JP6944678B2 - Optical fiber coupler for thermal lens analysis, thermal lens analyzer - Google Patents

Description

The present invention relates to an optical fiber coupler for thermal lens analysis that propagates two lights having different wavelengths used in a thermal lens analyzer from a light source toward a sample, and a thermal lens analyzer using the optical fiber coupler.

For example, microscale microspaces are expected to shorten mixing / reaction times, significantly reduce the amount of samples / reagents, and make them smaller devices, and are expected to be used in fields such as diagnosis and analysis. There is. For example, a microchannel (microchannel) consisting of grooves of several hundred μm or less is formed on a glass substrate (microchip) of several centimeters square, and a chemical system is integrated in this microchannel.

Further, in recent years, since nanoscale microspaces show unique properties of solution physical properties as compared with microscale microspaces, nanochannels (nanochannels, expansions) of several tens to several hundreds nm are placed on a glass substrate. The realization of innovative functional devices by forming nanochannels) and utilizing the unique chemical and physical properties of these nanochannels has attracted even greater attention. For example, by analyzing the protein of a single cell with a size of several tens of μm in the expanded nanospace, which is an overwhelmingly smaller space, it is unique to each cell, which was not known by the average of many cells so far. Functional analysis becomes possible and can be applied to cancer diagnosis. In addition, it is expected that it will be an ultra-sensitive analysis tool because it can measure with a single molecule by utilizing the fact that it is an ultrafine space.

In order to realize an innovative functional device equipped with channels such as microchannels and nanochannels, it is very important to create experiments and research tools to accurately grasp its performance (amount of substance). is important.

For example, for a sample solution in a microchannel, the molecular concentration of the sample solution (average number of a large number of molecules) can be measured with high accuracy by using a thermal lens microscope (TLM) (for example, patent). Reference 1).

JP-A-2002-296207

In a conventional thermal lens microscope (thermal lens analyzer), the first laser light of the first wavelength, which is the excitation light, and the second laser light of the second wavelength, which is the probe light, are emitted from different light sources. It is necessary to make it incident on one optical fiber and propagate it toward the prism. Conventionally, in order to propagate laser light having two wavelengths different from each other by one optical fiber, a plurality of mirrors or half mirrors are combined to match the two laser lights on one optical axis.

However, in such a configuration, the laser light is greatly attenuated by the mirror or half-mirror, and the optical axes of the two laser lights are likely to be displaced. Therefore, even a very small attenuation of the laser light has a great influence on the analysis accuracy. It was not realistic to use it for a microscope or the like.

On the other hand, using a conventional fusion type optical fiber coupler in which one end side of a plurality of optical fibers is fused to form one optical fiber, a first laser light having a first wavelength, which is excitation light, and a first laser light having a first wavelength are used. When propagating the second laser beam of the second wavelength, which is the probe light, with one optical fiber, even a fusion-type optical fiber coupler used for optical communication with little attenuation has a slight attenuation. When applied to a thermal lens microscope, the inventor of the present application generates a large background thermal lens signal due to such slight attenuation. Therefore, in the conventional fusion type optical fiber coupler, a low concentration sample by the thermal lens microscope is used. I found a problem that it cannot be used for the measurement of.

The present invention has been made in view of the above-mentioned situation, and is an optical fiber for thermal lens analysis capable of causing the laser light emitted from a light source to be incident on a thermal lens analyzer while suppressing the amount of attenuation of the intensity of the laser light to be extremely small. It is an object of the present invention to provide a coupler and a thermal lens analyzer equipped with the coupler.

That is, the optical fiber coupler for thermal lens analysis of the present invention has the following configuration.
An optical fiber coupler for thermal lens analysis used in a thermal lens analyzer that injects a plurality of laser beams having different wavelengths into a sample and analyzes the sample based on the thermal lens effect of the sample, and one end thereof has a first wavelength. A first optical fiber connected to a first light source that emits a first laser beam, a second optical fiber that is connected to a second light source that emits a second laser beam having a second wavelength at one end, the first optical fiber, and the above. The fusion portion includes at least a confluence portion where the second optical fibers merge and a fusion portion extending from the confluence portion and the first optical fiber and the second optical fiber being integrally fused. 1 It is characterized in that EL / Ab ≦ 0.25 is satisfied when the amount of loss of laser light is EL (db) and the absorbance of the sample is Ab.

According to the present invention, when the loss amount of the first laser light is EL (db) and the absorbance of the sample is Ab in the fused portion, the laser from the light source is satisfied by satisfying EL / Ab ≦ 0.25. Even if the thermal lens analyzer causes a decrease in analysis accuracy even if the light is slightly attenuated by the optical fiber, the laser light from multiple light sources can be incident without being attenuated, and the thermal lens analyzer is used. It is possible to analyze the low concentration sample.

Further, in the present invention, the first optical fiber and the second optical fiber are _{made of quartz glass whose core is doped with GeO 2} , and whose clad is made of quartz glass. The length of the fused portion to the other end side connected to the analyzer is 5 cm or less.

Further, in the present invention, the first optical fiber and the second optical fiber are characterized in that the core is made of quartz glass which is not doped with impurities.

Further, the thermal lens analyzer of the present invention has the following configuration.
A thermal lens analyzer including the optical lens analysis optical fiber coupler according to each of the above items, wherein the first light source, the second light source, the optical lens analysis optical fiber coupler, and the thermal lens measuring unit are used. The thermal lens measuring unit includes a lens body composed of one or a plurality of lenses for focusing the first laser beam and the second laser beam in the sample, and the second laser beam having the second wavelength. It is characterized by having a detector for detecting.

According to the optical fiber coupler for thermal lens analysis of the present invention, the optical fiber coupler for thermal lens analysis capable of making the laser beam emitted from the light source attenuate in an extremely small amount and incident on the thermal lens analyzer, and the optical fiber coupler for thermal lens analysis. It becomes possible to provide a thermal lens analyzer with improved analysis accuracy.

It is a schematic block diagram which shows the thermal lens microscope which is an example of the thermal lens analyzer provided with the optical fiber coupler for thermal lens analysis of this invention. It is an enlarged cross-sectional view of the main part which shows the optical fiber coupler for thermal lens analysis. It is a schematic diagram which shows the thermal lens microscope. It is a graph which shows the verification result of this invention. It is a graph which shows the attenuation characteristic of the optical fiber used in an Example.

Hereinafter, the optical fiber coupler for thermal lens analysis and the thermal lens analyzer according to the embodiment of the present invention will be described with reference to the drawings. It should be noted that each of the embodiments shown below is specifically described in order to better understand the gist of the invention, and is not limited to the present invention unless otherwise specified. In addition, the drawings used in the following description may be shown by enlarging the main parts for convenience in order to make the features of the present invention easy to understand, and the dimensional ratios of the respective components are the same as the actual ones. Is not always the case.

FIG. 1 is a schematic configuration diagram showing a thermal lens microscope which is an example of a thermal lens analyzer provided with an optical fiber coupler for thermal lens analysis of the present invention. Further, FIG. 2 is an enlarged cross-sectional view of a main part showing an optical fiber coupler for thermal lens analysis.
The thermal lens microscope B of the present embodiment includes a first light source B1, a second light source B2, an optical fiber coupler (optical fiber coupler for thermal lens analysis) B3, and a microscope main body B4.

The first light source B1 emits a first laser beam having a first wavelength (hereinafter, referred to as an excitation light S), which is an excitation light S described later. ^{The excitation light S may be Ar +} laser light having a wavelength (first wavelength) of 488 nm (or 476.5 nm). As the first light source B1, an argon laser device that emits ^{Ar + laser light is used.}

The second light source B2 emits a second laser beam having a second wavelength (hereinafter, referred to as a probe light P), which is a probe light P described later. The probe light P may be a He-Ne laser light having a wavelength (second wavelength) of 633 nm. As the second light source B2, a He-Ne laser device that emits a He-Ne laser beam is used.

The optical fiber coupler (optical fiber coupler for thermal lens analysis) B3 of the present invention is formed by fusing a plurality of optical fibers, a part of the first optical fiber 21 and the second optical fiber 22, which are two optical fibers in the present embodiment, to each other. From the separation part E1 in which the first optical fiber 21 and the second optical fiber 22 extend independently, the confluence part E2 in which the first optical fiber 21 and the second optical fiber 22 merge, and the confluence part E2. It is provided with a fusion section E3 that extends and the first optical fiber 21 and the second optical fiber 22 are integrally fused to form a single optical fiber.

The first optical fiber 21 and the second optical fiber 22 are composed of cores 21a and 22a, respectively, and claddings 21b and 22b surrounding the cores 21a and 22a, respectively. In such optical fibers 21 and 22, the material constituting the cladding 21b and 22b is selected to have a lower refractive index than the material constituting the cores 21a and 22a, so that the laser light refracts the inside of the cores 21a and 22a and the entire core 21a and 22a. It propagates by repeating reflection.

As the first optical fiber 21 and the second optical fiber 22, those having extremely little attenuation of the laser beam are selected. In the present embodiment, in the fusion section E3, when the loss amount of the excitation light (first laser light) S is EL (db) and the absorbance of the sample is Ab, the one that satisfies EL / Ab ≦ 0.25 is used. ..

In order to satisfy the above-mentioned EL / Ab ≦ 0.25, pure (imperfection-free) quartz glass (SiO ₂ ) with almost no attenuation is used as the cores 21a and 22a of the first optical fiber 21 and the second optical fiber 22. , Fluorine-doped quartz glass is used as the cladding 21b and 22b. With such a material structure, the amount of absorption loss of the first optical fiber 21 and the second optical fiber 22 with respect to the laser light of the first wavelength and the second wavelength in the entire optical fiber coupler B3 can be extremely reduced.

On the other hand, when quartz glass having no impurity doping is used for the cores 21a and 22a, it is difficult to fuse the two first optical fibers 21 and the second optical fiber 22 from the merging portion E2 to the fusion portion E3, which will be described later. There is. Therefore, quartz glass (SiO _{2 ) doped with germanium dioxide (GeO 2} ) can be used as the cores 21a and 22a of the first optical fiber 21 and the second optical fiber 22, and quartz glass can be used as the cladding 21b and 22b.

In this case, the germanium dioxide introduced to increase the refractive index of the cores 21a and 22a attenuates the laser light of the first wavelength and the second wavelength as compared with the pure quartz glass which is not doped with impurities. Therefore, when germanium dioxide-doped quartz glass is used as the cores 21a and 22a of the first optical fiber 21 and the second optical fiber 22, the length of the fused portion E3 described later is set to 5 cm or less to increase the length. It suppresses the increase in the amount of attenuation of the laser beam due to the above. By setting the length of the fused portion E3 to 5 cm or less in this way, when the loss amount of the excitation light (first laser beam) S is EL (db) and the absorbance of the sample is Ab in the fused portion E3. , EL / Ab ≦ 0.25 can be satisfied.

The merging portion E2 is a portion from a state in which the first optical fiber 21 and the second optical fiber 22 are brought into contact with each other in parallel until the first optical fiber 21 and the second optical fiber 22 are gradually fused into one. At the confluence E2, the first optical fiber 21 and the second optical fiber 22 are gradually stretched and heat-sealed.

The fusional portion E3 connected to the merging portion E2 is a portion where the first optical fiber 21 and the second optical fiber 22 are integrated by fusion and become one. The length of the fused portion E3 is preferably shortened as much as possible in order to reduce the amount of attenuation of the excitation light S and the probe light P. In particular, when germanium dioxide-doped quartz glass is used as the cores 21a and 22a of the first optical fiber 21 and the second optical fiber 22, the length of the fused portion E3 is set to 5 cm or less. As a result, EL / Ab ≦ 0.25 can be satisfied in the fused portion E3 when the loss amount of the excitation light (first laser light) S is EL (db) and the absorbance of the sample is Ab.

Connector C1 and C2 are formed at one end of the first optical fiber 21 and the second optical fiber 22 in the separation portion E1 constituting the optical fiber coupler B3, respectively, and the first light source B1 and the second light source B1 and the second light source B1 and the second are formed via the connectors C1 and C2, respectively. The first optical fiber 21 and the second optical fiber 22 are directly connected to the light source B2, respectively.
Further, a connector C3 is formed at the end of the fused portion E3 and is connected to the microscope main body portion B4.

The optical fiber coupler of the present invention (optical fiber coupler for thermal lens analysis) is obtained by fusing a plurality of optical fibers, for example, three or more optical fibers, in addition to combining two optical fibers into one as in the present embodiment. It may be a thing. In this case, laser light having different wavelengths emitted from three or more light sources can be emitted as laser light collected on one optical axis at the fusion splicer.

Next, an example of a thermal lens analyzer provided with the optical fiber coupler (optical fiber coupler for thermal lens analysis) B3 of the present invention will be described. In the following description, the configuration of the microscope main body B4 of the thermal lens microscope (TLM), which is a thermal lens analyzer, will be described.
FIG. 3 is an enlarged schematic view of a main part showing a detection portion of a thermal lens microscope (thermal lens analyzer).
In this embodiment, for example, in realizing a functional device that utilizes the chemical and physical properties of a channel (for example, a nanoscale or microscale microspace) formed on a glass substrate (microchip), the inside of the channel is realized. It is a thermal lens microscope that can be used as an experiment and research tool for capturing the amount of substance of a molecule. For example, the present invention relates to a thermal lens microscope capable of capturing molecules in a sample solution in a nanochannel at a single molecule level and accurately quantifying the number of molecules. Of course, the thermal lens microscope of this embodiment can be used not only for nanochannels but also for quantification and qualitative analysis of molecules of a sample solution in microchannels (microspaces of microscale) or channels of other sizes. be.

The microscope main body B4 of the thermal lens microscope B of the present embodiment includes a lens body 9, a color filter 14, a polarizing filter 15, and a detector 8 that constitute a thermal lens measuring unit.
The lens body 9 has a first wavelength (488 nm or 476.5 nm) emitted from a first light source B1 and a second light source B2 (see FIG. 1) and propagated on one optical axis by an optical fiber coupler B3. The excitation light S of the above and the probe light P of the second wavelength (633 nm) are incident.

The lens body 9 is formed by combining a plurality of lenses, and an objective lens is used in the present embodiment. The lens body 9 emits the probe light P1 and the excitation light S so as to narrow down the probe light P1 and the excitation light S into the sample solution 3 in the channel 2.

The color filter 14 receives the probe light P1 and the excitation light S that have passed through the sample solution 3 in the channel 2, removes the excitation light S, and allows only the probe light P1 to pass therethrough. The polarizing filter 15 allows the probe light P2, which is a part of the probe light P1 that has passed through the color filter 14, to pass through the pinhole. The detector 8 detects the intensity of the probe light P2 that has passed through the pinhole of the polarizing filter 15.

Two types of laser light, excitation light S and probe light P, are narrowed down to the sample solution 3 so that a beam spot (beam waist) is generated in the sample solution 3 in the channel 2 of the microscope main body B4 having such a configuration. When irradiated, a steep temperature distribution is generated in the optical path of the probe light P due to heat diffusion from the beam spot of the excitation light S. At this time, since the refractive index is proportional to the temperature change, the thermal lens 4 whose temperature distribution acts as an optical concave lens is formed in the microchannel 2. Then, since the thermal lens 4 having a different refractive index is formed according to the property of the sample solution 3 (the magnitude of the concentration of the molecule 3a), the intensity (signal) of the probe light P after being refracted by the thermal lens effect can be captured. , The molecular concentration of the sample solution 3 can be quantified.

According to the optical fiber coupler B3 for thermal lens analysis of the present invention and the thermal lens microscope (thermal lens analyzer) B using the same as described above, the first light source B1 which is the light source of the excitation light S of the first wavelength. The first optical fiber 21 connected to the lens, the second optical fiber 22 connected to the second light source B2 which is the light source of the probe light P of the second wavelength, and the confluence E2 where the first optical fiber 21 and the second optical fiber 22 merge. And at least a fused portion E3 in which the first optical fiber 21 and the second optical fiber 22 are integrally fused, and the loss amount of the excitation light (first laser light) S is set to EL (db) in the fused portion E3. ), When the absorbance of the sample is Ab, by satisfying EL / Ab ≦ 0.25, even if the laser light from the light source is slightly attenuated, the thermal lens may cause a decrease in analysis accuracy. Even with a thermal lens analyzer such as a microscope, laser light from multiple light sources can be incident without being attenuated, and low-concentration samples are analyzed using a thermal lens microscope (thermal lens analyzer). be able to.

Then, the core 21a of the first optical fiber 21 and the second optical fiber 22, 22a a silica glass doped with GeO _2, the cladding 21b, and 22b as the quartz glass, from the merging portion E2 side of the fusion part E3, thermal lens microscope (heat By reducing the length of the fused portion E3 to the other end side connected to the microscope main body portion B4 of the lens analyzer B to 5 cm or less, the excitation light (first laser beam) S of the fused portion E3 When the amount of loss is EL (db) and the absorbance of the sample is Ab, EL / Ab ≦ 0.25 can be satisfied.

Further, even if the cores 21a and 22a of the first optical fiber 21 and the second optical fiber 22 are made of quartz glass which is not doped with impurities, the loss amount of the excitation light (first laser light) S is set to EL (1st laser light) in the fused portion E3. db), EL / Ab ≦ 0.25 can be satisfied when the absorbance of the sample is Ab.

The thermal lens analyzer of the present invention is not limited to the thermal lens microscope, and any analyzer may be used as long as it utilizes the thermal lens effect by using laser light.

Although the embodiments of the present invention have been described above, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, replacements, and changes can be made without departing from the gist of the invention. These embodiments and modifications thereof are included in the scope and gist of the invention, as well as in the scope of the invention described in the claims and the equivalent scope thereof.

The effect of the present invention was verified. For verification, the thermal lens microscope B shown in the above-described embodiment was prepared. Then, a sample solution having a concentration in the range of 0 mol to 1 × 10 ^-4 mol was prepared, and an optical fiber coupler for thermal lens analysis (example of the present invention) having a fused portion length of 5 cm and the length of the fused portion were prepared. The concentration of the target substance was measured using an optical fiber coupler for thermal lens analysis (comparative example) having a size of 100 cm.
FIG. 4 shows the verification results graphically.
FIG. 5 is a graph showing the attenuation characteristics of the optical fiber used in the examples.
According to FIG. 5, the attenuation characteristic of the optical fiber used in the examples is 1 db / km in the laser light having a wavelength of 658 nm. In this case, when the length is 1 m, the amount of attenuation is 0.001 db, and the absorbance of 4 × 10 ^-4 or less cannot be measured due to the attenuation. If this is set to, for example, a length of 5 cm, the amount of attenuation is 0.00005db, and the absorbance of 2 × ^10-5 can be measured.
Then, according to the result shown in FIG. 4, in the example of the present invention ^{, the concentration increases linearly in the entire concentration range of 0 mol to 1 × 10 -4} mol, and the concentration increases from the low concentration range to the high concentration range. It was confirmed that the concentration of the substance to be measured can be detected accurately. On the other hand, in the comparative example, ^{the detection accuracy in the low concentration region of 10-6} mol or less was significantly inferior to that of the example of the present invention. The effect of the present invention was confirmed.

2 ... Microchannel (microscale microspace)
3 ... Sample solution 3a ... Molecule 4 ... Thermal lens 8 ... Detector 9 ... Lens body 21 ... First optical fiber 22 ... Second optical fiber 22
B ... Thermal lens microscope E3 ... Fusion part

Claims (4)

An optical fiber coupler for thermal lens analysis used in a thermal lens analyzer that injects a plurality of laser beams having different wavelengths into a sample and analyzes the sample based on the thermal lens effect of the sample.
A first optical fiber whose one end is connected to a first light source that emits a first laser beam of a first wavelength, and a second optical fiber that is connected to a second light source that emits a second laser beam of a second wavelength at one end. At least a confluence portion where the first optical fiber and the second optical fiber merge, and a fusion portion extending from the confluence portion and the first optical fiber and the second optical fiber are integrally fused are provided.
An optical fiber coupler for thermal lens analysis, characterized in that EL / Ab ≦ 0.25 is satisfied when the loss amount of the first laser beam is EL (db) and the absorbance of the sample is Ab in the fusion zone. .. The first optical fiber and the second optical fiber are _{made of quartz glass whose core is doped with GeO 2} , and whose clad is made of quartz glass, and are connected to the thermal lens analyzer from the confluence side of the fused portion. The optical fiber coupler for thermal lens analysis according to claim 1, wherein the length of the fused portion to the other end side is 5 cm or less. The optical fiber coupler for thermal lens analysis according to claim 1, wherein the first optical fiber and the second optical fiber are made of quartz glass whose core is not doped with impurities. A thermal lens analyzer comprising the optical fiber coupler for thermal lens analysis according to any one of claims 1 to 3.
It has the first light source, the second light source, the optical fiber coupler for thermal lens analysis, and a thermal lens measuring unit.
The thermal lens measuring unit is composed of one or a plurality of lenses, and detects a lens body that focuses the first laser beam and the second laser beam in the sample and the second laser beam of the second wavelength. A thermal lens analyzer characterized by being equipped with a device.

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