JP7087301B2 - Bioanalyzers, bioanalysis methods and programs - Google Patents

Description

The present invention relates to a technique for analyzing a living body.

Various measurement techniques for analyzing biological information such as pulse wave velocity have been conventionally proposed. For example, Patent Document 1 discloses a measuring device for measuring a pulse wave velocity using a cuff attached to each of the upper limbs and the lower limbs of a living body. Specifically, the pulse wave velocity of the living body is calculated by using the time difference between the pulse wave detected by the cuff on the upper limb side and the pulse wave detected by the cuff on the lower limb side.

Japanese Unexamined Patent Publication No. 2008-18835

In the technique of Patent Document 1, since it is necessary to attach a cuff to each of the upper limbs and the lower limbs of the living body, the burden on the subject is large. In consideration of the above circumstances, it is an object of the present invention to calculate an index relating to a blood vessel of a living body with high accuracy while reducing the physical load on the subject.

In order to solve the above problems, the bioanalyzer according to a preferred embodiment of the present invention has a blood volume integrated value obtained by integrating a blood volume index related to a living body blood volume for an integration period and a blood flow index related to a living body blood flow volume. It is provided with a blood vessel calculation unit that calculates a blood vessel index related to a blood vessel of a living body according to the accumulated blood flow value for the integration period. In the above configuration, since the blood vessel index is calculated according to the integrated blood flow rate value and the integrated blood flow rate value, a cuff is not required in principle. Therefore, it is possible to calculate the blood vessel index of the living body with high accuracy while reducing the physical load on the subject.

In a preferred embodiment of the present invention, the blood vessel index is calculated according to the ratio of the integrated blood flow rate and the integrated blood flow rate. In the above configuration, since the blood vessel index is calculated according to the ratio between the integrated blood volume value and the integrated blood flow value, the ratio between the integrated blood volume value and the integrated blood flow value correlates with the pulse wave velocity (specifically). It is possible to calculate the vascular index with high accuracy by utilizing the tendency of positive correlation).

In a preferred embodiment of the present invention, the vascular index is a pulse pressure index relating to pulse pressure.

In a preferred embodiment of the present invention, the blood vessel calculation unit calculates the ratio of the time-varying amplitude of the blood volume index to the time-varying amplitude of the blood flow index as an amplitude index relating to the time-varying amplitude of the blood flow velocity of the living body. The amplitude calculation unit, the resistance calculation unit that calculates the ratio between the blood volume integrated value and the blood flow integrated value as a resistance index related to the vascular resistance of the living body, and the pulse pressure index according to the amplitude index and the resistance index are calculated. It is equipped with a pulse pressure calculation unit. In the above configuration, the ratio of the amplitude of the time change of the blood volume index to the amplitude of the time change of the blood flow index is calculated as the amplitude index of the time change of the blood flow velocity of the living body, so that the time of the blood volume index is calculated. The amplitude index can be calculated with high accuracy by utilizing the tendency that the ratio of the amplitude of change and the amplitude of time change of the blood flow index correlates with the blood flow velocity. In addition, the amplitude index can be calculated while reducing the influence of the skin thickness. Furthermore, since the ratio between the integrated blood volume and the integrated blood flow is calculated as a resistance index related to the vascular resistance of the living body, the ratio between the integrated blood volume and the integrated blood flow correlates with the pulse wave velocity. The tendency can be used to calculate the resistance index with high accuracy. As a result, the tendency that the product of the ratio of the time change amplitude of the blood volume index and the time change amplitude of the blood flow index and the ratio of the blood volume integrated value and the blood flow integrated value correlates with the pulse pressure is used. Therefore, it is possible to calculate the pulse pressure index with high accuracy.

In a preferred embodiment of the present invention, the resistance calculation unit normalizes the integrated blood volume value obtained by integrating the value obtained by normalizing the blood volume index within the normalization range for the integration period and the blood flow index within the normalization range. The ratio of the numerical value to the integrated blood flow value accumulated for the integration period is calculated as a resistance index. In the above configuration, the blood volume integrated value obtained by integrating the value obtained by normalizing the blood volume index within the normalized range for the integration period and the blood obtained by integrating the value obtained by normalizing the blood flow index within the normalized range for the integration period. The ratio with the integrated flow rate is calculated as a resistance index. Taking advantage of the tendency that the ratio of the integrated blood volume value obtained by integrating the normalized value of the blood volume index and the integrated blood volume value obtained by integrating the normalized value of the blood flow index correlates with the pulse wave velocity. The resistance index can be calculated with high accuracy.

In a preferred embodiment of the present invention, the vascular index is a resistance index relating to vascular resistance of a living body. In the above configuration, the resistance index related to the vascular resistance of the living body is calculated as the blood vessel index, and the blood vessel index is calculated according to the ratio between the blood volume integrated value and the blood vessel integrated value. Therefore, the blood volume integrated value and blood The resistance index can be calculated with high accuracy by utilizing the tendency that the ratio with the integrated flow rate correlates with the pulse wave propagation velocity.

The bioanalytical device according to a preferred embodiment of the present invention is attached to the upper arm or wrist of a living body. According to the above aspects, the bioanalytical device can be easily attached to the living body.

In a preferred embodiment of the present invention, a blood volume index is used by using a light emitting unit that irradiates a living body with a laser beam, a light receiving unit that receives the laser light reflected inside the living body, and a detection signal indicating the light receiving level by the light receiving unit. The blood vessel calculation unit calculates the blood vessel index from the blood volume index and the blood vessel volume index calculated by the index calculation unit.

In a preferred embodiment of the present invention, the blood vessel calculation unit calculates the blood volume index by integrating the intensities of each frequency in the intensity spectrum with respect to the frequency of the detection signal for a predetermined frequency range.

In a preferred embodiment of the present invention, the blood vessel calculation unit calculates the blood flow index by integrating the product of the intensity of each frequency in the intensity spectrum with respect to the frequency of the detection signal and the frequency in a predetermined frequency range.

In the biological analysis method according to a preferred embodiment of the present invention, a blood volume integrated value obtained by integrating a blood volume index related to a living body blood volume for an integrated period and a blood volume integrated value obtained by integrating a blood flow index related to a living body blood volume for an integrated period are integrated. The vascular index for the blood vessels of the living body is calculated according to the ratio to the value.

The program according to a preferred embodiment of the present invention includes a blood volume integrated value obtained by integrating a blood volume index related to a living body blood volume for an integrated period and a blood volume integrated value obtained by integrating a blood flow index related to a living body blood volume for an integrated period. The computer functions as a blood vessel calculation unit that calculates blood vessel indexes related to blood vessels in the living body according to the ratio of blood vessels.

It is a side view of the bioanalysis apparatus which concerns on 1st Embodiment of this invention. It is a graph which shows the time change of blood pressure. It is a block diagram focusing on the function of a bioanalyzer. It is a graph which shows the time change of a blood volume index. It is a graph which shows the time change of a blood flow index. It is a graph which shows the relationship between the blood flow flow amplitude measured about a subject, and the amplitude of the time change of the calculated blood volume index, in the case of a plurality of cases where the skin thickness of a subject is changed. It is a graph which shows the relationship between the measured blood flow flow amplitude for a subject, and the amplitude of the time change of the calculated blood flow index for a plurality of cases where the skin thickness of a subject is changed. A graph showing the relationship between the measured blood flow velocity amplitude of a subject and the ratio of the time change amplitude of the blood volume index to the time change amplitude of the blood flow index for a plurality of cases in which the skin thickness of the subject is changed. Is. It is a graph which shows the time change of the normalized blood flow rate index, and the time change of the normalized blood flow rate index, respectively. It is a graph which showed the relationship between the pulse wave velocity actually measured about the subject, and the ratio of the blood volume integrated value and the blood flow integrated value, for a plurality of subjects. It is a graph which shows the relationship between the pulse pressure actually measured for a subject, and the product of an amplitude index and a resistance index, for each of a plurality of subjects. It is a flowchart of the bioanalysis process executed by the control device. It is a flowchart which shows the specific content of the process of calculating a resistance index. It is a block diagram of the bioanalyzing apparatus which concerns on 2nd Embodiment. It is a block diagram of the biological analysis apparatus which concerns on 3rd Embodiment. It is a graph which shows the time change of a blood flow index. It is a block diagram of the biological analysis apparatus which concerns on 4th Embodiment. It is a block diagram of the bioanalyzing apparatus which concerns on 5th Embodiment. It is a schematic diagram which shows the use example of the bioanalysis apparatus which concerns on 6th Embodiment. It is a schematic diagram which shows the other use example of the biological analysis apparatus which concerns on 6th Embodiment. It is a block diagram of an actual product. It is a graph which shows the relationship between the pulse pressure displayed about the actual product, and the pulse pressure displayed about the product of this application. It is a block diagram of the biological analysis apparatus in the modification. It is a block diagram of the biological analysis apparatus in the modification. It is a block diagram of the biological analysis apparatus in the modification. It is a block diagram of the biological analysis apparatus in the modification.

<First Embodiment>
FIG. 1 is a side view of the bioanalytical apparatus 100 according to the first embodiment of the present invention. The bioanalytical device 100 is a measuring device that non-invasively measures the biometric information of a subject. The bioanalyzing device 100 of the first embodiment measures the pulse pressure ΔP of a specific part (hereinafter referred to as “measurement part”) H in the body of the subject as biometric information. In the following description, the wrist or upper arm of the subject will be exemplified as the measurement site H. FIG. 2 is a graph showing the time-varying PT of blood pressure P. The difference between the systolic blood pressure (maximum blood pressure) Pmax and the diastolic blood pressure (minimum blood pressure) Pmin is the pulse pressure ΔP. In the first embodiment, the amount of change in blood pressure P during the analysis period (about 0.5 to 1 second) T corresponding to one beat of the beat is defined as the pulse pressure ΔP. The time length of the analysis period T is not limited to one beat. For example, a period longer than the time length corresponding to one beat may be set as the analysis period T. Pave in FIG. 2 is the mean blood pressure in the analysis period T.

Here, it is known that the blood pressure P can be expressed by the following equation (1) representing a water hammer. As understood from the equation (1), the blood pressure P is expressed as the product of the blood density ρ, the pulse wave velocity PWV, and the blood flow velocity V of the blood vessel.

Since the blood density ρ and the pulse wave velocity PWV have little time variation, the amount of change in the blood density ρ and the amount of change in the pulse wave velocity PWV in the analysis period T can be regarded as constant. Therefore, as shown in equation (2), the pulse pressure (that is, the amount of change in pressure in the analysis period T) ΔP is the blood density ρ, the pulse wave velocity PWV, and the amount of change in the blood flow velocity V in the analysis period T. (That is, the amplitude of the time change of the blood flow velocity of the living body) It is expressed as the product of ΔV. Since the blood density ρ varies from person to person, it can be set to a predetermined value (for example, 1070 kg / m ³ ). That is, it is possible to calculate the pulse pressure ΔP by calculating the pulse wave velocity PWV and the amplitude of the time change of the blood flow velocity of the blood flow velocity V (hereinafter referred to as “blood flow velocity amplitude”) ΔV. ..

The bioanalytical device 100 of FIG. 1 is attached to the measurement site H (upper arm or wrist). The bioanalytical device 100 of the first embodiment is a wristwatch-type portable device including a housing portion 12 and a belt 14. The bioanalytical device 100 is attached to the body of the subject by winding the belt 14 around the measurement site H.

FIG. 3 is a configuration diagram focusing on the function of the bioanalytical device 100. The bioanalytical device 100 of the first embodiment includes a control device 21, a storage device 22, a display device 23, and a detection device 30A. The control device 21 and the storage device 22 are installed inside the housing portion 12.

As exemplified in FIG. 1, the display device 23 (for example, a liquid crystal display panel) is installed on the surface of the housing portion 12 opposite to the measurement portion H. The display device 23 displays various images including the measurement results under the control of the control device 21.

The detection device 30A in FIG. 3 is an optical sensor module that generates a detection signal ZA according to the state of the measurement site H. Specifically, the detection device 30A includes a light emitting unit E and a light receiving unit R. The light emitting portion E and the light receiving portion R are installed, for example, at a position facing the measurement portion H (typically, a surface in contact with the measurement portion H) in the housing portion 12.

The light emitting unit E is a light source that irradiates the measurement site H with light. The light emitting unit E of the first embodiment irradiates the measurement site H (living body) with a coherent laser beam in a narrow band. For example, a light emitting element such as a VCSEL (Vertical Cavity Surface Emitting LASER) that emits laser light by resonance in a resonator is suitably used as a light emitting unit E. The light emitting unit E of the first embodiment irradiates the measurement site H with light having a predetermined wavelength (for example, 800 nm to 1300 nm) in the near infrared region, for example. The light emitting unit E emits light under the control of the control device 21. The light emitted by the light emitting unit E is not limited to near-infrared light.

The light incident on the measurement portion H from the light emitting portion E is repeatedly diffusely reflected while passing through the inside of the measurement portion H, and then emitted to the housing portion 12. Specifically, light that has passed through a blood vessel such as an artery existing inside the measurement site H (for example, a brachial artery, a radial artery, or an ulnar artery) and blood in the blood vessel is transmitted from the measurement site H to the housing portion 12 side. Emit.

The light receiving unit R receives the laser light reflected inside the measurement site H. Specifically, the light receiving unit R generates a detection signal ZA indicating the light receiving level of the light that has passed through the measurement site H. For example, a light receiving element such as a photodiode (PD) that generates an electric charge according to the light receiving intensity is used as the light receiving unit R. Specifically, a light receiving element in which a photoelectric conversion layer is formed of InGaAs (indium gallium arsenide) showing high sensitivity in the near infrared region is suitable as the light receiving portion R. As can be understood from the above description, the detection device 30A of the first embodiment is a reflection type optical sensor in which the light emitting unit E and the light receiving unit R are located on one side with respect to the measurement site H. However, a transmissive optical sensor in which the light emitting unit E and the light receiving unit R are located on opposite sides of the measurement portion H may be used as the detection device 30A. The detection device 30A includes, for example, a drive circuit that drives the light emitting unit E by supplying a drive current, and an output circuit that amplifies and A / D converts the output signal of the light receiving unit R (for example, an amplifier circuit and an A / D converter). ), But the illustration of each circuit is omitted in FIG.

The light that reaches the light receiving portion R is a component that is diffusely reflected by a tissue that is stationary inside the measurement site H (stationary tissue) and an object that moves inside the blood vessel inside the measurement site H (typically red blood cells). Includes diffusely reflected components. The frequency of light does not change before and after diffuse reflection in stationary tissue. On the other hand, before and after diffuse reflection in erythrocytes, the frequency of light changes by the amount of change (hereinafter referred to as "frequency shift amount") proportional to the movement speed (that is, blood flow velocity) of erythrocytes. That is, the light that passes through the measurement portion H and reaches the light receiving portion R contains a component that fluctuates (frequency shifts) by the frequency shift amount with respect to the frequency of the light emitted by the light emitting portion E. As understood from the above description, the detection signal ZA supplied to the control device 21 is an optical beat signal reflecting the frequency shift due to the blood flow inside the measurement site H.

The control device 21 in FIG. 3 is an arithmetic processing device such as a CPU (Central Processing Unit) or an FPGA (Field-Programmable Gate Array), and controls the entire bioanalysis device 100. The storage device 22 is composed of, for example, a non-volatile semiconductor memory, and stores a program executed by the control device 21 and various data used by the control device 21. It should be noted that a configuration in which the functions of the control device 21 are distributed in a plurality of integrated circuits, or a configuration in which some or all of the functions of the control device 21 are realized by a dedicated electronic circuit can also be adopted. Further, although the control device 21 and the storage device 22 are shown as separate elements in FIG. 3, the control device 21 including the storage device 22 can be realized by, for example, an ASIC (Application Specific Integrated Circuit) or the like.

The control device 21 of the first embodiment has a plurality of functions (index calculation unit 51A) for calculating the pulse pressure ΔP from the detection signal ZA generated by the detection device 30A by executing the program stored in the storage device 22. And the blood vessel calculation unit 53) is realized. A part of the functions of the control device 21 may be realized by a dedicated electronic circuit.

The index calculation unit 51A of FIG. 3 calculates the blood volume index MA and the blood flow index FA of the measurement site H from the detection signal ZA generated by the detection device 30A. The blood volume index MA (so-called MASS value) is an index relating to the blood volume of a living body (specifically, the number of red blood cells in a unit volume). Blood volume fluctuates in synchronization with the pulsation of the blood vessel diameter synchronized with the heartbeat. That is, the blood volume index MA also correlates with the blood vessel diameter. Therefore, the blood volume index MA can be paraphrased as an index of the blood vessel diameter (further, the cross-sectional area of the blood vessel) of the living body. On the other hand, the blood flow index FA (so-called FLOW value) is an index relating to the blood flow of a living body (that is, the volume of blood moving in an artery within a unit time).

The index calculation unit 51A calculates an intensity spectrum from the detection signal ZA, and calculates a blood volume index MA and a blood flow index FA from the intensity spectrum. The intensity spectrum is the distribution of the intensity (power or amplitude) G (f) of the signal component of the detection signal ZA at each frequency (Doppler frequency) on the frequency axis. A known frequency analysis such as Fast Fourier Transform (FFT) may be arbitrarily adopted for the calculation of the intensity spectrum. The calculation of the intensity spectrum is performed iteratively with a shorter cycle compared to the analysis period T.

The blood volume index MA is expressed by the following mathematical formula (3a). The symbol <I ² > in the equation (3a) is the average intensity over the entire band of the detection signal ZA, or the intensity G (0) (that is, the intensity of the DC component) at 0 Hz in the intensity spectrum.

As understood from the equation (3a), the blood volume index MA is obtained by integrating the intensity G (f) of each frequency f in the intensity spectrum with respect to the range between the lower limit value fL and the upper limit value fH on the frequency axis. It is calculated. The lower limit value fL is lower than the upper limit value fH. The blood volume index MA may be calculated by the following formula (3b) in which the integral of the formula (3a) is replaced with the sum (Σ). The symbol Δf in the equation (3b) is the bandwidth corresponding to one intensity G (f) on the frequency axis, and each rectangle when the intensity spectrum is approximated by a plurality of rectangles arranged on the frequency axis. Corresponds to the width. The calculation of the blood volume index MA is repeatedly performed in a shorter cycle as compared with the analysis period T. FIG. 4 is a time-varying MT of the blood volume index M (MA) calculated by the index calculation unit 51A for the analysis period T. In addition to the blood volume index MA of the first embodiment, the blood volume index MC exemplified in each of the embodiments described later is also calculated as the blood volume index M of the mathematical formula (3a) or the mathematical formula (3b). As can be understood from the above explanation, the blood volume index M is obtained from the intensity spectrum of the frequency of the light reflected and received inside the living body by the irradiation of the laser beam (specifically, the intensity of each frequency in the intensity spectrum). Calculated (accumulated over a given frequency range).

The blood flow index FA is expressed by the following mathematical formula (4a).

As understood from the equation (4a), the first-order moment (f × G (f)), which is the product of the intensity G (f) of each frequency f in the intensity spectrum and the frequency f, is the lower limit value on the frequency axis. The blood flow index FA is calculated by integrating the range between fL and the upper limit value fH. The blood flow index FA may be calculated by the following formula (4b) in which the integral of the formula (4a) is replaced with the sum (Σ). The calculation of the blood flow index FA is performed iteratively in a shorter cycle compared to the analysis period T. FIG. 5 is a time-varying FT of the blood flow index F (FA) calculated by the index calculation unit 51A for the analysis period T. In addition to the blood flow index FA of the first embodiment, the blood flow index FB exemplified in each of the embodiments described later is also calculated as the blood flow index F of the mathematical formula (4a) or the mathematical formula (4b). As can be understood from the above explanation, the blood flow index F is derived from the intensity spectrum of the frequency of the light reflected and received inside the living body by the irradiation of the laser beam (specifically, the intensity of each frequency in the intensity spectrum). It is calculated (by integrating the product with the frequency for a predetermined frequency range).

The blood vessel calculation unit 53 of FIG. 3 calculates the pulse pressure ΔP of the measurement site H by using the blood volume index MA and the blood flow rate index FA calculated by the index calculation unit 51A. The blood vessel calculation unit 53 of the first embodiment includes an amplitude calculation unit 531, a resistance calculation unit 533, and a pulse pressure calculation unit 535.

The amplitude calculation unit 531 calculates an index related to the blood flow velocity amplitude ΔV (hereinafter referred to as “amplitude index”) by using the blood volume index MA and the blood flow index FA generated by the index calculation unit 51A. Specifically, the amplitude calculation unit 531 calculates the amplitude index according to the amplitude ΔM of the time-varying MT of the blood volume index MA and the amplitude ΔF of the time-varying FT of the blood flow index F. As illustrated in FIG. 4, the amplitude ΔM is the difference between the maximum value Mmax and the minimum value Mmin of the blood volume index MA in the analysis period T. Further, as illustrated in FIG. 5, the amplitude ΔF is the difference between the maximum value Fmax and the minimum value Fmin of the blood flow index FA in the analysis period T.

FIG. 6 is a graph showing the relationship between the blood flow velocity amplitude ΔV actually measured for the subject and the amplitude ΔM specified by the index calculation unit 51A, and FIG. 7 shows the blood flow velocity amplitude ΔV actually measured for the subject. It is a graph which shows the relationship with the amplitude ΔF specified by the index calculation unit 51A. 6 and 7 show a plurality of cases in which the skin thickness of the subject was changed. Skin thickness is the distance from the surface of the skin to the blood vessels. The blood flow velocity amplitude ΔV is an actually measured value by a known measurement technique. As can be seen from FIGS. 6 and 7, each of the amplitude ΔM and the amplitude ΔF varies significantly depending on the skin thickness, although there is a correlation with the blood flow velocity amplitude ΔV. FIG. 8 shows the relationship between the blood flow velocity amplitude ΔV actually measured for the subject and the ratio of the amplitude ΔM and the amplitude ΔF specified by the index calculation unit 51A (specifically, the ratio of the amplitude ΔF to the amplitude ΔM). It is a graph which shows a plurality of cases which changed the skin thickness of. As can be seen from FIG. 8, the ratio of the amplitude ΔF to the amplitude ΔM (ΔF / ΔM) has a positive correlation with the blood flow velocity amplitude ΔV (when one increases, the other also increases), and depends on the skin thickness. It was found that the fluctuation was small. Based on the above findings, the amplitude calculation unit 531 of the first embodiment calculates the ratio (ΔF / ΔM) of the amplitude ΔM and the amplitude ΔF as an amplitude index.

The resistance calculation unit 533 of FIG. 3 calculates an index related to the pulse wave velocity PWV by using the blood volume index MA and the blood flow rate index FA generated by the index calculation unit 51A. The pulse wave velocity PWV correlates with vascular resistance. Specifically, when the vascular resistance is high, the pulse wave velocity PWV tends to increase. Based on this tendency, the index related to the pulse wave velocity PWV is called the "resistance index". That is, the resistance calculation unit 533 calculates the resistance index by using the blood volume index MA and the blood flow index FA. Specifically, the value obtained by integrating the blood volume index for the integration period (hereinafter referred to as "blood volume integrated value") SM and the value obtained by integrating the blood flow index for the integration period (hereinafter referred to as "blood volume integrated value") SF. The amplitude index is calculated accordingly. For example, the integration period coincides with the analysis period T (that is, the period corresponding to one beat of the beat). The integration period and the analysis period T may be different.

In the first embodiment, the amplitude index corresponds to the blood volume integrated value SM in which the normalized blood volume index MN is integrated for the analysis period T and the blood volume integrated value SF in which the normalized blood volume index FN is integrated for the analysis period T. Is calculated. The normalized blood volume index MN is a numerical value obtained by normalizing the blood volume index MA within the normalized range, and the normalized blood volume index FN is a numerical value obtained by normalizing the blood flow index FA within the normalized range.

FIG. 9 is a graph showing the time-varying MNT of the normalized blood flow rate index MN and the time-varying FNT of the normalized blood flow rate index FN, respectively. FIG. 9 shows a case where each of the blood volume index MA and the blood flow index FA is normalized to a normalization range of 0 or more and 1 or less. That is, the blood volume index MA and the blood flow rate index FA are normalized so that the minimum value Mmin and the minimum value Fmin in the analysis period T become 0 and the maximum value Mmax and the maximum value Fmax in the analysis period T become 1. Will be done. That is, the amplitude ΔMN of the normalized blood volume index MN and the amplitude ΔFN of the normalized blood flow index FN are 1. Specifically, the integrated blood volume value SM is the time-integrated value of the normalized blood volume index MN in the analysis period T, and the integrated blood flow value SF is the time-integrated value of the normalized blood volume index FN in the analysis period T. Is. The area of the area surrounded by the curve representing the time-varying MNT of the normalized blood volume index MN and the time axis (straight line of MN = 0) is the blood volume integrated value SM, and the time-varying FNT of the normalized blood volume index FN. It is also said that the area of the region surrounded by the curve representing the above and the time axis (straight line with FN = 0) is the blood flow integrated value SF.

FIG. 10 is a graph showing the relationship between the pulse wave velocity PWV actually measured for the subject and the ratio of the blood volume integrated value SM and the blood flow integrated value SF for a plurality of subjects. The pulse wave velocity PWV is an actually measured value by a known measurement technique. As can be seen from FIG. 10, the pulse wave velocity PWV correlates with the ratio of the integrated blood volume value SM and the integrated blood flow value SF (specifically, the ratio of the integrated blood volume value SF to the integrated blood volume value SM). The finding that it does is obtained. Based on the above findings, the resistance calculation unit 533 of the first embodiment calculates the ratio (SF / SM) of the blood volume integrated value SM and the blood flow volume integrated value SF as a resistance index.

The pulse pressure calculation unit 535 in FIG. 3 calculates the pulse pressure ΔP according to the amplitude index calculated by the amplitude calculation unit 531 and the resistance index calculated by the resistance calculation unit 533. Specifically, the pulse pressure calculation unit 535 calculates the pulse pressure ΔP according to the product of the amplitude index and the resistance index by using the above-mentioned mathematical formula (2). FIG. 11 is a graph showing the relationship between the pulse pressure ΔP actually measured for the subject and the product ((ΔF / ΔM) × (SF / SM)) of the amplitude index and the resistance index for each of the plurality of subjects. The pulse pressure ΔP is an actually measured value by a known measurement technique. As can be seen from FIG. 11, there is a correlation (specifically, a proportional relationship) between the product of the amplitude index and the resistance index and the pulse pressure ΔP. Therefore, the pulse pressure ΔP is expressed by the following mathematical formula (5a). As understood from the equation (5a), the pulse pressure ΔP can be calculated by multiplying the product of the amplitude index (ΔF / ΔM) and the resistance index (SF / SM) by a predetermined coefficient K. .. For example, the coefficient K is set according to the attributes of the subject (eg, age, gender and weight). As understood from the above description, the blood vessel calculation unit 53 functions as an element for calculating the pulse pressure ΔP according to the blood volume integrated value SM and the blood flow volume integrated value SF. The control device 21 causes the display device 23 to display the pulse pressure ΔP calculated by the blood vessel calculation unit 53.

FIG. 12 is a flowchart of a process (hereinafter referred to as “biological analysis process”) executed by the control device 21. The bioanalysis process of FIG. 12 is executed for each analysis period T on the time axis. When the bioanalysis process is started, the index calculation unit 51A generates a time-varying MT of the blood volume index MA in the analysis period T (Sa1). The above-mentioned formula (3a) or formula (3b) is used to calculate the blood volume index MA. Next, the index calculation unit 51A generates a time-varying FT of the blood flow index FA in the analysis period T (Sa2). The above-mentioned mathematical formula (4a) or mathematical formula (4b) is used to calculate the blood flow index FA.

The amplitude calculation unit 531 calculates the amplitude index according to the amplitude ΔM of the time change MT generated by the index calculation unit 51A and the amplitude ΔF of the time change FT (Sa3). Specifically, the ratio (ΔF / ΔM) of the amplitude ΔM and the amplitude ΔF is calculated as the amplitude index. Next, the resistance calculation unit 533 calculates the resistance index from the time change MT and the time change FT generated by the index calculation unit 51A (Sa4). Specifically, the ratio (SF / SM) of the integrated blood flow rate SM and the integrated blood flow rate SF is calculated as a resistance index. The pulse pressure calculation unit 535 calculates the pulse pressure ΔP according to the amplitude index calculated by the amplitude calculation unit 531 and the resistance index calculated by the resistance calculation unit 533 (Sa5). The process from step Sa3 to step Sa5 is a process of calculating the pulse pressure ΔP according to the blood volume integrated value SM and the blood flow rate integrated value SF. Specifically, the pulse pressure ΔP is calculated according to the product of the amplitude index and the resistance index. The control device 21 causes the display device 23 to display the pulse pressure ΔP calculated by the pulse pressure calculation unit 535 (Sa6). The order of the generation of the time-varying MT of the blood flow rate index MA (Sa1) and the generation of the time-varying FT of the blood flow rate index FA (Sa2) may be reversed. By executing the bioanalysis process described above for each analysis period T, a time series of a plurality of pulse pressures ΔP (that is, time changes of pulse pressure ΔP) is calculated.

FIG. 13 is a flowchart showing the specific contents of the process Sa4 for calculating the resistance index. The resistance calculation unit 533 calculates a normalized blood volume index MN and a normalized blood flow index FN in which each of the blood volume index MA and the blood flow volume index FA is normalized within the normalized range (Sa4-1). Next, the resistance calculation unit 533 calculates the blood volume integrated value SM and the blood flow integrated value SF obtained by integrating each of the normalized blood volume index MN and the normalized blood volume index FN for the analysis period T (Sa4-2). .. The resistance calculation unit 533 calculates the ratio (SF / SM) of the blood volume integrated value SM and the blood flow rate integrated value SF as a resistance index (Sa4-3).

As described above, in the first embodiment, the amplitude index (ΔF / ΔM) is calculated according to the amplitude ΔM of the time-varying MT of the blood volume index MA and the amplitude ΔF of the time-varying FT of the blood flow index FA. The resistance index (SF / SM) is calculated according to the blood volume integrated value SM and the blood flow volume integrated value SF, and the pulse pressure ΔP is calculated from the amplitude index and the resistance index. In principle, no cuff is required to calculate each of the above indexes (amplitude index, resistance index and pulse pressure ΔP). Therefore, it is possible to calculate the pulse pressure ΔP with high accuracy while reducing the physical load on the subject.

In the first embodiment, in particular, the product of the ratio of the amplitude ΔM to the amplitude ΔF (ΔF / ΔM) and the ratio of the blood volume integrated value SM to the blood flow integrated value SF (SF / SM) correlates with the pulse pressure ΔP. It is possible to calculate the pulse pressure ΔP with high accuracy by utilizing this tendency. Further, by taking the ratio of the amplitude ΔM of the blood volume index MA and the amplitude ΔF of the blood flow index FA, the amplitude index can be calculated with high accuracy even when the skin thickness changes.

<Second Embodiment>
A second embodiment of the present invention will be described. For the elements whose actions or functions are the same as those of the first embodiment in each of the embodiments exemplified below, the reference numerals used in the description of the first embodiment will be diverted and detailed description of each will be omitted as appropriate.

FIG. 14 is a block diagram of the bioanalytical device 100 according to the second embodiment. The bioanalytical device 100 of the second embodiment has a configuration in which a detection device 30B and a detection device 30C, an index calculation unit 51B, and an index calculation unit 51C are added to the bioanalysis device 100 of the first embodiment. In the first embodiment, the amplitude index and the resistance index are calculated using the detection signal ZA generated by the detection device 30A. On the other hand, in the second embodiment, the amplitude index is calculated using the detection signal ZA generated by the detection device 30A, and each of the two detection devices 30 (30B, 30C) separate from the detection device 30A is generated. The resistance index is calculated using the detection signal Z (ZB, ZC).

The detection device 30A of the second embodiment has the same configuration and function as that of the first embodiment, and generates a detection signal ZA according to the state of the measurement site H. The detection device 30B includes a light receiving unit R and a light emitting unit E similar to the detection device 30A, and generates a detection signal ZB according to the state of the measurement site H. Similarly, the detection device 30C includes a light receiving unit R and a light emitting unit E, and generates a detection signal ZC according to the state of the measurement site H. As the light emitting unit E of the detection device 30C, a light emitting element such as an LED (light emitting diode) that irradiates the measurement site H with incoherent light is preferably used. A VCSEL that emits coherent laser light may be used as the light emitting unit E. The light receiving unit R of the detection device 30C generates a detection signal ZC according to the light receiving level of the light passing through the measurement portion H, similarly to the light receiving unit R of the detection device 30B. The detection signal ZC is a signal representing a photoelectric volume pulse wave. A pressure sensor that generates a detection signal indicating the displacement of the surface of the measurement site H (that is, the displacement of the blood vessel diameter) may be adopted as the detection device 30C.

Similar to the first embodiment, the index calculation unit 51A of the second embodiment calculates the blood volume index MA and the blood flow rate index FA of the measurement site H from the detection signal ZA generated by the detection device 30A. Similar to the first embodiment, the index calculation unit 51A of the second embodiment calculates the amplitude index using the blood volume index MA and the blood flow index FA generated by the index calculation unit 51A.

The index calculation unit 51B calculates the blood flow index FB from the detection signal ZB generated by the detection device 30B. The blood flow index FB is calculated by the same method as the blood flow index FA (formula (4a) or formula (4b)). The index calculation unit 51C calculates the blood volume index MC from the detection signal ZC generated by the detection device 30C. As mentioned above, the blood volume index MA correlates with the blood vessel diameter. On the premise of the above relationship, the index calculation unit 51C calculates the displacement of the blood vessel diameter from the detection signal ZC, and calculates the blood volume index MC from the displacement of the blood vessel diameter.

The amplitude calculation unit 531 of the second embodiment calculates the amplitude index (ΔF / ΔM) from the blood volume index MA and the blood flow rate index FA calculated by the index calculation unit 51A, as in the first embodiment. The resistance calculation unit 533 of the second embodiment calculates the resistance index (SF / SM) from the blood flow index FB calculated by the index calculation unit 51B and the blood volume index MC calculated by the index calculation unit 51C. The method for calculating the resistance index is the same as that in the first embodiment. Similar to the first embodiment, the pulse pressure calculation unit 535 calculates the pulse pressure ΔP according to the amplitude index calculated by the amplitude calculation unit 531 and the resistance index calculated by the resistance calculation unit 533. Also in the second embodiment, the same effect as that of the first embodiment is realized.

<Third Embodiment>
In the first embodiment, the ratio (ΔF / ΔM) having a correlation with the blood flow velocity amplitude ΔV was calculated as an amplitude index. On the other hand, in the third embodiment, the blood flow velocity amplitude ΔV itself is calculated as an amplitude index. FIG. 15 is a block diagram of the bioanalytical device 100 according to the third embodiment. The bioanalyzing device 100 of the third embodiment has a configuration in which the detection device 30D is added to the bioanalyzing device 100 of the first embodiment.

The configuration and function of the detection device 30A of the third embodiment are the same as those of the first embodiment. The detection device 30D is an ultrasonic sensor module that generates a detection signal ZD according to the state of the measurement site H. Specifically, the detection device 30D includes a transmission unit ED and a reception unit RD. The transmitting unit ED transmits ultrasonic waves to the measurement site H. On the other hand, the receiving unit RD generates a detection signal ZD according to the reception level of the ultrasonic wave transmitted from the transmitting unit ED and passing through the measurement site H. For example, a piezoelectric element such as a piezoelectric ceramic is suitably used as a transmitting unit ED and a receiving unit RD.

The index calculation unit 51A of the third embodiment calculates the blood volume index MA and the blood flow index FA of the measurement site H from the detection signal ZA generated by the detection device 30A. The blood volume index MA and the blood flow index FA are calculated by the same method as in the first embodiment. Similar to the first embodiment, the resistance calculation unit 533 of the third embodiment calculates the resistance index by using the blood volume index MA and the blood flow index FA generated by the index calculation unit 51A.

The amplitude calculation unit 531 of the first embodiment calculated the amplitude index from the blood volume index MA and the blood flow volume index FA calculated by the index calculation unit 51A. On the other hand, the amplitude calculation unit 531 of the third embodiment directly calculates the amplitude index (blood flow velocity amplitude ΔV) from the detection signal ZD generated by the detection device 30D. Similar to the first embodiment, the pulse pressure calculation unit 535 calculates the pulse pressure ΔP according to the amplitude index (ΔV) calculated by the amplitude calculation unit 531 and the resistance index (SF / SM) calculated by the resistance calculation unit 533. Calculate.

Also in the third embodiment, the same effect as that of the first embodiment is realized. In particular, in the third embodiment, since the blood flow velocity amplitude ΔV is calculated as an amplitude index, the ratio (ΔF / ΔM) having a correlation with the blood flow velocity amplitude ΔV is calculated as an amplitude index with higher accuracy. It is possible to calculate the pulse pressure ΔP.

<Fourth Embodiment>
FIG. 16 is a graph showing the time-varying FT of the blood flow index F. As illustrated in FIG. 16, the area OF of the region surrounded by the curve representing the time-varying FT of the blood flow index F and the straight line of the minimum value Fmin is the blood obtained by integrating the normalized blood flow index FN for the analysis period T. It is equal to the product (ΔF × SF) of the flow integrated value SF and the amplitude ΔF. Further, the area OM of the region surrounded by the curve representing the time change MT of the blood volume index M and the straight line of the minimum value Mmin is the blood volume integrated value SM obtained by integrating the normalized blood volume index MN for the analysis period T. Equal to the product (ΔM × SM) with the amplitude ΔM. Therefore, the following formula (5b) is derived from the above formula (5a). As understood from the equation (5b), the pulse pressure ΔP is expressed as the product of the ratio of the area OF to the area OM (specifically, the ratio of the area OF to the area OM) and the coefficient K. For the above reasons, in the fourth embodiment, the pulse pressure ΔP is calculated from the area OF and the area OM.

FIG. 17 is a block diagram of the bioanalytical device 100 according to the fourth embodiment. The bioanalytical device 100 of the fourth embodiment has a configuration in which the amplitude calculation unit 531 and the resistance calculation unit 533 are deleted from the control device 21 of the bioanalysis device 100 of the first embodiment. Other configurations are the same as those in the first embodiment.

The pulse pressure calculation unit 535 of the fourth embodiment calculates the pulse pressure ΔP from the blood volume index MA and the blood flow rate index FA calculated by the index calculation unit 51A. The pulse pressure ΔP is calculated according to the integrated blood volume value SM in which the blood volume index MA is integrated for the analysis period T and the integrated blood volume value SF in which the blood flow index FA is integrated for the analysis period T. In the fourth embodiment, the pulse pressure calculation unit 535 calculates the area OM as the blood volume integrated value SM, and the area OF as the blood flow integrated value SF. That is, in the fourth embodiment, the process Sa3 for calculating the amplitude index and the process Sa4 for calculating the resistance index in FIG. 12 are omitted. Specifically, the pulse pressure calculation unit 535 calculates the area OM and the area OF, and calculates the pulse pressure ΔP by multiplying the ratio (OF / OM) of the area OF and the area OM by the coefficient K. The area OM corresponds to the blood volume integrated value SM obtained by integrating the blood volume index MA for the analysis period T, and the area OF corresponds to the blood flow integrated value SF obtained by integrating the blood volume index FA for the analysis period T.

Also in the fourth embodiment, as in the first embodiment, the effect that the cuff is unnecessary in principle is realized in the calculation of the pulse pressure ΔP. Therefore, it is possible to calculate the pulse pressure ΔP with high accuracy while reducing the physical load on the subject. In particular, in the fourth embodiment, the calculation of the amplitude ΔF and the amplitude ΔM and the normalization of the blood flow rate index F and the blood volume index M become unnecessary, so that the processing load for calculating the pulse pressure ΔP is reduced.

<Fifth Embodiment>
In the fifth embodiment, a configuration in which the blood pressure is calculated using the pulse pressure ΔP calculated in the first embodiment is illustrated. FIG. 18 is a block diagram of the bioanalytical device 100 according to the fifth embodiment. The bioanalytical device 100 of the fifth embodiment has a configuration in which the detection device 30E, the mean blood pressure calculation unit 55, and the blood pressure calculation unit 57 are added to the bioanalysis device 100 of the first embodiment. The mean blood pressure calculation unit 55 and the blood pressure calculation unit 57 are realized by the control device 21 executing the program stored in the storage device 22.

The detection device 30E is a detection device that generates a detection signal ZE according to the state of the measurement site H (specifically, the blood vessel inside the measurement site H). For example, a device such as an optical sensor module or an ultrasonic sensor module is suitably used as the detection device 30E. The mean blood pressure calculation unit 55 calculates the mean blood pressure Pave from the detection signal ZE generated by the detection device 30E. The mean blood pressure Pave in the analysis period T illustrated in FIG. 2 is calculated. Known techniques may be arbitrarily employed in the calculation of mean blood pressure Pave. The blood vessel calculation unit 53 calculates the pulse pressure ΔP as in the first embodiment.

The blood pressure calculation unit 57 in FIG. 18 calculates the blood pressure P from the pulse pressure ΔP calculated by the blood vessel calculation unit 53 and the mean blood pressure Pave calculated by the mean blood pressure calculation unit 55. The blood pressure calculation unit 57 of the fifth embodiment calculates systolic blood pressure Pmax and diastolic blood pressure Pmin. As exemplified in FIG. 2, the systolic blood pressure Pmax is the systolic blood pressure in the analysis period T, and the diastolic blood pressure Pmin is the diastolic blood pressure in the analysis period T. The following equations (6) and (7) are approximately established between the mean blood pressure Pave, the pulse pressure ΔP, the systolic blood pressure Pmax, and the diastolic blood pressure Pmin. The blood pressure calculation unit 57 calculates the systolic blood pressure Pmax by the following mathematical formula (6), and calculates the diastolic blood pressure Pmin by the following mathematical formula (7). The control device 21 causes the display device 23 to display the systolic blood pressure Pmax and the diastolic blood pressure Pmin calculated by the blood pressure calculation unit 57.

Also in the fifth embodiment, the same effect as that of the first embodiment is realized. In particular, in the fifth embodiment, since the blood pressure (systolic blood pressure Pmax and diastolic blood pressure Pmin) is calculated from the pulse pressure ΔP and the mean blood pressure Pave, the cuff is not required in principle in the calculation of the blood pressure.

<Sixth Embodiment>
FIG. 19 is a schematic diagram showing a usage example of the bioanalytical apparatus 100 in the sixth embodiment. As illustrated in FIG. 19, the bioanalytical device 100 includes a detection unit 71 and a display unit 72 that are configured as separate bodies from each other. The detection unit 71 includes the detection device 30 exemplified in each of the above-described embodiments. FIG. 19 illustrates a detection unit 71 in a form worn on the upper arm of a subject. As illustrated in FIG. 20, a detection unit 71 worn on the wrist of the subject is also suitable.

The display unit 72 includes the display device 23 exemplified in each of the above-described embodiments. For example, an information terminal such as a mobile phone or a smartphone is a suitable example of the display unit 72. However, the specific form of the display unit 72 is arbitrary. For example, a wristwatch-type information terminal that can be carried by the subject, or a dedicated information terminal of the bioanalytical device 100 may be used as the display unit 72.

An element for calculating the pulse pressure ΔP from the detection signal Z (hereinafter referred to as “calculation processing unit”) is mounted on the display unit 72, for example. The arithmetic processing unit includes the elements exemplified in FIG. 3 (index calculation unit 51 and blood vessel calculation unit 53). The detection signal Z generated by the detection device 30 of the detection unit 71 is transmitted to the display unit 72 by wire or wirelessly. The arithmetic processing unit of the display unit 72 calculates the pulse pressure ΔP from the detection signal Z and displays it on the display device 23. It is also possible to mount the mean blood pressure calculation unit 55 and the blood pressure calculation unit 57 exemplified in the fifth embodiment on the display unit 72.

The arithmetic processing unit may be mounted on the detection unit 71. The arithmetic processing unit calculates the pulse pressure ΔP from the detection signal Z generated by the detection device 30, and transmits data for displaying the pulse pressure ΔP to the display unit 72 by wire or wirelessly. The display device 23 of the display unit 72 displays the pulse pressure ΔP indicated by the data received from the detection unit 71. The arithmetic processing unit may transmit data for displaying the blood pressure calculated in the fifth embodiment to the display unit 72.

<Examination of the presence or absence of each configuration>
As illustrated in each of the above-described embodiments, the preferred embodiments of the present invention include a blood volume integrated value SM in which the blood volume index M is integrated for the integrated period, and a blood volume integrated value SF in which the blood volume index F is integrated for the integrated period. A configuration in which the pulse pressure ΔP is calculated according to the above (hereinafter referred to as “configuration A”) is adopted. The method of determining whether or not the actual bioanalytical device (hereinafter referred to as “actual product”) 90 adopts the configuration A will be described below. Hereinafter, the bioanalyzing device 100 confirmed to adopt the configuration A is referred to as "the product of the present application".

As illustrated in FIG. 21, the actual product 90 includes a detection device 91 including a light emitting unit E and a light receiving unit R, a processing unit 93 that calculates pulse pressure ΔPw from a detection signal output by the detection device 91, and a processing unit 93. It is provided with a display device 95 for displaying the pulse pressure ΔPw calculated by. It is assumed that a plurality of (for example, three or more types) test signals U having different waveforms within the analysis period T are sequentially supplied to the processing unit 93 of the actual product 90 and the control device of the product of the present application. For the actual product 90, each test signal U (U1, U2, U3) is supplied to the processing unit 93 (for example, wiring and terminals between the detection device 91 and the processing unit 93). For example, each test signal U is generated by a signal generator such as a pulse generator. The plurality of test signals U have different products ((ΔF / ΔM) × (SF / SM)) of the amplitude index and the resistance index. For example, among the products ((ΔF / ΔM) × (SF / SM)) calculated for each of the plurality of test signals U, a plurality of test signals so that the difference between the maximum value and the minimum value is more than doubled. Generate U. The test signal U may be generated for a waveform having a time length longer than the analysis period T.

It is assumed that the pulse pressure ΔPw of the subject is displayed as a measurement result on the display device 95 of the actual product 90. When the test signal U1 is supplied to the actual product 90, the pulse pressure ΔPw1 is displayed, when the test signal U2 is supplied to the actual product 90, the pulse pressure ΔPw2 is displayed, and when the test signal U3 is supplied to the actual product 90. It is assumed that the pulse pressure ΔPw3 is displayed. Further, the pulse pressure ΔP1 is displayed when the test signal U1 is supplied to the product of the present application, the pulse pressure ΔP2 is displayed when the test signal U2 is supplied to the product of the present application, and the pulse pressure ΔP2 is displayed when the test signal U3 is supplied to the product of the present application. It is assumed that the pressure ΔP3 is displayed.

FIG. 22 is a graph showing the relationship between the pulse pressure ΔPw displayed for the actual product 90 and the pulse pressure ΔP displayed for the product of the present application. When the configuration A is adopted for the actual product 90, the plurality of pulse pressures ΔPw (ΔPw1, ΔPw2, ΔPw3) measured by the actual product 90 and the plurality of pulse pressures ΔP (ΔP1, ΔP2, ΔP3) measured by the product of the present application are adopted. ) Is observed. Specifically, the correlation coefficient between the plurality of pulse pressures ΔPw displayed for the actual product 90 and the plurality of pulse pressures ΔP displayed for the product of the present application is 0.8 or more. In consideration of the above circumstances, the phase of the pulse pressure ΔPw calculated by supplying a plurality of test signals U to the actual product 90 and the pulse pressure ΔP calculated by supplying a plurality of test signals U to the product of the present application. When the number of relations is 0.8 or more, it is highly possible that the configuration A is adopted for the actual product 90. As the correlation coefficient, for example, Pearson's integrated correlation coefficient is suitable.

In the above description, the test signal U is supplied to the processing unit 93 of the actual product 90, but the light receiving unit R that generates the detection signal in the actual product 90 receives light such that the test signal U is generated. The pulse pressure ΔPw calculated in this way may be compared with the pulse pressure ΔP of the product of the present application. Further, in the above description, the pulse pressure ΔPw displayed on the display device 95 of the actual product 90 is compared with the pulse pressure ΔP displayed on the display device of the present product, but it is output from the processing unit 93 of the actual product 90. The presence or absence of the configuration A in the actual product 90 may be determined by comparing the data with the data output from the control device of the product of the present application.

In the above description, it is assumed for convenience that the actual product 90 displays the pulse pressure ΔPw, but the same applies when the actual product 90 displays the blood pressure P (systolic blood pressure Pmax and diastolic blood pressure Pmin) of the subject. By the method, it is possible to estimate the presence or absence of the configuration A in the actual product 90. That is, a plurality of blood pressures P measured by sequentially supplying a plurality of test signals U to the actual product 90 and a plurality of test signals U measured by sequentially supplying the product of the present application (fifth embodiment). Calculate the correlation coefficient between multiple blood pressures P. When the correlation coefficient is 0.8 or more, it is highly possible that the actual product 90 adopts the configuration A.

When the actual product 90 outputs the resistance index of the subject, the actual product 90 is provided with a configuration (hereinafter referred to as "configuration B") for calculating the ratio of the blood flow integrated value SM and the blood flow integrated value SF as the resistance index. It is possible to estimate whether or not to do so by the same method as described above. Specifically, a plurality of ratios (SF / SM) calculated by supplying a plurality of test signals U having different ratios (SF / SM) between the integrated blood volume value SM and the integrated blood flow value SF to the actual product 90. ) And the plurality of ratios (SF / SM) measured by sequentially supplying the plurality of test signals U to the product of the present application are calculated. When the correlation coefficient is 0.8 or more, it is highly possible that the actual product 90 adopts the configuration B.

When the actual product 90 outputs the amplitude index of the subject, whether or not the actual product 90 has a configuration (hereinafter referred to as “configuration C”) for calculating the ratio of the amplitude ΔM and the amplitude ΔF as the amplitude index is determined. It can be estimated by the same method as the above explanation. Specifically, a plurality of ratios (ΔF / ΔM) calculated by supplying a plurality of test signals U having different ratios (ΔF / ΔM) between the amplitude ΔM and the amplitude ΔF to the actual product 90, and a plurality of tests. The correlation coefficient with a plurality of ratios (ΔF / ΔM) calculated by sequentially supplying the signal U to the product of the present application is calculated. When the correlation coefficient is 0.8 or more, it is highly possible that the actual product 90 adopts the configuration B.

As described above, according to the configuration C, the effect that the amplitude index can be calculated with high accuracy even when the skin thickness changes is realized. Therefore, the presence or absence of the configuration C in the actual product 90 is also estimated by the following method. First, assuming a human body model in which a pseudo blood vessel through which blood flows is embedded, an amplitude index is calculated between the actual product 90 and the product of the present application for a plurality of cases in which the skin thickness of the human body model is changed. When the correlation coefficient between the plurality of amplitude indexes calculated by the actual product 90 and the plurality of amplitude indexes calculated by the product of the present application is 0.8 or more, the actual product 90 adopts the configuration C. There is a high possibility that it is. Further, for each of the actual product 90 and the product of the present application, the amplitude index is calculated between the actual product 90 and the product of the present application in a plurality of cases in which the distance between the light emitting unit E and the light receiving unit R is changed. When the correlation coefficient between the plurality of amplitude indexes calculated by the actual product 90 and the plurality of amplitude indexes calculated by the product of the present application is 0.8 or more, the actual product 90 adopts the configuration C. There is a high possibility that it is.

<Modification example>
Each of the above-exemplified forms can be variously modified. Specific modes of modification are illustrated below. It is also possible to appropriately merge two or more embodiments arbitrarily selected from the following examples.

(1) In the first embodiment, the ratio (SF / SM) of the integrated blood flow rate SM and the integrated blood flow rate SF is calculated as a resistance index, but the resistance index is not limited to the above examples. For example, the pulse wave velocity PWV itself can be calculated as a resistance index. FIG. 23 is a configuration diagram of the bioanalytical device 100 in the modified example. The bioanalytical device 100 in the modified example adds two detection devices 30 (30F, 30G) to the bioanalysis device 100 of the first embodiment, and replaces the resistance calculation unit 533 of the first embodiment with a PWV calculation unit 537. It is a configuration to be provided. Each detection device 30 (30F, 30G) is, for example, an optical sensor module similar to the detection device 30A, and generates a detection signal Z reflecting the state of the measurement site H. The PWV calculation unit 537 calculates the pulse wave velocity PWV as a resistance index by using the detection signal ZF generated by the detection device 30F and the detection signal ZG generated by the detection signal 30G. The pulse pressure calculation unit 535 calculates the pulse pressure ΔP according to the amplitude index calculated by the amplitude calculation unit 531 and the resistance index calculated by the PWV calculation unit 537. The above modifications can be applied to the second embodiment, the third embodiment, and the fifth embodiment.

(2) In each of the above-mentioned forms, the blood vessel calculation unit 53 calculates the pulse pressure ΔP, but the index calculated by the blood vessel calculation unit 53 is not limited to the pulse pressure ΔP. For example, using the calculated pulse pressure ΔP, the blood vessel calculation unit 53 may specify an index (for example, abnormal / high / normal, etc.) indicating the state of the pulse pressure ΔP of the subject. As understood from the above explanation, the index calculated by the blood vessel calculation unit 53 is comprehensively expressed as an index related to the pulse pressure ΔP (hereinafter referred to as “pulse pressure index”), and the pulse pressure index is the pulse pressure ΔP itself. And an index calculated using the pulse pressure ΔP.

Further, the blood vessel calculation unit 53 may calculate an index other than the pulse pressure index. Here, as arteriosclerosis progresses, vascular resistance tends to increase. As described above, since the resistance index correlates with vascular resistance, the resistance index can also be used as an index of arteriosclerosis. Therefore, the resistance index calculated by the blood vessel calculation unit 53 may be presented to the user. Specifically, the vascular resistance section calculates a resistance index according to the integrated blood volume value SM and the integrated blood flow value SF (calculates the ratio (SF / SM) as a resistance index), and displays the resistance index. Displayed on the device 23. Further, the blood vessel calculation unit 53 may calculate the ratio (SF / SM) and calculate the pulse wave velocity PWV from the ratio (SF / SM) as a resistance index. Further, the blood vessel calculation unit 53 may calculate, for example, an index indicating the degree of arteriosclerosis as a resistance index from the calculated ratio (SF / SM) or the pulse wave velocity PWV. That is, the resistance index is comprehensively expressed as an index relating to the vascular resistance of the living body. As understood from the above explanation, the index calculated by the blood vessel calculation unit 53 is comprehensively expressed as an index related to blood vessels (hereinafter referred to as “blood vessel index”), and the blood vessel index includes both a pulse pressure index and a resistance index. Is included. That is, the blood vessel calculation unit 53 calculates the blood vessel index according to the blood volume integrated value SM and the blood volume integrated value SF (typically according to the ratio of the blood volume integrated value SM and the blood flow integrated value SF). Functions as an element to do.

Further, the blood vessel calculation unit 53 may calculate the amplitude index and display the amplitude index on the display device 23. As understood from the above explanation, the amplitude index and the resistance index calculated by the blood vessel calculation unit 53 may be presented to the subject as independent indexes. Even in the configuration where the amplitude index or resistance index is calculated as an independent index, the cuff is not required in principle, so that each index can be calculated with high accuracy while reducing the physical load on the subject. ..

(3) In the first embodiment, the ratio (SF / SM) of the integrated blood volume value SM and the integrated blood flow value SF is calculated as the resistance index, but the value calculated as the resistance index is the ratio (SF / SM). Not limited. For example, a configuration in which the ratio (SF / SM) is substituted into a predetermined function to calculate the resistance index, or a configuration in which the ratio (SF / SM) is multiplied by a coefficient to calculate the resistance index can be adopted. Further, for example, a configuration in which the difference between the integrated blood flow rate SM and the integrated blood flow rate SF is calculated as a resistance index can be adopted. However, according to the configuration in which the resistance index is calculated using the ratio of the blood volume integrated value SM and the blood flow integrated value SF, the ratio of the blood volume integrated value SM and the blood flow integrated value SF is the pulse wave velocity. The resistance index can be calculated with high accuracy by using the tendency of correlation. The above modifications can be applied to the second embodiment, the third embodiment, and the fifth embodiment.

(4) In the first embodiment, the ratio (ΔF / ΔM) of the amplitude ΔF and the amplitude ΔM is calculated as the amplitude index, but the value calculated as the amplitude index is not limited to the ratio (ΔF / ΔM). For example, a configuration in which the ratio (ΔF / ΔM) is substituted into a predetermined function to calculate the amplitude index, or a configuration in which the ratio (ΔF / ΔM) is multiplied by a coefficient to calculate the amplitude index can be adopted. Further, for example, a configuration in which the difference between the amplitude ΔF and the amplitude ΔM is calculated as an amplitude index can be adopted. However, according to the configuration in which the amplitude index is calculated using the ratio of the amplitude ΔF and the amplitude ΔM, the tendency that the ratio (ΔF / ΔM) between the amplitude ΔM and the amplitude ΔF and the blood flow velocity correlate is used. , The amplitude index can be calculated with high accuracy. In addition, the amplitude index can be calculated while reducing the influence of the skin thickness.

(5) In each of the above-mentioned forms, the time-varying MT of the blood volume index M in one analysis period T was used for calculating the pulse pressure ΔP, but the time-varying MT of the blood volume index M in each of the plurality of analysis periods T. The time-varying MT averaged over a plurality of analysis periods T may be used to calculate the pulse pressure ΔP. As for the blood flow index F, the time change FT obtained by averaging the time change FT of the blood flow index F in each of the plurality of analysis periods T over the plurality of analysis periods T may be used for calculating the pulse pressure ΔP.

(6) In the first embodiment, each of the blood volume index MA and the blood flow index FA is normalized to the normalization range of 0 or more and 1 or less, but the blood volume index MA and the blood flow index FA are in the common range. Once normalized, the upper and lower limits of the normalization range are arbitrary. The above modifications can be applied to the second embodiment, the third embodiment, and the fifth embodiment.

(7) In each of the above-described embodiments, the bioanalytical device 100 configured as a single device is exemplified, but as shown in the following examples, a plurality of elements of the bioanalytical device 100 can be realized as devices that are separate from each other. .. In the following description, the element for calculating the pulse pressure ΔP from the detection signal ZA is referred to as “calculation processing unit 27”. The arithmetic processing unit 27 includes, for example, the elements exemplified in FIG. 3 (index calculation unit 51 and blood vessel calculation unit 53).

In each of the above-described embodiments, the bioanalytical device 100 including the detection device 30 (30A, 30B, 30C, 30D, 30E) is exemplified, but as illustrated in FIG. 24, the detection device 30 is referred to as the bioanalysis device 100. A separate configuration is also assumed. The detection device 30 is a portable optical sensor module mounted on the measurement site H such as the wrist or upper arm of the subject. The bioanalysis device 100 is realized by an information terminal such as a mobile phone or a smartphone. The bioanalytical device 100 may be realized by a wristwatch type information terminal. The detection signal Z generated by the detection device 30 is transmitted to the bioanalysis device 100 by wire or wirelessly. The arithmetic processing unit 27 of the bioanalytical device 100 calculates the pulse pressure ΔP from the detection signal Z and displays it on the display device 23. As understood from the above description, the detection device 30 may be omitted from the bioanalysis device 100.

In each of the above-described embodiments, the bioanalytical device 100 including the display device 23 is illustrated, but as illustrated in FIG. 25, a configuration in which the display device 23 is separate from the bioanalysis device 100 is also assumed. The arithmetic processing unit 27 of the bioanalytical device 100 calculates the pulse pressure ΔP from the detection signal Z, and transmits data for displaying the pulse pressure ΔP to the display device 23. The display device 23 may be a dedicated display device, but may be mounted on, for example, an information terminal such as a mobile phone or a smartphone, or a wristwatch-type information terminal that can be carried by a subject. The pulse pressure ΔP calculated by the arithmetic processing unit 27 of the bioanalytical device 100 is transmitted to the display device 23 by wire or wirelessly. The display device 23 displays the pulse pressure ΔP received from the bioanalytical device 100. As understood from the above description, the display device 23 may be omitted from the bioanalytical device 100.

As illustrated in FIG. 26, it is assumed that the detection device 30 and the display device 23 are separate from the bioanalysis device 100 (calculation processing unit 27). For example, the bioanalytical device 100 (calculation processing unit 27) is mounted on an information terminal such as a mobile phone or a smartphone.

It is also possible to mount the index calculation unit 51 on the detection device 30 in a configuration in which the detection device 30 and the bioanalysis device 100 are separated. The blood volume index M and the blood flow index F calculated by the index calculation unit 51 are transmitted from the detection device 30A to the bioanalysis device 100 by wire or wirelessly. As understood from the above description, the index calculation unit 51 may be omitted from the bioanalytical device 100.

(8) In each of the above-described embodiments, the wristwatch-type bioanalytical device 100 including the housing portion 12 and the belt 14 is exemplified, but the specific form of the bioanalytical device 100 is arbitrary. For example, a patch type that can be attached to the subject's body, an ear-mounted type that can be attached to the subject's ear, a finger-mounted type that can be attached to the subject's fingertips (for example, a nail-attached type), or a subject's head that can be attached. Any form of bioanalytical device 100, such as a head-mounted type, can be adopted.

(9) In each of the above-described embodiments, the pulse pressure ΔP of the subject is displayed on the display device 23, but the configuration for notifying the subject of the pulse pressure ΔP is not limited to the above examples. For example, it is also possible to notify the subject of the pulse pressure ΔP by voice. In the ear-worn bioanalytical apparatus 100 that can be worn on the selvage of the subject, a configuration in which the pulse pressure ΔP is notified by voice is particularly suitable. Further, it is not essential to notify the subject of the pulse pressure ΔP. For example, the pulse pressure ΔP calculated by the bioanalytical device 100 may be transmitted from the communication network to another communication device. Further, the pulse pressure ΔP may be stored in a portable recording medium that can be attached to and detached from the storage device 22 of the bioanalytical device 100 or the bioanalytical device 100.

(10) The bioanalytical device 100 according to each of the above-described embodiments is realized by the cooperation between the control device 21 and the program as described above. The program according to a preferred embodiment of the present invention may be provided and installed in a computer in a form stored in a computer-readable recording medium. It is also possible to provide a program stored in a recording medium included in a distribution server to a computer in the form of distribution via a communication network. The recording medium is, for example, a non-transitory recording medium, and an optical recording medium (optical disc) such as a CD-ROM is a good example, but a known arbitrary such as a semiconductor recording medium or a magnetic recording medium. Can include recording media in the form of. The non-transient recording medium includes any recording medium other than the transient propagation signal (transitory, propagating signal), and does not exclude the volatile recording medium.

100 ... Bioanalysis device, 12 ... Housing unit, 14 ... Belt, 21 ... Control device, 22 ... Storage device, 23 ... Display device, 27 ... Arithmetic processing unit, 30 ... Detection device, 51 ... Index calculation unit, 53 ... Blood vessel calculation unit, 55 ... mean blood pressure calculation unit, 57 ... blood pressure calculation unit, 513 ... amplitude calculation unit, 533 ... resistance calculation unit, 535 ... pulse pressure calculation unit, 537 ... PWV calculation unit, 71 ... detection unit, 72 ... display Unit, 90 ... actual product, 91 ... detection device, 93 ... processing unit, E ... light emitting unit, ED ... transmitting unit, R ... light receiving unit, RD ... receiving unit.

Claims (12)

The blood volume index related to the blood volume of the living body is integrated for the integrated period corresponding to one beat of the pulsation of the living body, and the blood volume index related to the blood flow volume of the living body is integrated for the integrated period. A biological analysis device provided with a blood vessel calculation unit that calculates a blood vessel index related to the blood vessel of the living body according to the integrated flow rate value. The bioanalytical device according to claim 1, which calculates the blood vessel index according to the ratio of the integrated blood volume value to the integrated blood volume value. The blood vessel index is the bioanalytical device according to claim 1 or 2, which is a pulse pressure index related to pulse pressure. The pulse pressure of the living body according to the integrated blood volume value obtained by accumulating the blood volume index related to the blood volume of the living body for the integration period and the integrated blood volume index obtained by accumulating the blood flow index relating to the blood flow volume of the living body for the integration period. Equipped with a blood vessel calculation unit that calculates the pulse pressure index for
The blood vessel calculation unit
An amplitude calculation unit that calculates the ratio of the time change amplitude of the blood volume index to the time change amplitude of the blood flow index as an amplitude index relating to the time change amplitude of the blood flow velocity of the living body.
A resistance calculation unit that calculates the ratio of the blood volume integrated value and the blood flow integrated value as a resistance index related to the vascular resistance of the living body.
A bioanalyzer including a pulse pressure calculation unit that calculates the pulse pressure index according to the amplitude index and the resistance index. The resistance calculation unit calculates the blood volume integrated value obtained by integrating the value obtained by normalizing the blood volume index within the normalized range for the integration period, and the value obtained by normalizing the blood flow index within the normalized range. The bioanalyzer according to claim 4, wherein the ratio with the integrated blood flow value integrated for the integration period is calculated as the resistance index. The blood vessel index is the biological analysis device according to claim 1 or 2, which is a resistance index relating to the vascular resistance of the living body. The biological analysis device according to any one of claims 1 to 6, which is attached to the upper arm or wrist of the living body. A light emitting part that irradiates a living body with laser light,
A light receiving unit that receives the laser beam reflected inside the living body, and a light receiving portion.
An index calculation unit that calculates a blood volume index relating to the blood volume of the living body and a blood flow index relating to the blood flow volume of the living body by using a detection signal indicating the light receiving level by the light receiving unit.
A blood vessel calculation unit that calculates a blood vessel index related to a blood vessel of a living body according to a blood volume integrated value obtained by integrating the blood volume index for an integrated period and a blood vessel integrated value obtained by accumulating the blood volume index for the integrated period. A bioanalyzer equipped with. A light emitting part that irradiates a living body with laser light,
A light receiving unit that receives the laser beam reflected inside the living body, and a light receiving portion.
An index calculation unit that calculates a blood volume index relating to the blood volume of the living body and a blood flow index relating to the blood flow volume of the living body by using a detection signal indicating the light receiving level by the light receiving unit.
A blood vessel calculation unit that calculates a blood vessel index related to a blood vessel of a living body according to a blood volume integrated value obtained by integrating the blood volume index for an integrated period and a blood vessel integrated value obtained by accumulating the blood volume index for the integrated period. Equipped with
The index calculation unit
A bioanalyzer that calculates the blood volume index by integrating the intensities of each frequency in the intensity spectrum with respect to the frequency of the detection signal for a predetermined frequency range. The index calculation unit
The bioanalyzer according to claim 8 or 9, wherein the product of the intensity of each frequency in the intensity spectrum relating to the frequency of the detection signal and the frequency is integrated over a predetermined frequency range to calculate the blood flow index. The blood volume index related to the blood volume of the living body is integrated for the integrated period corresponding to one beat of the pulsation of the living body, and the blood volume index related to the blood flow volume of the living body is integrated for the integrated period. A biological analysis method for calculating a blood vessel index relating to a blood vessel of the living body according to the ratio with the integrated flow rate value. The blood volume index related to the blood volume of the living body is integrated for the integrated period corresponding to one beat of the pulsation of the living body, and the blood volume index related to the blood flow volume of the living body is integrated for the integrated period. A program that makes a computer function as a blood vessel calculation unit that calculates blood vessel indexes related to the blood vessels of the living body according to the ratio with the integrated flow rate.

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