WO2003036278A1 - Micro-chemical system, and photothermal conversion spectroscopic method - Google Patents

Micro-chemical system, and photothermal conversion spectroscopic method Download PDF

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Publication number
WO2003036278A1
WO2003036278A1 PCT/JP2002/009463 JP0209463W WO03036278A1 WO 2003036278 A1 WO2003036278 A1 WO 2003036278A1 JP 0209463 W JP0209463 W JP 0209463W WO 03036278 A1 WO03036278 A1 WO 03036278A1
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WIPO (PCT)
Prior art keywords
light
lens
excitation light
detection light
detection
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Application number
PCT/JP2002/009463
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French (fr)
Japanese (ja)
Inventor
Jun Yamaguchi
Akihiko Hattori
Original Assignee
Nippon Sheet Glass Co., Ltd.
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Publication date
Application filed by Nippon Sheet Glass Co., Ltd. filed Critical Nippon Sheet Glass Co., Ltd.
Publication of WO2003036278A1 publication Critical patent/WO2003036278A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/171—Systems in which incident light is modified in accordance with the properties of the material investigated with calorimetric detection, e.g. with thermal lens detection

Definitions

  • the present invention relates to a microchemical system and a photothermal conversion spectroscopic analysis method. Background art.
  • microchemical system performs mixing, reaction, separation, extraction, detection, etc. of a sample solution (liquid containing a sample) in a fine channel formed in a small glass substrate or the like.
  • reactions performed in this microchemical system include a diazotization reaction, a nitration reaction, and an antigen-antibody reaction.
  • extraction and separation include solvent extraction, electrophoretic separation, and column separation.
  • Microchemical systems may use only a single function, such as for separation only, or may use a combination of multiple functions.
  • This electrophoresis apparatus includes a plate-like member with a flow path composed of two glass substrates bonded to each other. Since this member is plate-shaped, it can be used as a glass cavity tube with a circular or square cross section. It is harder to break and easier to handle.
  • Figure 4 shows the principle of the thermal lens.
  • the photothermal conversion effect is induced when the excitation light is condensed and irradiated on a very small sample solution via the objective lens of the microscope. Since the refractive index of many substances decreases as the temperature rises, the refractive index of the sample solution irradiated with the excitation light decreases as the temperature of the sample solution approaches the focusing center where the temperature rises greatly. In other words, the refractive index increases as the distance from the focusing center increases. This is because the temperature rise becomes smaller due to thermal diffusion as the distance from the focusing center increases. This refractive index distribution optically has the same effect as a concave lens, and this effect is called the thermal lens effect.
  • the magnitude of the thermal lens effect that is, the power of the concave lens is proportional to the light absorption of the sample solution.
  • the refractive index increases in proportion to the temperature, the change in the refractive index is reversed, so that a thermal lens effect having the same effect as the convex lens is generated.
  • the photothermal conversion spectroscopy is suitable for detecting the concentration of an extremely small sample because it observes a change in the refractive index of the sample solution caused by the diffusion of heat in the sample solution. .
  • a plate member with a flow path is disposed below an objective lens of a microscope, and excitation light of a predetermined wavelength output from an excitation light source enters the microscope.
  • This excitation light is focused and irradiated on the sample solution in the flow path of the plate member with the flow path by the objective lens of the microscope.
  • the focal position of the focused excitation light is located in the sample solution, and a thermal lens is formed around this focal position.
  • the detection light source outputs detection light having a wavelength different from that of the excitation light and enters the microscope.
  • the detection light emitted through the microscope is focused and irradiated on the thermal lens formed in the sample solution by the excitation light, passes through the sample solution, and diverges (when the thermal lens has the effect of a concave lens).
  • light is condensed (when the thermal lens has the effect of a convex lens).
  • the light diverged or condensed from the sample solution and emitted serves as signal light.
  • This signal light is received by the detector after passing through both the condenser lens and the filter or only the filter, and is detected.
  • the intensity of the detected signal light depends on the refractive index of the thermal lens formed in the sample solution.
  • the detection light may have the same wavelength as the excitation light, and the excitation light may also serve as the detection light.
  • the thermal lens is formed at the focal position of the excitation light, and a change in the refractive index of the thermal lens formed is detected by the detection light.
  • the photothermal conversion spectrometer described above is large in size because the light source, the optical system of the measurement unit and the detection unit (photoelectric conversion unit) are complicatedly configured, and lacks portability. For this reason, there is a problem that the place where the photothermal conversion spectrometer is installed and the operation of the device are limited, and further, there is a problem that the work efficiency of the user is poor.
  • the photothermal conversion spectrometer uses the excitation light and the detection light as Since it leads to the solution, it is necessary to prevent each part of the optical system such as the light source, mirror, lens, etc. from moving during the measurement, and therefore, to secure them, A surface plate is required. Furthermore, when the optical axes of the excitation light and the detection light are shifted due to changes in the environment such as temperature, a jig for adjusting the shift is required. These factors also cause the photothermal conversion spectrometer to become large and lack portability.
  • the excitation light is modulated in order to increase the S / N of the thermal lens signal obtained by the photothermal conversion spectrometer, but usually the excitation light modulator is placed on the optical path of the excitation light.
  • a chopper will be installed.
  • the chopper has a disk-shaped member, and a through-hole is opened in the disk-shaped member periodically along the circumference.
  • the chopper always rotates this disc-shaped member, but the rotation of this disc-shaped member causes vibration and generates air turbulence, and the size of the through hole opened in the disc-shaped member
  • the modulation period of the excitation light may not be completely constant due to unevenness in the pod position or deformation of the disk-shaped member. These become noises at the time of measurement and cause the measurement sensitivity of the photothermal conversion spectrometer to decrease.
  • FIG. 5A and 5B are diagrams showing the formation position of the thermal lens and the focal position of the detection light in the traveling direction of the excitation light, and FIG. 5A shows a case where the objective lens has chromatic aberration. 5B shows the case where the objective lens has no chromatic aberration.
  • the thermal lens 13 1 is formed at the focal position 13 2 of the excitation light, and the focal position 13 2 Since the focal position 13 3 of the detection light is formed at a position shifted by L, the change in the refractive index of the thermal lens 13 1 is regarded as the change in the focal length of the detection light. Can be detected.
  • the focus position 13 3 of the detection light is the thermal lens 13 3 formed at the focus position 13 2 of the excitation light. It almost matches the position of 1. For this reason, since the detection light does not undergo refraction by the thermal lens 131, a change in the refractive index of the thermal lens 131 cannot be detected.
  • the objective lens of a microscope is usually manufactured so as not to have chromatic aberration.
  • the focus position 133 of the detection light is heat generated at the focus position of the excitation light. It almost matches the position of lens 13 1 (Fig. 5B). Therefore, a change in the refractive index of the thermal lens 13 1 cannot be detected. For this reason, the position of the sample solution where the thermal lens 13 1 is formed is shifted from the focal position 13 3 of the detection light as shown in FIG. 6A or FIG.
  • the detection light is slightly diverged or condensed using a lens (not shown), and is incident on the objective lens 130, so that the focus position 133 of the detection light is changed. It has to be displaced from the thermal lens 13 1, and the sensitivity of the measurement may be sacrificed, and the user's work efficiency is also poor.
  • An object of the present invention is to provide a micro-mouth chemical system capable of performing measurement with high sensitivity, and a photothermal conversion spectroscopy method to be performed by the micro-mouth chemical system.
  • An object of the present invention is to provide a small-sized microchemical system that can improve efficiency. Disclosure of the invention
  • an excitation light source that outputs excitation light
  • a detection light source that outputs detection light
  • the excitation light and the detection light are combined.
  • An irradiating lens for irradiating the sample with the excitation light and the detection light guided by the guiding optics;
  • a detection unit configured to detect the detection light transmitted through the thermal lens generated by the sample irradiated with the excitation light, and an analysis unit configured to analyze the sample based on the detected detection light.
  • a microchemical system is provided.
  • the guiding optical system includes an optical fiber that guides the excitation light and the detection light.
  • the optical fiber propagates the excitation light and the detection light in a single mode.
  • the irradiation lens is fixed to an end of the optical fiber from which the excitation light and the detection light are emitted.
  • the irradiation lens is a gradient index lens.
  • the gradient index lens is a cylindrical lens.
  • the sample is irradiated with excitation light and detection light via an irradiation lens, and is generated by the sample that has been irradiated with the excitation light.
  • a photothermal spectroscopy method for detecting a detection light transmitted through a thermal lens and analyzing a sample, wherein the excitation light is modulated by an acousto-optic modulator is provided.
  • the excitation light applied to the sample is first-order diffracted light that is black-diffraction by the acoustic optical modulator.
  • FIG. 1 is a diagram showing a schematic configuration of a microphone chemical system according to a first embodiment of the present invention.
  • FIG. 2 is a diagram showing a schematic configuration of a microchemical system according to the second embodiment of the present invention.
  • FIG. 3 is a diagram illustrating a schematic configuration of a microchemical system according to a third embodiment of the present invention.
  • Figure 4 shows the principle of the thermal lens.
  • FIG. 5A and 5B are diagrams showing the formation position of the thermal lens and the focus position of the detection light in the traveling direction of the excitation light, and FIG. 5A shows a case where the objective lens has chromatic aberration. 5B shows a case where the objective lens has no chromatic aberration.
  • FIGS. 6A and 6B are diagrams showing the formation position of the thermal lens and the focus position of the detection light with respect to the traveling direction of the excitation light.
  • FIG. 6A shows that the thermal lens has a higher objective lens position than the detection light focus position.
  • FIG. 6B shows a case where the heat lens is formed at a position farther from the objective lens than the focal position of the detection light.
  • Fig. 7 is a diagram showing a method of detecting a change in the refractive index of a thermal lens in a conventional photothermal conversion analyzer.
  • a concave lens is inserted in the middle of the optical path to make the detection light divergent, and the focal length of the excitation light This shows the case where the focal position is located farther than the position.
  • FIG. 1 is a diagram showing a schematic configuration of a microchemical system according to a first embodiment of the present invention.
  • a microchemical system 1 includes an optical fiber unit 10 (hereinafter, an optical fiber unit 10) having a built-in lens.
  • the optical fiber unit 10 is located at the front end of the tube 104 (the lower side in the drawing). Side), there is a gradient index rod lens 102 as an objective lens, and an optical filter that propagates excitation light and detection light in a single mode from the rear end (upper side in the drawing). Fiber 1 01 has been inserted.
  • the input end of the optical fin 101 is connected to one end of a gradient index lens 102.
  • the optical fiber 10 also has the same outer diameter as the refractive index distributed type lens 102 at the one end side of the gradient index type lens 102 in the tube 104.
  • Ferrule 103 with an outside diameter of The ferrule 103 is for making the outer diameter of the optical fiber 101 the same as the outer diameter of the gradient index lens 102. 0 1 is mounted so as to pass through ferrule 103.
  • the optical fiber 101 is fixed by a ferrule 103, and the gradient index rod lens 102 and the ferrule 103 are fixed in a tube 104. .
  • the optical fiber 101 and the refractive index distribution type end lens 102 may be in close contact with each other or may have a gap.
  • the gate 10 is fixed by a jig 30 at a position where the emitted light vertically enters a plate-like member 20 with a flow path to be described later.
  • an excitation light source 105 that emits excitation light for exciting the sample solution, and information for analyzing the sample solution.
  • a detection light source 106 that emits detection light that irradiates the sample to detect light
  • an acousto-optic modulator 107 that is arranged on the optical path of the excitation light, and modulates the excitation light
  • Dick opening mirror 108 for making the primary light of the excitation light diffracted by the black diffraction of the detector 107 coaxial with the detection light
  • the excitation light and the detection light A lens 109 and the like for allowing the light to enter the firer 101 are provided.
  • the acousto-optic modulator 107 converts the light due to the acousto-optic interaction caused by ultrasonic waves.
  • This device uses diffraction. That is, a change in the refractive index (photoelastic effect) of the optical medium that occurs when an ultrasonic wave propagates through the optical medium is used.
  • the refractive index changes due to elastic strain and pressure (photoelasticity). Therefore, a refractive index fluctuation region in which the refractive index fluctuates in synchronization with the period of the propagating ultrasonic wave occurs in the optical medium. Light incident on the refractive index fluctuation region is diffracted. At this time, the intensity and the diffraction angle of the diffracted light change depending on the intensity and frequency of the propagating ultrasonic wave.
  • the excitation light When the excitation light is incident on the acousto-optic modulator 107 at an angle that satisfies the black condition, most of the ultrasound is diffracted as primary light while the ultrasound is applied to the acousto-optic medium, and When the light is not applied to the acousto-optic medium, the light is not diffracted and passes through the acousto-optic modulator 107.
  • the presence or absence of the application of this ultrasonic wave can be used for modulating the excitation light.
  • the 0th-order light transmitted through the acousto-optic modulator 107 is used as the excitation light
  • the 0th-order light does not become completely zero even while the ultrasonic wave is applied to the acousto-optic medium.
  • This residual light becomes noise at the time of photothermal conversion spectroscopic measurement, and the measurement sensitivity is reduced.
  • the primary light is used as the excitation light
  • the primary light exists only while the ultrasonic wave is being applied to the acousto-optic medium, and does not exist while the ultrasonic wave is not applied to the acousto-optic medium. not exist. Therefore, the primary light is introduced into the optical fiber 101 as excitation light.
  • the optical fiber 101 has a single mode having only one propagation mode.
  • the reason for using a photothermal conversion spectroscopy method to detect a very small amount of solute in a sample solution is to use excitation light. By reducing the aperture as small as possible, the energy used for photothermal conversion is increased, and the thermal lens generated by the excitation light is made a lens with little aberration.
  • the focal point of the excitation light becomes smaller.
  • the thermal lens generated by the excitation light it is desirable to narrow down the detection light as much as possible in order to increase the amount of detection light passing through this thermal lens as much as possible.
  • the optical fiber transmits the excitation light and the detection light in a single mode.
  • any optical fiber 101 can be used as long as it transmits the excitation light and the detection light.
  • the output light does not have a Gaussian distribution, and the output pattern of the output light changes depending on various conditions such as the degree of bending of the optical fiber 101. Therefore, stable emitted light cannot always be obtained. For this reason, it may be difficult to measure a small amount of solute and the measured value may not be stable. Therefore, as described above, the optical fiber 101 is preferably of a single mode.
  • the plate member 20 with a flow path has a flow path 204 through which the sample solution flows, and is composed of glass substrates 201, 202, and 203 bonded in three layers. Mix, stir, synthesize, and mix glass substrate 202 The above-mentioned flow path 204 through which the sample solution flows for separation, extraction, detection, etc. is formed.o
  • the material of the plate member 20 with a flow path is desirably glass from the viewpoint of durability and chemical resistance.
  • glass having high acid resistance and alkali resistance specifically, borosilicate glass, soda lime glass, and aluminoborosilicate Glass, quartz glass, etc. are preferred.
  • organic substances such as plastic.
  • Examples of the adhesive for bonding the glass substrates 201, 202, and 203 to each other include, for example, ultraviolet curable, thermosetting, two-component curable acrylic and epoxy organic adhesives. , And inorganic adhesives. Further, the glass substrates 201 to 203 may be fused to each other by heat fusion.
  • the photoelectric converter 401 for detecting the detection light separates the excitation light and the detection light.
  • a wavelength filter 403 for selectively transmitting only the detection light is provided.
  • the member having the pinhole is positioned on the optical path of the detection light and at a position upstream of the photoelectric converter 401. It may be arranged as follows. The signal obtained from the photoelectric converter 401 is sent to a lock-in amplifier 404 to synchronize it with the acousto-optic modulator 107 used to modulate the excitation light, and thereafter, Analyzed (analyzed) by computer 405.
  • the refractive index distribution type rod lens 102 is a columnar transparent lens whose refractive index continuously changes in the radial direction from the center line extending in the longitudinal direction.
  • Such a rod lens has a refractive index n 0 at a position radially r from the center line position, where n 0 is the refractive index at the center line position and g is the square distribution constant. (r) is approximately the quadratic equation of r
  • n (r) n . — (G 2 ⁇ 2) ⁇ r 2
  • the refractive index distributed lens 102 has its total length z. Where 0 ⁇ z. H? When selecting within the range of r / 2 g, both end faces are flat and have the same image forming properties as a normal convex lens, and the parallel incident light focuses from the output end to
  • Such a graded index lens 102 is manufactured, for example, by the following method.
  • the bottom surface of the refractive index distribution type lens 102 is flat, the end surface of the optical fiber 101 can be easily attached and the refractive index distribution type rod lens.
  • the optical axis of 102 and the optical axis of optical fiber 101 can be easily matched.
  • the refractive index load rod lens 102 has a cylindrical shape, the optical fiber unit 10 can be easily formed into a cylindrical shape. This makes it extremely easy to hold the optical fin—unit 10 by the jig 30.
  • the focal position of the excitation light emitted from the refractive index distribution type lens 102 needs to be located in the channel 204 of the plate member 20 with a channel. Refractive index The distributed lens 102 does not need to be in contact with the plate member 20 with the flow path, but if it does, it is bent by the thickness of the upper glass plate 201 of the plate member 20 with the flow path.
  • the focal length of the rate distribution type lens 102 can be adjusted. If the thickness of the upper glass plate 201 is not enough, insert a spacer for adjusting the focal length between the refractive index type aperture lens 102 and the upper glass plate 201. You may. If the focal position of the excitation light is fixed in the flow path 204 of the plate-like member 20 with a flow path in this manner, the focal length does not need to be adjusted. 1 can be reduced in size.
  • the refractive index distribution type lens 102 is set such that the focal position of the detection light slightly deviates from the focal position of the excitation light by ⁇ L (FIG. 5A).
  • the ⁇ L value changes depending on the thickness of the sample to be measured.
  • the value of ⁇ L represents the difference between the focal position of the detection light and the focal position of the excitation light
  • the value of ⁇ L can be used when the focal length of the detection light is longer than the focal length of the excitation light or shorter. The same result.
  • the tip of the optical fiber is processed into a spherical shape or the like to form a lens, it is possible to reduce the excitation light and detection light without attaching a lens to the tip of the optical fiber.
  • Excitation light and inspection because there is almost no chromatic aberration
  • the respective focal positions of the light emission become substantially the same. Therefore, there is a problem that the signal of the thermal lens is hardly detected.
  • the lens formed by adding the tip of the optical fiber has a large other aberration, so that there is a problem that the focus of the excitation light and the detection light is large. Therefore, in the present embodiment, the refractive index distribution type aperture lens 102 is attached to the tip of the optical fin 101.
  • the gradient index rod lens 102 is attached to the tip of the optical fiber 101 that propagates the excitation light and the detection light. Since it is not necessary to adjust the optical axis of the excitation light and the detection light and the optical axis of the gradient index rod lens 102 for each measurement, the work efficiency of the user can be improved. Furthermore, since a jig for matching the optical axes and a solid surface plate are unnecessary, the microchemical system 1 can be downsized.
  • the core diameter of the optical fiber 101 is smaller than that of a normal objective lens, the 0th-order light and the 1st-order light of the excitation light diffracted by the black diffraction of the acousto-optic modulator 107
  • the end face of the optical fiber 101 and the acousto-optic modulator 107 are not Since the distance can be reduced, the size of the microchemical system 1 can be further reduced.
  • FIG. 2 is a diagram showing a schematic configuration of a microchemical system according to the second embodiment of the present invention.
  • the microchemical system 2 according to the second embodiment has the same reference numerals as those of the microchemical system 1 according to the first embodiment. Description is omitted.
  • the excitation light and the detection light are coaxial.
  • a multiplexer 110 is provided in place of the die-cloth mirror.
  • the multiplexer 110 is connected to an optical fiber 101a for guiding excitation light and an optical fiber 110b for guiding detection light.
  • each of them is incident on the optical liner 101 aa 101 b and guided to the multiplexer 110, where They are multiplexed.
  • the multiplexed excitation light and detection light are distributed by the optical fiber 101 as in the case of the microphone chemistry system 1 according to the first embodiment. Guided to 0 2.
  • the multiplexer 110 When the multiplexer 110 is used as a means for multiplexing the excitation light and the detection light, the multiplexer 110 itself must be smaller than the dichroic mirror. When a jig for fixing the die mirror is unnecessary or necessary, a micro jig smaller than the jig for fixing the dichroic mirror can be used. This is useful for downsizing the system.
  • the micro-mouth chemical system 2 is more effective than the case where the excitation light and the detection light are multiplexed using the dike-mouth mirror. 2 can be further miniaturized, and the distance that the excitation light and detection light before being multiplexed propagate in space becomes shorter, so that they are less affected by external conditions such as vibration. The sensitivity is improved.
  • FIG. 3 is a diagram illustrating a schematic configuration of a microchemical system according to a third embodiment of the present invention.
  • FIG. 3 the same components and parts of the micro chemical system 3 according to the third embodiment as those of the micro ⁇ chemical system 1 according to the first embodiment are denoted by the same reference numerals. And the description is omitted.
  • the micro mouth chemical system 3 differs from the first and second embodiments in that the excitation light and the detection light are converted to spatial light using the objective lens 1303 without using an optical fiber.
  • the acousto-optic modulator 1 0 7 Since the angle of separation between the first-order light and the zero-order light diffracted by the first order is small, a long optical path length is required to make only the first-order light incident on the objective lens 130.
  • prism 1 1 1 is used to separate the zero-order light and the first-order light.
  • the prism 111 By using the prism 111, the distance between the acousto-optic modulator 107 and the objective lens 130 becomes shorter, so that the microchemical system can be miniaturized. Even if a mirror is used instead of the prism 111, the 0th-order light and the 1st-order light can be separated, but the prism has the advantage of being more compact. Industrial applicability
  • the acousto-optic modulator provided in the guiding optical system modulates the excitation light. Since there is no driving part, there is no vibration or air turbulence during modulation. Further, the acousto-optic modulator electrically controls the modulation period, so that the modulation period of the excitation light can be kept constant. For this reason, noise due to modulation is reduced, and measurement with high sensitivity is possible. In addition, since the user does not need to adjust the focal position of the detection light, the work efficiency of the user is improved, and since the acousto-optic modulator is small, the microchemical system can be downsized.
  • the excitation light and the detection light are guided by the optical fiber provided in the guidance optical system, so that the excitation light and the detection light are coaxial. Therefore, it is not necessary to adjust the optical axes of the excitation light and the detection light, so that the work efficiency of the user can be further improved.
  • the thermal lens generated by the excitation light has its aberration. It is small and can measure accurately.
  • the irradiation lens is fixed to the end of the optical fiber from which the excitation light and the detection light are emitted, the excitation light, the detection light, and the irradiation lens are fixed. All optical axes can be fixed. Therefore, there is no need to adjust the optical axis, and the work efficiency of the user is further improved.
  • a jig for adjusting the optical axis is not required, the size of the micro chemical system can be reduced.
  • the detection light and the excitation light have different frequencies, and the irradiation lens has chromatic aberration. Therefore, the focal positions of the excitation light and the detection light can be determined without using another optical system. Can be shifted. As a result, it is possible to prevent the micro chemical system from becoming large and contribute to miniaturization.
  • the irradiation lens is a gradient index lens
  • the irradiation lens can be extremely miniaturized. As a result, the size of the microchemical system can be further reduced.
  • the gradient index lens is a cylindrical rod lens, it can be easily held, and the optical axis of the optical fin and the optical axis of the rod lens can be easily maintained. And can be easily matched.
  • the excitation light is modulated by the acousto-optic modulator without the driving part, and the excitation light is modulated by the operation of the driving part accompanying the modulation.
  • the acousto-optic modulator determines the modulation speed electrically, the modulation period of the excitation light can always be kept constant. As a result, noise due to modulation is reduced, and measurement with high sensitivity becomes possible.
  • the excitation light applied to the sample is the first-order diffracted light that is black-diffraction by the acousto-optic modulator.
  • the light intensity can be completely reduced to zero.
  • SZN can be increased, and high-sensitivity measurement can be reliably performed.

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Abstract

A micro-chemical system capable of performing measurement of high sensitivity. The micro-chemical system (1) guides the excited light modulated by an acousto-optical modulator (107) and the detected light to an optical fiber unit (10) by an optical fiber (101) in a single mode. The optical fiber unit has a built-in a refractive index distribution type rod lens (102). The excited light and the detected light are irradiated toward a sample from the refractive index distribution type rod lens (102).

Description

明 細 書 マイ ク ロ化学システム及び光熱変換分光分析方法 技術分野  Description Micro chemical system and photothermal conversion spectroscopy
この発明は、 マイ ク ロ化学システム及び光熱変換分光分析方法に関す る。 背景技術 .  The present invention relates to a microchemical system and a photothermal conversion spectroscopic analysis method. Background art.
従来から、 化学反応の高速性や微少量の試料での反応、 オンサイ ト分 析等の観点から、 化学反応を微小空間で行う ための集積化技術が注目 さ れてお り 、 精力的な研究が世界的に進められている。  From the viewpoint of high-speed chemical reactions, reactions with very small amounts of samples, on-site analysis, etc., integrated technologies for performing chemical reactions in a minute space have been attracting attention. Is being promoted worldwide.
このよ う な集積化技術の 1 つと して、 所謂マイ ク ロ化学システムがあ る。 このマイ ク ロ化学システムは、 小さなガラス基板等に形成した微細 な流路の中で試料溶液 （試料を含む液体） の混合、 反応、 分離、 抽出、 検出等を行う ものである。 このマイ ク ロ化学システムで行う反応の例と しては、 ジァゾ化反応、 ニ ト ロ化反応、 抗原抗体反応などがある。 また、 抽出や分離の例と しては、 溶媒抽出、 電気泳動分離、 カ ラム分離な どが ある。 マイ ク ロ化学システムは、 分離だけを目的と したよ う な単一の機 能のみを使用 しても よ く 、 また、 複数の機能を組み合わせて使用 しても よい。  One such integration technology is the so-called microchemical system. This microchemical system performs mixing, reaction, separation, extraction, detection, etc. of a sample solution (liquid containing a sample) in a fine channel formed in a small glass substrate or the like. Examples of reactions performed in this microchemical system include a diazotization reaction, a nitration reaction, and an antigen-antibody reaction. Examples of extraction and separation include solvent extraction, electrophoretic separation, and column separation. Microchemical systems may use only a single function, such as for separation only, or may use a combination of multiple functions.
上記の機能のう ち、 分離のみを目的と したものと して、 極微量のタ ン パクや核酸等を分析する電気泳動装置が提案されている （例えば、 特開 平 8 — 1 7 8 8 9 7号公報） 。 この電気泳動装置は互いに接合された 2 枚のガラス基板からなる流路付き板状部材を備えている。 この部材は板 状であるので、 横断面が円形又は角形のガラスキヤ ビラ リ ーチューブに 比べて破損しに く く 、 取り扱いが容易である。 Among the above functions, an electrophoresis apparatus has been proposed that analyzes only trace amounts of proteins, nucleic acids, etc., for the purpose of separation only (for example, see Japanese Patent Application Laid-Open No. H8-17888). 97 publication). This electrophoresis apparatus includes a plate-like member with a flow path composed of two glass substrates bonded to each other. Since this member is plate-shaped, it can be used as a glass cavity tube with a circular or square cross section. It is harder to break and easier to handle.
このよ う なマイ ク ロ化学システムにおいては試料の量が微量なので、 高感度な検出方法が必須である。 このよ う な方法と して、 微細な流路内 の試料溶液が光を吸収する こ と によ って発生する熱レンズ効果を利用 し た光熱変換吸収分析法が確立されている。 この光熱変換分光分析法は、 試料溶液に集光照射された光を試料溶液中の溶質が吸収して熱エネルギ 一を放出 し、 この熱エネルギーによ って溶媒が局所的に温度上昇する こ と によつて試料溶液の屈折率が変化し、 も って熱レンズが形成される光 熱変換効果を利用する ものである。 この光熱変換分光分析法によ ってマ イ ク 口化学システムの実用化の道が開かれている。  In such a microchemical system, since the amount of sample is very small, a highly sensitive detection method is essential. As such a method, a photothermal conversion absorption analysis method utilizing the thermal lens effect generated by the absorption of light by a sample solution in a fine channel has been established. In this photothermal conversion spectroscopy, the solute in the sample solution absorbs the light focused and irradiated on the sample solution and emits heat energy, and the heat energy causes the solvent to locally rise in temperature. Thus, the refractive index of the sample solution changes, and the photothermal conversion effect of forming a thermal lens is used. This photothermal conversion spectroscopy has opened the way to the practical use of micro-mouth chemical systems.
図 4 は、 熱レンズの原理を示す図である。  Figure 4 shows the principle of the thermal lens.
図 4 において、 顕微鏡の対物レンズを介して励起光を極微少な試料溶 液に集光照射する と光熱変換効果が誘起される。 多く の物質では温度上 昇に伴い屈折率が小さ く なるので、励起光が集光照射された試科溶液は、 温度上昇の大き い集光中心に近づく ほど屈折率が小さ く なる。 言い換え る と、 集光中心から離れるほど屈折率は大き く なる。 これは、 集光中心 から離れるほど熱拡散によ って温度上昇が小さ く なるからである。 この 屈折率の分布は、 光学的には、 凹レンズと同 じ効果を齋すので、 この効 果は熱レンズ効果と呼ばれている。 この熱レンズ効果の大き さ、 即ち凹 レンズの度数は試料溶液の光吸収度に比例する。 なお、 屈折率が温度に 比例 して大き く なる場合は、 屈折率の変化は逆になるので凸レンズと同 じ効果を齎す熱レンズ効果が生じる。  In Fig. 4, the photothermal conversion effect is induced when the excitation light is condensed and irradiated on a very small sample solution via the objective lens of the microscope. Since the refractive index of many substances decreases as the temperature rises, the refractive index of the sample solution irradiated with the excitation light decreases as the temperature of the sample solution approaches the focusing center where the temperature rises greatly. In other words, the refractive index increases as the distance from the focusing center increases. This is because the temperature rise becomes smaller due to thermal diffusion as the distance from the focusing center increases. This refractive index distribution optically has the same effect as a concave lens, and this effect is called the thermal lens effect. The magnitude of the thermal lens effect, that is, the power of the concave lens is proportional to the light absorption of the sample solution. When the refractive index increases in proportion to the temperature, the change in the refractive index is reversed, so that a thermal lens effect having the same effect as the convex lens is generated.
このよ う に、 光熱変換分光分析法は、 試料溶液における熱の拡散に起 因する試料溶液の屈折率の変化を観察する ものであるので、 極微小試料 の濃度を検出するのに適している。  As described above, the photothermal conversion spectroscopy is suitable for detecting the concentration of an extremely small sample because it observes a change in the refractive index of the sample solution caused by the diffusion of heat in the sample solution. .
上記光熱変換分光分析法を実行する光熱変換分光分^装置の一例が特 開平 1 0— 2 3 2 2 1 0号公報に開示されている。 One example of a photothermal conversion spectrometer that performs the above photothermal conversion spectroscopy is It is disclosed in Japanese Unexamined Patent Publication No. Hei.
従来の光熱変換分光分析装置においては、 流路付き板状部材が顕微鏡 の対物レンズの下方に配置されており、 励起光光源から出力された所定 波長の励起光が顕微鏡に入射する。 この励起光は顕微鏡の対物レンズに よ り流路付き板状部材の流路内の試料溶液に集光照射される。 集光照射 された励起光の焦点位置は試料溶液中に位置し、 この焦点位置を中心と して熱レンズが形成される。  In a conventional photothermal conversion spectrometer, a plate member with a flow path is disposed below an objective lens of a microscope, and excitation light of a predetermined wavelength output from an excitation light source enters the microscope. This excitation light is focused and irradiated on the sample solution in the flow path of the plate member with the flow path by the objective lens of the microscope. The focal position of the focused excitation light is located in the sample solution, and a thermal lens is formed around this focal position.
一方、 検出光源からは、 波長が励起光と異なる検出光が出力されて顕 微鏡に入射する。 顕微鏡内を通って出射される検出光は、 励起光によ り 試料溶液中に形成された熱レンズに集光照射され、 試料溶液を透過して 発散 （熱レンズが凹レンズの効果を有する場合） 又は集光 （熱レンズが 凸レンズの効果を有する場合） する。 この試料溶液から発散又は集光し て出射された光は信号光と しての働きをする。 この信号光は、 集光レン ズ及ぴフ ィ ルタの双方又はフィ ルタのみを経た後に検出器に受光され、 検出される。 この検出された信号光の強度は、 試料溶液において形成さ れた熱レンズの屈折率に応じたものになる。 なお、 検出光は励起光と同 一の波長でもよ く、 励起光が検出光を兼ねること もできる。  On the other hand, the detection light source outputs detection light having a wavelength different from that of the excitation light and enters the microscope. The detection light emitted through the microscope is focused and irradiated on the thermal lens formed in the sample solution by the excitation light, passes through the sample solution, and diverges (when the thermal lens has the effect of a concave lens). Alternatively, light is condensed (when the thermal lens has the effect of a convex lens). The light diverged or condensed from the sample solution and emitted serves as signal light. This signal light is received by the detector after passing through both the condenser lens and the filter or only the filter, and is detected. The intensity of the detected signal light depends on the refractive index of the thermal lens formed in the sample solution. Note that the detection light may have the same wavelength as the excitation light, and the excitation light may also serve as the detection light.
このよ う に、 マイクロ化学システムである上記光熱変換分光分析装置 においては、 熱レンズは励起光の焦点位置に形成され、 且つ、 形成され た熱レンズの屈折率の変化は、 検出光によって検出される。  As described above, in the photothermal conversion spectrometer that is a microchemical system, the thermal lens is formed at the focal position of the excitation light, and a change in the refractive index of the thermal lens formed is detected by the detection light. You.
しかしながら、 上記の光熱変換分光分析装置は、 光源、 測定部や検出 部 （光電変換部） の光学系等が複雑に構成されていているので大型であ り、 可搬性に欠けている。 このため、 光熱変換分光分析装置を設置する 場所や装置の操作が限定されるという問題があり、 延いては、 ユーザの 作業効率が悪いという問題がある。  However, the photothermal conversion spectrometer described above is large in size because the light source, the optical system of the measurement unit and the detection unit (photoelectric conversion unit) are complicatedly configured, and lacks portability. For this reason, there is a problem that the place where the photothermal conversion spectrometer is installed and the operation of the device are limited, and further, there is a problem that the work efficiency of the user is poor.
また、 光熱変換分光分析装置は励起光及び検出光を空間光と して試料 溶液まで導いているので、 光源、 ミ ラー、 レンズ等の光学系の各部品が 測定中に動いて しま う こ と を防止しなければな らず、 このためにそれら を固定するための堅固な定盤が必要である。 さ ら に、 温度等の環境の変 化によ って励起光およ び検出光の光軸がずれた場合に、 そのずれを調整 するための治具が必要である。 これら も、 光熱変換分光分析装置を大型 に し、 可搬性に欠けたものになる原因となっている。 In addition, the photothermal conversion spectrometer uses the excitation light and the detection light as Since it leads to the solution, it is necessary to prevent each part of the optical system such as the light source, mirror, lens, etc. from moving during the measurement, and therefore, to secure them, A surface plate is required. Furthermore, when the optical axes of the excitation light and the detection light are shifted due to changes in the environment such as temperature, a jig for adjusting the shift is required. These factors also cause the photothermal conversion spectrometer to become large and lack portability.
また、 光熱変換分光分析装置にて得られる熱レンズ信号の S / Nを高 めるために励起光の変調を行うが、 通常、 励起光の変調装置と して、 励 起光の光路上にチョ ッパーが設置される。 このチ ヨ ッパ一は円盤状部材 を有してお り、 この円盤状部材には円周に沿って周期的に貫通口が開け られている。 チ ョ ッパーはこの円盤状部材を常に回転させているが、 こ の円盤状部材の回転は振動の原因になる と共に空気の乱れを発生させる , また、円盤状部材に開けられた貫通口の大き さや位置にムラが有つた り 、 円盤状部材の変形等によ つて励起光の変調周期が完全には一定にな らな かった り する。 これらは、 測定の際にノ イズとなって、 光熱変換分光分 折装置の測定感度を低下させる原因になる。  Also, the excitation light is modulated in order to increase the S / N of the thermal lens signal obtained by the photothermal conversion spectrometer, but usually the excitation light modulator is placed on the optical path of the excitation light. A chopper will be installed. The chopper has a disk-shaped member, and a through-hole is opened in the disk-shaped member periodically along the circumference. The chopper always rotates this disc-shaped member, but the rotation of this disc-shaped member causes vibration and generates air turbulence, and the size of the through hole opened in the disc-shaped member The modulation period of the excitation light may not be completely constant due to unevenness in the pod position or deformation of the disk-shaped member. These become noises at the time of measurement and cause the measurement sensitivity of the photothermal conversion spectrometer to decrease.
また、 光熱変換分光分析方法を用いるマイ ク 口化学システムにおいて は、 多 く の場合に励起光の焦点位置が検出光の焦点位置と異なっている こ とが必要である。 図 5 A及び 5 Bは、 励起光の進行方向に関する熱レ ンズの形成位置と検出光の焦点位置を示す図であ り、 図 5 Aは、 対物レ ンズに色収差が有る場合を示し、 図 5 Bは、 対物レンズに色収差がない 場合を示す。  In addition, in a microchemical system using photothermal conversion spectroscopy, it is often necessary that the focal position of the excitation light be different from the focal position of the detection light. 5A and 5B are diagrams showing the formation position of the thermal lens and the focal position of the detection light in the traveling direction of the excitation light, and FIG. 5A shows a case where the objective lens has chromatic aberration. 5B shows the case where the objective lens has no chromatic aberration.
対物レンズ 1 3 0 に色収差が有る場合は、 図 5 Aに示すよ う に、 励起 光の焦点位置 1 3 2 に熱レンズ 1 3 1 が形成される と共に、 この焦点位 置 1 3 2 から Δ Lだけずれた位置に検出光の焦点位置 1 3 3が形成され るので、 熱レンズ 1 3 1 の屈折率の変化を検出光の焦点距離の変化と し て検出する こ とができ る。 一方、 対物レンズ 1 3 0 に色収差がない場合 は、 図 5 B に示すよ う に、 検出光の焦点位置 1 3 3 は、 励起光の焦点位 置 1 3 2 に形成される熱レンズ 1 3 1 の位置と ほぼ一致する。このため、 検出光には熱レンズ 1 3 1 による屈折が起こ らないので、 熱レンズ 1 3 1 の屈折率の変化は検出できない。 When the objective lens 130 has chromatic aberration, as shown in FIG. 5A, the thermal lens 13 1 is formed at the focal position 13 2 of the excitation light, and the focal position 13 2 Since the focal position 13 3 of the detection light is formed at a position shifted by L, the change in the refractive index of the thermal lens 13 1 is regarded as the change in the focal length of the detection light. Can be detected. On the other hand, when the objective lens 130 has no chromatic aberration, as shown in FIG. 5B, the focus position 13 3 of the detection light is the thermal lens 13 3 formed at the focus position 13 2 of the excitation light. It almost matches the position of 1. For this reason, since the detection light does not undergo refraction by the thermal lens 131, a change in the refractive index of the thermal lens 131 cannot be detected.
しかしながら、 顕微鏡の対物レンズは、 通常、 色収差がないよ う に製 造されているので、 上記の理由によ り 、 検出光の焦点位置 1 3 3 は励起 光の焦点位置に形成される熱.レンズ 1 3 1 の位置とほぼ一致する （図 5 B ) 。 したがって、 熱レンズ 1 3 1 の屈折率の変化が検出できない。 こ のため、 測定の度に、 熱レンズ 1 3 1 が形成される試料溶液の位置を、 図 6 A又は図 6 B に示すよ う に、 検出光の焦点位置 1 3 3からずら した り、 図 7 に示すよ う に、 不図示のレンズを用いて検出光を若干に発散又 は集光させて対物レンズ 1 3 0 に入射させる こ と によ って検出光の焦点 位置 1 3 3 を熱レンズ 1 3 1 からずら した り しなければならず、 測定の 感度が犠牲になる こ とが有り、 また、 ユーザの作業効率も悪いという 問 題がある。  However, the objective lens of a microscope is usually manufactured so as not to have chromatic aberration.For the above-mentioned reasons, the focus position 133 of the detection light is heat generated at the focus position of the excitation light. It almost matches the position of lens 13 1 (Fig. 5B). Therefore, a change in the refractive index of the thermal lens 13 1 cannot be detected. For this reason, the position of the sample solution where the thermal lens 13 1 is formed is shifted from the focal position 13 3 of the detection light as shown in FIG. 6A or FIG. As shown in FIG. 7, the detection light is slightly diverged or condensed using a lens (not shown), and is incident on the objective lens 130, so that the focus position 133 of the detection light is changed. It has to be displaced from the thermal lens 13 1, and the sensitivity of the measurement may be sacrificed, and the user's work efficiency is also poor.
本発明の目的は、 高い感度で測定ができ るマイ ク 口化学システム及ぴ このマイ ク 口化学システムで実行する光熱変換分光分析方法を提供する こ と に有り 、 さ らには、 ユーザの作業効率を向上させる ことができ る小 型のマイ ク ロ化学システムを提供する こ とにある。 発明の開示  An object of the present invention is to provide a micro-mouth chemical system capable of performing measurement with high sensitivity, and a photothermal conversion spectroscopy method to be performed by the micro-mouth chemical system. An object of the present invention is to provide a small-sized microchemical system that can improve efficiency. Disclosure of the invention
上記目的を達成するために、 本発明の第.1 の態様によれば、 励起光を 出力する励起光光源と、 検出光を出力する検出光光源と、 前記励起光及 ぴ前記検出光を合わせて導く誘導光学系と、 当該誘導光学系によって導 かれた前記励起光及び前記検出光を試料に照射するための照射レンズと， 前記励起光の照射を受けた試料によ って生成される熱レンズを透過した 前記検出光を検出する検出手段と、 前記検出された検出光に基づいて試 料を分析する分析手段と を備えるマイ ク 口化学システムが提供される。 本発明の第 1 の態様において、 前記誘導光学系は、 前記励起光及び前 記検出光を導く 光フ ァ イバ一を備える こ とが好ま しい。 To achieve the above object, according to a first aspect of the present invention, an excitation light source that outputs excitation light, a detection light source that outputs detection light, the excitation light and the detection light are combined. An irradiating lens for irradiating the sample with the excitation light and the detection light guided by the guiding optics; A detection unit configured to detect the detection light transmitted through the thermal lens generated by the sample irradiated with the excitation light, and an analysis unit configured to analyze the sample based on the detected detection light. A microchemical system is provided. In the first aspect of the present invention, it is preferable that the guiding optical system includes an optical fiber that guides the excitation light and the detection light.
本発明の第 1 の態様において、 前記光フ ァ イバ一は前記励起光及び前 記検出光をシングルモー ドで伝搬する ものである こ とが好ま しい。  In the first aspect of the present invention, it is preferable that the optical fiber propagates the excitation light and the detection light in a single mode.
本発明の第 1 の態様において、 前記照射レンズは、 前記励起光及び前 記検出光が出射する前記光ファイバ一の端部に固定されるこ とが好ま し い。  In the first aspect of the present invention, it is preferable that the irradiation lens is fixed to an end of the optical fiber from which the excitation light and the detection light are emitted.
本発明の第 1 の態様において、 前記照射レンズは屈折率分布型レンズ である こ とが好ま しい。  In the first embodiment of the present invention, it is preferable that the irradiation lens is a gradient index lens.
本発明の第 1 の態様において、 前記屈折率分布型レンズは円柱状の口 ッ ドレンズである こ とが好ま しい。  In the first aspect of the present invention, it is preferable that the gradient index lens is a cylindrical lens.
上記目的を達成するために、 本発明の第 2 の態様によれば、 励起光及 ぴ検出光を照射レンズを介して試料に照射して、 前記励起光の照射を受 けた試料によって生成される熱レンズを透過した前記検出光を検出 して 試料を分析する光熱分光分析方法において、 前記励起光を音響光学変調 器によ って変調するこ と を特徴とする光熱分光分析方法が提供される。 本発明の第 2 の態様において、 前記試料に照射する励起光は、 前記音 響光学変調器によ ってブラ ッ ク回折された 1 次回折光である こ とが好ま しい。 図面の簡単な説明  In order to achieve the above object, according to a second aspect of the present invention, the sample is irradiated with excitation light and detection light via an irradiation lens, and is generated by the sample that has been irradiated with the excitation light. A photothermal spectroscopy method for detecting a detection light transmitted through a thermal lens and analyzing a sample, wherein the excitation light is modulated by an acousto-optic modulator is provided. . In the second aspect of the present invention, it is preferable that the excitation light applied to the sample is first-order diffracted light that is black-diffraction by the acoustic optical modulator. BRIEF DESCRIPTION OF THE FIGURES
図 1 は、 本発明の第 1 の実施の形態に係るマイ ク 口化学システムの概 略構成を示す図である。 図 2 は、 本発明の第 2 の実施の形態に係るマイ ク ロ化学システムの概 略構成を示す図である。 FIG. 1 is a diagram showing a schematic configuration of a microphone chemical system according to a first embodiment of the present invention. FIG. 2 is a diagram showing a schematic configuration of a microchemical system according to the second embodiment of the present invention.
図 3 は、 本発明の第 3 の実施の形態に係るマイ ク ロ化学システムの概 略構成を示す図である。  FIG. 3 is a diagram illustrating a schematic configuration of a microchemical system according to a third embodiment of the present invention.
図 4 は、 熱レンズの原理を示す図である。  Figure 4 shows the principle of the thermal lens.
図 5 A及ぴ 5 B は、 励起光の進行方向に関する熱レンズの形成位置と 検出光の焦点位置を示す図であ り 、 図 5 Aは、 対物レンズに色収差が有 る場合を示し、 図 5 Bは、 対物レンズに色収差がない場合を示す。  5A and 5B are diagrams showing the formation position of the thermal lens and the focus position of the detection light in the traveling direction of the excitation light, and FIG. 5A shows a case where the objective lens has chromatic aberration. 5B shows a case where the objective lens has no chromatic aberration.
図 6 A及び 6 B は、 励起光の進行方向に関する熱レンズの形成位置と 検出光の焦点位置を示す図であ り 、 図 6 Aは、 熱レンズが検出光の焦点 位置よ り も対物レンズ寄り に形成される場合を示し、 図 6 Bは、 熱レン ズが検出光の焦点位置よ り も対物レンズから遠い位置に形成される場合 を示す。  FIGS. 6A and 6B are diagrams showing the formation position of the thermal lens and the focus position of the detection light with respect to the traveling direction of the excitation light. FIG. 6A shows that the thermal lens has a higher objective lens position than the detection light focus position. FIG. 6B shows a case where the heat lens is formed at a position farther from the objective lens than the focal position of the detection light.
図 7 は、 従来の光熱変換分析装置における熱レンズの屈折率の変化を 検出する方法を示す図であ り、 光路の途中に凹レンズを入れて検出光を 発散光と し、 励起光の焦点距離位置よ り も遠方に焦点位置が位置する よ う に した場合を示す。 発明を実施するための最良の形態  Fig. 7 is a diagram showing a method of detecting a change in the refractive index of a thermal lens in a conventional photothermal conversion analyzer.A concave lens is inserted in the middle of the optical path to make the detection light divergent, and the focal length of the excitation light This shows the case where the focal position is located farther than the position. BEST MODE FOR CARRYING OUT THE INVENTION
以下、 図面を参照しながら本発明の実施の形態に係るマイ ク ロ化学シ ステム を詳細に説明する。  Hereinafter, a microchemical system according to an embodiment of the present invention will be described in detail with reference to the drawings.
図 1 は、 本発明の第 1 の実施の形態に係るマイ ク ロ化学システムの概 略構成を示す図である。  FIG. 1 is a diagram showing a schematic configuration of a microchemical system according to a first embodiment of the present invention.
図 1 において、 マイ クロ化学システム 1 はレンズを内蔵する光フ ア イ バーュニ ッ ト 1 0 (以下光ファイバ一ュニ ッ ト 1 0 ) を備えている。 光 フ ァ イ バーュニ ッ ト 1 0 はチューブ 1 0 4 内の前端側 （図面上では下 側） に対物レンズと しての屈折率分布型ロ ッ ドレンズ 1 0 2 を有してお り 、 後端側 （図面上では上側） から励起光及び検出光をシングルモー ド で伝搬する光フ ァ イバ一 1 0 1 が揷入されている。 この光フ ァ イ ノ 一 1 0 1 の揷入端は屈折率分布型口 ッ ドレンズ 1 0 2 の一端に接続されてい る o In FIG. 1, a microchemical system 1 includes an optical fiber unit 10 (hereinafter, an optical fiber unit 10) having a built-in lens. The optical fiber unit 10 is located at the front end of the tube 104 (the lower side in the drawing). Side), there is a gradient index rod lens 102 as an objective lens, and an optical filter that propagates excitation light and detection light in a single mode from the rear end (upper side in the drawing). Fiber 1 01 has been inserted. The input end of the optical fin 101 is connected to one end of a gradient index lens 102.
光フ ァイバ一 1 0 には、 さ らに、 チューブ 1 0 4 内で屈折率分布型口 ッ ドレンズ 1 0 2 の上記一端側に、 屈折率分布型口 ッ ドレンズ 1 0 2 の 外径と同一の外径を有する フエルール 1 0 3 が組み込まれている。 この フエルール 1 0 3 は、 光フ ァイバ一 1 0 1 の外径を屈折率分布型口 ッ ド レンズ 1 0 2 の外径と同一にするためのものであ り 、 光フ ァイ ノ 一 1 0 1 はフェル一ル 1 0 3 を貫通する よ う に取り 付けられている。 光フ ア イ パー 1 0 1 はフエルール 1 0 3 によ って固定されており 、 屈折率分布型 ロ ッ ドレンズ 1 0 2 と フエルール 1 0 3 とはチューブ 1 0 4内に固定さ れている。 こ こで、 光ファイバ^ " 1 0 1 と屈折率分布型口ン ドレンズ 1 0 2 と は密着していても よいし、 隙間が有っても よい。 この光フ ァ イ ノ 一ュニ ッ ト 1 0 は出射光が後述する流路付き板状部材 2 0 に垂直に入射 する位置に治具 3 0 によって固定されている。  The optical fiber 10 also has the same outer diameter as the refractive index distributed type lens 102 at the one end side of the gradient index type lens 102 in the tube 104. Ferrule 103 with an outside diameter of The ferrule 103 is for making the outer diameter of the optical fiber 101 the same as the outer diameter of the gradient index lens 102. 0 1 is mounted so as to pass through ferrule 103. The optical fiber 101 is fixed by a ferrule 103, and the gradient index rod lens 102 and the ferrule 103 are fixed in a tube 104. . Here, the optical fiber 101 and the refractive index distribution type end lens 102 may be in close contact with each other or may have a gap. This optical fiber unit The gate 10 is fixed by a jig 30 at a position where the emitted light vertically enters a plate-like member 20 with a flow path to be described later.
光フ ァ イバ一 1 0 1 の挿入端とは反対側の端部近傍には、 試料溶液を 励起するための励起光を出射する励起光光源 1 0 5、 試料溶液を分析等 するための情報を検出するために試料に照射する検出光を出射する検出 光光源 1 0 6 、 励起光の光路上に配置された、 励起光を変調するための 音響光学変調器 1 0 7、 この音響光学変調器 1 0 7 のブラ ッ ク回折によ つて回折された励起光の 1次光と検出光と を同軸にするためのダイ ク 口 イ ツ ク ミ ラー 1 0 8、 励起光及び検出光を光フ ア イパー 1 0 1 に入射さ せるためのレンズ 1 0 9等が配設されている。  In the vicinity of the end opposite to the insertion end of the optical fiber 101, there is an excitation light source 105 that emits excitation light for exciting the sample solution, and information for analyzing the sample solution. A detection light source 106 that emits detection light that irradiates the sample to detect light, an acousto-optic modulator 107 that is arranged on the optical path of the excitation light, and modulates the excitation light, Dick opening mirror 108 for making the primary light of the excitation light diffracted by the black diffraction of the detector 107 coaxial with the detection light, and the excitation light and the detection light A lens 109 and the like for allowing the light to enter the firer 101 are provided.
音響光学変調器 1 0 7 は、 超音波によ る音響光学相互作用による光の 回折を利用 した装置である。 即ち、 光学媒体に超音波を伝搬させる と き に生じる光学媒体の屈折率の変化 （光弾性効果） を利用 したものである。 光学媒体内に超音波を伝搬させる と、 光学媒体内の弾性歪みや圧力が変 化して光学媒体内を伝搬するが、 弾性媒体では弾性歪や圧力によつて屈 折率が変化する （光弾性効果） ため、 光学媒体内には伝搬する超音波の 周期と同期して屈折率が変動する屈折率変動領域が生じる。 この屈折率 変動領域に入射した光は回折を受ける。 この と きの回折光の強度や回折 角は伝搬する超音波の強度や周波数によ り変化する。 The acousto-optic modulator 107 converts the light due to the acousto-optic interaction caused by ultrasonic waves. This device uses diffraction. That is, a change in the refractive index (photoelastic effect) of the optical medium that occurs when an ultrasonic wave propagates through the optical medium is used. When ultrasonic waves propagate in an optical medium, elastic strain and pressure in the optical medium change and propagate in the optical medium. However, in an elastic medium, the refractive index changes due to elastic strain and pressure (photoelasticity). Therefore, a refractive index fluctuation region in which the refractive index fluctuates in synchronization with the period of the propagating ultrasonic wave occurs in the optical medium. Light incident on the refractive index fluctuation region is diffracted. At this time, the intensity and the diffraction angle of the diffracted light change depending on the intensity and frequency of the propagating ultrasonic wave.
超音波が伝搬している音響光学媒体内に生成する回折格子に、 ブラ ッ ク条件を満足する角度で光を入射させる とブラ ッ ク回折が生じ、 回折を 受けない 0次光と光強度の高い 1 次光とが得られる。  When light is incident on a diffraction grating generated in an acousto-optic medium in which ultrasonic waves are propagated at an angle that satisfies the black conditions, black diffraction occurs, and the 0th-order light and the light intensity that do not undergo diffraction are generated. High primary light is obtained.
ブラ ッ ク条件を満足する角度で励起光を音響光学変調器 1 0 7へ入射 させる と、 超音波を音響光学媒体に印加している間はほとんどが 1 次光 と して回折され、 超音波を音響光学媒体に.印加していない間は回折され ずに音響光学変調器 1 0 7 を透過する。 この超音波の印加の有無を励起 光の変調に利用する こ とができる。 音響光学変調器 1 0 7 を透過した 0 次光を励起光と して用いた場合は、 超音波を音響光学媒体に印加してい る間も 0次光が完全にはゼロ とはならないため、 この残存光が光熱変換 分光分析測定の際のノ イズとな り 、 測定感度が低下する。 一方、 1 次光 を励起光と して用いた場合は、 1次光は超音波を音響光学媒体に印加し ている間だけ存在し、 超音波を音響光学媒体に印加していない間は全く 存在しない。 よ って、 1 次光を励起光と して光フ ァイバ 1 0 1へ導入 する。  When the excitation light is incident on the acousto-optic modulator 107 at an angle that satisfies the black condition, most of the ultrasound is diffracted as primary light while the ultrasound is applied to the acousto-optic medium, and When the light is not applied to the acousto-optic medium, the light is not diffracted and passes through the acousto-optic modulator 107. The presence or absence of the application of this ultrasonic wave can be used for modulating the excitation light. When the 0th-order light transmitted through the acousto-optic modulator 107 is used as the excitation light, the 0th-order light does not become completely zero even while the ultrasonic wave is applied to the acousto-optic medium. This residual light becomes noise at the time of photothermal conversion spectroscopic measurement, and the measurement sensitivity is reduced. On the other hand, when the primary light is used as the excitation light, the primary light exists only while the ultrasonic wave is being applied to the acousto-optic medium, and does not exist while the ultrasonic wave is not applied to the acousto-optic medium. not exist. Therefore, the primary light is introduced into the optical fiber 101 as excitation light.
この音響光学変調器 1 0 7 は全く可動部分がない上に、 電気信号によ つて音響光学媒体への超音波の印加を制御 しているので振動が生じない ( また、 電気信号で変調周期を制御 しているために、 屈折率の変動周期が 変化せず常に一定となる。 この結果、 光熱変換分光分析装置による測定 に際して検出光に生じるノ イズが小さ く な り 、 高感度の測定が可能とな る。 On the absence of this acousto-optic modulator 1 0 7 at all moving parts, since the control the application of ultrasound to by connexion acoustooptic medium into an electrical signal vibrations do not occur (also the modulation period an electrical signal Control, the fluctuation period of the refractive index It is always constant without change. As a result, noise generated in the detection light at the time of measurement by the photothermal conversion spectrometer becomes small, and high-sensitivity measurement becomes possible.
光フ ァイバ一 1 0 1 を伝搬モー ドを 1 つ しか持たないシングルモー ド のものと したのは、 光熱変換分光分析方法を利用 して試料溶液中の微量 な溶質を検出する場合、 励起光をでき るだけ小さ く 絞る こ とによって光 熱変換に利用されるエネルギーを高く する と と と も に、 励起光によ って 生成する熱レンズを収差の少ないレンズにするためである。  The optical fiber 101 has a single mode having only one propagation mode.The reason for using a photothermal conversion spectroscopy method to detect a very small amount of solute in a sample solution is to use excitation light. By reducing the aperture as small as possible, the energy used for photothermal conversion is increased, and the thermal lens generated by the excitation light is made a lens with little aberration.
シングルモ一 ドの光フ ァイバ一 1 0 1 から出射される光は常にガウス 分布になるので、 励起光の焦点が小さ く なる。 また、 励起光によって生 成された熱レンズが小さい場合、 この熱レンズを透過する検出光の光量 をでき る限り多 く するためには、 検出光もでき る限り小さ く 絞る こ とが 望ま しい。 この点から も、 光ファ イバ一は励起光及ぴ検出光をシングル モー ドで伝搬する ものが好ま しい。  Since the light emitted from the single-mode optical fiber 101 always has a Gaussian distribution, the focal point of the excitation light becomes smaller. In addition, when the thermal lens generated by the excitation light is small, it is desirable to narrow down the detection light as much as possible in order to increase the amount of detection light passing through this thermal lens as much as possible. . From this viewpoint, it is preferable that the optical fiber transmits the excitation light and the detection light in a single mode.
なお、 光フ ァ イバ一 1 0 1 は励起光及び検出光を透過させる ものであ ればどのよ う なものでも使用でき る。 しかしながら、 マルチモー ド光フ アイバーを使用 した場合は、 出射光がガウス分布にならない上に、 光フ ァィパー 1 0 1 の曲がり具合等の種々の条件によ つて出射光の出射パタ ーンが変化するので、 必ずしも安定な出射光が得られない。 このため、 微量な溶質の測定が困難になる と と もに測定値が安定しない場合がある < したがって、 上述のよ う に光フ ァイバ一 1 0 1 はシングルモー ドのもの が好ま しい。  It should be noted that any optical fiber 101 can be used as long as it transmits the excitation light and the detection light. However, when a multi-mode optical fiber is used, the output light does not have a Gaussian distribution, and the output pattern of the output light changes depending on various conditions such as the degree of bending of the optical fiber 101. Therefore, stable emitted light cannot always be obtained. For this reason, it may be difficult to measure a small amount of solute and the measured value may not be stable. Therefore, as described above, the optical fiber 101 is preferably of a single mode.
上述したよ う に光フ ァイバ一ュニッ ト 1 0 からの出射光は流路付き板 状部材 2 0 に垂直に入射する。 流路付き板状部材 2 0 は試料溶液を流す 流路 2 0 4 を有してお り、 3層に重ねて接着されたガラス基板 2 0 1、 2 0 2、 2 0 3 から成る。 ガラス基板 2 0 2 には混合、 攪拌、 合成、 分 離、 抽出、 検出等の際に試料溶液を流す上記の流路 2 0 4が形成されて いる o As described above, the light emitted from the optical fiber unit 10 is perpendicularly incident on the plate member 20 with the flow path. The plate member 20 with a flow path has a flow path 204 through which the sample solution flows, and is composed of glass substrates 201, 202, and 203 bonded in three layers. Mix, stir, synthesize, and mix glass substrate 202 The above-mentioned flow path 204 through which the sample solution flows for separation, extraction, detection, etc. is formed.o
この流路付き板状部材 2 0 の材料は耐久性、 耐薬品性の面からガラス が望ま しい。 特に、 細胞等の生体試料、 例えば D N A解析に使用する場 合を考慮する と、 耐酸性、 耐アルカ リ性の高いガラス、 具体的には、 硼 珪酸ガラス、 ソーダラ イ ム ガラス、 アルミ ノ硼珪酸ガラス、 石英ガラス 等が好ま しい。 しかし、 用途を限定するこ と によ ってプラスチッ ク等の 有機物を用いて製造したものを使用する こ と もでき る。  The material of the plate member 20 with a flow path is desirably glass from the viewpoint of durability and chemical resistance. In particular, considering the use in biological samples such as cells, for example, in DNA analysis, glass having high acid resistance and alkali resistance, specifically, borosilicate glass, soda lime glass, and aluminoborosilicate Glass, quartz glass, etc. are preferred. However, by limiting the use, it is also possible to use those manufactured using organic substances such as plastic.
ガラス基板 2 0 1、 2 0 2、 2 0 3 同士を接着させる接着剤には、 例 えば、 紫外線硕化型、 熱硬化型、 2液硬化型のアク リ ル系及びエポキシ 系の有機接着剤、 並びに無機接着剤等がある。 また、 熱融着によ ってガ ラス基板 2 0 1〜 2 0 3 同士を融着させても よい。  Examples of the adhesive for bonding the glass substrates 201, 202, and 203 to each other include, for example, ultraviolet curable, thermosetting, two-component curable acrylic and epoxy organic adhesives. , And inorganic adhesives. Further, the glass substrates 201 to 203 may be fused to each other by heat fusion.
流路付き板状部材 2 0 を間に入れて光フ ァ ィバーュニ ッ ト 1 0 に対向 する位置には、 検出光を検出するための光電変換器 4 0 1 、 励起光と検 出光と を分離して検出光のみを選択的に透過させる波長フィ ルタ 4 0 3 が配設されている。 検出光の一部のみを選択的に透過させるために、 ピ ンホールが形成された部材をそのピンホールが検出光の光路上で且つ光 電変換器 4 0 1 よ り も上流の位置に位置する よ う に配置しても よい。 光 電変換器 4 0 1 よ り得られた信号は、 励起光を変調するために用いられ た音響光学変調器 1 0 7 と同期させるためにロ ッ ク イ ンアンプ 4 0 4 に 送られ、 その後コ ンピューター 4 0 5で解析 （分析） される。  At the position facing the optical fiber unit 10 with the plate-shaped member 20 with a flow path in between, the photoelectric converter 401 for detecting the detection light separates the excitation light and the detection light. A wavelength filter 403 for selectively transmitting only the detection light is provided. In order to selectively transmit only a part of the detection light, the member having the pinhole is positioned on the optical path of the detection light and at a position upstream of the photoelectric converter 401. It may be arranged as follows. The signal obtained from the photoelectric converter 401 is sent to a lock-in amplifier 404 to synchronize it with the acousto-optic modulator 107 used to modulate the excitation light, and thereafter, Analyzed (analyzed) by computer 405.
こ こで、 屈折率分布型口 ッ ドレ ンズ 1 0 2 の説明をする。 屈折率分布 型ロ ッ ドレンズ 1 0 2 は円柱状の透明なレンズであ り 、 長手方向に延び る中心線位置から半径方向に屈折率が連続的に変化する ものである。 こ のよ う なロ ッ ドレンズは、 中心線位置の屈折率を n 0、 2乗分布定数を g と して、 中心線位置から半径方向に r の距離にある位置の屈折率 n ( r ) が近似的に r の 2 次方程式 Here, the refractive index distribution type aperture lens 102 will be described. The refractive index distribution type rod lens 102 is a columnar transparent lens whose refractive index continuously changes in the radial direction from the center line extending in the longitudinal direction. Such a rod lens has a refractive index n 0 at a position radially r from the center line position, where n 0 is the refractive index at the center line position and g is the square distribution constant. (r) is approximately the quadratic equation of r
n ( r ) = n 。 — （ g 2ノ 2 ) ♦ r 2 | n (r) = n . — (G 2ノ 2) ♦ r 2 |
で表される集束性光伝送体と して知られている。 It is known as a convergent light transmitter represented by
屈折率分布型ロ ン ドレンズ 1 0 2 は、 その全長 z 。 を 0 < z 。く ？r / 2 gの範囲内で選択する場合、 両端面が平坦であ り ながら通常の凸レン ズと同 じ結像性を有し、 平行入射光線の焦点が出射端から、  The refractive index distributed lens 102 has its total length z. Where 0 <z. H? When selecting within the range of r / 2 g, both end faces are flat and have the same image forming properties as a normal convex lens, and the parallel incident light focuses from the output end to
s 0 = c 0 t ^ g z 0 ) / n 0 g  s 0 = c 0 t ^ g z 0) / n 0 g
の位置に作られる。 Made in the position.
このよ う な屈折率分布型口 ッ ドレンズ 1 0 2 は、 例えば以下のよ う な 方法で製造される。  Such a graded index lens 102 is manufactured, for example, by the following method.
即ち、 モル百分率で S i 0 2 ： 5 7〜 6 3 %、 B 2 0 a ： 1 7〜 2 3 %、 N a 2 0 ： 5〜 1 7 %、 T 1 2 0 ： 3〜 1 5 %を主成分とする雨端面が 平坦なガラスロ ッ ドを形成した後、 このガラスロ ッ ドを硝酸カ リ ウム塩 等のイ オ ン交換媒体中で処理し、 ガラス中のタ リ ゥムイ オン及ぴナ ト リ ゥムイ オンとィ ォン交換媒体中のカ リ ウムイ オン と をィ ォン交換して、 ガラスロ ッ ド内に中心から周辺に向けて連続的に低減する屈折率分布を 生じさせる。 このよ う に して、 屈折率分布型口 ッ ドレンズが製造される。 屈折率分布型口 ッ ドレンズ 1 0 2 の底面が平面であるので、 光フ アイ ノ 一 1 0 1 の端面を容易に取り付ける こ とができ る と と もに、 屈折率分 布型ロ ッ ドレンズ 1 0 2 の光軸と光フ アイパー 1 0 1 の光軸と を容易に 一致させるこ とができ る。 また、 屈折率分布型ロ ッ ドレンズ 1 0 2 は円 柱形であるので光フ ァ イバ一ュニ ッ ト 1 0 も容易に円柱形に形成する こ とができ る。 これによ つて、 治具 3 0 よる光ファ イ ノ —ユニ ッ ト 1 0 の 保持が極めて容易である。 That, S i 0 2 in a molar percentage: 5 7~ 6 3%, B 2 0 a: 1 7~ 2 3%, N a 2 0: 5~ 1 7%, T 1 2 0: 3~ 1 5% After forming a glass rod with a flat rain end surface containing as a main component, this glass rod is treated in an ion exchange medium such as potassium nitrate to remove the terion ions and glass in the glass. The ion exchange between the stream ion and the potassium ion in the ion exchange medium results in a refractive index distribution that continuously decreases from the center to the periphery in the glass rod. In this way, a gradient index lens is manufactured. Since the bottom surface of the refractive index distribution type lens 102 is flat, the end surface of the optical fiber 101 can be easily attached and the refractive index distribution type rod lens. The optical axis of 102 and the optical axis of optical fiber 101 can be easily matched. In addition, since the refractive index load rod lens 102 has a cylindrical shape, the optical fiber unit 10 can be easily formed into a cylindrical shape. This makes it extremely easy to hold the optical fin—unit 10 by the jig 30.
屈折率分布型口 ッ ドレンズ 1 0 2から出射した励起光の焦点位置は、 流路付き板状部材 2 0 の流路 2 0 4の中に位置する必要がある。 屈折率 分布型口 ッ ドレンズ 1 0 2 は流路付き板状部材 2 0 に接触している必要 はないが、 接触させる場合は流路付き板状部材 2 0 の上部ガラス板 2 0 1 の厚みで屈折率分布型口 ッ ドレンズ 1 0 2 の焦点距離を調整でき る。 上部ガラス板 2 0 1 の厚みが足り ない場合は、 屈折率分布型口 ッ ド レン ズ 1 0 2 と上部ガラス板 2 0 1 との間に焦点距離を調整するためのスぺ 一サーを入れても よい。 このよ う に励起光の焦点位置を流路付き板状部 材 2 0 の流路 2 0 4の中に固定してお く 場合は焦点距離の調整も不要に なるので、 マイ ク ロ化学システム 1 を小型化でき る。 The focal position of the excitation light emitted from the refractive index distribution type lens 102 needs to be located in the channel 204 of the plate member 20 with a channel. Refractive index The distributed lens 102 does not need to be in contact with the plate member 20 with the flow path, but if it does, it is bent by the thickness of the upper glass plate 201 of the plate member 20 with the flow path. The focal length of the rate distribution type lens 102 can be adjusted. If the thickness of the upper glass plate 201 is not enough, insert a spacer for adjusting the focal length between the refractive index type aperture lens 102 and the upper glass plate 201. You may. If the focal position of the excitation light is fixed in the flow path 204 of the plate-like member 20 with a flow path in this manner, the focal length does not need to be adjusted. 1 can be reduced in size.
屈折率分布型口 ッ ドレンズ 1 0 2 は、 励起光の焦点位置に対して検出 光の焦点位置が僅かに Δ Lだけずれる よ う に設定されている （図 5 A )。  The refractive index distribution type lens 102 is set such that the focal position of the detection light slightly deviates from the focal position of the excitation light by ΔL (FIG. 5A).
I c は、 共焦点長 （ n m ) と して、 I c = ;r · ( d / 2 ) 2 / λ χ 計算される。 こ こで、 d は d = l . Z S X A i / N Aで算出されるニァ リ ーディ ス クであ り 、 は励起光の波長 （ n m ) であ り 、 N Aは、 屈 折率分布型ロ ッ ドレンズ 1 0 2 の開口数である。 光フ ァ イバ一を用いる 場合は、 光フ ァ イバ一の出射光の開口数が小さいので、 大き な開口数を 有するロ ン ドレンズを用いたと きの共焦点長の計算には光フ ァ イノ ーの 開口数を用いる。 I c is calculated as a confocal length (nm), and I c =; r · (d / 2) 2 / λχ . Here, d is a near disk calculated by d = l.ZSXA i / NA, is the wavelength (nm) of the excitation light, and NA is a refractive index distribution rod lens. It is a numerical aperture of 102. When an optical fiber is used, the numerical aperture of the light emitted from the optical fiber is small. Therefore, when calculating a confocal length when a land lens having a large numerical aperture is used, the optical fiber is used for calculation. Use the numerical aperture of
上記 Δ L値は、 測定する試料の厚みによつて変化する。 共焦点長よ り も厚みが薄い試料を測定する場合は 上記 A L値は、 A L = " 3 · I c である こ とが最も好ま しい。  The ΔL value changes depending on the thickness of the sample to be measured. When measuring a sample having a thickness smaller than the confocal length, it is most preferable that the above-mentioned AL value is AL = “3 · I c.
この Δ Lの値は、 検出光の焦点位置と励起光の焦点位置の差を表して いるので、 検出光の焦点距離が励起光の焦点距離よ り も長い場合であつ ても、 短い場合であっても 同 じ結果になる。  Since the value of ΔL represents the difference between the focal position of the detection light and the focal position of the excitation light, the value of ΔL can be used when the focal length of the detection light is longer than the focal length of the excitation light or shorter. The same result.
光フ ァ ィパーの先端を球形等に加工してレンズと した場合は、 光フ ァ ィバーの先端にレンズを取り付けな く ても励起光及び検出光を絞る こ と が可能であるが、 この場合、 色収差がほとんどないために励起光及ぴ検 出光の夫々の焦点位置がほぼ同じになる。 このため、 熱レンズの信号が ほと んど検出されないという 問題がある。 また、 光フ ァ イバ一先端を加 ェしてレンズにしたものは他の収差が大きいので、 励起光及び検出光の 焦点が大きいという 問題も ある。 したがって、 本実施の形態では光フ ァ ィノ 一 1 0 1 の先端に屈折率分布型口 ッ ドレンズ 1 0 2 が取り付けられ ている。 If the tip of the optical fiber is processed into a spherical shape or the like to form a lens, it is possible to reduce the excitation light and detection light without attaching a lens to the tip of the optical fiber. Excitation light and inspection because there is almost no chromatic aberration The respective focal positions of the light emission become substantially the same. Therefore, there is a problem that the signal of the thermal lens is hardly detected. In addition, the lens formed by adding the tip of the optical fiber has a large other aberration, so that there is a problem that the focus of the excitation light and the detection light is large. Therefore, in the present embodiment, the refractive index distribution type aperture lens 102 is attached to the tip of the optical fin 101.
本実施の形態に係るマイ ク 口化学システム 1 によれば、 屈折率分布型 ロ ッ ドレンズ 1 0 2 は、 励起光及び検出光を伝搬する光フ アイバー 1 0 1 の先端に取り付けられているので、 測定毎に励起光と検出光との光軸 及ぴ屈折率分布型ロ ッ ドレンズ 1 0 2 の光軸を調整する必要が無いので ユーザの作業効率を向上させる こ とができ る。 さ らに、 光軸を一致させ るための治具及ぴ堅固な定盤が不用であるので、 マイ ク ロ化学システム 1 を小型化できる。  According to the micro mouth chemical system 1 according to the present embodiment, the gradient index rod lens 102 is attached to the tip of the optical fiber 101 that propagates the excitation light and the detection light. Since it is not necessary to adjust the optical axis of the excitation light and the detection light and the optical axis of the gradient index rod lens 102 for each measurement, the work efficiency of the user can be improved. Furthermore, since a jig for matching the optical axes and a solid surface plate are unnecessary, the microchemical system 1 can be downsized.
また、 通常の対物レンズに対して光フ ァイバ一 1 0 1 のコア径が小さ いため、 音響光学変調器 1 0 7 のブラ ッ ク回折によ つて回折された励起 光の 0次光と 1 次光のう ち、 1次光のみを選択的に光フ ァイ ノ 一 1 0 1 のコ アに入射させる場合に、 光フ ァイバ一 1 0 1 の端面と音響光学変調 器 1 0 7 との距離を短く でき るので、 マイ ク ロ化学システム 1 をさ らに 小型化でき る。  In addition, since the core diameter of the optical fiber 101 is smaller than that of a normal objective lens, the 0th-order light and the 1st-order light of the excitation light diffracted by the black diffraction of the acousto-optic modulator 107 When only the primary light of the light is selectively incident on the core of the optical fiber 101, the end face of the optical fiber 101 and the acousto-optic modulator 107 are not Since the distance can be reduced, the size of the microchemical system 1 can be further reduced.
図 2 は、 本発明の第 2 の実施の形態に係るマイ ク ロ化学システムの概 略構成を示す図である。  FIG. 2 is a diagram showing a schematic configuration of a microchemical system according to the second embodiment of the present invention.
図 2 において、 第 2 の実施の形態に係るマイ クロ化学システム 2 は、 第 1 の実施の形態に係るマイ ク ロ化学システム 1 と対応する構成部材及 ぴ部分には同一の符合を付して説明を省略する。  In FIG. 2, the microchemical system 2 according to the second embodiment has the same reference numerals as those of the microchemical system 1 according to the first embodiment. Description is omitted.
本実施の形態に係るマイ ク ロ化学システム 2 では、 第 1 の実施の形態 に係るマイ クロ化学システム 1 と は異な り、 励起光及び検出光を同軸に する手段と してダイ ク ロイ ツ ク ミ ラーに代えて合波器 1 1 0 が配設され ている。 また、 合波器 1 1 0 には励起光を導く光フ ァ イバ一 1 0 1 a と 検出光を導く 光フ ァ イノ 一 1 0 1 b とが接続されている。 これによ り 、 励起光及び検出光を同軸にする以前にそれぞれを光ラ ア イバー 1 0 1 a 1 0 1 b に入射して合波器 1 1 0 まで導き、 合波器 1 1 0で合波させて いる。 合波された励起光及び検出光は、 第 1 の実施の形態に係るマイ ク 口化学システム 1 の場合と同様に、 光フ ァイバ一 1 0 1 によ って屈折率 分布型ロ ッ ドレンズ 1 0 2 まで導かれる。 励起光及び検出光を合波する 手段に合波器 1 1 0 を用いた場合、 合波器 1 1 0 自体がダイ ク ロイ ツ ク ミ ラー よ り も小さいこ と、 合波器 1 1 0 を固定してお く ための冶具が不 要か或いは必要な場合でも ダイ ク ロィ ッ ク ミ ラ一を固定してお く ための 冶具よ り も小さい治具でよいためにマイ ク ロ化学シス テムの小型化に有 利である。 In the microchemical system 2 according to the present embodiment, unlike the microchemical system 1 according to the first embodiment, the excitation light and the detection light are coaxial. For this purpose, a multiplexer 110 is provided in place of the die-cloth mirror. The multiplexer 110 is connected to an optical fiber 101a for guiding excitation light and an optical fiber 110b for guiding detection light. As a result, before the excitation light and the detection light are made coaxial, each of them is incident on the optical liner 101 aa 101 b and guided to the multiplexer 110, where They are multiplexed. The multiplexed excitation light and detection light are distributed by the optical fiber 101 as in the case of the microphone chemistry system 1 according to the first embodiment. Guided to 0 2. When the multiplexer 110 is used as a means for multiplexing the excitation light and the detection light, the multiplexer 110 itself must be smaller than the dichroic mirror. When a jig for fixing the die mirror is unnecessary or necessary, a micro jig smaller than the jig for fixing the dichroic mirror can be used. This is useful for downsizing the system.
本発明の第 2の実施の形態に係るマイ ク 口化学システム 2 によれば、 ダイ ク 口イ ツ ク ミ ラーを用いて励起光及び検出光を合波させる場合よ り もマイ ク 口化学システム 2 を一層に小型化でき る と と共に、 合波される 以前の励起光及び検出光が空間を伝搬する距離が短く なるために振動等 の外的条件による影響を受けに く く なるので、 測定感度が向上する。 図 3 は、 本発明の第 3 の実施の形態に係るマイ ク ロ化学システムの概 略構成を示す図である。  According to the micro-mouth chemical system 2 according to the second embodiment of the present invention, the micro-mouth chemical system is more effective than the case where the excitation light and the detection light are multiplexed using the dike-mouth mirror. 2 can be further miniaturized, and the distance that the excitation light and detection light before being multiplexed propagate in space becomes shorter, so that they are less affected by external conditions such as vibration. The sensitivity is improved. FIG. 3 is a diagram illustrating a schematic configuration of a microchemical system according to a third embodiment of the present invention.
図 3 において、 第 3 の実施の形態に係るマイ ク ロ化学システム 3 は、 第 1 の実施の形態に係るマイ ク α化学システム 1 と同 じ構成部材及ぴ部 分には同一の符合を付して説明を省略する。  In FIG. 3, the same components and parts of the micro chemical system 3 according to the third embodiment as those of the micro α chemical system 1 according to the first embodiment are denoted by the same reference numerals. And the description is omitted.
本実施の形態に係るマイ ク 口化学シス テム 3 では、 第 1及び 2 の実施 の形態と は異な り 、 光フ ァイバ一を用いずに励起光及び検出光を空間光 で対物レンズ 1 3 0 まで導いている。 この場合、 音響光学変調器 1 0 7 で回折される 1 次光と 0次光との分離'角度が小さいため、 1次光のみを 対物レンズ 1 3 0 に入射させるためには長い光路長が必要になる。 この 問題を解決するため、 0次光と 1次光の分離にプリ ズム 1 1 1 を使用す る。 プリ ズム 1 1 1 を使用する こ とによつて音響光学変調器 1 0 7 と対 物レンズ 1 3 0 との間隔が短く なるのでマイ ク ロ化学システム を小型化 でき る。 プリズム 1 1 1 のかわり にミ ラーを用いても 0 次光と 1次光の 分離は可能であるが、 プリ ズムの方がよ り小型化でき る という利点があ る。 産業上の利用可能性 Unlike the first and second embodiments, the micro mouth chemical system 3 according to the present embodiment differs from the first and second embodiments in that the excitation light and the detection light are converted to spatial light using the objective lens 1303 without using an optical fiber. Leading up to. In this case, the acousto-optic modulator 1 0 7 Since the angle of separation between the first-order light and the zero-order light diffracted by the first order is small, a long optical path length is required to make only the first-order light incident on the objective lens 130. To solve this problem, prism 1 1 1 is used to separate the zero-order light and the first-order light. By using the prism 111, the distance between the acousto-optic modulator 107 and the objective lens 130 becomes shorter, so that the microchemical system can be miniaturized. Even if a mirror is used instead of the prism 111, the 0th-order light and the 1st-order light can be separated, but the prism has the advantage of being more compact. Industrial applicability
以上詳細に説明 したよ う に、 本発明に係るマイ ク ロ化学システム によ れば、 誘導光学系に配設された音響光学変調器が励起光を変調するが、 この音響光学変調器には駆動部分がないので、 変調の際に振動や空気の 乱れ等の発生は皆無である。 また、 音響光学変調器は電気的に変調周期 を制御する ものであるので励起光の変調周期を常に一定にできる。 この ため、 変調に伴う ノ ィズが減少するので、 高い感度の測定が可能になる。 また、 ユーザは検出光の焦点位置の調節等をする必要がないのでユーザ の作業効率が向上し、 音響光学変調器は小型であるので、 マイ ク ロ化学 システムを小型化できる。  As described above in detail, according to the microchemical system according to the present invention, the acousto-optic modulator provided in the guiding optical system modulates the excitation light. Since there is no driving part, there is no vibration or air turbulence during modulation. Further, the acousto-optic modulator electrically controls the modulation period, so that the modulation period of the excitation light can be kept constant. For this reason, noise due to modulation is reduced, and measurement with high sensitivity is possible. In addition, since the user does not need to adjust the focal position of the detection light, the work efficiency of the user is improved, and since the acousto-optic modulator is small, the microchemical system can be downsized.
本発明に係るマイ ク ロ化学システムでは、 誘導光学系に備えた光フ ァ ィパーによつて励起光及び検出光が導かれるので、 励起光と検出光は同 軸になる。 従って、 励起光と検出光との光軸を調整する必要がないので ユーザの作業効率をさ らに向上でき る。  In the microchemical system according to the present invention, the excitation light and the detection light are guided by the optical fiber provided in the guidance optical system, so that the excitation light and the detection light are coaxial. Therefore, it is not necessary to adjust the optical axes of the excitation light and the detection light, so that the work efficiency of the user can be further improved.
本発明に係るマイ ク ロ化学システムでは、 光フ ァ イバ一を伝搬する励 起光及ぴ検出光はシングルモー ドであるので、 励起光によ って生成され る熱レンズは、 その収差が小さ く 、 も って正確な測定ができる。 本発明に係るマイ ク ロ化学システムでは、 励起光及ぴ検出光が出射す る光フ ァ イバ一の端部に照射レンズが固定されているので、 励起光、 検 出光、 及ぴ照射レンズの全ての光軸を固定する こ とができ る。 したがつ て、 光軸の調整が不要であ り、 ュ一ザの作業効率がよ り 向上する。 また、 光軸調整用の治具等が不要であるのでマイ ク 口化学システムをよ り小型 ィ匕でき る。 In the microchemical system according to the present invention, since the excitation light and the detection light propagating through the optical fiber are in single mode, the thermal lens generated by the excitation light has its aberration. It is small and can measure accurately. In the microchemical system according to the present invention, since the irradiation lens is fixed to the end of the optical fiber from which the excitation light and the detection light are emitted, the excitation light, the detection light, and the irradiation lens are fixed. All optical axes can be fixed. Therefore, there is no need to adjust the optical axis, and the work efficiency of the user is further improved. In addition, since a jig for adjusting the optical axis is not required, the size of the micro chemical system can be reduced.
本発明に係るマイ ク ロ化学システムでは、 検出光と励起光とでは周波 数が異な り、 照射レンズは色収差を有するので、 励起光と検出光の焦点 位置を別の光学系を使用せずにずらすこ とができ る。 これによ つて、 マ イ ク 口化学システムの大型化を防ぎ小型化に貢献できる。  In the microchemical system according to the present invention, the detection light and the excitation light have different frequencies, and the irradiation lens has chromatic aberration. Therefore, the focal positions of the excitation light and the detection light can be determined without using another optical system. Can be shifted. As a result, it is possible to prevent the micro chemical system from becoming large and contribute to miniaturization.
本発明に係るマイ ク ロ化学システムでは、 照射レンズは屈折率分布型 レンズであるので、 照射レンズを極めて小型化でき る。 これによ つて、 マイ ク ロ化学システムを よ り一層に小型化でき る。  In the microchemical system according to the present invention, since the irradiation lens is a gradient index lens, the irradiation lens can be extremely miniaturized. As a result, the size of the microchemical system can be further reduced.
本発明に係るマイ ク ロ化学システムでは、 屈折率分布型レンズは円柱 状のロ ッ ドレンズであるので容易に保持でき る と と も に光フ ァ イノ ーの 光軸とロ ッ ドレンズの光軸と を容易に合わせる こ とができ る。  In the microchemical system according to the present invention, since the gradient index lens is a cylindrical rod lens, it can be easily held, and the optical axis of the optical fin and the optical axis of the rod lens can be easily maintained. And can be easily matched.
以上詳細に説明 したよ う に、 本発明に係る光熱変換分光分析方法によ れば、 駆動部分のない音響光学変調器によつて励起光を変調するので、 変調に伴う駆動部分の動作に起因する振動や空気の乱れ等の発生が皆無 である。 ，また、 音響光学変調器は電気的に変調速度を決定するので励起 光の変調周期を常に一定にでき る。 これらによ り 変調に伴う ノ イズが減 少するので、 高い感度の測定が可能になる。  As described above in detail, according to the photothermal conversion spectroscopy method according to the present invention, the excitation light is modulated by the acousto-optic modulator without the driving part, and the excitation light is modulated by the operation of the driving part accompanying the modulation. There is no vibration or turbulence in the air. Also, since the acousto-optic modulator determines the modulation speed electrically, the modulation period of the excitation light can always be kept constant. As a result, noise due to modulation is reduced, and measurement with high sensitivity becomes possible.
本発明に係る光熱変換分光分析方法では、試料に照射される励起光は、 音響光学変調器によ ってブラ ッ ク回折された 1 次回折光であるので、 励 起光を遮断したと きの光量を完全にゼロにする こ とができる。この結果、 S Z Nを高く でき る こ と にな り、 確実に高に感度の測定が可能と なる。  In the photothermal conversion spectroscopy method according to the present invention, the excitation light applied to the sample is the first-order diffracted light that is black-diffraction by the acousto-optic modulator. The light intensity can be completely reduced to zero. As a result, SZN can be increased, and high-sensitivity measurement can be reliably performed.

Claims

請 求 の 範 囲 The scope of the claims
1 . 励起光を出力する励起光光源と、 検出光を出力する検出光光源と、 前記励起光及び前記検出光を合わせて導く誘導光学系と、 当該誘導光学 系によ つて導かれた前記励起光及び前記検出光を試料に照射するための 照射レンズと、 前記励起光の照射を受けた試料によって生成される熱レ ンズを透過した前記検出光を検出する検出手段と、 前記検出された検出 光に基づいて試料を分析する分析手段と を備えるマイ ク ロ化学シス テム において、 1. An excitation light source that outputs excitation light, a detection light source that outputs detection light, an induction optical system that guides the excitation light and the detection light together, and the excitation that is guided by the induction optical system. An irradiation lens for irradiating the sample with light and the detection light; a detection unit for detecting the detection light transmitted through a heat lens generated by the sample irradiated with the excitation light; and the detected detection A microchemical system comprising: an analysis means for analyzing a sample based on light;
前記誘導光学系に配設され、 前記励起光を変調する音響光学変調器を 備えるこ と を特徴とするマイ ク ロ化学システム。  A microchemical system, comprising: an acousto-optic modulator that is arranged in the guiding optical system and modulates the excitation light.
2 . 前記誘導光学系は前記励起光及び前記検出光を導く 光フ ァ イバ—を 備える こ と を特徴とする請求の範囲第 1項記載のマイ ク ロ化学システム。 2. The microchemical system according to claim 1, wherein the guiding optical system includes an optical fiber for guiding the excitation light and the detection light.
3 . 前記光フ ア イバーは前記励起光及び前記検出光をシングルモー ドで 伝搬する も のである こ と を特徴とする請求の範囲第 2項記載のマイ クロ 化学システム。 3. The microchemical system according to claim 2, wherein the optical fiber propagates the excitation light and the detection light in a single mode.
4 . 前記照射レンズは、 前記励起光及び前記検出光が出射する前記光フ ア イバーの端部に固定されたこ と を特徴とする請求の範囲第 2項記載の マイ ク ロ化学システム。  4. The microchemical system according to claim 2, wherein the irradiation lens is fixed to an end of the optical fiber from which the excitation light and the detection light are emitted.
5 . 前記照射レンズは、 前記励起光及び前記検出光が出射する前記光フ ア イバーの端部に固定されたこ と を特徴とする請求の範囲第 3項記載の マイ ク ロ化学システム。 5. The microchemical system according to claim 3, wherein the irradiation lens is fixed to an end of the optical fiber from which the excitation light and the detection light are emitted.
6 . 前記検出光の周波数は前記励起光の周波数とは異な り、 前記照射レ ンズは色収差を有する ものである こ と を特徴とする請求の範囲第 1 乃至 5項のいずれか 1項に記載のマイ クロ化学システム。  6. The frequency of the detection light is different from the frequency of the excitation light, and the irradiation lens has a chromatic aberration. Microchemical system.
7 . 前記照射レンズは屈折率分布型レンズである こ と を特徴とする請求 の範囲第 1 乃至 5項のいずれか 1 項に記載のマイ ク ロ化学システム。7. The illumination lens is a gradient index lens. 6. The microchemical system according to any one of paragraphs 1 to 5.
8 . 前記照射レ ンズは屈折率分布型レ ンズである こ と を特徴とする請求 の範囲第 6項に記載のマイ ク ロ化学システム。 8. The microchemical system according to claim 6, wherein the irradiation lens is a refractive index distribution type lens.
9 . 前記屈折率分布型レンズは円柱状の口 ッ ドレンズであるこ と を特徴 とする請求項 7記載のマイ ク口化学システム。  9. The micro mouth chemical system according to claim 7, wherein the gradient index lens is a cylindrical lens.
1 0 . 前記屈折率分布型レ ンズは円柱状のロ ッ ドレンズである こ と を特 徴とする請求項 8記載のマイ クロ化学システム。  10. The microchemical system according to claim 8, wherein the refractive index distribution type lens is a cylindrical rod lens.
1 1 . 励起光及び検出光を照射レンズを介して試料に照射し、 前記励起 光の照射を受けた試料によ って生成される熱レンズを透過した前記検出 光を検出 して試料を分析する光熱分光分析方法において、  11 1. Irradiate the sample with excitation light and detection light via the irradiation lens, and analyze the sample by detecting the detection light transmitted through the thermal lens generated by the sample irradiated with the excitation light. Photothermal spectroscopy method,
前記励起光を音響光学変調器によ って変調するこ と を特徴とする光熱 分光分析方法。  A photothermal spectroscopic analysis method, wherein the excitation light is modulated by an acousto-optic modulator.
1 2 . 前記試料に照射する励起光は、 前記音響光学変調器によ ってブラ ッ ク 回折された 1次回折光である こ と を特徴とする請求の範囲第 1 1項 記載の光熱変換分光分析方法。  12. The photothermal conversion spectroscopy according to claim 11, wherein the excitation light applied to the sample is a first-order diffracted light that is black-diffraction by the acousto-optic modulator. Analysis method.
PCT/JP2002/009463 2001-10-22 2002-09-13 Micro-chemical system, and photothermal conversion spectroscopic method WO2003036278A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000002677A (en) * 1998-06-15 2000-01-07 Asahi Chem Ind Co Ltd Analyzer
JP2001059829A (en) * 1999-08-25 2001-03-06 Univ Osaka Sangyo Photothermal lens type sample analyzer
EP1087223A1 (en) * 1998-06-12 2001-03-28 Asahi Kasei Kogyo Kabushiki Kaisha Analyzer

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1087223A1 (en) * 1998-06-12 2001-03-28 Asahi Kasei Kogyo Kabushiki Kaisha Analyzer
JP2000002677A (en) * 1998-06-15 2000-01-07 Asahi Chem Ind Co Ltd Analyzer
JP2001059829A (en) * 1999-08-25 2001-03-06 Univ Osaka Sangyo Photothermal lens type sample analyzer

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