Hemoglobin concentration measuring device, blood glucose measuring device, and hemoglobin concentration measuring method

Abstract

This invention provides a hemoglobin concentration measuring device, a blood glucose measuring device, and a hemoglobin concentration measuring method that can easily measure the hemoglobin concentration in the blood of a living organism. [Solution] The hemoglobin concentration measuring device 100 includes: an optical output unit 3 that outputs measurement light L containing at least light of a first wavelength and light of a second wavelength to a living body 6; an optical detection unit 4 that detects the measurement light L output by the optical output unit 3 and transmitted through the living body 6; a signal acquisition unit 51 that acquires a total hemoglobin signal and a surrounding tissue signal based on the detection result of the optical detection unit 4; and a hemoglobin concentration estimation unit 52 that estimates the hemoglobin concentration based on the total hemoglobin signal and surrounding tissue signal acquired when the blood flow state is a first state and the total hemoglobin signal and surrounding tissue signal acquired when the blood flow state is a second state.

Description

Technical Field

[0001] The present disclosure relates to a hemoglobin concentration measuring device, a blood glucose level measuring device, and a hemoglobin concentration measuring method.

Background Art

[0002] As a technology related to a hemoglobin concentration measuring device, for example, a spectrophotometer described in Patent Document 1 is known. In the spectrophotometer described in Patent Document 1, a plurality of lights are irradiated onto a tissue site (living body) containing blood or the like, the light attenuated by the tissue site is received by a detector, and a detector output corresponding to the absorption of light in the tissue site is generated. The generated detector output is processed by a normalizer to generate a normalized pre-echogram, and the ratio of the fractional volume of the analyte in the blood volume is calculated based on the pre-echogram.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] In a hemoglobin concentration measuring device, in measuring the hemoglobin concentration, for example, it may be necessary to output light in a relatively long wavelength range to the living body in order to detect the pulsation of plasma. In this case, it is difficult to cope with the configuration as mounted on an existing standard device, and a light source such as a special LED corresponding to the light is required separately.

[0005] The present disclosure has been made in view of the above circumstances, and an object thereof is to provide a hemoglobin concentration measuring device, a blood glucose level measuring device, and a hemoglobin concentration measuring method that can easily measure the hemoglobin concentration of the blood of a living body.

Means for Solving the Problems

[0006] As a result of diligent investigation, the Discloser has found that the optical path length from when the measurement light is output from the optical output unit until it passes through the living body and is detected by the photodetector unit does not change significantly even when blood flow changes, as long as the relatively shallow region from the epidermis to the dermis to the subcutaneous layer is observed. Therefore, the detection results from the photodetector unit show that when the blood flow state of the living body changes from state 1 to state 2, the signal value related to the blood of the living body increases (or decreases), while the signal value related to surrounding tissues other than the blood of the living body decreases (or increases). Furthermore, the Discloser has conducted further diligent investigations and found that when the blood flow state of the living body changes from state 1 to state 2, the higher (or lower) the hemoglobin concentration of the blood of the living body, the larger (or smaller) the ratio of the change in the blood signal to the change in the signal related to surrounding tissues becomes, thus completing this disclosure.

[0007] In other words, the hemoglobin concentration measuring device according to the present disclosure is [1] "a device for measuring the hemoglobin concentration of a living organism's blood, comprising: an optical output unit that outputs measurement light including at least light of a first wavelength and light of a second wavelength different from the first wavelength to the living organism; an optical detection unit that detects the measurement light output by the optical output unit and transmitted through the living organism; a signal acquisition unit that acquires a first signal relating to the blood of the living organism and a second signal relating to surrounding tissue other than the blood of the living organism based on the detection result of the optical detection unit; and a hemoglobin concentration estimation unit that estimates the hemoglobin concentration based on the first signal and the second signal acquired by the signal acquisition unit when the blood flow state of the living organism is in a first state, and the first signal and the second signal acquired by the signal acquisition unit when the blood flow state is in a second state different from the first state."

[0008] This hemoglobin concentration measuring device outputs measurement light, including light of first and second wavelengths, to a living organism to acquire a first signal related to the blood of the organism and a second signal related to the surrounding tissues other than the blood of the organism. Then, based on the first and second signals when the blood flow state is in state 1 and the first and second signals when the blood flow state is in state 2, the hemoglobin concentration can be estimated using the aforementioned finding that the ratio of the change in the first signal related to blood to the change in the second signal related to surrounding tissues changes with hemoglobin concentration.Therefore, special wavelengths of light (separate special light source) are not required to measure hemoglobin concentration, and the measurement can be realized with a configuration such as that incorporated in existing standard devices.According to this disclosure, it is possible to easily measure the hemoglobin concentration of the blood of a living organism.

[0009] The hemoglobin concentration measuring device according to this disclosure may also be [2] "the hemoglobin concentration measuring device according to [1] above, wherein the hemoglobin concentration estimation unit estimates the hemoglobin concentration based on the amount of change between the first signal when the blood flow state is in the first state and the first signal when the blood flow state is in the second state, and the amount of change between the second signal when the blood flow state is in the first state and the second signal when the blood flow state is in the second state." In this case, it becomes possible to estimate the hemoglobin concentration by specifically utilizing the above-mentioned finding that the ratio of the fluctuation of the first signal relating to blood to the fluctuation of the second signal relating to surrounding tissue changes with hemoglobin concentration.

[0010] The hemoglobin concentration measuring device according to the present disclosure is described in [2] above, wherein the first signal includes a total hemoglobin signal relating to the total hemoglobin in the blood of the living organism, the second signal includes a peripheral tissue signal relating to the peripheral tissue, and the hemoglobin concentration estimation unit estimates the hemoglobin concentration according to formula (1). Hemoglobin concentration = α × |ΔTotalHb| / (|ΔTotalHb|+|ΔTissue|)…(1) however, α: predetermined coefficient, ΔTotalHb: difference between the total hemoglobin signal value in the first state and the total hemoglobin signal value in the second state, ΔTissue: difference between the peripheral tissue signal value in the first state and the peripheral tissue signal value in the second state. In this case, it becomes possible to estimate the hemoglobin concentration by making more specific use of the above-mentioned finding that the ratio of the change in the first signal to the change in the second signal changes with hemoglobin concentration.

[0011] The hemoglobin concentration measuring device according to the present disclosure is described in [2] above, wherein the measuring light includes light of a third wavelength different from the first and second wavelengths, the first signal includes an oxygenated hemoglobin signal relating to oxygenated hemoglobin in the blood of the living organism and a deoxygenated hemoglobin signal relating to deoxygenated hemoglobin in the blood of the living organism, the second signal includes a peripheral tissue signal relating to the peripheral tissue, and the hemoglobin concentration estimation unit estimates the hemoglobin concentration according to formula (2). Hemoglobin concentration = α × |ΔOxyHb + ΔDeoxyHb| / (|ΔOxyHb+ΔDeoxyHb|+|ΔTissue|)…(2) However, α may be a predetermined coefficient, ΔOxyHb may be the difference between the oxygenated hemoglobin signal value in the first state and the oxygenated hemoglobin signal value in the second state, ΔDeoxyHb may be the difference between the deoxygenated hemoglobin signal value in the first state and the deoxygenated hemoglobin signal value in the second state, and ΔTissue may be the difference between the peripheral tissue signal value in the first state and the peripheral tissue signal value in the second state. In this case, it becomes possible to estimate the hemoglobin concentration by making more specific use of the above-mentioned finding that the ratio of the change in the first signal to the change in the second signal changes with hemoglobin concentration.

[0012] The hemoglobin concentration measuring device according to this disclosure may be [5] "the hemoglobin concentration measuring device according to any one of [1] to [4] above, wherein the hemoglobin concentration estimation unit corrects at least one of the first signal and the second signal based on the skin tone of the living organism." For example, if the skin tone of a living organism is dark, when the blood flow state changes from a first state to a second state, an error may occur due to the skin tone such that the ratio of the fluctuation of the first signal to the fluctuation of the second signal becomes smaller. In this disclosure, this error can be reduced by correcting at least one of the first signal and the second signal based on the skin tone.

[0013] The blood glucose measuring device according to this disclosure is a blood glucose measuring device comprising: [6] "a hemoglobin concentration measuring device as described in any of [1] to [5] above; a blood glucose estimation unit that calculates the temporal phase difference between an oxygenated hemoglobin signal relating to oxygenated hemoglobin in the blood of the living organism and a deoxygenated hemoglobin signal relating to deoxygenated hemoglobin in the blood of the living organism, and estimates the blood glucose level of the living organism based on the calculated temporal phase difference; and a blood glucose correction unit that corrects the blood glucose level estimated by the blood glucose estimation unit using the hemoglobin concentration estimated by the hemoglobin concentration estimation unit." With this blood glucose measuring device, the hemoglobin concentration of the blood of the living organism can be easily measured using the hemoglobin concentration measuring device, and the estimated blood glucose level can be corrected using the hemoglobin concentration to accurately determine the blood glucose level.

[0014] The hemoglobin concentration measurement method according to this disclosure is [7] "a method for measuring the hemoglobin concentration of a living organism's blood, comprising: an optical output step of outputting measurement light, which includes at least light of a first wavelength and light of a second wavelength different from the first wavelength, to the living organism; an optical detection step of detecting the measurement light output in the optical output step and transmitted through the living organism; a signal acquisition step of acquiring a first signal relating to the blood of the living organism and a second signal relating to surrounding tissue other than the blood of the living organism, based on the detection result of the optical detection step; and a hemoglobin concentration estimation step of estimating the hemoglobin concentration based on the first signal and the second signal acquired in the signal acquisition step when the blood flow state of the living organism is in a first state, and the first signal and the second signal acquired in the signal acquisition step when the blood flow state is in a second state different from the first state." In this hemoglobin concentration measurement method as well, special wavelengths of light are not required to measure the hemoglobin concentration, making it possible to easily measure the hemoglobin concentration of a living organism's blood. [Effects of the Invention]

[0015] This disclosure makes it possible to provide a hemoglobin concentration measuring device, a blood glucose measuring device, and a hemoglobin concentration measuring method that can easily measure the hemoglobin concentration in the blood of a living organism. [Brief explanation of the drawing]

[0016] [Figure 1] Figure 1 is a conceptual diagram showing a blood glucose measuring device equipped with a hemoglobin concentration measuring device according to the first embodiment. [Figure 2] Figure 2 is a graph showing an example of the detection results of the light detection unit in Figure 1. [Figure 3] Figure 3 is a block diagram showing the functional configuration of the ECU in Figure 1. [Figure 4] Figure 4(a) is a schematic diagram showing the measurement light passing through a living organism with standard blood flow conditions. Figure 4(b) is a diagram illustrating the light-absorbing elements present throughout the entire optical path of the measurement light in Figure 4(a). [Figure 5]Fig. 5(a) is a schematic diagram showing measurement light transmitted through a living body in a high blood flow state. Fig. 5(b) is a diagram for explaining light absorption elements present in the entire optical path of the measurement light in Fig. 5(a). [Figure 6] Fig. 6(a) is a graph showing fluctuations in blood signals and peripheral tissue signals. Fig. 6(b) is another graph showing fluctuations in blood signals and peripheral tissue signals. [Figure 7] Fig. 7 is a graph showing examples of total hemoglobin signals and peripheral tissue signals. [Figure 8] Fig. 8 is a diagram for explaining the setting of skin tone. [Figure 9] Fig. 9(a) is a flowchart showing a method for measuring hemoglobin concentration. Fig. 9(b) is another flowchart showing a method for measuring hemoglobin concentration. [Figure 10] Fig. 10(a) is a schematic diagram showing an example of the movement of a subject. Fig. 10(b) is a schematic diagram showing the continuation of Fig. 10(a). Fig. 10(c) is a schematic diagram showing the continuation of Fig. 10(b). [Figure 11] Fig. 11 is a flowchart showing a method for measuring blood glucose level. [Figure 12] Fig. 12(a) is a graph showing total hemoglobin signals and peripheral tissue signals of a subject with a pale complexion. Fig. 12(b) is a graph showing total hemoglobin signals and peripheral tissue signals of a subject with a ruddy complexion. [Figure 13] Fig. 13(a) is a graph showing total hemoglobin signals and peripheral tissue signals of a false positive subject. Fig. 13(b) is a graph showing total hemoglobin signals and peripheral tissue signals of a false negative subject. [Figure 14] Fig. 14 is a graph showing an example of the detection result of the light detection unit according to the second embodiment. [Figure 15] Fig. 15 is a graph showing examples of oxygenated hemoglobin signals, deoxygenated hemoglobin signals, and peripheral tissue signals.

Embodiments for Carrying Out the Invention

[0017] The embodiments will be described in detail below with reference to the drawings. In the drawings, the same or corresponding parts are denoted by the same reference numerals, and redundant descriptions are omitted.

[0018] [First Embodiment] The blood glucose measuring device 1 shown in Figure 1 is, for example, a wearable device, a smartphone, or a pulse oximeter. Examples of wearable devices include smartwatches and smart rings. The blood glucose measuring device 1 in this embodiment is a device that can be worn by the body 6 at all times and is a smartwatch.

[0019] The blood glucose meter 1 measures the blood glucose level of the user, a living organism 6. The blood glucose meter 1 includes a hemoglobin concentration measuring device 100, which is a device for measuring the hemoglobin concentration (hereinafter also simply referred to as "hemoglobin concentration") of the blood of the living organism 6. The living organism 6 has a superficial tissue 61 and an internal tissue 62 located deeper inside the living organism 6 than the superficial tissue 61. The surface 61a of the superficial tissue 61 is the surface of the skin of the living organism 6. The superficial tissue 61 and the internal tissue 62 constitute the dermis. The living organism 6 is, for example, a human body such as a subject.

[0020] The blood glucose measuring device 1 comprises a main unit 2, an optical output unit 3, an optical detection unit 4, and an ECU (Electronic Control Unit) 50. The main unit 2 has a front 2a and a back 2b facing the opposite side of the front 2a. On the front 2a side of the main unit 2, input / output devices such as a display, speaker, and microphone are provided for inputting and outputting various information of the blood glucose measuring device 1. The display here is a touch panel display that allows various settings and input / output of information. User information, including the skin tone of the body 6, can be input to the main unit 2 via the touch panel display. The blood glucose measuring device 1 is attached to the body 6 so that the back 2b is in contact with the skin of the body 6.

[0021] The optical output unit 3 is located on the main body 2. The optical output surface of the optical output unit 3 is exposed from the back surface 2b of the main body 2. The optical output unit 3 has a light source that outputs measurement light (light) L to the living organism 6. The light source is, for example, a light-emitting diode (LED), a laser diode (LD), or a superluminescent diode (SLD). The measurement light L is emitted from the back surface 2b. The measurement light L emitted from the optical output unit 3 propagates inside the living organism 6 and is then emitted again from the living organism 6. The optical output unit 3 is controlled by the ECU 50.

[0022] The wavelength range of the measurement light L is, for example, from the red wavelength range of visible light to the near-infrared region (670 nm to 1000 nm). In other words, the optical output unit 3 outputs measurement light L that is included in the range from the red wavelength range of visible light to the near-infrared region. The optical output unit 3 outputs measurement light L that includes, for example, multiple lights with different wavelengths. The measurement light L includes, for example, visible light to near-infrared light.

[0023] In this embodiment, the optical output unit 3 has a first light source and a second light source. The first light source emits light of a first wavelength. The second light source emits light of a second wavelength. The first wavelength is, for example, 805 nm ± 50 nm. The second wavelength is different from the first wavelength, for example, 525 nm ± 50 nm. The first and second wavelengths are peak wavelengths. The first and second wavelengths may be, for example, average values ​​of the emission peak wavelength range. The optical output unit 3 may also have a single light source that outputs probe light (e.g., white light) containing wavelength components of the first and second wavelengths as measurement light L.

[0024] The photodetector 4 is located on the main body 2. The photodetector 4 is separated from the optical output unit 3. The photodetector surface of the photodetector 4 is exposed from the back surface 2b of the main body 2. The photodetector 4 has a photodetector element that detects the measurement light (transmitted light) L output by the optical output unit 3 and transmitted through the living organism 6. The photodetector element is, for example, a photodiode (PD). The photodetector 4 may also have a preamplifier that amplifies the photocurrent output from the photodetector element, and an A / D conversion circuit that converts the signal amplified by the preamplifier into a digital signal. The photodetector 4 may also have a CCD image sensor or a CMOS image sensor. The photodetector 4 transmits a signal regarding the intensity of the measurement light L to the ECU 50.

[0025] As shown in Figure 2, the photodetector 4 detects at least the first data D1 and the second data D2. The first data D1 is the change in the intensity of the first wavelength of measurement light L when it passes through the living organism 6 and is incident on the photodetector 4. The second data D2 is the change in the intensity of the second wavelength of measurement light L when it passes through the living organism 6 and is incident on the photodetector 4. The first data D1 and the second data D2 are biological signals that fluctuate depending on the concentration of substances in the living organism 6.

[0026] The ECU50 is located in the main unit 2. The ECU50 is an electronic control unit having a CPU (Central Processing Unit), ROM (Read Only Memory), and RAM (Random Access Memory), etc. The ECU50 performs various processes, for example, by executing a program stored in the ROM or RAM using the CPU. The ECU50 calculates the pulse rate of the living body 6 based on the detection result of the light detection unit 4. The method for calculating the pulse rate is not particularly limited, and various known methods may be used. The ECU50 estimates the hemoglobin concentration in the blood of the living body 6 and the blood glucose level of the living body 6 based on the detection result of the light detection unit 4 (details will be described later). The ECU50 may be composed of a single electronic control unit, or it may be composed of multiple electronic control units that can communicate with each other. The pulse rate may also be detected by a heart rate sensor.

[0027] As shown in Figure 3, the ECU 50 has a functional configuration comprising a signal acquisition unit 51, a hemoglobin concentration estimation unit 52, a blood glucose level estimation unit 53, and a blood glucose level correction unit 54. The signal acquisition unit 51 acquires a total hemoglobin signal (first signal) and a peripheral tissue signal (second signal) based on the detection result of the photodetector unit 4. The total hemoglobin signal is a blood signal relating to the blood of the living organism 6. The total hemoglobin signal is a signal relating to the total hemoglobin in the blood of the living organism 6, and here, the total hemoglobin signal is waveform data relating to the concentration of total hemoglobin. The peripheral tissue signal is a signal relating to the peripheral tissues other than the blood of the living organism 6, and here, it is waveform data relating to the peripheral tissues including the dermal tissue other than the blood of the living organism 6.

[0028] Specifically, the signal acquisition unit 51 calculates the oxygenated hemoglobin signal and the deoxygenated hemoglobin signal based on the detection results of the photodetector unit 4. The signal acquisition unit 51 acquires the total hemoglobin signal by adding the oxygenated hemoglobin signal and the deoxygenated hemoglobin signal together. The oxygenated hemoglobin signal and the deoxygenated hemoglobin signal are blood signals relating to the blood of the living organism 6. The oxygenated hemoglobin signal is a signal relating to oxygenated hemoglobin (O2Hb) in the blood of the living organism 6, and here it is waveform data relating to the concentration of oxygenated hemoglobin. The deoxygenated hemoglobin signal is a signal relating to deoxygenated hemoglobin (HHb) in the blood of the living organism 6, and here it is waveform data relating to the concentration of deoxygenated hemoglobin. Hereinafter, the oxygenated hemoglobin signal, the deoxygenated hemoglobin signal, and the total hemoglobin signal will be collectively referred to as the blood signal (first signal).

[0029] For example, the signal acquisition unit 51 calculates the oxygenated hemoglobin signal, the deoxygenated hemoglobin signal, and the surrounding tissue signal by applying spectroscopic calculation processing based on the Modified Beer-Lambert (MBL) method to the first data D1 and the second data D2. The MBL method is one of the methods that utilizes the property that the optical signal intensity of transmitted light changes depending on the concentration of a substance. For example, the signal acquisition unit 51 calculates the amount of change in the intensity of the first and second data D1 and D2, which is the difference between the intensity of the first and second data D1 and D2 at the first time and the intensity of the first and second data D1 and D2 at the second time. Based on the amount of change in the intensity of the first and second data D1 and D2 and the extinction coefficients of oxygenated hemoglobin, deoxygenated hemoglobin, and surrounding tissue for the first and second data D1 and D2, the signal acquisition unit 51 calculates the amount of change in oxygenated hemoglobin, deoxygenated hemoglobin, and surrounding tissue over time. The signal acquisition unit 51 calculates the oxygenated hemoglobin signal, the deoxygenated hemoglobin signal, and the surrounding tissue signal by continuously calculating the relative changes over time of oxygenated hemoglobin, deoxygenated hemoglobin, and surrounding tissue.

[0030] The hemoglobin concentration estimation unit 52 estimates the hemoglobin concentration based on the total hemoglobin signal and the surrounding tissue signal. First, the principle of hemoglobin concentration estimation in the hemoglobin concentration estimation unit 52 will be explained.

[0031] As shown in Figures 4(a) and 5(a), the measurement light L output from the optical output unit 3 penetrates the surrounding tissue 60, including the dermal tissue of the living organism 6, and the blood 65 in multiple capillaries, and is detected by the optical detection unit 4. When the blood flow state of the living organism 6 is, for example, a standard state, the light-absorbing elements present in the entire optical path of the measurement light L, as shown in Figure 4(b), consist of multiple elements B1 derived from blood and multiple elements E1 derived from surrounding tissue. On the other hand, when the blood flow state of the living organism 6 is, for example, a high blood flow state with higher blood flow than the standard state, the light-absorbing elements present in the entire optical path of the measurement light L, as shown in Figure 5(b), consist of multiple elements B2 derived from blood and multiple elements E2 derived from surrounding tissue.

[0032] Here, it can be seen that the optical path length from when the measurement light L is output by the optical output unit 3 until it passes through the living body 6 and is detected by the photodetector unit 4 does not change significantly even when the blood flow rate changes (in particular, as far as observing the relatively shallow region from the surface of the skin (epidermis to dermis to subcutaneous layer), it can be seen that it does not change significantly even when the blood flow rate changes). Therefore, when the blood flow state of the living body 6 changes from a standard state to a high blood flow state, the amount of blood 65 flowing through the capillaries increases compared to when the blood flow state of the living body 6 is in a standard state. As shown in Figures 4(b) and 5(b), the proportion of multiple elements B2 derived from blood among the light-absorbing elements present in the entire optical path of the measurement light L increases. When such a change in the proportion of light-absorbing elements in the optical path of the measurement light L is observed, for example, by near-infrared spectroscopy, it appears as an increase in the blood signal P1 and a decrease in the surrounding tissue signal P2, as shown in Figure 6(a).

[0033] At this time, as shown in Figure 6(b), it is found that the higher the hemoglobin concentration of blood 65, the more pronounced the increase in blood signal P1 in relation to the fluctuation (drift) of surrounding tissue signal P2 (the opposite is true when the hemoglobin concentration is low). In other words, when the blood flow state of organism 6 changes from state 1 to state 2, it is found that the higher (or lower) the hemoglobin concentration of the blood in organism 6, the larger (or smaller) the ratio of the fluctuation of blood signal P1 to the fluctuation of surrounding tissue signal P2. Therefore, by comparing the relationship between the decrease (or increase) of surrounding tissue signal P2 and the increase (or decrease) of blood signal P1, it is possible to estimate the dimensional hemoglobin concentration (mg / dL) of blood 65.

[0034] Therefore, the hemoglobin concentration estimation unit 52 of this embodiment estimates the hemoglobin concentration based on the total hemoglobin signal and surrounding tissue signal acquired by the signal acquisition unit 51 when the blood flow state of the living body 6 is in a first state, and the total hemoglobin signal and surrounding tissue signal acquired by the signal acquisition unit 51 when the blood flow state of the living body 6 is in a second state different from the first state.

[0035] Specifically, the hemoglobin concentration estimation unit 52 estimates the hemoglobin concentration based on the change in the total hemoglobin signal when the blood flow state is the first state and the total hemoglobin signal when the blood flow state is the second state, and the change in the surrounding tissue signal when the blood flow state is the first state and the surrounding tissue signal when the blood flow state is the second state. More specifically, the hemoglobin concentration estimation unit 52 calculates ΔTotalHb and ΔTissue and estimates the hemoglobin concentration according to equation (1). Hemoglobin concentration = α × |ΔTotalHb| / (|ΔTotalHb|+|ΔTissue|)…(1) however, α: predetermined coefficient, ΔTotalHb: difference between the total hemoglobin signal value in the first state and the total hemoglobin signal value in the second state, ΔTissue: difference between the peripheral tissue signal value in the first state and the peripheral tissue signal value in the second state.

[0036] Note that α is a statistically determined coefficient for value assignment and is not particularly limited. ΔTotalHb corresponds to the fluctuation of the non-pulsating component of the total hemoglobin signal. ΔTissue corresponds to the fluctuation of the non-pulsating component of the peripheral tissue signal.

[0037] For example, in the example of the total hemoglobin signal P11 and peripheral tissue signal P2 shown in Figure 7, the hemoglobin concentration estimation unit 52 determines ΔTotalHb, which is the change in the total hemoglobin signal P11, and ΔTissue, which is the change in the peripheral tissue signal P2, between time t0 when the blood flow state is standard and time t1 when the blood flow state is low. The hemoglobin concentration estimation unit 52 introduces the determined ΔTotalHb and ΔTissue into equation (1) and estimates the hemoglobin concentration. Note that the example in Figure 7 simulates the total hemoglobin signal P11 and peripheral tissue signal P2 of a healthy subject with normal hemoglobin concentration, and for the sake of explanation, the ratio of ΔTotalHb to ΔTissue is normalized to 1:1. Also, in the example in Figure 7, each signal is offset so that it is (0,0) at time t0, which is the reference time (similarly in Figures 12, 13, and 15).

[0038] The hemoglobin concentration estimation unit 52 corrects at least one of the total hemoglobin signal P11 and the surrounding tissue signal P2 based on the skin tone of the living organism 6. The skin tone corresponds to the density of the skin color of the living organism 6. The skin tone can be obtained, for example, based on user information input via the touch panel display of the main unit 2. For example, if the skin tone is darker than the first threshold, the hemoglobin concentration estimation unit 52 corrects the surrounding tissue signal P2 to be smaller because the surrounding tissue signal P2 becomes larger due to the skin tone. Also, for example, if the skin tone is lighter than the second threshold, the hemoglobin concentration estimation unit 52 corrects the surrounding tissue signal P2 to be larger because the surrounding tissue signal P2 becomes smaller due to the skin tone.

[0039] As an example, the user may set the skin tone as follows: As shown in Figure 8, a color bar 71 with continuously changing colors is displayed on the touch panel display of the main unit 2, and a frame-shaped selection area 72 is displayed on the color bar 71. The color bar 71 is a band-shaped object containing colors corresponding to various skin tones. The user moves the selection area 72 or the color bar 71 on the touch panel display, positions the color closest to the user's skin tone within the selection area 72, selects it, and then inputs a confirmation command. As a result, the color selected by the selection area 72 is set as the skin tone.

[0040] The blood glucose level estimation unit 53 calculates the temporal phase difference between the oxygenated hemoglobin signal and the deoxygenated hemoglobin signal, and estimates the metabolic level or blood glucose level of the living organism 6 based on the calculated temporal phase difference. As an example, the blood glucose level estimation unit 53 calculates the temporal phase difference as the time difference between the bottom point, peak point, or notch point of the waveform of the oxygenated hemoglobin signal and the bottom point, peak point, or notch point of the waveform of the deoxygenated hemoglobin signal. The blood glucose level estimation unit 53 calculates the blood glucose level of the living organism 6 using the formula G = a1 × Δθ - b1. G is the blood glucose level of the living organism 6, Δθ is the temporal phase difference, and a1 and b1 are coefficients determined according to the glucose metabolic capacity and measurement site of the living organism 6.

[0041] The blood glucose level correction unit 54 corrects the blood glucose level estimated by the blood glucose level estimation unit 53 using the hemoglobin concentration estimated by the hemoglobin concentration estimation unit 52. For example, the blood glucose level correction unit 54 corrects the blood glucose level estimated by the blood glucose level estimation unit 53 by multiplying it by a gain value or weight value corresponding to the hemoglobin concentration, based on the relationship that the metabolic or blood glucose index calculated from the temporal phase difference of the hemoglobin signal is proportional to the hemoglobin concentration. In the above, the main unit 2, the optical output unit 3, the photodetector unit 4, the signal acquisition unit 51 of the ECU 50, and the hemoglobin concentration estimation unit 52 constitute the hemoglobin concentration measuring device 100.

[0042] Next, the method for measuring hemoglobin concentration using the blood glucose measuring device 1 (hemoglobin concentration measuring device 100) will be explained with reference to the flowcharts in Figures 9(a) and 9(b). In the following, "living body 6" refers to the subject.

[0043] First, we will describe an example of the subject's actions when measuring the hemoglobin concentration in the subject's blood. As shown in Figure 10(a), subject 6T attaches the blood glucose meter 1 to, for example, their finger (step S1). Subject 6T inputs user information, including skin tone, via the touch panel display of the main unit 2 (step S2). Subject 6T assumes a resting posture and sets the blood flow state to a standard blood flow state (step S3).

[0044] Subject 6T, in a resting position, touches, for example, the measurement start button on the touch panel display of the main unit 2 to begin measuring hemoglobin concentration (step S4). As shown in Figure 10(b), subject 6T changes their posture to an arm-raised position with their arms raised vertically, following, for example, an audio guide from the speaker of the main unit 2, thereby reducing blood flow and creating a low blood flow state (step S5). As shown in Figure 10(c), subject 6T returns their posture from the arm-raised position to a resting position, following, for example, an audio guide from the speaker of the main unit 2 (step S6). After that, subject 6T finishes measuring hemoglobin concentration (step S7).

[0045] Furthermore, in the actions of subject 6T described above, instead of changing posture between a resting position and an arm-raised position, the posture may be changed between a position where the arms are extended horizontally straight at heart level and a position where the arms are extended downwards. Alternatively, instead of changing posture between a resting position and an arm-raised position, the arms may be compressed with a cuff or the like to forcibly block blood flow, or natural fluctuations over time may be utilized. In other words, when measuring hemoglobin concentration, it is not limited to changing posture between a resting position and an arm-raised position; it is sufficient if the signal level of the signal acquired by the signal acquisition unit 51 can be forcibly changed using an external force or passively changed by the internal or spontaneous activity of the living body.

[0046] Next, the process of measuring hemoglobin concentration using the hemoglobin concentration measuring device 100 will be described. First, measurement light L is output from the light output unit 3 to the subject 6T (step S11: light output step). The measurement light L transmitted through the subject 6T is detected by the light detection unit 4 (step S12: light detection step). Based on the detection result of step S12, the signal acquisition unit 51 acquires the total hemoglobin signal P11 and the surrounding tissue signal P2 (step S13: signal acquisition step).

[0047] Based on the fluctuations in total hemoglobin signal P11 and peripheral tissue signal P2 between the standard blood flow state and the low blood flow state of subject 6T, the hemoglobin concentration estimation unit 52 estimates the hemoglobin concentration according to equation (1) (Step S14: Hemoglobin concentration estimation step). The values ​​of total hemoglobin signal P11 and peripheral tissue signal P2 when the blood flow state is standard blood flow may be the initial values ​​at the start of measurement in step S4. The values ​​of total hemoglobin signal P11 and peripheral tissue signal P2 when the blood flow state is low blood flow may be the values ​​immediately before step S6.

[0048] Next, the method for measuring the blood glucose level of subject 6T using the blood glucose measuring device 1 will be explained with reference to the flowchart in Figure 11. First, the blood glucose estimation unit 53 calculates the temporal phase difference between the oxygenated hemoglobin signal and the deoxygenated hemoglobin signal (step S21). The blood glucose estimation unit 53 estimates the blood glucose level of subject 6T based on the calculated temporal phase difference (step S22). The blood glucose correction unit 54 corrects the estimated blood glucose level using the hemoglobin concentration estimated in step S14 (step S23).

[0049] The example in Figure 12(a) shows an example simulating the total hemoglobin signal P11 and peripheral tissue signal P2 of an anemic subject, and the example in Figure 12(b) shows an example simulating the total hemoglobin signal P11 and peripheral tissue signal P2 of an hyperemia subject. For example, if a healthy subject is subject 6T and ΔTotalHb and ΔTissue are approximately equal (see Figure 7), then if an anemic subject with a low hemoglobin concentration is subject 6T, as shown in Figure 12(a), even if the peripheral tissue signal P2 increases, the decrease in the total hemoglobin signal P11 is small. On the other hand, if a hyperemia subject with a high hemoglobin concentration is subject 6T, as shown in Figure 12(b), the decrease in the total hemoglobin signal P11 when the peripheral tissue signal P2 increases is large. In this embodiment, by utilizing this relationship, it is possible to estimate the hemoglobin concentration by the hemoglobin concentration estimation unit 52.

[0050] In other words, the hemoglobin concentration measuring device 100 of this embodiment can estimate hemoglobin concentration by utilizing the knowledge that the ratio of ΔTotalHb, which is the variation in the total hemoglobin signal P11, to ΔTissue, which is the variation in the surrounding tissue signal P2, changes with hemoglobin concentration. Therefore, special wavelengths of light (e.g., wavelengths of 1000 nm or more) and separate special light sources are not required to measure hemoglobin concentration, and it becomes possible to measure hemoglobin concentration with a configuration similar to that found in existing standard devices. This makes it possible to easily measure hemoglobin concentration.

[0051] In the hemoglobin concentration measuring device 100 of this embodiment, the hemoglobin concentration estimation unit 52 estimates the hemoglobin concentration based on ΔTotalHb and ΔTissue. In this case, it is possible to estimate the hemoglobin concentration by specifically utilizing the knowledge that the ratio of ΔTissue to ΔTotalHb changes with hemoglobin concentration.

[0052] In the hemoglobin concentration measuring device 100 of this embodiment, the hemoglobin concentration estimation unit 52 estimates the hemoglobin concentration according to equation (1). In this case, it becomes possible to estimate the hemoglobin concentration by making more specific use of the knowledge that the ratio of ΔTissue to ΔTotalHb changes with hemoglobin concentration.

[0053] Figure 13(a) is a graph showing an example of simulating the total hemoglobin signal P11 and peripheral tissue signal P2 of a false-positive subject. The example in Figure 13(a) shows a case where subject 6T, who is hypernecological due to skin tone, is misdiagnosed as anemic. Ideally, in hypernecological subjects, the decrease in total hemoglobin signal P11 should be larger than the increase in peripheral tissue signal P2. However, when the skin tone is dark, as shown in Figure 13(a), the increase in peripheral tissue signal P2 is large, and the change in total hemoglobin signal P11 becomes relatively small compared to the change in peripheral tissue signal P2. As a result, the ratio of ΔTissue to ΔTotalHb tends to be similar to that of anemic subjects.

[0054] Figure 13(b) is a graph showing an example of simulating the total hemoglobin signal P11 and peripheral tissue signal P2 of a false-negative subject. The example in Figure 13(b) shows a case where subject 6T, who is anemic due to skin tone, is misidentified as a healthy subject. Normally, in anemic subjects, the decrease in total hemoglobin signal P11 should be smaller than the increase in peripheral tissue signal P2. However, when skin tone is pale, as shown in Figure 13(b), the increase in peripheral tissue signal P2 is smaller, and the changes in both total hemoglobin signal P11 and peripheral tissue signal P2 are small, resulting in a ratio of ΔTissue to ΔTotalHb that tends to be similar to that of a healthy subject.

[0055] In this regard, in the hemoglobin concentration measuring device 100 of this embodiment, the hemoglobin concentration estimation unit 52 corrects the surrounding tissue signal P2 based on the skin tone of the living organism 6. This makes it possible to reduce errors that may occur due to skin tone regarding the ratio of ΔTissue to ΔTotalHb.

[0056] The blood glucose measuring device 1 of this embodiment includes a hemoglobin concentration measuring device 100, a blood glucose estimation unit 53 that estimates the blood glucose level of the living body 6, and a blood glucose correction unit 54 that corrects the blood glucose level estimated by the blood glucose estimation unit 53 using the hemoglobin concentration estimated by the hemoglobin concentration estimation unit 52. With this blood glucose measuring device 1, the hemoglobin concentration can be easily measured by the hemoglobin concentration measuring device 100, and the estimated blood glucose level can be corrected using the hemoglobin concentration, making it possible to determine the blood glucose level with high accuracy.

[0057] In the hemoglobin concentration measurement method of this embodiment, similar effects and advantages as the hemoglobin concentration measuring device 100 are achieved, namely, the absence of special wavelengths of light for measuring hemoglobin concentration, making it possible to perform the measurement with a configuration similar to that found in existing standard devices. This makes it possible to easily measure hemoglobin concentration.

[0058] [Second Embodiment] Next, a second embodiment will be described. In the description of the second embodiment, explanations that overlap with those of the first embodiment will be omitted as appropriate.

[0059] In this embodiment, the optical output unit 3 has a first light source, a second light source, and a third light source. The first light source emits light of a first wavelength. The second light source emits light of a second wavelength. The third light source emits light of a third wavelength. The first wavelength is, for example, 910 nm ± 50 nm. The second wavelength is different from the first wavelength, for example, 660 nm ± 50 nm. The third wavelength is different from the first and second wavelengths, for example, 525 nm ± 50 nm. The first to third wavelengths may be, for example, peak wavelengths or average values ​​of the emission peak wavelength range. The optical output unit 3 may also have a single light source that outputs probe light (e.g., white light) containing wavelength components of the first to third wavelengths as measurement light L.

[0060] As shown in Figure 14, the photodetector 4 detects first data D1, second data D2, and third data D3. First data D1 is, for example, the change in the intensity of the light when light of the first wavelength of the measurement light L passes through the living organism 6 and is incident on the photodetector 4. Second data D2 is, for example, the change in the intensity of the light when light of the second wavelength of the measurement light L passes through the living organism 6 and is incident on the photodetector 4. Third data D3 is, for example, the change in the intensity of the light when light of the third wavelength of the measurement light L passes through the living organism 6 and is incident on the photodetector 4. First to third data D1 to D3 are biological signals that fluctuate depending on the concentration of substances in the living organism 6.

[0061] The signal acquisition unit 51 calculates the oxygenated hemoglobin signal and the deoxygenated hemoglobin signal as the first signal and the surrounding tissue signal as the second signal based on the detection results of the photodetector unit 4. The hemoglobin concentration estimation unit 52 in this embodiment estimates the hemoglobin concentration based on the oxygenated hemoglobin signal, the deoxygenated hemoglobin signal and the surrounding tissue signal acquired by the signal acquisition unit 51 when the blood flow state of the living body 6 is in the first state, and the oxygenated hemoglobin signal, the deoxygenated hemoglobin signal and the surrounding tissue signal acquired by the signal acquisition unit 51 when the blood flow state of the living body 6 is in the second state.

[0062] Specifically, the hemoglobin concentration estimation unit 52 estimates the hemoglobin concentration based on the change between the oxygenated hemoglobin signal when the blood flow state is the first state and the oxygenated hemoglobin signal when the blood flow state is the second state, the change between the deoxygenated hemoglobin signal when the blood flow state is the first state and the deoxygenated hemoglobin signal when the blood flow state is the second state, and the change between the peripheral tissue signal when the blood flow state is the first state and the peripheral tissue signal when the blood flow state is the second state. More specifically, the hemoglobin concentration estimation unit 52 calculates ΔOxyHb, ΔDeoxyHb, and ΔTissue, and estimates the hemoglobin concentration according to equation (2). Hemoglobin concentration = α × |ΔOxyHb + ΔDeoxyHb| / (|ΔOxyHb+ΔDeoxyHb|+|ΔTissue|)…(2) However, α is a predetermined coefficient, ΔOxyHb is the difference between the oxygenated hemoglobin signal value in the first state and the oxygenated hemoglobin signal value in the second state, ΔDeoxyHb is the difference between the deoxygenated hemoglobin signal value in the first state and the deoxygenated hemoglobin signal value in the second state, and ΔTissue is the difference between the peripheral tissue signal value in the first state and the peripheral tissue signal value in the second state.

[0063] Note that α is a statistically determined coefficient for value assignment and is not particularly limited. α may be the same as or different from α in equation (1). ΔOxyHb corresponds to the fluctuation of the non-pulsating component of the oxygenated hemoglobin signal. ΔDeoxyHb corresponds to the fluctuation of the non-pulsating component of the deoxygenated hemoglobin signal.

[0064] For example, in the case of the oxygenated hemoglobin signal P21, deoxygenated hemoglobin signal P31, and peripheral tissue signal P2 shown in Figure 15, the hemoglobin concentration estimation unit 52 determines the change in oxygenated hemoglobin signal P21, ΔOxyHb, the change in deoxygenated hemoglobin signal P31, and ΔTissue, the change in peripheral tissue signal P2, between time t0 when the blood flow state is standard and time t1 when the blood flow state is low. The hemoglobin concentration estimation unit 52 introduces the determined ΔOxyHb, ΔDeoxyHb, and ΔTissue into equation (2) to estimate the hemoglobin concentration.

[0065] As described above, the hemoglobin concentration measuring device 100 of this embodiment also makes it possible to easily measure hemoglobin concentration. Furthermore, it is found that the ratio of ΔTissue to ΔOxyHb + ΔDeoxyHb changes with hemoglobin concentration. Therefore, the hemoglobin concentration estimation unit 52 of this embodiment estimates the hemoglobin concentration based on ΔOxyHb, ΔDeoxyHb, and ΔTissue. Specifically, the hemoglobin concentration estimation unit 52 estimates the hemoglobin concentration according to equation (2). In this case, it becomes possible to estimate the hemoglobin concentration by making more specific use of the finding that the ratio of ΔTissue to ΔOxyHb + ΔDeoxyHb changes with hemoglobin concentration.

[0066] [Differentiation] The embodiments described above are not limited to the above-described embodiments.

[0067] In the above embodiment, the use of the measured hemoglobin concentration is not particularly limited and can be applied to various purposes. For example, the hemoglobin concentration estimated by the hemoglobin concentration estimation unit 52 may be used to correct blood glucose values ​​obtained with other optical blood glucose meters.

[0068] For example, based on the hemoglobin concentration estimated by the hemoglobin concentration estimation unit 52, anemia screening may be performed, anemia management may be performed, the risk of fainting may be evaluated, detected and notified, or acute blood concentration fluctuations (dehydration or bleeding) may be detected. For example, the hemoglobin concentration estimated by the hemoglobin concentration estimation unit 52 may be used in combination with other indicators as a new vital sign indicator. For example, the hemoglobin concentration estimated by the hemoglobin concentration estimation unit 52 may be used as an indicator of menstrual severity, as an indicator to evaluate the basal metabolic capacity of athletes, as an indicator to evaluate the effects of high-altitude hypoxic training, or as an indicator to evaluate and detect the effects of autologous blood transfusion doping.

[0069] In the above embodiment, the ECU 50 was provided in the main unit 2, but the ECU 50 does not have to be provided in the main unit 2, and may be provided in, for example, a server that can communicate with the main unit 2. In the above embodiment, the optical output unit 3 may include a broadband light source. For example, a white LED can be used as the broadband light source. When the optical output unit 3 includes a broadband light source in this way, the photodetector 4 may include a spectrometer.

[0070] The components in the above embodiments and modifications are not limited to the materials and shapes described above, and various materials and shapes can be applied. Furthermore, the components in the above embodiments and modifications can be arbitrarily applied to the components in other embodiments or modifications. The numerical values ​​above may include errors due to measurement, manufacturing, and design. The term "equal" above includes not only cases where they are exactly equal, but also cases where they are approximately equal. [Explanation of Symbols]

[0071] 1...Blood glucose measuring device, 3...Light output unit, 4...Light detection unit, 6...Living body, 6T...Subject (living body), 51...Signal acquisition unit, 52...Hemoglobin concentration estimation unit, 53...Blood glucose estimation unit, 54...Blood glucose correction unit, 65...Blood, 100...Hemoglobin concentration measuring device, L...Measurement light.

Claims

1. A device for measuring the hemoglobin concentration in the blood of a living organism, A light output unit that outputs measurement light, which includes at least light of a first wavelength and light of a second wavelength different from the first wavelength, to the living organism, A photodetector that detects the measurement light output by the light output unit and transmitted through the living body, A signal acquisition unit acquires a first signal relating to the blood of the living organism and a second signal relating to surrounding tissues other than the blood of the living organism, based on the detection results of the light detection unit. A hemoglobin concentration measuring device comprising: a first signal and a second signal acquired by the signal acquisition unit when the blood flow state of the living organism is in a first state, and a hemoglobin concentration estimation unit that estimates the hemoglobin concentration based on the first signal and a second signal acquired by the signal acquisition unit when the blood flow state is in a second state different from the first state.

2. The hemoglobin concentration measuring device according to claim 1, wherein the hemoglobin concentration estimation unit estimates the hemoglobin concentration based on the amount of change between the first signal when the blood flow state is in the first state and the first signal when the blood flow state is in the second state, and the amount of change between the second signal when the blood flow state is in the first state and the second signal when the blood flow state is in the second state.

3. The first signal includes a total hemoglobin signal relating to the total hemoglobin in the blood of the living organism, and the second signal includes a peripheral tissue signal relating to the peripheral tissue. The hemoglobin concentration measuring device according to claim 2, wherein the hemoglobin concentration estimation unit estimates the hemoglobin concentration according to formula (1). Hemoglobin concentration = α × |ΔTotalHb| / (|ΔTotalHb|+|ΔTissue|)…(1) however, α: predetermined coefficient, ΔTotalHb: difference between the total hemoglobin signal value in the first state and the total hemoglobin signal value in the second state, ΔTissue: difference between the peripheral tissue signal value in the first state and the peripheral tissue signal value in the second state.

4. The measurement light includes light of a third wavelength different from the first and second wavelengths, The first signal includes an oxygenated hemoglobin signal relating to oxygenated hemoglobin in the blood of the living organism, and a deoxygenated hemoglobin signal relating to deoxygenated hemoglobin in the blood of the living organism, The second signal includes peripheral tissue signals relating to the peripheral tissue, The hemoglobin concentration measuring device according to claim 2, wherein the hemoglobin concentration estimation unit estimates the hemoglobin concentration according to formula (2). Hemoglobin concentration = α × |ΔOxyHb + ΔDeoxyHb| / (|ΔOxyHb+ΔDeoxyHb|+|ΔTissue|)…(2) however, α: predetermined coefficient, ΔOxyHb: difference between the oxygenated hemoglobin signal value in the first state and the oxygenated hemoglobin signal value in the second state, ΔDeoxyHb: difference between the deoxygenated hemoglobin signal value in the first state and the deoxygenated hemoglobin signal value in the second state, ΔTissue: difference between the peripheral tissue signal value in the first state and the peripheral tissue signal value in the second state.

5. The hemoglobin concentration measuring device according to claim 1 or 2, wherein the hemoglobin concentration estimation unit corrects at least one of the first signal and the second signal based on the skin tone of the living organism.

6. A hemoglobin concentration measuring device according to claim 1, A blood glucose level estimation unit calculates the temporal phase difference between the oxygenated hemoglobin signal related to the oxygenated hemoglobin in the blood of the living organism and the deoxygenated hemoglobin signal related to the deoxygenated hemoglobin in the blood of the living organism, and estimates the blood glucose level of the living organism based on the calculated temporal phase difference. A blood glucose measuring device comprising: a blood glucose correction unit that corrects the blood glucose level estimated by the blood glucose level estimation unit using the hemoglobin concentration estimated by the hemoglobin concentration estimation unit.

7. A method for measuring the hemoglobin concentration in the blood of a living organism, A light output step of outputting measurement light to the living organism, which includes at least light of a first wavelength and light of a second wavelength different from the first wavelength; A photodetection step for detecting the measurement light output in the light output step and transmitted through the living organism, A signal acquisition step, based on the detection result of the light detection step, acquires a first signal relating to the blood of the living organism and a second signal relating to surrounding tissue other than the blood of the living organism. A hemoglobin concentration measurement method comprising: a hemoglobin concentration estimation step of estimating the hemoglobin concentration based on the first signal and the second signal acquired in the signal acquisition step when the blood flow state of the living organism is in a first state, and the first signal and the second signal acquired in the signal acquisition step when the blood flow state is in a second state different from the first state.

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