JP2018149157A - Biological information acquisition system and biological information acquisition method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a biological information acquisition system capable of measuring density of a prescribed substance of an organism with excellent reliability, and a biological information acquisition method.SOLUTION: A biological information acquisition system includes: a light source for emitting excitation light and irradiating an organism; a sensor substance for being embedded into the organism, and including a signal substance receiving the excitation light and discharging first light according to density of a prescribed substance in the organism and a reference substance discharging second light not affected by the density; a first light-receiving part for receiving the first light; and a second light-receiving part for receiving the second light. The biological information acquisition system corrects a light-receiving result of the first light-receiving part by a light-receiving result of the second light-receiving part and calculates the density.SELECTED DRAWING: Figure 3

Description

  Along with the recent improvement in health-consciousness, blood glucose, lactic acid levels, antibody levels, and enzyme levels in body fluids such as blood, interstitial fluid, saliva, and sweat in specific individuals are measured over time to improve health. Management is carried out.

  For example, for diabetics, measuring blood glucose levels over time (monitoring) is particularly important.

  Here, diabetic patients are classified into type I and type II depending on their symptoms, but both do not have normal insulin secretion from the pancreas, which prevents the body organs from taking glucose (glucose) normally, Metabolic abnormalities cause weight loss. Furthermore, if a high blood glucose level is maintained for a long time, serious symptoms such as “diabetic retinopathy”, “diabetic nephropathy”, “diabetic microangiopathy”, “diabetic neuropathy”, etc. It is known that complications will develop. In order to prevent the onset of such serious complications, patients with persistent hyperglycemia are treated with insulin to administer insulin by injection to maintain blood glucose levels within the normal range. is the current situation.

  Since patients with type I diabetes have no secretion of insulin due to pancreatic disease, they must measure blood sugar levels by blood sampling several times a day (minimum before meals and 4 times before going to bed) and administer insulin. As for the timing of administration, in order to suppress an excessive increase in postprandial blood glucose level, the blood glucose level before meal is measured, the calorie of the meal amount is calculated, the dose of insulin is determined, and injection is administered before meal . In addition, what is known as an increase in blood glucose level is a symptom called a “disease phenomenon”, and the blood glucose level increases at dawn 8 to 10 hours after going to bed. However, in order to cope with this physiological phenomenon, it is necessary to wake up once before dawn, measure blood sugar level by blood sampling, and administer insulin if blood sugar level is high.

  From the above, there is a need for a device that can measure blood glucose level at a desired timing. As this device, for example, using a blood glucose level sensor, the glucose concentration in a patient's blood or interstitial fluid can be measured using excitation light. Proposals have been made for measurement using a luminescent substance that emits fluorescence upon irradiation.

  As a basic principle of glucose quantitative measurement using this fluorescent substance, the fluorescent substance emits fluorescence having different wavelengths (peak wavelengths) when glucose is bonded and when glucose is not bonded. Therefore, irradiate the fluorescent material with excitation light, measure the emission intensity of the fluorescence emitted when the fluorescent substance is bound to glucose, and calculate the amount of glucose based on this emission intensity. Is possible. This is because it is possible to monitor the blood glucose level by using such a fluorescent substance.

  By the way, in recent years, as a measuring device that automatically monitors a blood glucose level, which is required to be measured at the timing as described above, over time (continuously) in order to improve the QOL of the patient and the patient's family. A device for the purpose of monitoring a glucose level in a patient's interstitial fluid for a long period of time by implanting a blood glucose sensor in the body (dermis), a so-called continuous glucose monitor (CGM) device using a fluorescent substance has been proposed. Has been made.

  In this continuous glucose monitor (CGM) device, for example, the concentration of glucose in the interstitial fluid using the fluorescent substance is obtained by setting the above-described film (sensor) containing the fluorescent substance in the dermis. It has been proposed to carry out the measurement of chronologically (continuously) and automatically.

  For example, in Patent Document 1, the main body of the measuring apparatus is formed in a capsule shape, and a film (fluorescent indicator) containing a fluorescent material is provided on the outer peripheral portion of the main body, and the fluorescent material is irradiated with excitation light inside the main body. A measuring apparatus having a configuration in which a light source (radiation source) that receives light and a light receiving unit (detector) that receives fluorescence emitted from a fluorescent material is embedded in the body (dermis) has been proposed.

  In Patent Document 2, the fluorescent material is a gel-like bead (gel bead), the gel bead is embedded in the body (dermis), and the body of the measuring device is irradiated with excitation light to the fluorescent material. And a light receiving unit (photodetector) for receiving fluorescence emitted from a fluorescent material, and a measuring apparatus configured to attach the main body to the epidermis has been proposed.

  However, in the measuring devices of Cited Documents 1 and 2, noise caused by outside light other than the light source such as sunlight and illumination light occurs, or in the measuring device of Cited Document 2, the distance between the fluorescent material and the light receiving unit is increased. A difference occurs every time the main body is mounted on the epidermis, and as a result, a deviation occurs in the emission intensity of the fluorescence received by the light receiving unit. For this reason, the glucose concentration calculated based on the emission intensity of the fluorescence emitted from the fluorescent substance also causes a deviation. Therefore, there is a problem that the glucose concentration cannot be measured with excellent reliability in the measurement by the measuring apparatus having such a configuration.

  In addition to such a problem, in addition to the measurement device (biological information acquisition system) that calculates the glucose concentration in the interstitial fluid based on the measured emission intensity of the fluorescent substance, the lactic acid value in the body fluid, the amount of antibody, This also occurs in a measuring apparatus (biological information acquisition system) that calculates a predetermined substance such as an enzyme amount based on the emission intensity of a fluorescent substance.

JP 2011-107129 A JP 2014-40443 A

  One of the objects of the present invention is to provide a biological information acquisition system and a biological information acquisition method capable of measuring the concentration of a predetermined substance in a living body with excellent reliability.

Such an object is achieved by the present invention described below.
The biological information acquisition system of the present invention comprises a light source for emitting excitation light and irradiating the living body
A sensor substance for embedding in the living body, which receives the excitation light and emits a first light according to the concentration of the predetermined substance in the living body, and a second light that is not affected by the concentration A reference substance to be released, and a sensor substance comprising:
A first light receiving unit for receiving the first light;
A second light receiving unit for receiving the second light,
The light reception result of the first light receiving unit is corrected by the light reception result of the second light receiving unit, and the density is calculated.

  Thereby, in the biological information acquisition system of the present invention, the concentration of the predetermined substance can be measured with excellent reliability.

  In the biological information acquisition system of the present invention, the separation distance between the second light receiving unit and the sensor substance can be obtained based on the intensity of the second light received by the second light receiving unit. preferable.

  As described above, by using the intensity of the second light received by the second light receiving unit as the light reception result of the second light receiving unit, the second light receiving unit and the sensor substance are used. The separation distance can be obtained.

  In the biological information acquisition system of the present invention, it is preferable that the corrected density is obtained based on the separation distance and the intensity of the first light received by the first light receiving unit.

  As described above, by using the intensity of the first light received by the first light receiving unit as the light reception result of the first light receiving unit, the intensity of the first light and the separation distance are used. The corrected density can be obtained.

  In the biological information acquisition system of the present invention, it is preferable that the correction is performed by synchronously detecting the light reception result of the first light receiving unit and the light reception result of the second light receiving unit using the frequency of the light source.

  By using such synchronous detection, in particular, noise caused by external light such as sunlight or illumination light entering at least one of the first light receiving unit and the second light receiving unit can be more reliably reduced. Can do. As a result, the calculated concentration of the predetermined substance can be obtained with higher reliability.

  In the biological information acquisition system of the present invention, it is preferable to have a calculation unit that calculates the density by correcting the light reception result of the first light receiving unit with the light reception result of the second light receiving unit.

  By providing such a calculation part, the said density | concentration can be calculated | required using the body information system of this invention.

  In the biological information acquisition system of the present invention, it is preferable that the predetermined substance is glucose.

  The biological information acquisition system of the present invention is preferably applied to the calculation of the concentration of glucose as the predetermined substance, and can measure the glucose concentration as the predetermined substance with excellent reliability.

The biological information acquiring method of the present invention receives excitation light from a light source and emits a signal substance that emits first light according to the concentration of a predetermined substance in the living body and second light that is not affected by the concentration. An excitation light irradiating step for irradiating the sensor substance, which includes a reference substance, and is previously embedded in the living body, with the excitation light;
A first light receiving step of receiving the first light using a first light receiving unit and obtaining a light reception result of the first light receiving unit;
A second light receiving step of receiving the second light using a second light receiving unit and obtaining a light reception result of the second light receiving unit;
And a calculation step of correcting the light reception result of the first light receiving unit with the light reception result of the second light receiving unit to obtain the density.

Thereby, in the biological information acquisition method of the present invention, the concentration of the predetermined substance can be measured with excellent reliability.

  In the biological information acquisition method of the present invention, in the calculating step, the second light receiving unit is separated from the sensor substance based on the intensity of the second light received by the second light receiving unit. It is preferable to determine the distance.

  As described above, by using the intensity of the second light received by the second light receiving unit as the light reception result of the second light receiving unit, the second light receiving unit and the sensor substance are used. The separation distance can be obtained.

  In the biological information acquisition method of the present invention, in the calculation step, the corrected density is obtained based on the separation distance and the intensity of the first light received by the first light receiving unit. preferable.

  As described above, by using the intensity of the first light received by the first light receiving unit as the light reception result of the first light receiving unit, the intensity of the first light and the separation distance can be used. The corrected density can be obtained.

It is a perspective view showing typically a 1st embodiment of a living body information acquisition system of the present invention. It is a side view which shows the state which mounted | wore the skin with the detection element which 1st Embodiment of the biometric information acquisition system of this invention has. It is a longitudinal cross-sectional view which shows the main-body part with which the detection element shown in FIG. 2 is provided. It is a block diagram which shows the circuit structure of the biometric information acquisition system shown in FIG. It is a flowchart which shows the measuring method which measures glucose concentration using the biometric information acquisition system of 1st Embodiment. It is a longitudinal cross-sectional view which shows the main-body part with which the detection element which 2nd Embodiment of the biometric information acquisition system of this invention has is provided. It is a flowchart which shows the measuring method which measures glucose concentration using the biometric information acquisition system of 2nd Embodiment.

  Hereinafter, a biological information acquisition system and a biological information acquisition method of the present invention will be described in detail based on embodiments shown in the accompanying drawings.

  In this embodiment, the biological information acquisition system (measuring device) of the present invention uses the intensity of fluorescence emitted from the fluorescent substance (signal substance) in a state where the glucose concentration in the interstitial liquid is in contact with the interstitial liquid. Based on the above, a case where the present invention is applied to a continuous glucose monitor (CGM) device (implantable continuous blood glucose meter) that continuously and automatically monitors over a long period will be described as an example.

  That is, a case where the concentration of glucose as a predetermined substance (target substance) is automatically measured over time using a continuous glucose monitor (CGM) device will be described as an example. In this continuous glucose monitor (CGM) device, the concentration of glucose as a predetermined substance (glucose concentration) emits (releases) fluorescence (first light) having a predetermined wavelength in accordance with the binding with glucose. It is calculated by measuring the fluorescence intensity of (signal substance) and using this intensity.

<Biological information acquisition system (measuring device)>
<< First Embodiment >>
First, a first embodiment of the biological information acquisition system of the present invention will be described.

  FIG. 1 is a perspective view schematically showing a first embodiment of the biological information acquisition system of the present invention, and FIG. 2 is a state in which the detection element of the first embodiment of the biological information acquisition system of the present invention is attached to the skin. FIG. 3 is a longitudinal sectional view showing a main body provided in the detection element shown in FIG. 2, and FIG. 4 is a block diagram showing a circuit configuration of the biological information acquisition system shown in FIG. In the following description, the upper side in FIGS. 2 and 3 is referred to as “upper” and the lower side is referred to as “lower”.

  As shown in FIGS. 1 and 2, the biological information acquisition system 101 (optical sensor) is based on the detection element 100, the circuit unit 400 for obtaining the intensity based on the glucose concentration in the detection element 100, and the obtained intensity. A control unit 210 having a calculation unit 200 for calculating a glucose concentration, a monitor (display unit) 151 for displaying a measurement value (glucose concentration) obtained by calculation by the control unit 210, and various operations such as input An operation unit 212 that performs the above operation, a connector 131 that connects the detection element 100 to the control unit 210, and a wiring 132 that connects the detection element 100 and the connector 131. In the present embodiment, the control unit 210, the monitor 151, the operation unit 212, and the connector 131 provided in the biological information acquisition system 101 are provided in the main body 155, and the detection element 100 and the main body 155 are connected by the wiring 132.

  As shown in FIGS. 1 to 3, the detection element 100 includes a main body 110 attached to the skin epidermis 501 and a sensor film 120 embedded (detained) in the dermis 502.

  In the detection element 100, the main body 110 irradiates the sensor film 120 embedded in the dermis 502 with excitation light, and this excitation light causes the fluorescent substance contained in the sensor film 120 to emit fluorescence, The main body 110 receives the fluorescence.

  At this time, the fluorescence wavelength (peak wavelength) emitted from the fluorescent material differs depending on whether glucose is bonded to the fluorescent material or not, and is emitted when glucose is bonded to the fluorescent material. The intensity of the wavelength is dependent on the glucose concentration contained in the interstitial fluid contained in the dermis 502. Therefore, the glucose concentration is calculated based on this intensity.

  In the present embodiment, the sensor film 120 (sensor substance) has a film shape as a whole, and is embedded in a living body (dermis 502). Then, upon receiving the excitation light, glucose contained in the interstitial fluid is bound to emit fluorescence (first light) having a unique wavelength (peak wavelength; first wavelength), and It contains a fluorescent substance (signal substance) that emits light with an intensity (fluorescence intensity) corresponding to the glucose concentration in the interstitial fluid.

  As this fluorescent substance, for example, 9,10-bis [N- [2- (5,5-dimethylborinan-2-yl) benzyl] -N- [6 ′-[(acryloyl polyethylene glycol-3400) carbonyl Amino] -n-hexylamino] methyl] -2-acetylanthracene (F-PEG-AAm) and the like. When such a fluorescent substance is included in the sensor film 120, it receives excitation light from the main body 110, and emits fluorescence (first light) with an intensity corresponding to the glucose concentration in the interstitial fluid.

  Furthermore, in the present invention, in addition to the fluorescent substance, the sensor film 120 is not affected by the presence or absence of glucose in the interstitial fluid, and has fluorescence (second light) having a specific wavelength (peak wavelength; second wavelength). ) Is included. At this time, the wavelength (second wavelength) of the fluorescence (second light) emitted from the reference substance is different from the wavelength (first wavelength) of the fluorescence (first light) emitted from the fluorescent substance. Selected.

  As the reference substance, the above-mentioned fluorescent substance coated so that it does not come into contact with the interstitial fluid can be used, and a lanthanide complex as described in JP-A-63-70151 can be used against oxygen. The thing coated so that it may not contact is mentioned. By including such a reference substance in the sensor film 120, the excitation light from the main body 110 is received, and the fluorescence (with the intensity corresponding to the intensity of the excitation light (depending on the glucose concentration in the interstitial fluid) ( Second light) is emitted.

  As described above, in the present invention, the sensor film 120 (sensor substance) receives excitation light and emits (releases) fluorescence (first light) corresponding to glucose (predetermined substance) in the interstitial fluid (living body). ) And a reference substance that emits (releases) fluorescence (second light) that is not affected by the concentration of glucose in the interstitial fluid.

  In addition, the fluorescent substance and the reference substance may be included in the sensor film 120 as separate bodies, but are preferably included as a linked body. Thereby, since the content of the fluorescent substance and the reference substance contained in the sensor film 120 becomes uniform, it is possible to accurately vary the intensity of the first light and the second light emitted by the excitation light. It can be suppressed or prevented.

  Further, the depth at which the sensor film 120 is embedded (detained) in the dermis 502 is usually set such that the distance from the epidermis 501 is preferably about 1 mm to 10 mm, and more preferably about 2 mm to 4 mm. By setting the depth within such a range, the excitation light from the main body 110 can reach the sensor film 120, and the first light and the second light emitted from the sensor film 120 are transmitted to the main body. Part 110 can be reached.

  In the present embodiment, the sensor film 120 having a film shape is embedded as the sensor substance to be embedded in the living body. However, the sensor substance is not limited to this, and the sensor substance may have a shape such as a particle shape, a gel shape, or a scale shape. Is not limited.

  The main body 110 is disposed in a housing 150 whose overall shape is a dome shape, and in a hollow portion provided in the housing 150, irradiates the sensor film 120 with excitation light, and has a first wavelength from the sensor film 120. And a detector 300 that receives the fluorescence (first light) and the second wavelength fluorescence (second light).

  The casing 150 includes an adhesive layer on the lower surface, and the main body 110 is attached (fixed) to the outer skin 501 by bringing the lower surface into contact with the outer skin 501. In addition, the lower surface of the housing 150 is light transmissive, so that the excitation light from the detection unit 300 is irradiated onto the sensor film 120 via the lower surface of the housing 150, and the first light from the sensor film 120 is irradiated. Light and second light are introduced into the detection unit 300 via the lower surface of the housing 150.

  As illustrated in FIG. 3, the detection unit 300 includes a substrate 310, a light source 320 that emits excitation light, a first light receiving unit 330, and a second light receiving unit 340.

  The substrate 310 (base substrate) supports each part constituting the detection unit 300, that is, the light source 320, the first light receiving unit 330, and the second light receiving unit 340. In addition, wiring 132 is connected to the substrate 310, and each unit constituting the detection unit 300 and the control unit 210 are electrically connected.

  The light source 320 emits excitation light and irradiates the skin (epidermis 501) that is a living body with the excitation light, so that the excitation light is applied to the sensor film 120 embedded (detained) in the dermis 502 in the deep part. For irradiating.

  The light source 320 is not particularly limited as long as the fluorescent material and the reference material included in the sensor film 120 include excitation light that emits the first light and the second light, respectively. For example, a light emitting diode (LED ), Organic electroluminescent elements (organic EL elements), various light emitting elements such as laser light emitting elements. The excitation light emitted from the light source 320 (various light emitting elements) may include any of infrared light, visible light, and ultraviolet light.

  The first light receiving unit 330 receives the fluorescence (first light) emitted from the fluorescent material when the sensor film 120 is irradiated with the excitation light, and the intensity (first intensity) of the first light. It is for measuring.

  The first light receiving unit 330 is not particularly limited, and examples thereof include a photodiode, a phototransistor, a photoconductive cell, and an image sensor.

  In the present embodiment, an optical filter 335 such as a high-pass filter or a band-pass filter that allows light including the first wavelength (first light) to pass on the photosensitive surface of the first light receiving unit 330. Is provided. The optical filter 335 is preferably one that cuts light (second light) including the second wavelength. Accordingly, the optical filter 335 suppresses or prevents the first light receiving unit 330 from receiving the excitation light from the light source 320 and the second light from the reference material, and the first light from the fluorescent material. The first light is selectively introduced into the first light receiving unit 330 while allowing the light to pass therethrough. As a result, noise caused by the excitation light and the second light, and also external light such as sunlight and illumination light can be reduced, so that the detection accuracy of the first light can be improved.

  The second light receiving unit 340 receives the fluorescence (second light) emitted from the reference material when irradiated with the excitation light in the sensor film 120, and the intensity of the second light (second intensity). It is for measuring.

  As this 2nd light-receiving part 340, the thing similar to what was mentioned by the 1st light-receiving part 330 mentioned above can be used.

  In the present embodiment, an optical filter 345 such as a high-pass filter or a band-pass filter that allows passage of light including the second wavelength (second light) is formed on the photosensitive surface of the second light receiving unit 340. Is provided. The optical filter 345 preferably cuts light including the first wavelength (first light). As a result, the optical filter 345 suppresses or prevents the second light receiving unit 340 from receiving the excitation light from the light source 320 and the first light from the signal substance, and the second light from the reference substance. Is allowed to pass through, and the second light is selectively introduced into the second light receiving unit 340. As a result, noise caused by the excitation light and the first light, and also external light such as sunlight and illumination light can be reduced, so that the detection accuracy of the second light can be improved.

  The control unit 210 is provided in the main body 155 and is configured by combining, for example, a CPU and a memory. The control unit 210 operates each unit such as the detection element 100 and the monitor 151 (display unit), that is, the biological information acquisition system 101. Control the overall operation.

  As shown in FIG. 4, the control unit 210 includes a storage unit 261, a circuit unit 400 as a detection unit driving unit that drives each unit of the detection unit 300, a data display instruction unit 299, and a calculation unit 200.

  The storage unit 261 includes an OS for controlling the overall operation of the biological information acquisition system 101, a program for realizing various functions, and the first light receiving unit 330 and the second light receiving unit 340 respectively measured by the first light receiving unit 330 and the second light receiving unit 340. Various data including a plurality of calibration curves for calculating the glucose concentration based on the first intensity and the second intensity are stored. Further, the storage unit 261 includes a temporary storage area for temporarily storing the measured first intensity, second intensity, and the like.

  Then, the storage unit 261 stores data indicating a change over time in the glucose concentration calculated using the calibration curve based on the measured first intensity and second intensity.

  The data display instruction unit 299 causes the monitor (display unit) 151 to display the glucose concentration calculated by the calculation unit 200 using the calibration curve, the date and time when the glucose concentration was measured, and the like.

  For example, the circuit unit 400 controls driving of each unit included in the detection unit 300 based on measurement conditions set by the operation of the operation unit 212 by the measurer.

  Specifically, the circuit unit 400 includes a light source driving unit 400A that controls driving of the light source 320, a first light receiving driving unit 400B that controls driving of the first light receiving unit 330, and a second light receiving unit 340. And a second light receiving drive unit 400C for controlling the driving of.

  In the circuit unit 400 having such a configuration, first, the light source driving unit 400A is operated to irradiate the living body, that is, the sensor film 120 embedded in the living body (dermis 502) with excitation light using the light source 320. Then, by the operation of the first light receiving drive unit 400B, the first light receiving unit 330 receives the fluorescence (first light) emitted from the fluorescent material by the irradiation of the excitation light, and thereby the intensity of the first light. (First intensity) is acquired, and then transmitted to the calculation unit 200. Further, by the operation of the second light receiving drive unit 400C, the second light receiving unit 340 receives the fluorescence (second light) emitted from the reference material by the irradiation of the excitation light, thereby the intensity of the second light. (Second intensity) is acquired and then transmitted to the calculation unit 200.

  The calculation unit 200 executes a calculation process by reading a program stored in the storage unit 261, and includes a separation distance calculation unit 200B and a glucose concentration calculation unit 200A.

  The separation distance calculation unit 200B reads from the storage unit 261 a calibration curve indicating the relationship between the second intensity acquired by the second light receiving unit 340 and the separation distance between the main body unit 110 and the sensor film 120, and The distance between the main body 110 and the sensor film 120 is derived from the calibration curve and the second intensity acquired by the second light receiving unit 340.

  In other words, the separation distance calculation unit 200 </ b> B is based on the intensity of the second light received by the second light receiving unit 340 (second intensity), that is, the main body 110, that is, the second light receiving unit 340 and the sensor film 120. It is for calculating | requiring the separation distance with (sensor substance).

  In addition, the glucose concentration calculation unit 200A includes a plurality of calibration curves prepared in correspondence with the size of the separation distance, and the relationship between the first intensity acquired by the first light receiving unit 330 and the glucose concentration. From the storage unit 261, a value that matches the size of the separation distance calculated by the separation distance calculation unit 200B is read from the storage unit 261. Further, from the calibration curve and the first intensity acquired by the first light receiving unit 330, This is for determining the glucose concentration (predetermined substance) in the material fluid.

  That is, the glucose concentration calculation unit 200 </ b> A is for obtaining the corrected glucose (predetermined substance) concentration based on the intensity (first intensity) of the first light received by the first light receiving unit 330. It is.

  The glucose concentration calculated by the calculation unit 200 is displayed on the monitor 151 by the operation of the data display instruction unit 299.

  Now, in the biological information acquisition system 101 of this embodiment having such a configuration, the second light receiving unit 340 is used to measure the intensity of the second light (second intensity; the light receiving result of the second light receiving unit 340). Further, based on a calibration curve indicating the relationship between the second intensity and the separation distance between the main body 110 and the sensor film 120, which is stored in the storage unit 261 in advance, the main body in the separation distance calculation unit 200B. The separation distance between the portion 110 and the sensor film 120 is calculated.

  Then, the relationship between the glucose concentration and the first intensity acquired by the first light receiving unit 330 prepared in advance corresponding to the size of the separation distance stored in the storage unit 261 in advance is shown. Among the calibration curves, the one that matches the size of the separation distance calculated by the separation distance calculation unit 200B is read. Then, based on the read calibration curve, the first light intensity measured using the first light receiving unit 330 (first intensity; light reception result of the first light receiving unit 330) is used. The glucose concentration calculation unit 200A calculates a glucose concentration (predetermined substance) as an object.

  In this way, in consideration of the separation distance between the main body 110 and the sensor film 120 calculated by the separation distance calculation unit 200B, the glucose concentration calculation unit 200A (calculation unit 200) performs an operation on the subject in the glucose concentration calculation unit 200A. The glucose concentration (predetermined substance) is calculated. That is, the light reception result of the first light receiving unit 330 is corrected by the light reception result of the second light receiving unit 340, and the glucose concentration (predetermined substance) is calculated. The glucose concentration can be measured with excellent reliability without depending on the mounting position of the unit 110.

  In addition, it is assumed that external light such as sunlight or illumination light passes through the lower surface of the main body 110 and reaches the detection unit 300, and both the first light receiving unit 330 and the second light receiving unit 340 receive light. However, since both of them receive light and become a baseline, it is possible to accurately suppress or prevent adverse effects on the calculated glucose concentration. Therefore, from this point of view, according to the biological information acquisition system 101, the glucose concentration can be measured with excellent reliability.

(Measuring method)
The measurement of the glucose concentration in the interstitial fluid using the biological information acquisition system 101 of the first embodiment as described above is specifically performed by, for example, the following first method and second method. To be implemented.

  FIG. 5 is a flowchart illustrating a measurement method for measuring a glucose concentration using the biological information acquisition system according to the first embodiment.

[First method]
First, a first method for measuring the glucose concentration using the biological information acquisition system 101 of the first embodiment will be described.

  [1A] First, the measurer (user) embeds the sensor film 120 in the dermis 502 and stabilizes the sensor film 120 by contacting the interstitial fluid with the sensor film 120 (S1a).

  At this time, the measurer inputs measurement conditions such as a period (time) for measuring the glucose concentration by operating the operation unit 212.

  [2A] Next, the control unit 210 operates the light source driving unit 400A to operate the light source 320 and irradiate the skin (living body) with excitation light (excitation light irradiation step; S2a).

  Thereby, excitation light is irradiated to the sensor film 120 embedded in the dermis 502 of the living body. That is, a signal substance that receives excitation light from the light source 320 and emits first light according to the concentration of glucose (predetermined substance) in the living body, and a reference substance that emits second light that is not influenced by the concentration The sensor film 120 (sensor material) previously embedded in the dermis 502 of the skin (living body) is irradiated with excitation light. As a result, the fluorescent material contained in the sensor film 120 emits fluorescence (first light) having the peak wavelength of the first wavelength by the excitation light, and the reference material contained in the sensor film 120 is the second material. Fluorescence (second light) having a peak wavelength is emitted.

  [3A] Next, the control unit 210 activates the first light receiving drive unit 400B, so that the fluorescence (first light) emitted from the fluorescent material in the step [2A] is converted into the first light receiving unit. 330 receives light and measures the intensity of the first light at the first wavelength (first intensity; light reception result of the first light receiving unit 330) (first light receiving step; S3a). Then, the first intensity is temporarily stored in the storage unit 261.

  [4A] Next, the control unit 210 activates the second light receiving drive unit 400C, thereby causing the second light receiving unit 340 to emit the fluorescence (second light) emitted from the reference material in the step [2A]. And the intensity of the second light at the second wavelength (second intensity; light reception result of the second light receiving unit 340) is measured (second light receiving step; S4a). Then, the second intensity is temporarily stored in the storage unit 261.

  Note that the order of the step [3A] and the main step [4A] may be substantially the same or may be reversed.

  [5A] Next, the control unit 210 operates the calculation unit 200 (separation distance calculation unit 200B) to thereby obtain the second intensity acquired by the second light receiving unit 340, the main body unit 110, and the sensor film 120. A calibration curve indicating the relationship with the separation distance and the second intensity measured in the step [4A] are extracted from the storage unit 261, and the calibration curve is used to obtain the main body 110 and the sensor film 120. Is determined (S5a).

  That is, based on the intensity (second intensity) of the second light received by the second light receiving unit 340, the main body 110 (the light source 320, the first light receiving unit 330, and the second light receiving unit 340), A separation distance from the sensor film 120 (sensor substance) is obtained.

  [6A] Next, the control unit 210 operates the calculation unit 200 (glucose concentration calculation unit 200A) to obtain the size of the separation distance between the main body 110 and the sensor film 120 obtained in the step [5A]. A corresponding calibration curve indicating the relationship between the first intensity acquired by the first light receiving unit 330 and the glucose concentration is extracted from the storage unit 261. Furthermore, the 1st intensity | strength measured in the said process [3A] is taken out from the memory | storage part 261, and the glucose concentration in interstitial fluid is calculated | required using the taken out calibration curve (S6a).

  That is, in the interstitial fluid corrected based on the separation distance obtained in the step [5A] and the intensity of the first light received by the first light receiving unit 330 (first intensity). The glucose concentration (concentration of a predetermined substance) is determined.

  Thus, in consideration of the separation distance between the main body 110 and the sensor film 120 calculated by the separation distance calculation unit 200B in the step [5A], in this step [6A], the glucose concentration calculation unit 200A Since the glucose concentration (predetermined substance) as the object is calculated, it is possible to measure the glucose concentration with excellent reliability without being influenced by the embedded position of the sensor film 120 or the mounting position of the main body 110. it can.

  Further, in the step [3A] and the step [4A], external light such as sunlight or illumination light passes through the lower surface of the main body 110 and reaches the detection unit 300, and the first light receiving unit 330 and Even if both the second light receiving unit 340 receive light, both receive light and this becomes a baseline, so that adverse effects on the calculated glucose concentration can be accurately suppressed or prevented. Therefore, from this point of view, according to the biological information acquisition system 101, the glucose concentration can be measured with excellent reliability.

  In this measurement method, the light reception result of the first light receiving unit 330 is converted into the second light receiving unit by the step [5A] for obtaining the separation distance and the step [6A] for obtaining the concentration of glucose (predetermined substance). A calculation step for correcting the light reception result of 340 to obtain the concentration of the predetermined substance is configured.

  [7A] Next, the control unit 210 operates the data display instruction unit 299 to display the glucose concentration calculated in the step [6A] on the monitor 151 (display unit) (S7a).

  In addition to this display, the glucose concentration is stored in the storage unit 261 as necessary.

  The steps [2A] to [6A] may be performed once, but the steps [2A] to [6A] are repeatedly performed, and the average value of the glucose concentration measured during this time is repeated. Since the glucose concentration is averaged by determining the glucose concentration, the glucose concentration can be determined with higher reliability.

  Then, the steps [2A] to [6A] as described above are repeatedly performed at a predetermined interval, whereby the glucose concentration in the interstitial fluid is continuously measured.

[Second method]
Next, a second method for measuring the glucose concentration using the biological information acquisition system 101 of the first embodiment will be described.

  However, in the second method, among the steps [1A] to [7A] in the first method described above, the steps [2A] to [4A] are different, and the other steps are the same. Therefore, the description thereof will be omitted, and the steps [2B] to [4B] different from the steps [2A] to [4A] will be described below.

  [2B] First, after the step [1A], the control unit 210 operates the light source driving unit 400A to operate the light source 320 and irradiate the skin (living body) with excitation light (excitation light irradiation step). S2a).

  At this time, in the second method, the control unit 210 irradiates the excitation light as a carrier wave that has been modulated to show a periodic change such as a sine wave.

  As a result, the sensor film 120 is irradiated with excitation light as the carrier wave. Therefore, the fluorescent material and the reference material contained in the sensor film 120 that emit light by the excitation light have the same frequency and phase as the carrier wave, respectively. The first light and the second light having

  [3B] Next, the control unit 210 operates the first light receiving drive unit 400B to cause the first light having the same frequency and phase as the carrier wave emitted from the fluorescent material in the step [2B]. The light is received using the first light receiving unit 330, and the intensity of the first light at the first wavelength (first intensity; light reception result of the first light receiving unit 330) is measured (first Light receiving step; S3a). The intensity (first intensity) of the first light at the first wavelength also has the same frequency and phase as the carrier wave. The first intensity and the carrier wave are multiplied (multiplied). The detected first intensity is obtained by synchronous detection. Thereafter, the detected first intensity is temporarily stored in the storage unit 261.

  [4B] Next, the control unit 210 activates the second light receiving drive unit 400C to cause the second light having the same frequency and phase as the carrier wave emitted from the reference material in the step [2B]. Light is received using the second light receiving unit 340, and the intensity of the second light at the second wavelength (second intensity; light reception result of the second light receiving unit 340) is measured (second light receiving). Step; S4a). The intensity (second intensity) of the second light at the second wavelength also has the same frequency and phase as the carrier wave, but the second intensity and the carrier wave are multiplied (multiplied). The detected second intensity is obtained by synchronous detection. Thereafter, the detected second intensity is temporarily stored in the storage unit 261.

  In the second method, the order of the step [3B] and the main step [4B] may be substantially the same or may be reversed.

  Through the above-described steps [2B] to [4B], the light reception result of the first light receiving unit 330 and the light reception result of the second light receiving unit 340 are obtained using the frequency of the light source 320 (carrier wave). Are corrected for synchronous detection.

  According to the correction using such synchronous detection, in particular, noise caused by external light such as sunlight or illumination light entering at least one of the first light receiving unit 330 and the second light receiving unit 340 is further reduced. It can be reliably reduced. As a result, the calculated glucose concentration (concentration of the predetermined substance) is obtained with higher reliability.

<< Second Embodiment >>
Next, a second embodiment of the biological information acquisition system of the present invention will be described.

  FIG. 6 is a longitudinal sectional view showing a main body provided in a detection element included in the second embodiment of the biological information acquisition system of the present invention.

  Hereinafter, the biometric information acquisition system 101 according to the second embodiment will be described with a focus on differences from the biometric information acquisition system 101 according to the first embodiment, and description of similar matters will be omitted.

  The biometric information acquisition system 101 of the second embodiment is the first except that the configuration of the detection unit 300 included in the main body 110 shown in FIG. 6 and the glucose concentration measurement method using the biometric information acquisition system 101 are different. This is the same as the biological information acquisition system 101 of the embodiment.

  That is, in the biological information acquisition system 101 of the second embodiment, the detection unit 300 includes two light sources, a first light source 325 and a second light source 326, as light sources that emit excitation light.

  Of these two light sources, the first light source 325 irradiates the living body with excitation light (first excitation light) in which the fluorescent substance contained in the sensor film 120 emits fluorescence (first light). The second light source 326 irradiates the living body with excitation light (second excitation light) in which the reference material included in the sensor film 120 emits fluorescence (second light).

  At this time, the first light source 325 may be either the one having a wavelength region in which the reference material irradiates the living body with the excitation light that emits fluorescence, or the one having the wavelength region not irradiating, but the latter. It is preferable. Accordingly, it is possible to prevent the reference material included in the sensor film 120 from emitting fluorescence when the first light source 325 is irradiated with excitation light. Therefore, the signal substance is prevented from being emitted by the excitation light from the first light source 325 when the second light source 326 irradiates the sensor film 120 (reference substance). Therefore, the occurrence of noise due to this is prevented, and the measurement accuracy of the measurement of glucose concentration is improved.

  In addition, the second light source 326 may be either one having a wavelength region in which the fluorescent material irradiates the living body with excitation light that emits fluorescence, or one having a wavelength region that does not irradiate, but the latter is preferable. . This can prevent the fluorescent material included in the sensor film 120 from emitting fluorescence when the second light source 326 is irradiated with excitation light. Therefore, when the sensor film 120 (fluorescent material) is irradiated by the first light source 325, the fluorescent material is prevented from being emitted by the excitation light from the second light source 326. Therefore, the occurrence of noise due to this is prevented, and the measurement accuracy of the measurement of glucose concentration is improved.

(Measuring method)
Specifically, the measurement of the glucose concentration in the interstitial fluid using the biological information acquisition system 101 of the second embodiment as described above is performed by, for example, the following third method and fourth method. To be implemented.

  FIG. 7 is a flowchart illustrating a measurement method for measuring a glucose concentration using the biological information acquisition system according to the second embodiment.

[Third method]
First, a third method for measuring the glucose concentration using the biological information acquisition system 101 of the second embodiment will be described.

  [1C] First, the measurer (user) stabilizes the sensor film 120 by embedding the sensor film 120 in the dermis 502 and bringing the interstitial fluid into contact with the sensor film 120 (S1b).

  At this time, the measurer inputs measurement conditions such as a period (time) for measuring the glucose concentration by operating the operation unit 212.

  [2C] Next, the control unit 210 operates the light source driving unit 400A to operate the first light source 325, and the skin (living body) is irradiated with excitation light (first excitation light) (first excitation light). 1 excitation light irradiation step; S2b).

  Thereby, excitation light (first excitation light) is irradiated to the sensor film 120 embedded in the dermis 502 of the living body. As a result, the fluorescent material contained in the sensor film 120 emits fluorescence (first light) having a peak wavelength of the first wavelength by the first excitation light.

  [3C] Next, the control unit 210 activates the first light receiving drive unit 400B, whereby the fluorescence (first light) emitted from the fluorescent material in the step [2C] is converted into the first light receiving unit 330. Is used to measure the intensity of the first light at the first wavelength (first intensity; light reception result of the first light receiving unit 330) (first light receiving step; S3b). Then, the first intensity is temporarily stored in the storage unit 261.

  [4C] Next, the control unit 210 operates the light source driving unit 400A to operate the second light source 326, and the skin (living body) is irradiated with excitation light (second excitation light) (first excitation light). 2 excitation light irradiation step; S4b).

  Thereby, excitation light (second excitation light) is irradiated to the sensor film 120 embedded in the dermis 502 of the living body. As a result, the reference material included in the sensor film 120 emits fluorescence (second light) having a peak wavelength of the second wavelength by the second excitation light.

  [5C] Next, the control unit 210 activates the second light receiving drive unit 400C, so that the fluorescence (second light) emitted from the reference material in the step [4C] is converted into the second light receiving unit 340. And the intensity of the second light at the second wavelength (second intensity; light reception result of the second light receiving unit 340) is measured (second light receiving step; S5b). Then, the second intensity is temporarily stored in the storage unit 261.

  The order of the step [2C] and the step [3C] and the step [4C] and the step [5C] may be substantially the same or reversed. It is preferred that the order is as described above or reversed. Thereby, since it is possible to reliably suppress or prevent the occurrence of crosstalk between the first light and the second light, the first intensity measurement by the step [2C] and the step [3C]. The accuracy is improved, and the measurement accuracy of the second intensity is improved by the step [4C] and the step [5C].

  [6C] Next, the control unit 210 operates the calculation unit 200 (separation distance calculation unit 200B) to thereby obtain the second intensity acquired by the second light receiving unit 340, the main body unit 110, and the sensor film 120. A calibration curve indicating the relationship with the separation distance and the second intensity measured in the step [5C] are taken out from the storage unit 261, and the main body 110 and the sensor film 120 are Is determined (S6b).

  [7C] Next, the control unit 210 operates the calculation unit 200 (glucose concentration calculation unit 200A) to obtain the size of the separation distance between the main body unit 110 and the sensor film 120 obtained in the step [6C]. A corresponding calibration curve indicating the relationship between the first intensity acquired by the first light receiving unit 330 and the glucose concentration is extracted from the storage unit 261. Further, the first intensity measured in the step [3C] is extracted from the storage unit 261, and the glucose concentration in the interstitial fluid is obtained using the extracted calibration curve (S7b).

  That is, in the interstitial fluid corrected based on the separation distance obtained in the step [6C] and the intensity of the first light received by the first light receiving unit 330 (first intensity). The glucose concentration (concentration of a predetermined substance) is determined.

  [8C] Next, the control unit 210 operates the data display instruction unit 299 to display the glucose concentration calculated in the step [7C] on the monitor 151 (display unit) (S8b).

  In addition to this display, the glucose concentration is stored in the storage unit 261 as necessary.

  The step [2C] to the step [7C] may be performed once, but the step [2C] to the step [7C] are repeatedly performed, and the average value of the glucose concentration measured during this time is repeated. Since the glucose concentration is averaged by determining the glucose concentration, the glucose concentration can be determined with higher reliability.

  Then, the steps [2C] to [7C] as described above are repeatedly performed at a predetermined interval, whereby the glucose concentration in the interstitial fluid is continuously measured.

[Fourth method]
Next, a fourth method for measuring the glucose concentration using the biological information acquisition system 101 of the second embodiment will be described.

  However, in the fourth method, among the steps [1C] to [8C] in the third method described above, the steps [2C] to [5C] are different, and the other steps are the same. Therefore, the description thereof will be omitted, and the steps [2D] to [5D] different from the steps [2C] to [5C] will be described below.

  [2D] First, after the step [1C], the control unit 210 operates the light source driving unit 400A to operate the first light source 325, and the excitation light (first excitation light) is applied to the skin (living body). ) Is irradiated (first excitation light irradiation step; S2b).

  At this time, in the fourth method, the control unit 210 irradiates the first excitation light as a carrier wave that has been modulated to exhibit a periodic change such as a sine wave.

  Accordingly, since the excitation light is irradiated as the carrier wave to the sensor film 120, the fluorescent material contained in the sensor film 120 that emits light by the first excitation light has the same frequency and phase as the carrier wave. Emits first light.

  [3D] Next, the control unit 210 operates the first light receiving drive unit 400B, and in the step [2D], the first light having the same frequency and phase as the carrier wave emitted from the fluorescent material is emitted. The light is received using the first light receiving unit 330, and the intensity of the first light at the first wavelength (first intensity; light reception result of the first light receiving unit 330) is measured (first Light receiving step; S3b). The intensity (first intensity) of the first light at the first wavelength also has the same frequency and phase as the carrier wave. The first intensity and the carrier wave are multiplied (multiplied). The detected first intensity is obtained by synchronous detection. Thereafter, the detected first intensity is temporarily stored in the storage unit 261.

  [4D] Next, the control unit 210 operates the light source driving unit 400A to operate the second light source 326, and the skin (living body) is irradiated with excitation light (second excitation light) (first excitation light). 2 excitation light irradiation step; S4b).

  At this time, in the fourth method, the control unit 210 irradiates the second excitation light as a carrier wave that has been modulated to exhibit a periodic change such as a sine wave.

  Accordingly, since the excitation light is irradiated as the carrier wave to the sensor film 120, the reference material included in the sensor film 120 that emits light by the second excitation light has the same frequency and phase as the carrier wave. Second light is emitted.

  [5D] Next, the control unit 210 activates the second light receiving drive unit 400C to cause the second light having the same frequency and phase as the carrier wave, in which the reference material emits light in the step [2D]. Light is received using the second light receiving unit 340, and the intensity of the second light at the second wavelength (second intensity; light reception result of the second light receiving unit 340) is measured (second light receiving). Step; S5b). The intensity (second intensity) of the second light at the second wavelength also has the same frequency and phase as the carrier wave, but the second intensity and the carrier wave are multiplied (multiplied). The detected second intensity is obtained by synchronous detection. Thereafter, the detected second intensity is temporarily stored in the storage unit 261.

  In the fourth method, the order of the step [2D] and the step [3D] and the step [4D] and the step [5D] may be almost the same or reversed. However, it is preferable that the above order or the reverse order be used. Specifically, it is preferable that the phase relationship between the first pumping light (carrier wave) and the second pumping light (carrier wave) is orthogonal. Thereby, since it is possible to reliably suppress or prevent the occurrence of crosstalk between the first light and the second light, measurement of the first intensity by the step [2D] and the step [3D]. The accuracy is improved, and the measurement accuracy of the second intensity is improved by the step [4D] and the step [5D].

  In addition, according to such correction using synchronous detection, noise caused by external light such as sunlight or illumination light entering at least one of the first light receiving unit 330 and the second light receiving unit 340 is particularly generated. Can be more reliably reduced. As a result, the calculated glucose concentration (the concentration of the predetermined substance) can be obtained as having higher reliability.

  Although the biological information acquisition system and the biological information acquisition method of the present invention have been described based on the illustrated embodiment, the present invention is not limited to this.

  For example, the configuration of each part in the biological information acquisition system (measurement device) of the present invention can be replaced with any configuration having the same function. In addition, any other component may be added to the present invention.

  In addition to inserting the sensor film 120 (sensor substance) into the dermis 502, it may be inserted into the subcutaneous tissue 503.

  Further, in the measuring device, the intensity measured by the detection element may be transmitted to the circuit unit without using the wiring. For example, the intensity or the like is transmitted to the circuit unit wirelessly through a communication unit. You may make it do.

  Further, in the measurement apparatus, the detection element and the display unit are not limited to being connected via wiring, and may be formed integrally.

  In addition, the biological information acquisition system of the present invention can be applied to a measuring device that automatically calculates the glucose concentration in the interstitial fluid over time based on the measured intensity, as well as the lactic acid level in the body fluid, the antibody The present invention can be similarly applied to a measuring apparatus that automatically calculates a predetermined substance as a target substance such as an amount and an enzyme amount over time based on intensity.

  Furthermore, the light emitted by irradiating the signal substance and the reference substance with excitation light is not limited to fluorescence but may be phosphorescence.

  Moreover, the biological information acquisition method of the present invention may include one or more arbitrary steps.

DESCRIPTION OF SYMBOLS 100 ... Detection element 101 ... Biometric information acquisition system, 110 ... Main body part, 120 ... Sensor film, 131 ... Connector, 132 ... Wiring, 150 ... Case, 151 ... Monitor, 155 ... Main body, 200 ... Calculation part, 200A ... Glucose concentration calculation unit, 200B: separation distance calculation unit, 210 ... control unit, 212 ... operation unit, 261 ... storage unit, 299 ... data display instruction unit, 300 ... detection unit, 310 ... substrate, 320 ... light source, 325 ... first 1 light source, 326... Second light source, 330... First light receiving section, 335... Optical filter, 340... Second light receiving section, 345. 1st light reception drive part, 400C ... 2nd light reception drive part, 501 ... epidermis, 502 ... dermis, 503 ... subcutaneous tissue

Claims (9)

A light source for emitting excitation light and irradiating the living body;
A sensor substance for embedding in the living body, which receives the excitation light and emits a first light according to the concentration of the predetermined substance in the living body, and a second light that is not affected by the concentration A reference substance to be released, and a sensor substance comprising:
A first light receiving unit for receiving the first light;
A second light receiving unit for receiving the second light,
A biological information acquisition system, wherein the concentration is calculated by correcting a light reception result of the first light receiving unit with a light reception result of the second light receiving unit.   The biological information acquisition system according to claim 1, wherein a separation distance between the second light receiving unit and the sensor substance is obtained based on the intensity of the second light received by the second light receiving unit.   The biological information acquisition system according to claim 2, wherein the density obtained by the correction is obtained based on the separation distance and the intensity of the first light received by the first light receiving unit.   4. The correction according to claim 1, wherein the correction is performed by synchronously detecting a light reception result of the first light receiving unit and a light reception result of the second light receiving unit using a frequency of the light source. 5. Biological information acquisition system.   5. The biological information acquisition according to claim 1, further comprising: a calculation unit that calculates the concentration by correcting a light reception result of the first light receiving unit based on a light reception result of the second light receiving unit. system.   The biological information acquisition system according to any one of claims 1 to 5, wherein the predetermined substance is glucose. A signal substance that emits first light according to the concentration of the predetermined substance in the living body in response to excitation light from the light source, and a reference substance that emits second light that is not affected by the concentration, and An excitation light irradiation step for irradiating the excitation light to the sensor substance previously embedded in the living body;
A first light receiving step of receiving the first light using a first light receiving unit and obtaining a light reception result of the first light receiving unit;
A second light receiving step of receiving the second light using a second light receiving unit and obtaining a light reception result of the second light receiving unit;
A biological information acquisition method comprising: a calculation step of correcting the light reception result of the first light receiving unit with the light reception result of the second light receiving unit to obtain the concentration.   8. The calculation step according to claim 7, wherein a separation distance between the second light receiving unit and the sensor substance is obtained based on the intensity of the second light received by the second light receiving unit. Biological information acquisition method.   The biological information acquisition method according to claim 8, wherein in the calculation step, the corrected density is obtained based on the separation distance and the intensity of the first light received by the first light receiving unit.

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