CN112351735A

CN112351735A - Nondestructive measuring device

Info

Publication number: CN112351735A
Application number: CN201880095412.4A
Authority: CN
Inventors: 木暮一也
Original assignee: Tongsheng Electronic Development Co ltd
Current assignee: Tongsheng Electronic Development Co ltd
Priority date: 2018-07-20
Filing date: 2018-07-20
Publication date: 2021-02-09
Anticipated expiration: 2038-07-20
Also published as: WO2020017028A1; CN112351735B

Abstract

The invention discloses a device for measuring the ascending and descending amount of a substance changing with time and the changing amount of the substance changing with time with light with high precision and displaying the result. A sample containing a substance to be measured is irradiated with light from at least two light sources, the light from at least one light source is used to measure a change with respect to a component other than the substance to be measured, and the light used to measure the substance to be measured is used to measure the change in the substance to be measured. In order to measure the amount of change of a substance to be measured with high accuracy, the amount of change of a substance other than the substance to be measured is used as a correction value. The measurement was performed 3 times at a fixed time, the difference between the 1 st measurement value and the 3 rd measurement value was calculated, the time differential value of the difference between the 1 st and 2 nd measurement values was calculated, and the difference between the 1 st and 3 rd measurement values and the time differential value between the 1 st and 2 nd measurement values were used as the final results.

Description

Nondestructive measuring device

Technical Field

The present invention relates to a nondestructive measurement device that nondestructively measures, calculates, and displays a relative change amount of an amount of increase and decrease of a substance to be measured from a reference time and a time differential value of the change amount.

Background

When the amount of a substance contained in a sample that changes with time is measured with time, particularly when time change is an important factor, it is desirable to perform the measurement in a nondestructive manner. One of the means for non-destructive measurement is a light-based measurement method such as spectroscopic analysis. One of the applicable methods is a non-invasive blood glucose value measurement technique. This is a technique for identifying a blood glucose level from the amount of change in physical properties such as light absorbance and polarized light according to the concentration of a blood glucose level. As a representative technique, a plurality of methods based on the near-infrared spectrum analysis shown in fig. 1 have been reported in the past. This method is a method of measuring the mass (concentration) of a substance to be measured from the intensity distribution of the spectral spectrum, but in order to identify the substance to be measured from the spectral intensity distribution, a calibration curve representing the basic spectral intensity distribution is necessary, and in order to create this calibration curve, a method of efficiently creating the calibration curve using simulation techniques or the like has been proposed, but a large amount of analysis of measurement data is necessary.

Further, this analysis method is mainly applied under specific conditions, and there is a problem that it is very difficult to apply the method to an unspecified plurality of samples. This is because components other than the substance to be measured are very different. Due to physical variations, individual differences, etc., it is almost impossible to apply the assay widely. The method based on the spectral analysis is basically a method of measuring the absorbance of light, but other methods using polarized light can be said to be the same. As a result, if the problem in measuring a substance that changes with time by light over time is carefully solved, it is attributed to the problems of reproducibility and measurement accuracy due to the generation of a calibration curve, physical variations, and the like. It is difficult to realize a nondestructive measuring apparatus for measuring the amount of a substance changing with time by light over time.

Documents of the prior art

Patent document

Patent document 1: japanese patent No. 3692751

Non-patent document 1: application of 2003 Infrared Spectroscopy for non-invasive blood component determination, IEEJ Trans. EIS. Vol.127, No.5,686-

Disclosure of Invention

Problems to be solved by the invention

The problem to be solved is that, although it can be understood that the measurement value changes with time due to light, the measurement accuracy is low due to the manufacturing accuracy and physical variation of the calibration curve, and it is difficult to measure the mass (concentration) of the substance to be measured, and it is therefore difficult to realize a nondestructive measurement apparatus using light.

Means for solving the problems

The present invention changes the way of thinking about measuring a substance by light, and measures and calculates the relative change amount and the time change amount of a substance to be measured from a certain time to a certain time without creating a calibration curve. The main feature is to adopt a method of performing measurement by using the light emitting section as a point of action for applying pressure to a measurement site and adjusting an optical axis for measurement in real time.

Effects of the invention

The nondestructive measurement device of the present invention does not directly measure the mass (concentration) of a substance to be measured, but can realize nondestructive measurement by light with excellent reproducibility as an index in place of the mass (concentration) of the substance to be measured.

The state of a rapid increase in the mass (concentration) of a substance to be measured, which has hitherto not been found by discrete measurement, can be detected by a nondestructive method.

Drawings

FIG. 1 shows an example of a configuration of a nondestructive measurement apparatus using spectroscopic analysis.

FIG. 2 is an example of changes in diet and blood glucose values.

Fig. 3 is a situation of the displacement action and the tilting action of the actuator lens.

Fig. 4 shows an optical unit structure using transmitted light.

Fig. 5 shows an optical unit structure using reflected light.

Fig. 6 shows a configuration in which an optical unit is incorporated in a holding mechanism.

Fig. 7 is a circuit block diagram of a measurement device centering on an analog circuit.

Fig. 8 shows the case of the LD 1-based adjustment period and the LD 2-based measurement period.

Fig. 9 is a circuit block diagram centered on digital processing by an MPU.

Fig. 10 is an example of a graph showing dds values of final measurement results from the measurement values.

Detailed Description

Example 1

Hereinafter, a case of applying the present invention to measurement of a blood glucose level according to one embodiment of the present invention will be described with reference to the drawings. Of course, the present invention is not limited to the blood glucose level, and can be applied to the measurement of the change of a substance to be measured with time, which is important, for example, the measurement of the change of photosynthesis of plants.

In the case of measuring the blood glucose level by a non-destructive method using light (hereinafter referred to as "non-invasive" in the case of measuring the blood glucose level), various methods have been proposed, and identification is performed by the absorbance and the degree of diffusion of light. It is known that the degree of diffusion is proportional to the concentration of blood glucose level, and therefore, the light quantity is measured using a photoelectric element (hereinafter, PD), but the sensitivity varies depending on the size (area) of the PD, and the size is set to be equal to or larger than the optical path of the light to be used (the size is determined in accordance with the range of the degree of diffusion assumed). In this case, the amount of light detected by PD is absorbed by blood glucose, becomes small, and diffuses into the tissue (diffuser) through blood glucose. Therefore, the amount of light detected by PD increases the absorbance by the degree of diffusion, and the amount measured by PD increases the detection sensitivity of the change in blood glucose value. The measurement value obtained by superimposing the absorbance and the diffusivity is set as a basic detection amount. The absorbance was determined from the measured amount. Further, since the absorption light changes with temperature, the temperature of the measurement portion is measured, and the value corrected by correcting the temperature is the final absorption light.

First, the properties of the blood glucose level are confirmed here. Blood glucose is one of the components in blood, but there are many substances having light absorption properties in the vicinity of a wavelength called near infrared rays in addition to blood glucose. When a meal is eaten, the blood glucose level rises after about 20 to 40 minutes from the meal as a response change of a normal human body, and the blood glucose level reaches a value approximately equal to that before the meal about 2 hours after the meal due to the action of insulin or the like. The reason for this is that substances other than blood sugar are components produced from various organs or the like or components produced by reaction, and the change in blood sugar level is very slow compared to the change in blood sugar level. Therefore, the factor of the change in absorbance or diffusivity in a short time of about 2 hours is almost certainly the blood glucose level. Although there is a possibility that the change is blood glucose and water, water can be separated by observing the absorbance of a light source having a wavelength different from the wavelength of the absorption spectrum of blood glucose. That is, the amount of change in blood glucose level can be corrected by the difference between the absorbance sensitivity characteristic due to moisture and the absorbance sensitivity of blood glucose level. However, 2 sources must be viewed coaxially. In order to perform identification other than blood glucose, blood glucose levels cannot be originally identified without creating a calibration curve based on a large amount of data, and such a variation in blood glucose levels does not require a calibration curve. Thus, the basic feature of the present apparatus is to measure the amount of increase or decrease in blood glucose level. In addition, when the amount of change in the increase or decrease in blood glucose level is measured as in the present measurement, errors due to individual differences such as skin pigment and skin condition can be cancelled out, and therefore, the measurement accuracy and reproducibility can be improved.

In the case of healthy blood glucose levels in living organisms, the blood glucose levels are approximately the same as those before meals, about 2 hours after meals. However, in the so-called sugar metabolism of diabetes, the amount of change thereof is characterized. Fig. 2 is a general example of temporal changes in blood glucose level.

Therefore, 3 measurements were performed before, about 30 minutes, and about 2 hours after a meal, and the judgment was performed. This is similar to the glucose tolerance test of clinical diagnosis of diabetes. In severe cases (12c), the blood glucose levels before, 30 minutes, and 2 hours after meals may not change. Therefore, the time variation and the time differential value of the measurement value are calculated, and the composite determination of the variation and the real-time differential value is performed.

Generally, the measurement of a blood glucose level by health diagnosis or the like is a so-called fasting blood glucose level. Even if the measured value is slightly high, the severity may be overlooked. The response of recessive diabetes may be a rapid increase in blood glucose level after a meal, and the symptom may be detected by the time differential value.

Next, a solution to the physical variation will be described.

When using optical measurement, the change in the optical path length causes an error and reduces the accuracy. Therefore, it is very inconvenient that the optical path length is limited to a certain position so as not to change. In consideration of convenience, the method of measurement using reflected light is more preferable, but when the region to which light is actually applied changes, the subcutaneous tissue of the measurement region may also change, which may cause a decrease in accuracy. In addition, the accuracy is also degraded due to the incident state of light, vibration, and the like. Therefore, as the structure of the measurement device, a structure for restricting the measurement site is first adopted. Which is a structure for holding an earlobe, an interphalangeal space, etc., for example (fig. 6). Thus, the measurement is performed at a substantially fixed position. In addition, the ear lobe and the interphalangeal area may be less susceptible to the change in the pigment. Further, it is known that the absorbance also changes when the temperature changes, and it can be expected that the temperature does not change greatly at a portion where the nip can be made.

By adopting the clamping structure, the optical path length can be kept constant, and a constant pressure can be applied to the measurement site, and the pressure can suppress the change in blood flow. When using optical measurement, hemoglobin in blood is most affected, and its change causes a decrease in measurement accuracy. This is because the blood flow changes greatly particularly after meals and the like. Even if the measurement site is limited to a certain extent, if a blood vessel exists in the subcutaneous tissue and the blood vessel is included in the optical path, the accuracy can be expected to be lowered. Therefore, the optical path is reduced, and an actuator (the same structure as an optical pickup such as a CD or DVD, not shown) is used to provide an adjustment mechanism for adjusting the irradiation position of the portion to maximize the detection light. In addition, the mechanism is provided with a mechanism which can restrain the subconscious muscle movement and adjust the incident state in real time, thereby ensuring the precision. Fig. 3 is an explanatory diagram of measurement performed by moving the actuator. However, even with this adjustment mechanism, there are physical variations that cannot be corrected. Therefore, the blood glucose level is corrected by a light source of another wavelength that is disposed coaxially with the light beam for measuring the blood glucose level and that adopts the same optical path, and the correction of the physical variation is also performed. It is considered that the physical variation may occur because the physical variation is changed similarly to the variation in the wavelength of the blood glucose level measurement.

Fig. 4 shows an optical basic structure. The near infrared light source (in this configuration, a semiconductor laser diode is used) emits light coaxially by using a plurality of different wavelengths. As the wavelength, a light source (measurement light: 23a) having a wavelength around 1500nm, a light source (LD 2, hereinafter) having a 2 nd wavelength, and a light source (reference light: 23b) having a wavelength of 1300nm, and a light source (LD 1, hereinafter) having a 1 st wavelength, are used. The light source desirably employs a laser. The reason for this is that the emission wavelength range is very narrow, and it can be considered as a single wavelength process. Of course, a light source having emission characteristics in which the variation is about 10nm in a range regarded as a single wavelength may be used.

The reason why the wavelength around 1300nm is selected is that the light source has a wavelength that exhibits high absorbance for water but does not exhibit large absorbance for glucose, and the light source is combined with the light source to correct the amount of detection by the measurement light based on the change in absorbance, as the amount of change in the amount of water and the amount of physical change. The correction method may be a difference method or a ratio method. Further, the actuator described later is electrically controlled so as to maximize the amount of light detected at the wavelength, based on the detected amount of the reference light, which is used as a control amount for performing vibration of the measurement portion, correction of the light incident state, and avoidance of an obstacle on the optical path. Fig. 4 shows a configuration in which transmitted light is used for a measurement region, and fig. 5 shows a configuration for detecting diffuse reflected light, and both of them are detected in a state in which irradiation light passes through the inside of the measurement region. Light from the light sources (23a, 23b) is converged into a small-diameter beam by the lenses (24a,24b), forming collimated light (14). The reason for converging the light flux into a small-diameter light flux is that the light flux can be reduced in cost while maintaining the brightness without using a light source having a large output. In addition, the optical path can be avoided when an obstacle (specifically, a blood vessel (13)) exists, the light beam becomes coaxial light by PBS (25a,25b) and the like, but the 2 light sources do not emit light at the same time, and the optical path has a function of correcting the position of the measurement site (21) by an actuator lens (22), the actuator is capable of shifting (16) and tilting (15) and performing real-time adjustment, the response speed of the actuator for the adjustment is not necessarily high, but may be a characteristic of the same degree as that of the so-called subconscious muscle movement, and the portions (20a,20b) actually in contact with the measurement site have a function of eliminating the influence of light directly reflected from the surface, and also function as a point of action for applying a predetermined pressure (18) to the measurement site.

As a mechanism for holding the optical structure, a clamping structure is adopted. The reason for this is because, as described above, the restriction of the measurement site and the restriction of the blood flow are applied. Fig. 6 shows this structure, and the optical structure described above, i.e., the structure of fig. 4 and 5, is incorporated therein. In the housing (27) of fig. 6, the light (14) from the light source is guided by the mirror (29), but a configuration may be adopted in which the light is guided to the actuator lens by an optical fiber or the like (not shown). Although fig. 6 shows a configuration of transmitting light, the same mechanism may be used for diffuse reflection, and the optical structure shown in fig. 5 may be incorporated. In this case, a light-collecting objective lens (20b) disposed on the PD side of the structure that transmits light serves as a measurement object support member (26).

Fig. 7 is a basic circuit block diagram. Although fig. 7 shows a configuration using transmitted light, a circuit using diffuse reflected light has the same configuration. The OSC1(30a) (not shown) is a signal used for measurement, and is, for example, a signal obtained by AC-modulating an optical output at 1 Khz. The measurement value is the amplitude of the signal absorbed and diffused by the measurement site of the signal of OSC1(30a) detected by PD (17). The OSC2(30b) is used to switch between the light source 1(23a) (hereinafter referred to as LD1) and the light source 2(23b) (hereinafter referred to as LD2), and light is alternately emitted by switching between the light source switching circuit (31) so that LD2 stops when LD1 emits light and LD1 stops when LD2 emits light. For example, LD1 emits light when the output of OSC2(30b) is H, and LD2 emits light when the output is L. LD1 is a reference light, and LD2 is a measurement light. The output of the PD (17) (common to the reference light and the measurement light) is subjected to IV conversion (35) and amplified by a synchronous AMP (36). The light source driving circuits 1,2 (hereinafter referred to as LDDs 1,2) (32a,32b) have a high-frequency superimposing function (34) in the laser diode, and are used in a single-mode to multi-mode oscillation mode in order to avoid instability of laser light emission by reflected light, and the light output is kept constant by an APC circuit (not shown) such as a front monitor and a rear monitor diode. In addition, a temperature sensor (34) is provided to correct for temperature-induced variations. The RMS circuit (37) outputs an effective value of the detected signal and inputs the effective value to servo amplifiers (38, 40). A circuit (41b) for holding the output of an RMS circuit (37) when an LD1 emits light and a servo circuit for automatically controlling the amount of light emitted by an LD1 by calculating the difference between a reference voltage (39) (corresponding to the reference light amount) input to an LD1 servo amplifier are formed. By this operation, the light quantity of the reference light received by the PD (17) is constant, excluding the influence of the basic transmission quantity. The LD1 servo amplifier 38 calculates the input quantity of the LDD1 32a, and when the output is large, it indicates that the attenuation of the light in the object 21 is large, and the control quantity of the LD1 becomes the reference value of the LD 2. The reference value automatically determines the optical power required for basic measurement in the object (21) to be measured. By using the LD1 detection amount as the reference of LD2 measurement light, the physical displacement and the displacement of the water content of the object (21) are corrected. Since the physical displacement (variation in the structure of the object (21)) is considered to be attenuation characteristics (not affecting light absorption characteristics and diffusion characteristics) common to LD1 and LD2, the amount detected by LD1 reflects the amount of correction of the physical displacement and the amount of correction of absorbance based on moisture that may be displaced over time. Further, the output of the LD2 can be kept constant by calculating the difference between the value of the output of the circuit (41c) that holds the output of the RMS circuit (37) when the LD2 emits light and the value of the output of the circuit (41a) that holds the control amount of the LD1, and setting the difference as the control output of the LD 2. (an optimum value is obtained in advance for the ratio between the amount of light emitted from LD1 and the amount of light emitted from LD2, and the gain of LDD is determined according to the ratio.) A circuit (41a) for holding the control amount of LD1 (when the output of OSC2(30b) is, for example, H, the output from the RMS circuit (37) of LD1 is held by an LD1 detection value holding circuit (41b), and when the output is L, the output of a measurement value correction circuit (42) for calculating the difference between the control amounts held by an LD2 detection holding circuit (41 c)) and LD2 finally becomes a measurement value in which the detection amount of LD2 is corrected for physical displacement and moisture displacement. In the present apparatus, the measurement was performed 3 times with time shifts. The method of obtaining the final result by the 3 measurements will be described later.

The actuator lens (22) is adjusted by the light emission period (49) of the LD 1. When the primary light emission is performed, the center of the light beam can be detected by calculating the difference (43) between the outputs (17s,17b) of the sub-PDs on the main PD (17) side, and the center of the intensity of the light detected by the PD becomes the center of the PD by this operation. In the configuration of fig. 7, when the output (35S) of S is large, the light intensity distribution detection circuit outputs (+) compared to the reference voltage, and drives the shift drive circuit (44B) to reduce the output, and when the output (35B) of B is large, the output (-) compared to the reference voltage, and therefore, the shift drive circuit (44B) is driven to reduce the output, contrary to the case of the S (35S) signal. The drive of LD1 for measurement and the drive of the displacement drive mechanism (47) are performed simultaneously, and after the detection amount of LD1 is obtained, the detection based on LD2 is performed during the light emission period (50) of LD2, and the final measurement value is obtained. Fig. 8 shows switching between LD1 and LD 2. In addition, the SNR of the measurement value is improved by using an average value (overlap value). In this example, the modulation signal (30c) is a continuous signal, but the same is true for a pulse with a low duty ratio. When the actuator lens has a tilt function, first, before measurement, control outputs are measured for reference light by the LD1 during a plurality of LD1 light emission periods (49), outputs from a tilt drive reference voltage generation circuit (46) using an extremely small MPU or the like are obtained each time the tilt drive mechanism (48) is driven by changing the outputs, and after a state in which the LD1 control amount is minimized is obtained, a regulation and measurement cycle by the shift drive mechanism is entered. The present tilt drive mechanism (48) and the present shift drive mechanism (47) provide real-time adjustment for eliminating the influence of the tissue structure of the measurement site and for correcting the offset due to vibration and the like.

Example 2

In fig. 7, the structure of an analog servo circuit is shown as a circuit, but it is needless to say that the circuit may be realized by digital processing by an MPU (52) or the like. Further, since the servo loop is analog, the light emission of the LD1 and the LD2 is performed by the waveform (30c) from the oscillator as shown in fig. 9, but even if the light emission is performed by the short pulse light emission (30d), for example, the pulse light emission of about 10ns to 30ns, the temperature rise of the measurement portion due to the energy of the light can be avoided by the pulse light emission. By suppressing the temperature rise, the measurement accuracy can be expected to be improved. In addition, since the human skin is the site to be measured in the case of a blood glucose level, there is a possibility that the light may cause a burn when the irradiation is continuously performed with very strong light. The safety region of the human body with respect to the intensity (energy) of the light is determined according to a reference established by international safety standards. In addition, the synchronous amplifier (36) can also be realized by digital signal processing. As a result, the LD1 and LD2 control amounts themselves of the servo circuits are detected amounts corresponding to the absorbance and the diffusibility. The structure at this time is shown in fig. 9. First, a value (36a) for light emission (light emission control amount is a predetermined amount) of an LD1 is input after analog-to-digital conversion a plurality of times, a drive amount of a tilt drive circuit (45b) is changed, a drive amount for minimizing the detection amount of an LD1 is detected, and an optimum state of tilt is obtained, and in this state, adjustment by a shift drive mechanism (47) is performed, so that signals (35s,35b) from a sub PD are input to an MPU (52) after analog-to-digital conversion, calculation (calculation equivalent to a light intensity distribution detection circuit (43)) is performed in the MPU (52), and a shift drive circuit (44b) is driven so that the PD (17) becomes the center of a light beam. The series of tilt control and shift control is performed before the measurement of LD1 and LD 2. When the

LDs

1 and 2 are driven, the MPUs (52) drives the

LDs

1 and 2, but the OSC1(30a) modulates and controls the LD1 on/off signal (32d) and the LD2 on/off signal (32 e). In the measurement, first, the LD1 light emission control amount (32c) is adjusted so that the output from the MPU becomes a constant amount each time, and a detection amount is obtained so that the value (36a) inputted after analog-to-digital conversion becomes a predetermined value (corresponding to the LD1 reference voltage generation circuit (39)) as the detection value of the LD 1. Then, similarly, the light emission control amount (32f) of the LD2 is adjusted so that the value input to the MPU (36a) after analog-to-digital conversion becomes a constant value with reference to the amount detected by the LD 1. The LD2 light emission control amount (32f) at this time is set as a detection amount based on the LD 2. Then, the value obtained by subtracting the detection amount by the LD1 from the detection amount by the LD2 by the MPU 52 and correcting the result with a signal 33a from the temperature correction sensor 33 (the correction amount is experimentally obtained based on the value obtained by the absorbance characteristics based on the temperature) becomes the final measurement value. With this configuration, the blood glucose level to be measured is assumed to be in the range of 50mg/dl to 200 mg/dl. SMBG, which is actually used for the treatment of diabetes, is required to be in the range of about 0mg/dl to 900 mg/dl. If this range is assumed, a considerable laser output may be required, but by narrowing the range, low power consumption and cost reduction can be achieved.

Hereinafter, the processing of the measurement values 3 times and the output of the final result, which are characteristic of the present apparatus, will be described based on the operation of the specific apparatus. First, a pre-meal operation switch (54a) is operated to measure a pre-meal value. The measured value at this time was (t1, S1). Then, after about 30 minutes from the meal, the measurement is performed by operating the after-meal operation switch (54 b). The measured value at this time was (t2, S2). Then, after about 2 hours, the measurement was performed by operating the after-meal operation switch. The measured value at this time was (t3, S3). (determination after 30 minutes, 2 hours, etc. is made by a timer (55) inside the apparatus.) from the measured value, ds is determined as S3-S1. This value becomes the basic measurement of the device. Next, dts is obtained as (s2-s1)/(t2-t 1). The value is a time differential value indicating how much the value changes in a short time, and the result of the determination from the value of ds and the value of dts is displayed on a display (53) as a device. This value represents the rate of increase in blood glucose level. It is known that the blood glucose level significantly varies depending on the metabolic state, dietary pattern, and content, and even if the blood glucose level is normal in the fasting state, the blood glucose level may rapidly increase by diet. This rising blood glucose level is called a blood glucose level spike, and a case where the value of this spike is large is also called recessive diabetes. When the time differential value is large, it is estimated that a large blood glucose level spike exists. In the measurement of a normal blood glucose level, when the peak of the blood glucose level is detected, it is necessary to measure the maximum value by continuously measuring the blood glucose level. In the present embodiment, the measurement equivalent to the measurement of a blood glucose level spike is performed without continuous measurement. In the present measurement method, the difference and the change rate of the measurement value are calculated in a short time, so that the deviation from the accuracy is canceled out, and the measurement accuracy and the reproducibility are improved.

The graph of fig. 10 is a graph in which the final determination value is obtained. The horizontal axis represents the value of ds (56), and the vertical axis represents the final measurement result dds (57). In this space, the plurality of curves corresponds to dts (58). The ds, dts, and dds characteristics indicate that dds (57) is high even when the ds (56) value is low and the dts (57) value is high. For example, which dts (58) curve is selected by normalizing the dts value to a value of about 20. (the dts curve is drawn by a method of specifying the dts curve as a product specification based on the medical examination standard of the actual blood glucose level)

If the ds value (56) and dts (58) correspond to the regions shown in fig. 10(59), the measurement value may be abnormal or the measurement result may be abnormal. In this case, the display 53 blinks while displaying dds (57) values, indicating that attention must be paid to the processing of the measurement results. For example, ds values may be small when sugar metabolism is abnormal (severe). In addition, the dts value may be small. This state corresponds to a case where the blood glucose level is very high before a meal and the blood glucose level does not further increase with diet. In addition, regarding the setting of the region shown in (59), 3 kinds of charts are prepared assuming that breakfast, lunch, and dinner, and which chart to select can be determined according to the measured time period. For example, if the timer (55) is a morning time period, a considerable time may have elapsed since the previous day of diet, and the blood glucose level may have decreased, and a graph corresponding to this time may be used. The finally obtained dds value is displayed on a display, and the measurement device displays a numerical value. Or instead displayed with a color gradient. The value and color are mapped (60) to, for example, "blue" with reference to a value of dds of 0 and "red" with the maximum value.

Industrial applicability of the invention

The present invention can adopt a new index for health management in place of blood glucose levels, and can be applied to diagnostic equipment for early detection of recessive diabetes, which cannot be detected by measuring fasting blood glucose levels at present. In addition, the method of measuring the state of change, for example, the change in sugar produced by photosynthesis of plants, can be applied to agricultural control equipment.

Description of the symbols

1 light source

2 aperture

3a Objective lens (for coupling)

3b Objective lens (for focusing)

4 optical fiber

5 object to be measured

6 shutter

7 analytic grating

8 reflecting mirror

9 photoelectric element array

10 AD converter

11 processor

Example of temporal Change in Normal blood glucose level 12a

Example of temporal Change in abnormal sugar metabolism

12c example of temporal Change in abnormal sugar metabolism (Severe)

13 blood vessels, etc

14 light beam

15 actuator lens after tilting

16 displaced actuator lens

17 PD (photoelectric element)

18 optical path

19 applying pressure

20a objective lens for emitting light

20b objective lens for light collection

21 object to be measured

22 actuator lens

23a light source 1

23b light source 2

24a collimator lens 1

24b collimator lens 2

25a PBS (for Synthesis)

25b PBS (for reflected light separation)

26 object supporting member

27 device frame

28 fulcrum

29 mirror

17s PD side sub PD(s)

17b PD side sub PD (b)

30a OSC1 (oscillator for signal)

30b OSC2 (Signal generator for switching light source)

30c OSC1 output (light source modulation output)

30d LD1, LD2 pulse luminous waveform

31 light source change-over switch

32a light source drive circuit 1(LDD1)

32b light source drive circuit 2(LDD2)

33 temperature correction sensor

34 multi-light emitting oscillator

35I/V conversion circuit

36 synchronous amplifying circuit

37 RMS (effective value circuit)

38 LD1 servo amplifier

39 LD1 reference voltage generating circuit

40 LD2 servo amplifier

41a LD1 controlled variable holding circuit

41b LD1 luminescence detection value holding circuit

41c LD2 luminescence detection value holding circuit

42 measured value correction circuit

43 light intensity distribution detection circuit

44a shift driving buffer circuit

44b shift drive circuit

45a tilt drive buffer circuit

45b tilt driving circuit

46 inclined driving reference voltage generating circuit

47 displacement driving mechanism

48 tilting drive mechanism

30 OSC1 output (light source modulation output)

49 LD1 light emitting period, actuator lens adjusting mechanism

50 LD2 light-emitting period (measuring period)

51 OSC2 output

32c LD1 light-emitting quantity control quantity signal

32d LD1 ON/OFF control Signal

32e LD2 ON/OFF control signal

32f LD2 light-emitting quantity control quantity signal

33a temperature sensor signal

36a PD side sub-PD signal input

36b PD side sub-PD signal input

52 MPU

53 display device

54a operating switch (before meal)

54b operating switch (after meal)

55 timer

Calculated value of 56 ds

57 dds Final measurement results

58 dts curve

59 flicker to display the blood sugar level

60 dds display color mapping

Claims

1. A non-destructive measuring device for measuring the concentration of a substance,

having a light emitting section, a light receiving section, and a control section, and having an optical measurement section for measuring the concentration of an internal substance in a site to be measured, a display section for displaying the measurement result, and a communication function for outputting the measurement result to the outside,

the light emitting unit outputs light emitted at a single wavelength having an emission wavelength of 1 st wavelength and 2 nd wavelength to the measurement site alone,

the light receiving units detect light from the light source that has passed through the inside of the measurement site at the measurement site,

the control unit includes a calculation processing unit that converts light from the light source passing through the inside of the measurement site into a 1 st absorbance and a 2 nd absorbance, which are ratios at which light from the light source passing through the inside of the measurement site is absorbed by the measurement substance in the inside of the measurement site, respectively, of the 1 st wavelength and the 2 nd wavelength, corrects and calculates the 2 nd absorbance using the 1 st absorbance, and the control unit holds the measurement value as a 1 st measurement value, performs the same measurement again after a lapse of a certain time, holds the measurement value as a 2 nd measurement value by the control unit, measures the measurement value by the same measurement method after a lapse of a certain time, and holds the measurement value as a 3 rd measurement value by the control unit,

the control unit calculates the difference between the 1 st measurement value and the 3 rd measurement value as the change in concentration of the measurement substance in the measurement site, calculates the difference between the 1 st measurement value and the 2 nd measurement value as the rate of change with time in the elapsed time period from the measurement time of the 1 st measurement value to the measurement of the 2 nd measurement value, outputs the data of the amount of change in concentration and the data of the rate of change with time to the display unit, and transmits the data to the outside through communication.

2. A nondestructive measurement device characterized in that,

the substance to be measured at the measurement site according to the concentration change amount data and the temporal change rate data according to claim 1 is a blood glucose level in vivo.

3. A nondestructive measurement device characterized in that,

has a function of displaying the concentration change amount data and the time change rate data of claim 1.

4. A nondestructive measurement device characterized in that,

has a communication function for outputting the concentration change amount data and the time rate data according to claim 1 to an external device.

5. The nondestructive measurement device according to claim 1 or claim 2,

as the correction operation, the 1 st absorbance is subtracted from the 2 nd absorbance of claim 1 to obtain the measured value.

6. The nondestructive measurement device according to claim 1 or claim 2,

as the correction operation, the measured value is obtained by dividing the 2 nd absorbance of claim 1 by the 1 st absorbance.

7. The nondestructive measurement device according to any one of claims 1 to 6,

the color display device has a 2-dimensional data table having the density change data value according to claim 1 and the time change rate data value according to claim 1 as axes, and has a function of performing an operation of converting a value preset in the data table of the measured density change data value and the measured time change rate data value into a color, and displaying the color on the display unit according to claim 1.

8. The nondestructive measurement device according to any one of claims 1 to 7,

the device has a mechanism for correcting the irradiation position and angle of the light to be irradiated to the measurement site.

9. The nondestructive measurement device according to any one of claims 1 to 8,

the measurement device has a structure for applying a predetermined pressure to a measurement site including a measurement substance using a light emission site as a point of action for applying the predetermined pressure to the measurement site, and a structure for measuring the measurement substance inside the measurement site with the predetermined pressure applied to the measurement site.