WO2013146244A1 - Sensing device and sensing method - Google Patents

Sensing device and sensing method Download PDF

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Publication number
WO2013146244A1
WO2013146244A1 PCT/JP2013/056929 JP2013056929W WO2013146244A1 WO 2013146244 A1 WO2013146244 A1 WO 2013146244A1 JP 2013056929 W JP2013056929 W JP 2013056929W WO 2013146244 A1 WO2013146244 A1 WO 2013146244A1
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WIPO (PCT)
Prior art keywords
measurement
measurement mode
mode
sensing device
concentration
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PCT/JP2013/056929
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French (fr)
Japanese (ja)
Inventor
松本淳
深井利夫
大澤孝明
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テルモ株式会社
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Application filed by テルモ株式会社 filed Critical テルモ株式会社
Priority to JP2014507635A priority Critical patent/JP6109813B2/en
Publication of WO2013146244A1 publication Critical patent/WO2013146244A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters

Definitions

  • the present invention relates to a sensing device and a sensing method for quantifying an analyte concentration intermittently or continuously.
  • a sensing device for quantifying the concentration of the analyte has been developed by utilizing the property that the fluorescence intensity changes due to the interaction between the analyte and the labeled compound.
  • an apparatus has been proposed in which a sensor unit is embedded in the body of a subject and glucose concentration can be continuously quantified (see Japanese Patent Nos. 4593957 and 4558448).
  • Japanese Patent No. 4593957 and Japanese Patent No. 4558448 aims to improve the light receiving sensitivity by improving the structure of the device.
  • the fluorescent sensor can be used for a long time (long term). There is plenty of room for stable use.
  • the present invention has been made in order to solve the above-described problems, and while maintaining the follow-up ability of the quantitative measurement with respect to the concentration change of the analyte, the electronic parts constituting the sensor unit, various substances related to measurement, etc.
  • An object is to provide a sensing device and a sensing method capable of suppressing deterioration.
  • the sensing device is a device for intermittently or continuously quantifying the concentration of an analyte, the sensor unit acquiring a measurement signal correlated with the concentration of the analyte according to a predetermined sampling interval, and the sensor A measurement mode switching unit that switches between a first measurement mode in which the intensity of the measurement signal acquired by the unit is relatively low, and a second measurement mode in which the intensity of the measurement signal is relatively higher than that in the first measurement mode. It is characterized by providing.
  • the first measurement mode in which the intensity of the measurement signal acquired by the sensor unit is relatively low and the measurement mode for switching the second measurement mode in which the intensity of the measurement signal is relatively higher than that in the first measurement mode. Since a switching unit is provided, it is possible to use a combination of two different measurement modes depending on the situation, and while maintaining the follow-up of quantitative measurement with respect to changes in analyte concentration, it is related to the electronic components and measurement that make up the sensor. Deterioration of various substances can be suppressed.
  • the sensor unit has an energy source that radiates energy, and obtains the measurement signal by applying the energy radiated from the energy source to a labeling substance.
  • the energy source when the energy source is controlled to be relatively reduced when the measurement mode switching unit switches to the first measurement mode, the energy source is controlled and the second measurement mode is switched. It is preferable to further include an energy source controller that controls the energy source so that the amount of radiation of the energy is relatively large. In the case of a sensor that obtains a measurement signal triggered by energy emission, reducing the quantitative frequency greatly contributes to the reduction of power consumption, and thus is particularly effective.
  • the measurement mode switching unit switches the measurement frequency in the first measurement mode to be higher than the measurement frequency in the second measurement mode.
  • the measurement mode switching unit switches from the first measurement mode to the second measurement mode according to the concentration of the analyte quantified at least once during the first measurement mode.
  • the measurement mode switching unit switches from the first measurement mode to the second measurement mode according to the number of measurements.
  • an interval determination unit that determines the sampling interval.
  • the interval determination unit determines the sampling interval according to the concentration of the analyte in the first measurement mode.
  • the interval determination unit may calculate a sampling interval when the concentration of the analyte is greater than or equal to a first threshold and / or less than or equal to a second threshold (less than the first threshold) in the remaining concentration range. It is preferable to determine a smaller value.
  • the energy source control unit controls the radiation amount of the energy according to the concentration of the analyte in the first measurement mode.
  • the energy source control unit controls the energy source so as to increase the radiation amount of the energy as the concentration of the analyte decreases.
  • a measurement accuracy determination unit that determines statistical errors as measurement accuracy in the first measurement mode and the second measurement mode, respectively.
  • the measurement accuracy determination unit determines a ratio of the statistical error in the second measurement mode to the statistical error in the first measurement mode within a range of 1/100 or more and 1/2 or less.
  • the sensor unit includes an optical sensor that acquires the measurement signal from a light phenomenon generated by applying the energy to the labeling substance or the subject.
  • the energy source is an excitation light source that emits excitation light as the energy for promoting generation of fluorescence for obtaining the measurement signal toward the labeling substance, and the energy source control unit is configured to follow the sampling interval. It is preferable to control the excitation light source so that the excitation light is emitted.
  • the sensing method is a method using a sensing device that quantifies the concentration of an analyte intermittently or continuously, and uses the sensor unit provided in the sensing device to perform the analyte according to a predetermined sampling interval.
  • the sensor unit has an energy source that radiates energy, and in the obtaining step, the measurement signal is obtained by applying the energy radiated from the energy source to a labeling substance.
  • the energy source is controlled so that the radiation amount of the energy becomes relatively small when switched to the first measurement mode, and the radiation amount of the energy when switched to the second measurement mode.
  • the method further includes a control step of controlling the energy source so that the number of the energy sources is relatively large.
  • the switching step it is preferable to switch so that the measurement frequency in the first measurement mode is higher than the measurement frequency in the second measurement mode.
  • the switching step it is preferable to switch from the first measurement mode to the second measurement mode according to the concentration of the analyte determined at least once during the first measurement mode.
  • the switching step it is preferable to switch from the first measurement mode to the second measurement mode according to the number of measurements.
  • an interval determining step for determining the sampling interval.
  • the sampling interval is determined according to the concentration of the analyte in the first measurement mode.
  • a sampling interval when the concentration of the analyte is not less than a first threshold and / or not more than a second threshold (smaller than the first threshold) is set as the sampling interval in the remaining concentration range. It is preferable to determine a smaller value.
  • the radiation amount of the energy is controlled according to the concentration of the analyte in the first measurement mode.
  • control step it is preferable to control the energy source so as to increase the radiation amount of the energy as the concentration of the analyte decreases.
  • an accuracy determination step for determining statistical errors as measurement accuracy in the first measurement mode and the second measurement mode, respectively.
  • a ratio of the statistical error in the second measurement mode to the statistical error in the first measurement mode is determined in a range of 1/100 or more and 1/2 or less.
  • the sensor unit includes an optical sensor that acquires the measurement signal from a light phenomenon generated by applying the energy to the labeling substance or the subject.
  • the energy source is an excitation light source that emits excitation light as the energy that promotes generation of fluorescence for obtaining the measurement signal toward the labeling substance, and in the control step, the excitation is performed according to the sampling interval. It is preferable to control the excitation light source so as to emit light.
  • the first measurement mode in which the intensity of the measurement signal acquired by the sensor unit is relatively low, and the intensity of the measurement signal is relatively lower than that in the first measurement mode. Since the high second measurement mode is switched, two different measurement modes can be used in combination depending on the situation, and the sensor unit is configured while maintaining the follow-up of the quantitative measurement for the concentration change of the analyte. Deterioration of electronic parts and various substances related to measurement can be suppressed.
  • FIG. 9A is a graph showing a plot of blood glucose level obtained by successively quantifying the concentration change shown in FIG.
  • FIG. 9B is a graph showing a plot of blood glucose level obtained by successively quantifying the concentration change shown in FIG. 8 using only the D mode. It is a graph which shows the plot of the blood glucose level obtained by quantifying the density
  • FIG. 12A is a second table for explaining measurement conditions in each measurement mode.
  • FIG. 12B is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. 12A.
  • FIG. 13A is a third table for explaining measurement conditions in each measurement mode.
  • FIG. 13B is a graph showing a plot of blood glucose levels obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. 13A. It is a graph showing the 3rd density
  • FIG. 16A is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 14 using only the D mode.
  • FIG. 16B is a graph showing a tendency of the tracking error obtained from the quantitative result shown in FIG. 16A.
  • FIG. 17A is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG.
  • FIG. 17B is a graph showing the tendency of the tracking error obtained from the quantitative result shown in FIG. 17A. It is a 5th table
  • FIG. 19A is a graph showing a part of a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG.
  • FIG. 19B is a graph showing a part of a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. It is a 6th table
  • the sensing device 10 includes a sensor unit 12 (including a fluorescence sensor 14 and a temperature sensor 15), a sensor control circuit 16, a calculation unit 18, a power supply circuit 20, a ROM 22, and a RAM 24.
  • the clock generator 26, the input unit 27, and the display 28 are basically provided.
  • the fluorescence sensor 14 acquires a measurement signal (hereinafter referred to as a fluorescence signal) corresponding to the intensity of the fluorescence F due to the interaction between the analyte A and the labeled compound.
  • the fluorescence F may be light resulting from the binding or dissociation between the analyte A and the labeling compound, or may be light resulting from the binding or dissociation between the third component different from the analyte A and the labeling compound.
  • the concentration of analyte A can be quantified based on the fluorescence signal.
  • the temperature sensor 15 acquires a signal corresponding to the environmental temperature in the vicinity of the fluorescent sensor 14 (hereinafter referred to as a temperature signal).
  • the sensor unit 12 is not limited to the above-described form, and a measurement signal correlated with the concentration of the analyte A from a phenomenon (for example, a light phenomenon) generated by applying energy to the labeling substance or the subject. It only needs to be acquired.
  • a phenomenon for example, a light phenomenon
  • an optical sensor that measures absorbance, Raman scattered light intensity, or the like, or a chemical sensor that measures temperature, electrical resistance, or the like may be used.
  • the sensor control circuit 16 drives the fluorescence sensor 14 and the temperature sensor 15, and controls the fluorescence signal and the temperature signal so as to be acquired.
  • the calculation unit 18 is composed of a CPU, an MPU, and the like, reads a program recorded in the ROM 22 and executes various signal processing described later.
  • the power supply circuit 20 supplies power to each component in the sensing device 10 including the calculation unit 18.
  • the RAM 24 can read or write various data necessary for carrying out the sensing method according to the present invention in addition to the fluorescence signal input via the fluorescence sensor 14 and the temperature signal input via the temperature sensor 15. is there.
  • the clock generator 26 generates a clock signal at a predetermined cycle and supplies it to the calculation unit 18 side. Thereby, the calculating part 18 can control the acquisition timing of a fluorescence signal and a temperature signal.
  • the input unit 27 is provided so as to be able to input various information (for example, measurement mode setting parameters) used for the calculation in the calculation unit 18.
  • various information for example, measurement mode setting parameters
  • a push button may be used, or a touch panel incorporated in the display device 28 may be used.
  • the display 28 visualizes and displays various information related to the concentration of the analyte A quantified by the calculation unit 18.
  • the display 28 is a display module capable of monochrome or color display, and may be composed of a liquid crystal panel, an organic EL (Electro-Luminescence), an inorganic EL panel, or the like.
  • the sensor unit 12 includes a substantially rectangular casing 30.
  • the inside of the housing 30 is hollow, and can accommodate the fluorescent sensor 14, the base material 32, and the six metal wires 34, 35, 36.
  • the housing 30 and the base material 32 are each formed of a resin such as polyimide, parylene (polyparaxylylene), or cyclic polyolefin. Further, in order to block external light, the material may contain a light blocking material such as carbon black.
  • one surface (entrance surface 38) of the housing 30 is made of hydrogel, carbon black, and the like, and has characteristics of allowing the analyte A to pass and blocking external light.
  • the fluorescent sensor 14 includes, in order from the bottom to the top, a substrate 40 made of silicon or the like, a photodiode (Photo Diode: hereinafter referred to as “PD”) element 42, a first protective film (not shown), a filter 44, and light emission.
  • PD Photodiode
  • a diode (Light (Emitting Diode: hereinafter also referred to as “LED”) element 46 (energy source, excitation light source), a second protective film 48 made of epoxy resin or the like, and an indicator layer 50 are included.
  • a PD element 42 is formed on the surface of the substrate 40.
  • the PD element 42 is a photoelectric conversion element that converts the fluorescence F into an electrical signal.
  • various photoelectric conversion elements such as a photoconductor (photoconductor) or a phototransistor (Phototransistor, PT) may be used.
  • the PD element 42 and the metal wire 34 are electrically connected by means such as a bonding wire 52 or a through wiring.
  • the filter 44 is an absorptive optical filter that blocks the wavelength band of the excitation light E emitted from the LED element 46 and passes the fluorescence F on the longer wavelength side than the wavelength band.
  • a silicon film such as polycrystalline silicon, a silicon carbide film, or a gallium phosphide film may be used.
  • the LED element 46 is a light emitting element that emits excitation light E that promotes generation of fluorescence F for obtaining a fluorescence signal.
  • various types of light emitting elements such as an organic EL element, an inorganic EL element, or a laser diode element may be used.
  • the indicator layer 50 emits fluorescence F corresponding to the concentration of analyte A (for example, glucose) that has entered from the entry surface 38.
  • the indicator layer 50 is made of a base material containing a fluorescent dye as a labeling compound.
  • a labeled compound for example, a substance that reversibly binds to analyte A such as a ruthenium organic complex, a phenylboronic acid derivative, or a fluorescein-labeled dextran as a fluorescent dye
  • a third component for example, rhodamine-labeled concanavalin A.
  • a third component may be included in the base material of the indicator layer 50 together with the labeling compound. Alternatively, another mechanism for mixing the third component may be provided.
  • a temperature sensor 15 capable of acquiring a temperature signal in the vicinity of the fluorescence sensor 14 is also arranged inside the housing 30.
  • an optical type such as a fluorescence thermometer, a thermistor type, a metal thin film resistance type, or a semiconductor type based on the temperature characteristics of the forward current of the PN junction may be used.
  • a semiconductor type sensor it can be formed on the substrate 40 like the PD element 42.
  • the metal wires 34, 35, and 36 are formed of a conductor such as gold, aluminum, or copper, and have a function of increasing rigidity in addition to a role as electric wiring in the housing 30.
  • the sensor unit 12 is electrically connected to the sensor control circuit 16 (see FIG. 1) via metal wires 34-36.
  • the metal wire 34 includes two metal wires 34a and 34b.
  • the metal wire 35 is composed of two metal wires 35a and 35b.
  • the metal wire 36 is composed of two metal wires 36a and 36b. For example, by providing an insulating layer (not shown) between the metal wire 34 (or the metal wire 35) and the metal wire 36, the two may be electrically insulated.
  • the sensor control circuit 16 can acquire the fluorescence signal from the PD element 42 via the metal wire 34. Further, the sensor control circuit 16 can supply driving power to the LED element 46 via the metal wire 35. Furthermore, the sensor control circuit 16 can acquire the temperature signal from the temperature sensor 15 via the metal wire 36.
  • the concentration of the analyte A in the body of the subject can be continuously measured by causing the subject to puncture and hold the needle tip. At that time, a part of the analyte A enters the inside of the housing 30 from the entry surface 38 and stays around the indicator layer 50.
  • the sensor control circuit 16 supplies a drive power signal to the LED element 46 through the metal wire 35 of the fluorescent sensor 14, whereby the excitation light E is emitted. Then, the excitation light E from the LED element 46 is incident on the indicator layer 50.
  • the indicator layer 50 emits fluorescence F having an intensity corresponding to the concentration of the analyte A by the interaction between the analyte A and the labeling compound or by the interaction with the addition of the third component.
  • Fluorescence F from the indicator layer 50 is transmitted through the LED element 46, the filter 44, etc., and then photoelectrically converted by the PD element 42, transmitted through the metal wire 34 as a fluorescence signal, and supplied to the sensor control circuit 16 side.
  • a temperature signal from the temperature sensor 15 is transmitted through the metal wire 36 and supplied to the sensor control circuit 16 side.
  • the fluorescence sensor 14 acquires a fluorescence signal
  • the temperature sensor 15 acquires a temperature signal. 2 and 3 can be applied to various uses such as an enzyme sensor, a glucose sensor, a pH sensor, an immune sensor, or a microorganism sensor.
  • the structure of the sensor part 12 can take various structures, without being restricted to this structure.
  • the sensor control circuit 16 and the arithmetic unit 18 that are physically separated are provided so as to be able to communicate with each other wirelessly, whereby the sensor unit 12 is quantified intermittently or continuously with the sensor unit 12 completely embedded in the body of the subject. Is possible.
  • the sensor control circuit 16 includes a light source control unit 60 (energy source control unit) that drives and controls the LED element 46 so as to emit the excitation light E at a predetermined time and / or light amount, and a fluorescence signal acquired from the PD element 42.
  • a fluorescence signal acquisition unit 62 that acquires the fluorescence intensity F (t).
  • the light source control unit 60 changes the driving power for driving the LED element 46, specifically the current value, the voltage value, and the pulse control method (number or width of these pulses), etc.
  • the light emission intensity of F (the time integral value thereof) can be changed.
  • the calculation unit 18 includes a measurement instruction unit 64 that instructs the sensor control circuit 16 (light source control unit 60) to start measurement using the fluorescence sensor 14, and an interval determination unit 66 that determines a sampling interval Ts for measurement. And a measurement accuracy determination unit 68 that determines a statistical error as a measurement error level (device error Er) caused by the sensing device 10 and a first measurement mode (hereinafter referred to as “M (Monitor) mode”). ) And the second measurement mode (hereinafter sometimes referred to as “D (Determine) mode”) and the analyte A based on the fluorescence intensity F (t) from the fluorescence signal acquisition unit 62.
  • a concentration quantification unit 72 for quantifying the concentration [A (t)] (hereinafter also simply referred to as [A]).
  • the “first measurement mode” means a mode in which light is received and measured in a state where the energy amount of the fluorescence F acquired by the fluorescence sensor 14 is relatively low.
  • the “second measurement mode” means a mode in which light is received and measured in a state where the energy amount of the fluorescence F acquired by the fluorescence sensor 14 is relatively high.
  • Fluorescence intensity F (t) tends to increase as the amount of excitation light E increases in the range in which the fluorescent sensor 14 can operate normally.
  • the power consumption in the first measurement mode is relatively smaller than the power consumption in the second measurement mode.
  • the dynamic range of the fluorescence intensity F (t) in the second measurement mode is relatively larger than the dynamic range of the fluorescence intensity F (t) in the first measurement mode. That is, assuming that the signal-to-noise ratio in the first and second measurement modes is the same, the noise amount in the second measurement mode is relative to the noise amount in the first measurement mode. Become smaller.
  • the first measurement mode is suitable for constantly monitoring the change in the concentration [A (t)], and the second measurement mode quantifies the concentration [A (t)] with high accuracy. It can be said that it is suitable for.
  • step S1 the calculation unit 18 performs initial setting of measurement conditions.
  • a user such as a doctor designates a mode suitable for the subject via the input unit 27. This mode is prepared according to the dynamics of the subject, for example, after meals, at bedtime, during exercise, and the like.
  • step S2 and the subsequent steps are executed, an interrupt process is generated in response to an operation from the input unit 27, so that the process returns to step S1 to reflect changes in various parameters as needed.
  • the interval determination unit 66 determines the sampling interval Ts in the M mode and the D mode, respectively.
  • the measurement accuracy determination unit 68 determines measurement errors in the M mode and D mode (specifically, the excitation light amount Pe or the device error Er).
  • the measurement mode switching unit 70 switches to any one of the M mode and the D mode.
  • step S2 the calculation unit 18 determines whether or not there is a measurement / quantification instruction for the analyte A. Specifically, the arithmetic unit 18 counts the number of pulses of the clock signal input from the clock generator 26, and when the count reaches an upper limit value (corresponding to the sampling interval Ts when converted to time), it is quantitative. It is determined that there is an instruction. On the other hand, if the count upper limit value has not been reached, it remains in step S2 until it reaches.
  • the measurement instruction unit 64 identifies the type of measurement mode from the signal supplied from the measurement mode switching unit. When it is identified that the mode is the M mode, the measurement instruction unit 64 outputs an instruction signal for starting the measurement in the M mode to the light source control unit 60. Then, the light source control unit 60 causes the LED element 46 to emit light by supplying relatively small driving power.
  • the excitation light E is light having a relatively small light amount (energy amount) and is emitted toward the indicator layer 50 (that is, the analyte A, the labeling compound, or the third component) (step S4).
  • the measurement instruction unit 64 outputs an instruction signal to the effect that the measurement in the D mode is started to the light source control unit 60. Then, the light source control unit 60 causes the LED element 46 to emit light by supplying relatively large driving power.
  • the excitation light E is light having a relatively large light amount (energy amount) and is emitted toward the indicator layer 50 (step S5).
  • step S6 the sensor control circuit 16 (fluorescence signal acquisition unit 62) detects the fluorescence F (see FIG. 3) due to the interaction between the analyte A and the labeling compound via the fluorescence sensor 14. As the light amount of the excitation light E increases, the emission intensity of the fluorescence F increases, so the emission intensity of the fluorescence F in the first measurement mode becomes smaller than the emission intensity of the fluorescence F in the second measurement mode.
  • the fluorescence signal acquisition unit 62 acquires a fluorescence signal corresponding to the intensity of the fluorescence F, converts the fluorescence signal into the fluorescence intensity F (t) (or as it is), and supplies it to the calculation unit 18 side. Then, the calculation unit 18 temporarily stores the fluorescence intensity F (t) or the fluorescence signal in the RAM 24.
  • the sensor control circuit 16 may acquire the temperature signal via the temperature sensor 15 in synchronization (or asynchronously) with the acquisition of the fluorescence signal.
  • the concentration quantification unit 72 quantifies the concentration [A (t)] of the analyte A using the acquired fluorescence intensity F (t), the quantification coefficient read from the RAM 24, and the like.
  • the concentration [A (t)] can be quantified by various methods suitable for the material of the fluorescent dye, the nature of the chemical reaction, and the like.
  • step S8 the calculation unit 18 determines whether the current measurement mode is the M mode or the D mode. When it is determined that the mode is the M mode, the calculation unit 18 proceeds to the next step (S10) without executing step S9.
  • the calculation unit 18 causes the display device 28 to display various information related to the concentration [A (t)] quantified in step S7 (step S9).
  • concentration [A (t)] quantified in the D mode is selectively displayed, a quantitative value with high measurement accuracy can always be notified to the user.
  • a mark indicating the latest trend for example, the rising state, the falling state, and the flat state
  • rend means a variation tendency of the density [A (t)] in a predetermined time width.
  • the measurement mode switching unit 70 determines the next measurement mode.
  • the measurement mode switching unit 70 switches to either the M mode or the D mode based on various information such as the number of times of measurement and the history of the fluorescence intensity F (t).
  • the measurement mode switching unit 70 switches from the M mode to the D mode (in accordance with the concentration [A (t)] of the analyte A determined at least once in the M mode (first measurement mode). Switch to the second measurement mode.
  • the measurement mode switching unit 70 switches from the M mode to the D mode according to the number of times of measurement (for example, 5 times or more and 500 times or less). Details will be described later.
  • step S11 the interval determination unit 66 and / or the measurement accuracy determination unit 68 determines whether or not the measurement condition needs to be changed. Various determination conditions may be provided. If it is determined that no change is necessary, the process proceeds to the next step (S13) without executing step S12.
  • the interval determination unit 66 and / or the measurement accuracy determination unit 68 appropriately change the measurement conditions (step S12).
  • the measurement accuracy determination unit 68 determines the ratio of the excitation light amount Pe in the D mode to the excitation light amount Pe in the M mode (hereinafter referred to as the light amount ratio) according to the concentration [A (t)] of the analyte A. It may be changed.
  • This light quantity ratio is preferably 2 or more and 100 or less, and more preferably 10 or more and 50 or less.
  • the ratio of the apparatus error Er in the D mode to the apparatus error Er in the M mode (hereinafter referred to as “error ratio”) is approximately 1 /. 100 to 1/2, or 1/50 to 1/10.
  • error ratio the ratio of the apparatus error Er in the D mode to the apparatus error Er in the M mode
  • step S13 the calculation unit 18 determines whether or not there is an instruction to end the series of quantitative operations. If it is determined that the end instruction has not been given, the process returns to step S2, and steps S2 to S13 are repeated thereafter. On the other hand, when there is an end instruction, the sensing device 10 ends the quantitative operation of the analyte A.
  • FIG. 6 is a first table for explaining measurement conditions in each measurement mode. This table shows a sampling interval Ts (unit: min), an excitation light amount Pe (unit: cd / m 2), and an apparatus error Er (unit: mg / ml) in each measurement mode.
  • the excitation light amount Pe is “weak” (dynamic range is “narrow”)
  • the sampling interval Ts is 10 [min] at the maximum
  • the excitation light amount Pe is “strong” (dynamic range is “wide”)
  • M mode and D mode are executed synchronously and alternatively.
  • the M mode is executed.
  • a predetermined interrupt condition for example, at least one of the first condition and the second condition is satisfied
  • a mode interrupt is generated and the D mode is preferentially executed.
  • the first condition is when the D-mode sampling interval Ts matches (or exceeds) 10 [min].
  • the second condition is that the absolute value ⁇ of the difference between the quantitative value in the M mode and the quantitative value in the most recent D mode (corresponding to the “change amount” in FIG. 7) is a predetermined threshold Th [mg. / Dl].
  • FIG. 7 is a schematic explanatory diagram illustrating the result of time-series switching in the measurement mode. This figure shows the type of measurement mode, blood glucose level [mg / dl], and amount of change [mg / dl] at the time [min] from the start of measurement.
  • the measurement is performed with high accuracy by the D mode, and as a result, a quantitative value of 100 [mg / dl] is obtained.
  • the calculation unit 18 obtains the concentration [A (t)] of the analyte A as time series data for each quantification time t while appropriately switching between the M mode and the D mode.
  • FIG. 8 is a graph showing the first change in blood glucose concentration.
  • the horizontal axis of the graph is time (unit: min), and the vertical axis of the graph is glucose concentration, so-called blood glucose level (unit: mg / dl).
  • This change in blood glucose level simulates a change in blood glucose level in the body after meals of the subject.
  • the maximum gradient is approximately 10 [mg / (dl ⁇ min)], and it is assumed that there is a sudden change in the subject.
  • FIG. 9A is a graph showing a plot of blood glucose level obtained by successively quantifying the concentration change shown in FIG. 8 using only the M mode.
  • the moving average of this graph almost coincides with the graph shown in FIG. However, each data of this graph has a large deviation (variation) with respect to the moving average.
  • FIG. 9B is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 using only the D mode.
  • Each plot position is generally projected on the graph shown in FIG. That is, in the D mode, it means that the amount is determined with high accuracy within the range of 0 to 400 [mg / dl].
  • the sampling interval Ts increases, the time delay increases and the immediacy of measurement is lost. As shown in FIG.
  • concentration [A (t)] is displayed on the display device 28 for each fixed amount, the user may not be able to detect a sudden change (high blood sugar, low blood sugar) of the state of the subject from the transition of the display value. .
  • the device error Er it is desirable to minimize the device error Er and to minimize the sampling interval Ts.
  • the frequency of battery replacement increases. Further, when the high-intensity excitation light E is emitted at a high frequency, deterioration of the fluorescent dye is promoted.
  • FIG. 10 is a graph showing a plot of blood glucose levels obtained by switching the M mode and D mode and sequentially quantifying the concentration change shown in FIG.
  • FIG. 11 is a graph showing a plot of blood sugar levels obtained by sequentially quantifying the second concentration change according to the measurement conditions shown in FIG.
  • the second density change has a flat characteristic as compared with the first density change (see FIG. 8).
  • the measurement in the D mode is executed a total of 26 times within the measurement time range (between 0 and 400 [min]).
  • the intensity of the measurement signal (fluorescence F) acquired by the fluorescence sensor 14 is relatively low, and the intensity of the measurement signal (fluorescence F) is lower than that in the first measurement mode. Since the measurement mode switching unit 70 for switching the relatively high second measurement mode (D mode) is provided, two different measurement modes can be used in combination depending on the situation, and the quantitative measurement with respect to the concentration change of the analyte A can be performed. While maintaining the followability, it is possible to suppress deterioration of the electronic components constituting the fluorescent sensor 14 and various substances related to measurement.
  • a sensing method according to the first modification will be described with reference to FIGS. 12A to 13B.
  • the sensing method according to this modification is different from the sensing method according to this embodiment (see FIG. 6) in the measurement conditions (particularly, interrupt generation conditions) in the D mode.
  • an appropriate device error Er is set according to the threshold value Th that is one of the interrupt conditions.
  • FIG. 12B is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. 12A.
  • the number of quantitative points substantially equal to that in FIG. 10 is obtained in the range of 0 to 50 [min] or 100 to 250 [min].
  • the quantitative result of FIG. 10 can be substantially reproduced without setting the maximum interval of the D mode (10 [min] in the example of FIG. 6).
  • FIG. 13A shows the measurement conditions when the excitation light amount Pe in the M mode is set to “more weak” with respect to FIG. 12A.
  • Other measurement conditions are the same as those shown in FIG. 12A.
  • FIG. 13B is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. 13A.
  • a peak value in the vicinity of 50 [min] can be detected, but the number of quantitative points in the range of 0 to 50 [min] or 100 to 250 [min] is reduced. .
  • the device error Er mixed in the quantitative value affects the positive (or negative) change amount as a negative (or positive) canceling component, and D It is inferred that the mode frequency was irregularly reduced.
  • the value of the device error Er may be determined in consideration of the threshold Th in order to sufficiently secure the quantification frequency in the D mode. Specifically, it is preferable that the range is 1 ⁇ (Th / Er) ⁇ 2 and 0 ⁇ Th + Er ⁇ 200 [mg / dl].
  • the sensing method according to the second modification will be described with reference to FIGS. 14 to 17B.
  • the sensing method according to this modification is different from the sensing method according to this embodiment (see FIG. 6) in that the apparatus error Er in the M mode can be set variably.
  • FIG. 14 is a graph showing a third change in blood glucose concentration.
  • the horizontal axis of the graph is time (unit: min), and the vertical axis of the graph is glucose concentration, so-called blood glucose level (unit: mg / dl).
  • a sudden rise fluctuation occurs in the range of 0 to 60 [min]
  • a sudden fall fluctuation occurs in the range of 320 to 350 [min].
  • the excitation light amount Pe is “variable” (the dynamic range is “variable”).
  • the light source control unit 60 controls the excitation light amount Pe from the LED element 46 according to the concentration [A] of the analyte A. This [A] is the most recent quantitative value in D mode (unit: [mg / dl]).
  • the light source control unit 60 sets the excitation light amount Pe as the concentration [A] decreases. What is necessary is just to control the LED element 46 so that it may increase.
  • the excitation light amount Pe is sequentially executed by the measurement accuracy determination unit 68 and supplied to the light source control unit 60 side via the measurement instruction unit 64.
  • the difference is that the threshold Th of the second condition is variable.
  • FIG. 16A is a graph showing a plot of blood glucose levels obtained by sequentially quantifying the concentration change shown in FIG. 14 using only the D mode.
  • FIG. 16B is a graph showing a tendency of the tracking error obtained from the quantitative result shown in FIG. 16A.
  • the tracking error shown in FIG. 16B and FIG. 17B is defined by (change amount of quantitative value between D modes) / (quantitative value in D mode) ⁇ 100 [%].
  • the maximum positive value of the tracking error is approximately 50% (near 140 [mg / dl]).
  • the negative maximum value of the tracking error is approximately 30% (200, 260 [mg / dl] vicinity). That is, as can be understood from FIGS. 16A and 16B, when the blood sugar level changes rapidly, a tracking error tends to occur.
  • FIG. 17A is a graph showing a plot of blood sugar levels obtained by sequentially quantifying the concentration change shown in FIG. 14 according to the measurement conditions shown in FIG.
  • FIG. 17B is a graph showing the tendency of the tracking error obtained from the quantitative result shown in FIG. 17A.
  • the positive maximum value of the tracking error is approximately 20% (80 to 150 [mg / dl] vicinity).
  • the negative maximum value of the tracking error is approximately 20% (near 250 [mg / dl]).
  • the reduction in error was significant.
  • the degree of freedom in design is increased by changing the excitation light amount Pe or the threshold value Th according to the concentration [A] of the analyte A.
  • the excitation light amount Pe as the concentration [A] decreases, the measurement accuracy in the M mode in the hypoglycemic state is improved.
  • a sensing method according to the third modification will be described with reference to FIGS. 18 to 19B.
  • the sensing method according to this modification is different from the sensing method according to this embodiment (see FIG. 6) in that the apparatus error Er in the M mode can be set variably.
  • the light source control unit 60 determines the device error Er according to the magnitude relationship between the density [A] and a predetermined threshold value.
  • FIG. 19A is a graph showing a part of a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG.
  • FIG. 19B is a graph showing a part of a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG.
  • the definition of the horizontal axis and the vertical axis of the graph is the same as that of the graph of FIG. 8, but for the convenience of explanation, a specific range is shown in an enlarged manner.
  • the number of quantification points (quantitative frequency) by the D mode. Is increasing.
  • the user can check a value with a small difference from the actual concentration on the display 28 (see FIG. 1), and the possibility of the hypoglycemic state being expressed It can be detected sooner.
  • the sensing method according to the fourth modification will be described with reference to FIG.
  • the sensing method according to this modification is different from the sensing method according to this embodiment (see FIG. 6) in that a plurality of types of sampling intervals Ts in the M mode (first measurement mode) are provided.
  • FIG. 20 is a sixth table for explaining the measurement conditions in each measurement mode.
  • the sampling interval Ts in the M mode is determined according to the zone and / or trend attributes.
  • a zone is an element of each range when a predetermined concentration range (for example, 0 to 500 [mg / dl]) is divided into a plurality of ranges.
  • the interval determination unit 66 sets the “High” zone when the latest quantitative value in the D mode exceeds 200 [mg / dl] (first threshold), and the blood glucose level is 100 to 200 [mg / dl. ] In the “Middle” zone, and when the blood glucose level falls below 100 [mg / dl] (second threshold; smaller than the first threshold), it is determined to belong to the “Low” zone.
  • the interval determination unit 66 obtains a regression line from a plurality of most recent quantitative values, and when the gradient is larger than a predetermined positive value, the “rising” state, and when the gradient is smaller than a predetermined negative value, “ It is determined that the state is “down”, and in other cases it is “flat”.
  • the interval determination unit 66 may sequentially determine the sampling interval Ts according to the concentration [A] of the analyte A and / or its trend in the M mode.
  • the blood glucose level is determined by determining the sampling interval Ts when the concentration [A] of the analyte A is not less than the first threshold and / or not more than the second threshold to be smaller than the sampling interval Ts in the remaining concentration range. The accuracy of capturing the time-series peaks is improved.
  • the predetermined concentration range is classified into a plurality of zones, and the sampling interval Ts is determined according to the affiliation of each zone with respect to the obtained quantitative value, whereby the change in the concentration [A (t)] is changed. It can be grasped globally and timely quantification without excess or deficiency becomes possible. Further, by considering not only whether or not a plurality of zones belong but also trends, it is possible to capture changes in concentration [A (t)] from different viewpoints, which is more effective.

Abstract

The present invention relates to a sensing device and a sensing method for quantifying the concentration of an analyte intermittently or continuously. A measurement signal related to the concentration of an analyte (A) is obtained according to a predetermined sampling interval by using a sensor unit (12). Then, switching is performed between a first measurement mode (M mode) in which the intensity of the measurement signal is relatively low, and a second measurement mode (D mode) in which the intensity of the measurement signal is relatively higher than the first measurement mode.

Description

センシング装置及びセンシング方法Sensing device and sensing method
　この発明は、アナライトの濃度を間欠的又は連続的に定量するセンシング装置及びセンシング方法に関する。 The present invention relates to a sensing device and a sensing method for quantifying an analyte concentration intermittently or continuously.
　近時、例えば、アナライトと標識化合物との相互作用により蛍光強度が変化する性質を利用して、前記アナライトの濃度を定量するセンシング装置が開発されている。一適用例として、被検体の体内にセンサ部を埋め込み、グルコース濃度の連続定量を可能にする装置が提案されている（特許第４５９３９５７号公報及び特許第４５５８４４８号公報参照）。この装置を用いて糖尿病患者の血糖値の時系列データを取得・解析することで、血糖値を安定化するための薬剤の投与プロトコール設定や、生活習慣の改善指導を適切に行える。 Recently, for example, a sensing device for quantifying the concentration of the analyte has been developed by utilizing the property that the fluorescence intensity changes due to the interaction between the analyte and the labeled compound. As an application example, an apparatus has been proposed in which a sensor unit is embedded in the body of a subject and glucose concentration can be continuously quantified (see Japanese Patent Nos. 4593957 and 4558448). By using this device to acquire and analyze time series data of blood glucose levels of diabetic patients, it is possible to appropriately set the administration protocol of drugs for stabilizing blood glucose levels and provide guidance on improving lifestyle habits.
　しかしながら、特許第４５９３９５７号公報及び特許第４５５８４４８号公報に開示された技術的思想は、装置の構造の改良により受光感度を向上させることを目的としており、例えば、長時間（長期）にわたって蛍光センサを安定的に使用可能にする余地が十分にある。 However, the technical idea disclosed in Japanese Patent No. 4593957 and Japanese Patent No. 4558448 aims to improve the light receiving sensitivity by improving the structure of the device. For example, the fluorescent sensor can be used for a long time (long term). There is plenty of room for stable use.
　本発明は、上記した課題を解決するためになされたものであって、アナライトの濃度変化に対する定量の追従性を維持しつつも、センサ部を構成する電子部品、計測に関わる各種物質等の劣化を抑制可能なセンシング装置及びセンシング方法を提供することを目的とする。 The present invention has been made in order to solve the above-described problems, and while maintaining the follow-up ability of the quantitative measurement with respect to the concentration change of the analyte, the electronic parts constituting the sensor unit, various substances related to measurement, etc. An object is to provide a sensing device and a sensing method capable of suppressing deterioration.
　本発明に係るセンシング装置は、アナライトの濃度を間欠的又は連続的に定量する装置であって、所定のサンプリング間隔に従って前記アナライトの濃度に相関する計測信号を取得するセンサ部と、前記センサ部により取得される前記計測信号の強度が相対的に低い第１計測モード、及び前記第１計測モードよりも前記計測信号の強度が相対的に高い第２計測モードを切り替える計測モード切替部とを備えることを特徴とする。 The sensing device according to the present invention is a device for intermittently or continuously quantifying the concentration of an analyte, the sensor unit acquiring a measurement signal correlated with the concentration of the analyte according to a predetermined sampling interval, and the sensor A measurement mode switching unit that switches between a first measurement mode in which the intensity of the measurement signal acquired by the unit is relatively low, and a second measurement mode in which the intensity of the measurement signal is relatively higher than that in the first measurement mode. It is characterized by providing.
　このように、センサ部により取得される計測信号の強度が相対的に低い第１計測モード、及び前記第１計測モードよりも前記計測信号の強度が相対的に高い第２計測モードを切り替える計測モード切替部を設けたので、状況に応じて異なる２つの計測モードを組み合わせて使用可能になり、アナライトの濃度変化に対する定量の追従性を維持しつつも、センサを構成する電子部品、計測に関わる各種物質等の劣化を抑制できる。 As described above, the first measurement mode in which the intensity of the measurement signal acquired by the sensor unit is relatively low, and the measurement mode for switching the second measurement mode in which the intensity of the measurement signal is relatively higher than that in the first measurement mode. Since a switching unit is provided, it is possible to use a combination of two different measurement modes depending on the situation, and while maintaining the follow-up of quantitative measurement with respect to changes in analyte concentration, it is related to the electronic components and measurement that make up the sensor. Deterioration of various substances can be suppressed.
　また、前記センサ部は、エネルギーを放射するエネルギー源を有し、前記エネルギー源から放射された前記エネルギーを標識物質に対して与えることで前記計測信号を取得することが好ましい。 Further, it is preferable that the sensor unit has an energy source that radiates energy, and obtains the measurement signal by applying the energy radiated from the energy source to a labeling substance.
　さらに、前記計測モード切替部により前記第１計測モードに切り替えられた場合に前記エネルギーの放射量が相対的に少なくなるように前記エネルギー源を制御するとともに、前記第２計測モードに切り替えられた場合に前記エネルギーの放射量が相対的に多くなるように前記エネルギー源を制御するエネルギー源制御部をさらに備えることが好ましい。エネルギーの放射がトリガとなって計測信号を得るセンサの場合、定量頻度を減らすことが消費電力の低減に大きく寄与するため、特に効果的である。 Further, when the energy source is controlled to be relatively reduced when the measurement mode switching unit switches to the first measurement mode, the energy source is controlled and the second measurement mode is switched. It is preferable to further include an energy source controller that controls the energy source so that the amount of radiation of the energy is relatively large. In the case of a sensor that obtains a measurement signal triggered by energy emission, reducing the quantitative frequency greatly contributes to the reduction of power consumption, and thus is particularly effective.
　さらに、前記計測モード切替部は、前記第１計測モードによる計測頻度が前記第２計測モードによる計測頻度よりも高くなるように切り替えることが好ましい。これにより、濃度変化を監視する場合に第１計測モードを用い、濃度を精度良く定量する場合に第２計測モードを用いる計測・定量の形態が実現可能であり、濃度変化に対する定量の追従性を維持しつつも、センサを構成する電子部品、計測に関わる各種物質等の劣化を抑制できる。 Furthermore, it is preferable that the measurement mode switching unit switches the measurement frequency in the first measurement mode to be higher than the measurement frequency in the second measurement mode. As a result, it is possible to realize a measurement / quantification form using the first measurement mode when monitoring the concentration change and using the second measurement mode when accurately quantifying the concentration. While maintaining, it is possible to suppress deterioration of electronic components constituting the sensor and various substances related to measurement.
　さらに、前記計測モード切替部は、前記第１計測モードの際に少なくとも１回定量された前記アナライトの濃度に応じて、前記第１計測モードから前記第２計測モードに切り替えることが好ましい。 Furthermore, it is preferable that the measurement mode switching unit switches from the first measurement mode to the second measurement mode according to the concentration of the analyte quantified at least once during the first measurement mode.
　さらに、前記計測モード切替部は、計測回数に応じて前記第１計測モードから前記第２計測モードに切り替えることが好ましい。 Furthermore, it is preferable that the measurement mode switching unit switches from the first measurement mode to the second measurement mode according to the number of measurements.
　さらに、前記サンプリング間隔を決定する間隔決定部をさらに備えることが好ましい。 Furthermore, it is preferable to further include an interval determination unit that determines the sampling interval.
　さらに、前記間隔決定部は、前記第１計測モードで、前記アナライトの濃度に応じて前記サンプリング間隔を決定することが好ましい。 Furthermore, it is preferable that the interval determination unit determines the sampling interval according to the concentration of the analyte in the first measurement mode.
　さらに、前記間隔決定部は、前記アナライトの濃度が第１閾値以上及び／又は第２閾値（前記第１閾値よりも小さい。）以下でのサンプリング間隔を、残余の濃度範囲での前記サンプリング間隔よりも小さい値に決定することが好ましい。 Further, the interval determination unit may calculate a sampling interval when the concentration of the analyte is greater than or equal to a first threshold and / or less than or equal to a second threshold (less than the first threshold) in the remaining concentration range. It is preferable to determine a smaller value.
　さらに、前記エネルギー源制御部は、前記第１計測モードで、前記アナライトの濃度に応じて前記エネルギーの放射量を制御することが好ましい。 Furthermore, it is preferable that the energy source control unit controls the radiation amount of the energy according to the concentration of the analyte in the first measurement mode.
　さらに、エネルギー源制御部は、前記アナライトの濃度が減少するにつれて前記エネルギーの放射量を増加するように前記エネルギー源を制御することが好ましい。 Furthermore, it is preferable that the energy source control unit controls the energy source so as to increase the radiation amount of the energy as the concentration of the analyte decreases.
　さらに、前記第１計測モード及び前記第２計測モードにおける計測精度としての統計誤差をそれぞれ決定する計測精度決定部をさらに備えることが好ましい。 Furthermore, it is preferable to further include a measurement accuracy determination unit that determines statistical errors as measurement accuracy in the first measurement mode and the second measurement mode, respectively.
　さらに、前記計測精度決定部は、前記第１計測モードでの前記統計誤差に対する前記第２計測モードでの前記統計誤差の比を１／１００以上１／２以下の範囲で決定することが好ましい。 Furthermore, it is preferable that the measurement accuracy determination unit determines a ratio of the statistical error in the second measurement mode to the statistical error in the first measurement mode within a range of 1/100 or more and 1/2 or less.
　さらに、前記センサ部は、前記標識物質又は被検体に前記エネルギーを与えて発生させた光現象から前記計測信号を取得する光学センサを含むことが好ましい。 Furthermore, it is preferable that the sensor unit includes an optical sensor that acquires the measurement signal from a light phenomenon generated by applying the energy to the labeling substance or the subject.
　さらに、前記エネルギー源は、前記計測信号を得るための蛍光の発生を促す前記エネルギーとしての励起光を前記標識物質に向けて放射する励起光源であり、前記エネルギー源制御部は、前記サンプリング間隔に従って前記励起光を放射させるように前記励起光源を制御することが好ましい。 Further, the energy source is an excitation light source that emits excitation light as the energy for promoting generation of fluorescence for obtaining the measurement signal toward the labeling substance, and the energy source control unit is configured to follow the sampling interval. It is preferable to control the excitation light source so that the excitation light is emitted.
　本発明に係るセンシング方法は、アナライトの濃度を間欠的又は連続的に定量するセンシング装置を用いた方法であって、前記センシング装置が備えるセンサ部を用いて、所定のサンプリング間隔に従って前記アナライトの濃度に相関する計測信号を取得する取得ステップと、前記センサにより取得される前記計測信号の強度が相対的に低い第１計測モード、及び前記第１計測モードよりも前記計測信号の強度が相対的に高い第２計測モードを切り替える切替ステップとを備えることを特徴とする。 The sensing method according to the present invention is a method using a sensing device that quantifies the concentration of an analyte intermittently or continuously, and uses the sensor unit provided in the sensing device to perform the analyte according to a predetermined sampling interval. An acquisition step of acquiring a measurement signal correlated with the concentration of the first measurement mode, a first measurement mode in which the intensity of the measurement signal acquired by the sensor is relatively low, and an intensity of the measurement signal relative to that of the first measurement mode. And a switching step for switching the second measurement mode that is relatively high.
　また、前記センサ部は、エネルギーを放射するエネルギー源を有し、前記取得ステップでは、前記エネルギー源から放射された前記エネルギーを標識物質に対して与えることで前記計測信号を取得することが好ましい。 Further, it is preferable that the sensor unit has an energy source that radiates energy, and in the obtaining step, the measurement signal is obtained by applying the energy radiated from the energy source to a labeling substance.
　さらに、前記第１計測モードに切り替えられた場合に前記エネルギーの放射量が相対的に少なくなるように前記エネルギー源を制御するとともに、前記第２計測モードに切り替えられた場合に前記エネルギーの放射量が相対的に多くなるように前記エネルギー源を制御する制御ステップをさらに備えることが好ましい。 Further, the energy source is controlled so that the radiation amount of the energy becomes relatively small when switched to the first measurement mode, and the radiation amount of the energy when switched to the second measurement mode. Preferably, the method further includes a control step of controlling the energy source so that the number of the energy sources is relatively large.
　さらに、前記切替ステップでは、前記第１計測モードによる計測頻度が前記第２計測モードによる計測頻度よりも高くなるように切り替えることが好ましい。 Furthermore, in the switching step, it is preferable to switch so that the measurement frequency in the first measurement mode is higher than the measurement frequency in the second measurement mode.
　さらに、前記切替ステップでは、前記第１計測モードの際に少なくとも１回定量された前記アナライトの濃度に応じて、前記第１計測モードから前記第２計測モードに切り替えることが好ましい。 Furthermore, in the switching step, it is preferable to switch from the first measurement mode to the second measurement mode according to the concentration of the analyte determined at least once during the first measurement mode.
　さらに、前記切替ステップでは、計測回数に応じて前記第１計測モードから前記第２計測モードに切り替えることが好ましい。 Furthermore, in the switching step, it is preferable to switch from the first measurement mode to the second measurement mode according to the number of measurements.
　さらに、前記サンプリング間隔を決定する間隔決定ステップをさらに備えることが好ましい。 Furthermore, it is preferable to further include an interval determining step for determining the sampling interval.
　さらに、前記間隔決定ステップでは、前記第１計測モードで、前記アナライトの濃度に応じて前記サンプリング間隔を決定することが好ましい。 Further, in the interval determination step, it is preferable that the sampling interval is determined according to the concentration of the analyte in the first measurement mode.
　さらに、前記間隔決定ステップでは、前記アナライトの濃度が第１閾値以上及び／又は第２閾値（前記第１閾値よりも小さい。）以下でのサンプリング間隔を、残余の濃度範囲での前記サンプリング間隔よりも小さい値に決定することが好ましい。 Further, in the interval determination step, a sampling interval when the concentration of the analyte is not less than a first threshold and / or not more than a second threshold (smaller than the first threshold) is set as the sampling interval in the remaining concentration range. It is preferable to determine a smaller value.
　さらに、前記制御ステップでは、前記第１計測モードで、前記アナライトの濃度に応じて前記エネルギーの放射量を制御することが好ましい。 Furthermore, in the control step, it is preferable that the radiation amount of the energy is controlled according to the concentration of the analyte in the first measurement mode.
　さらに、前記制御ステップでは、前記アナライトの濃度が減少するにつれて前記エネルギーの放射量を増加するように前記エネルギー源を制御することが好ましい。 Furthermore, in the control step, it is preferable to control the energy source so as to increase the radiation amount of the energy as the concentration of the analyte decreases.
　さらに、前記第１計測モード及び前記第２計測モードにおける計測精度としての統計誤差をそれぞれ決定する精度決定ステップをさらに備えることが好ましい。 Furthermore, it is preferable to further include an accuracy determination step for determining statistical errors as measurement accuracy in the first measurement mode and the second measurement mode, respectively.
　さらに、前記精度決定ステップでは、前記第１計測モードでの前記統計誤差に対する前記第２計測モードでの前記統計誤差の比を１／１００以上１／２以下の範囲で決定することが好ましい。 Further, in the accuracy determination step, it is preferable that a ratio of the statistical error in the second measurement mode to the statistical error in the first measurement mode is determined in a range of 1/100 or more and 1/2 or less.
　さらに、前記センサ部は、前記標識物質又は被検体に前記エネルギーを与えて発生させた光現象から前記計測信号を取得する光学センサを含むことが好ましい。 Furthermore, it is preferable that the sensor unit includes an optical sensor that acquires the measurement signal from a light phenomenon generated by applying the energy to the labeling substance or the subject.
　さらに、前記エネルギー源は、前記計測信号を得るための蛍光の発生を促す前記エネルギーとしての励起光を前記標識物質に向けて放射する励起光源であり、前記制御ステップでは、前記サンプリング間隔に従って前記励起光を放射させるように前記励起光源を制御することが好ましい。 Further, the energy source is an excitation light source that emits excitation light as the energy that promotes generation of fluorescence for obtaining the measurement signal toward the labeling substance, and in the control step, the excitation is performed according to the sampling interval. It is preferable to control the excitation light source so as to emit light.
　本発明に係るセンシング装置及びセンシング方法によれば、センサ部により取得される計測信号の強度が相対的に低い第１計測モード、及び前記第１計測モードよりも前記計測信号の強度が相対的に高い第２計測モードを切り替えるようにしたので、状況に応じて異なる２つの計測モードを組み合わせて使用可能になり、アナライトの濃度変化に対する定量の追従性を維持しつつも、センサ部を構成する電子部品、計測に関わる各種物質等の劣化を抑制できる。 According to the sensing device and the sensing method of the present invention, the first measurement mode in which the intensity of the measurement signal acquired by the sensor unit is relatively low, and the intensity of the measurement signal is relatively lower than that in the first measurement mode. Since the high second measurement mode is switched, two different measurement modes can be used in combination depending on the situation, and the sensor unit is configured while maintaining the follow-up of the quantitative measurement for the concentration change of the analyte. Deterioration of electronic parts and various substances related to measurement can be suppressed.
本実施形態に係るセンシング装置の概略ブロック図である。It is a schematic block diagram of the sensing device concerning this embodiment. 図１に示すセンサ部の概略断面構成を表す模式図である。It is a schematic diagram showing the schematic cross-sectional structure of the sensor part shown in FIG. 図１に示すセンサ部の概略構造を説明するための分解斜視図である。It is a disassembled perspective view for demonstrating the schematic structure of the sensor part shown in FIG. 図１に示す演算部の機能ブロック図である。It is a functional block diagram of the calculating part shown in FIG. 図１に示すセンシング装置の動作説明に供されるフローチャートである。It is a flowchart with which operation | movement description of the sensing apparatus shown in FIG. 1 is provided. 各計測モードでの計測条件を説明する第１の表である。It is a 1st table | surface explaining the measurement conditions in each measurement mode. 計測モードの時系列的な切替結果を例示する概略説明図である。It is a schematic explanatory drawing which illustrates the time-series switching result of measurement mode. 血中グルコースの第１の濃度変化を表すグラフである。It is a graph showing the 1st density | concentration change of blood glucose. 図９Ａは、Ｍモードのみを用いて図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。図９Ｂは、Ｄモードのみを用いて図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを表すグラフである。FIG. 9A is a graph showing a plot of blood glucose level obtained by successively quantifying the concentration change shown in FIG. 8 using only the M mode. FIG. 9B is a graph showing a plot of blood glucose level obtained by successively quantifying the concentration change shown in FIG. 8 using only the D mode. 図６に示す計測条件に従って図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。It is a graph which shows the plot of the blood glucose level obtained by quantifying the density | concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. 図６に示す計測条件に従って第２の濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。It is a graph which shows the plot of the blood glucose level obtained by quantifying the 2nd density | concentration change sequentially according to the measurement conditions shown in FIG. 図１２Ａは、各計測モードでの計測条件を説明する第２の表である。図１２Ｂは、図１２Ａに示す計測条件に従って図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。FIG. 12A is a second table for explaining measurement conditions in each measurement mode. FIG. 12B is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. 12A. 図１３Ａは、各計測モードでの計測条件を説明する第３の表である。図１３Ｂは、図１３Ａに示す計測条件に従って図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。FIG. 13A is a third table for explaining measurement conditions in each measurement mode. FIG. 13B is a graph showing a plot of blood glucose levels obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. 13A. 血中グルコースの第３の濃度変化を表すグラフである。It is a graph showing the 3rd density | concentration change of blood glucose. 各計測モードでの計測条件を説明する第４の表である。It is a 4th table | surface explaining the measurement conditions in each measurement mode. 図１６Ａは、Ｄモードのみを用いて図１４に示す濃度変化を遂次定量することで、得られた血糖値のプロットを表すグラフである。図１６Ｂは、図１６Ａに示す定量結果から得られた追従誤差の傾向を示すグラフである。FIG. 16A is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 14 using only the D mode. FIG. 16B is a graph showing a tendency of the tracking error obtained from the quantitative result shown in FIG. 16A. 図１７Ａは、図１５に示す計測条件に従って図１４に示す濃度変化を遂次定量することで、得られた血糖値のプロットを表すグラフである。図１７Ｂは、図１７Ａに示す定量結果から得られた追従誤差の傾向を示すグラフである。FIG. 17A is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 14 according to the measurement conditions shown in FIG. FIG. 17B is a graph showing the tendency of the tracking error obtained from the quantitative result shown in FIG. 17A. 各計測モードでの計測条件を説明する第５の表である。It is a 5th table | surface explaining the measurement conditions in each measurement mode. 図１９Ａは、図６に示す計測条件に従って図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットの一部を表すグラフである。図１９Ｂは、図６に示す濃度変化を遂次定量することで、得られた血糖値のプロットの一部を表すグラフである。FIG. 19A is a graph showing a part of a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. FIG. 19B is a graph showing a part of a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 各計測モードでの計測条件を説明する第６の表である。It is a 6th table | surface explaining the measurement conditions in each measurement mode.
　以下、本発明に係るセンシング方法についてこれを実施するセンシング装置との関係において好適な実施形態を挙げ、添付の図面を参照しながら詳細に説明する。 Hereinafter, preferred embodiments of the sensing method according to the present invention will be described in relation to a sensing device that implements the sensing method, and will be described in detail with reference to the accompanying drawings.
［本実施形態（構成）］
　先ず、本実施形態に係るセンシング装置１０の構成について、図１～図３を参照しながら説明する。 [This embodiment (configuration)]
First, the configuration of the sensing device 10 according to the present embodiment will be described with reference to FIGS. 1 to 3.
　図１に示すように、センシング装置１０は、センサ部１２（蛍光センサ１４及び温度センサ１５を含む。）と、センサ制御回路１６と、演算部１８と、電源回路２０と、ＲＯＭ２２と、ＲＡＭ２４と、クロック発生器２６と、入力部２７と、表示器２８とを基本的に備える。 As shown in FIG. 1, the sensing device 10 includes a sensor unit 12 (including a fluorescence sensor 14 and a temperature sensor 15), a sensor control circuit 16, a calculation unit 18, a power supply circuit 20, a ROM 22, and a RAM 24. The clock generator 26, the input unit 27, and the display 28 are basically provided.
　蛍光センサ１４（光学センサともいう）は、アナライトＡと標識化合物との相互作用による蛍光Ｆの強度に応じた計測信号（以下、蛍光信号という。）を取得する。蛍光Ｆは、アナライトＡと標識化合物との結合又は解離に起因する光でもよいし、アナライトＡと異なる第３成分と標識化合物との結合又は解離に起因する光であってもよい。いずれの蛍光Ｆであっても、蛍光信号に基づいてアナライトＡの濃度を定量可能である。温度センサ１５は、蛍光センサ１４近傍での環境温度に応じた信号（以下、温度信号という。）を取得する。 The fluorescence sensor 14 (also referred to as an optical sensor) acquires a measurement signal (hereinafter referred to as a fluorescence signal) corresponding to the intensity of the fluorescence F due to the interaction between the analyte A and the labeled compound. The fluorescence F may be light resulting from the binding or dissociation between the analyte A and the labeling compound, or may be light resulting from the binding or dissociation between the third component different from the analyte A and the labeling compound. For any fluorescence F, the concentration of analyte A can be quantified based on the fluorescence signal. The temperature sensor 15 acquires a signal corresponding to the environmental temperature in the vicinity of the fluorescent sensor 14 (hereinafter referred to as a temperature signal).
　なお、センサ部１２は上記した形態に限定されるものではなく、標識物質又は被検体にエネルギーを与えて発生させた現象（例えば、光現象）から、アナライトＡの濃度に相関する計測信号を取得可能であればよい。例えば、蛍光センサ１４に代替して、吸光度、ラマン散乱光強度等を計測する光学センサや、温度、電気抵抗等を計測する化学センサを用いてもよい。 The sensor unit 12 is not limited to the above-described form, and a measurement signal correlated with the concentration of the analyte A from a phenomenon (for example, a light phenomenon) generated by applying energy to the labeling substance or the subject. It only needs to be acquired. For example, instead of the fluorescent sensor 14, an optical sensor that measures absorbance, Raman scattered light intensity, or the like, or a chemical sensor that measures temperature, electrical resistance, or the like may be used.
　センサ制御回路１６は、蛍光センサ１４及び温度センサ１５を駆動し、蛍光信号及び温度信号を取得可能に制御する。演算部１８は、ＣＰＵ、ＭＰＵ等で構成されており、ＲＯＭ２２に記録されたプログラムを読み出し、後述する各種信号処理を実行する。 The sensor control circuit 16 drives the fluorescence sensor 14 and the temperature sensor 15, and controls the fluorescence signal and the temperature signal so as to be acquired. The calculation unit 18 is composed of a CPU, an MPU, and the like, reads a program recorded in the ROM 22 and executes various signal processing described later.
　電源回路２０は、演算部１８を含むセンシング装置１０内の各構成要素に電力を供給する。ＲＡＭ２４は、蛍光センサ１４を介して入力された蛍光信号、温度センサ１５を介して入力された温度信号の他、本発明に係るセンシング方法を実施するために必要な各種データを読出し又は書込み可能である。クロック発生器２６は、所定周期でクロック信号を発生し、演算部１８側に供給する。これにより、演算部１８は、蛍光信号及び温度信号の取得タイミングの制御が可能である。 The power supply circuit 20 supplies power to each component in the sensing device 10 including the calculation unit 18. The RAM 24 can read or write various data necessary for carrying out the sensing method according to the present invention in addition to the fluorescence signal input via the fluorescence sensor 14 and the temperature signal input via the temperature sensor 15. is there. The clock generator 26 generates a clock signal at a predetermined cycle and supplies it to the calculation unit 18 side. Thereby, the calculating part 18 can control the acquisition timing of a fluorescence signal and a temperature signal.
　入力部２７は、演算部１８での演算に供される各種情報（例えば、計測モードの設定パラメータ）を入力可能に設けられている。例えば、押圧式ボタンであってもよいし、表示器２８に組み込まれたタッチパネルであってもよい。表示器２８は、演算部１８により定量されたアナライトＡの濃度に関する各種情報を可視化して表示する。表示器２８は、モノクロ又はカラー表示可能な表示モジュールであり、液晶パネル、有機ＥＬ（Electro-Luminescence）、無機ＥＬパネル等で構成されてもよい。 The input unit 27 is provided so as to be able to input various information (for example, measurement mode setting parameters) used for the calculation in the calculation unit 18. For example, a push button may be used, or a touch panel incorporated in the display device 28 may be used. The display 28 visualizes and displays various information related to the concentration of the analyte A quantified by the calculation unit 18. The display 28 is a display module capable of monochrome or color display, and may be composed of a liquid crystal panel, an organic EL (Electro-Luminescence), an inorganic EL panel, or the like.
　次いで、センサ部１２の構造について、図２及び図３を参照しながら詳細に説明する。 Next, the structure of the sensor unit 12 will be described in detail with reference to FIGS.
　図２に示すように、センサ部１２は、概略矩形状の筐体３０を備える。筐体３０内部は中空であり、蛍光センサ１４と、母材３２と、６本の金属線３４、３５、３６とを収容可能である。筐体３０及び母材３２は、例えばポリイミド、パリレン（ポリパラキシリレン）、又は環状ポリオレフィン等の樹脂でそれぞれ形成されている。また、外部光を遮光するため、材料中にカーボンブラック等の光遮断性材料を含有させてもよい。また、筐体３０の一面（進入面３８）は、ハイドロゲルとカーボンブラック等とからなり、アナライトＡを通過させるとともに、外部光を遮断する特性を有する。 As shown in FIG. 2, the sensor unit 12 includes a substantially rectangular casing 30. The inside of the housing 30 is hollow, and can accommodate the fluorescent sensor 14, the base material 32, and the six metal wires 34, 35, 36. The housing 30 and the base material 32 are each formed of a resin such as polyimide, parylene (polyparaxylylene), or cyclic polyolefin. Further, in order to block external light, the material may contain a light blocking material such as carbon black. In addition, one surface (entrance surface 38) of the housing 30 is made of hydrogel, carbon black, and the like, and has characteristics of allowing the analyte A to pass and blocking external light.
　蛍光センサ１４は、下方から上方の順に、シリコン等からなる基体４０と、フォトダイオード（Photo Diode：以下「ＰＤ」ともいう。）素子４２と、図示しない第１保護膜と、フィルタ４４と、発光ダイオード（Light Emitting Diode：以下「ＬＥＤ」ともいう。）素子４６（エネルギー源、励起光源）と、エポキシ樹脂等からなる第２保護膜４８と、インジケータ層５０とから構成されている。 The fluorescent sensor 14 includes, in order from the bottom to the top, a substrate 40 made of silicon or the like, a photodiode (Photo Diode: hereinafter referred to as “PD”) element 42, a first protective film (not shown), a filter 44, and light emission. A diode (Light （Emitting Diode: hereinafter also referred to as “LED”) element 46 (energy source, excitation light source), a second protective film 48 made of epoxy resin or the like, and an indicator layer 50 are included.
　基体４０の表面には、ＰＤ素子４２が形成されている。ＰＤ素子４２は、蛍光Ｆを電気信号に変換する光電変換素子である。ＰＤ素子４２に代替して、フォトコンダクタ（光導電体）、又はフォトトランジスタ（Photo Transistor、PT）等の各種光電変換素子を用いてもよい。なお、ＰＤ素子４２と金属線３４とは、ボンディングワイヤ５２、又は貫通配線等の手段により、電気的に結線されている。 A PD element 42 is formed on the surface of the substrate 40. The PD element 42 is a photoelectric conversion element that converts the fluorescence F into an electrical signal. Instead of the PD element 42, various photoelectric conversion elements such as a photoconductor (photoconductor) or a phototransistor (Phototransistor, PT) may be used. The PD element 42 and the metal wire 34 are electrically connected by means such as a bonding wire 52 or a through wiring.
　フィルタ４４は、ＬＥＤ素子４６が発光する励起光Ｅの波長帯域は遮断し、且つ、前記波長帯域よりも長波長側の蛍光Ｆを通過する吸収型光学フィルタである。光学フィルタとして、多結晶シリコン等のシリコン膜、炭化シリコン膜、又はガリウムリン膜等を用いてもよい。 The filter 44 is an absorptive optical filter that blocks the wavelength band of the excitation light E emitted from the LED element 46 and passes the fluorescence F on the longer wavelength side than the wavelength band. As the optical filter, a silicon film such as polycrystalline silicon, a silicon carbide film, or a gallium phosphide film may be used.
　ＬＥＤ素子４６は、蛍光信号を得るための蛍光Ｆの発生を促す励起光Ｅを放射する発光素子である。ＬＥＤ素子４６に代替して、有機ＥＬ素子、無機ＥＬ素子、又はレーザーダイオード素子等多様な種類の発光素子を用いてもよい。ここでは、蛍光Ｆの検出量（ＰＤ素子４２での受光量）を増加させるため、蛍光Ｆの光透過率が高い発光素子を選択することが好ましい。 The LED element 46 is a light emitting element that emits excitation light E that promotes generation of fluorescence F for obtaining a fluorescence signal. Instead of the LED element 46, various types of light emitting elements such as an organic EL element, an inorganic EL element, or a laser diode element may be used. Here, in order to increase the detection amount of the fluorescence F (the amount of light received by the PD element 42), it is preferable to select a light emitting element having a high light transmittance of the fluorescence F.
　インジケータ層５０は、進入面３８から進入したアナライトＡ（例えば、グルコース）の濃度に応じた蛍光Ｆを発光する。インジケータ層５０は、標識化合物としての蛍光色素が含まれたベース材料から構成されている。標識化合物（例えば、蛍光色素として、ルテニウム有機錯体やフェニルボロン酸誘導体、フルオロセイン標識デキストラン等のアナライトＡと可逆結合する物質）と第３成分（例えば、ローダミン－標識コンカナバリンＡ）との解離により蛍光Ｆを発光させる場合、インジケータ層５０のベース材料に標識化合物と併せて第３成分を含めてもよい。あるいは、第３成分を混入するための別異の機構を設けてもよい。 The indicator layer 50 emits fluorescence F corresponding to the concentration of analyte A (for example, glucose) that has entered from the entry surface 38. The indicator layer 50 is made of a base material containing a fluorescent dye as a labeling compound. By dissociation of a labeled compound (for example, a substance that reversibly binds to analyte A such as a ruthenium organic complex, a phenylboronic acid derivative, or a fluorescein-labeled dextran as a fluorescent dye) and a third component (for example, rhodamine-labeled concanavalin A). When the fluorescent light F is emitted, a third component may be included in the base material of the indicator layer 50 together with the labeling compound. Alternatively, another mechanism for mixing the third component may be provided.
　図３に示すように、筐体３０の内部には、蛍光センサ１４近傍での温度信号を取得可能な温度センサ１５（図１参照）も配設されている。温度センサ１５として、蛍光温度計等の光学型、サーミスタ型、金属薄膜抵抗型、又はＰＮ接合の順方向電流の温度特性を基礎におく半導体型等を用いてもよい。なお、半導体型センサの場合、ＰＤ素子４２と同様に、基体４０上に形成可能である。 As shown in FIG. 3, a temperature sensor 15 (see FIG. 1) capable of acquiring a temperature signal in the vicinity of the fluorescence sensor 14 is also arranged inside the housing 30. As the temperature sensor 15, an optical type such as a fluorescence thermometer, a thermistor type, a metal thin film resistance type, or a semiconductor type based on the temperature characteristics of the forward current of the PN junction may be used. In the case of a semiconductor type sensor, it can be formed on the substrate 40 like the PD element 42.
　金属線３４、３５、３６は、金、アルミニウム又は銅等の導電体で形成され、筐体３０内の電気配線としての役割に加えて、剛性増加の機能を有する。センサ部１２は、金属線３４～３６を介してセンサ制御回路１６（図１参照）と電気的に接続されている。図３に示すように、金属線３４は、２本の金属線３４ａ、３４ｂで構成されている。金属線３５は、２本の金属線３５ａ、３５ｂで構成されている。金属線３６は、２本の金属線３６ａ、３６ｂで構成されている。例えば、金属線３４（又は金属線３５）と金属線３６との間に図示しない絶縁層を設けることで、両者を電気的に絶縁してもよい。 The metal wires 34, 35, and 36 are formed of a conductor such as gold, aluminum, or copper, and have a function of increasing rigidity in addition to a role as electric wiring in the housing 30. The sensor unit 12 is electrically connected to the sensor control circuit 16 (see FIG. 1) via metal wires 34-36. As shown in FIG. 3, the metal wire 34 includes two metal wires 34a and 34b. The metal wire 35 is composed of two metal wires 35a and 35b. The metal wire 36 is composed of two metal wires 36a and 36b. For example, by providing an insulating layer (not shown) between the metal wire 34 (or the metal wire 35) and the metal wire 36, the two may be electrically insulated.
　これにより、金属線３４を介して、センサ制御回路１６は、ＰＤ素子４２からの蛍光信号を取得可能である。また、金属線３５を介して、センサ制御回路１６は、ＬＥＤ素子４６に駆動電力を供給可能である。さらに、金属線３６を介して、センサ制御回路１６は、温度センサ１５からの温度信号を取得可能である。 Thereby, the sensor control circuit 16 can acquire the fluorescence signal from the PD element 42 via the metal wire 34. Further, the sensor control circuit 16 can supply driving power to the LED element 46 via the metal wire 35. Furthermore, the sensor control circuit 16 can acquire the temperature signal from the temperature sensor 15 via the metal wire 36.
　次に、センサ部１２の動作について説明する。例えば、センサ部１２が針状である場合、被検体に針先端部を穿刺・保持させることで、前記被検体の体内のアナライトＡの濃度を連続して測定可能である。その際、一部のアナライトＡは、進入面３８から筐体３０の内部に進入して、インジケータ層５０周辺に滞在している。 Next, the operation of the sensor unit 12 will be described. For example, when the sensor unit 12 has a needle shape, the concentration of the analyte A in the body of the subject can be continuously measured by causing the subject to puncture and hold the needle tip. At that time, a part of the analyte A enters the inside of the housing 30 from the entry surface 38 and stays around the indicator layer 50.
　先ず、センサ制御回路１６は、蛍光センサ１４の金属線３５を介して、ＬＥＤ素子４６に駆動電力信号を供給することで、励起光Ｅは発光される。そして、ＬＥＤ素子４６からの励起光Ｅは、インジケータ層５０に入射される。そして、インジケータ層５０は、アナライトＡと標識化合物との相互作用により、あるいは第３成分を加えた相互作用により、アナライトＡの濃度に応じた強度の蛍光Ｆを発する。 First, the sensor control circuit 16 supplies a drive power signal to the LED element 46 through the metal wire 35 of the fluorescent sensor 14, whereby the excitation light E is emitted. Then, the excitation light E from the LED element 46 is incident on the indicator layer 50. The indicator layer 50 emits fluorescence F having an intensity corresponding to the concentration of the analyte A by the interaction between the analyte A and the labeling compound or by the interaction with the addition of the third component.
　インジケータ層５０からの蛍光Ｆは、ＬＥＤ素子４６、フィルタ４４等を透過された後、ＰＤ素子４２により光電変換され、蛍光信号として金属線３４を伝送され、センサ制御回路１６側に供給される。あわせて、温度センサ１５からの温度信号は、金属線３６を伝送され、センサ制御回路１６側に供給される。 Fluorescence F from the indicator layer 50 is transmitted through the LED element 46, the filter 44, etc., and then photoelectrically converted by the PD element 42, transmitted through the metal wire 34 as a fluorescence signal, and supplied to the sensor control circuit 16 side. In addition, a temperature signal from the temperature sensor 15 is transmitted through the metal wire 36 and supplied to the sensor control circuit 16 side.
　このようにして、蛍光センサ１４は蛍光信号を取得するとともに、温度センサ１５は温度信号を取得する。なお、図２及び図３に示すセンサ部１２は、酵素センサ、グルコースセンサ、ｐＨセンサ、免疫センサ、又は微生物センサ等、多様な用途に適用可能である。また、センサ部１２の構成は、本構成に限られることなく種々の構成を採り得ることはいうまでもない。例えば、物理的に分離されたセンサ制御回路１６及び演算部１８の間を無線で通信可能に設けることで、センサ部１２を被検体の体内に完全に埋め込んだ状態で間欠的又は連続的に定量可能である。 In this way, the fluorescence sensor 14 acquires a fluorescence signal, and the temperature sensor 15 acquires a temperature signal. 2 and 3 can be applied to various uses such as an enzyme sensor, a glucose sensor, a pH sensor, an immune sensor, or a microorganism sensor. Moreover, it cannot be overemphasized that the structure of the sensor part 12 can take various structures, without being restricted to this structure. For example, the sensor control circuit 16 and the arithmetic unit 18 that are physically separated are provided so as to be able to communicate with each other wirelessly, whereby the sensor unit 12 is quantified intermittently or continuously with the sensor unit 12 completely embedded in the body of the subject. Is possible.
　続いて、図１に示す演算部１８の構成について、図４の機能ブロック図を参照しながら説明する。なお、本図では、演算部１８以外の他の構成要素に関して、本発明に係るセンシング方法に密接に関連する構成要素を中心に図示している。 1 will be described with reference to the functional block diagram of FIG. In addition, in this figure, regarding other structural elements other than the calculation unit 18, the structural elements closely related to the sensing method according to the present invention are mainly illustrated.
　センサ制御回路１６は、所定の時点及び／又は光量で励起光Ｅを放射するようにＬＥＤ素子４６を駆動制御する光源制御部６０（エネルギー源制御部）と、ＰＤ素子４２から取得した蛍光信号を蛍光強度Ｆ（ｔ）として取得する蛍光信号取得部６２とを備える。光源制御部６０は、ＬＥＤ素子４６を駆動する駆動電力、具体的には電流値、電圧値、これらのパルス制御方法（パルスの数又は幅）等を変更することで、励起光Ｅ、ひいては蛍光Ｆの発光強度（の時間積分値）を変更可能である。 The sensor control circuit 16 includes a light source control unit 60 (energy source control unit) that drives and controls the LED element 46 so as to emit the excitation light E at a predetermined time and / or light amount, and a fluorescence signal acquired from the PD element 42. A fluorescence signal acquisition unit 62 that acquires the fluorescence intensity F (t). The light source control unit 60 changes the driving power for driving the LED element 46, specifically the current value, the voltage value, and the pulse control method (number or width of these pulses), etc. The light emission intensity of F (the time integral value thereof) can be changed.
　演算部１８は、蛍光センサ１４を用いた計測を開始する旨をセンサ制御回路１６（光源制御部６０）に対して指示する計測指示部６４と、計測のサンプリング間隔Ｔｓを決定する間隔決定部６６と、センシング装置１０に起因する計測の誤差レベル（装置誤差Ｅｒ）としての統計誤差を決定する計測精度決定部６８と、第１計測モード（以下、「Ｍ（Monitor）モード」という場合がある。）及び第２計測モード（以下、「Ｄ（Determine）モード」という場合がある。）を切り替える計測モード切替部７０と、蛍光信号取得部６２からの蛍光強度Ｆ（ｔ）に基づいてアナライトＡの濃度［Ａ（ｔ）］（以下、単に［Ａ］とも表記する。）を定量する濃度定量部７２とを備える。 The calculation unit 18 includes a measurement instruction unit 64 that instructs the sensor control circuit 16 (light source control unit 60) to start measurement using the fluorescence sensor 14, and an interval determination unit 66 that determines a sampling interval Ts for measurement. And a measurement accuracy determination unit 68 that determines a statistical error as a measurement error level (device error Er) caused by the sensing device 10 and a first measurement mode (hereinafter referred to as “M (Monitor) mode”). ) And the second measurement mode (hereinafter sometimes referred to as “D (Determine) mode”) and the analyte A based on the fluorescence intensity F (t) from the fluorescence signal acquisition unit 62. A concentration quantification unit 72 for quantifying the concentration [A (t)] (hereinafter also simply referred to as [A]).
　なお、本明細書において、「第１計測モード」とは、蛍光センサ１４により取得される蛍光Ｆのエネルギー量が相対的に低い状態で、受光・計測するモードを意味する。また、「第２計測モード」とは、蛍光センサ１４により取得される蛍光Ｆのエネルギー量が相対的に高い状態で、受光・計測するモードを意味する。 In the present specification, the “first measurement mode” means a mode in which light is received and measured in a state where the energy amount of the fluorescence F acquired by the fluorescence sensor 14 is relatively low. The “second measurement mode” means a mode in which light is received and measured in a state where the energy amount of the fluorescence F acquired by the fluorescence sensor 14 is relatively high.
　蛍光センサ１４として正常に動作可能な範囲において、励起光Ｅの光量が増加するにつれて、蛍光強度Ｆ（ｔ）が大きくなる傾向がある。この場合、第１計測モードにおける消費電力は、第２計測モードにおける消費電力よりも相対的に小さくなる。一方、第２計測モードにおける蛍光強度Ｆ（ｔ）のダイナミックレンジは、第１計測モードにおける蛍光強度Ｆ（ｔ）のダイナミックレンジよりも相対的に大きくなる。つまり、第１及び第２計測モードでのＳＮ比（signal-to-noise ratio）が同じであると仮定すると、第２計測モードでのノイズ量は、第１計測モードでのノイズ量よりも相対的に小さくなる。上記した計測上の特性を考慮すると、第１計測モードは濃度［Ａ（ｔ）］の変動を常時監視する場合に適しており、第２計測モードは濃度［Ａ（ｔ）］を精度良く定量する場合に適していると言える。 Fluorescence intensity F (t) tends to increase as the amount of excitation light E increases in the range in which the fluorescent sensor 14 can operate normally. In this case, the power consumption in the first measurement mode is relatively smaller than the power consumption in the second measurement mode. On the other hand, the dynamic range of the fluorescence intensity F (t) in the second measurement mode is relatively larger than the dynamic range of the fluorescence intensity F (t) in the first measurement mode. That is, assuming that the signal-to-noise ratio in the first and second measurement modes is the same, the noise amount in the second measurement mode is relative to the noise amount in the first measurement mode. Become smaller. Considering the above-mentioned measurement characteristics, the first measurement mode is suitable for constantly monitoring the change in the concentration [A (t)], and the second measurement mode quantifies the concentration [A (t)] with high accuracy. It can be said that it is suitable for.
　以下、説明の便宜のため、上記したノイズ量、より詳細には電気ノイズ、光量ノイズ等を含む、システム全体としての統計誤差を「装置誤差Ｅｒ」という。本明細書中において、濃度［Ａ（ｔ）］が一定の環境下で、統計的に有意なサンプル数だけ定量して得た標準偏差σを用いて、装置誤差ＥｒをＥｒ＝４σと定義する。この値は、正規分布（ガウス分布）上で約９５％の範囲内に含まれる定量幅を示している。 Hereinafter, for convenience of explanation, a statistical error of the entire system including the above-described noise amount, more specifically, electric noise, light amount noise, and the like will be referred to as “device error Er”. In the present specification, the apparatus error Er is defined as Er = 4σ using a standard deviation σ obtained by quantifying a statistically significant number of samples under a constant concentration [A (t)]. . This value indicates the quantitative range included in the range of about 95% on the normal distribution (Gaussian distribution).
［本実施形態（動作）］
　続いて、センシング装置１０の動作について、図４の機能ブロック図及び図５のフローチャートを主に参照しながら詳細に説明する。なお、本明細書では、アナライトＡとしてグルコースを用いた定量結果を中心に説明する。 [This embodiment (operation)]
Next, the operation of the sensing device 10 will be described in detail with reference mainly to the functional block diagram of FIG. 4 and the flowchart of FIG. In addition, in this specification, it demonstrates focusing on the quantitative result using glucose as the analyte A.
　ステップＳ１において、演算部１８は、計測条件の初期設定を行う。設定に先立ち、ユーザ（医師等）は、入力部２７を介して、被検体に適したモードを指定する。このモードは、例えば、食後、就寝時、運動時等、被検体の動態に応じてそれぞれ用意されている。なお、ステップＳ２以降が実行されている場合であっても、入力部２７からの操作に応じて割り込み処理が発生することでステップＳ１に戻り、各種パラメータの変更内容を随時反映させることができる。 In step S1, the calculation unit 18 performs initial setting of measurement conditions. Prior to setting, a user (such as a doctor) designates a mode suitable for the subject via the input unit 27. This mode is prepared according to the dynamics of the subject, for example, after meals, at bedtime, during exercise, and the like. Even when step S2 and the subsequent steps are executed, an interrupt process is generated in response to an operation from the input unit 27, so that the process returns to step S1 to reflect changes in various parameters as needed.
　具体的には、間隔決定部６６は、Ｍモード及びＤモードでのサンプリング間隔Ｔｓをそれぞれ決定する。また、計測精度決定部６８は、Ｍモード及びＤモードでの計測誤差（詳細には、励起光量Ｐｅ又は装置誤差Ｅｒ）をそれぞれ決定する。さらに、計測モード切替部７０は、Ｍモード及びＤモードのうちいずれか一方の計測モードに切り替える。 Specifically, the interval determination unit 66 determines the sampling interval Ts in the M mode and the D mode, respectively. In addition, the measurement accuracy determination unit 68 determines measurement errors in the M mode and D mode (specifically, the excitation light amount Pe or the device error Er). Furthermore, the measurement mode switching unit 70 switches to any one of the M mode and the D mode.
　ステップＳ２において、演算部１８は、アナライトＡの計測・定量指示があったか否かを判別する。具体的には、演算部１８は、クロック発生器２６から入力されたクロック信号のパルス数をカウントし、カウント上限値（時間に換算すると、サンプリング間隔Ｔｓに相当する。）に到達した場合、定量指示があったと判別する。一方、前記カウント上限値に到達していない場合、到達するまでステップＳ２に留まる。 In step S2, the calculation unit 18 determines whether or not there is a measurement / quantification instruction for the analyte A. Specifically, the arithmetic unit 18 counts the number of pulses of the clock signal input from the clock generator 26, and when the count reaches an upper limit value (corresponding to the sampling interval Ts when converted to time), it is quantitative. It is determined that there is an instruction. On the other hand, if the count upper limit value has not been reached, it remains in step S2 until it reaches.
　ステップＳ３において、計測指示部６４は、計測モード切替部７０から供給された信号から、計測モードの種別を識別する。Ｍモードであると識別された場合、計測指示部６４は、Ｍモードでの計測を開始する旨の指示信号を光源制御部６０に向けて出力する。そして、光源制御部６０は、相対的に小さい駆動電力を供給することでＬＥＤ素子４６を発光させる。この場合、励起光Ｅは、相対的に少ない光量（エネルギー量）からなる光であり、インジケータ層５０（すなわち、アナライトＡ、標識化合物又は第３成分）に向けて放射される（ステップＳ４）。 In step S3, the measurement instruction unit 64 identifies the type of measurement mode from the signal supplied from the measurement mode switching unit. When it is identified that the mode is the M mode, the measurement instruction unit 64 outputs an instruction signal for starting the measurement in the M mode to the light source control unit 60. Then, the light source control unit 60 causes the LED element 46 to emit light by supplying relatively small driving power. In this case, the excitation light E is light having a relatively small light amount (energy amount) and is emitted toward the indicator layer 50 (that is, the analyte A, the labeling compound, or the third component) (step S4). .
　一方、Ｄモードであると識別された場合、計測指示部６４は、Ｄモードでの計測を開始する旨の指示信号を光源制御部６０に向けて出力する。そして、光源制御部６０は、相対的に大きい駆動電力を供給することでＬＥＤ素子４６を発光させる。この場合、励起光Ｅは、相対的に多い光量（エネルギー量）からなる光であり、インジケータ層５０に向けて放射される（ステップＳ５）。 On the other hand, when it is identified as the D mode, the measurement instruction unit 64 outputs an instruction signal to the effect that the measurement in the D mode is started to the light source control unit 60. Then, the light source control unit 60 causes the LED element 46 to emit light by supplying relatively large driving power. In this case, the excitation light E is light having a relatively large light amount (energy amount) and is emitted toward the indicator layer 50 (step S5).
　ステップＳ６において、センサ制御回路１６（蛍光信号取得部６２）は、蛍光センサ１４を介して、アナライトＡと標識化合物との相互作用による蛍光Ｆ（図３参照）を検出する。励起光Ｅの光量が増加するにつれて、蛍光Ｆの発光強度が大きくなるので、第１計測モードにおける蛍光Ｆの発光強度は、第２計測モードにおける蛍光Ｆの発光強度よりも小さくなる。 In step S6, the sensor control circuit 16 (fluorescence signal acquisition unit 62) detects the fluorescence F (see FIG. 3) due to the interaction between the analyte A and the labeling compound via the fluorescence sensor 14. As the light amount of the excitation light E increases, the emission intensity of the fluorescence F increases, so the emission intensity of the fluorescence F in the first measurement mode becomes smaller than the emission intensity of the fluorescence F in the second measurement mode.
　蛍光信号取得部６２は、蛍光Ｆの強度に応じた蛍光信号を取得し、この蛍光信号を蛍光強度Ｆ（ｔ）に変換した上で（あるいはそのままの値で）演算部１８側に供給する。そして、演算部１８は、蛍光強度Ｆ（ｔ）又は蛍光信号をＲＡＭ２４に一時的に記憶させる。なお、センサ制御回路１６は、蛍光信号の取得に同期して（あるいは非同期的に）、温度センサ１５を介して温度信号を取得してもよい。 The fluorescence signal acquisition unit 62 acquires a fluorescence signal corresponding to the intensity of the fluorescence F, converts the fluorescence signal into the fluorescence intensity F (t) (or as it is), and supplies it to the calculation unit 18 side. Then, the calculation unit 18 temporarily stores the fluorescence intensity F (t) or the fluorescence signal in the RAM 24. The sensor control circuit 16 may acquire the temperature signal via the temperature sensor 15 in synchronization (or asynchronously) with the acquisition of the fluorescence signal.
　ステップＳ７において、濃度定量部７２は、取得した蛍光強度Ｆ（ｔ）、ＲＡＭ２４から読み出した定量係数等を用いて、アナライトＡの濃度［Ａ（ｔ）］を定量する。ここで、蛍光強度Ｆ（ｔ）及び濃度［Ａ（ｔ）］の相関関係は計測モードに応じて異なるため、計測モードにそれぞれ適した定量係数が用いられる。なお、濃度［Ａ（ｔ）］の定量方法は、蛍光色素の材質、化学反応の性質等に適した種々の手法を採ることができる。 In step S7, the concentration quantification unit 72 quantifies the concentration [A (t)] of the analyte A using the acquired fluorescence intensity F (t), the quantification coefficient read from the RAM 24, and the like. Here, since the correlation between the fluorescence intensity F (t) and the concentration [A (t)] varies depending on the measurement mode, a quantitative coefficient suitable for each measurement mode is used. The concentration [A (t)] can be quantified by various methods suitable for the material of the fluorescent dye, the nature of the chemical reaction, and the like.
　ステップＳ８において、演算部１８は、今回の計測モードがＭモードであるかＤモードであるかを判別する。Ｍモードであると判別された場合、演算部１８は、ステップＳ９を実行せずに次のステップ（Ｓ１０）に進む。 In step S8, the calculation unit 18 determines whether the current measurement mode is the M mode or the D mode. When it is determined that the mode is the M mode, the calculation unit 18 proceeds to the next step (S10) without executing step S9.
　一方、Ｄモードであると判別された場合、演算部１８は、ステップＳ７で定量された濃度［Ａ（ｔ）］に関する各種情報を表示器２８に表示させる（ステップＳ９）。ここで、Ｄモードで定量された濃度［Ａ（ｔ）］を選択的に表示するようにしたので、計測精度が高い定量値をユーザに対して常に報知できる。なお、ステップＳ７で定量された濃度［Ａ（ｔ）］を示す文字の他、直近のトレンド（例えば、上昇状態、下降状態、平坦状態）を示すマーク等を表示器２８に表示させてもよい。「トレンド」は、所定の時間幅における濃度［Ａ（ｔ）］の変動傾向を意味する。 On the other hand, when it is determined that the mode is the D mode, the calculation unit 18 causes the display device 28 to display various information related to the concentration [A (t)] quantified in step S7 (step S9). Here, since the concentration [A (t)] quantified in the D mode is selectively displayed, a quantitative value with high measurement accuracy can always be notified to the user. In addition to the characters indicating the concentration [A (t)] quantified in step S7, a mark indicating the latest trend (for example, the rising state, the falling state, and the flat state) may be displayed on the display 28. . “Trend” means a variation tendency of the density [A (t)] in a predetermined time width.
　ステップＳ１０において、計測モード切替部７０は、次の計測モードを決定する。計測モード切替部７０は、計測回数、蛍光強度Ｆ（ｔ）の履歴等の各種情報に基づいて、Ｍモード及びＤモードのうちいずれか一方に切り替える。本実施形態では、計測モード切替部７０は、Ｍモード（第１計測モード）の際に少なくとも１回定量されたアナライトＡの濃度［Ａ（ｔ）］に応じて、ＭモードからＤモード（第２計測モード）に切り替える。あるいは、計測モード切替部７０は、計測回数（例えば、５回以上５００回以下）に応じてＭモードからＤモードに切り替える。詳細については後述する。 In step S10, the measurement mode switching unit 70 determines the next measurement mode. The measurement mode switching unit 70 switches to either the M mode or the D mode based on various information such as the number of times of measurement and the history of the fluorescence intensity F (t). In the present embodiment, the measurement mode switching unit 70 switches from the M mode to the D mode (in accordance with the concentration [A (t)] of the analyte A determined at least once in the M mode (first measurement mode). Switch to the second measurement mode. Alternatively, the measurement mode switching unit 70 switches from the M mode to the D mode according to the number of times of measurement (for example, 5 times or more and 500 times or less). Details will be described later.
　ステップＳ１１において、間隔決定部６６及び／又は計測精度決定部６８は、計測条件の変更が必要か否かを判別する。種々の判別条件を設けてもよい。変更が不要であると判別された場合、ステップＳ１２を実行することなく次のステップ（Ｓ１３）に進む。 In step S11, the interval determination unit 66 and / or the measurement accuracy determination unit 68 determines whether or not the measurement condition needs to be changed. Various determination conditions may be provided. If it is determined that no change is necessary, the process proceeds to the next step (S13) without executing step S12.
　一方、変更が必要であると判別された場合、間隔決定部６６及び／又は計測精度決定部６８は、計測条件を適宜変更する（ステップＳ１２）。例えば、計測精度決定部６８は、アナライトＡの濃度［Ａ（ｔ）］に応じて、Ｍモードでの励起光量Ｐｅに対するＤモードでの励起光量Ｐｅの比（以下、光量比という。）を変更してもよい。この光量比は、２以上１００以下であることが好ましく、１０以上５０以下であることが一層好ましい。例えば、濃度［Ａ（ｔ）］が蛍光信号に略比例する場合、Ｍモードでの装置誤差Ｅｒに対するＤモードでの装置誤差Ｅｒの比（以下、「誤差比」という。）は、概ね１／１００～１／２、あるいは１／５０～１／１０である。なお、Ｄモードの計測では、定量精度を確保するため、８ビット（２５６レベル）以上の蛍光信号が取得できるように調整することが望ましい。 On the other hand, when it is determined that a change is necessary, the interval determination unit 66 and / or the measurement accuracy determination unit 68 appropriately change the measurement conditions (step S12). For example, the measurement accuracy determination unit 68 determines the ratio of the excitation light amount Pe in the D mode to the excitation light amount Pe in the M mode (hereinafter referred to as the light amount ratio) according to the concentration [A (t)] of the analyte A. It may be changed. This light quantity ratio is preferably 2 or more and 100 or less, and more preferably 10 or more and 50 or less. For example, when the density [A (t)] is substantially proportional to the fluorescence signal, the ratio of the apparatus error Er in the D mode to the apparatus error Er in the M mode (hereinafter referred to as “error ratio”) is approximately 1 /. 100 to 1/2, or 1/50 to 1/10. In the D-mode measurement, it is desirable to adjust so that a fluorescent signal of 8 bits (256 levels) or more can be acquired in order to ensure quantitative accuracy.
　ステップＳ１３において、演算部１８は、この一連の定量動作の終了指示があったか否かを判別する。終了指示がなかったと判別された場合、ステップＳ２に戻り、以下ステップＳ２～Ｓ１３を繰り返す。一方、終了指示があった場合、センシング装置１０は、アナライトＡの定量動作を終了する。 In step S13, the calculation unit 18 determines whether or not there is an instruction to end the series of quantitative operations. If it is determined that the end instruction has not been given, the process returns to step S2, and steps S2 to S13 are repeated thereafter. On the other hand, when there is an end instruction, the sensing device 10 ends the quantitative operation of the analyte A.
　次いで、各計測モードの時系列的な切替例について、図６及び図７を参照しながら説明する。 Next, a time-series switching example of each measurement mode will be described with reference to FIGS.
　図６は、各計測モードでの計測条件を説明する第１の表である。本表は、各計測モードにおける、サンプリング間隔Ｔｓ（単位：ｍｉｎ）、励起光量Ｐｅ（単位は、例えばｃｄ／ｍ２）、及び装置誤差Ｅｒ（単位：ｍｇ／ｍｌ）をそれぞれ示す。 FIG. 6 is a first table for explaining measurement conditions in each measurement mode. This table shows a sampling interval Ts (unit: min), an excitation light amount Pe (unit: cd / m 2), and an apparatus error Er (unit: mg / ml) in each measurement mode.
　Ｍモード（第１計測モード）では、サンプリング間隔ＴｓをＴｓ＝１［ｍｉｎ］とし、励起光量Ｐｅを「弱い」（ダイナミックレンジを「狭い」）とし、装置誤差ＥｒをＥｒ＝２０［ｍｇ／ｄｌ］とする。Ｄモード（第２計測モード）では、サンプリング間隔Ｔｓを最大で１０［ｍｉｎ］とし、励起光量Ｐｅを「強い」（ダイナミックレンジを「広い」）とし、装置誤差ＥｒをＥｒ＝１［ｍｇ／ｄｌ］とする。 In the M mode (first measurement mode), the sampling interval Ts is Ts = 1 [min], the excitation light amount Pe is “weak” (dynamic range is “narrow”), and the device error Er is Er = 20 [mg / dl. ]. In the D mode (second measurement mode), the sampling interval Ts is 10 [min] at the maximum, the excitation light amount Pe is “strong” (dynamic range is “wide”), and the apparatus error Er is Er = 1 [mg / dl. ].
　Ｍモード及びＤモードは、それぞれ同期的且つ択一的に実行される。そして、原則的にはＭモードが実行されるが、所定の割り込み条件、例えば第１条件及び第２条件の少なくとも一方を満たす場合、モード割り込みが発生し、Ｄモードが優先的に実行される。ここで、第１条件は、Ｄモードのサンプリング間隔Ｔｓが１０［ｍｉｎ］に一致した（あるいは超えた）場合である。また、第２条件は、Ｍモードでの定量値と、直近のＤモードでの定量値との差（図７の「変化量」に相当する。）の絶対値Δが所定の閾値Ｔｈ［ｍｇ／ｄｌ］を越える場合である。 M mode and D mode are executed synchronously and alternatively. In principle, the M mode is executed. However, when a predetermined interrupt condition, for example, at least one of the first condition and the second condition is satisfied, a mode interrupt is generated and the D mode is preferentially executed. Here, the first condition is when the D-mode sampling interval Ts matches (or exceeds) 10 [min]. The second condition is that the absolute value Δ of the difference between the quantitative value in the M mode and the quantitative value in the most recent D mode (corresponding to the “change amount” in FIG. 7) is a predetermined threshold Th [mg. / Dl].
　図７は、計測モードの時系列的な切替結果を例示する概略説明図である。本図は、計測開始からの時点［ｍｉｎ］における、計測モードの種別、血糖値［ｍｇ／ｄｌ］、及び変化量［ｍｇ／ｄｌ］を表す。ここでは、図６に示すように、閾値Ｔｈは、Ｔｈ＝２０［ｍｇ／ｄｌ］に設定されたとする。 FIG. 7 is a schematic explanatory diagram illustrating the result of time-series switching in the measurement mode. This figure shows the type of measurement mode, blood glucose level [mg / dl], and amount of change [mg / dl] at the time [min] from the start of measurement. Here, as shown in FIG. 6, it is assumed that the threshold Th is set to Th = 20 [mg / dl].
　時点ｔ＝１においてＤモードにより高精度に計測され、その結果、１００［ｍｇ／ｄｌ］の定量値を得たとする。その後、時点ｔ＝２での計測前にＭモードに切り替えられ、それ以降は原則的にはＭモードにより消費電力を抑制して計測・定量される。計測の都度、直近のＤモードでの定量値（ここでは、時点ｔ＝１での１００［ｍｇ／ｄｌ］）に対する変化量の絶対値Δが２０［ｍｇ／ｄｌ］を超えるか否かについて判別される。 Suppose that at time t = 1, the measurement is performed with high accuracy by the D mode, and as a result, a quantitative value of 100 [mg / dl] is obtained. Thereafter, the mode is switched to the M mode before the measurement at the time point t = 2, and thereafter, in principle, the power consumption is suppressed and the measurement / quantification is performed in the M mode. For each measurement, it is determined whether or not the absolute value Δ of the amount of change with respect to the quantitative value in the most recent D mode (here, 100 [mg / dl] at time t = 1) exceeds 20 [mg / dl]. Is done.
　時点ｔ＝２～１０での変化量はいずれも、－２０～２０［ｍｇ／ｄｌ］の範囲内にあるので、Ｍモードによる計測が継続的に実行される。そして、Ｄモードによる直近の計測から起算して１０［ｍｉｎ］に到達した場合、すなわち時点ｔ＝１１において、モード割り込み（Ｄモードへの切り替え）の後に計測・定量される。 Since the amount of change at the time point t = 2 to 10 is in the range of −20 to 20 [mg / dl], the measurement in the M mode is continuously executed. Then, when 10 [min] is reached from the latest measurement in the D mode, that is, at time t = 11, measurement / quantification is performed after mode interruption (switching to the D mode).
　そして、時点ｔ＝１２での計測前にＭモードに切り替えられ、それ以降は原則的にはＭモードにより計測・定量される。計測の都度、直近のＤモードでの定量値（ここでは、時点ｔ＝１１での１０６［ｍｇ／ｄｌ］）に対する変化量の絶対値Δが２０［ｍｇ／ｄｌ］を超えるか否かについて判別される。時点ｔ＝１７における定量値が１３０［ｍｇ／ｄｌ］であり、上記した変化量の絶対値Δが２０［ｍｇ／ｄｌ］を超えているので、次回（時点ｔ＝１８）の計測の際、モード割り込み（Ｄモードへの切り替え）が発生する。 Then, the mode is switched to the M mode before the measurement at the time point t = 12, and thereafter, in principle, measurement / quantification is performed in the M mode. For each measurement, it is determined whether or not the absolute value Δ of the amount of change with respect to the quantitative value in the latest D mode (here, 106 [mg / dl] at time t = 11) exceeds 20 [mg / dl]. Is done. Since the quantitative value at the time t = 17 is 130 [mg / dl] and the absolute value Δ of the change amount exceeds 20 [mg / dl], at the time of the next measurement (time t = 18), A mode interrupt (switch to D mode) occurs.
　同様に、時点ｔ＝２２における定量値が１５６［ｍｇ／ｄｌ］であり、直近のＤモードでの定量値（ここでは、時点ｔ＝１８での１２５［ｍｇ／ｄｌ］）に対する変化量の絶対値Δ（３１［ｍｇ／ｄｌ］）は２０［ｍｇ／ｄｌ］を超えるので、次回（時点ｔ＝２３）の計測の際、モード割り込み（Ｄモードへの切り替え）が発生する。 Similarly, the quantitative value at the time point t = 22 is 156 [mg / dl], and the absolute value of the change amount with respect to the quantitative value in the latest D mode (here, 125 [mg / dl] at the time point t = 18). Since the value Δ (31 [mg / dl]) exceeds 20 [mg / dl], a mode interruption (switching to the D mode) occurs at the next measurement (time t = 23).
　同様に、時点ｔ＝２４での計測前にＭモードに切り替えられ、直近のＤモードでの定量値（ここでは、時点ｔ＝２３での１５１［ｍｇ／ｄｌ］）に対する時点ｔ＝２４での変化量の絶対値Δ（２２［ｍｇ／ｄｌ］）は２０［ｍｇ／ｄｌ］を超えるので、次回（時点ｔ＝２５）の計測の際、モード割り込み（Ｄモードへの切り替え）が発生する。 Similarly, the mode is switched to the M mode before the measurement at the time t = 24, and the quantitative value in the latest D mode (here, 151 [mg / dl] at the time t = 23) at the time t = 24. Since the absolute value Δ (22 [mg / dl]) of the change amount exceeds 20 [mg / dl], a mode interruption (switching to the D mode) occurs at the next measurement (time t = 25).
　同様に、時点ｔ＝２６での計測前にＭモードに切り替えられ、直近のＤモードでの定量値（ここでは、時点ｔ＝２５での１６３［ｍｇ／ｄｌ］）に対する時点ｔ＝２９での変化量の絶対値Δ（３４［ｍｇ／ｄｌ］）は２０［ｍｇ／ｄｌ］を超えるので、次回（時点ｔ＝３０）の計測の際、モード割り込み（Ｄモードへの切り替え）が発生する。 Similarly, the mode is switched to the M mode before the measurement at the time point t = 26, and the quantitative value in the latest D mode (here, 163 [mg / dl] at the time point t = 25) at the time point t = 29. Since the absolute value Δ (34 [mg / dl]) of the change amount exceeds 20 [mg / dl], a mode interruption (switching to the D mode) occurs at the next measurement (time t = 30).
　このように、演算部１８は、Ｍモード及びＤモードを適宜切り替えながら、定量時点ｔ毎の時系列データとしてのアナライトＡの濃度［Ａ（ｔ）］を得る。続いて、本発明に係るセンシング方法を用いた場合の定量精度について、図８～図１１を参照しながら説明する。 In this way, the calculation unit 18 obtains the concentration [A (t)] of the analyte A as time series data for each quantification time t while appropriately switching between the M mode and the D mode. Next, the quantitative accuracy when the sensing method according to the present invention is used will be described with reference to FIGS.
　図８は、血中グルコースの第１の濃度変化を表すグラフである。グラフの横軸は時間（単位：ｍｉｎ）であり、グラフの縦軸はグルコースの濃度、いわゆる血糖値（単位：ｍｇ／ｄｌ）である。この血糖値の変化は、被検体の食後における体内の血糖値の経時的変化を模擬している。本グラフにおいて、最大勾配は概ね１０［ｍｇ／（ｄｌ・ｍｉｎ）］であり、被検体内で急激な変動が起こった事例を想定している。 FIG. 8 is a graph showing the first change in blood glucose concentration. The horizontal axis of the graph is time (unit: min), and the vertical axis of the graph is glucose concentration, so-called blood glucose level (unit: mg / dl). This change in blood glucose level simulates a change in blood glucose level in the body after meals of the subject. In this graph, the maximum gradient is approximately 10 [mg / (dl · min)], and it is assumed that there is a sudden change in the subject.
　図９Ａは、Ｍモードのみを用いて図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。ここで、サンプリング間隔ＴｓはＴｓ＝１［ｍｉｎ］とし、励起光量Ｐｅを「弱い」（すなわち、装置誤差Ｅｒ＝２０［ｍｇ／ｄｌ］）とした。本グラフの移動平均は、図８に示すグラフに概ね一致する。しかし、本グラフの個々のデータは、移動平均に対する偏差（ばらつき）が大きくなっている。これに対し、定量精度の観点から、サンプリング間隔Ｔｓを小さくしつつ、Ｄモードを常時用いて定量することが望ましい。 FIG. 9A is a graph showing a plot of blood glucose level obtained by successively quantifying the concentration change shown in FIG. 8 using only the M mode. Here, the sampling interval Ts was Ts = 1 [min], and the excitation light amount Pe was “weak” (that is, the apparatus error Er = 20 [mg / dl]). The moving average of this graph almost coincides with the graph shown in FIG. However, each data of this graph has a large deviation (variation) with respect to the moving average. On the other hand, from the viewpoint of quantitative accuracy, it is desirable to use the D mode at all times while reducing the sampling interval Ts.
　図９Ｂは、Ｄモードのみを用いて図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。ここで、サンプリング間隔ＴｓはＴｓ＝１０［ｍｉｎ］とし、励起光量Ｐｅを「強い」（すなわち、装置誤差Ｅｒ＝１［ｍｇ／ｄｌ］）とした。各プロットの位置は、いずれも図８に示すグラフ上に概ね投影される。すなわち、Ｄモードでは、０～４００［ｍｇ／ｄｌ］の範囲内で高精度に定量されることを意味する。ところが、サンプリング間隔Ｔｓが大きくなるにつれて時間遅延が増加し、計測の即時性が失われる。図９Ｂに示すように、血糖値が急激に増加（又は減少）する時間帯、具体的には０～５０［ｍｉｎ］、又は１００～２５０［ｍｉｎ］の範囲において、直近の定量値と現在の血糖値との間に乖離（最大で、１００［ｍｇ／ｄｌ］程度）が生じる。特に、定量の都度に濃度［Ａ（ｔ）］を表示器２８に表示させる場合、ユーザは、表示値の遷移から被検体の状態の急変（高血糖、低血糖）を察知できない可能性がある。 FIG. 9B is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 using only the D mode. Here, the sampling interval Ts was Ts = 10 [min], and the excitation light amount Pe was “strong” (that is, the apparatus error Er = 1 [mg / dl]). Each plot position is generally projected on the graph shown in FIG. That is, in the D mode, it means that the amount is determined with high accuracy within the range of 0 to 400 [mg / dl]. However, as the sampling interval Ts increases, the time delay increases and the immediacy of measurement is lost. As shown in FIG. 9B, the most recent quantitative value and the current value in the time zone during which the blood glucose level rapidly increases (or decreases), specifically in the range of 0 to 50 [min] or 100 to 250 [min]. There is a divergence (at most, about 100 [mg / dl]) between the blood glucose level. In particular, when the concentration [A (t)] is displayed on the display device 28 for each fixed amount, the user may not be able to detect a sudden change (high blood sugar, low blood sugar) of the state of the subject from the transition of the display value. .
　このように、計測上の観点から、装置誤差Ｅｒを極力小さくし、且つ、サンプリング間隔Ｔｓを極力小さくすることが望ましい。このためには、蛍光Ｆの発光強度及び頻度を高くする必要があり、蛍光センサ１４を構成する電子部品、計測に関わる各種物質等の劣化、すなわち短寿命化を招く可能性もある。具体的には、センシング装置１０の可搬性を考慮して電池により電力を供給する場合、励起光Ｅに供給する電力を増加すると電池の交換頻度が多くなる。また、高強度の励起光Ｅを高頻度で放射すると蛍光色素の劣化が促進される。 Thus, from the viewpoint of measurement, it is desirable to minimize the device error Er and to minimize the sampling interval Ts. For this purpose, it is necessary to increase the emission intensity and frequency of the fluorescence F, and there is a possibility that deterioration of electronic components constituting the fluorescence sensor 14, various substances related to measurement, etc., that is, shortening of the service life may be caused. Specifically, in the case where power is supplied by a battery in consideration of the portability of the sensing device 10, if the power supplied to the excitation light E is increased, the frequency of battery replacement increases. Further, when the high-intensity excitation light E is emitted at a high frequency, deterioration of the fluorescent dye is promoted.
　そこで、本発明に係るセンシング方法を用いることで、濃度［Ａ（ｔ）］に対する定量の追従性を維持しつつも、蛍光センサ１４の劣化を抑制できる。 Therefore, by using the sensing method according to the present invention, it is possible to suppress the deterioration of the fluorescence sensor 14 while maintaining the quantitative follow-up performance with respect to the concentration [A (t)].
　図１０は、Ｍモード及びＤモードを切り替えて図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。説明の便宜のため、図１０、並びに、後述する図１１、図１２Ｂ、図１３Ｂ、図１７Ａ、図１９Ａ及び図１９Ｂのグラフには、Ｄモードによる定量点のみをプロットし、Ｍモードによる定量点の表記を省略している。また、Ｄモードにおいて、サンプリング間隔ＴｓはＴｓ＝２０［ｍｉｎ］に、閾値Ｔｈは、Ｔｈ＝２５［ｍｉｎ］にそれぞれ設定されたとする。 FIG. 10 is a graph showing a plot of blood glucose levels obtained by switching the M mode and D mode and sequentially quantifying the concentration change shown in FIG. For convenience of explanation, FIG. 10 and the graphs of FIG. 11, FIG. 12B, FIG. 13B, FIG. 17A, FIG. 19A and FIG. The notation of is omitted. In the D mode, the sampling interval Ts is set to Ts = 20 [min], and the threshold Th is set to Th = 25 [min].
　図１０から理解されるように、０～５０［ｍｉｎ］、又は１００～２５０［ｍｉｎ］の範囲において、図９Ｂ（Ｄモードのみで計測）と比べて、Ｄモードによる定量点の数（定量頻度）が増加している。換言すれば、２つの計測モードを適宜切り替えることで、急激な濃度変化に対する追従性が向上すると言える。なお、隣接するプロット間において、Ｍモードでの計測・定量が少なくとも１回実行されているが、蛍光Ｆ（励起光Ｅ）の強度が相対的に抑制されているので、蛍光センサ１４に対する負荷が少なくなっている。 As can be understood from FIG. 10, in the range of 0 to 50 [min] or 100 to 250 [min], the number of quantification points in D mode (quantification frequency) compared to FIG. 9B (measured only in D mode). ) Has increased. In other words, it can be said that the followability to a sudden density change is improved by appropriately switching between the two measurement modes. In addition, although measurement and fixed_quantity | quantitative_assay in M mode are performed at least once between adjacent plots, since the intensity | strength of the fluorescence F (excitation light E) is restrained relatively, the load with respect to the fluorescence sensor 14 is carried out. It is running low.
　図１１は、図６に示す計測条件に従って第２の濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。第２の濃度変化は、第１の濃度変化（図８参照）と比べて平坦な特性を有する。 FIG. 11 is a graph showing a plot of blood sugar levels obtained by sequentially quantifying the second concentration change according to the measurement conditions shown in FIG. The second density change has a flat characteristic as compared with the first density change (see FIG. 8).
　図１１から理解されるように、Ｄモードによる計測は、計測時間の範囲内（０～４００［ｍｉｎ］の間）に合計２６回だけ実行される。一方、第２条件による割り込み処理を設けない場合、Ｄモードによる計測は、計測時間の範囲内に合計４０回（＝４００／１０）だけ実行される。すなわち、本切替手法を適用することで、Ｄモードによる計測回数を約３０％だけ削減可能である。このように、比較的平坦な濃度変化に対しても、蛍光センサ１４に対する負荷を低減する効果が得られる。 As can be understood from FIG. 11, the measurement in the D mode is executed a total of 26 times within the measurement time range (between 0 and 400 [min]). On the other hand, when interrupt processing based on the second condition is not provided, the measurement in the D mode is executed 40 times (= 400/10) in total within the measurement time range. That is, by applying this switching method, the number of measurements in the D mode can be reduced by about 30%. Thus, the effect of reducing the load on the fluorescence sensor 14 can be obtained even with a relatively flat density change.
　以上のように、蛍光センサ１４により取得される計測信号（蛍光Ｆ）の強度が相対的に低い第１計測モード（Ｍモード）、及び第１計測モードよりも計測信号（蛍光Ｆ）の強度が相対的に高い第２計測モード（Ｄモード）を切り替える計測モード切替部７０を設けたので、状況に応じて異なる２つの計測モードを組み合わせて使用可能になり、アナライトＡの濃度変化に対する定量の追従性を維持しつつも、蛍光センサ１４を構成する電子部品、計測に関わる各種物質等の劣化を抑制できる。 As described above, the intensity of the measurement signal (fluorescence F) acquired by the fluorescence sensor 14 is relatively low, and the intensity of the measurement signal (fluorescence F) is lower than that in the first measurement mode. Since the measurement mode switching unit 70 for switching the relatively high second measurement mode (D mode) is provided, two different measurement modes can be used in combination depending on the situation, and the quantitative measurement with respect to the concentration change of the analyte A can be performed. While maintaining the followability, it is possible to suppress deterioration of the electronic components constituting the fluorescent sensor 14 and various substances related to measurement.
　また、エネルギーの放射がトリガとなって計測信号を得るセンサの場合、定量頻度を減らすことが消費電力の低減に大きく寄与するため、特に効果的である。さらに蛍光センサ１４の場合、蛍光色素の劣化を抑制する効果もある。 Also, in the case of a sensor that obtains a measurement signal triggered by energy emission, reducing the quantitative frequency greatly contributes to the reduction of power consumption, which is particularly effective. Further, in the case of the fluorescent sensor 14, there is an effect of suppressing the deterioration of the fluorescent dye.
［変形例］
　続いて、本実施形態の第１～第４変形例に係るセンシング方法及びその効果について、図１２Ａ～図２０を参照しながら説明する。 [Modification]
Next, sensing methods and effects according to first to fourth modifications of the present embodiment will be described with reference to FIGS. 12A to 20.
　第１変形例に係るセンシング方法について、図１２Ａ～図１３Ｂを参照しながら説明する。本変形例に係るセンシング方法は、本実施形態に係るセンシング方法（図６参照）と比べて、Ｄモードでの計測条件（特に、割り込み発生条件）が異なっている。本変形例では、割り込み条件の１つである閾値Ｔｈに応じて、適切な装置誤差Ｅｒを設定している。 A sensing method according to the first modification will be described with reference to FIGS. 12A to 13B. The sensing method according to this modification is different from the sensing method according to this embodiment (see FIG. 6) in the measurement conditions (particularly, interrupt generation conditions) in the D mode. In this modification, an appropriate device error Er is set according to the threshold value Th that is one of the interrupt conditions.
　図１２Ａ（第２の表）に示すように、変化量（図７参照）の絶対値Δが閾値Ｔｈ＝２５［ｍｉｎ］を越える場合にのみ、モード割り込みが発生し、Ｄモード（第２計測モード）が実行される。なお、Ｍモード（第１計測モード）での計測条件は、図６に示す計測条件と同一である。 As shown in FIG. 12A (second table), only when the absolute value Δ of the amount of change (see FIG. 7) exceeds the threshold Th = 25 [min], a mode interrupt is generated and the D mode (second measurement) is performed. Mode) is executed. Note that the measurement conditions in the M mode (first measurement mode) are the same as the measurement conditions shown in FIG.
　図１２Ｂは、図１２Ａに示す計測条件に従って図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。本図から理解されるように、０～５０［ｍｉｎ］、又は１００～２５０［ｍｉｎ］の範囲において、図１０（本実施形態）と略同等の定量点の数が得られる。換言すれば、Ｄモードの最大間隔（図６例では、１０［ｍｉｎ］）を設定することなく、図１０の定量結果を略再現できる。 FIG. 12B is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. 12A. As can be understood from the figure, the number of quantitative points substantially equal to that in FIG. 10 (this embodiment) is obtained in the range of 0 to 50 [min] or 100 to 250 [min]. In other words, the quantitative result of FIG. 10 can be substantially reproduced without setting the maximum interval of the D mode (10 [min] in the example of FIG. 6).
　一方、図１３Ａ（第３の表）は、図１２Ａに対して、Ｍモードにおける励起光量Ｐｅを「更に弱い」とした場合の計測条件を示す。この場合、Ｍモードの装置誤差Ｅｒは、Ｅｒ＝４０［ｍｇ／ｄｌ］であったとする。なお、その他の計測条件は、図１２Ａに示す計測条件と同一である。 On the other hand, FIG. 13A (third table) shows the measurement conditions when the excitation light amount Pe in the M mode is set to “more weak” with respect to FIG. 12A. In this case, it is assumed that the apparatus error Er in the M mode is Er = 40 [mg / dl]. Other measurement conditions are the same as those shown in FIG. 12A.
　図１３Ｂは、図１３Ａに示す計測条件に従って図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。本図から理解されるように、５０［ｍｉｎ］近傍のピーク値を検出可能であるが、０～５０［ｍｉｎ］、又は１００～２５０［ｍｉｎ］の範囲における定量点の数が少なくなっている。これは、トレンドが上昇状態（又は下降状態）である場合、定量値に混入した装置誤差Ｅｒが、負（又は正）の相殺成分として、正（又は負）の変化量に影響を与え、Ｄモードの定量頻度を不規則に低下させたためと推認される。 FIG. 13B is a graph showing a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. 13A. As can be seen from this figure, a peak value in the vicinity of 50 [min] can be detected, but the number of quantitative points in the range of 0 to 50 [min] or 100 to 250 [min] is reduced. . This is because when the trend is in an up state (or down state), the device error Er mixed in the quantitative value affects the positive (or negative) change amount as a negative (or positive) canceling component, and D It is inferred that the mode frequency was irregularly reduced.
　このように、トレンドが上昇状態（又は下降状態）である場合に、Ｄモードでの定量頻度を十分に確保するため、閾値Ｔｈを考慮して、装置誤差Ｅｒの値を決定してもよい。具体的には、１≦（Ｔｈ／Ｅｒ）≦２、且つ、０＜Ｔｈ＋Ｅｒ≦２００［ｍｇ／ｄｌ］の範囲であることが好ましい。 As described above, when the trend is in the rising state (or the falling state), the value of the device error Er may be determined in consideration of the threshold Th in order to sufficiently secure the quantification frequency in the D mode. Specifically, it is preferable that the range is 1 ≦ (Th / Er) ≦ 2 and 0 <Th + Er ≦ 200 [mg / dl].
　第２変形例に係るセンシング方法について、図１４～図１７Ｂを参照しながら説明する。本変形例に係るセンシング方法は、Ｍモードでの装置誤差Ｅｒを可変に設定できる点が、本実施形態に係るセンシング方法（図６参照）と異なっている。 The sensing method according to the second modification will be described with reference to FIGS. 14 to 17B. The sensing method according to this modification is different from the sensing method according to this embodiment (see FIG. 6) in that the apparatus error Er in the M mode can be set variably.
　図１４は、血中グルコースの第３の濃度変化を表すグラフである。グラフの横軸は時間（単位：ｍｉｎ）であり、グラフの縦軸はグルコースの濃度、いわゆる血糖値（単位：ｍｇ／ｄｌ）である。本グラフにおいて、０～６０［ｍｉｎ］の範囲で急激な上昇変動が、３２０～３５０［ｍｉｎ］の範囲で急激な下降変動がそれぞれ生じている。 FIG. 14 is a graph showing a third change in blood glucose concentration. The horizontal axis of the graph is time (unit: min), and the vertical axis of the graph is glucose concentration, so-called blood glucose level (unit: mg / dl). In this graph, a sudden rise fluctuation occurs in the range of 0 to 60 [min], and a sudden fall fluctuation occurs in the range of 320 to 350 [min].
　図１５（第４の表）に示すように、Ｍモード（第１計測モード）では、サンプリング間隔ＴｓをＴｓ＝１［ｍｉｎ］とし、励起光量Ｐｅを「可変」（ダイナミックレンジを「可変」）とする。本変形例において、光源制御部６０（図４参照）は、アナライトＡの濃度［Ａ］に応じて、ＬＥＤ素子４６からの励起光量Ｐｅを制御する。この［Ａ］は、Ｄモードでの直近の定量値（単位は［ｍｇ／ｄｌ］）である。 As shown in FIG. 15 (fourth table), in the M mode (first measurement mode), the sampling interval Ts is Ts = 1 [min], the excitation light amount Pe is “variable” (the dynamic range is “variable”). And In the present modification, the light source control unit 60 (see FIG. 4) controls the excitation light amount Pe from the LED element 46 according to the concentration [A] of the analyte A. This [A] is the most recent quantitative value in D mode (unit: [mg / dl]).
　例えば、Ｅｒ＝０．１・［Ａ］（単位は［ｍｇ／ｄｌ］）の関係を常に満たすため、光源制御部６０（図４参照）は、濃度［Ａ］が減少するにつれて励起光量Ｐｅを増加するようにＬＥＤ素子４６を制御すればよい。この励起光量Ｐｅは、計測精度決定部６８により遂次実行されるとともに、計測指示部６４を介して光源制御部６０側に供給される。 For example, in order to always satisfy the relationship of Er = 0.1 · [A] (unit: [mg / dl]), the light source control unit 60 (see FIG. 4) sets the excitation light amount Pe as the concentration [A] decreases. What is necessary is just to control the LED element 46 so that it may increase. The excitation light amount Pe is sequentially executed by the measurement accuracy determination unit 68 and supplied to the light source control unit 60 side via the measurement instruction unit 64.
　また、Ｄモード（第２計測モード）では、図６と基本的に同様であるが、第２条件の閾値Ｔｈが可変である点が異なる。計測モード切替部７０は、具体的にはＴｈ＝０．１５・［Ａ］（単位は［ｍｇ／ｄｌ］）として閾値Ｔｈを決定する。 In the D mode (second measurement mode), which is basically the same as that in FIG. 6, the difference is that the threshold Th of the second condition is variable. Specifically, the measurement mode switching unit 70 determines the threshold Th as Th = 0.15 · [A] (unit: [mg / dl]).
　以下、第２変形例に係るセンシング方法の効果について、図１６Ａ～図１７Ｂを参照しながら説明する。なお、比較例として、図９Ｂと同様に、サンプリング間隔Ｔｓ＝１０［ｍｉｎ］、装置誤差Ｅｒ＝１［ｍｇ／ｄｌ］であるＤモードのみを用いた定量も併せて実施した。 Hereinafter, effects of the sensing method according to the second modification will be described with reference to FIGS. 16A to 17B. As a comparative example, as in FIG. 9B, quantification using only the D mode with the sampling interval Ts = 10 [min] and the apparatus error Er = 1 [mg / dl] was also performed.
　図１６Ａは、Ｄモードのみを用いて図１４に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。図１６Ｂは、図１６Ａに示す定量結果から得られた追従誤差の傾向を示すグラフである。ここで、図１６Ｂ及び図１７Ｂに示す追従誤差は、（Ｄモード間の定量値の変化量）／（Ｄモードでの定量値）×１００［％］で定義される。 FIG. 16A is a graph showing a plot of blood glucose levels obtained by sequentially quantifying the concentration change shown in FIG. 14 using only the D mode. FIG. 16B is a graph showing a tendency of the tracking error obtained from the quantitative result shown in FIG. 16A. Here, the tracking error shown in FIG. 16B and FIG. 17B is defined by (change amount of quantitative value between D modes) / (quantitative value in D mode) × 100 [%].
　図１６Ｂに示すように、追従誤差の正の最大値は概ね５０％（１４０［ｍｇ／ｄｌ］近傍）である。また、追従誤差の負の最大値は概ね３０％（２００、２６０［ｍｇ／ｄｌ］近傍）である。つまり、図１６Ａ及び図１６Ｂから理解されるように、血糖値が急激に変化する際、追従誤差が発生し易い傾向がある。 As shown in FIG. 16B, the maximum positive value of the tracking error is approximately 50% (near 140 [mg / dl]). Moreover, the negative maximum value of the tracking error is approximately 30% (200, 260 [mg / dl] vicinity). That is, as can be understood from FIGS. 16A and 16B, when the blood sugar level changes rapidly, a tracking error tends to occur.
　図１７Ａは、図１５に示す計測条件に従って図１４に示す濃度変化を遂次定量することで、得られた血糖値のプロットを示すグラフである。図１７Ｂは、図１７Ａに示す定量結果から得られた追従誤差の傾向を示すグラフである。 FIG. 17A is a graph showing a plot of blood sugar levels obtained by sequentially quantifying the concentration change shown in FIG. 14 according to the measurement conditions shown in FIG. FIG. 17B is a graph showing the tendency of the tracking error obtained from the quantitative result shown in FIG. 17A.
　図１７Ｂに示すように、追従誤差の正の最大値は概ね２０％（８０～１５０［ｍｇ／ｄｌ］近傍）である。また、追従誤差の負の最大値は概ね２０％（２５０［ｍｇ／ｄｌ］近傍）である。特に、低～中血糖領域では、誤差の低減が顕著であった。 As shown in FIG. 17B, the positive maximum value of the tracking error is approximately 20% (80 to 150 [mg / dl] vicinity). The negative maximum value of the tracking error is approximately 20% (near 250 [mg / dl]). In particular, in the low to moderate blood glucose region, the reduction in error was significant.
　このように、アナライトＡの濃度［Ａ］に応じて励起光量Ｐｅ又は閾値Ｔｈを変更することで設計の自由度が高くなる。例えば、濃度［Ａ］が減少するにつれて励起光量Ｐｅを増加させることで、低血糖状態におけるＭモードでの計測精度が向上する。 Thus, the degree of freedom in design is increased by changing the excitation light amount Pe or the threshold value Th according to the concentration [A] of the analyte A. For example, by increasing the excitation light amount Pe as the concentration [A] decreases, the measurement accuracy in the M mode in the hypoglycemic state is improved.
　第３変形例に係るセンシング方法について、図１８～図１９Ｂを参照しながら説明する。本変形例に係るセンシング方法は、Ｍモードでの装置誤差Ｅｒを可変に設定できる点が、本実施形態に係るセンシング方法（図６参照）と異なっている。 A sensing method according to the third modification will be described with reference to FIGS. 18 to 19B. The sensing method according to this modification is different from the sensing method according to this embodiment (see FIG. 6) in that the apparatus error Er in the M mode can be set variably.
　図１８（第５の表）に示すように、Ｍモード（第１計測モード）では、サンプリング間隔ＴｓをＴｓ＝１［ｍｉｎ］とし、励起光量Ｐｅを「可変」（ダイナミックレンジを「可変」）とする。本変形例において、光源制御部６０（図４参照）は、濃度［Ａ］と所定の閾値との間の大小関係に応じて装置誤差Ｅｒを決定する。 As shown in FIG. 18 (fifth table), in the M mode (first measurement mode), the sampling interval Ts is Ts = 1 [min], and the excitation light amount Pe is “variable” (the dynamic range is “variable”). And In this modification, the light source control unit 60 (see FIG. 4) determines the device error Er according to the magnitude relationship between the density [A] and a predetermined threshold value.
　具体的には、Ｄモードでの直近の定量値（濃度［Ａ］）を取得した後、計測精度決定部６８は、［Ａ］≧１００［ｍｇ／ｄｌ］を満たす場合はＥｒ＝２０［ｍｇ／ｄｌ］に、［Ａ］＜１００［ｍｇ／ｄｌ］を満たす場合はＥｒ＝１０［ｍｇ／ｄｌ］に決定する。 Specifically, after acquiring the latest quantitative value (concentration [A]) in the D mode, the measurement accuracy determination unit 68 determines that Er = 20 [mg] when [A] ≧ 100 [mg / dl] is satisfied. / Dl] is determined as Er = 10 [mg / dl] when [A] <100 [mg / dl] is satisfied.
　図１９Ａは、図６に示す計測条件に従って図８に示す濃度変化を遂次定量することで、得られた血糖値のプロットの一部を表すグラフである。図１９Ｂは、図６に示す濃度変化を遂次定量することで、得られた血糖値のプロットの一部を表すグラフである。グラフの横軸及び縦軸の定義は図８のグラフと同じであるが、説明の便宜のため、特定の範囲を拡大して表記している。 FIG. 19A is a graph showing a part of a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. 8 according to the measurement conditions shown in FIG. FIG. 19B is a graph showing a part of a plot of blood glucose level obtained by sequentially quantifying the concentration change shown in FIG. The definition of the horizontal axis and the vertical axis of the graph is the same as that of the graph of FIG. 8, but for the convenience of explanation, a specific range is shown in an enlarged manner.
　図１９Ａ及び図１９Ｂから理解されるように、血糖値が低い範囲Ｒ１（２５０～３００［ｍｉｎ］）及び範囲Ｒ２（３３０～３７０［ｍｉｎ］）において、Ｄモードによる定量点の数（定量頻度）が多くなっている。これにより、ユーザは、リスクの高い低血糖近傍の血糖値のとき、実際の濃度との差が小さい値を表示器２８（図１参照）で確認可能であり、低血糖状態の発現可能性をより早く察知できる。 As understood from FIGS. 19A and 19B, in the range R1 (250 to 300 [min]) and the range R2 (330 to 370 [min]) where the blood glucose level is low, the number of quantification points (quantitative frequency) by the D mode. Is increasing. As a result, when the blood glucose level is close to low blood sugar at high risk, the user can check a value with a small difference from the actual concentration on the display 28 (see FIG. 1), and the possibility of the hypoglycemic state being expressed It can be detected sooner.
　第４変形例に係るセンシング方法について、図２０を参照しながら説明する。本変形例に係るセンシング方法は、Ｍモード（第１計測モード）でのサンプリング間隔Ｔｓを複数種類設けている点が、本実施形態に係るセンシング方法（図６参照）と異なっている。 The sensing method according to the fourth modification will be described with reference to FIG. The sensing method according to this modification is different from the sensing method according to this embodiment (see FIG. 6) in that a plurality of types of sampling intervals Ts in the M mode (first measurement mode) are provided.
　図２０は、各計測モードでの計測条件を説明する第６の表である。本表に示すように、Ｍモードでのサンプリング間隔Ｔｓは、ゾーン及び／又はトレンドの属性に応じて決定される。ゾーンとは、所定の濃度範囲（例えば、０～５００［ｍｇ／ｄｌ］）を複数の範囲に区分した場合における各範囲の要素である。 FIG. 20 is a sixth table for explaining the measurement conditions in each measurement mode. As shown in this table, the sampling interval Ts in the M mode is determined according to the zone and / or trend attributes. A zone is an element of each range when a predetermined concentration range (for example, 0 to 500 [mg / dl]) is divided into a plurality of ranges.
　本変形例では、間隔決定部６６は、Ｄモードでの直近の定量値が２００［ｍｇ／ｄｌ］（第１閾値）を越える場合に「Ｈｉｇｈ」ゾーン、血糖値が１００～２００［ｍｇ／ｄｌ］である場合に「Ｍｉｄｄｌｅ」ゾーン、血糖値が１００［ｍｇ／ｄｌ］（第２閾値；第１閾値よりも小さい。）を下回る場合に「Ｌｏｗ」ゾーンに属するとそれぞれ判別する。また、間隔決定部６６は、直近の複数の定量値から回帰直線を求め、その勾配が所定の正値よりも大きい場合に「上昇」状態、この勾配が所定の負値よりも小さい場合に「下降」状態、それ以外の場合は「平坦」状態であるとそれぞれ判別する。 In this modification, the interval determination unit 66 sets the “High” zone when the latest quantitative value in the D mode exceeds 200 [mg / dl] (first threshold), and the blood glucose level is 100 to 200 [mg / dl. ] In the “Middle” zone, and when the blood glucose level falls below 100 [mg / dl] (second threshold; smaller than the first threshold), it is determined to belong to the “Low” zone. In addition, the interval determination unit 66 obtains a regression line from a plurality of most recent quantitative values, and when the gradient is larger than a predetermined positive value, the “rising” state, and when the gradient is smaller than a predetermined negative value, “ It is determined that the state is “down”, and in other cases it is “flat”.
　本図に示すように、間隔決定部６６は、定量値が「Ｈｉｇｈ」ゾーンに属し、且つ、トレンドが「上昇」状態である場合、サンプリング間隔ＴｓをＴｓ＝１［ｍｉｎ］に決定する。一方、間隔決定部６６は、定量値が「Ｈｉｇｈ」ゾーンに属しても、トレンドが「下降」状態又は「平坦」状態である場合、サンプリング間隔ＴｓをＴｓ＝５［ｍｉｎ］に決定する。すなわち、血糖値の経時的変化が最高ピーク時に到達する前であると推定された状態下では、相対的に小さいサンプリング間隔Ｔｓが設定される。 As shown in this figure, the interval determination unit 66 determines the sampling interval Ts to be Ts = 1 [min] when the quantitative value belongs to the “High” zone and the trend is in the “rising” state. On the other hand, even if the quantitative value belongs to the “High” zone, the interval determination unit 66 determines the sampling interval Ts to be Ts = 5 [min] if the trend is in the “down” state or the “flat” state. That is, a relatively small sampling interval Ts is set in a state where it is estimated that the change in blood glucose level over time is before reaching the maximum peak.
　また、間隔決定部６６は、定量値が「Ｍｉｄｄｌｅ」ゾーンに属する場合、現在のトレンド（上昇、下降、平坦）にかかわらずサンプリング間隔Ｔｓを相対的に大きい値、例えばＴｓ＝５［ｍｉｎ］に決定する。 Further, when the quantitative value belongs to the “Middle” zone, the interval determination unit 66 sets the sampling interval Ts to a relatively large value, for example, Ts = 5 [min], regardless of the current trend (up, down, flat). decide.
　さらに、間隔決定部６６は、定量値が「Ｌｏｗ」ゾーンに属し、且つ、トレンドが「上昇」状態又は「平坦」状態である場合、サンプリング間隔ＴｓをＴｓ＝５［ｍｉｎ］に決定する。一方、間隔決定部６６は、定量値が「Ｌｏｗ」ゾーンに属しても、トレンドが「下降」状態である場合、サンプリング間隔ＴｓをＴｓ＝１［ｍｉｎ］に決定する。すなわち、血糖値の経時的変化が最低ピーク時を脱する前であると推定された状態下では、相対的に小さいサンプリング間隔Ｔｓが設定される。 Furthermore, the interval determination unit 66 determines the sampling interval Ts to be Ts = 5 [min] when the quantitative value belongs to the “Low” zone and the trend is in the “rising” state or the “flat” state. On the other hand, the interval determination unit 66 determines the sampling interval Ts to be Ts = 1 [min] when the trend is in the “down” state even though the quantitative value belongs to the “Low” zone. That is, a relatively small sampling interval Ts is set under a state in which it is estimated that the change in blood glucose level with time is before the minimum peak.
　すなわち、間隔決定部６６は、Ｍモードで、アナライトＡの濃度［Ａ］及び／又はそのトレンドに応じてサンプリング間隔Ｔｓを遂次決定してもよい。特に、アナライトＡの濃度［Ａ］が第１閾値以上及び／又は第２閾値以下でのサンプリング間隔Ｔｓを、残余の濃度範囲でのサンプリング間隔Ｔｓよりも小さい値に決定することで、血糖値の時系列のピークを捉える確度が向上する。 That is, the interval determination unit 66 may sequentially determine the sampling interval Ts according to the concentration [A] of the analyte A and / or its trend in the M mode. In particular, the blood glucose level is determined by determining the sampling interval Ts when the concentration [A] of the analyte A is not less than the first threshold and / or not more than the second threshold to be smaller than the sampling interval Ts in the remaining concentration range. The accuracy of capturing the time-series peaks is improved.
　このように、所定の濃度範囲を複数のゾーンに分類し、得られた定量値についての各ゾーンの属否に応じてサンプリング間隔Ｔｓを決定することで、濃度［Ａ（ｔ）］の変化を大局的に捉えることができ、過不足ない適時の定量が可能になる。また、複数のゾーンの属否のみならずトレンドを併せて考慮することで、異なる観点から濃度［Ａ（ｔ）］の変化を大局的に捉えることが可能になり、一層効果的である。 In this way, the predetermined concentration range is classified into a plurality of zones, and the sampling interval Ts is determined according to the affiliation of each zone with respect to the obtained quantitative value, whereby the change in the concentration [A (t)] is changed. It can be grasped globally and timely quantification without excess or deficiency becomes possible. Further, by considering not only whether or not a plurality of zones belong but also trends, it is possible to capture changes in concentration [A (t)] from different viewpoints, which is more effective.
　なお、この発明は、上述した実施形態に限定されるものではなく、この発明の主旨を逸脱しない範囲で自由に変更できることは勿論である。 It should be noted that the present invention is not limited to the above-described embodiment, and it is needless to say that the present invention can be freely changed without departing from the gist of the present invention.

Claims (30)

  1. 　アナライト（Ａ）の濃度を間欠的又は連続的に定量するセンシング装置（１０）であって、
    　所定のサンプリング間隔に従って前記アナライト（Ａ）の濃度に相関する計測信号を取得するセンサ部（１２）と、
    　前記センサ部（１２）により取得される前記計測信号の強度が相対的に低い第１計測モード、及び前記第１計測モードよりも前記計測信号の強度が相対的に高い第２計測モードを切り替える計測モード切替部（７０）と
    　を備えることを特徴とするセンシング装置（１０）。     A sensing device (10) for quantifying the concentration of an analyte (A) intermittently or continuously,
    A sensor unit (12) for acquiring a measurement signal correlated with the concentration of the analyte (A) according to a predetermined sampling interval;
    Measurement that switches between a first measurement mode in which the intensity of the measurement signal acquired by the sensor unit (12) is relatively low, and a second measurement mode in which the intensity of the measurement signal is relatively higher than that in the first measurement mode. A sensing device (10) comprising: a mode switching unit (70).
  2. 　請求項１記載のセンシング装置（１０）において、
    　前記センサ部（１２）は、エネルギー（Ｅ）を放射するエネルギー源（４６）を有し、前記エネルギー源（４６）から放射された前記エネルギー（Ｅ）を標識物質に対して与えることで前記計測信号を取得することを特徴とするセンシング装置（１０）。     The sensing device (10) according to claim 1, wherein
    The sensor unit (12) includes an energy source (46) that emits energy (E), and the measurement is performed by applying the energy (E) emitted from the energy source (46) to a labeling substance. A sensing device (10) characterized by acquiring a signal.
  3. 　請求項２記載のセンシング装置（１０）において、
    　前記計測モード切替部（７０）により前記第１計測モードに切り替えられた場合に前記エネルギー（Ｅ）の放射量が相対的に少なくなるように前記エネルギー源（４６）を制御するとともに、前記第２計測モードに切り替えられた場合に前記エネルギー（Ｅ）の放射量が相対的に多くなるように前記エネルギー源（４６）を制御するエネルギー源制御部（６０）をさらに備えることを特徴とするセンシング装置（１０）。     The sensing device (10) according to claim 2,
    When the measurement mode switching unit (70) is switched to the first measurement mode, the energy source (46) is controlled so that the radiation amount of the energy (E) is relatively reduced, and the second A sensing device further comprising: an energy source control unit (60) for controlling the energy source (46) so that a radiation amount of the energy (E) is relatively increased when switched to a measurement mode. (10).
  4. 　請求項１～３のいずれか１項に記載のセンシング装置（１０）において、
    　前記計測モード切替部（７０）は、前記第１計測モードによる計測頻度が前記第２計測モードによる計測頻度よりも高くなるように切り替えることを特徴とするセンシング装置（１０）。     The sensing device (10) according to any one of claims 1 to 3,
    The sensing device (10), wherein the measurement mode switching unit (70) switches the measurement frequency in the first measurement mode to be higher than the measurement frequency in the second measurement mode.
  5. 　請求項１～４のいずれか１項に記載のセンシング装置（１０）において、
    　前記計測モード切替部（７０）は、前記第１計測モードの際に少なくとも１回定量された前記アナライト（Ａ）の濃度に応じて、前記第１計測モードから前記第２計測モードに切り替えることを特徴とするセンシング装置（１０）。     The sensing device (10) according to any one of claims 1 to 4,
    The measurement mode switching unit (70) switches from the first measurement mode to the second measurement mode according to the concentration of the analyte (A) quantified at least once during the first measurement mode. A sensing device (10) characterized by:
  6. 　請求項１～５のいずれか１項に記載のセンシング装置（１０）において、
    　前記計測モード切替部（７０）は、計測回数に応じて前記第１計測モードから前記第２計測モードに切り替えることを特徴とするセンシング装置（１０）。     The sensing device (10) according to any one of claims 1 to 5,
    The measurement mode switching unit (70) switches from the first measurement mode to the second measurement mode in accordance with the number of measurements.
  7. 　請求項１～６のいずれか１項に記載のセンシング装置（１０）において、
    　前記サンプリング間隔を決定する間隔決定部（６６）をさらに備えることを特徴とするセンシング装置（１０）。     The sensing device (10) according to any one of claims 1 to 6,
    The sensing device (10), further comprising an interval determination unit (66) for determining the sampling interval.
  8. 　請求項７記載のセンシング装置（１０）において、
    　前記間隔決定部（６６）は、前記第１計測モードで、前記アナライト（Ａ）の濃度に応じて前記サンプリング間隔を決定することを特徴とするセンシング装置（１０）。     The sensing device (10) according to claim 7,
    The sensing device (10), wherein the interval determination unit (66) determines the sampling interval according to the concentration of the analyte (A) in the first measurement mode.
  9. 　請求項８記載のセンシング装置（１０）において、
    　前記間隔決定部（６６）は、前記アナライト（Ａ）の濃度が第１閾値以上及び／又は第２閾値（前記第１閾値よりも小さい。）以下でのサンプリング間隔を、残余の濃度範囲での前記サンプリング間隔よりも小さい値に決定することを特徴とするセンシング装置（１０）。     The sensing device (10) according to claim 8,
    The interval determination unit (66) sets a sampling interval when the concentration of the analyte (A) is not less than a first threshold and / or not more than a second threshold (smaller than the first threshold) in a remaining concentration range. A sensing device (10) characterized in that the value is determined to be smaller than the sampling interval.
  10. 　請求項３記載のセンシング装置（１０）において、
    　前記エネルギー源制御部（６０）は、前記第１計測モードで、前記アナライト（Ａ）の濃度に応じて前記エネルギー（Ｅ）の放射量を制御することを特徴とするセンシング装置（１０）。     The sensing device (10) according to claim 3,
    The energy source control unit (60) controls the radiation amount of the energy (E) according to the concentration of the analyte (A) in the first measurement mode.
  11. 　請求項１０記載のセンシング装置（１０）において、
    　前記エネルギー源制御部（６０）は、前記アナライト（Ａ）の濃度が減少するにつれて前記エネルギー（Ｅ）の放射量を増加するように前記エネルギー源（４６）を制御することを特徴とするセンシング装置（１０）。     Sensing device (10) according to claim 10,
    The energy source control unit (60) controls the energy source (46) to increase the radiation amount of the energy (E) as the concentration of the analyte (A) decreases. Device (10).
  12. 　請求項１～１１のいずれか１項に記載のセンシング装置（１０）において、
    　前記第１計測モード及び前記第２計測モードにおける計測精度としての統計誤差をそれぞれ決定する計測精度決定部（６８）をさらに備えることを特徴とするセンシング装置（１０）。     The sensing device (10) according to any one of claims 1 to 11,
    The sensing device (10), further comprising a measurement accuracy determination unit (68) for determining statistical errors as measurement accuracy in the first measurement mode and the second measurement mode, respectively.
  13. 　請求項１２記載のセンシング装置（１０）において、
    　前記計測精度決定部（６８）は、前記第１計測モードでの前記統計誤差に対する前記第２計測モードでの前記統計誤差の比を１／１００以上１／２以下の範囲で決定することを特徴とするセンシング装置（１０）。     The sensing device (10) according to claim 12,
    The measurement accuracy determination unit (68) determines a ratio of the statistical error in the second measurement mode to the statistical error in the first measurement mode within a range of 1/100 or more and 1/2 or less. Sensing device (10).
  14. 　請求項３記載のセンシング装置（１０）において、
    　前記センサ部（１２）は、前記標識物質又は被検体に前記エネルギー（Ｅ）を与えて発生させた光現象から前記計測信号を取得する光学センサ（１４）を含むことを特徴とするセンシング装置（１０）。     The sensing device (10) according to claim 3,
    The sensor unit (12) includes an optical sensor (14) that obtains the measurement signal from a light phenomenon generated by applying the energy (E) to the labeling substance or a subject. 10).
  15. 　請求項１４記載のセンシング装置（１０）において、
    　前記エネルギー源（４６）は、前記計測信号を得るための蛍光（Ｆ）の発生を促す前記エネルギー（Ｅ）としての励起光を前記標識物質に向けて放射する励起光源であり、
    　前記エネルギー源制御部（６０）は、前記サンプリング間隔に従って前記励起光を放射させるように前記励起光源を制御する
    　ことを特徴とするセンシング装置（１０）。     The sensing device (10) according to claim 14,
    The energy source (46) is an excitation light source that emits excitation light as the energy (E) that promotes generation of fluorescence (F) for obtaining the measurement signal toward the labeling substance,
    The energy source control unit (60) controls the excitation light source to emit the excitation light according to the sampling interval. The sensing device (10),
  16. 　アナライト（Ａ）の濃度を間欠的又は連続的に定量するセンシング装置（１０）を用いた方法であって、
    　前記センシング装置（１０）が備えるセンサ部（１２）を用いて、所定のサンプリング間隔に従って前記アナライト（Ａ）の濃度に相関する計測信号を取得する取得ステップと、
    　前記センサ部（１２）により取得される前記計測信号の強度が相対的に低い第１計測モード、及び前記第１計測モードよりも前記計測信号の強度が相対的に高い第２計測モードを切り替える切替ステップと
    　を備えることを特徴とするセンシング方法。     A method using a sensing device (10) for quantifying the concentration of an analyte (A) intermittently or continuously,
    An acquisition step of acquiring a measurement signal correlated with the concentration of the analyte (A) according to a predetermined sampling interval using the sensor unit (12) included in the sensing device (10);
    Switching between a first measurement mode in which the intensity of the measurement signal acquired by the sensor unit (12) is relatively low, and a second measurement mode in which the intensity of the measurement signal is relatively higher than that in the first measurement mode. A sensing method comprising the steps of:
  17. 　請求項１６記載のセンシング方法において、
    　前記センサ部（１２）は、エネルギー（Ｅ）を放射するエネルギー源（４６）を有し、
    　前記取得ステップでは、前記エネルギー源（４６）から放射された前記エネルギー（Ｅ）を標識物質に対して与えることで前記計測信号を取得する
    　ことを特徴とするセンシング方法。     The sensing method according to claim 16, wherein
    The sensor unit (12) has an energy source (46) that radiates energy (E),
    In the acquisition step, the measurement signal is acquired by applying the energy (E) radiated from the energy source (46) to a labeling substance.
  18. 　請求項１７記載のセンシング方法において、
    　前記第１計測モードに切り替えられた場合に前記エネルギー（Ｅ）の放射量が相対的に少なくなるように前記エネルギー源（４６）を制御するとともに、前記第２計測モードに切り替えられた場合に前記エネルギー（Ｅ）の放射量が相対的に多くなるように前記エネルギー源（４６）を制御する制御ステップをさらに備えることを特徴とするセンシング方法。     The sensing method according to claim 17,
    The energy source (46) is controlled so that the radiation amount of the energy (E) is relatively reduced when the mode is switched to the first measurement mode, and when the mode is switched to the second measurement mode, the energy source (46) is controlled. The sensing method characterized by further comprising the control step which controls the said energy source (46) so that the radiation | emission amount of energy (E) may become relatively large.
  19. 　請求項１６～１８のいずれか１項に記載のセンシング方法において、
    　前記切替ステップでは、前記第１計測モードによる計測頻度が前記第２計測モードによる計測頻度よりも高くなるように切り替えることを特徴とするセンシング方法。     The sensing method according to any one of claims 16 to 18,
    In the switching step, the sensing method is characterized in that switching is performed so that the measurement frequency in the first measurement mode is higher than the measurement frequency in the second measurement mode.
  20. 　請求項１６～１９のいずれか１項に記載のセンシング方法において、
    　前記切替ステップでは、前記第１計測モードの際に少なくとも１回定量された前記アナライト（Ａ）の濃度に応じて、前記第１計測モードから前記第２計測モードに切り替えることを特徴とするセンシング方法。     The sensing method according to any one of claims 16 to 19,
    In the switching step, sensing is performed by switching from the first measurement mode to the second measurement mode according to the concentration of the analyte (A) quantified at least once in the first measurement mode. Method.
  21. 　請求項１６～２０のいずれか１項に記載のセンシング方法において、
    　前記切替ステップでは、計測回数に応じて前記第１計測モードから前記第２計測モードに切り替えることを特徴とするセンシング方法。     The sensing method according to any one of claims 16 to 20,
    In the switching step, the sensing method is characterized by switching from the first measurement mode to the second measurement mode according to the number of times of measurement.
  22. 　請求項１６～２１のいずれか１項に記載のセンシング方法において、
    　前記サンプリング間隔を決定する間隔決定ステップをさらに備えることを特徴とするセンシング方法。     The sensing method according to any one of claims 16 to 21,
    The sensing method further comprising an interval determining step for determining the sampling interval.
  23. 　請求項２２記載のセンシング方法において、
    　前記間隔決定ステップでは、前記第１計測モードで、前記アナライト（Ａ）の濃度に応じて前記サンプリング間隔を決定することを特徴とするセンシング方法。     The sensing method according to claim 22, wherein
    In the interval determination step, the sampling interval is determined in accordance with the concentration of the analyte (A) in the first measurement mode.
  24. 　請求項２３記載のセンシング方法において、
    　前記間隔決定ステップでは、前記アナライト（Ａ）の濃度が第１閾値以上及び／又は第２閾値（前記第１閾値よりも小さい。）以下でのサンプリング間隔を、残余の濃度範囲での前記サンプリング間隔よりも小さい値に決定することを特徴とするセンシング方法。     The sensing method according to claim 23, wherein
    In the interval determination step, the sampling interval when the concentration of the analyte (A) is not less than the first threshold and / or not more than the second threshold (smaller than the first threshold) is used as the sampling in the remaining concentration range. A sensing method characterized by determining a value smaller than the interval.
  25. 　請求項１８記載のセンシング方法において、
    　前記制御ステップでは、前記第１計測モードで、前記アナライト（Ａ）の濃度に応じて前記エネルギー（Ｅ）の放射量を制御することを特徴とするセンシング方法。     The sensing method according to claim 18,
    In the control step, the radiation amount of the energy (E) is controlled according to the concentration of the analyte (A) in the first measurement mode.
  26. 　請求項２５記載のセンシング方法において、
    　前記制御ステップでは、前記アナライト（Ａ）の濃度が減少するにつれて前記エネルギー（Ｅ）の放射量を増加するように前記エネルギー源（４６）を制御することを特徴とするセンシング方法。     The sensing method according to claim 25, wherein
    In the control step, the energy source (46) is controlled to increase the radiation amount of the energy (E) as the concentration of the analyte (A) decreases.
  27. 　請求項１６～２６のいずれか１項に記載のセンシング方法において、
    　前記第１計測モード及び前記第２計測モードにおける計測精度としての統計誤差をそれぞれ決定する精度決定ステップをさらに備えることを特徴とするセンシング方法。     The sensing method according to any one of claims 16 to 26,
    A sensing method, further comprising an accuracy determining step for determining statistical errors as measurement accuracy in the first measurement mode and the second measurement mode, respectively.
  28. 　請求項２７記載のセンシング方法において、
    　前記精度決定ステップでは、前記第１計測モードでの前記統計誤差に対する前記第２計測モードでの前記統計誤差の比を１／１００以上１／２以下の範囲で決定することを特徴とするセンシング方法。     The sensing method according to claim 27,
    In the accuracy determining step, a ratio of the statistical error in the second measurement mode to the statistical error in the first measurement mode is determined within a range of 1/100 or more and 1/2 or less. .
  29. 　請求項１８記載のセンシング方法において、
    　前記センサ部（１２）は、前記標識物質又は被検体に前記エネルギー（Ｅ）を与えて発生させた光現象から前記計測信号を取得する光学センサ（１４）を含むことを特徴とするセンシング方法。     The sensing method according to claim 18,
    The sensor unit (12) includes an optical sensor (14) for acquiring the measurement signal from a light phenomenon generated by applying the energy (E) to the labeling substance or the subject.
  30. 　請求項２９記載のセンシング方法において、
    　前記エネルギー源（４６）は、前記計測信号を得るための蛍光（Ｆ）の発生を促す前記エネルギー（Ｅ）としての励起光を前記標識物質に向けて放射する励起光源であり、
    　前記制御ステップでは、前記サンプリング間隔に従って前記励起光を放射させるように前記励起光源を制御する
    　ことを特徴とするセンシング方法。     The sensing method according to claim 29,
    The energy source (46) is an excitation light source that emits excitation light as the energy (E) that promotes generation of fluorescence (F) for obtaining the measurement signal toward the labeling substance,
    In the control step, the excitation light source is controlled to emit the excitation light according to the sampling interval.
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