FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
[See section 10, Rule 13]
NON-INVASIVE SUBSTANCE ANALYSIS APPARATUS
MITSUBISHI ELECTRIC CORPORATION A CORPORATION ORGANISED AND
EXISTING UNDER THE LAWS OF JAPAN, WHOSE ADDRESS IS 7-3,
MARUNOUCHI 2-CHOME, CHIYODA-KU, TOKYO 1008310, JAPAN
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE
INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED.
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DESCRIPTION
TECHNICAL FIELD
[0001] The present disclosure relates to a non-invasive substance analysis apparatus.
5 BACKGROUND ART
[0002] Japanese National Patent Publication No. 2017-519214 (PTL 1) discloses a noninvasive analysis system including an optical medium, an infrared light source, a probe
light source, and a photodiode. Specifically, a biological sample is placed on the optical
medium. The infrared light source emits infrared light. The infrared light is applied
10 to the biological sample through the optical medium. The infrared light is absorbed by
the biological sample, which causes the biological sample to generate heat. A degree
of absorption heat of the biological sample depends on an amount or concentration of a
biological component in the sample or on a surface of the sample.
[0003] The probe light source emits probe light, which is visible light, toward the optical
15 medium. The probe light is totally internally reflected at an interface between the
optical medium and the biological sample, and exits from the optical medium. The
absorption heat of the biological sample is transferred to the optical medium to change a
refractive index of the optical medium. The change in refractive index of the optical
medium affects the total internal reflection of the probe light at the interface between the
20 optical medium and the biological sample, which causes a change in traveling direction
of the probe light exiting from the optical medium. The photodiode functions as an
optical position sensor to detect the change in traveling direction of the probe light. The
amount or concentration of the biological component is measured from the change in
traveling direction of the probe light detected by the photodiode. For example, when
25 the sample is a skin of a patient, a blood glucose level of the patient is measured as the
biological component.
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CITATION LIST
PATENT LITERATURE
[0004] PTL 1: Japanese National Patent Publication No. 2017-519214
SUMMARY OF INVENTION
5 TECHNICAL PROBLEM
[0005] However, in the non-invasive analysis system disclosed in PTL 1, the absorption
heat of the biological sample quickly diffuses throughout the optical medium.
Therefore, the change in traveling direction of the probe light caused by the absorption
heat of the biological sample is small, and thus, the biological component in the sample
10 or on the surface of the sample cannot be analyzed accurately. The present disclosure
has been made in view of the above-described problem, and an object thereof is to
provide a non-invasive substance analysis apparatus capable of more accurately
analyzing a substance in a sample or on a surface of the sample.
SOLUTION TO PROBLEM
15 [0006] A non-invasive substance analysis apparatus according to the present disclosure
includes: a sample support plate; an excitation light source; and a temperature sensor.
The sample support plate has a first main surface including a sample placement region,
and a second main surface opposite to the first main surface. The excitation light source
emits excitation light toward a sample placed on the sample placement region. The
20 temperature sensor is provided on the first main surface. A through hole extending
from the sample placement region to the second main surface is provided in the sample
support plate. The excitation light is applied to the sample through the through hole.
ADVANTAGEOUS EFFECTS OF INVENTION
[0007] In the non-invasive substance analysis apparatus according to the present
25 disclosure, the through hole through which the excitation light passes is provided in the
sample support plate. Therefore, the excitation light reaches the sample at a stronger
light intensity, without being absorbed by the sample support plate. The absorption heat
of the sample increases. In addition, the absorption heat of the sample becomes less
likely to escape in a thickness direction (a direction in which the first main surface and
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the second main surface face each other) of the sample support plate. A temperature
signal output from the temperature sensor during irradiation of the sample with the
excitation light increases. Therefore, a substance in the sample or on a surface of the
sample can be analyzed more accurately.
5 BRIEF DESCRIPTION OF DRAWINGS
[0008] Fig. 1 is a schematic plan view of a non-invasive substance analysis apparatus
according to a first embodiment.
Fig. 2 is a schematic cross-sectional view of the non-invasive substance analysis
apparatus according to the first embodiment taken along a cross-sectional line II-II shown
10 in Fig. 1.
Fig. 3 is a schematic partially enlarged cross-sectional view of the non-invasive
substance analysis apparatus according to the first embodiment.
Fig. 4 is a circuit diagram of a lock-in amplifier.
Fig. 5 is a diagram showing a flowchart of a non-invasive substance analysis
15 method according to the first embodiment.
Fig. 6 is a diagram showing simulation results of normalized temperature
variations in Example 1 and Comparative Examples 1-1 and 1-2.
Fig. 7 is a schematic cross-sectional view of a non-invasive substance analysis
apparatus according to a modification of the first embodiment.
20 Fig. 8 is a schematic cross-sectional view of a non-invasive substance analysis
apparatus according to a second embodiment.
Fig. 9 is a diagram showing simulation results of normalized temperature
variations in Example 2 and Comparative Examples 2-1 and 2-2.
Fig. 10 is a schematic plan view of a non-invasive substance analysis apparatus
25 according to a third embodiment.
Fig. 11 is a schematic cross-sectional view of the non-invasive substance analysis
apparatus according to the third embodiment taken along a cross-sectional line XI-XI
shown in Fig. 10.
Fig. 12 is a schematic plan view of a non-invasive substance analysis apparatus
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according to a fourth embodiment.
Fig. 13 is a schematic cross-sectional view of the non-invasive substance analysis
apparatus according to the fourth embodiment taken along a cross-sectional line XIIIXIII shown in Fig. 12.
5 Fig. 14 is a schematic plan view of a non-invasive substance analysis apparatus
according to a fifth embodiment.
Fig. 15 is a schematic cross-sectional view of the non-invasive substance analysis
apparatus according to the fifth embodiment taken along a cross-sectional line XV-XV
shown in Fig. 14.
10 Fig. 16 is a schematic plan view of a non-invasive substance analysis apparatus
according to a sixth embodiment.
Fig. 17 is a schematic cross-sectional view of the non-invasive substance analysis
apparatus according to the sixth embodiment taken along a cross-sectional line XVIIXVII shown in Fig. 16.
15 DESCRIPTION OF EMBODIMENTS
[0009] Embodiments will be described below. The same configurations are denoted by
the same reference numerals and description thereof will not be repeated.
[0010] First Embodiment
A non-invasive substance analysis apparatus 1 according to a first embodiment
20 will be described with reference to Figs. 1 to 4. Referring to Figs. 1 and 2, non-invasive
substance analysis apparatus 1 includes a sample support plate 10, an excitation light
source 20, an optical chopper 22, temperature sensors 25 and 26, a lock-in amplifier 34,
a signal processing unit 37, and a substance analysis unit 38.
[0011] Sample support plate 10 has a main surface 10a, and a main surface 10b opposite
25 to main surface 10a. Main surface 10a includes a sample placement region 12 on which
sample 15 is placed. Sample 15 is a biological sample such as, for example, a finger, a
wrist, an arm, an earlobe, or a lip of a patient. In the present embodiment, sample
support plate 10 is formed by a substrate 11. Substrate 11 is made of a material that is
opaque to excitation light 21. Substrate 11 is made of, for example, plastic such as
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polyethylene, polycarbonate, polyurethane, or acrylic resin, or glass.
[0012] A through hole 13 extending from sample placement region 12 to main surface
10b is provided in sample support plate 10. A size of sample 15 is larger than a size of
through hole 13 in a plan view of main surface 10a.
5 [0013] Excitation light source 20 emits excitation light 21 toward sample 15 placed on
sample placement region 12. A wavelength of excitation light 21 is determined in
accordance with an absorption wavelength of a substance in sample 15 or on a surface of
sample 15. Excitation light 21 is, for example, mid-infrared light. The wavelength of
excitation light 21 is, for example, equal to or more than 6.0 m. The wavelength of
10 excitation light 21 may be equal to or more than 8.0 m. The wavelength of excitation
light 21 is, for example, equal to or less than 13.0 m. The wavelength of excitation
light 21 may be equal to or less than 11.0 m. Excitation light 21 may be light having
a plurality of wavelengths. For example, when non-invasive substance analysis
apparatus 1 is used to measure a blood glucose level of the patient, a wavelength range
15 of excitation light 21 is a wavelength range including a wavelength of a fingerprint
spectrum of glucose (e.g., a wavelength range of equal to or more than 8.5 m and equal
to or less than 10 m). Excitation light source 20 is, for example, a quantum cascade
laser that can emit broadband mid-infrared light. Sample 15 may be irradiated with
reference light that is not absorbed by the substance in sample 15 or on the surface of
20 sample 15, together with excitation light 21.
[0014] Optical chopper 22 subjects excitation light 21 to periodical intensity modulation.
Optical chopper 22 includes a plurality of rotating blades, for example. The plurality
of rotating blades are made of a material that is opaque to excitation light 21. When
excitation light 21 is blocked by one of the plurality of rotating blades, sample 15 is not
25 irradiated with excitation light 21. In contrast, when excitation light 21 passes through
a space between a pair of rotating blades adjacent to each other, of the plurality of rotating
blades, sample 15 is irradiated with excitation light 21. In this way, optical chopper 22
subjects excitation light 21 emitted from excitation light source 20 to intensity
modulation. Optical chopper 22 transmits, to lock-in amplifier 34 through an electrical
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wire 30, a reference signal having the same frequency as an intensity modulation
frequency of excitation light 21 subjected to intensity modulation.
[0015] Excitation light 21 subjected to intensity modulation by optical chopper 22 enters
sample support plate 10 from the main surface 10b side. Excitation light 21 is applied
5 to sample 15 through through hole 13. Excitation light 21 travels on a central axis 13c
of through hole 13, for example. When excitation light 21 passes through optical
chopper 22, sample 15 is irradiated with excitation light 21. Excitation light 21 is
absorbed by the substance in sample 15 or on the surface of sample 15. The absorption
of excitation light 21 by the substance in sample 15 or on the surface of sample 15 causes
10 sample 15 to generate absorption heat. In contrast, when excitation light 21 is blocked
by optical chopper 22, sample 15 is not irradiated with excitation light 21 and sample 15
does not generate the absorption heat. Therefore, a temperature of sample 15 varies in
accordance with the intensity modulation frequency of excitation light 21.
[0016] The substance in sample 15 or on the surface of sample 15 is, for example, a
15 biological component. When non-invasive substance analysis apparatus 1 is used to
obtain the blood glucose level of the patient, the substance analyzed by non-invasive
substance analysis apparatus 1 is glucose present in an interstitial fluid in epidermis of
the patient.
[0017] Each of temperature sensors 25 and 26 is provided on main surface 10a. Each
20 of temperature sensors 25 and 26 is provided in sample placement region 12. When
sample 15 is placed on sample placement region 12, each of temperature sensors 25 and
26 comes into contact with sample 15 to detect the temperature of sample 15. Each of
temperature sensors 25 and 26 detects the temperature of sample 15 and outputs a
temperature signal corresponding to the temperature to lock-in amplifier 34.
25 Specifically, temperature sensor 25 detects a temperature of a portion of sample 15 with
which temperature sensor 25 is in contact, and outputs a temperature signal
corresponding to the temperature to lock-in amplifier 34. Temperature sensor 26
detects a temperature of a portion of sample 15 with which temperature sensor 26 is in
contact, and outputs a temperature signal corresponding to the temperature to lock-in
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amplifier 34.
[0018] Since the temperature of sample 15 varies in accordance with the intensity
modulation frequency of excitation light 21, the temperature signal output from each of
temperature sensors 25 and 26 also varies in accordance with the intensity modulation
5 frequency of excitation light 21. For example, each of temperature sensors 25 and 26
outputs a minimum value of the temperature signal when sample 15 is not irradiated with
excitation light 21, and outputs a maximum value of the temperature signal when sample
15 is irradiated with excitation light 21. A difference between the maximum value and
the minimum value of the temperature signal is an amplitude of the temperature signal.
10 The amplitude of the temperature signal of each of temperature sensors 25 and 26
corresponds to a temperature variation of sample 15 measured by each of temperature
sensors 25 and 26 during analysis of sample 15. In the present embodiment, "during
analysis of sample 15" refers to a time period during which sample 15 is irradiated with
excitation light 21 subjected to intensity modulation.
15 [0019] Temperature sensors 25 and 26 are disposed near through hole 13. A distance
d1 between each of temperature sensors 25 and 26 and through hole 13 is, for example,
equal to or less than 50 m. Distance d1 may be equal to or less than 20 m, or may be
equal to or less than 10 m. Distance d1 is equal to or less than 10 of the size of
through hole 13 (e.g., a diameter of through hole 13). Distance d1 may be equal to or
20 less than 5 of the size of through hole 13. Temperature sensors 25 and 26 are disposed
to be rotationally symmetrical with respect to central axis 13c of through hole 13 in a
plan view of main surface 10a.
[0020] Referring to Fig. 3, each of temperature sensors 25 and 26 includes a temperature
sensor main body 27. Each of temperature sensors 25 and 26 may further include a
25 protective film 28.
[0021] Temperature sensor main body 27 is, for example, a thermocouple, a thermopile,
a thermistor, or a diode.
[0022] In the thermocouple, two dissimilar material pieces are brought into contact with
each other and the temperature of sample 15 is measured from the thermoelectromotive
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force generated at a contact portion of the two dissimilar material pieces. Each of the
two material pieces that form the thermocouple is made of, for example, iron, a coppernickel alloy, copper, a nickel-chromium alloy, a nickel-aluminum alloy, a nickel-silicon
alloy, a nickel chromium silicon alloy, platinum, a platinum-rhodium alloy, bismuth,
5 antimony, or a combination thereof. Each of the two material pieces that form the
thermocouple may be made of p-type polysilicon and n-type polysilicon. The
thermopile is formed by connecting a plurality of thermocouples.
[0023] An electrical resistance of the thermistor changes in accordance with a
temperature of the thermistor. The temperature of sample 15 is detected from the
10 electrical resistance of the thermistor. The thermistor is preferably made of a material
having a large temperature resistance coefficient. The thermistor is made of, for
example, vanadium oxide, NiMoCo oxide, Ti, polycrystalline silicon, amorphous silicon,
amorphous silicon germanium, MnO3, or YBaCuO.
[0024] A forward voltage of the diode changes in accordance with a temperature of the
15 diode. The temperature of sample 15 is detected from the forward voltage of the diode.
The diode is, for example, an Si diode.
[0025] Protective film 28 covers temperature sensor main body 27. Protective film 28
prevents sample 15 from coming into contact with temperature sensor main body 27. It
is desirable that protective film 28 should have a low thermal conductivity (e.g., a thermal
20 conductivity of 0.5 W/(m•K) or less) and a small thickness (e.g., a thickness of 10 m or
less). Since the thermal conductivity of protective film 28 is low, the absorption heat
of sample 15 is less likely to quickly diffuse throughout sample support plate 10. Since
protective film 28 is thin, the absorption heat of sample 15 is efficiently conducted to
temperature sensor main body 27, even when the thermal conductivity of protective film
25 28 is low.
[0026] Referring to Fig. 2, lock-in amplifier 34 is connected to optical chopper 22 by
electrical wire 30. Lock-in amplifier 34 receives, from optical chopper 22, the reference
signal having the same frequency as the intensity modulation frequency of excitation
light 21 subjected to intensity modulation. Referring to Figs. 1 and 2, lock-in amplifier
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34 is connected to each of temperature sensors 25 and 26 by an electrical wire 32. Lockin amplifier 34 receives the temperature signal corresponding to the temperature of
sample 15 from each of temperature sensors 25 and 26. Specifically, lock-in amplifier
34 receives, from temperature sensor 25, the temperature signal corresponding to the
5 temperature of the portion of sample 15 with which temperature sensor 25 is in contact.
Lock-in amplifier 34 receives, from temperature sensor 26, the temperature signal
corresponding to the temperature of the portion of sample 15 with which temperature
sensor 26 is in contact.
[0027] Lock-in amplifier 34 performs synchronous detection of the temperature signal
10 received from each of temperature sensors 25 and 26 with the reference signal received
from optical chopper 22. In this way, lock-in amplifier 34 outputs a temperature
variation signal of temperature sensor 25 and a temperature variation signal of
temperature sensor 26. The temperature variation signal of temperature sensor 25 is a
temperature variation signal corresponding to the temperature variation of sample 15
15 measured by temperature sensor 25 during analysis of sample 15. The temperature
variation signal of temperature sensor 26 is a temperature variation signal corresponding
to the temperature variation of sample 15 measured by temperature sensor 26 during
analysis of sample 15.
[0028] The operation of lock-in amplifier 34 will be specifically described with reference
20 to Fig. 4. Lock-in amplifier 34 includes a multiplier 35 and a low pass filter 36.
Multiplier 35 multiplies the temperature signal of temperature sensor 25 and the
reference signal. Multiplier 35 outputs a DC component proportional to the amplitude
of the temperature signal of temperature sensor 25, and an AC component that varies at
a frequency that is twice as high as the intensity modulation frequency of excitation light
25 21. Low pass filter 36 removes the AC component and allows the DC component to
pass therethrough. In this way, lock-in amplifier 34 outputs the DC component
proportional to the amplitude of the temperature signal of temperature sensor 25. The
amplitude of the temperature signal of temperature sensor 25 corresponds to the
temperature variation of the portion of sample 15 with which temperature sensor 25 is in
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contact during analysis of sample 15. Therefore, the DC component is the temperature
variation signal of temperature sensor 25.
[0029] Similarly, lock-in amplifier 34 outputs a DC component proportional to the
amplitude of the temperature signal of temperature sensor 26. The DC component is
5 the temperature variation signal of temperature sensor 26.
[0030] Referring to Figs. 1 and 2, signal processing unit 37 is connected to lock-in
amplifier 34. Signal processing unit 37 receives the temperature variation signal of
temperature sensor 25 and the temperature variation signal of temperature sensor 26 from
lock-in amplifier 34. Signal processing unit 37 calculates an average of the temperature
10 variation signal of temperature sensor 25 and the temperature variation signal of
temperature sensor 26. Signal processing unit 37 outputs an average temperature
variation signal corresponding to the average of the temperature variation signal of
temperature sensor 25 and the temperature variation signal of temperature sensor 26.
Signal processing unit 37 is, for example, a microcomputer including a processor and a
15 storage device. The processor executes a program stored in the storage device, whereby
signal processing unit 37 operates.
[0031] Substance analysis unit 38 is connected to signal processing unit 37. Substance
analysis unit 38 receives the average temperature variation signal from signal processing
unit 37. Substance analysis unit 38 analyzes the substance in sample 15 or on the
20 surface of sample 15 based on the average temperature variation signal.
[0032] For example, substance analysis unit 38 specifies the type of the substance in
sample 15 or on the surface of sample 15 and calculates an amount or concentration of
the substance, by referring to a data table in which the wavelength of excitation light 21
and the type of the substance are associated with each other and a data table in which the
25 magnitude of the average temperature variation signal and the amount or concentration
of the substance are associated with each other. Substance analysis unit 38 is, for
example, a microcomputer including a processor and a storage device. These data
tables are stored in the storage device. The processor executes a program stored in the
storage device, whereby substance analysis unit 38 operates.
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[0033] A thermal conductivity of substrate 11 may be equal to or less than 5 W/(m•K),
may be equal to or less than 2 W/(m•K), may be equal to or less than 1 W/(m•K), or may
be equal to or less than 0.3 W/(m•K), for example. Therefore, the absorption heat
generated in sample 15 by irradiation of sample 15 with excitation light 21 becomes less
5 likely to quickly diffuse throughout substrate 11, and the temperature variation signal of
each of temperature sensors 25 and 26 increases. The substance in sample 15 or on the
surface of sample 15 can be analyzed with a higher degree of accuracy.
[0034] It is preferable that the thermal conductivity of substrate 11 should be lower than
a thermal conductivity of sample 15. For example, when sample 15 is a human skin,
10 the thermal conductivity of sample 15 is about 0.5 W/(m•K). When substrate 11 is
made of plastic, the thermal conductivity of substrate 11 is equal to or more than 0.1
W/(m•K) and equal to or less than 0.3 W/(m•K). Therefore, the absorption heat
generated in sample 15 by irradiation of sample 15 with excitation light 21 becomes less
likely to quickly diffuse throughout substrate 11, and the temperature variation signal of
15 each of temperature sensors 25 and 26 increases. The substance in sample 15 or on the
surface of sample 15 can be analyzed with a higher degree of accuracy.
[0035] A thermal diffusion length L of the absorption heat of sample 15 is given by the
following Expression (1):
[0036]
𝐿 = √
𝛼
𝜋𝑓 20 … (1)
[0037] where f represents a frequency of the absorption heat of sample 15 (intensity
modulation frequency of excitation light 21), and  represents a thermal diffusion
coefficient of sample 15.
[0038] In light of Expression (1) above, the frequency of the absorption heat of sample
25 15 (intensity modulation frequency of excitation light 21) is set to be, for example, equal
to or more than 5 Hz and equal to or less than 100 Hz, in order to analyze the substance
(e.g., glucose in an interstitial fluid) present in sample 15 that is distant by several tens
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of micrometers or more from the surface of sample 15.
[0039] A non-invasive substance analysis method according to the present embodiment
using non-invasive substance analysis apparatus 1 will be described with reference to
mainly Fig. 5.
5 [0040] The non-invasive substance analysis method according to the present
embodiment includes placing sample 15 on sample placement region 12 (S1). When
there is a difference between the temperature of sample support plate 10 and the
temperature of sample 15, the heat moves between sample support plate 10 and sample
15. This movement of the heat makes detection of the temperature variation signals
10 difficult, and thus, makes analysis of the substance in sample 15 or on the surface of
sample 15 difficult. Thus, step S2 described below is not performed until a thermal
equilibrium state is achieved between sample support plate 10 and sample 15. The
achievement of the thermal equilibrium state between sample support plate 10 and
sample 15 can be detected by temperature sensors 25 and 26. For example, when a
15 change in temperature signals of temperature sensors 25 and 26 per unit time becomes
equal to or less than a threshold value (e.g., 0.1C/min), it is determined that the thermal
equilibrium state is achieved between sample support plate 10 and sample 15, and step
S2 is performed.
[0041] The non-invasive substance analysis method according to the present
20 embodiment includes irradiating sample 15 with excitation light 21 subjected to intensity
modulation by optical chopper 22 (S2). Optical chopper 22 transmits the reference
signal having the same frequency as the intensity modulation frequency of excitation
light 21 to lock-in amplifier 34 through electrical wire 30.
[0042] When excitation light 21 passes through optical chopper 22, excitation light 21 is
25 absorbed by the substance in sample 15 or on the surface of sample 15, which causes
sample 15 to generate the absorption heat. In contrast, when excitation light 21 is
blocked by optical chopper 22, sample 15 does not generate the absorption heat.
Therefore, the temperature signals output from temperature sensors 25 and 26 vary in
accordance with the intensity modulation frequency of excitation light 21.
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[0043] The non-invasive substance analysis method according to the present
embodiment includes obtaining the temperature variation signal of temperature sensor
25 and the temperature variation signal of temperature sensor 26 (S3).
[0044] Specifically, lock-in amplifier 34 receives the reference signal from optical
5 chopper 22 and receives the temperature signal from temperature sensor 25. Lock-in
amplifier 34 includes multiplier 35 and low pass filter 36. Multiplier 35 multiplies the
temperature signal of temperature sensor 25 and the reference signal. Multiplier 35
outputs the DC component proportional to the amplitude of the temperature signal of
temperature sensor 25, and the AC component that varies at a frequency that is twice as
10 high as the intensity modulation frequency of excitation light 21. Low pass filter 36
removes the AC component and allows the DC component to pass therethrough. In this
way, lock-in amplifier 34 outputs the DC component proportional to the amplitude of the
temperature signal of temperature sensor 25. The DC component is the temperature
variation signal of temperature sensor 25.
15 [0045] Similarly, lock-in amplifier 34 outputs the DC component proportional to the
amplitude of the temperature signal of temperature sensor 26. The DC component is
the temperature variation signal of temperature sensor 26.
[0046] The non-invasive substance analysis method according to the present
embodiment includes obtaining the average of the temperature variation signal of
20 temperature sensor 25 and the temperature variation signal of temperature sensor 26 as
the average temperature variation signal (S4). Specifically, signal processing unit 37
receives the temperature variation signal of temperature sensor 25 and the temperature
variation signal of temperature sensor 26 from lock-in amplifier 34. Signal processing
unit 37 calculates the average of the temperature variation signal of temperature sensor
25 25 and the temperature variation signal of temperature sensor 26 as the average
temperature variation signal. Signal processing unit 37 outputs the average temperature
variation signal to substance analysis unit 38.
[0047] The non-invasive substance analysis method according to the present
embodiment includes analyzing the substance in sample 15 or on the surface of sample
- 15 -
15 based on the average temperature variation signal (S5). Substance analysis unit 38
receives the average temperature variation signal from signal processing unit 37. For
example, substance analysis unit 38 specifies the type of the substance in sample 15 or
on the surface of sample 15 and calculates the amount or concentration of the substance,
5 by referring to the data table in which the wavelength of excitation light 21 and the type
of the substance are associated with each other and the data table in which the magnitude
of the average temperature variation signal and the amount or concentration of the
substance are associated with each other.
[0048] Referring to Fig. 6, the functions of non-invasive substance analysis apparatus 1
10 according to the present embodiment will be described by comparing Example 1 of the
present embodiment with Comparative Examples 1-1 and 1-2.
[0049] In Example 1, substrate 11 is made of a material that does not allow excitation
light 21 to pass therethrough (e.g., plastic or glass). In addition, in Example 1, a
diameter of through hole 13 is 36 m and a diameter of a light irradiation region 21b of
15 excitation light 21 is 30 m. Although Comparative Example 1-1 is similar to Example
1, through hole 13 is not formed in substrate 11. Although Comparative Example 1-2
is similar to Comparative Example 1-1, a transmittance of substrate 11 with respect to
excitation light 21 is assumed to be 100 in Comparative Example 1-2. A normalized
temperature variation in Fig. 6 is a temperature variation at each point of main surface
20 10a in each of Example 1, Comparative Example 1-1 and Comparative Example 1-2,
which is normalized by a temperature variation at an edge of through hole 13 in main
surface 10a in Example 1. The temperature variation at each point of main surface 10a
is given by a difference between a temperature at each point of main surface 10a when
sample 15 is not irradiated with excitation light 21 and a temperature at each point of
25 main surface 10a when sample 15 is irradiated with excitation light 21.
[0050]In Example 1, through hole 13 is provided in sample support plate 10. Therefore,
excitation light 21 reaches sample 15 at a stronger light intensity, without being absorbed
by sample support plate 10. The absorption heat of sample 15 increases. In addition,
a thermal conductivity of the air (0.024 W/(m•K)) in through hole 13 is lower than the
- 16 -
thermal conductivity of substrate 11 (e.g., a thermal conductivity of plastic: equal to or
more than about 0.1 W/(m•K) and about 0.3 W/(m•K), a thermal conductivity of glass:
equal to or more than about 0.5 W/(m•K) and about 0.7 W/(m•K)). Therefore, the
absorption heat of sample 15 becomes less likely to escape in a thickness direction (a
5 direction in which main surface 10a and main surface 10b face each other) of sample
support plate 10. The temperature variation of main surface 10a during analysis of
sample 15 becomes larger. In Example 1, the substance in sample 15 or on the surface
of sample 15 can be analyzed more accurately.
[0051] In contrast, in Comparative Example 1-1, substrate 11 is made of a material that
10 does not allow excitation light 21 to pass therethrough. Therefore, excitation light 21
does not reach sample 15 and the absorption heat of sample 15 is not generated. The
temperature variation of main surface 10a during analysis of sample 15 is zero. In
Comparative Example 1-1, the substance in sample 15 or on the surface of sample 15
cannot be analyzed accurately.
15 [0052] In Comparative Example 1-2, the transmittance of substrate 11 with respect to
excitation light 21 is assumed to be 100 and excitation light 21 reaches sample 15.
Therefore, the temperature variation of main surface 10a during analysis of sample 15 is
not zero. However, in Comparative Example 1-2, through hole 13 is not provided in
substrate 11. Therefore, in Comparative Example 1-2, the absorption heat of sample 15
20 diffuses in the thickness direction (the direction in which main surface 10a and main
surface 10b face each other) of sample support plate 10 more quickly than in Example 1.
The temperature variation of main surface 10a in Comparative Example 1-2 is smaller
than the temperature variation of main surface 10a in Example 1. In Comparative
Example 1-2, the substance in sample 15 or on the surface of sample 15 cannot be
25 analyzed accurately.
[0053] (Modification)
Sample support plate 10 (substrate 11) may be made of a material that is
transparent to excitation light 21. The number of temperature sensors 25 and 26 may
be three or more.
- 17 -
[0054] Temperature sensor 26 may be omitted and the number of temperature sensor 25
may be one. In this case, signal processing unit 37 is omitted. Substance analysis unit
38 receives the temperature variation signal of temperature sensor 25 from lock-in
amplifier 34. Substance analysis unit 38 analyzes the substance in sample 15 or on the
5 surface of sample 15 based on the temperature variation signal of temperature sensor 25.
In step S3, the temperature variation signal of temperature sensor 25 is obtained, step S4
is omitted, and in step S5, the substance in sample 15 or on the surface of sample 15 is
analyzed based on the temperature variation signal of temperature sensor 25.
[0055] As shown in Fig. 7, non-invasive substance analysis apparatus 1 may further
10 include a beam splitter 23 and a photodetector 24. Excitation light 21 subjected to
intensity modulation by optical chopper 22 enters beam splitter 23. Beam splitter 23
divides excitation light 21 into excitation light 21 traveling toward sample 15 and
excitation light 21 traveling toward photodetector 24. Beam splitter 23 causes a part of
excitation light 21 subjected to intensity modulation by optical chopper 22 to enter
15 photodetector 24. Photodetector 24 detects the intensity of excitation light 21 subjected
to intensity modulation. Photodetector 24 is, for example, a photodiode.
Photodetector 24 is connected to lock-in amplifier 34 by electrical wire 30.
Photodetector 24 outputs, to lock-in amplifier 34, the reference signal corresponding to
the intensity of excitation light 21 subjected to intensity modulation.
20 [0056] According to the modification shown in Fig. 7, an influence of variations in
intensity of excitation light 21 can be removed from the temperature variation signals of
temperature sensors 25 and 26. Even when the intensity of excitation light 21 varies,
the substance in sample 15 or on the surface of sample 15 can be analyzed more
accurately.
25 [0057] The effects of non-invasive substance analysis apparatus 1 according to the
present embodiment will be described.
Non-invasive substance analysis apparatus 1 according to the present
embodiment includes: sample support plate 10; excitation light source 20; and at least
one temperature sensor (e.g., temperature sensor 25, 26). Sample support plate 10 has
- 18 -
a first main surface (main surface 10a) including sample placement region 12, and a
second main surface (main surface 10b) opposite to the first main surface. Excitation
light source 20 emits excitation light 21 toward sample 15 placed on sample placement
region 12. The at least one temperature sensor is provided on the first main surface.
5 Through hole 13 extending from sample placement region 12 to the second main surface
is provided in sample support plate 10. Excitation light 21 is applied to sample 15
through through hole 13.
[0058] In non-invasive substance analysis apparatus 1, through hole 13 through which
excitation light 21 passes is provided in sample support plate 10. Therefore, excitation
10 light 21 reaches sample 15 at a stronger light intensity, without being absorbed by sample
support plate 10. The absorption heat of sample 15 increases. In addition, the
absorption heat of sample 15 becomes less likely to escape in the thickness direction (the
direction in which the first main surface (main surface 10a) and the second main surface
(main surface 10b) face each other) of sample support plate 10. The temperature signal
15 output from the at least one temperature sensor (e.g., temperature sensor 25, 26) during
irradiation of sample 15 with excitation light 21 increases. Therefore, the substance in
sample 15 or on the surface of sample 15 can be analyzed more accurately.
[0059] In non-invasive substance analysis apparatus 1, a material that is opaque to
excitation light 21 can be used as sample support plate 10 (substrate 11). A wide range
20 of choice of the material of sample support plate 10 (substrate 11) is offered. By using
a material (e.g., plastic or glass) that is opaque to excitation light 21 but has a low thermal
conductivity as the material of sample support plate 10 (substrate 11), the temperature
signal output from the at least one temperature sensor (e.g., temperature sensor 25, 26)
during irradiation of sample 15 with excitation light 21 increases. Therefore, the
25 substance in sample 15 or on the surface of sample 15 can be analyzed more accurately.
[0060] In non-invasive substance analysis apparatus 1 according to the present
embodiment, the at least one temperature sensor (e.g., temperature sensor 25, 26) is
provided in sample placement region 12 and comes into contact with sample 15.
[0061] Therefore, the absorption heat of sample 15 is efficiently conducted to the at least
- 19 -
one temperature sensor (e.g., temperature sensor 25, 26). The temperature signal output
from the at least one temperature sensor during irradiation of sample 15 with excitation
light 21 increases. The substance in sample 15 or on the surface of sample 15 can be
analyzed more accurately.
5 [0062] Non-invasive substance analysis apparatus 1 according to the present
embodiment further includes substance analysis unit 38. Substance analysis unit 38
analyzes the substance in sample 15 or on the surface of sample 15 based on the
temperature variation signal of the at least one temperature sensor (e.g., temperature
sensor 25, 26). The temperature variation signal of the at least one temperature sensor
10 corresponds to a temperature variation of sample 15 measured by the at least one
temperature sensor during analysis of sample 15.
[0063] Noise included in the temperature signal output from the at least one temperature
sensor (e.g., temperature sensor 25, 26) is removed from the temperature variation signal.
The substance in sample 15 or on the surface of sample 15 can be analyzed more
15 accurately.
[0064] Non-invasive substance analysis apparatus 1 according to the present
embodiment further includes signal processing unit 37 and substance analysis unit 38.
The at least one temperature sensor includes a plurality of temperature sensors 25 and 26.
Signal processing unit 37 outputs an average of a plurality of temperature variation
20 signals. Each of the plurality of temperature variation signals corresponds to a
temperature variation of sample 15 measured by a corresponding one of the plurality of
temperature sensors 25 and 26 during analysis of sample 15. Substance analysis unit
38 analyzes the substance in sample 15 or on the surface of sample 15 based on the
average of the plurality of temperature variation signals.
25 [0065] Noise included in the temperature signals output from temperature sensors 25 and
26 is removed from the temperature variation signals. In addition, the average of the
plurality of temperature variation signals reduces variations among the plurality of
temperature variation signals. Therefore, the substance in sample 15 or on the surface
of sample 15 can be analyzed more accurately.
- 20 -
[0066] In non-invasive substance analysis apparatus 1 according to the present
embodiment, the at least one temperature sensor (e.g., temperature sensor 25, 26)
includes temperature sensor main body 27. Temperature sensor main body 27 is a
thermocouple, a thermopile, a thermistor, or a diode.
5 [0067] Therefore, the probe light source that emits the probe light to measure the
absorption heat of sample 15 and the optical position sensor that detects deflection of the
probe light become unnecessary. Non-invasive substance analysis apparatus 1 can be
reduced in size.
[0068] The at least one temperature sensor (e.g., temperature sensor 25, 26) further
10 includes protective film 28 that covers temperature sensor main body 27.
[0069] Protective film 28 prevents sample 15 from coming into contact with temperature
sensor main body 27. Therefore, the lifetime of temperature sensor main body 27 is
lengthened.
[0070] Second Embodiment
15 A non-invasive substance analysis apparatus 1b according to a second
embodiment will be described with reference to Fig. 8. Although non-invasive
substance analysis apparatus 1b according to the present embodiment is configured
similarly to non-invasive substance analysis apparatus 1 according to the first
embodiment, non-invasive substance analysis apparatus 1b according to the present
20 embodiment is different from non-invasive substance analysis apparatus 1 according to
the first embodiment mainly in the following points.
[0071] In non-invasive substance analysis apparatus 1b, sample support plate 10 includes
a low-thermal-conductivity film 14, in addition to substrate 11.
[0072] Substrate 11 according to the present embodiment has a thermal conductivity
25 higher than that of substrate 11 according to the first embodiment. In the present
embodiment, the thermal conductivity of substrate 11 may be higher than that of sample
15. In the present embodiment, substrate 11 is made of, for example, a semiconductor
substrate such as silicon (thermal conductivity: about 160 W/(m•K)). Since substrate
11 is made of a semiconductor material, through hole 13 having a small size (e.g., a
- 21 -
diameter of several tens of micrometers) can be easily formed using a semiconductor
micromachining process.
[0073] Low-thermal-conductivity film 14 is provided on substrate 11. Low-thermalconductivity film 14 has a thermal conductivity lower than that of substrate 11. The
5 thermal conductivity of low-thermal-conductivity film 14 is, for example, equal to or less
than 20 of the thermal conductivity of substrate 11. The thermal conductivity of lowthermal-conductivity film 14 may be equal to or less than 10 of the thermal
conductivity of substrate 11, may be equal to or less than 5 of the thermal conductivity
of substrate 11, may be equal to or less than 2 of the thermal conductivity of substrate
10 11, or may be equal to or less than 1 of the thermal conductivity of substrate 11. Lowthermal-conductivity film 14 is made of, for example, silicon dioxide (thermal
conductivity: 1.4 W/(m•K)).
[0074] Main surface 10a is formed by low-thermal-conductivity film 14. A part of
main surface 10a may be formed by low-thermal-conductivity film 14. Sample
15 placement region 12 is formed by low-thermal-conductivity film 14. Each of
temperature sensors 25 and 26 is provided on low-thermal-conductivity film 14.
Through hole 13 is provided in both of substrate 11 and low-thermal-conductivity film
14.
[0075] Referring to Fig. 9, the functions of non-invasive substance analysis apparatus 1b
20 according to the present embodiment will be described by comparing Example 2 of the
present embodiment with Comparative Examples 2-1 and 2-2.
[0076] In Example 2, substrate 11 is made of silicon and low-thermal-conductivity film
14 is made of silicon dioxide. In addition, in Example 2, a diameter of through hole 13
is 36 m and a diameter of light irradiation region 21b of excitation light 21 is 30 m.
25 Although Comparative Example 2-1 is similar to Example 2, through hole 13 is not
formed in substrate 11. Although Comparative Example 2-2 is similar to Comparative
Example 2-1, a transmittance of substrate 11 with respect to excitation light 21 is
assumed to be 100 in Comparative Example 2-2. A normalized temperature variation
in Fig. 9 is a temperature variation at each point of main surface 10a in each of Example
- 22 -
2, Comparative Example 2-1 and Comparative Example 2-2, which is normalized by a
temperature variation at an edge of through hole 13 in main surface 10a in Example 2.
The temperature variation at each point of main surface 10a is given by a difference
between a temperature at each point of main surface 10a when sample 15 is not irradiated
5 with excitation light 21 and a temperature at each point of main surface 10a when sample
15 is irradiated with excitation light 21.
[0077]In Example 2, through hole 13 is provided in sample support plate 10. Therefore,
excitation light 21 reaches sample 15 at a stronger light intensity, without being absorbed
by sample support plate 10. The absorption heat of sample 15 increases. In addition,
10 the thermal conductivity of the air (0.024 W/(m•K)) in through hole 13 is lower than the
thermal conductivity of substrate 11 (e.g., thermal conductivity of silicon: about 160
W/(m•K)). Therefore, the absorption heat of sample 15 becomes less likely to escape
in the thickness direction (the direction in which main surface 10a and main surface 10b
face each other) of sample support plate 10. The temperature variation of main surface
15 10a during analysis of sample 15 becomes larger. In Example 1, the substance in
sample 15 or on the surface of sample 15 can be analyzed more accurately.
[0078] In contrast, in Comparative Example 2-1, although through hole 13 is not
provided in sample support plate 10, substrate 11 is made of silicon and allows excitation
light 21 to pass therethrough. Therefore, excitation light 21 reaches sample 15 and the
20 temperature variation of main surface 10a is not zero. However, in Comparative
Example 2-1, a part of excitation light 21 is reflected at main surface 10b or absorbed by
substrate 11. Therefore, the intensity of excitation light 21 reaching sample 15 in
Comparative Example 2-1 is lower than the intensity of excitation light 21 reaching
sample 15 in Example 2. Furthermore, in Comparative Example 2-1, the absorption
25 heat of sample 15 diffuses in the thickness direction (the direction in which main surface
10a and main surface 10b face each other) of sample support plate 10 more quickly than
in Example 2. As a result, the temperature variation of main surface 10a in Comparative
Example 2-1 is smaller than the temperature variation of main surface 10a in Example 2.
In Comparative Example 2-1, the substance in sample 15 or on the surface of sample 15
- 23 -
cannot be analyzed accurately.
[0079] In Comparative Example 2-2, through hole 13 is not provided in substrate 11.
Therefore, in Comparative Example 2-2, the absorption heat of sample 15 diffuses in the
thickness direction (the direction in which main surface 10a and main surface 10b face
5 each other) of sample support plate 10 more quickly than in Example 2. The
temperature variation of main surface 10a in Comparative Example 2-2 is smaller than
the temperature variation of main surface 10a in Example 2. In Comparative Example
2-2, the substance in sample 15 or on the surface of sample 15 cannot be analyzed
accurately.
10 [0080] Non-invasive substance analysis apparatus 1b according to the present
embodiment further provides the following effects, in addition to the effects of noninvasive substance analysis apparatus 1 according to the first embodiment.
[0081] In non-invasive substance analysis apparatus 1b according to the present
embodiment, sample support plate 10 includes substrate 11 and low-thermal15 conductivity film 14. Low-thermal-conductivity film 14 is provided on substrate 11
and has a thermal conductivity lower than that of substrate 11. At least a part of the
first main surface (main surface 10a) is formed by low-thermal-conductivity film 14.
The at least one temperature sensor (e.g., temperature sensor 25, 26) is provided on lowthermal-conductivity film 14.
20 [0082] Low-thermal-conductivity film 14 makes it less likely that the absorption heat of
sample 15 escapes in the thickness direction (the direction in which main surface 10a and
main surface 10b face each other) of sample support plate 10. The temperature signal
output from the at least one temperature sensor (e.g., temperature sensor 25, 26) during
irradiation of sample 15 with excitation light 21 increases. Therefore, the substance in
25 sample 15 or on the surface of sample 15 can be analyzed more accurately.
[0083] Third Embodiment
A non-invasive substance analysis apparatus 1c according to a third embodiment
will be described with reference to Figs. 10 and 11. Although non-invasive substance
analysis apparatus 1c according to the present embodiment is configured similarly to
- 24 -
non-invasive substance analysis apparatus 1 according to the first embodiment, noninvasive substance analysis apparatus 1c according to the present embodiment is
different from non-invasive substance analysis apparatus 1 according to the first
embodiment mainly in the following points.
5 [0084] Non-invasive substance analysis apparatus 1c further includes reference
temperature sensors 40 and 41. Reference temperature sensors 40 and 41 are
configured similarly to temperature sensors 25 and 26. Specifically, each of reference
temperature sensors 40 and 41 includes temperature sensor main body 27 (see Fig. 3).
Each of reference temperature sensors 40 and 41 may further include protective film 28
10 (see Fig. 3) that covers temperature sensor main body 27.
[0085] Each of reference temperature sensors 40 and 41 is provided on main surface 10a.
Each of reference temperature sensors 40 and 41 is provided in sample placement region
12 and comes into contact with sample 15. Each of reference temperature sensors 40
and 41 outputs a reference temperature signal corresponding to the temperature of sample
15 15 to lock-in amplifier 34. Specifically, reference temperature sensor 40 outputs a
reference temperature signal corresponding to a temperature of a portion of sample 15
with which reference temperature sensor 40 is in contact. Reference temperature sensor
41 outputs a reference temperature signal corresponding to a temperature of a portion of
sample 15 with which reference temperature sensor 41 is in contact.
20 [0086] When sample 15 is a living body, thermal variations of sample 15 (such as, for
example, variations in body temperature of the living body) or movement of sample 15
(such as, for example, contraction or relaxation of a muscle included in sample 15 or
variations in position of sample 15) may occur during analysis of the substance in sample
15 or on the surface of sample 15. Each of reference temperature sensors 40 and 41
25 detects temperature variations caused by the thermal variations or movement of sample
15, without being affected by the absorption heat of sample 15. Therefore, a distance
d2 between each of reference temperature sensors 40 and 41 and through hole 13 is longer
than a distance d1 between each of temperature sensors 25 and 26 and through hole 13 in
a plan view of main surface 10a. Distance d2 is, for example, ten times or more as long
- 25 -
as distance d1. Distance d2 may be twenty times or more as long as distance d1. In one
example, distance d1 is 5 m and distance d2 is 200 m.
[0087] Reference temperature sensors 40 and 41 are disposed to be rotationally
symmetrical with respect to central axis 13c of through hole 13 in a plan view of main
5 surface 10a. Therefore, each of reference temperature sensors 40 and 41 can more
accurately detect the temperature variations caused by the thermal variations or
movement of sample 15.
[0088] Reference temperature sensor 40 is disposed in the same direction as temperature
sensor 25 with respect to central axis 13c of through hole 13 in a plan view of main
10 surface 10a. Therefore, variations in reference temperature signal of reference
temperature sensor 40 caused by the thermal variations or movement of sample 15 during
analysis of sample 15 are similar to the variations in temperature signal of temperature
sensor 25 caused by the thermal variations or movement of sample 15 during analysis of
sample 15. Reference temperature sensor 40 can more accurately detect the variations
15 in temperature signal of temperature sensor 25 caused by the thermal variations or
movement of sample 15 during analysis of sample 15, without being affected by the
absorption heat of sample 15.
[0089] Reference temperature sensor 41 is disposed in the same direction as temperature
sensor 26 with respect to central axis 13c of through hole 13 in a plan view of main
20 surface 10a. Therefore, variations in temperature signal of reference temperature
sensor 41 caused by the thermal variations or movement of sample 15 during analysis of
sample 15 are similar to the variations in temperature signal of temperature sensor 26
caused by the thermal variations or movement of sample 15 during analysis of sample
15. Reference temperature sensor 41 can more accurately detect the variations in
25 temperature signal of temperature sensor 26 caused by the thermal variations or
movement of sample 15 during analysis of sample 15, without being affected by the
absorption heat of sample 15.
[0090] Similarly to the first embodiment, lock-in amplifier 34 outputs the temperature
variation signal of temperature sensor 25 and the temperature variation signal of
- 26 -
temperature sensor 26 to signal processing unit 37. The temperature variation signal of
temperature sensor 25 and the temperature variation signal of temperature sensor 26 are
affected by the variations in temperature signals caused by the thermal variations or
movement of sample 15 during analysis of sample 15, in addition to the absorption heat
5 of sample 15. In order to accurately analyze the substance in sample 15 or on the
surface of sample 15, it is necessary to remove the influence of the variations in
temperature signals caused by the thermal variations or movement of sample 15 during
analysis of sample 15 from the temperature variation signal of temperature sensor 25 and
the temperature variation signal of temperature sensor 26.
10 [0091] Thus, signal processing unit 37 receives the reference temperature signal of
reference temperature sensor 40 and the reference temperature signal of reference
temperature sensor 41. Signal processing unit 37 calculates a variation of the reference
temperature signal of reference temperature sensor 40 during analysis of sample 15 as a
reference temperature variation signal of reference temperature sensor 40. Signal
15 processing unit 37 calculates a variation of the reference temperature signal of reference
temperature sensor 41 during analysis of sample 15 as a reference temperature variation
signal of reference temperature sensor 41.
[0092] Signal processing unit 37 calculates a difference between the temperature
variation signal of temperature sensor 25 and the reference temperature variation signal
20 of reference temperature sensor 40 as a calibrated temperature variation signal of
temperature sensor 25. The calibrated temperature variation signal of temperature
sensor 25 is a temperature variation signal of temperature sensor 25 due to the absorption
heat of sample 15, from which the influence of the variationsin temperature signal caused
by the thermal variations or movement of sample 15 during analysis of sample 15 has
25 been removed. Similarly, signal processing unit 37 calculates a difference between the
temperature variation signal of temperature sensor 26 and the reference temperature
variation signal of reference temperature sensor 41 as a calibrated temperature variation
signal of temperature sensor 26. The calibrated temperature variation signal of
temperature sensor 26 is a temperature variation signal of temperature sensor 26 due to
- 27 -
the absorption heat of sample 15, from which the influence of the variations in
temperature signal caused by the thermal variations or movement of sample 15 during
analysis of sample 15 has been removed.
[0093] Signal processing unit 37 calculates an average of the calibrated temperature
5 variation signal of temperature sensor 25 and the calibrated temperature variation signal
of temperature sensor 26 as an average calibrated temperature variation signal.
Substance analysis unit 38 analyzes the substance in sample 15 or on the surface of
sample 15 based on the average calibrated temperature variation signal.
[0094] (Modification)
10 Temperature sensor 26 may be omitted and the number of temperature sensor 25
may be one. In this case, signal processing unit 37 outputs the calibrated temperature
variation signal of temperature sensor 25 to substance analysis unit 38. Substance
analysis unit 38 analyzes the substance in sample 15 or on the surface of sample 15 based
on the calibrated temperature variation signal of temperature sensor 25.
15 [0095] Non-invasive substance analysis apparatus 1c according to the present
embodiment further provides the following effects, in addition to the effects of noninvasive substance analysis apparatus 1 according to the first embodiment.
[0096] Non-invasive substance analysis apparatus 1c according to the present
embodiment further includes reference temperature sensor 40, 41 provided on the first
20 main surface (main surface 10a). Reference temperature sensor 40, 41 is provided in
sample placement region 12 and comes into contact with sample 15. In a plan view of
the first main surface, a second distance (distance d2) between each of reference
temperature sensors 40 and 41 and through hole 13 is ten times or more as long as a first
distance (distance d1) between each of temperature sensors 25 and 26 and through hole
25 13.
[0097] Each of reference temperature sensors 40 and 41 detects the temperature
variations during analysis of sample 15, without being affected by the absorption heat of
sample 15. Therefore, each of reference temperature sensors 40 and 41 can more
accurately detect the temperature variations caused by the absorption heat of sample 15,
- 28 -
without being affected by the variations in temperature signal caused by the thermal
variations or movement of sample 15 during analysis of sample 15. The substance in
sample 15 or on the surface of sample 15 can be analyzed more accurately.
[0098] In non-invasive substance analysis apparatus 1c according to the present
5 embodiment, signal processing unit 37 calculates the calibrated temperature variation
signal of the at least one temperature sensor by calibrating the temperature variation
signal of the at least one temperature sensor (e.g., temperature sensor 25, 26) with the
reference temperature variation signal of reference temperature sensor 40, 41.
Substance analysis unit 38 analyzes the substance in sample 15 or on the surface of
10 sample 15 based on the calibrated temperature variation signal of the at least one
temperature sensor.
[0099] By calibrating the temperature variation signal of the at least one temperature
sensor (e.g., temperature sensor 25, 26) with the reference temperature variation signal
of each of reference temperature sensors 40 and 41, the temperature variations caused by
15 the absorption heat of sample 15 can be detected more accurately, without being affected
by the variations in temperature signal caused by the thermal variations or movement of
sample 15 during analysis of sample 15. Therefore, the substance in sample 15 or on
the surface of sample 15 can be analyzed more accurately.
[0100] Fourth Embodiment
20 A non-invasive substance analysis apparatus 1d according to a fourth
embodiment will be described with reference to Figs. 12 and 13. Although noninvasive substance analysis apparatus 1d according to the present embodiment is
configured similarly to non-invasive substance analysis apparatus 1 according to the first
embodiment, non-invasive substance analysis apparatus 1d according to the present
25 embodiment is different from non-invasive substance analysis apparatus 1 according to
the first embodiment mainly in the following points.
[0101] Non-invasive substance analysis apparatus 1d further includes an optical medium
45. Optical medium 45 allows excitation light 21 to pass therethrough. A
transmittance of optical medium 45 with respect to excitation light 21 is higher than the
- 29 -
transmittance of sample support plate 10 (substrate 11) with respect to excitation light
21. When excitation light 21 is mid-infrared light, optical medium 45 is made of, for
example, chalcogenide glass (SSbSnGe).
[0102] Optical medium 45 closes through hole 13. A part of sample placement region
5 12 is formed by optical medium 45. The whole of sample placement region 12 may be
formed by optical medium 45. Sample 15 can be placed on optical medium 45. A
part of through hole 13 is filled with optical medium 45. A portion of through hole 13
that is more proximal to main surface 10b than optical medium 45 is a cavity that is not
filled with optical medium 45. Excitation light 21 is applied to sample 15 through
10 optical medium 45 and the cavity. The whole of through hole 13 may be filled with
optical medium 45.
[0103] A thermal conductivity of optical medium 45 is lower than the thermal
conductivity of substrate 11. The thermal conductivity of optical medium 45 may be
equal to or less than 10 of the thermal conductivity of substrate 11, may be equal to or
15 less than 5 of the thermal conductivity of substrate 11, or may be equal to or less than
2 of the thermal conductivity of substrate 11. For example, substrate 11 is made of
silicon (thermal conductivity: about 160 W/(m•K)) and optical medium 45 is made of
chalcogenide glass (thermal conductivity: 0.36 W/(m•K)). The thermal conductivity of
the air (0.024 W/(m•K)) in the cavity is lower than the thermal conductivity of substrate
20 11.
[0104] Non-invasive substance analysis apparatus 1d according to the present
embodiment provides the following effects similar to the effects of non-invasive
substance analysis apparatus 1 according to the first embodiment.
[0105] Non-invasive substance analysis apparatus 1d according to the present
25 embodiment further includes optical medium 45 that allows excitation light 21 to pass
therethrough. Optical medium 45 closes through hole 13. At least a part of sample
placement region 12 is formed by optical medium 45. Excitation light 21 is applied to
sample 15 through optical medium 45.
[0106] Therefore, excitation light 21 reaches sample 15 at a stronger light intensity,
- 30 -
without being absorbed by sample support plate 10. The absorption heat of sample 15
increases. In addition, the absorption heat of sample 15 becomes less likely to escape
in the thickness direction (the direction in which the first main surface (main surface 10a)
and the second main surface (main surface 10b) face each other) of sample support plate
5 10. The temperature signal output from each of temperature sensors 25 and 26 during
irradiation of sample 15 with excitation light 21 increases. The substance in sample 15
or on the surface of sample 15 can be analyzed more accurately.
[0107] Sample 15 can be placed on optical medium 45. Therefore, even when the size
of sample 15 is smaller than the size of through hole 13, or even when sample 15 is a
10 liquid, the substance in sample 15 or on the surface of sample 15 can be analyzed.
[0108] Optical medium 45 that is transparent to excitation light 21 such as mid-infrared
light is more expensive and lower in mechanical strength than sample support plate 10
(substrate 11). Since optical medium 45 is provided in through hole 13 of sample
support plate 10 (substrate 11), an amount of used optical medium 45 is reduced, as
15 compared with when the whole of sample support plate 10 (substrate 11) is formed by
optical medium 45. Therefore, the mechanical strength of non-invasive substance
analysis apparatus 1d can be increased and the cost of non-invasive substance analysis
apparatus 1d can be reduced.
[0109] In non-invasive substance analysis apparatus 1d according to the present
20 embodiment, sample support plate 10 includes substrate 11. Optical medium 45 has a
thermal conductivity lower than that of substrate 11.
[0110] Therefore, the absorption heat of sample 15 becomes less likely to escape in the
thickness direction (the direction in which the first main surface (main surface 10a) and
the second main surface (main surface 10b) face each other) of sample support plate 10.
25 The temperature signal output from each of temperature sensors 25 and 26 during
irradiation of sample 15 with excitation light 21 increases. Therefore, the substance in
sample 15 or on the surface of sample 15 can be analyzed more accurately.
[0111] Fifth Embodiment
A non-invasive substance analysis apparatus 1e according to a fifth embodiment
- 31 -
will be described with reference to Figs. 14 and 15. Although non-invasive substance
analysis apparatus 1e according to the present embodiment is configured similarly to
non-invasive substance analysis apparatus 1d according to the fourth embodiment, noninvasive substance analysis apparatus 1e according to the present embodiment is
5 different from non-invasive substance analysis apparatus 1d according to the fourth
embodiment mainly in the following points.
[0112] In a plan view of main surface 10a, the size of through hole 13 according to the
present embodiment is larger than the size of through hole 13 according to the fourth
embodiment and the size of optical medium 45 according to the present embodiment is
10 larger than the size of optical medium 45 according to the fourth embodiment. For
example, each of the diameter of through hole 13 and the diameter of optical medium 45
according to the present embodiment is 200 m in a plan view of main surface 10a. In
the present embodiment, each of temperature sensors 25 and 26 is disposed on optical
medium 45. Similarly to the fourth embodiment, in the present embodiment as well,
15 the thermal conductivity of optical medium 45 is lower than the thermal conductivity of
substrate 11. Each of temperature sensors 25 and 26 is disposed outside light irradiation
region 21b of excitation light 21 in a plan view of main surface 10a.
[0113] Non-invasive substance analysis apparatus 1e according to the present
embodiment further provides the following effects, in addition to the effects of non20 invasive substance analysis apparatus 1d according to the fourth embodiment.
[0114] In non-invasive substance analysis apparatus 1e according to the present
embodiment, the at least one temperature sensor (e.g., temperature sensor 25, 26) is
disposed on optical medium 45 having a thermal conductivity lower than that of substrate
11.
25 [0115] Therefore, the absorption heat of sample 15 also becomes less likely to escape in
a direction in which the first main surface extends, in addition to the thickness direction
(the direction in which the first main surface (main surface 10a) and the second main
surface (main surface 10b) face each other) of sample support plate 10. The
temperature signal output from the at least one temperature sensor (e.g., temperature
- 32 -
sensor 25, 26) during irradiation of sample 15 with excitation light 21 increases.
Therefore, the substance in sample 15 or on the surface of sample 15 can be analyzed
more accurately.
[0116] Sixth Embodiment
5 A non-invasive substance analysis apparatus 1f according to a sixth embodiment
will be described with reference to Figs. 16 and 17. Although non-invasive substance
analysis apparatus 1f according to the present embodiment is configured similarly to noninvasive substance analysis apparatus 1 according to the first embodiment, non-invasive
substance analysis apparatus 1f according to the present embodiment is different from
10 non-invasive substance analysis apparatus 1 according to the first embodiment mainly in
the following points.
[0117] Non-invasive substance analysis apparatus 1f includes a temperature sensor 50,
instead of temperature sensors 25 and 26 (see Figs. 1 and 2). Temperature sensor 50
includes a first optical waveguide 51, a waveguide-type ring resonator 52, a second
15 optical waveguide 53, and a clad layer 54. Temperature sensor 50 may further include
terminal portions 55 and 56.
[0118] Substrate 11 supports first optical waveguide 51, waveguide-type ring resonator
52, second optical waveguide 53, and clad layer 54. Substrate 11 has main surface 10b.
Substrate 11 is, for example, a silicon substrate.
20 [0119] Probe light emitted from a probe light source 58 enters first optical waveguide 51.
A wavelength of the probe light may be shorter than the wavelength of excitation light
21. For example, probe light source 58 is a laser diode for optical communication and
the wavelength of the probe light is equal to or more than 1100 nm and equal to or less
than 1700 nm.
25 [0120] First optical waveguide 51 includes an end 51a on which the probe light is
incident, and an end 51b opposite to end 51a. First optical waveguide 51 has a
refractive index higher than that of clad layer 54. The probe light propagates through
first optical waveguide 51. First optical waveguide 51 is, for example, a silicon
waveguide.
- 33 -
[0121] Waveguide-type ring resonator 52 is optically coupled to first optical waveguide
51. Waveguide-type ring resonator 52 has a refractive index higher than that of clad
layer 54. The probe light propagates through waveguide-type ring resonator 52.
Waveguide-type ring resonator 52 has the thermo-optical effect. Waveguide-type ring
5 resonator 52 is, for example, a silicon waveguide. A thermo-optical coefficient of
silicon is 2.3  10−4
(K−1
). Silicon has a relatively large thermo-optical coefficient
among optical materials for optical waveguides. Through hole 13 is formed inside
waveguide-type ring resonator 52.
[0122] Second optical waveguide 53 is optically coupled to waveguide-type ring
10 resonator 52. Second optical waveguide 53 has a refractive index higher than that of
clad layer 54. The probe light propagates through second optical waveguide 53.
Second optical waveguide 53 is disposed symmetrically to first optical waveguide 51
with respect to waveguide-type ring resonator 52 in a plan view of main surface 10a.
Second optical waveguide 53 includes an end 53a optically coupled to a light intensity
15 detector 59, and an end 53b opposite to end 53a. Ends 51a and 53a are located on the
same side with respect to waveguide-type ring resonator 52. Ends 51b and 53b are
located on the same side with respect to waveguide-type ring resonator 52.
[0123] Clad layer 54 separates first optical waveguide 51, waveguide-type ring resonator
52 and second optical waveguide 53 from substrate 11. Clad layer 54 covers first
20 optical waveguide 51, waveguide-type ring resonator 52 and second optical waveguide
53. Clad layer 54 has main surface 10a. A thermal conductivity of clad layer 54 is
smaller than the thermal conductivity of substrate 11. Clad layer 54 is made of, for
example, silica-based glass.
[0124] Terminal portion 55 is provided at end 51b of first optical waveguide 51.
25 Terminal portion 56 is provided at end 53b of second optical waveguide 53. Each of
terminal portions 55 and 56 scatters or absorbs the probe light and reduces the return
light of the probe light traveling to waveguide-type ring resonator 52, probe light source
58 and light intensity detector 59. Each of terminal portions 55 and 56 includes, for
example, a tapered waveguide that easily scatters the light outside the waveguide, and an
- 34 -
electrode (e.g., a metal electrode) that absorbs the scattered light.
[0125] The absorption of excitation light 21 by the substance in sample 15 or on the
surface of sample 15 causes sample 15 to generate absorption heat. The absorption heat
of sample 15 is conducted to waveguide-type ring resonator 52, which causes a change
5 in temperature of waveguide-type ring resonator 52. Waveguide-type ring resonator 52
has the thermo-optical effect. Therefore, when the temperature of waveguide-type ring
resonator 52 changes, the refractive index of waveguide-type ring resonator 52 changes,
which causes a change in coupling rate of the probe light from first optical waveguide 51
to second optical waveguide 53 through waveguide-type ring resonator 52.
10 [0126] Light intensity detector 59 is, for example, a photodiode. Light intensity
detector 59 detects a light intensity of the probe light from first optical waveguide 51 to
second optical waveguide 53 through waveguide-type ring resonator 52. Light intensity
detector 59 is connected to lock-in amplifier 34. Light intensity detector 59 outputs a
light intensity signal of the probe light to lock-in amplifier 34.
15 [0127] Lock-in amplifier 34 performs synchronous detection of the light intensity signal
of the probe light received from light intensity detector 59 with the excitation light
intensity signal received from photodetector 24. Lock-in amplifier 34 outputs a DC
component proportional to an amplitude of the light intensity signal of light intensity
detector 59. The DC component corresponds to a temperature variation of sample 15
20 during analysis of sample 15, and is a temperature variation signal of temperature sensor
50. Lock-in amplifier 34 outputs the temperature variation signal of temperature sensor
50 to substance analysis unit 38.
[0128] Substance analysis unit 38 receives the temperature variation signal of
temperature sensor 50 from lock-in amplifier 34. Substance analysis unit 38 analyzes
25 the substance in sample 15 or on the surface of sample 15 based on the temperature
variation signal of temperature sensor 50.
[0129] Non-invasive substance analysis apparatus 1f according to the present
embodiment provides the following effects similar to the effects of non-invasive
substance analysis apparatus 1 according to the first embodiment.
- 35 -
[0130] In non-invasive substance analysis apparatus 1f according to the present
embodiment, temperature sensor 50 includes first optical waveguide 51 on which the
probe light is incident, waveguide-type ring resonator 52 optically coupled to first optical
waveguide 51, and second optical waveguide 53 optically coupled to waveguide-type
5 ring resonator 52 and light intensity detector 59 to detect an intensity of the probe light.
[0131] In non-invasive substance analysis apparatus 1f, through hole 13 through which
excitation light 21 passes is provided in sample support plate 10. Therefore, excitation
light 21 reaches sample 15 at a stronger light intensity, without being absorbed by sample
support plate 10. The absorption heat of sample 15 increases. In addition, the
10 absorption heat of sample 15 becomes less likely to escape in the thickness direction (the
direction in which the first main surface (main surface 10a) and the second main surface
(main surface 10b) face each other) of sample support plate 10. The temperature signal
output from temperature sensor 50 during irradiation of sample 15 with excitation light
21 increases. Therefore, the substance in sample 15 or on the surface of sample 15 can
15 be analyzed more accurately.
[0132] It should be understood that the first to sixth embodiments disclosed herein are
illustrative and non-restrictive in every respect. At least two of the first to sixth
embodiments disclosed herein may be combined unless they are inconsistent. The
scope of the present disclosure is defined by the terms of the claims, rather than the
20 description above, and is intended to include any modifications within the scope and
meaning equivalent to the terms of the claims.
REFERENCE SIGNS LIST
[0133] 1, 1b, 1c, 1d, 1e, 1f non-invasive substance analysis apparatus; 10 sample support
plate; 10a, 10b main surface; 11 substrate; 12 sample placement region; 13 through hole;
25 13c central axis; 14 low-thermal-conductivity film; 15 sample; 20 excitation light source;
21 excitation light; 21b light irradiation region; 22 optical chopper; 23 beam splitter; 24
photodetector; 25, 26, 50 temperature sensor; 27 temperature sensor main body; 28
protective film; 30, 32 electrical wire; 34 lock-in amplifier; 35 multiplier; 36 low pass
filter; 37 signal processing unit; 38 substance analysis unit; 40, 41 reference temperature
- 36 -
sensor; 45 optical medium; 51 first optical waveguide; 51a, 51b end; 52 waveguide-type
ring resonator; 53 second optical waveguide; 53a, 53b end; 54 clad layer; 55, 56 terminal
portion; 58 probe light source; 59 light intensity detector.

WE CLAIM:
[Claim 1] A non-invasive substance analysis apparatus comprising:
a sample support plate having a first main surface including a sample placement
5 region, and a second main surface opposite to the first main surface;
an excitation light source to emit excitation light toward a sample placed on the
sample placement region; and
at least one temperature sensor provided on the first main surface, wherein
a through hole extending from the sample placement region to the second main
10 surface is provided in the sample support plate, and
the excitation light is applied to the sample through the through hole.
[Claim 2] The non-invasive substance analysis apparatus according to claim 1,
wherein
15 the at least one temperature sensor is provided in the sample placement region
and comes into contact with the sample.
[Claim 3] The non-invasive substance analysis apparatus according to claim 1
or 2, wherein
20 the sample support plate includes a substrate and a low-thermal-conductivity film
provided on the substrate and having a thermal conductivity lower than that of the
substrate,
at least a part of the first main surface is formed by the low-thermal-conductivity
film, and
25 the at least one temperature sensor is provided on the low-thermal-conductivity
film.
[Claim 4] The non-invasive substance analysis apparatus according to any one
of claims 1 to 3, further comprising
- 38 -
a substance analysis unit, wherein
the substance analysis unit analyzes a substance in the sample or on a surface of
the sample based on a temperature variation signal of the at least one temperature sensor,
and
5 the temperature variation signal corresponds to a temperature variation of the
sample measured by the at least one temperature sensor during analysis of the sample.
[Claim 5] The non-invasive substance analysis apparatus according to any one
of claims 1 to 3, further comprising:
10 a signal processing unit; and
a substance analysis unit, wherein
the at least one temperature sensor includes a plurality of temperature sensors,
the signal processing unit outputs an average of a plurality of temperature
variation signals,
15 each of the plurality of temperature variation signals corresponds to a temperature
variation of the sample measured by a corresponding one of the plurality of temperature
sensors during analysis of the sample, and
the substance analysis unit analyzes a substance in the sample or on a surface of
the sample based on the average of the plurality of temperature variation signals.
20
[Claim 6] The non-invasive substance analysis apparatus according to any one
of claims 1 to 3, further comprising
a reference temperature sensor provided on the first main surface, wherein
the reference temperature sensor is provided in the sample placement region and
25 comes into contact with the sample, and
in a plan view of the first main surface, a second distance between the reference
temperature sensor and the through hole is ten times or more as long as a first distance
between the at least one temperature sensor and the through hole.
- 39 -
[Claim 7] The non-invasive substance analysis apparatus according to claim 6,
further comprising:
a signal processing unit; and
a substance analysis unit, wherein
5 the signal processing unit calculates a calibrated temperature variation signal of
the at least one temperature sensor by calibrating a temperature variation signal of the at
least one temperature sensor with a reference temperature variation signal of the
reference temperature sensor,
the substance analysis unit analyzes a substance in the sample or on a surface of
10 the sample based on the calibrated temperature variation signal,
the temperature variation signal corresponds to a temperature variation of the
sample measured by the at least one temperature sensor during analysis of the sample,
and
the reference temperature variation signal corresponds to a temperature variation
15 of the sample measured by the reference temperature sensor during analysis of the sample.
[Claim 8] The non-invasive substance analysis apparatus according to claim 1
or 2, further comprising
an optical medium that allows the excitation light to pass therethrough, wherein
20 the optical medium closes the through hole,
at least a part of the sample placement region is formed by the optical medium,
and
the excitation light is applied to the sample through the optical medium.
25 [Claim 9] The non-invasive substance analysis apparatus according to claim 8,
wherein
the sample support plate includes a substrate, and
the optical medium has a thermal conductivity lower than that of the substrate.
- 40 -
[Claim 10] The non-invasive substance analysis apparatus according to claim 8
or 9, wherein
the at least one temperature sensor is disposed on the optical medium.
5 [Claim 11] The non-invasive substance analysis apparatus according to any one
of claims 1 to 10, wherein
the at least one temperature sensor includes a temperature sensor main body, and
the temperature sensor main body is a thermocouple, a thermopile, a thermistor,
or a diode.
10
[Claim 12] The non-invasive substance analysis apparatus according to claim
11, wherein
the at least one temperature sensor further includes a protective film that covers
the temperature sensor main body.
15
[Claim 13] The non-invasive substance analysis apparatus according to any one
of claims 1 to 5, wherein
the at least one temperature sensor includes a first optical waveguide on which
probe light is incident, a waveguide-type ring resonator optically coupled to the first
20 optical waveguide, and a second optical waveguide optically coupled to the waveguidetype ring resonator and a light intensity detector to detect an intensity of the probe light.