WO1997033514A1 - Procede et appareil d'analyse dichromatique circulaire - Google Patents
Procede et appareil d'analyse dichromatique circulaire Download PDFInfo
- Publication number
- WO1997033514A1 WO1997033514A1 PCT/JP1996/000623 JP9600623W WO9733514A1 WO 1997033514 A1 WO1997033514 A1 WO 1997033514A1 JP 9600623 W JP9600623 W JP 9600623W WO 9733514 A1 WO9733514 A1 WO 9733514A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- light
- laser
- laser light
- circular dichroism
- sample
- Prior art date
Links
- 238000004458 analytical method Methods 0.000 title claims description 27
- 238000000034 method Methods 0.000 title claims description 11
- 230000003287 optical effect Effects 0.000 claims abstract description 26
- 238000001514 detection method Methods 0.000 claims abstract description 25
- 238000002983 circular dichroism Methods 0.000 claims description 55
- 230000001678 irradiating effect Effects 0.000 claims description 22
- 230000005684 electric field Effects 0.000 claims description 14
- 239000004065 semiconductor Substances 0.000 claims description 8
- 238000002835 absorbance Methods 0.000 claims description 6
- 229910000530 Gallium indium arsenide Inorganic materials 0.000 claims description 5
- KXNLCSXBJCPWGL-UHFFFAOYSA-N [Ga].[As].[In] Chemical group [Ga].[As].[In] KXNLCSXBJCPWGL-UHFFFAOYSA-N 0.000 claims description 5
- 230000001360 synchronised effect Effects 0.000 claims description 2
- 230000003321 amplification Effects 0.000 claims 1
- 238000003199 nucleic acid amplification method Methods 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 abstract description 34
- 230000010287 polarization Effects 0.000 abstract description 20
- 239000000523 sample Substances 0.000 description 46
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 31
- 239000008103 glucose Substances 0.000 description 31
- 239000000306 component Substances 0.000 description 26
- 239000008280 blood Substances 0.000 description 22
- 210000004369 blood Anatomy 0.000 description 22
- 238000005259 measurement Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 238000010586 diagram Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 5
- 239000013307 optical fiber Substances 0.000 description 4
- 239000012472 biological sample Substances 0.000 description 3
- 238000001320 near-infrared absorption spectroscopy Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 238000002834 transmittance Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000012503 blood component Substances 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 244000089409 Erythrina poeppigiana Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000009776 Rathbunia alamosensis Nutrition 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 238000004847 absorption spectroscopy Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 210000000624 ear auricle Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 238000004476 mid-IR spectroscopy Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
Classifications
-
- 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
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/21—Polarisation-affecting properties
Definitions
- the present invention relates to a circular dichroism analysis method and a circular dichroism analyzer, and more particularly to a circular dichroism analysis method and a circular dichroism analysis capable of non-invasively quantitative analysis of optically active components in blood without collecting blood.
- a circular dichroism analysis method and a circular dichroism analyzer relate to a circular dichroism analysis method and a circular dichroism analysis capable of non-invasively quantitative analysis of optically active components in blood without collecting blood.
- the current blood glucose port measurement method has many problems if it is a simple method for frequent measurement by the patient himself.Therefore, blood glucose concentration can be measured noninvasively without collecting blood. There is a strong desire for a method to do this.
- the measurement accuracy was insufficient, and it was difficult to quantify the blood glucose concentration in a normal range.
- the biggest cause is that the absorption band of glucose in the near-infrared region has stronger water absorption than glucose in any band, and the majority of human components are water and the glucose is very small. Therefore, the absorption by water is an offset in the absorbance measurement, causing a large error.
- Molecules of many biological components such as glucose are molecules with optically asymmetric optical rotation. At the wavelength of the absorption band, such molecules have right-handed circularly polarized light and It has the property that the absorption coefficients for circularly polarized light are different. This property is called circular dichroism. However, even molecules in the body are mirror-image symmetric with water molecules and do not have circular dichroism. Therefore, when the target component has optical rotation, the sample is irradiated with the polarization of light having an absorption band wavelength unique to the target component alternately changed between right-handed circularly polarized light and left-handed circularly polarized light to irradiate the sample.
- the sample is subjected to circular dichroism analysis by measuring the difference between the absorbance of the sample and that of clockwise circularly polarized light, the offset due to water absorption can be removed and only the absorption by the target component can be measured.
- conventional circular dichroism analyzers use light whose wavelength is selected by a spectroscope from light from an incoherent light source such as a halogen lamp, so that a sample with poor transmittance and thickness like a living body is used. There is a problem in that the light intensity is weak to analyze the light.
- An object of the present invention is to remove the offset due to water absorption in the quantification of blood glucose concentration by near-infrared absorption spectroscopy, and to make it possible to quantify glucose strain only by measuring absorption at a single wavelength.
- An object of the present invention is to provide a circular dichroism analysis method and a circular dichroism analyzer.
- Another object of the present invention is to provide a circular dichroism analysis method and a circular dichroism analyzer which can measure a glucose concentration in blood easily and with sufficient accuracy and can analyze blood noninvasively. .
- right-handed circularly polarized light and left-handed circularly polarized light are alternated by combining first and second laser lights having a predetermined difference frequency and having orthogonal polarization planes. Generating modulated light having the difference frequency, and irradiating the sample with the modulated light. Furthermore, the intensity of the light transmitted through the sample is measured with a photodetector, the modulated component of the output of the photodetector is lock-in detected, and the difference between the absorbance of the sample for left-handed circularly polarized light and the absorbance for right-handed circularly polarized light is measured.
- the amplified light obtained by amplifying the light from the sample that is, the transmitted light, the diffusely reflected light or the scattered light, by the optical amplifier may be repeatedly irradiated on the sample.
- the first and second laser beams having a predetermined difference frequency are The electric fields of the first and second laser beams are multiplexed by making them orthogonal to each other to generate modulated light having the clockwise circularly polarized light and counterclockwise circularly polarized light alternately at the difference frequency, and irradiate the modulated light to the sample.
- the present invention is characterized in that a circular dichroism analyzer having a lock-in detecting means for detecting the output from the light detecting means in a lock-in manner.
- the first and second laser lights having a predetermined difference frequency are multiplexed by making the electric fields of the first and second laser lights orthogonal to each other, and the clockwise circularly polarized light and the counterclockwise circularly polarized light are alternately changed.
- an irradiating means for generating modulated light having a difference frequency and irradiating the sample with the modulated light and an optical amplifier for amplifying light from the sample, that is, transmitted light, diffusely reflected light or scattered light.
- At least one amplified light irradiating means for irradiating the sample with the wide light obtained by the above, a light detecting means for measuring the intensity of light, ie, transmitted light, diffuse reflected light or scattered light, from the sample generated by the amplified light; Lock-in detection means for lock-in detecting the output from the light detection means using a beat signal generated by the first laser light and the second laser light as a reference signal; Characteristic in analyzer.
- the light emitted from one laser light source is split into two laser light beams, and at least one of the two laser light beams is incident on the acousto-optic modulator, so that the two laser light beams
- a first laser beam and a second laser beam having a difference frequency of two laser beams may be obtained, and each of the two laser beams may be incident on a separate acousto-optic modulator, thereby obtaining the two laser beams.
- a first laser beam and a second laser beam having a predetermined difference frequency may be obtained.
- the first laser light and the second laser light are laser light having a wavelength of 7500 nm to 5500 nm, and preferably have a wavelength of 1550 nm to 1650 nm, Alternatively, it is a laser beam of 2200 nm to 2300 nm.
- the detector for example, an indium gallium arsenide semiconductor photodiode can be used.
- light having a specific absorption wavelength is irradiated to a molecule having optical rotation, and different absorption coefficients are measured for right-handed circularly polarized light and left-handed circularly polarized light.
- the sample is irradiated with polarization-modulated light having clockwise circularly polarized light and counterclockwise circularly polarized light alternately in a frequency range, and transmitted light or diffuse reflected light is intensity-modulated by the circular dichroism of the sample.
- the difference between the absorption coefficients of right-handed circularly polarized light and left-handed circularly polarized light can be obtained.
- Glucose in blood is contained in living organisms in the form of an aqueous solution.
- Water molecules do not have circular dichroism and there is no difference in absorption coefficient between clockwise circularly polarized light and counterclockwise circularly polarized light. Thereby, the water absorption can be removed.
- biological components other than glucose and water, such as proteins have little absorption at wavelengths of 1550 nm to 1650 nm or 2200 nm to 2300 nm.
- FIG. 1 is a conceptual diagram showing a device configuration of the first embodiment.
- FIG. 2 is a diagram showing the relationship between the output of the mouth suck-in amplifier of FIG. 1 and the glucose concentration in the sample.
- FIG. 3 is a conceptual diagram showing the device configuration of the second embodiment.
- FIG. 4 is a conceptual diagram showing an apparatus configuration of the third embodiment.
- FIG. 5 is a conceptual diagram showing an apparatus configuration of the fourth embodiment. BEST MODE FOR CARRYING OUT THE INVENTION
- FIG. 1 is a conceptual diagram illustrating the configuration of the rice bunker according to the first embodiment.
- This device consists of laser 1, 1 ', beam splitter 1, sample 3, photodetector 4, 4', analyzer 5, lock-in amplifier 6, splitter 7, reference oscillator 8, phase frequency comparator 9, PID (proportional / integral / differential) controller 10
- Laser 1 and laser 1 ′ are semiconductor lasers, the output is linearly polarized, so that the polarization plane of the output light of laser 1 is parallel to the paper and the polarization plane of the output light of laser 1 ′ is perpendicular to the paper. is set up.
- the polarization direction of the analyzer 5 depends on the polarization plane of either the component reflected by the beam splitter 2 of the output light of the laser beam 1 or the component transmitted through the beam splitter 12 of the output light of the laser 1 ′. It is also set at 45 degrees.
- the measurement target of circular dichroism is glucose.
- the absorption wavelength of glucose in the near infrared is about 1560 nm.
- a difference of about 10MHz is provided in terms of frequency.
- polarization-modulated light in which clockwise circularly polarized light and counterclockwise circularly polarized light alternately appear at the difference frequency between laser 1 and laser 1 'is obtained.
- the electric field vector of right-handed circularly polarized light and the electric field vector of left-handed circularly polarized light are expressed by (Equation 1) and (Equation 2), respectively.
- ⁇ is the frequency of light.
- the electric field of light in which right-handed circularly polarized light and left-handed circularly polarized light appear alternately is expressed by (Equation 3).
- Equation 4 is a superposition of two linearly polarized light beams whose frequencies are slightly different and whose polarization directions are orthogonal to each other. 3 is a modulation frequency, which is ⁇ ⁇ ⁇ . Accordingly, by superimposing two linearly polarized lights having frequencies different from each other by a modulation frequency and orthogonal to each other in polarization direction, it is possible to obtain polarized light modulated light in which clockwise circularly polarized light and counterclockwise circularly polarized light alternately appear.
- One of the polarization-modulated lights obtained in this way is transmitted through the analyzer 5 so that the polarization plane of the output component of the laser 1 and the polarization plane of the output component of the laser 1 'are made identical to each other.
- the detected beat signal is obtained at the difference frequency between laser 1 and laser 1 '.
- the Glan-Thomson polarizing prism is used as the analyzer 5.
- the only required performance of the analyzer 5 is that a sufficiently large intensity modulation is applied to the transmitted light. A value of about 10 is sufficient, and a film polarizing plate may be used.
- This beat signal is split in half by a divider 7, one of which is used as a reference signal for a mouth-in amplifier 6.
- the other one of the polarized light is incident on the sample 3, and the transmitted light is detected by the photodetector 4.
- the output signal of the photodetector 4 is input to the lock-in amplifier 6.
- the light incident on the photodetector 4 is intensity-modulated at the difference frequency between the laser 1 and the laser 1 'due to the circular dichroism of the sample 3, and as a result, the output signal of the photodetector 4 is modulated at this difference frequency.
- the modulated component of the output of the photodetector 4 is lock-in detected by the lock-in amplifier 6 using the beat signal, which is the output signal of the photodetector 4 ', as a reference signal.
- the output of the lock-in amplifier 6 is converted to the concentration of the substance to be measured on the analytical data processing display section 20 using predetermined calibration curve data. Further, the analysis data processing display section 20 displays the concentration of the measurement target substance.
- the other phase of the beat signal divided by the divider 7 is compared with the phase of the 10 MHz stable reference oscillator 8 by the phase frequency comparator 9, and is proportional to the displacement of the beat signal frequency from the reference oscillator frequency.
- the obtained error signal is obtained.
- p ID control The device 10 controls the frequency by injecting current into the laser 1 in accordance with the error signal, and forms a feedback loop in which the beat signal frequency and the reference oscillator frequency are synchronized.
- the frequency noise remaining in the bit signal is 10 kHz / s.
- the beat signal as a reference signal for lock-in detection
- stable lock-in detection can be performed irrespective of some frequency noise remaining in the bit signal. Therefore, the performance of the feedback loop for stabilizing the frequency of the beat signal does not need to be very high.
- the residual frequency noise of the beat signal may be 10 times that of the present embodiment.
- a pair of lasers whose outputs match within 1% is used as laser 1 and laser 1 ′, and modulation in which almost perfect clockwise circular polarization and almost perfect counterclockwise circular polarization appear alternately. I was able to get light. Even when using a set of L-lasers whose output does not match well, the output of the laser should be almost matched using a variable ND filter or a polarizing plate to obtain the same degree of modulation as in the present embodiment. Can be.
- the finger of the subject is used as the measurement site of the biological sample to be measured. However, another site, for example, an earlobe or a palm may be used.
- FIG 2 shows the results of a glucose tolerance test performed on a subject using a commercially available blood glucose concentration meter that uses an enzyme color reaction (horizontal axis) and the output of the lock-in amplifier 6 in Figure 1 (horizontal axis). (Vertical axis).
- a straight line passing through the origin is drawn as a calibration curve, and the output of the mouth-in amplifier indicates the circular dichroism of the sample, and the output of the glucose concentration in the sample is independent of the absorption by water. It reflects the fact that it is proportional. Therefore, the glucose concentration in the sample 3 can be accurately determined from the output of the Rockin amplifier 6 without being affected by the offset of absorption by water.
- the frequency of mouth lock-in detection is desirably in a region where the amplitude noise of laser light is small.
- laser light has large amplitude noise below MHz and higher than that, and in the frequency domain, it is possible to obtain detection sensitivity close to the shot noise limit, which is the theoretical detection limit, as long as the photodetector and electrical amplifier follow. it can. Also, it is better that the fluctuation of the difference frequency is sufficiently smaller than the difference frequency.
- a high-frequency mouth-in amplifier having a bandwidth of 20 MHz and a photodetector are used as the mouth-in amplifier, and the modulation frequencies for mouth-in detection, ie, laser 1 and laser 1 ′, are used.
- the modulation frequencies for mouth-in detection ie, laser 1 and laser 1 ′.
- using a faster photodetector and a lock-in amplifier would allow for hundreds of millimeters of frequency.
- the light that passes through the sample 3 and then enters the photodetector 4 is absorbed by the sample 3, so it is desirable that the intensity be as strong as possible.
- a polarization beam splitter having a reflectance and a transmittance of 2% and 96% for ⁇ -polarized light and a reflectance and a transmittance of 96% and 2% for S-polarized light, respectively, is used as the beam splitter 1.
- the beam splitter is used for multiplexing beams, but another element having the same effect, for example, an optical coupler may be used.
- the two lasers are installed so that the polarization planes are orthogonal to each other.
- the L laser itself is not arranged as such, and a phase delay plate is used to make the polarization planes orthogonal. It may be. It is also possible to integrate the laser chip and other optical elements on the same substrate.
- glucose is measured, and a single-mode semiconductor laser that outputs 1560 nm monochromatic light, which is one of the absorption wavelengths of glucose in the near-infrared light, as ImW as laser 1 and laser 1 ′ is used.
- a single-mode semiconductor laser that outputs 1560 nm monochromatic light which is one of the absorption wavelengths of glucose in the near-infrared light, as ImW as laser 1 and laser 1 ′ is used.
- a single-mode semiconductor laser that outputs 1560 nm monochromatic light, which is one of the absorption wavelengths of glucose in the near-infrared light, as ImW as laser 1 and laser 1 ′ is used.
- a single-mode semiconductor laser that outputs 1560 nm monochromatic light, which is one of the absorption wavelengths of glucose in the near-infrared light, as ImW as laser 1 and laser 1 ′ is used.
- the same result can be obtained by using another laser that outputs light of the same wavelength.
- an indium gallium arsenide semiconductor photodiode is used as a photodetector having the highest spectral sensitivity at a wavelength of 1560 nm of the semiconductor laser used and a small dark current.
- a laser as a light source enables non-invasive measurement of thick biological samples with poor permeability that could not be measured with a conventional circular dichroic spectrometer.
- two laser beams having a predetermined difference frequency and multiplexing them with a polarizing beam splitter it is possible to obtain light that is equivalently polarization-modulated.
- Power consumption can be reduced to about 1 Z100 compared to the case where By setting the modulation frequency to a high frequency above MHz, which is impossible with the conventional polarization modulation method, it is possible to detect light in a high frequency region where the laser's amplitude noise is small, and the measurement frequency is reduced due to the high modulation frequency. Becomes possible.
- FIG. 3 is a conceptual diagram illustrating a device configuration according to the second embodiment.
- the apparatus according to the present embodiment has mirrors 11 and 11 ′, sound modulators 12 and 12 ′, and has a laser 1, a photodetector 4 and 4 ′, a beam splitter 2 and 2 ′.
- the same components as those in the first embodiment were used for the sample 3, the lock-in amplifier 6, and the like.
- the main difference in the configuration between the second embodiment and the first embodiment is that instead of using two lasers having different frequencies, one laser 1 and an alum optical modulator 12 1 2 'means that two lights with different frequencies are obtained.
- the polarization plane of the laser 1 is set so that the transmitted light intensity and the reflected light intensity of the beam splitter 12 are equal.
- Beam splitter 2 transmitted light and anti-elbow The light is shifted in frequency by +80 MHz and +81 MHz by the acousto-optic modulator 12 and the acousto-optic modulator 12 ′, respectively, and then combined by the beam splitter 12.
- the light exiting the beam splitter 2 is modulated light in which clockwise circularly polarized light and counterclockwise circularly polarized light appear at a difference frequency of 1 MHz.
- the lock-in detection method is the same as that of the first embodiment. In this embodiment, the frequency noise of the acousto-optic modulator is reduced by using the bit signal as the reference signal for the lock-in detection. Regardless, stable lock-in detection can be performed.
- an acousto-optic modulator it is possible to use an acousto-optic modulator to set the modulation frequency to a frequency higher than MHz, which is impossible with a modulation method using a conventional piezo-elastic modulator.
- the stability of the difference frequency is particularly high even if there is no device for stabilizing the difference frequency. Is obtained.
- FIG. 4 is a conceptual diagram illustrating an apparatus configuration according to the third embodiment.
- the light source for irradiating the sample and the signal processing after detection of the transmitted light use the same configuration as in the second embodiment.
- n optical amplifiers 13 &. Pass light n + 1 times through the sample using 13: 1 and prisms 143-14-1n.
- the light transmitted through the sample 3 is incident on the optical amplifiers 13a to l3n before the sample 3 is irradiated again, and after the intensity is recovered, the output light of the optical amplifier is output by the prism. Reflect and irradiate sample 3.
- the intensity of the light transmitted through the sample is about 1/1000, that is, about 130 dB with respect to the intensity of the incident light.
- a gain variable with a maximum gain of 40 dB is used as an optical amplifier to sufficiently recover this loss. Fiber amplifier was used.
- the same light source as that of the second embodiment is used as the light source for irradiating the sample, but a light source having the same configuration as that of the first embodiment may be used.
- the light emitted from the laser is viesotropic like the conventional circular dichroism analyzer S Modulation may be performed using a modulator.
- the unique effect of the present embodiment is that if the light once transmitted through the sample 3 is transmitted twice as it is, the intensity of the final transmitted light becomes 180 000,000 of the intensity of the incident light, making detection difficult.
- the sensitivity can be improved n + 1 times by doubling the optical path length by transmitting the light n + 1 times through the sample without reducing the final transmitted light intensity. it can.
- FIG. 5 is a conceptual diagram showing an apparatus configuration of the fourth embodiment.
- This embodiment basically uses the same configuration as the third embodiment, but instead of using a prism to allow light to pass through the sample a plurality of times, an optical fiber whose input and output are coupled to an optical fiber Using the optical amplifiers 15 and 15 ', the output light of the optical amplifier is guided again by the optical fiber to the vicinity of the sample, and then irradiates the sample.
- the optical detector with the optical fiber connected to the input side Use 16 to detect the transmitted light of the sample. According to this embodiment, the same effect as that of the third embodiment can be obtained, and at the same time, the optical path in the sample can be set to almost the same narrow area within a few millimeters in width. Information can be extracted selectively.
- the first to fourth embodiments described above are merely examples of the present invention, and the present invention is not limited to a device for analyzing blood, but includes any optical activity in a living body. It can be widely used in all biochemical analyzers as a method for determining the target components.
- a simple device configuration is used, and a laser light source having a wavelength of an absorption band specific to a target component is used. This makes it possible to remove the absorption by water from the absorption by biological samples, measure only the absorption by the target component, and accurately and non-invasively quantify the concentration of the target component in the living body.
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Abstract
Cette invention concerne un procédé et un appareil faisant appel à deux faisceaux de lumière polarisée de manière linéaire, lesquels faisceaux possèdent des plans de polarisation orthogonaux l'un par rapport à l'autre, ainsi qu'une différence de fréquence prédéterminée. Ces deux faisceaux sont combinés de manière à obtenir une modulation permettant de générer en alternance une lumière gauche ou droite polarisée de manière circulaire. Cette lumière modulée est émise en direction d'un échantillon (3), tandis que l'intensité de la lumière traversant l'échantillon (3) est mesurée à l'aide d'un détecteur optique (4). La composante de modulation de la sortie du détecteur optique (4) est détectée par un processus de détection de blocage, ceci de manière à mesurer la différence entre les facteurs d'absorption de l'échantillon qui ont été obtenus, d'une part, avec la lumière gauche polarisée de manière circulaire, et d'autre part, avec la lumière droite polarisée de manière circulaire.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/JP1996/000623 WO1997033514A1 (fr) | 1996-03-13 | 1996-03-13 | Procede et appareil d'analyse dichromatique circulaire |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/JP1996/000623 WO1997033514A1 (fr) | 1996-03-13 | 1996-03-13 | Procede et appareil d'analyse dichromatique circulaire |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997033514A1 true WO1997033514A1 (fr) | 1997-09-18 |
Family
ID=14153039
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP1996/000623 WO1997033514A1 (fr) | 1996-03-13 | 1996-03-13 | Procede et appareil d'analyse dichromatique circulaire |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1997033514A1 (fr) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005107592A1 (fr) * | 2004-05-06 | 2005-11-17 | Nippon Telegraph And Telephone Corporation | Dispositif de mesure de concentration de composant et méthode de contrôle de dispositif de mesure de concentration de composant |
| WO2012141300A1 (fr) * | 2011-04-15 | 2012-10-18 | 株式会社グローバルファイバオプティックス | Dispositif de mesure de dichroïsme circulaire pour un corps vivant, procédé de mesure de dichroïsme circulaire pour un corps vivant, dispositif de mesure de taux de glycémie non invasif et procédé de mesure de taux de glycémie non invasif |
| JP2013523362A (ja) * | 2010-04-13 | 2013-06-17 | ヴィヴァンタム ゲーエムベーハー | 生体組織における生物学的、化学的、及び/又は生理学的パラメータを決定するための装置及び方法 |
| JP2020096834A (ja) * | 2018-12-17 | 2020-06-25 | ゼット スクエア リミテッド | 強化されたマルチコアファイバ内視鏡 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4843383A (fr) * | 1971-09-27 | 1973-06-22 | ||
| JPS5194986A (fr) * | 1974-10-01 | 1976-08-20 | ||
| JPH03173535A (ja) * | 1989-12-01 | 1991-07-26 | Matsushita Electric Ind Co Ltd | グルコース無侵襲計測方法 |
| JPH05503777A (ja) * | 1990-01-11 | 1993-06-17 | リサーチ・コーポレィション・テクノロジーズ・インコーポレイテッド | 円二色性及び分光光度吸収検出法及びその装置 |
-
1996
- 1996-03-13 WO PCT/JP1996/000623 patent/WO1997033514A1/fr active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4843383A (fr) * | 1971-09-27 | 1973-06-22 | ||
| JPS5194986A (fr) * | 1974-10-01 | 1976-08-20 | ||
| JPH03173535A (ja) * | 1989-12-01 | 1991-07-26 | Matsushita Electric Ind Co Ltd | グルコース無侵襲計測方法 |
| JPH05503777A (ja) * | 1990-01-11 | 1993-06-17 | リサーチ・コーポレィション・テクノロジーズ・インコーポレイテッド | 円二色性及び分光光度吸収検出法及びその装置 |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005107592A1 (fr) * | 2004-05-06 | 2005-11-17 | Nippon Telegraph And Telephone Corporation | Dispositif de mesure de concentration de composant et méthode de contrôle de dispositif de mesure de concentration de composant |
| US8332006B2 (en) | 2004-05-06 | 2012-12-11 | Nippon Telegraph And Telephone Corporation | Constituent concentration measuring apparatus and constituent concentration measuring apparatus controlling method |
| US9008742B2 (en) | 2004-05-06 | 2015-04-14 | Nippon Telegraph And Telephone Corporation | Constituent concentration measuring apparatus and constituent concentration measuring apparatus controlling method |
| US9060691B2 (en) | 2004-05-06 | 2015-06-23 | Nippon Telegraph And Telephone Corporation | Constituent concentration measuring apparatus and constituent concentration measuring apparatus controlling method |
| US9198580B2 (en) | 2004-05-06 | 2015-12-01 | Nippon Telegraph And Telephone Corporation | Constituent concentration measuring apparatus and constituent concentration measuring apparatus controlling method |
| JP2013523362A (ja) * | 2010-04-13 | 2013-06-17 | ヴィヴァンタム ゲーエムベーハー | 生体組織における生物学的、化学的、及び/又は生理学的パラメータを決定するための装置及び方法 |
| WO2012141300A1 (fr) * | 2011-04-15 | 2012-10-18 | 株式会社グローバルファイバオプティックス | Dispositif de mesure de dichroïsme circulaire pour un corps vivant, procédé de mesure de dichroïsme circulaire pour un corps vivant, dispositif de mesure de taux de glycémie non invasif et procédé de mesure de taux de glycémie non invasif |
| JP2020096834A (ja) * | 2018-12-17 | 2020-06-25 | ゼット スクエア リミテッド | 強化されたマルチコアファイバ内視鏡 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5372135A (en) | Blood constituent determination based on differential spectral analysis | |
| US6070093A (en) | Multiplex sensor and method of use | |
| US7254432B2 (en) | Method and device for non-invasive measurements of blood parameters | |
| JP4756218B2 (ja) | 光伝搬モードを用いる物質内の光不均質性およびその他特性の測定 | |
| CN100512752C (zh) | 光程可选择的无创人体成分检测方法及检测装置 | |
| US6442408B1 (en) | Method for quantification of stratum corneum hydration using diffuse reflectance spectroscopy | |
| US5774213A (en) | Techniques for measuring difference of an optical property at two wavelengths by modulating two sources to have opposite-phase components at a common frequency | |
| WO2006040841A1 (fr) | Instrument de mesure non invasive de la glycemie | |
| US6741875B1 (en) | Method for determination of analytes using near infrared, adjacent visible spectrum and an array of longer near infrared wavelengths | |
| JP4472794B2 (ja) | グルコース濃度の定量装置 | |
| KR20170107429A (ko) | 스펙트럼 샘플 반응을 측정하기 위한 방법 및 장치 | |
| CA2383727A1 (fr) | Procede de determination d'analytes au moyen d'un spectre visible adjacent, a infrarouge proche et reseau de longueurs d'onde plus longues a infrarouge proche | |
| JPH11128209A (ja) | 血中成分濃度の無血測定方法及び装置 | |
| WO1995005120A1 (fr) | Procede non-invasif de mesure du taux de sucre sanguin et instrument de mesure utilise a cet effet | |
| KR20090086202A (ko) | 3개 다이오드 광학 브리지 시스템 | |
| JPH07501230A (ja) | ヒト又は動物の組織の成分を測定するための装置 | |
| US7107087B2 (en) | Method and apparatus for measuring a concentration of a component in a subject | |
| US9759714B2 (en) | Methods and apparatus for normalizing path length in non-invasive glucose monitoring | |
| CA2369793A1 (fr) | Procede pouvant ameliorer le calibrage d'un appareil de controle sanguin | |
| JP4329360B2 (ja) | グルコース濃度の定量装置 | |
| WO1997033514A1 (fr) | Procede et appareil d'analyse dichromatique circulaire | |
| JP3694291B2 (ja) | 血糖値の無侵襲測定装置 | |
| JP2000023947A (ja) | 生体光計測方法 | |
| JP2004020539A (ja) | 赤外円二色性測定装置および赤外円二色性測定方法 | |
| JP2007313286A (ja) | 光学的生体情報測定方法及びその装置 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): CN JP KR US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| 122 | Ep: pct application non-entry in european phase |