becomes smaller as the blood vessel BV becomes thinner. Specifically, the blood flow velocities vb of arterioles, venules and capillaries are, for example, about 5 mm / s, 2.5 mm / s and 1 mm / s, respectively. These blood flow velocities vb may be further slowed down depending on the physical condition of the person to be measured, individual differences, and the like.

When measuring the Raman spectrum, the shorter the focal length, the easier it is to measure. Specifically, the measurement of the Raman spectrum of blood flowing through capillaries located at a depth Dv of 1 to 2 mm from the body surface Sf is the measurement of blood flowing through arterioles or venules at a position deeper than the body surface Sf from the capillaries. It is easier than the measurement of the Raman spectrum of.

In addition, the blood glucose level differs depending on the measurement location or the blood collection position. In addition, the time change of the blood glucose level, such as the rise of the blood glucose level after a meal, differs depending on the position of the blood vessel BV in the living body LB. When the blood glucose level is measured by Raman spectroscopy, calibration is performed using the actual measured value in order to convert the intensity of Raman scattered light into the blood glucose level. When calibrating using the blood glucose measurement value of a conventional invasive glucose meter, for example, blood collected from the capillaries of the fingertips of the hand is often the measurement target, and the blood glucose level at the position of the capillaries of the fingertips of the hand. Is the standard. Therefore, the closer the non-invasive blood glucose measurement position using Raman spectroscopy to the blood glucose measurement position or blood collection position used for calibration, the more accurate calibration can be performed. Therefore, even when the blood glucose level is measured by Raman spectroscopy, it is desirable to measure the blood glucose in the capillaries of the fingertips of the hand because more accurate measurement can be performed.

That is, while it is desired to measure the Raman spectrum of blood in the capillaries, since the blood flow velocity vb is small in the capillaries, the same blood cells are irradiated with the excitation light for a long time, so that the possibility of burning the blood cells increases.

Further, for example, in order to measure the Raman spectrum with a good S / N ratio, it is conceivable to use CARS (Coherent anti-Stokes Raman spectroscopy) as in the monitor described in Patent Document 1, but CARS is strongly excited. The need for light increases the likelihood of burning blood cells.

When blood cells are burnt by irradiating with strong excitation light, an abnormal spectrum Sa different from the normal spectrum Sn is obtained as a measurement result. The abnormal spectrum Sa exhibits various characteristics, and as an example, since strong light is generated when blood cells are burnt, the signal intensity is higher than that of the normal spectrum Sn, as shown in FIG. For this reason, for example, it becomes difficult to accurately measure blood glucose in blood.

Therefore, the blood measuring device according to the embodiment of the present invention solves such a problem by the following configuration and operation.

[Basic configuration and operation]
With reference to FIG. 1 again, for example, the processing unit 7 holds the exposure time Te. Here, the exposure time Te is set by the user, for example. The user sets the exposure time Te according to the blood flow velocity vb or the like of the blood to be measured. Specifically, for example, when the blood flow velocity vb in the blood vessel BV to be measured is large, the exposure time Te is increased to the extent that the blood cells are not burnt, and the blood flow velocity vb in the blood vessel BV to be measured is small. , Reduce the exposure time Te to the extent that blood cells do not burn.

When the processing unit 7 receives, for example, the movement completion information described later from the control unit 3, the processing unit 7 outputs a measurement command including the exposure time Te to the detector 4, and receives a spectrum from the detector 4 as a response to the measurement command.

When the processing unit 7 receives a spectrum from the detector 4, for example, the processing unit 7 outputs the received spectrum to the determination unit 5 and the calculation unit 6.

For example, the determination unit 5 performs a determination process for determining whether or not the irradiation position Ep is the blood vessel position of the living body LB a plurality of times based on the spectrum detected by the detector 4.

Specifically, the determination unit 5 performs determination processing based on, for example, a peak in the spectrum.

More specifically, when the determination unit 5 receives a spectrum from the processing unit 7, for example, the determination unit 5 analyzes the received spectrum and attempts to detect a peak derived from a blood component such as hemoglobin. For example, when the determination unit 5 detects a peak derived from a blood component, it determines that the irradiation position Ep is the blood vessel position of the living body LB, and outputs blood vessel detection information indicating the determination result to the control unit 3 and the calculation unit 6. ..

On the other hand, if the determination unit 5 cannot detect the peak derived from the blood component, for example, it determines that the irradiation position Ep is not the blood vessel position of the living body LB, and the blood vessel non-detection information indicating the determination result is transmitted to the control unit 3 and the calculation unit. Output to 6.

The determination unit 5 may perform determination processing based on the bandwidth of the peak based on Rayleigh scattering of the excitation light in the spectrum. More specifically, when the determination unit 5 acquires the bandwidth of the peak and detects the Doppler shift based on Rayleigh scattering of erythrocytes in the acquired bandwidth, the irradiation position Ep is the blood vessel position of the living body LB. Is determined. On the other hand, if the determination unit 5 cannot detect the Doppler shift, for example, it determines that the irradiation position Ep is not the blood vessel position of the living body LB.

The control unit 3 adjusts the irradiation position Ep of the excitation light to the living body LB by the optical system 2. More specifically, the control unit 3 adjusts the irradiation position Ep so that a plurality of spectra are detected while changing the irradiation position Ep.

For example, the control unit 3 changes the irradiation position Ep after the determination process is performed, and performs the determination process again. Specifically, the control unit 3 changes the irradiation position Ep each time the determination process is performed. That is, the control unit 3 limits the time during which the excitation light is continuously irradiated to the same irradiation position Ep.

For example, the scanning mirror 34 can rotate about two axes that pass through the center of the mirror, are included in the mirror surface, and are orthogonal to each other under the control of the control unit 3. The irradiation position Ep of the excitation light in the living body LB is, for example, the optical axis direction of the objective lens 35 by changing the reflection direction of the excitation light by rotating the scanning mirror 34 with the two axes as rotation axes. It is scanned in a direction (hereinafter, also referred to as a horizontal direction) orthogonal to the vertical direction (also referred to as a vertical direction).

More specifically, the control unit 3 recognizes that, for example, when the blood vessel detection information or the blood vessel non-detection information is received from the determination unit 5, one determination process is performed, and controls the scanning mirror 34 to determine the irradiation position Ep. Move it laterally.

At this time, for example, the control unit 3 may move the irradiation position Ep according to a predetermined pattern in the lateral direction, may move the irradiation position Ep randomly, or may move the irradiation position Ep between the two predetermined points. Ep may be reciprocated.

The control unit 3 may move an optical element or the like other than the scanning mirror 34 in the blood measuring device 101 as necessary in order to move the irradiation position Ep in the lateral direction.

Further, the configuration is not limited to the configuration in which the irradiation position Ep is changed by rotating the scanning mirror 34, and the irradiation position Ep is changed by arranging a plurality of optical systems 2 and switching the optical system 2 used for measurement. Good. Further, a plurality of scanning mirrors 34 and objective lenses 35, which are a part of the optical system 2, may be arranged, and the irradiation position Ep may be changed by switching the scanning mirror 34 and the objective lens 35 used for measurement. ..

For example, when the movement of the irradiation position Ep is completed, the control unit 3 outputs the movement completion information indicating that the movement of the irradiation position Ep is completed to the processing unit 7.

The control unit 3 is not limited to the configuration in which the movement completion information is output to the processing unit 7 when the movement of the irradiation position Ep is completed, and the movement is completed after waiting for a predetermined time or a random time after the movement of the irradiation position Ep is completed. The information may be output to the processing unit 7. Further, the control unit 3 may be configured to periodically output the movement completion information to the processing unit 7 by performing the above-mentioned standby.

In the blood measuring device 101, for example, a plurality of spectra detected by the detector 4 are integrated, and numerical information regarding a substance contained in the blood of the living body LB is measured based on the integrated result.

More specifically, the arithmetic unit 6 integrates, for example, a plurality of spectra detected by the detector 4. Specifically, when the calculation unit 6 receives the blood vessel detection information from the determination unit 5, for example, the calculation unit 6 stores the corresponding spectrum received from the processing unit 7 in the storage unit 8. For example, when the number of spectra stored in the storage unit 8 reaches a predetermined number, the calculation unit 6 integrates the predetermined number of spectra stored in the storage unit 8 and outputs the integrated spectrum, which is the integrated spectrum, to the analysis unit 9.

Further, the calculation unit 6 excludes, for example, the spectrum corresponding to the irradiation position Ep determined not to be the blood vessel position in the determination process from the integration target. Specifically, when the calculation unit 6 receives the blood vessel non-detection information from the determination unit 5, for example, the calculation unit 6 discards the corresponding spectrum received from the processing unit 7.

When the analysis unit 9 receives the integrated spectrum from the calculation unit 6, for example, the analysis unit 9 analyzes the received integrated spectrum. More specifically, the analysis unit 9 calculates the blood glucose concentration in the blood in the blood vessel BV from the integrated spectrum using, for example, a calibration curve or a conversion coefficient, and illustrates the calculated blood glucose concentration together with the completion information indicating the completion of the measurement. Do not display on the display.

As described above, in the blood measuring device 101, the time Tp during which the excitation light is continuously irradiated to the same irradiation position Ep is limited. This time Tp can be changed, for example. Here, the time Tp is, for example, the sum of the exposure time Te and the time required for the determination process.

[motion]
The blood measuring device includes a computer, and an arithmetic processing unit such as a CPU in the computer reads a program including a part or all of each step of the flowchart shown below from a memory (not shown) and executes the program. The program for this device can be installed externally. The program of this device is distributed in a state of being stored in a recording medium.

FIG. 3 is a flowchart defining an operation procedure when the blood measuring device according to the first embodiment of the present invention analyzes blood in a living body.

With reference to FIG. 3, for example, it is assumed that the light source 10 outputs excitation light with a constant power.

First, the blood measuring device 101 measures the spectrum of the scattered light based on the excitation light focused on the irradiation position Ep (step S102).

Next, the blood measuring device 101 analyzes the measured spectrum (step S104), and determines whether or not the irradiation position Ep is the blood vessel position based on the analysis result (step S106).

When the blood measuring device 101 determines that the irradiation position Ep is not the blood vessel position (NO in step S106), the measured spectrum is discarded (step S108).

On the other hand, when the blood measuring device 101 determines that the irradiation position Ep is the blood vessel position (YES in step S106), the measured spectrum is stored (step S116).

Next, the blood measuring device 101 confirms whether or not a predetermined number of spectra are stored (step S118).

The blood measuring device 101 changes the irradiation position Ep (step S110) when the measured spectrum is discarded (step S108) or when it is confirmed that a predetermined number of spectra are not stored (NO in step S118).

Next, the blood measuring device 101 newly measures the spectrum of the scattered light based on the excitation light focused on the changed irradiation position Ep (step S102).

On the other hand, when the blood measuring device 101 confirms that a predetermined number of spectra are stored (YES in step S118), each stored spectrum is integrated (step S112).

Next, the blood measuring device 101 analyzes the integrated spectrum and calculates, for example, the blood glucose concentration in blood in the blood vessel BV (step S114).

In the step S108, the blood measuring device 101 is configured to discard the spectrum of the non-blood vessel position every time the spectrum is measured, but the present invention is not limited to this. For example, in step S108, the blood measuring device 101 is configured to mark and store the spectrum of the non-vascular position without discarding it, and to discard the marked spectrum collectively in step S112. You may.

Further, the blood measuring device according to the first embodiment of the present invention integrates a plurality of spectra detected by the detector 4, and based on the integrated result, numerical information regarding a substance contained in the blood of the living body LB is obtained. The configuration is to be measured, but the present invention is not limited to this. The integration process of the plurality of spectra detected by the detector 4 and the measurement process of the numerical information regarding the substance contained in the blood of the living body LB based on the integration result are performed by a terminal such as a computer provided outside the blood measuring device 101. The configuration may be performed by the device. That is, the calculation unit 6, the storage unit 8 and the analysis unit 9 in the blood measurement device 101 may be provided outside the blood measurement device 101.

By the way, a technique capable of satisfactorily measuring blood is desired beyond the techniques described in Non-Patent Document 1 and Patent Document 1.

On the other hand, in the blood measuring device according to the first embodiment of the present invention, the optical system 2 irradiates the living body LB with excitation light from the light source 10 and emits Raman scattered light from the living body LB to the spectroscope 1. Lead to. The control unit 3 adjusts the irradiation position Ep of the excitation light to the living body LB by the optical system 2. The detector 4 detects the spectrum of Raman scattered light using the light of each wavelength dispersed by the spectroscope 1. A plurality of spectra detected by the detector 4 are integrated, and based on the integrated result, numerical information regarding a substance contained in the blood of the living body LB is measured. Then, the control unit 3 adjusts the irradiation position Ep so that a plurality of spectra are detected while changing the irradiation position Ep.

With such a configuration, it is possible to avoid a situation in which the excitation light is continuously irradiated to the same position, so that damage to the blood can be reduced even when blood is present at the irradiation position Ep, for example. .. This allows a good spectrum of undamaged blood to be measured. Therefore, blood can be measured well.

Further, in the blood measuring device according to the first embodiment of the present invention, the determination unit 5 determines whether or not the irradiation position Ep is the blood vessel position of the living body LB based on the spectrum detected by the detector 4. Judgment Judgment processing is performed. The determination unit 5 performs the determination process a plurality of times. Then, the control unit 3 changes the irradiation position Ep after the determination process is performed.

With such a configuration, the irradiation position Ep can be changed at an appropriate timing based on the judgment process while performing a judgment process useful for confirming the quality of the measured spectrum, so that blood damage is more reliably reduced. can do.

Further, in the blood measuring device according to the first embodiment of the present invention, the calculation unit 6 integrates a plurality of spectra detected by the detector 4. Then, the calculation unit 6 excludes the spectrum corresponding to the irradiation position Ep determined not to be the blood vessel position in the determination process from the integration target.

In this way, the spectrum based on the Raman scattered light from the irradiation position Ep determined to be not the blood vessel position is excluded from the integration target, so that the spectrum of normal blood can be selected and integrated, which is better. The spectrum can be obtained.

Further, in the blood measuring device according to the first embodiment of the present invention, the time Tp during which the excitation light is continuously irradiated to the same irradiation position Ep is limited. The time Tp can be changed.

With such a configuration, for example, the time Tp can be set according to the blood flow velocity vb in the blood vessel BV to be measured, so that a better spectrum of blood can be measured while more reliably reducing blood damage. It is possible to provide a device that is as easy to use as possible.

The blood measuring device according to the first embodiment of the present invention is configured to change the irradiation position Ep each time the determination process is performed, but the present invention is not limited to this. The blood measuring device 101 is configured to determine whether or not the irradiation time of the excitation light to the same position exceeds the time Tp, and change the irradiation position Ep when the irradiation time exceeds the time Tp. You may.

Next, other embodiments of the present invention will be described with reference to the drawings. The same or corresponding parts in the drawings are designated by the same reference numerals, and the description thereof will not be repeated.

<Second Embodiment>
The present embodiment relates to a blood measuring device that changes the irradiation range of the excitation light or changes the irradiation intensity of the excitation light as compared with the blood measuring device according to the first embodiment. Except for the contents described below, the device is the same as the blood measuring device according to the first embodiment.

[Structure of blood measuring device]
FIG. 4 is a diagram showing a configuration of a blood measuring device according to a second embodiment of the present invention.

With reference to FIG. 4, the blood measuring device 102 includes a spectroscope 1, an optical system 2, a control unit 43, a detector 4, a determination unit 5, a calculation unit 6, a processing unit 7, and a storage unit. 8, an analysis unit 9, and a light source 10 are provided.

The configuration and operation of the spectroscope 1, the optical system 2, the detector 4, the determination unit 5, the calculation unit 6, the processing unit 7, the storage unit 8, the analysis unit 9, and the light source 10 in the blood measurement device 102 are shown in FIG. The same applies to the spectroscope 1, the optical system 2, the detector 4, the determination unit 5, the calculation unit 6, the processing unit 7, the storage unit 8, the analysis unit 9, and the light source 10 in the measuring device 101, respectively.

The optical system 2 irradiates the living body LB with the light from the light source 10 and guides the Raman scattered light from the living body LB to the spectroscope 1.

The detector 4 detects the spectrum of Raman scattered light dispersed by the spectroscope 1. Specifically, for example, when the detector 4 receives a measurement command from the processing unit 7, the detector 4 measures and measures the spectrum by accumulating the intensity of the scattered light diffracted by the diffraction grating 1b for each wavelength with the exposure time Te. The generated spectrum is output to the processing unit 7.

When the processing unit 7 receives, for example, the change completion information Ia or the movement completion information described later from the control unit 43, the processing unit 7 outputs a measurement command including the exposure time Te to the detector 4, and the detector 4 responds to the measurement command. Receives a spectrum from.

When the processing unit 7 receives a spectrum from the detector 4, for example, the processing unit 7 outputs the received spectrum to the determination unit 5 and the calculation unit 6.

The determination unit 5 performs determination processing for determining whether or not the irradiation position Ep is the blood vessel position of the living body LB based on the spectrum detected by the detector 4, for example.

For example, when the determination unit 5 detects a peak derived from a blood component in the determination process, the determination unit 5 determines that the irradiation position Ep is the blood vessel position of the living body LB, and outputs the blood vessel detection information indicating the determination result to the control unit 43 and the calculation unit 6. Output to.

On the other hand, if the determination unit 5 cannot detect the peak derived from the blood component in the determination process, for example, the determination unit 5 determines that the irradiation position Ep is not the blood vessel position of the living body LB, and controls the blood vessel non-detection information indicating the determination result. And output to the calculation unit 6.

For example, the control unit 43 changes the irradiation position Ep when it is determined in the determination process that it is not the blood vessel position.

For example, the objective lens 35 can move along the optical axis of the excitation light under the control of the control unit 43. For example, when the objective lens 35 moves in this way, the focal point of the excitation light, that is, the irradiation position Ep moves in the vertical direction.

The control unit 43 performs a search process for searching the blood vessel position, for example, at the start of measurement of its own blood measuring device 102.

More specifically, the control unit 43 controls, for example, at least one of the scanning mirror 34 and the objective lens 35 to move the irradiation position Ep to at least one of the horizontal direction and the vertical direction. For example, when the movement of the irradiation position Ep is completed, the control unit 43 outputs the movement completion information to the processing unit 7.

When the control unit 43 receives the blood vessel non-detection information from the determination unit 5 as a result of the determination process based on the spectrum after the movement of the irradiation position Ep, the irradiation position Ep is further applied to at least one of the horizontal direction and the vertical direction. It is moved and the movement completion information is output to the processing unit 7.

On the other hand, when the control unit 43 receives the blood vessel detection information from the determination unit 5 as a result of the determination process based on the spectrum after the movement of the irradiation position Ep, for example, the search process ends.

The control unit 43 adjusts the irradiation range Ea of the excitation light to the living body LB by the optical system 2. Here, as shown in FIG. 4, the irradiation range Ea is a range Ea in which the excitation light is irradiated, for example, on the body surface Sf of the living body LB. Further, as shown in FIG. 4, the irradiation intensity Ei is the power per unit area in the irradiation range Ea on the body surface Sf of the living body LB, for example.

More specifically, after the spectrum is detected by the detector 4, the control unit 43 performs the adjustment process AP2 for increasing the irradiation range Ea and then returning it to the original state. For example, the control unit 43 performs the adjustment process AP2 when it is determined in the determination process that it is the blood vessel position.

Specifically, the control unit 43 stores the position of the objective lens 35 at the end of the search process. Then, the control unit 43 increases the irradiation range Ea by moving the objective lens 35 in a direction approaching the living body LB, for example, at the timing when the blood vessel detection information is received from the determination unit 5.

With such a configuration, the focus of the excitation light moves away from the body surface Sf, so that the energy of the excitation light received by the same blood cell of blood in the blood vessel BV can be reduced. As a result, the damage to the blood can be suppressed.

The control unit 43 may reduce the irradiation range Ea by moving the objective lens 35 in a direction away from the living body LB at the above timing.

With such a configuration, the focus of the excitation light moves in the direction closer to the body surface Sf, so that the energy of the excitation light received by the same blood cell of blood in the blood vessel BV can be reduced. As a result, the damage to the blood can be suppressed.

After moving the objective lens 35, for example, the control unit 43 waits for a standby time Tw. For example, when the standby time Tw elapses, the control unit 43 restores the irradiation range Ea by moving the objective lens 35 to the stored position, changes the irradiation range Ea, and then restores the irradiation range Ea. The indicated change completion information Ia is output to the processing unit 7.

When the processing unit 7 receives the change completion information Ia from the control unit 43, for example, the processing unit 7 outputs a measurement command including the exposure time Te to the detector 4.

The detector 4 detects a new spectrum after the adjustment processing AP2 is performed. Specifically, for example, when the detector 4 receives a measurement command from the processing unit 7, the detector 4 measures a new spectrum by accumulating the intensity of the scattered light diffracted by the diffraction grating 1b for each wavelength with an exposure time Te. .. Then, the detector 4 outputs, for example, the measured new spectrum to the processing unit 7.

As described above, in the blood measuring device 102, in order to detect the spectrum, the living body LB is irradiated with excitation light having an irradiation range Ea of a predetermined size and an irradiation intensity Ei of a predetermined size, and an irradiation range of a predetermined size is used. The duration Ta that becomes Ea is limited. This duration Ta can be changed, for example. Here, the duration Ta is, for example, the sum of the exposure time Te and the time required for the determination process.

In the blood measuring device according to the second embodiment of the present invention, the control unit 43 moves the objective lens 35 to increase the irradiation range Ea after the spectrum is detected by the detector 4, and then the irradiation range Ea is increased. The configuration is such that the irradiation range Ea is restored by moving the objective lens 35 to the memorized position, but the present invention is not limited to this. The control unit 43 may be configured to increase the irradiation range Ea and then decrease the irradiation range Ea. Further, even when the control unit 43 increases the irradiation range Ea and then returns it to the original state, the irradiation range Ea after returning may be slightly different from the original irradiation range Ea.

[motion]
FIG. 5 is a flowchart defining an operation procedure when the blood measuring device according to the second embodiment of the present invention analyzes blood in a living body.

With reference to FIG. 5, first, the blood measuring device 102 measures the spectrum of the scattered light based on the excitation light focused on the irradiation position Ep (step S202).

Next, the blood measuring device 102 analyzes the measured spectrum (step S204), and determines whether or not the irradiation position Ep is the blood vessel position based on the analysis result (step S206).

When the blood measuring device 102 determines that the irradiation position Ep is not the blood vessel position (NO in step S206), the measured spectrum is discarded (step S208).

Next, the blood measuring device 102 changes the irradiation position Ep (step S210).

Next, the blood measuring device 102 newly measures the spectrum of the scattered light based on the excitation light focused on the changed irradiation position Ep (step S202).

On the other hand, when the blood measuring device 102 determines that the irradiation position Ep is the blood vessel position (YES in step S206), the blood measuring device 102 saves the measured spectrum (step S212).

Next, when the blood measuring device 102 confirms that a predetermined number of spectra are not stored (NO in step S214), the irradiation range Ea is changed (step S216).

Next, the blood measuring device 102 waits for a waiting time Tw (step S218).

Next, the blood measuring device 102 restores the irradiation range Ea (step S220).

Next, the blood measuring device 102 newly measures the spectrum of the scattered light based on the excitation light focused on the irradiation position Ep (step S202).

On the other hand, when the blood measuring device 102 confirms that a predetermined number of spectra are stored (YES in step S214), each stored spectrum is integrated (step S222).

Next, the blood measuring device 102 analyzes the integrated spectrum and calculates, for example, the blood glucose concentration in blood in the blood vessel BV (step S224).

[Structure of modified example of blood measuring device]
FIG. 6 is a diagram showing a configuration of a modified example of the blood measuring device according to the second embodiment of the present invention.

With reference to FIG. 6, the blood measuring device 103, which is a modification of the blood measuring device 102, includes a control unit 53 instead of the control unit 43 as compared with the blood measuring device 102 shown in FIG.

The configuration and operation of the spectroscope 1, the optical system 2, the detector 4, the determination unit 5, the calculation unit 6, the processing unit 7, the storage unit 8, the analysis unit 9, and the light source 10 in the blood measurement device 103 are shown in FIG. The same applies to the spectroscope 1, the optical system 2, the detector 4, the determination unit 5, the calculation unit 6, the processing unit 7, the storage unit 8, the analysis unit 9, and the light source 10 in the measuring device 102, respectively.

The optical system 2 irradiates the living body LB with the light from the light source 10 and guides the Raman scattered light from the living body LB to the spectroscope 1. When the detector 4 receives a measurement command from the processing unit 7, for example, the detector 4 measures the spectrum by accumulating the intensity of the scattered light diffracted by the diffraction grating 1b for each wavelength with the exposure time Te, and the measured spectrum is used as the processing unit. Output to 7.

When the processing unit 7 receives, for example, the change completion information Ii or the movement completion information described later from the control unit 53, the processing unit 7 outputs a measurement command including the exposure time Te to the detector 4, and the detector 4 responds to the measurement command. Receives a spectrum from.

When the processing unit 7 receives a spectrum from the detector 4, for example, the processing unit 7 outputs the received spectrum to the determination unit 5 and the calculation unit 6.

The determination unit 5 performs determination processing for determining whether or not the irradiation position Ep is the blood vessel position of the living body LB based on the spectrum detected by the detector 4, for example.

For example, the control unit 53 changes the irradiation position Ep when it is determined in the determination process that it is not the blood vessel position.

The control unit 53 performs a search process for searching the blood vessel position, for example, at the start of measurement of its own blood measuring device 103.

More specifically, the control unit 53 controls, for example, at least one of the scanning mirror 34 and the objective lens 35 to move the irradiation position Ep to at least one of the horizontal direction and the vertical direction. For example, when the movement of the irradiation position Ep is completed, the control unit 53 outputs the movement completion information to the processing unit 7.

When the control unit 53 receives the blood vessel non-detection information from the determination unit 5 as a result of the determination processing based on the spectrum after the movement of the irradiation position Ep, the irradiation position Ep is further applied to at least one of the horizontal direction and the vertical direction. It is moved and the movement completion information is output to the processing unit 7.

On the other hand, when the control unit 53 receives the blood vessel detection information from the determination unit 5 as a result of the determination process based on the spectrum after the movement of the irradiation position Ep, for example, the search process ends.

The control unit 53 adjusts the irradiation intensity Ei of the excitation light to the living body LB by the optical system 2. More specifically, after the spectrum is detected by the detector 4, the control unit 53 performs an adjustment process AP3 that reduces the irradiation intensity Ei and then restores the spectrum. For example, the control unit 53 performs the adjustment process AP3 when it is determined in the determination process that it is the blood vessel position.

Specifically, for example, the light source 10 can change the power of the laser beam to be output according to the control by the control unit 53.

Further, the control unit 53 stores, for example, the power value of the output light of the light source 10 at the end of the search process. Then, the control unit 53 controls to reduce the power of the output light of the light source 10 at the timing when the blood vessel detection information is received from the determination unit 5.

With such a configuration, the irradiation intensity Ei of the excitation light is reduced, so that the energy of the excitation light received by the same blood cells of blood in the blood vessel BV can be reduced. As a result, the damage to the blood can be suppressed.

The control unit 53, for example, waits for a standby time of Tw after controlling to reduce the power of the output light of the light source 10. For example, when the standby time Tw elapses, the control unit 53 restores the irradiation intensity Ei of the excitation light by controlling to return the power of the output light of the light source 10 to the stored power value, and the irradiation intensity Ei. The change completion information Ii indicating that the change was made and then restored is output to the processing unit 7.

When the processing unit 7 receives the change completion information Ii from the control unit 53, for example, the processing unit 7 outputs a measurement command including the exposure time Te to the detector 4.

As described above, in the blood measuring device 103, in order to detect the spectrum, the living body LB is irradiated with the excitation light of the irradiation range Ea of a predetermined size and the irradiation intensity Ei of a predetermined size, and the irradiation intensity of a predetermined size is applied. The duration Ti that becomes Ei is limited. This duration Ti can be changed, for example. Here, the duration Ti is, for example, the sum of the exposure time Te and the time required for the determination process.

[motion]
FIG. 7 is a flowchart in which a modified example of the blood measuring device according to the second embodiment of the present invention defines an operation procedure when analyzing blood in a living body.

With reference to FIG. 7, the operations of steps S302 to S314 are the same as the operations of steps S202 to S214 shown in FIG. 5, respectively.

Next, when the blood measuring device 103 confirms that a predetermined number of spectra are not stored (NO in step S314), the irradiation intensity Ei is changed (step S316).

Next, the blood measuring device 103 waits for a waiting time Tw (step S318).

Next, the blood measuring device 103 restores the irradiation intensity Ei (step S320).

The operation of steps S322 to S324 is the same as the operation of steps S222 to S224 shown in FIG.

In the blood measuring device according to the second embodiment of the present invention, the duration Ta that is the irradiation range Ea of a predetermined size or the duration Ti that is the irradiation intensity Ei of a predetermined size is limited. However, it is not limited to this. The blood measuring device may have a configuration in which both the duration Ta and the duration Ti are limited.

Further, the blood measuring device according to the second embodiment of the present invention integrates a plurality of spectra detected by the detector 4, and based on the integrated result, numerical information regarding a substance contained in the blood of the living body LB is obtained. The configuration is to be measured, but the present invention is not limited to this. The integration process of the plurality of spectra detected by the detector 4 and the measurement process of the numerical information regarding the substance contained in the blood of the living body LB based on the integration result are performed by a computer or the like provided outside the blood measuring device 102 or 103. The configuration may be performed by the terminal device of. That is, the calculation unit 6, the storage unit 8 and the analysis unit 9 in the blood measurement device 102 or 103 may be provided outside the blood measurement device 102 or 103, respectively.

Further, in the blood measuring device according to the second embodiment of the present invention, the control unit 53 stores the power of the output light of the light source 10 after controlling to reduce the power of the output light of the light source 10. The configuration is such that the irradiation intensity Ei of the excitation light is restored by controlling the return to the set power value, but the present invention is not limited to this. The control unit 53 may have a configuration in which the irradiation intensity Ei is decreased and then the irradiation intensity Ei is increased. Further, even when the control unit 53 reduces the irradiation intensity Ei and then restores it, the irradiation intensity Ei after returning may be slightly different from the original irradiation intensity Ei.

As described above, in the blood measuring apparatus according to the second embodiment of the present invention, the optical system 2 irradiates the living body LB with excitation light from the light source 10 and emits Raman scattered light from the living body LB to the spectroscope 1. Lead to. The control unit 43 adjusts the irradiation range Ea of the excitation light to the living body LB by the optical system 2. The detector 4 detects the spectrum of Raman scattered light dispersed by the spectroscope 1. A plurality of spectra detected by the detector 4 are integrated, and based on the integrated result, numerical information regarding a substance contained in the blood of the living body LB is measured. After the spectrum is detected by the detector 4, the control unit 43 performs the adjustment processing AP2 that increases the irradiation range Ea and then restores the spectrum. The detector 4 detects a new spectrum after the adjustment processing AP2 is performed.

With such a configuration, it is possible to avoid a situation in which the excitation light is continuously focused at the same position. Therefore, even when blood is present at the irradiation position Ep of the excitation light on the living body LB, the blood is concerned. Damage can be reduced. This allows a good spectrum of undamaged blood to be measured. Therefore, blood can be measured well.

Further, in the blood measuring device according to the second embodiment of the present invention, the optical system 2 irradiates the living body LB with excitation light from the light source 10 and guides Raman scattered light from the living body LB to the spectroscope 1. The control unit 53 adjusts the irradiation intensity Ei of the excitation light to the living body LB by the optical system 2. The detector 4 detects the spectrum of Raman scattered light dispersed by the spectroscope 1. A plurality of spectra detected by the detector 4 are integrated, and based on the integrated result, numerical information regarding a substance contained in the blood of the living body LB is measured. After the spectrum is detected by the detector 4, the control unit 53 performs an adjustment process AP3 that reduces the irradiation intensity Ei and then restores the spectrum. The detector 4 detects a new spectrum after the adjustment processing AP3 is performed.

With such a configuration, it is possible to avoid a situation in which the excitation light is continuously irradiated to the same position with a strong intensity, so that even when blood is present at the irradiation position Ep of the excitation light on the living body LB, for example. Damage to the blood can be reduced. This allows a good spectrum of undamaged blood to be measured. Therefore, blood can be measured well.

Further, in the blood measuring device according to the second embodiment of the present invention, the determination unit 5 determines that the irradiation position Ep of the excitation light to the living body LB is the blood vessel of the living body LB based on the spectrum detected by the detector 4. Determine if it is a position. Then, the control unit 43 performs the adjustment processing AP2 when it is determined in the determination process that it is the blood vessel position, and changes the irradiation position Ep when it is determined in the determination process that it is not the blood vessel position.

With such a configuration, for example, the blood vessel position can be searched more reliably at the start of measurement, and blood damage is more reliably reduced while performing a judgment process useful for confirming the quality of the measured spectrum. be able to.

Further, in the blood measuring device according to the second embodiment of the present invention, the determination unit 5 determines that the irradiation position Ep of the excitation light to the living body LB is the blood vessel of the living body LB based on the spectrum detected by the detector 4. Determine if it is a position. Then, the control unit 53 changes the irradiation position Ep when it is determined in the determination process that it is not the blood vessel position, and performs the adjustment process AP3 when it is determined in the determination process that it is the blood vessel position.

With such a configuration, it is possible to more reliably reduce blood damage while more reliably searching for the blood vessel position, for example, at the start of measurement.

Further, in the blood measuring device according to the second embodiment of the present invention, the calculation unit 6 integrates a plurality of spectra detected by the detector 4. Then, the calculation unit 6 excludes the spectrum corresponding to the irradiation position Ep determined not to be the blood vessel position in the determination process from the integration target.

In this way, the spectrum based on the Raman scattered light from the irradiation position Ep determined to be not the blood vessel position is excluded from the integration target, so that the spectrum of normal blood can be selected and integrated, which is better. The spectrum can be obtained.

Further, in the blood measuring apparatus according to the second embodiment of the present invention, the living body LB is irradiated with excitation light having an irradiation range Ea of a predetermined size and an irradiation intensity Ei of a predetermined size in order to detect a spectrum. , At least one of a duration Ta having an irradiation range Ea of a predetermined size and a duration Ti having an irradiation intensity Ei of a predetermined size is limited. The limited duration Ta or Ti can be changed.

With such a configuration, for example, the duration Ta or Ti can be set according to the blood flow velocity vb in the blood vessel BV to be measured, so that the damage to the blood is more reliably reduced and the blood is better. It is possible to provide an easy-to-use device capable of measuring various spectra.

Since other configurations and operations are the same as those of the blood measuring device according to the first embodiment, detailed description will not be repeated here.

It is also possible to appropriately combine some or all of the components and operations of the devices according to the first embodiment and the second embodiment of the present invention.

It should be considered that the above embodiments are exemplary in all respects and not restrictive. The scope of the present invention is shown by the scope of claims rather than the above description, and is intended to include all modifications within the meaning and scope equivalent to the scope of claims.

1 Spectrometer 1a Slit 1b Diffraction grating 2 Optical system 3 Control unit 4 Detector 5 Judgment unit 6 Calculation unit 7 Processing unit 8 Storage unit 9 Analysis unit 10 Light source 31 Collimating lens 32 Band pass filter 33 Dichroic mirror 34 Scanning mirror 35 Objective lens 36 Band pass filter 37 Condensing lens 43 Control unit 53 Control unit 101, 102, 103 Blood measuring device

Claims (7)

With a spectroscope
An optical system that irradiates a living body with excitation light from a light source and guides Raman scattered light from the living body to the spectroscope.
A detector for detecting a spectrum of the Raman scattered light with the light of each wavelength that is split by the spectrometer,
A determination unit that performs determination processing for determining whether or not the irradiation position of the excitation light is the position of a blood vessel in the living body based on the spectrum of the Raman scattered light detected by the detector .
As the spectrum of the Raman scattered light from blood vessels in the evaluation unit the inside the living body irradiation position changes Shinano et multiple excitation light based on the determination result by are detected, respectively, to the living body by the optical system A control unit that adjusts the irradiation position of the excitation light of
An analysis unit that measures numerical information contained in the blood of the living body based on the integration result of the spectra of Raman scattered light from the plurality of blood vessels in the living body.
A blood measuring device including. Before Symbol judging unit performs a plurality of times said determination processing,
The blood measuring device according to claim 1, wherein the control unit changes the irradiation position of the excitation light after the determination process is performed. The blood measuring device further
A calculation unit that integrates the spectra of Raman scattered light from the plurality of blood vessels in the living body detected by the detector is provided.
The blood measurement according to claim 1 , wherein the calculation unit excludes the spectrum of Raman scattered light corresponding to the irradiation position of the excitation light determined to be not the position of the blood vessel in the living body in the determination process from the integration target. apparatus. Are time limits the excitation light is irradiated to the same irradiation elevation position continuously,
The blood measuring device according to any one of claims 1 to 3, wherein the time can be set and changed. With a spectroscope
An optical system that irradiates a living body with excitation light from a light source and guides Raman scattered light from the living body to the spectroscope.
A detector for detecting a spectrum of the Raman scattered light split by the spectrometer,
A determination unit that performs determination processing for determining whether or not the irradiation position of the excitation light is the position of a blood vessel in the living body based on the spectrum of the Raman scattered light detected by the detector, and the optical system. It is a control unit that adjusts the irradiation range or irradiation intensity of the excitation light to the living body, and the determination process by the determination unit determines that the irradiation position of the excitation light is the position of a blood vessel in the living body. In some cases, after the detector detects the spectrum of Raman scattered light from the blood vessel in the living body, the irradiation range is increased and then restored, or the irradiation intensity is decreased and then restored. A control unit that performs processing and changes the irradiation position of the excitation light when it is determined in the determination process that the irradiation position of the excitation light is not the position of a blood vessel in the living body.
It is provided with an analysis unit that measures numerical information about a substance contained in the blood of the living body based on the integration result of the spectra of Raman scattered light from a plurality of blood vessels in the living body detected by the detector.
The detector is a blood measuring device that detects a spectrum of Raman scattered light from a new blood vessel in the living body after the adjustment process is performed. The blood measuring device further
A calculation unit that integrates a plurality of spectra of Raman scattered light from the plurality of blood vessels in the living body detected by the detector is provided.
The blood measurement according to claim 5 , wherein the calculation unit excludes the spectrum of Raman scattered light corresponding to the irradiation position of the excitation light determined to be not the position of the blood vessel in the living body in the determination process from the integration target. apparatus. In order to detect the spectrum of Raman scattered light from the blood vessels in the living body, the living body is irradiated with the excitation light having an irradiation range of a predetermined size and an irradiation intensity of a predetermined size, and the irradiation of the predetermined size is performed. At least one of the range duration and the duration of the predetermined magnitude of irradiation intensity is limited.
The blood measuring device according to claim 5 or 6, wherein the limited duration can be set and changed.

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