JP6886666B2 - Biosensor - Google Patents

Description

The present invention relates to a biosensor, and more specifically to a biosensor using an organic microdisk structure.

A microcavity represented by a microdisk structure can confine light with high efficiency by repeating total reflection at an interface, and can bring out a high interaction between a substance and light. Therefore, it is expected to be applied to minute lasers capable of oscillating at an ultra-low threshold, optical signal processing, integrated optical circuits, high-sensitivity sensors such as biosensors, and the like.
As a material for forming a microdisk, an organic substance has advantages such as being able to dope various pigments, being low in cost, and being easy to mold, as compared with an inorganic substance.

However, in general, since the organic microdisk structure is mainly produced by a method requiring heating such as a photolithography method (see Non-Patent Documents 1 to 3), a dye for detection and analysis of proteins and the like is used. It has been difficult to develop a directly doped organic microdisk biosensor.

International Publication No. 2016/039259

OPTICS EXPRESS, Vol. 19, No.12, pp.11451 (2011) Applied Physics Letters 97, 063304 (2010) OPTICS EXPRESS, Vol.19, No.10, pp.10009 (2011)

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a biosensor using a dye-doped organic microdisk structure.

The present inventors have produced an organic microdisk structure using a predetermined fluorine-containing hyperbranched polymer, a triazine-based hyperbranched polymer exhibiting a high refractive index, and a laser dye, which are produced by an inkjet method, at a low threshold value. It has already been reported that laser oscillation is possible (see Patent Document 1).
Based on this finding, the present inventors have conducted further diligent studies, and as a result, when a protein or the like is adsorbed on the surface of the organic microdisk structure, the spectrum of the oscillating light shifts. We have found that the disk structure can be suitably used as a biosensor, and completed the present invention.

That is, the present invention
1. 1. A biosensor comprising a clad layer containing a fluorine-containing hyperbranched polymer and a core layer containing a fluorine-free triazine-based hyperbranched polymer and a laser dye.
2. 1 biosensor in which the laser dye is a rhodamine dye,
3. 3. A method for detecting an object to be detected using 1 or 2 biosensors, which comprises a step of adsorbing the object to be detected on the core layer of the organic microdisk structure and an organic microdisk on which the object to be detected is adsorbed. The step of irradiating the structure with the excitation laser from the core layer side and the laser oscillation light emitted from the organic microdisk structure excited by the excitation laser are subjected to the excitation light through a filter that blocks the excitation light. Provided is a detection method comprising a step of measuring with a spectroscope after removal.

In the organic microdisk structure used in the biosensor of the present invention, the spectrum of the laser oscillation light shifts due to the adsorption of proteins or the like on the surface thereof. Therefore, by observing and measuring the spectrum, biomolecules such as proteins can be observed. Adsorption can be measured efficiently.

It is a figure which shows the time-dependent change of the spectrum shift in the adsorption of the microdisk surface which constitutes the biosensor of this invention, and albumin.

Hereinafter, the present invention will be described in more detail.
The biosensor according to the present invention includes a microdisk structure including a clad layer containing a fluorine-containing hyperbranched polymer (hereinafter, hyperbranched polymer is referred to as HBP) and a core layer containing a fluorine-free triazine-based HBP and a laser dye. ..

The fluorine-containing HBP constituting the clad layer is not particularly limited as long as it is an HBP containing a fluorine atom, but a non-triazine-based HBP is preferable, and an acrylic-based HBP is more preferable.
In particular, the acrylic-based fluorine-containing HBP disclosed in International Publication No. 2010/137724 is preferable, and among them, a monomer having two or more (meth) acrylic groups in the molecule, a fluoroalkyl group in the molecule, and at least Acrylo-based HBP obtained by solution-polymerizing a monomer having one (meth) acrylic group in an organic solvent in the presence of 5 to 200 mol% of a polymerization initiator with respect to the total molar amount of the monomer is preferable.

In the present invention, the refractive index of the fluorine-containing HBP may be lower than that of the triazine-based HBP used for the core layer, but in the present invention, it is preferably 1.5 or less.
The weight average molecular weight of the fluorine-containing HBP is not particularly limited, but in the present invention, it is preferably 1,000 to 200,000, more preferably 2,000 to 100,000, and 5,000 to 60, 000 is even more preferable.
The weight average molecular weight in the present invention is the average molecular weight obtained in terms of standard polystyrene by gel permeation chromatography (hereinafter referred to as GPC) analysis (hereinafter, the same applies).

Specific examples of the monomer having two or more (meth) acrylic groups in the molecule include ethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, propylene glycol di (meth) acrylate, and neopentyl glycol di. (Meta) Acrylate, Trimethylol Propanetri (Meta) Acrylate, Ditrimethylol Propanetetra (Meta) Acrylate, Glycotrimethyl (Meta) Acryloyl, Pentaerythritol Tetra (Meta) Acryloyl, Acryloyl Titanium Tri (Meta) Acrylate, 1,6- Hexandiol di (meth) acrylate, 2-methyl-1,8-octanediol di (meth) acrylate, 1,9-nonanediol di (meth) acrylate, 1,10-decanediol di (meth) acrylate, tricyclo Decandimethanol di (meth) acrylate, dioxane glycol di (meth) acrylate, 2-hydroxy-1-acryloyloxy-3-methacryloyloxypropane, 2-hydroxy-1,3-di (meth) acryloyloxypropane, 9, 9-Bis [4- (2- (meth) acryloyloxyethoxy) phenyl] fluorene, undecylenoxyethylene glycol di (meth) acrylate, bis [4- (meth) acryloylthiophenyl] sulfide, bis [2-( Meta) acryloylthioethyl] sulfide, 1,3-adamantandiol di (meth) acrylate, 1,3-adamantandimethanol di (meth) acrylate, polyethylene glycol (molecular weight 300) di (meth) acrylate, polypropylene glycol (molecular weight 500) ) Di (meth) acrylate and the like.

Specific examples of monomers having a fluoroalkyl group and at least one (meth) acrylic group in the molecule include 2,2,2-trifluoroethyl (meth) acrylate, 2,2,3,3,3-penta. Fluoropropyl (meth) acrylate, 2- (perfluorobutyl) ethyl (meth) acrylate, 2- (perfluorohexyl) ethyl (meth) acrylate, 2- (perfluorooctyl) ethyl (meth) acrylate, 2- (per) Fluorodecyl) ethyl (meth) acrylate, 2- (perfluoro-3-methylbutyl) ethyl (meth) acrylate, 2- (perfluoro-5-methylhexyl) ethyl (meth) acrylate, 2- (perfluoro-7-) Methyloctyl) ethyl (meth) acrylate, 1H, 1H, 3H-tetrafluoropropyl (meth) acrylate, 1H, 1H, 5H-octafluoropentyl (meth) acrylate, 1H, 1H, 7H-dodecafluoroheptyl (meth) acrylate , 1H, 1H, 9H-hexadecafluorononyl (meth) acrylate, 1H-1- (trifluoromethyl) trifluoroethyl (meth) acrylate, 1H, 1H, 3H-hexafluorobutyl (meth) acrylate, 3-per Fluorobutyl-2-hydroxypropyl (meth) acrylate, 3-perfluorohexyl-2-hydroxypropyl (meth) acrylate, 3-perfluorooctyl-2-hydroxypropyl (meth) acrylate, 3- (perfluoro-3-3) Methylbutyl) -2-hydroxypropyl (meth) acrylate, 3- (perfluoro-5-methylhexyl) -2-hydroxypropyl (meth) acrylate, 3- (perfluoro-7-methyloctyl) -2-hydroxypropyl ( Meta) acrylate and the like can be mentioned.

As the polymerization initiator, an azo-based polymerization initiator is preferable, and specific examples thereof include 2,2'-azobisisobutyronitrile, 2,2'-azobis (2-methylbutyronitrile), and 2 , 2'-azobis (2,4-dimethylvaleronitrile), 1,1'-azobis (1-cyclohexanecarbonitrile), 2,2'-azobis (4-methoxy-2,4-dimethylvaleronitrile), 2 -(Carbamoylazo) isobutyronitrile, 2,2'-azobis {2-methyl-N- [1,1-bis (hydroxymethyl) -2-hydroxyethyl] propionamide}, 2,2'-azobis { 2-Methyl-N- [2- (1-hydroxybutyl)] propionamide}, 2,2'-azobis [2-methyl-N- (2-hydroxyethyl) propionamide], 2,2'-azobis [ N- (2-propenyl) -2-methylpropionamide], 2,2'-azobis (N-butyl-2-methylpropionamide), 2,2'-azobis (N-cyclohexyl-2-methylpropionamide) , 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 2,2'-azobis [2- (2-imidazolin-2-yl) propane] disulfate dihydroate , 2,2'-azobis [2- [1- (2-hydroxyethyl) -2-imidazolin-2-yl] propane] dihydrochloride, 2,2'-azobis [2- (2-imidazolin-2-yl] ) Propane], 2,2'-azobis (1-imino-1-pyrrolidino-2-methylpropane) dihydrochloride, 2,2'-azobis (2-methylpropionamidine) dihydrochloride, 2,2'-azobis [ N- (2-carboxyethyl) -2-methylpropion amidine] tetrahydrate, etc., 2,2'-azobisisobutyrate dimethyl, 4,4'-azobis-4-cyanovaleric acid, 2,2'-azobis (2, 4,4-trimethylpentane), 1,1'-azobis (1-acetoxy-1-phenylethane), dimethyl 1,1'-azobis (1-cyclohexanecarboxylate), 4,4'-azobis (4-cyano) Pentanoic acid), 4,4'-azobis (4-cyanopentanoate-2- (perfluoromethyl) ethyl), 4,4'-azobis (4-cyanopentanoate-2- (perfluorobutyl) ethyl), 4,4'-Azobis (4-cyanopentanoate-2- (perfluorohexyl) d) Chill) and the like can be mentioned, but 2,2'-azobisisobutyrate dimethyl and 2,2'-azobis (2,4,4-trimethylpentane) are preferable.

Examples of the organic solvent used for the polymerization are aromatic hydrocarbon solvents such as benzene, toluene, xylene, ethylbenzene, and tetralin; aliphatic or alicyclic solvents such as n-hexane, n-heptane, mineral spirit, and cyclohexane. Solvents: Halogen-based hydrocarbon solvents such as methyl chloride, methyl bromide, methyl iodide, methylene dichloride, chloroform, carbon tetrachloride, trichloroethylene, perchloroethylene, orthodichlorobenzene; ethyl acetate, butyl acetate, methoxybutyl acetate, Ester-based or ester ether-based solvents such as methyl cellosolve acetate, ethyl cellosolve acetate, and propylene glycol monomethyl ether acetate; ether-based solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane, methyl cellosolve, ethyl cellosolve, butyl cellosolve, and propylene glycol monomethyl ether. Solvents: Ketone solvents such as acetone, methyl ethyl ketone, methyl isobutyl ketone, di-n-butyl ketone, cyclohexanone; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, 2-ethylhexyl alcohol, benzyl Alcohol-based solvents such as alcohol; amide-based solvents such as N, N-dimethylformamide and N, N-dimethylacetamide; sulfoxide-based solvents such as dimethylsulfoxide, heterocyclic compound-based solvents such as N-methyl-2-pyrrolidone These may be used alone or in combination of two or more.
The temperature of the polymerization reaction is preferably 50 to 200 ° C, more preferably 70 to 150 ° C.

On the other hand, as the fluorine-free triazine-based HBP constituting the core layer, the triazine ring-containing HBP having a high refractive index disclosed in International Publication No. 2010/128661 is preferable, and among them, it has a high refractive index. An HBP having a repeating unit structure represented by the following formula is preferable.

In the formula, the above Ar represents any group represented by the following formula.

In particular, considering the balance between the high refractive index and the solubility in an organic solvent, the Ar group represented by the following formula is more preferable.

The refractive index of the triazine-based HBP is preferably about 1.65 to 1.90, more preferably 1.65 to 1.80, in consideration of the sensitivity of the sensor.
The weight average molecular weight of the triazine-based HBP is preferably 500 to 500,000, more preferably 50,000 or less, and more preferably 30,000 or less, from the viewpoint of further increasing the solubility and lowering the viscosity of the second ink. 10,000 or less is even more preferable.
The triazine-based HBP used in the present invention can be produced by the method described in International Publication No. 2010/128661. For example, the triazine-based HBP having an m-phenylene group as an Ar group is cyanuric halide and m-phenylenediamine. Can be obtained by reacting in a suitable organic solvent.
At this time, examples of the organic solvent include the same as above.

The laser dye contained in the core layer is not particularly limited, and may be appropriately selected from conventionally known dyes.
Specific examples thereof include carbon-condensed ring-based dyes such as anthracene derivatives, tetracene derivatives, pyrene derivatives, rubrene derivatives, decacyclene derivatives, and perylene derivatives, xanthene-based dyes, cyanine-based dyes, coumarin-based dyes, quinacridone-based dyes, and squalium-based dyes. , Styryl dyes, phenoxanthene dyes, metal or metal-free phthalocyanine, benzidine, iridium complexes, metal complexes composed of central metals consisting of Al, Zn, Be or rare earth metals, and metal complexes composed of ligands. Of these, organic dyes are preferable, and in the biosensor of the present invention, xanthene-based dyes are more preferable, and rhodamine dyes are even more preferable.

The rhodamine dye is available as a commercially available product, and examples of the commercially available product include rhodamine B, rhodamine 6G, rhodamine 19, rhodamine 101, rhodamine 110, and rhodamine 123.

As described in Patent Document 1, the organic microdisk structure used in the present invention prints a first ink containing a fluorine-containing HBP on a substrate by an inkjet method to form a clad layer, and does not contain fluorine. A second ink containing a triazine-based HBP and a laser dye can be printed on the clad layer by an inkjet method to form a core layer, and then the clad layer is etched with a solvent that dissolves only fluorine-containing HBP. it can.

As the organic solvent used for the first ink preparation, one having a dissolving ability of fluorine-containing HBP is preferable, and examples of such an organic solvent include those exemplified as the above-mentioned polymerization solvent, and in particular, 1 , 4-Dioxane and other ether solvents are suitable.
The concentration of fluorine-containing HBP in the first ink is preferably 5 to 20% by mass, more preferably 7 to 15% by mass, from the viewpoint of thickening the film by inkjet coating.
The viscosity of the first ink is not particularly limited as long as it can be applied by inkjet, but the concentration of the fluorine-containing HBP is preferably 1 to 30 mPa · s at 25 ° C. and 3 to 20 mPa · s. s is more preferable.
Further, since the clad layer produced by the first ink serves as a base on which the core layer is produced, a low viscosity (~ 20 mPa · s) is preferable in order to improve the flatness of the surface.

The substrate on which the clad layer is formed by using the first ink is not particularly limited as long as it has resistance to the solvent contained in the first ink and the etchant used in the subsequent etching step. For example, a glass substrate, a quartz substrate, an ITO substrate, an IZO substrate, a substrate made of metal or an oxide thereof, a resin substrate such as polyethylene terephthalate (PET), or the like can be used. Suitable.

The spot diameter at the time of inkjet printing the first ink on the substrate varies depending on the diameter of the inkjet nozzle used and cannot be unconditionally specified, but in the present invention, it is about 100 to 500 μm and 150 to 150. About 350 μm is preferable, and about 220 to 320 μm is more preferable.
The number of times of inkjet printing at the time of forming the clad layer may be one or a plurality of times, but it is preferably 2 to 10 times in order to form a clad layer having a sufficient thickness and an area and a flat surface capable of covering the core layer. Is preferably laminated by repeating printing 3 to 7 times.
The thickness of the clad layer is not particularly limited, but is usually about 0.5 to 3 μm.

On the other hand, as the organic solvent used for the second ink preparation, one having a triazine-based HBP-dissolving ability is preferable, and examples of such an organic solvent include those exemplified as the above-mentioned polymerization solvent. , Cyclohexanone and other ketone solvents are suitable.
The concentration of triazine-based HBP in the second ink is preferably 5 to 20% by mass, more preferably 7 to 15% by mass, from the viewpoint of thickening the film by inkjet coating.
The viscosity of the second ink is not particularly limited as long as it can be applied by inkjet, but the concentration of the triazine-based HBP is preferably 1 to 30 mPa · s at 25 ° C. and 3 to 20 mPa · s. s is more preferable.
Further, low viscosity (~ 20 mPa · s) is preferable in order to improve the flatness of the disk surface required for low threshold laser oscillation.

The concentration of the dye in the second ink is not particularly limited, but is preferably about 0.1 to 10 mM in the ink, and more preferably about 4 to 10 mM.

The spot diameter at the time of inkjet printing the second ink on the clad layer cannot be unconditionally specified because it varies depending on the diameter of the inkjet nozzle used, but it is preferable that the second ink is smaller than the clad layer. In the invention, it is about 10 μm to 200 μm, preferably about 50 to 150 μm, and more preferably about 50 to 120 μm.
The number of times of inkjet printing at the time of forming the core layer may be one or a plurality of times, but when the second ink of the present invention is used, a core layer having a sufficient thickness can be formed by one printing.
The thickness of the core layer is not particularly limited, but is usually about 0.5 to 3 μm.

After producing a laminate of a clad layer and a core layer by inkjet printing as described above, the clad layer is etched with a solvent that dissolves only fluorine-containing HBP to produce an organic microdisk structure having a desired shape. To do.
The solvent (etchant) used in the etching step is not particularly limited as long as it is a solvent that dissolves only fluorine-containing HBP, but it is preferable to use an ether solvent such as 1,4-dioxane.

The number of etchings is not particularly limited, but is usually 0.1 to 1 μL, preferably 0.1 to 0.5 μL of solvent for 0.1 to 10 seconds, preferably 0.5 to 2 seconds. Etching may be performed about 1 to 5 times.
The solvent may be removed by using an appropriate method such as washing or suction.

In the organic microdisk structure used in the present invention, when an object to be detected is adsorbed on the surface of the core layer, the spectrum of the laser oscillation light emitted from the organic microdisk structure shifts, and by observing and measuring it, the spectrum is observed and measured. Adsorption of the object to be detected can be detected.
Further, even when an antibody is adsorbed directly on the surface of the core layer or via another protein such as albumin and the antigen is bound to the antibody on the surface of the core layer by an antigen-antibody reaction, the organic microdisk structure is also formed. The spectrum of the laser oscillating light emitted from is shifted, and by observing and measuring it, the object to be detected (antigen) can be detected.

In detecting the object to be detected, it is preferable to use a microspectroscopy system that combines the organic microdisk structure, an excitation laser, and an optical microscope.
The excitation laser is not particularly limited, but a solid-state laser such as an Nd: YAG laser or an Er: YAG laser is preferable.
The laser oscillation light emitted from the excited microdisk is removed from the excitation light through a filter that blocks the excitation light, and then focused on a spectroscope such as an optical fiber-coupled spectroscope using an optical microscope to collect the spectrum. It is preferable to analyze.

Hereinafter, the present invention will be described in more detail with reference to Production Examples and Examples, but the present invention is not limited to the following Examples. The devices used are as follows.
[1] Inkjet printing equipment: Inkjet head (Microjet, IJK-200S), high-precision desktop robot (Musashi Engineering, SHOTmini SL), piezo driver (Hantech, MC6), pressure driver (SMC) , CN03) Inkjet printing process was performed at room temperature (25 ° C.) and atmospheric pressure.
During printing of the clad layer and the core layer, the distance between the substrate and the inkjet nozzle was maintained at ~ 1 mm.
The moving speed of the inkjet head was set to a low speed of 2 mm / s in order to suppress turbulence of the ejected ink due to air turbulence.

[Production Example 1] Production of First Ink Ethylene glycol dimethacrylate, 1H, 1H, 5H-octafluoropentyl methacrylate and 2,2'-azobisiso according to the same procedure as in Example 1 of International Publication No. 2010/137724. A fluorine-containing acrylic HBP produced from methyl butyrate was dissolved in 1,4-dioxane to produce a first ink of 10% by mass.

[Production Example 2] Production of Second Ink According to the same procedure as in Example 98 of International Publication No. 2010/128661, m-phenylenediamine, 2,4,6-trichloro-1,3,5-triazine and aniline The triazine-based HBP and the laser dye Rhodamine 6G (manufactured by Exiton) produced from the above were dissolved in cyclohexanone to produce a second ink having a polymer of 10% by mass and a dye of 5 mM.

[Manufacturing Example 3] Preparation of Microdisk Structure A microdisk structure was produced by the following method in order of the method described in International Publication No. 2016/0392959.
(1) Clad layer forming step Using a 70 μm diameter inkjet nozzle, the first ink obtained in Production Example 1 was ejected and laminated on a PET substrate for 20 shots and printed to form a clad layer.
(2) Core layer forming step Next, using a 50 μm diameter inkjet nozzle, the second ink prepared in Production Example 2 is ejected into the center of the previously formed clad layer for printing by ejecting one shot to have a diameter of 100 μm. A core layer was formed, and a laminated body of a clad layer and a core layer was prepared.
(3) Etching step Using 1,4-dioxane as an etchant, 0.2 μL of etchant is added to one laminate in one etching and etching is performed for 1 second, and then from the side surface direction of the laminate. The process of sucking with clean paper to remove the etching was repeated twice to obtain a microdisk structure. The etching step was performed manually at room temperature (25 ° C.) under atmospheric pressure while checking with a microscope (manufactured by NIKON, manufactured by ECLIPSE TE2000-U).
In addition, 62 mM of laser dye rhodamine 6G was added to the produced organic microdisk structure in order to cause laser oscillation. In addition, the thickness around the edge of the microdisk was set to about 1 μm so that the laser could oscillate in the whispering-gallery mode (WGM), which is a unique comb-shaped optical waveguide mode.

[Example 1]
The adsorption characteristics of albumin were evaluated using the microdisc prepared in Production Example 3 above.
The measurement configuration according to this embodiment comprises a microspectroscopy system in which an excitation laser and an optical microscope are combined.
The second harmonic of the Q-switched pulse-driven Nd: YAG laser (PNG-002025-040, Nanolase Corp.) was used as the excitation laser. The wavelength and pulse repetition frequencies were 532 nm and 10 Hz, respectively. The energy of the excitation pulse was set to 5.1 μJ.
The excitation laser pulse was focused through a plano-convex lens (f = 20 mm) with a diameter of 300 μm so that the entire microdisk was uniformly excited.
The laser oscillation light emitted from the excited microdisk is removed by a filter that blocks a wavelength of 532 nm, and then an optical fiber-coupled spectroscope (NIKON, ECLIPSE TE2000-U, 400 times) is used. The light was focused on the optical fiber input end face of MS7504, wavelength resolution> 0.04 nm, manufactured by Solar TII.
Since the amount of laser oscillating light emitted from the microdisk is extremely small, the integration time of the spectroscope was set to 30 seconds. This corresponds to the integration of laser oscillation light for 300 pulses.

The albumin adsorption characterization was performed by measuring the spectral shift of WGM due to changes in the refractive index environment outside the microdisk.
The refractive index environment changes in the order of (1) pure water, (2) albumin aqueous solution (20 mg / mL), and (3) pure water in order to capture changes in the albumin solution environment at a certain time with respect to water. Then, the change over time of the spectrum shift was measured for three peaks having a wavelength of about 603 nm (Mode # 603), about 604 nm (Mode # 604), and about 605 nm (Mode # 605). The results are shown in FIG.
As shown in FIG. 1, in all the processes (1) to (3), the wavelength is shifted to the short wavelength side as a whole, but this is caused by the decrease in gain due to the deterioration of the dye due to the laser oscillation. There is. In the pure water environment of (1), a linear spectral shift due to deterioration of the dye can be confirmed. Here, it can be seen that the amount of spectral shift slightly decreases and deviates from the linearity when the environment is changed to the albumin aqueous solution (2). This is a result of the linear spectrum shift accompanying the deterioration of the dye combined with the spectrum shift to the long wavelength side in the opposite direction due to albumin adsorption. Then, when the environment is returned to the pure water environment as in (3), the spectral shift due to albumin adsorption is settled, and the same spectral shift amount as the initial pure water environment is exhibited. At this time, the oscillation wavelength is higher than that on the straight line in the pure water environment of (1). This indicates that albumin is stably and quantitatively adsorbed.
As described above, it can be seen that the biosensor using the organic microdisk structure of the present invention can efficiently measure the adsorption of proteins such as albumin.

Claims (3)

A microdisk structure including a clad layer containing a fluorine-containing hyperbranched polymer and a core layer containing a fluorine-free triazine-based hyperbranched polymer and a laser dye .
Biosensor characterized that you measure the spectral shift of the laser oscillation light by adsorption of the detected object to the surface of the core layer. The biosensor according to claim 1, wherein the laser dye is a rhodamine dye. A method for detecting an object to be detected using the biosensor according to claim 1 or 2.
A step of adsorbing the object to be detected on the core layer of the organic microdisk structure, and
A step of irradiating the organic microdisk structure on which the object to be detected is adsorbed with an excitation laser from the core layer side,
The laser oscillation light emitted from the organic microdisk structure excited by the excitation laser is characterized by including a step of removing the excitation light through a filter that blocks the excitation light and then measuring with a spectroscope. Detection method to be performed.

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