JP2003043048A - Exposure method for photostimulable phosphor layer on storage phosphor sheet and unit for biochemical analysis used for the same and storage phosphor sheet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an exposure method for a photostimulable phosphor layer on a storage phosphor sheet which can prevent a noise caused by the scattering of an electron beam (β-rays) from being generated in data for biochemical analysis. SOLUTION: In the exposure method for the photostimulable phosphor sheet on the storage phosphor sheet, a unit for biochemical analysis wherein a specific bond substance is dropped on one face, a substance originated from a living body labeled with a radioactive marker substance is bonded specifically to the specifically combined substance, a plurality of sporlike regions 3 are formed and an electrode 4 is installed on the other face and the storage phosphor sheet 10 in which the photostimulable phosphor layer 12 is provided in a region on one face corresponding to the plurality of spotlike regions in the unit for biochemical analysis and in which an electrode 11 is installed on the other face are made opposed to each other in a separated state, an electric field is applied in such a way that the unit for biochemical analysis becomes negative and that the storage phosphor sheet becomes positive, and the photostimulable phosphor layer is exposed by the radioactive marker substance.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method of exposing a stimulable phosphor layer of a stimulable phosphor sheet, a biochemical analysis unit and a stimulable phosphor sheet used therefor, and more specifically, It is possible to specifically bind to a substance of biological origin, and a plurality of spot-like regions containing a specific binding substance whose base sequence, base length, composition, etc. are known are formed at high density on the carrier surface, A biochemical analysis unit obtained by selectively labeling a plurality of spot-shaped regions with a radioactive labeling substance is brought into close contact with the stimulable phosphor layer, and the stimulable phosphor layer is exposed with the radioactive labeling substance. Then
Irradiating the stimulable phosphor layer with excitation light and photoelectrically detecting the stimulable light emitted from the stimulable phosphor layer to generate biochemical analysis data and analyze substances derived from living organisms. Even when
Exposure of the stimulable phosphor layer of the stimulable phosphor sheet that can prevent noise due to scattering of electron beams (β rays) emitted from radiolabeled substances in the data for biochemical analysis The present invention relates to a method, a biochemical analysis unit and a stimulable phosphor sheet used therefor.

[0002]

2. Description of the Related Art When a radiation is irradiated, the energy of the radiation is absorbed, stored and recorded, and then excited by using an electromagnetic wave of a specific wavelength range. A photostimulable phosphor having the property of emitting a stimulating amount of light is used as a radiation detection material, and a substance having a radioactive label is administered to an organism, and then the organism or tissue of the organism is treated. A portion of the sample is used as a sample, and this sample is overlapped with a stimulable phosphor sheet provided with a stimulable phosphor layer for a certain period of time to store and record radiation energy in the stimulable phosphor. , Scanning the stimulable phosphor layer with electromagnetic waves to excite the stimulable phosphor and photoelectrically detecting the stimulable light emitted from the stimulable phosphor to generate a digital image signal. Image processing, CRT On a recording material such as a display unit or on the photographic film, the autoradiographic analyzing system is configured to reproduce an image has been known (for example, Kokoku 1-70884 and JP Kokoku 1-70
882, Japanese Patent Publication No. 4-3962, etc.).

An autoradiography analysis system using a stimulable phosphor sheet as a radiation detecting material not only requires a chemical treatment called a developing treatment, unlike the case where a photographic film is used, but also was obtained. By subjecting the digital data to data processing, there is an advantage that the analysis data can be reproduced or a quantitative analysis by a computer can be performed as desired.

On the other hand, there is known a fluorescence analysis system using a fluorescent substance such as a fluorescent dye as a labeling substance instead of the radioactive labeling substance in the autoradiography analysis system. According to this fluorescence analysis system, by detecting the fluorescence emitted from the fluorescent substance, the gene sequence, the expression level of the gene, the metabolism, absorption, and excretion routes of the administered substance in the experimental mouse, the state, the separation of the protein, Identification or evaluation of molecular weight and characteristics can be performed. For example, a solution containing plural kinds of protein molecules to be electrophoresed is electrophoresed on the gel support, and then the gel support is subjected to fluorescence. An image is generated by staining the electrophoresed protein by immersing it in a solution containing a dye, exciting the fluorescent dye with excitation light, and detecting the resulting fluorescence, and then producing an image on the gel support. The position and quantitative distribution of protein molecules can be detected. Alternatively, by Western blotting,
A probe and a protein molecule prepared by transferring at least a part of the electrophoresed protein molecule onto a transfer support such as nitrocellulose and labeling an antibody that specifically reacts with the target protein with a fluorescent dye are prepared. By selectively associating and selectively labeling a protein molecule that binds only to an antibody that specifically reacts,
By exciting the fluorescent dye with the excitation light and detecting the generated fluorescence, an image can be generated and the position and quantitative distribution of the protein molecule on the transfer support can be detected. In addition, after adding a fluorescent dye to a solution containing a plurality of DNA fragments to be electrophoresed, the plurality of DNA fragments are electrophoresed on a gel support, or on a gel support containing a fluorescent dye. , A plurality of DNA fragments are electrophoresed, or a plurality of DNA fragments are electrophoresed on a gel support, and then the gel support is immersed in a solution containing a fluorescent dye. DNA fragments are labeled, a fluorescent dye is excited by excitation light, and the resulting fluorescence is detected to generate an image, and the distribution of DNA on the gel support is detected, or a plurality of DNAs are detected.
The fragments are electrophoresed on a gel support, followed by DNA
Denaturation, and then by Southern blotting, at least a part of the denatured DNA fragment is transferred onto a transfer support such as nitrocellulose, and DNA or RNA complementary to the target DNA is fluorescent dye. A probe DNA or probe RN prepared by hybridizing a probe prepared by labeling with
Only the DNA fragment complementary to A is selectively labeled, the fluorescent dye is excited by the excitation light, and the resulting fluorescence is detected to generate an image, so that the DNA of interest on the transfer support is detected. The distribution can be detected. further,
DN containing a target gene labeled with a labeling substance
A DNA probe complementary to A is prepared, hybridized with the DNA on the transcription support, and the enzyme is allowed to bind to the complementary DNA labeled with a labeling substance, and then contacted with a fluorescent substrate for fluorescence. An image is generated by changing the substrate to a fluorescent substance that emits fluorescence, exciting the generated fluorescent substance with excitation light, and detecting the generated fluorescence,
It is also possible to detect the distribution of the target DNA on the transcription support. This fluorescence analysis system has an advantage that gene sequences and the like can be easily detected without using radioactive substances.

Similarly, a substance derived from a living body such as a protein or a nucleic acid is immobilized on a support and is selectively labeled with a labeling substance which causes chemiluminescence by contacting with a chemiluminescent substrate. A selectively labeled biological substance is brought into contact with a chemiluminescent substrate, and chemiluminescence in the visible light wavelength region generated by the contact between the chemiluminescent substrate and the labeled substance is photoelectrically detected to obtain a digital image signal. Chemiluminescence for generating information, reproducing the chemiluminescence image on a display material such as a CRT or a recording material such as a photographic film by performing image processing, and obtaining information on a substance of biological origin such as gene information. Analysis systems are also known.

Furthermore, in recent years, cells at different positions on the surface of a carrier such as a slide glass plate or a membrane filter,
Viruses, hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, cDNA
A specific binding substance, such as A, DNA, or RNA, which can be specifically bound to a substance of biological origin and whose base sequence, base length, composition, etc. is known, is dropped using a spotter device. , Forming a large number of independent spots, then cells, viruses, hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, c
A substance derived from a living body, such as DNA, DNA, or mRNA, which is collected from the living body by extraction or isolation, or which is further subjected to a chemical treatment, a chemical modification, or the like, such as a fluorescent substance or a dye. A substance labeled with a labeling substance is bound to a specific binding substance by hybridization or the like, to a microarray that is specifically bound,
A microarray analysis system has been developed which irradiates excitation light and photoelectrically detects light such as fluorescence emitted from a labeling substance such as a fluorescent substance or a dye to analyze a substance derived from a living body. According to this microarray analysis system,
A large number of spots of specific binding substances are formed at high density at different positions on the surface of a carrier such as a slide glass plate or a membrane filter, and the substance of biological origin labeled with the labeling substance is hybridized, thus In time, there is an advantage that it is possible to analyze a substance of biological origin.

In addition, cells, viruses, hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, cDNAs, DNAs, RNAs, etc. derived from living organisms are located at different positions on the surface of a carrier such as a membrane filter. The specific binding substance that can specifically bind to the substance of which the base sequence, base length, composition, etc. are known is dropped using a spotter device to form a large number of independent spots. , Then, cells, viruses, hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, cDNAs, DNAs, mRNAs, etc., collected from the living body by extraction or isolation, or
Furthermore, a substance derived from a living body, which has been subjected to a chemical treatment, a chemical modification, or the like, and which is labeled with a radioactive labeling substance, is specifically bound to a specific binding substance by hybridization or the like. Macro array,
The stimulable phosphor layer containing the stimulable phosphor is brought into close contact with the stimulable phosphor sheet, and the stimulable phosphor layer is exposed.
After that, the photostimulable phosphor layer is irradiated with excitation light, the photostimulable light emitted from the photostimulable phosphor layer is photoelectrically detected, and biochemical analysis data is generated. A macroarray analysis system using a radiolabeled substance for analyzing is also developed.

[0008]

However, in a macro array analysis system using a radioactive labeling substance as a labeling substance, when the stimulable phosphor layer is exposed, it is formed on the surface of a carrier such as a membrane filter. Since the radiation energy of the radio-labeled substance contained in the spot-shaped area is very large, the electron beam (β-ray) emitted from the radio-labeled substance is scattered and the radio-labeled substance contained in the adjacent spot-shaped area The electron beam (β-ray) emitted from the radiolabeled substance incident on the region of the stimulable phosphor layer to be exposed or adhering to the surface of a carrier such as a membrane filter between adjacent spot-shaped regions Then, noise is generated in the data for biochemical analysis generated by photoelectrically detecting the stimulable stimulus light, and noise is generated in the adjacent spots. It becomes difficult to separate the data between the spot-shaped regions, which lowers the resolution, and when the amount of radiation in each spot-shaped region is quantified and the substance derived from the living body is analyzed, the quantitativeness deteriorates. However, when spot-like regions are formed close to each other in order to increase the density, the resolution is remarkably lowered and the quantitativeness is remarkably deteriorated.

In order to prevent the noise caused by the scattering of the electron beam (β-ray) emitted from the radio-labeled substance contained in the adjacent spot-like regions and solve the problem, it is inevitable There is a problem in that it is necessary to increase the distance between the matched spot-shaped areas, the density of the spot-shaped areas decreases, and the inspection efficiency decreases.

Therefore, according to the present invention, a plurality of spot-shaped regions containing a specific binding substance capable of specifically binding to a substance derived from a living body and having a known base sequence, base length, composition, etc. A unit for biochemical analysis, which was formed on the surface at high density and selectively labeled multiple spot-like regions with a radioactive labeling substance, was placed in close contact with the stimulable phosphor layer to produce a stimulable substance. Exposing the phosphor layer with a radioactive labeling substance, irradiating the stimulable phosphor layer with excitation light, and photoelectrically detecting the stimulable light emitted from the stimulable phosphor layer for biochemical analysis. Even when generating data and analyzing substances of biological origin, it is necessary to prevent noise caused by scattering of electron beams (β rays) emitted from radiolabeled substances from being generated in the biochemical analysis data. Exposure of stimulable phosphor layer of stimulable phosphor sheet It is an object to provide a unit and the stimulable phosphor sheet for biochemical analysis using the law and it.

[0011]

The object of the present invention is to:
On one surface, a specific binding substance having a known structure or property is dropped, and a substance of biological origin labeled with a radioactive labeling substance is specifically bound to the specific binding substance,
A plurality of spot-shaped regions are formed apart from each other, and on the other surface, a biochemical analysis unit having electrodes,
At least a region of one surface corresponding to the plurality of spot-shaped regions of the biochemical analysis unit, a stimulable phosphor layer is provided, the other surface, a stimulable phosphor sheet provided with an electrode. In a separated state, they are opposed to each other, an electric field is applied so that the biochemical analysis unit becomes negative, and the stimulable phosphor sheet becomes positive, and the stimulable phosphor layer is formed by the radioactive labeling substance. It is achieved by a method of exposing a stimulable phosphor layer of a stimulable phosphor sheet, which comprises exposing.

According to the present invention, an electric field is applied so that the biochemical analysis unit becomes negative and the stimulable phosphor sheet becomes positive so that the biochemical analysis unit is included in a plurality of spot-shaped regions. Since the stimulable phosphor layer formed on the stimulable phosphor sheet is exposed by the radioactive labeling substance present in the stimulable phosphor sheet, the radioactive labels contained in the plurality of spot-like regions of the biochemical analysis unit are exposed. The spread of the electron beam (β-ray) emitted from the substance is effectively prevented, and the electron beams (β-ray) emitted from the radiolabeled substances contained in the adjacent spot-like regions are mixed. Therefore, even if the spot-shaped regions are formed on one surface of the biochemical analysis unit at a high density, the radio-labeled substance contained in each spot-shaped region prevents Noise caused by exposure of the region of the stimulable phosphor layer to be exposed by the electron beam (β-ray) emitted from the radiolabeled substance contained in the adjacent spot-shaped regions to biochemical analysis It can be prevented from being generated in the application data, and the quantitativeness of biochemical analysis can be significantly improved.

In a preferred aspect of the present invention, the higher the electric field, the distance between the one surface of the biochemical analysis unit and the stimulable phosphor layer of the stimulable phosphor sheet. Is set to a large value to expose the stimulable phosphor layer.

[0014] In a further preferred aspect of the present invention, at least the surface is insulated between the one surface of the biochemical analysis unit and the stimulable phosphor layer of the stimulable phosphor sheet. And a spacer having a plurality of through holes spaced apart from each other, the plurality of spot-shaped regions are respectively interposed so as to face the photostimulable phosphor layer through the through holes. The photostimulable phosphor layer is exposed to light.

According to a preferred embodiment of the present invention, at least the surface of the biochemical analysis unit has an insulating property between one surface and the stimulable phosphor layer of the stimulable phosphor sheet. , A spacer having a plurality of through holes spaced apart from each other is interposed so that a plurality of spot-shaped regions respectively face the stimulable phosphor layer through the through holes, and the stimulable phosphor is formed. Since the layer is configured to be exposed, one side of the biochemical analysis unit and the stimulable phosphor layer of the stimulable phosphor sheet have the smallest spread of the electron beam (β-ray). The photostimulable phosphor layer can be exposed at a desired distance so that the spot-shaped regions are formed on one surface of the biochemical analysis unit with high density. Also due to the radioactive labeling substance contained in each spot-shaped area. Noise caused by exposure of the region of the stimulable phosphor layer to be exposed by the electron beam (β-ray) emitted from the radiolabeled substance contained in the adjacent spot-shaped regions to biochemical analysis It can be prevented from being generated in the application data, and the quantitativeness of biochemical analysis can be significantly improved.

In a preferred embodiment of the present invention, the spacer is formed of a material that attenuates radiation energy.

According to a further preferred embodiment of the present invention, since the spacers are made of a material that attenuates radiation energy, the electron beam emitted from the radio-labeled substance contained in each of the spot-shaped regions ( It is possible to more reliably prevent the (β-rays) from mixing with the electron beams (β-rays) emitted from the radio-labeled substances contained in the adjacent spot-shaped areas. , The regions of the stimulable phosphor layer to be exposed by the radio-labeled substance contained in each of the spot-shaped regions are adjacent to each other even when formed in high density on one surface of the biochemical analysis unit. Noise caused by exposure is generated in the biochemical analysis data by the electron beam (β-ray) emitted from the radiolabel substance contained in the spot-shaped region. It is possible to prevent the door, it is possible to greatly improve the quantitative characteristic of the biochemical analysis.

In a preferred embodiment of the present invention, when the spacer transmits radiation through the spacer by a distance equal to the distance between the adjacent through holes,
It has the property of attenuating radiation energy to 1/5 or less.

[0019] In a further preferred aspect of the present invention, the radiation energy is reduced to 1/10 or less when the radiation is transmitted through the spacer by a distance equal to the distance between the adjacent through holes. It has the property of attenuating.

[0020] In a further preferred aspect of the present invention, the radiation energy is reduced to 1/50 or less when the spacer transmits radiation in a distance equal to a distance between the adjacent through holes. It has the property of attenuating.

[0021] In a further preferred aspect of the present invention, the radiation energy is reduced to 1/100 or less when the spacer transmits radiation in a distance equal to a distance between the adjacent through holes. It has the property of attenuating.

In a further preferred aspect of the present invention, the radiation energy of the spacer is reduced to 1/500 or less when the radiation passes through the spacer by a distance equal to a distance between the adjacent through holes. It has the property of attenuating.

[0023] In a further preferred aspect of the present invention, the radiation energy is reduced to 1/1000 or less when the spacer penetrates the spacer by a distance equal to a distance between the adjacent through holes. It has the property of attenuating.

In the present invention, the material used to form the spacer preferably has a property of attenuating radiation energy, but is not particularly limited, and it is an inorganic compound material or an organic compound material. Any of the above can be used, and metallic materials, ceramic materials or plastic materials are particularly preferably used.

In the present invention, examples of the inorganic compound material that can be used to form the spacer and can attenuate the radiation energy include gold, silver, copper,
Zinc, aluminum, titanium, tantalum, chromium, iron,
Metals such as nickel, cobalt, lead, tin and selenium; alloys such as brass, stainless steel and bronze; silicon materials such as silicon, amorphous silicon, glass, quartz, silicon carbide and silicon nitride; aluminum oxide, magnesium oxide, zirconium oxide, etc. Metal oxides of the above; inorganic salts such as tungsten carbide, calcium carbonate, calcium sulfate, hydroxyapatite, gallium arsenide and the like. These may have any structure in a polycrystalline sintered body such as single crystal, amorphous, or ceramic.

In the present invention, a polymer compound is preferably used as an organic compound material that can be used to form a spacer and can attenuate radiation energy. For example, a polyolefin such as polyethylene or polypropylene; polymethyl Acrylic resin such as methacrylate, butyl acrylate / methyl methacrylate copolymer; polyacrylonitrile; polyvinyl chloride; polyvinylidene chloride; polyvinylidene fluoride; polytetrafluoroethylene; polychlorotrifluoroethylene; polycarbonate; polyethylene naphthalate and polyethylene terephthalate Polyester; Nylon 6, Nylon 6,6, Nylon such as Nylon 4,10; Polyimide; Polysulfone; Polyphenylene sulfide; Polydiph Phenolic resins such as novolak; silicone resin such vinylsiloxane epoxy resin;
Polyurethane; polystyrene; butadiene-styrene copolymers; polysaccharides such as cellulose, cellulose acetate, nitrocellulose, starch, calcium alginate, hydroxypropylmethylcellulose; chitin; chitosan;
Urushi; polyamides such as gelatin, collagen and keratin, and copolymers of these high molecular compounds can be mentioned. These may be composite materials, and may be filled with metal oxide particles, glass fibers, or the like, if desired, or may be used by blending with an organic compound material.

Generally, the higher the specific gravity, the higher the radiation attenuating ability, and therefore the spacer has a specific gravity of 1.0 g / cm ^3.
It is preferably formed of the above compound material or composite material, and has a specific gravity of 1.5 g / cm ³ or more, 23 g /
It is particularly preferred that it is formed of a compound material or composite material having a cm ³ or less.

In a further preferred aspect of the present invention, as the electric field is higher, a spacer having a larger thickness is used as the spacer, and the spacer is provided on the one surface of the biochemical analysis unit and on the stimulable phosphor sheet. The photostimulable phosphor layer is configured to be exposed by being interposed between the photostimulable phosphor layer and the photostimulable phosphor layer.

[0029] In a further preferred aspect of the present invention, a plurality of photostimulable fluorescent dyes are provided only in a region of one surface of the stimulable phosphor sheet facing the plurality of spot-shaped regions of the biochemical analysis unit. Body layer regions are formed separately from each other.

According to a further preferred embodiment of the present invention, a plurality of photostimulable phosphor layers are provided only in the region of one surface of the stimulable phosphor sheet facing the plurality of spot-like regions of the biochemical analysis unit. Since the regions are formed so as to be separated from each other, even if the spot-shaped regions are formed on one surface of the biochemical analysis unit at a high density, the spot-shaped regions will not be affected by the radioactive labeling substance contained in each spot-shaped region. It is possible to more reliably prevent the stimulable phosphor layer to be exposed from being exposed to the electron beam (β-ray) emitted from the radiolabeled substance contained in the adjacent spot-shaped regions. Therefore, the region of the stimulable phosphor layer to be exposed by the radio-labeled substance contained in each spot-shaped region is the electron beam emitted from the radio-labeled substance contained in the adjacent spot-shaped region (β line By this, it is possible to prevent the noise due to the exposure from being generated in the biochemical analysis data, so that it is possible to significantly improve the quantitativeness of the biochemical analysis.

[0031] In a further preferred aspect of the present invention, the spacer is arranged so that the plurality of spot-shaped regions and the plurality of stimulable phosphor layer regions face each other through the through holes, respectively. The plurality of photostimulable phosphor layer regions are exposed with the interposition therebetween.

According to a further preferred embodiment of the present invention, the spacer is interposed so that the plurality of spot-shaped regions and the plurality of stimulable phosphor layer regions respectively face each other through the through holes. Since it is configured to expose a plurality of photostimulable phosphor layer regions, even if the spot-shaped regions are formed at high density on one surface of the biochemical analysis unit, each of the spot-shaped regions is formed. The stimulable phosphor layer region to be exposed by the radioactive labeling substance contained in
The electron beam (β-ray) emitted from the radio-labeled substance contained in the adjacent spot-shaped regions can prevent the exposure more surely, and therefore, can be contained in each of the spot-shaped regions. That the region of the stimulable phosphor layer to be exposed by the radioactive labeling substance present is exposed by the electron beam (β-ray) emitted from the radioactive labeling substance contained in the adjacent spot-shaped regions It is possible to prevent the generated noise from being generated in the biochemical analysis data, and it is possible to significantly improve the quantitativeness of the biochemical analysis.

In another preferred embodiment of the present invention, the stimulable phosphor layer is formed on substantially the entire surface of the stimulable phosphor sheet.

[0034] In a preferred aspect of the present invention, a plurality of absorptive regions made of an absorptive material are formed on the one surface of the biochemical analysis unit so as to be separated from each other, and the plurality of spot-shaped regions are formed. Are formed in the plurality of absorptive regions.

In another preferred embodiment of the present invention, the biochemical analysis unit is made of an adsorptive material.

In the present invention, a porous material or a fibrous material is preferably used as the absorptive material for forming the absorptive region or the biochemical analysis unit. The porous material and the fiber material may be used together to form the adsorptive region.

In the present invention, the porous material used to form the adsorptive region or the biochemical analysis unit may be either an organic material or an inorganic material, or an organic / inorganic composite.

In the present invention, the organic porous material used to form the adsorptive region or the biochemical analysis unit is not particularly limited, but a carbon material such as activated carbon or a membrane filter can be formed. Porous materials are preferably used. Specifically, nylons such as nylon 6, nylon 6,6 and nylon 4,10, cellulose derivatives such as nitrocellulose, cellulose acetate, cellulose acetate butyrate, collagen, alginic acid, calcium alginate, alginic acid / polylysine polyion complex, etc. Examples thereof include alginic acids, polyolefins such as polyethylene and polypropylene, polyfluorides such as polyvinyl chloride, polyvinylidene chloride, polyvinylidene fluoride and polytetrafluoride, and copolymers or composites thereof.

In the present invention, the inorganic porous material used to form the adsorptive region or the biochemical analysis unit is not particularly limited, but examples thereof include platinum, gold, iron, silver and nickel. , A metal such as aluminum, a metal oxide such as alumina, silica, titania and zeolite, a metal salt such as hydroxyapatite and calcium sulfate, and a complex thereof.

The above object of the present invention is also to provide a specific binding substance having a known structure or property dropped on one surface, and a substance of biological origin labeled with a radioactive labeling substance is specifically bound to form a plurality of substances. This is achieved by the biochemical analysis unit characterized in that the spot-shaped regions of are formed so as to be separated from each other, and electrodes are provided on the other surface.

According to the present invention, the unit for biochemical analysis has a specific binding substance having a known structure or property dropped on one surface thereof, and a substance derived from a living body labeled with a radioactive labeling substance is specifically A plurality of spot-shaped regions of the biochemical analysis unit and at least the biochemical analysis unit are combined because a plurality of spot-shaped regions are formed apart from each other and the electrode is provided on the other surface. In a region of one surface corresponding to, a stimulable phosphor layer is provided on the other surface, and a stimulable phosphor sheet having an electrode is provided on the other surface in a separated state, facing each other, and a unit for biochemical analysis is provided. Is negative, and the electric field is applied so that the stimulable phosphor sheet becomes positive, and the stimulable phosphor layer is exposed by the radiolabeled substance, so that multiple spot-shaped regions of the biochemical analysis unit are exposed. Including The electron beam (β-ray) emitted from the radioactively labeled substance is effectively prevented from spreading, and the electron beam (β-ray) emitted from the radioactively labeled substance contained in the adjacent spot-shaped regions Therefore, even if the spot-shaped regions are formed on one surface of the biochemical analysis unit at a high density, the radio-labeled substance contained in each of the spot-shaped regions can be prevented. The noise caused by the exposure of the region of the stimulable phosphor layer to be exposed by the electron beam (β-ray) emitted from the radiolabeled substance contained in the adjacent spot-like regions to biochemical noise It can be prevented from being generated in the analysis data, and the quantitativeness of the biochemical analysis can be significantly improved.

In a preferred embodiment of the present invention, the biochemical analysis unit is substantially entirely formed of an adsorptive material.

In another preferred aspect of the present invention, only the plurality of spot-shaped regions are formed of an adsorptive material.

The object of the invention is also to provide at least the area of one side to be exposed by the radiolabeling substance,
This is achieved by a stimulable phosphor sheet characterized in that a stimulable phosphor layer is formed and an electrode is provided on the other surface.

According to the present invention, the stimulable phosphor sheet is
At least one region to be exposed by the radioactive labeling substance, a stimulable phosphor layer is formed on the region on one side, and the other face is provided with an electrode, so at least a plurality of spot-shaped regions on which the sample should be dropped. Is formed of an adsorptive material, and the spot-like regions of the biochemical analysis unit equipped with electrodes on the side opposite to the surface of the spot-like regions where the sample should be dropped have specific structures or characteristics that are known. After dropping the solution of the binding substance and hybridizing the substance of biological origin labeled with the radiolabeled substance, a plurality of stimulable phosphor layers and biochemical analysis units formed on the stimulable phosphor sheet are formed. The stimulable phosphor sheet and the biochemical analysis unit are made to face each other in a separated state so that the spot-shaped regions correspond to each other, and the biochemical analysis unit becomes negative, and the stimulable phosphor sheet The stimulable phosphor layer is exposed with a radiolabeling substance by applying an electric field so that the radioactivity becomes positive, so that the radiolabeling substance contained in multiple spot-like regions of the biochemical analysis unit The emitted electron beam (β-ray) is effectively prevented from spreading,
It is possible to prevent the electron beams (β-rays) emitted from the radiolabeled substances contained in the adjacent spot-shaped regions from being mixed with each other. Areas of the stimulable phosphor layer to be exposed by the radioactive labeling substance contained in each of the spot-shaped regions, even if formed on the surface at high density, are included in the adjacent spot-shaped regions. It is possible to prevent the noise caused by exposure from being generated in the data for biochemical analysis by the electron beam (β-ray) emitted from the substance, and greatly improve the quantitativeness of biochemical analysis. It is possible to let

In a preferred embodiment of the present invention, a plurality of photostimulable phosphor layer regions are separated from each other only in the region of the one surface of the phosphor phosphor sheet to be exposed by the radiolabel substance. Is formed.

According to a preferred embodiment of the present invention, a plurality of stimulable phosphor layer regions are spaced apart from each other only in the region of one surface of the phosphor phosphor sheet to be exposed by the radioactive labeling substance. Therefore, even if the spot-shaped areas are formed on one surface of the biochemical analysis unit with high density, the photosensitivity to be exposed by the radiolabel substance contained in each of the spot-shaped areas is high. It is possible to more surely prevent the phosphor layer region from being exposed to the electron beam (β-ray) emitted from the radio-labeled substance contained in the adjacent spot-shaped regions. The stimulable phosphor layer regions to be exposed by the radioactive labeling substance contained in each of the regions are changed to the electron beam (β-ray) emitted from the radioactive labeling substance contained in the adjacent spot-shaped regions. Therefore, it is possible to prevent noise due to exposure from being generated in the biochemical analysis data, and it is possible to significantly improve the quantitativeness of the biochemical analysis.

In another preferred embodiment of the present invention, the stimulable phosphor layer is formed on substantially the entire surface of the stimulable phosphor sheet.

In the present invention, the stimulable phosphor contained in the stimulable phosphor layer region is capable of accumulating radiation energy, is excited by electromagnetic waves, and accumulates the energy of the radiation in the form of light. It is not particularly limited as long as it can be emitted by the above, but it is preferable that it can be excited by light in the visible light wavelength range. In particular,
For example, the alkaline earth metal fluorohalide-based phosphor (Ba1) disclosed in U.S. Pat. No. 4,239,968.
-XM ²⁺ x) FX: yA (where M ²⁺ is Mg, C
a, Sr, Zn and at least one alkaline earth metal element selected from the group consisting of Cd, X is Cl, at least one halogen selected from the group consisting of Br and I, A is Eu, Tb, Ce, Tm, Dy, Pr, Ho,
At least one trivalent metal element selected from the group consisting of Nd, Yb and Er, x is 0 ≦ x ≦ 0.6, and y is 0 ≦
y ≦ 0.2. ), The alkaline earth metal fluorohalide-based phosphor SrFX: Z disclosed in JP-A-2-276997 (where X is at least one halogen selected from the group consisting of Cl, Br and I, Z Is E
u or Ce. ), A europium-activated composite halogen-based phosphor BaFX · xNaX ′: aEu ²⁺ disclosed in JP-A-59-56479 (wherein X and X ′ are both groups consisting of Cl, Br and I). Is at least one halogen selected from the group, and x is 0 <x
≦ 2, a is 0 <a ≦ 0.2. ), JP-A-58-6
MOX: xCe, which is a cerium-activated trivalent metal oxyhalogen-based phosphor disclosed in Japanese Patent No. 9281 (here,
M is Pr, Nd, Pm, Sm, Eu, Tb, Dy, H
At least one trivalent metal element selected from the group consisting of o, Er, Tm, Yb and Bi, X is one or both of Br and I, and x is 0 <x <0.1. ), L which is a cerium-activated rare earth oxyhalogen-based phosphor disclosed in US Pat. No. 4,539,137.
nOX: xCe (where Ln is at least one rare earth element selected from the group consisting of Y, La, Gd and Lu, X is at least one halogen selected from the group consisting of Cl, Br and I, and x is 0 <X ≦ 0.1) and the europium-activated composite halogen-based phosphor M ^II FX disclosed in US Pat. No. 4,962,047.
・ AM ^I X '・ bM' ^II X ^" 2 ・ cM ^III X ^'" 3 ・ x
A: yEu ²⁺ (where M ^II is Ba, Sr and Ca
At least one alkaline earth metal element selected from the group consisting of, M ^I is at least one alkali metal element selected from the group consisting of Li, Na, K, Rb and Cs, and M ′ ^II is a group consisting of Be and Mg. more least one trivalent metal element selected, M ^III is Al, Ga, I
At least one trivalent metal element selected from the group consisting of n and Tl, A is at least one metal oxide, X is at least one halogen selected from the group consisting of Cl, Br and I, X ′, X ^″ And X ^''' is F, Cl,
It is at least one halogen selected from the group consisting of Br and I, a is 0 ≦ a ≦ 2, b is 0 ≦ b ≦ 1
0 ⁻² and c are 0 ≦ c ≦ 10 ⁻² , and a + b + c
≧ 10 ⁻² , x is 0 <x ≦ 0.5, and y is 0.
<Y ≦ 0.2. ) Can be preferably used.

[0050]

Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

FIG. 1 is a schematic perspective view of a biochemical analysis unit according to a preferred embodiment of the present invention.

As shown in FIG. 1, in the present embodiment, the biochemical analysis unit 1 includes an adsorptive substrate 2 formed of nylon 6, and the surface of the adsorptive substrate 2 is specifically bound. A solution of a substance, for example, cDNA is regularly dropped at regular intervals to form a large number of substantially circular spot-shaped regions 3 containing a specific binding substance.

Although not shown exactly in FIG. 1, in the present embodiment, there are 120 rows x 1 spot-like regions 3 each having a substantially circular shape having a size of about 0.07 mm 2.
It is regularly formed in a matrix of 60 rows, totaling 1
9200 spot-shaped regions 3 are formed.

FIG. 2 is a schematic front view of the spotting device.

As shown in FIG. 2, the spotting device 5 is provided with an injector 6 and a CCD camera 7, and CC
With the D camera 7, the tip of the injector 6 and the cD
While observing the position of the surface of the adsorptive substrate 2 to which the solution containing the specific binding substance such as NA should be dropped, the injector 6
Therefore, the solution of the specific binding substance is configured to be dropped, and it is guaranteed that the solution of the specific binding substance can be accurately dropped to a desired position on the surface of the adsorptive substrate 2.

FIG. 3 is a schematic vertical sectional view of a hybridization reaction container.

As shown in FIG. 3, the hybridization reaction container 8 has a rectangular cross section, and a hybridization reaction solution 9 containing a substance derived from a living body labeled with a radioactive labeling substance is contained therein. .

Upon hybridization, a specific binding substance such as cDNA is attached to the surface of the adsorbent substrate 2.
The biochemical analysis unit 1 on which a large number of spot-shaped regions 3 are formed by regular dropping is inserted into the hybridization reaction container 8.

As a result, the specific binding substance such as cDNA contained in the large number of spot-like regions 3 formed on the absorptive substrate 2 is labeled with a radioactive labeling substance and contained in the hybridization reaction solution 9. Substances derived from living organisms are selectively hybridized.

FIG. 4 is a schematic perspective view of a stimulable phosphor sheet according to a preferred embodiment of the present invention.

As shown in FIG. 4, the stimulable phosphor sheet 10 includes a support 11, and a stimulable phosphor layer 12 is uniformly formed on one surface of the support 11. . An electrode 14 is provided on the other surface of the support 11.

FIG. 5 shows that the stimulable phosphor sheet 10 is formed on the stimulable phosphor sheet 10 by the radioactive labeling substance selectively contained in the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. It is a schematic sectional drawing which shows the method of exposing the stimulable phosphor layer 12 which was exposed.

As shown in FIG. 5, prior to exposure,
The electrode 4 is attached to the surface of the biochemical analysis unit 1 opposite to the surface of the adsorptive substrate 2 on which the large number of spot-shaped regions 3 are formed.

Next, as shown in FIG. 5, a spacer 15 is formed on one surface of the support 11 of the stimulable phosphor sheet 10 and on the surface of the stimulable phosphor layer 12 formed uniformly.
Is set.

In this embodiment, the spacer 15 is
As shown in FIG. 6, it is formed of stainless steel having a property of attenuating radiation energy, and as shown in FIG. , Through hole 16
And its surface is covered with an insulating layer (not shown).

Next, the surface of the absorptive substrate 2 of the biochemical analysis unit 1 in which a large number of spot-shaped regions 3 are formed contacts the spacer 15, and a large number of spot-shaped regions 3 are formed.
The biochemical analysis unit 1 is set on the spacers 15 so as to be located in the through holes 16 of the spacers 15, respectively.

Furthermore, the electrode 4 provided on the biochemical analysis unit 1 is connected to the positive electrode of the DC power source 17, and the electrode 14 provided on the stimulable phosphor sheet 10 is connected.
Is connected to the negative pole of the DC power supply 17.

As a result, an electric field is generated so that the biochemical analysis unit 1 side is negative and the stimulable phosphor sheet 10 side is positive.

Thus, the photostimulable phosphor sheet 10 formed by the radioactive labeling substance selectively contained in the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1 is stimulated. The exposure of the luminescent phosphor layer 12 is started.

Upon exposure, an electron beam (β-ray) is emitted from the radiolabeled substance selectively contained in the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. , So that the biochemical analysis unit 1 side is negative and the stimulable phosphor sheet 10 side is positive,
Since the electric field is applied, the electron beam (β-ray) emitted from each of the spot-shaped regions 3 is prevented from expanding the beam diameter and goes straight.

In addition, the spacer 15 is made of stainless steel having a property of attenuating radiation energy, and corresponds to the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. position,
Since each has a through hole 16, the electron beam (β-ray) emitted from each spot-like region 3 is
Going straight through the corresponding through-holes 16 of the
The light is incident on the region of the stimulable phosphor layer 12 that faces each other, and only the region of the stimulable phosphor layer 12 that faces each spot-shaped region 3 is exposed.

Thus, the radiation data of the radioactive labeling substance is recorded on the stimulable phosphor layer 12 formed on the stimulable phosphor sheet 10.

FIG. 6 shows the radiation data of the radiolabeled substance recorded in the stimulable phosphor layer 12 formed on one surface of the support 11 of the stimulable phosphor sheet 10 for reading biochemical analysis. FIG. 8 is a schematic perspective view showing an example of a scanner that generates data, and FIG. 7 is a schematic perspective view showing details of the vicinity of the photomultiplier.

The scanner shown in FIG. 6 is formed on the support 11 of the stimulable phosphor sheet 10 and the fluorescence data of a fluorescent substance such as a fluorescent dye recorded on a fluorescent sample such as a gel support or a transfer support. Photostimulable phosphor layer 12
The first laser excitation light source 21 which emits the laser light 24 having a wavelength of 640 nm and 532n.
A second laser excitation light source 22 which emits a laser beam 24 having a wavelength of m and a third laser which emits a laser beam 24 having a wavelength of 473 nm.
Laser excitation light source 23.

In the present embodiment, the first laser excitation light source 21 is composed of a semiconductor laser light source, and the second laser excitation light source 21
Laser excitation light source 22 and third laser excitation light source 23
Is composed of a second harmonic generation element.

The laser light 24 generated by the first laser excitation light source 21 is collimated by the collimator lens 25 and then reflected by the mirror 26. The first dichroic mirror 27 and 532 nm that transmit the laser light 4 of 640 nm and reflect the light of wavelength 532 nm are transmitted through the optical path of the laser light 24 emitted from the first laser excitation light source 21 and reflected by the mirror 26. A second dichroic mirror 28 that transmits light of the above wavelength and reflects light of the wavelength of 473 nm is provided, and the laser light 24 generated by the first laser excitation light source 21 is provided.
Passes through the first dichroic mirror 27 and the second dichroic mirror 28 and enters the mirror 29.

On the other hand, the laser light 24 generated from the second laser excitation light source 22 is passed by the collimator lens 30.
After being made into parallel light, the first dichroic mirror 27
Is reflected by the second dichroic mirror 28, the direction of which is changed by 90 degrees, the light is transmitted through the second dichroic mirror 28, and is incident on the mirror 29.

The laser light 24 generated from the third laser excitation light source 23 is collimated by the collimator lens 31 and then reflected by the second dichroic mirror 28 so that its direction is 90 degrees. After being changed, it is incident on the mirror 29.

The laser light 24 that has entered the mirror 29 is reflected by the mirror 29, and then enters the mirror 32 and is reflected.

Laser light 2 reflected by the mirror 32
A perforated mirror 34 formed by a concave mirror having a hole 33 formed in the center is arranged in the optical path of No. 4, and the laser light 24 reflected by the mirror 32 passes through the hole 33 of the perforated mirror 34. It passes through and enters the concave mirror 38.

The laser light 24 incident on the concave mirror 38
Is reflected by the concave mirror 38, and the optical head 3
It is incident on 5.

The optical head 35 is provided with a mirror 36 and an aspherical lens 37. The laser beam 24 incident on the optical head 35 is reflected by the mirror 36, and the aspherical lens 37 causes the glass plate of the stage 40 to be reflected. It is incident on the stimulable phosphor sheet 10 placed on 41 or a fluorescent sample such as a gel support or a transfer support.

When the laser light 24 is incident on the stimulable phosphor layer 12 of the stimulable phosphor sheet 10, the stimulable phosphor layer 12 formed in the stimulable phosphor sheet 10 has a stimulable property. The phosphor is excited to emit photostimulable light 45, and laser light 24 is emitted to a fluorescent sample such as a gel support or a transfer support.
Is incident, the fluorescent dye is excited and the fluorescence 45 is emitted.

The photostimulable light 45 emitted from the stimulable phosphor sheet 10 or the fluorescence 45 emitted from the gel support, the transfer support or the like is reflected on the mirror 36 by the aspherical lens 37 provided on the optical head 35. Focused, mirror 3
6 is reflected to the same side as the optical path of the laser beam 24,
The parallel light is incident on the concave mirror 38.

The photostimulable light 45 or fluorescent light 45 that has entered the concave mirror 38 is reflected by the concave mirror 38,
The light enters the perforated mirror 34.

The photostimulable light 45 or the fluorescence 45 incident on the perforated mirror 34 is reflected downward by the perforated mirror 34 formed by a concave mirror to enter the filter unit 48, as shown in FIG. Then, light of a predetermined wavelength is cut off, enters the photomultiplier 50, and is detected photoelectrically.

As shown in FIG. 7, the filter unit 48 includes four filter members 51a, 51b, 51c,
51d, the filter unit 48 is configured to be movable in the left-right direction in FIG. 7 by a motor (not shown).

FIG. 8 is a schematic sectional view taken along the line AA of FIG.

As shown in FIG. 8, the filter member 51
a includes a filter 52a, and the filter 52a uses the first laser excitation light source 21 and uses the biochemical analysis unit 1
Is a filter member used when exciting a fluorescent substance such as a fluorescent dye contained in a large number of absorptive regions 4 formed on the substrate 2 to read the fluorescence 45, and cuts light having a wavelength of 640 nm. , And has a property of transmitting light having a wavelength longer than 640 nm.

FIG. 9 is a sectional view taken along the line BB of FIG.

As shown in FIG. 9, the filter member 51
b includes a filter 52b, and the filter 52b uses the second laser excitation light source 22 and uses the biochemical analysis unit 1
Is a filter member used when exciting a fluorescent substance such as a fluorescent dye contained in a large number of absorptive regions 4 formed on the substrate 2 to read the fluorescence 45, and cuts light having a wavelength of 532 nm. It has a property of transmitting light having a wavelength longer than 532 nm.

FIG. 10 is a sectional view taken along the line CC of FIG.

As shown in FIG. 10, the filter member 5
1c includes a filter 52c, and the filter 52c includes a third filter 52c.
When a fluorescent substance such as a fluorescent dye contained in a large number of absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1 is excited by using the laser excitation light source 23 of FIG. It is a filter member used, 473n
It has a property of cutting light having a wavelength of m and transmitting light having a wavelength longer than 473 nm.

FIG. 11 is a sectional view taken along the line DD of FIG.

As shown in FIG. 11, the filter member 5
1d includes a filter 52d, and the filter 52d includes a first
The stimulable phosphor sheet 1 using the laser excitation light source 21 of
No. 45 of the stimulable phosphor layer region 12 formed on the support 11 of 0. A stimulable phosphor layer region 1 which is a filter used when reading
2 has a property of transmitting only the light in the wavelength region of the stimulated emission light 45 emitted from No. 2 and cutting the light of the wavelength of 640 nm.

Therefore, depending on the laser excitation light source to be used, the filter members 51a, 51b, 51c, 51d.
Is selectively located in front of the photomultiplier 50, the photomultiplier 50 can photoelectrically detect only the light to be detected.

The analog data photoelectrically detected by the photomultiplier 50 and generated are converted into digital data by the A / D converter 53 and sent to the data processor 54.

Although not shown in FIG. 6, the optical head 35 is moved by the scanning mechanism in the main scanning direction indicated by arrow X in FIG. 6 and in the sub-scanning direction indicated by arrow Y orthogonal to the main scanning direction. All stimulable phosphor layer regions 12 formed movably on the support 11 of the stimulable phosphor sheet 10 and all absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1. But the laser light 24
Is configured to be scanned by.

FIG. 12 is a schematic plan view of the scanning mechanism of the optical head.

In FIG. 12, for simplification, the optical system except the optical head 15 and the optical paths of the laser light 24 and the stimulable light 45 or the fluorescent light 45 are omitted.

As shown in FIG. 12, the optical head 35
The scanning mechanism that scans the substrate includes a substrate 60, and a sub-scanning pulse motor 61 and a pair of rails 62, 62 are provided on the substrate 60.
And 6 are fixed on the substrate 60 and are movable on the substrate 60 in the sub-scanning direction indicated by the arrow Y in FIG.
3 and 3 are provided.

A threaded hole (not shown) is formed in the movable substrate 63, and a threaded rod 64 rotated by the sub-scanning pulse motor 61 is formed in this hole. Engaged.

A main scanning pulse motor 65 is provided on the movable substrate 63, and the main scanning pulse motor 65 connects the endless belt 66 to adjacent spot-shaped regions formed in the biochemical analysis unit 1. It is configured such that it can be driven intermittently at a pitch equal to the distance of 3.

The optical head 35 includes an endless belt 66.
Is fixed to the main scanning pulse motor 65,
When the endless belt 66 is driven, it is configured to move in the main scanning direction indicated by an arrow X in FIG.

In FIG. 12, 67 is the optical head 35.
Is a linear encoder for detecting the position in the main scanning direction, and 68 is a slit of the linear encoder 67.

Therefore, when the endless belt 66 is driven in the main scanning direction by the main scanning pulse motor 65 and the scanning of one line is completed, the substrate 63 is intermittently moved in the sub scanning direction by the sub scanning pulse motor 61. By being moved, the optical head 35 is moved in the main scanning direction indicated by arrow X and the sub-scanning direction indicated by arrow Y in FIG. 12, and the stimulable phosphor sheet 10 or the gel support is supported by the laser beam 24. The entire surface of the fluorescent sample, such as the body or transfer support, is scanned.

FIG. 13 is a block diagram showing a control system, an input system and a drive system of the scanner shown in FIG.

As shown in FIG. 13, the control system of the scanner includes a control unit 70 for controlling the operation of the entire scanner, and the input system of the scanner is operated by the user to output various instruction signals. A keyboard 71 capable of inputting is provided.

As shown in FIG. 13, the drive system of the scanner includes a main scanning pulse motor 65 for moving the optical head 35 in the main scanning direction and a sub scanning pulse motor 61 for moving the optical head 35 in the sub scanning direction. A filter unit motor 72 for moving the filter unit 48 including the four filter members 51a, 51b, 51c, 51d is provided.

The control unit 70 includes a first laser excitation light source 21, a second laser excitation light source 22 or a third laser excitation light source 22.
In addition to selectively outputting a drive signal to the laser excitation light source 23, the drive signal can be output to the filter unit motor 72.

The scanner configured as described above is used in the following manner in the absorptive substrate 2 of the biochemical analysis unit 1.
Of the radioactive labeling substance recorded on the stimulable phosphor sheet 10 by exposing the stimulable phosphor layer 12 with the radioactive labeling substance selectively contained in the large number of spot-shaped regions 3 formed in The data is read and biochemical analysis data is generated.

First, the user places the stimulable phosphor sheet 10 on the glass plate 41 of the stage 40 so that the stimulable phosphor layer 12 contacts the surface of the glass plate 41.

Next, the user operates the keyboard 7
An instruction signal to the effect that the radiation data recorded in the stimulable phosphor layer 12 formed on the support 11 of the stimulable phosphor sheet 10 should be read is input to 1.

The instruction signal input to the keyboard 71 is
When the control unit 70 receives the instruction signal and receives the instruction signal, the control unit 70 outputs a drive signal to the filter unit motor 72 in accordance with the instruction signal to move the filter unit 48 and release the photostimulable phosphor. Only the light in the wavelength range of stimulated light is transmitted, and 640
A filter 52 having a property of cutting light having a wavelength of nm
The filter member 51d provided with d is positioned in the optical path of the stimulated emission light 45.

Next, the control unit 70 outputs a drive signal to the first laser excitation light source 21, activates the first laser excitation light source 21, and causes the laser light 24 having a wavelength of 640 nm to be emitted.

The laser light 24 emitted from the first laser excitation light source 21 is made into parallel light by the collimator lens 25, and then enters the mirror 26 and is reflected.

Laser light 2 reflected by the mirror 26
4 passes through the first dichroic mirror 27 and the second dichroic mirror 28, and enters the mirror 29.

The laser beam 24 incident on the mirror 29 is reflected by the mirror 29 and further incident on the mirror 32 and reflected.

Laser light 2 reflected by the mirror 32
4 passes through the hole 33 of the perforated mirror 34 and enters the concave mirror 38.

The laser light 24 incident on the concave mirror 38
Is reflected by the concave mirror 38, and the optical head 3
It is incident on 5.

Laser light 24 incident on the optical head 35
Is reflected by the mirror 36 and is condensed by the aspherical lens 37 on the stimulable phosphor layer 12 of the stimulable phosphor sheet 10 placed on the stage 40 glass plate 41.

As a result, the stimulable phosphor contained in the stimulable phosphor layer 12 formed on the stimulable phosphor sheet 10 was
Excited light 45 is emitted from the stimulable phosphor that is excited by the laser light 24 and exposed by the radioactive labeling substance.

The photostimulable light 45 emitted from the photostimulable phosphor contained in the photostimulable phosphor layer 12 is collected by the aspherical lens 37 provided in the optical head 35, and is reflected by the mirror 36.
Is reflected to the same side as the optical path of the laser light 24, becomes parallel light, and is incident on the concave mirror 38.

The photostimulable light 45 incident on the concave mirror 38 is
It is reflected by the concave mirror 38 and enters the perforated mirror 34.

Photostimulation 45 incident on the perforated mirror 34
Is reflected downward by the perforated mirror 34 formed by the concave mirror, and enters the filter 52d of the filter unit 48, as shown in FIG.

The filter 52d has a property of transmitting only the light in the wavelength range of the stimulable light emitted from the stimulable phosphor and cutting off the light of the wavelength of 640 nm, and therefore, the excitation light of 640 nm. The light having the wavelength of is cut off, and only the light in the wavelength range of the photostimulated light is transmitted through the filter 52d and is photoelectrically detected by the photomultiplier 50.

As described above, the optical head 35 includes the substrate 6
The main scanning pulse motor 65 provided in FIG. 2 moves the substrate 62 in the main scanning direction indicated by the arrow X in FIG. 12, and the sub scanning pulse motor 61 moves the substrate 62 in FIG. The stimulable phosphor sheet 10 is moved in the sub-scanning direction indicated by the arrow Y.
The entire surface of the stimulable phosphor layer 12 formed on the support 11 is scanned by the laser light 24, and the stimulable phosphor 45 emitted from the stimulable phosphor contained in the stimulable phosphor layer 12 By photoelectrically detecting with the photomultiplier 50, the radiation data of the radiolabeled substance recorded in the stimulable phosphor layer 12 can be read to generate analog data for biochemical analysis.

The analog data photoelectrically detected by the photomultiplier 50 and generated are converted into digital data by the A / D converter 53 and sent to the data processor 54.

On the other hand, when reading fluorescence data such as a fluorescent dye recorded on a fluorescent sample such as a gel support or a transfer support, the user first needs to read the gel support or the transfer support on which the fluorescence data is recorded. But,
It is set on the glass plate 41 of the stage 40.

Next, the user operates the keyboard 7
When the type of the fluorescent substance is input to 1, the input fluorescent substance from the first laser excitation light source 21, the second laser excitation light source 22 and the third laser excitation light source 23 by the control unit 70. A laser excitation light source that emits a laser beam 24 having a wavelength that can efficiently excite light is selected, and the three filter members 51a, 51
The property of cutting the light of the wavelength of the laser light 24 used to excite the input fluorescent substance from b and 51c and transmitting the light having a wavelength longer than the wavelength of the laser light 24 used to excite the fluorescent substance. A filter member having is selected.

After that, the first laser excitation light source 21 and the second laser excitation light source 21
Laser excitation light source 22 or third laser excitation light source 2
3 is activated, the entire surface of the gel support or the transfer support is scanned by the laser beam 24, and the fluorescence 45 emitted from the fluorescent material is converted by the photomultiplier 50.
Photoelectrically detected, analog data is generated, A /
The data is digitized by the D converter to generate biochemical analysis data.

According to this embodiment, the support of the stimulable phosphor sheet 10 is made by the radiolabel substance contained in the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. When exposing the photostimulable phosphor layer 12 formed on the substrate 11, the electric field is applied so that the biochemical analysis unit 1 side becomes negative and the stimulable phosphor sheet 10 side becomes positive, so that a spot shape is formed. The electron beam (β-ray) emitted from each of the regions 3 is prevented from expanding its beam diameter, and goes straight, and thus the region of the stimulable phosphor layer 12 facing each of the spot-shaped regions 3 is prevented. Since only the region of the stimulable phosphor layer 12 facing the spot-shaped region 3 is exposed to the light, the spot-shaped region 3 is exposed.
Of the electron beam (β-ray) emitted from the radio-labeled substance contained in each of the
Line) is effectively prevented, and therefore, even when the spot-shaped regions 3 are formed on the absorptive substrate 2 of the biochemical analysis unit 1 at a high density, the spot-shaped regions 3 are included in each of the spot-shaped regions 3. That the region of the stimulable phosphor layer 12 to be exposed by the radioactive labeling substance contained therein is exposed by the electron beam (β-ray) emitted from the radioactive labeling substance contained in the adjacent spot-like regions. It is possible to prevent the noise caused by the from being generated in the biochemical analysis data, and it is possible to significantly improve the quantitativeness of the biochemical analysis.

Further, according to this embodiment, the spacer 1
5 is formed of stainless steel having a property of attenuating radiation energy, and through holes 16 are provided at positions corresponding to a large number of spot-shaped regions 3 of the absorptive substrate 2 of the biochemical analysis unit 1. Therefore, the electron beams (β
The line) goes straight through the corresponding through-hole 16 of the spacer 15 and faces the spot-like region 3 of the stimulable phosphor layer 1.
2 and exposes only the region of the stimulable phosphor layer 12 facing the spot-shaped region 3,
The electron beam (β-ray) emitted from the radio-labeled substance contained in each spot-shaped region 3 is emitted from the radio-labeled substance contained in the adjacent spot-shaped region 3 (β-ray). Since it is effectively prevented from mixing with the spot-shaped area 3, the biochemical analysis unit 1
The regions of the stimulable phosphor layer 12 to be exposed by the radioactive labeling substance contained in each spot-shaped region 3 are adjacent spot-shaped regions even when formed in high density on the absorptive substrate 2 of FIG. It is possible to prevent noise caused by exposure from being generated in the data for biochemical analysis by the electron beam (β-ray) emitted from the radiolabeled substance contained in 3. It is possible to greatly improve the quantitativeness of.

FIG. 14 is a schematic perspective view of a stimulable phosphor sheet according to another preferred embodiment of the present invention.

As shown in FIG. 14, in the stimulable phosphor sheet 80 according to this embodiment, a large number of substantially circular stimulable phosphor layer regions 82 are formed on one surface of a support 81.
Are spaced apart from each other and are formed in a dot shape, and an electrode 84 is provided on the other surface of the support 81.

A large number of stimulable phosphor layer regions 82 are formed in the same pattern as the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1,
Each of them has substantially the same size as the large number of spot-shaped regions 3.

Therefore, although not accurately shown in FIG. 14, in this embodiment, the support 81 of the stimulable phosphor sheet 80 has a substantially circular luminescent material having a size of about 0.07 mm 2. Exhaust phosphor layer region 82 is 12
The matrix is regularly formed in a matrix of 0 columns × 160 rows, and a total of 19200 stimulable phosphor layer regions 82 are formed.

Also in this embodiment, in the same manner as in the above embodiment, the absorptive substrate 2 of the biochemical analysis unit 1 is
A solution containing a specific binding substance such as cDNA is dripped to form a large number of spot-like regions 3, and the hybridization reaction container 8 shown in FIG. The substance is selectively hybridized with the specific binding substance contained in the large number of spot-like regions 3 formed on the adsorptive substrate 2 of the biochemical analysis unit 1 and becomes radioactive to the biochemical analysis unit 1. Radiation data of labeled substances are recorded.

Next, the stimulable phosphor sheet 80 is superposed on the biochemical analysis unit 1 and selectively included in a large number of spot-like regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. A large number of stimulable phosphor layer regions 82 formed on the support 81 of the stimulable phosphor sheet 80 are exposed to the radioactive labeling substance, and the radioactive labeling substance recorded in the biochemical analysis unit 1 The radiation data is transferred to a large number of stimulable phosphor layer regions 82 formed on the support 81 of the stimulable phosphor sheet 80.

FIG. 15 shows the support of the stimulable phosphor sheet 80 by the radioactive labeling substance selectively contained in the large number of spot-like regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. It is a schematic sectional drawing which shows the method of exposing the many photostimulable phosphor layer area | region 82 formed in 81.

Just as in the above embodiment, as shown in FIG. 15, the surface of the absorptive substrate 2 of the biochemical analysis unit 1 on which a large number of spot-like regions 3 are formed prior to the exposure. The electrode 4 is attached to the opposite surface.

Also in this embodiment, the spacer 15 is
As shown in FIG. 15, the spacer 15 is formed of stainless steel having a property of attenuating radiation energy, and the spacer 15 includes a large number of spot-shaped regions 3 and accumulative properties formed on the absorptive substrate 2 of the biochemical analysis unit 1. Through holes 16 are provided at positions corresponding to a large number of stimulable phosphor layer regions 82 formed on the support 81 of the phosphor sheet 80, and the surface thereof is covered with an insulating layer (not shown). ing.

As shown in FIG. 15, upon exposure, first, a large number of stimulable phosphor layer regions 82 formed on the support 81 of the stimulable phosphor sheet 80 are respectively formed in the through holes 16 of the spacer 15. The spacer 15 is set on the surface of the stimulable phosphor sheet 80 so as to be positioned inside.

Next, a large number of spot-like regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1 are respectively located in corresponding stimulable phosphor layer regions 82 of the stimulable phosphor sheet 80. The biochemical analysis unit 1 is set on the spacer 15 so as to be positioned in the through hole 16 of the spacer 15.

Further, the electrode 4 provided on the biochemical analysis unit 1 is connected to the positive electrode of the DC power source 17, and the electrode 84 provided on the stimulable phosphor sheet 80.
Is connected to the negative pole of the DC power supply 17.

As a result, an electric field is generated so that the biochemical analysis unit 1 side becomes negative and the stimulable phosphor sheet 80 side becomes positive.

Thus, the radioactive labeling substance selectively contained in the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1 causes the support 81 of the stimulable phosphor sheet 80 to adhere to the support 81. The formed many stimulable phosphor layer regions 82 are exposed.

At the time of exposure, an electron beam (β-ray) is emitted from the radiolabeled substance selectively contained in the large number of spot-like regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. , So that the biochemical analysis unit 1 side is negative and the stimulable phosphor sheet 80 side is positive,
Since an electric field is applied, the electron beam (β-ray) emitted from each spot-shaped region 3 of the biochemical analysis unit 1 is
The beam diameter is prevented from expanding, and the beam travels straight.

Further, the spacer 15 is made of stainless steel having a property of attenuating radiation energy, and has a large number of spot-like regions 3 and accumulative fluorescence formed on the absorptive substrate 2 of the biochemical analysis unit 1. Through-holes 16 are formed at positions corresponding to a large number of photostimulable phosphor layer regions 82 formed on the support 81 of the body sheet 80.
Therefore, the electron beam (β-ray) emitted from each of the spot-shaped regions 3 travels straight through the corresponding through hole 16 of the spacer 15 and opposes the spot-shaped region 3 with a stimulable phosphor. It is incident on the layer region 82 and the spot-like region 3
Only the photostimulable phosphor layer region 82 facing each of these is exposed.

Thus, a large number of stimulable phosphor layer regions 82 formed on the support 81 of the stimulable phosphor sheet 80 are
Radiation data of radiolabeled substances are recorded.

The radiation data of the radioactive labeling substance recorded in the large number of stimulable phosphor layer regions 82 formed on the support 81 of the stimulable phosphor sheet 80 are the same as in the above-mentioned embodiment, and the radiation data of FIG. Through the scanner shown in FIG. 13 to FIG. 13, data is read and biochemical analysis data is generated.

According to this embodiment, the stimulable phosphor sheet 80 is prepared by the radioactive labeling substance selectively contained in the large number of spot-shaped regions 3 formed on the adsorptive substrate 2 of the biochemical analysis unit 1. When a large number of photostimulable phosphor layer regions 82 formed on the support 81 are exposed, an electric field is applied so that the biochemical analysis unit 1 side becomes negative and the stimulable phosphor sheet 80 side becomes positive. Therefore, the electron beam (β-ray) emitted from each of the spot-shaped regions 3
The beam diameter is prevented from expanding and goes straight,
Therefore, since the photostimulable phosphor layer regions 82 facing the respective spot-shaped regions 3 are made incident and only the photostimulable phosphor layer regions 82 opposed to the spot-shaped regions 3 are exposed, the spot-shaped regions 3 are exposed. The electron beam (β-ray) emitted from the radio-labeled substance contained in each of the two is mixed with the electron beam (β-ray) emitted from the radio-labeled substance contained in the adjacent spot-shaped regions 3. This is effectively prevented, and therefore, even if the spot-shaped regions 3 are formed on the absorptive substrate 2 of the biochemical analysis unit 1 with high density,
The stimulable phosphor layer regions 82 to be exposed by the radioactive labeling substance contained in each of the spot-shaped regions 3 are emitted from the radioactive labeling substance contained in the adjacent spot-shaped regions 3 (β The line) can prevent noise due to exposure from being generated in the biochemical analysis data, and can significantly improve the quantitativeness of the biochemical analysis.

Further, according to this embodiment, the spacer 1
5 is made of stainless steel having a property of attenuating radiation energy, and a large number of spot-like regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1 and a stimulable phosphor sheet corresponding thereto Since a large number of stimulable phosphor layer regions 82 of 80 are positioned in the through holes 16 formed in the spacer 15, the electron beam (β-ray) emitted from each of the spot-shaped regions 3 is
It goes straight through the corresponding through hole 16 of the spacer 15 and faces the spot-shaped region 3 thereof, and enters only the stimulable phosphor layer region 82 located in the through hole 16 of the spacer 15 to form a spot-shaped region. Only the stimulable phosphor layer regions 82 facing each of the regions 3 are exposed, and therefore, the electron beams (β-rays) emitted from the radiolabel substance contained in each of the spot-shaped regions 3 are adjacent to each other. Electron beam (β
Line) is effectively prevented from being mixed, so that even if the spot-shaped regions 3 are formed on the absorptive substrate 2 of the biochemical analysis unit 1 at a high density, they are included in each of the spot-shaped regions 3. The stimulable phosphor layer regions 82 to be exposed by the radioactive labeling substance are adjacent spot-like regions 3
Of the electron beam (β
The line) can prevent noise due to exposure from being generated in the biochemical analysis data, and can significantly improve the quantitativeness of the biochemical analysis.

FIG. 16 is a schematic perspective view of a stimulable phosphor sheet according to another preferred embodiment of the present invention.

As shown in FIG. 16, the stimulable phosphor sheet 90 according to this embodiment includes a support 91, and one surface of the support 91 has a large number of substantially circular recesses (not shown). ) Are formed so as to be spaced apart from each other, and the stimulable phosphor is embedded in a large number of concave portions to form a large number of substantially circular stimulable phosphor layer regions 92 in a dot shape. An electrode 94 is provided on the other surface of the.

As shown in FIG. 16, a large number of stimulable phosphor layer regions 92 have the same pattern as the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. Each of the plurality of spot-shaped regions 3 has a size substantially the same as that of the spot-shaped regions 3 and is formed so that its surface is smoothly continuous with the surface of the support 91.

Therefore, although not accurately shown in FIG. 16, in this embodiment, the support 91 of the stimulable phosphor sheet 90 has a substantially circular luminescent material having a size of about 0.07 mm 2. The exhaustive phosphor layer region 92 has 12
A total of 19200 stimulable phosphor layer regions 92 are formed in a matrix of 0 columns × 160 rows.

Also in this embodiment, in the same manner as in the above embodiment, the absorptive substrate 2 of the biochemical analysis unit 1 is
A solution containing a specific binding substance such as cDNA is dripped to form a large number of spot-like regions 3, and the hybridization reaction container 8 shown in FIG. The substance is selectively hybridized with the specific binding substance contained in the large number of spot-like regions 3 formed on the adsorptive substrate 2 of the biochemical analysis unit 1 and becomes radioactive to the biochemical analysis unit 1. Radiation data of labeled substances are recorded.

Next, the stimulable phosphor sheet 90 is superposed on the biochemical analysis unit 1 and selectively included in a large number of spot-like regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. A large number of stimulable phosphor layer regions 92 formed on the support 91 of the stimulable phosphor sheet 90 are exposed to the radioactive labeling substance and the radioactive labeling substance recorded in the biochemical analysis unit 1 The radiation data is transferred to a large number of stimulable phosphor layer regions 92 formed on the support 91 of the stimulable phosphor sheet 90.

FIG. 17 shows the support of the stimulable phosphor sheet 90 by the radioactive labeling substance selectively contained in the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. FIG. 9 is a schematic cross-sectional view showing a method of exposing a large number of stimulable phosphor layer regions 92 formed on 91.

In exactly the same manner as in the above embodiment, as shown in FIG. 17, the surface of the absorptive substrate 2 of the biochemical analysis unit 1 on which a large number of spot-shaped regions 3 are formed prior to the exposure. The electrode 4 is attached to the opposite surface.

Also in this embodiment, the spacer 15 is
As shown in FIG. 17, the spacer 15 is formed of stainless steel having a property of attenuating radiation energy, and the spacer 15 includes a large number of spot-shaped regions 3 and accumulative regions formed on the absorptive substrate 2 of the biochemical analysis unit 1. Through holes 16 are provided at positions corresponding to a large number of stimulable phosphor layer regions 92 formed on the support 91 of the phosphor sheet 90, and the surface thereof is covered with an insulating layer (not shown). ing.

As shown in FIG. 17, upon exposure, first, a large number of stimulable phosphor layer regions 92 formed on the support 91 of the stimulable phosphor sheet 90 are respectively formed in the through holes 16 of the spacer 15. The spacer 15 is set on the surface of the stimulable phosphor sheet 90 so as to be located inside.

Next, a large number of spot-like regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1 are respectively located in corresponding stimulable phosphor layer regions 92 of the stimulable phosphor sheet 90. The biochemical analysis unit 1 is set on the spacer 15 so as to be positioned in the through hole 16 of the spacer 15.

Further, the electrode 4 provided on the biochemical analysis unit 1 is connected to the positive electrode of the DC power supply 17, and the electrode 94 provided on the stimulable phosphor sheet 90 is used.
Is connected to the negative pole of the DC power supply 17.

As a result, an electric field is generated so that the biochemical analysis unit 1 side is negative and the stimulable phosphor sheet 90 side is positive.

Thus, the radioactive labeling substance selectively contained in the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1 is formed on the support 91 of the stimulable phosphor sheet 90. The large number of stimulable phosphor layer regions 92 thus exposed are exposed.

At the time of exposure, an electron beam (β-ray) is emitted from the radioactive labeling substance selectively contained in the large number of spot-like regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. Make the biochemical analysis unit 1 side negative and the stimulable phosphor sheet 90 side positive.
Since the electric field is applied, the electron beams (β
The line is prevented from expanding its beam diameter and goes straight.

Further, the spacer 15 is made of stainless steel having a property of attenuating radiation energy, and has a large number of spot-like regions 3 and accumulative fluorescence formed on the absorptive substrate 2 of the biochemical analysis unit 1. Through-holes 16 are formed at positions corresponding to a large number of stimulable phosphor layer regions 92 formed on the support 91 of the body sheet 90.
Therefore, the electron beam (β-ray) emitted from each of the spot-shaped regions 3 travels straight through the corresponding through hole 16 of the spacer 15 and opposes the spot-shaped region 3 with a stimulable phosphor. Only the photostimulable phosphor layer region 92 which is incident on the layer region 92 and faces the spot-shaped region 3 is exposed.

Thus, a large number of stimulable phosphor layer regions 92 formed on the support 91 of the stimulable phosphor sheet 90 are
Radiation data of radiolabeled substances are recorded.

The radiation data of the radiolabeled substance recorded in the large number of stimulable phosphor layer regions 92 formed on the support 91 of the stimulable phosphor sheet 90 is the same as in the above-described embodiment, and the radiation data of FIG. Through the scanner shown in FIG. 13 to FIG. 13, data is read and biochemical analysis data is generated.

According to this embodiment, the stimulable phosphor sheet 90 is prepared by the radioactive labeling substance selectively contained in the large number of spot-shaped regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1. When a large number of photostimulable phosphor layer regions 92 formed on the support 91 are exposed, an electric field is applied so that the biochemical analysis unit 1 side becomes negative and the stimulable phosphor sheet 90 side becomes positive. Therefore, the electron beam (β-ray) emitted from each of the spot-shaped regions 3
The beam diameter is prevented from expanding and goes straight,
Therefore, since the photostimulable phosphor layer regions 92 facing the respective spot-shaped regions 3 are made incident and only the photostimulable phosphor layer regions 92 opposed to the spot-shaped regions 3 are exposed, the spot-shaped regions 3 are exposed. The electron beam (β-ray) emitted from the radio-labeled substance contained in each of the two is mixed with the electron beam (β-ray) emitted from the radio-labeled substance contained in the adjacent spot-shaped regions 3. This is effectively prevented, and therefore, even if the spot-shaped regions 3 are formed on the absorptive substrate 2 of the biochemical analysis unit 1 with high density,
The stimulable phosphor layer regions 92 to be exposed by the radioactive labeling substance contained in each of the spot-shaped regions 3 are electron beams (β) emitted from the radioactive labeling substance contained in the adjacent spot-shaped regions 3. The line) can prevent noise due to exposure from being generated in the biochemical analysis data, and can significantly improve the quantitativeness of the biochemical analysis.

Further, according to this embodiment, the spacer 1
5 is made of stainless steel having a property of attenuating radiation energy, and a large number of spot-like regions 3 formed on the absorptive substrate 2 of the biochemical analysis unit 1 and a stimulable phosphor sheet corresponding thereto Since a large number of 90 stimulable phosphor layer regions 92 are positioned in the through holes 16 formed in the spacer 15, the electron beam (β-ray) emitted from each of the spot-shaped regions 3 is
It goes straight through the corresponding through-hole 16 of the spacer 15 and is incident on the photostimulable phosphor layer region 92 located inside the through-hole 16 of the spacer 15 facing each of the spot-like regions 3 and the spot thereof. Only the stimulable phosphor layer region 92 facing the stripe-shaped region 3 is exposed, and therefore the electron beams (β-rays) emitted from the radiolabeled substances contained in each spot-shaped region 3 are adjacent to each other. Electron beam (β-ray) emitted from the radiolabeled substance contained in the spot-shaped region 3
Since the spot-shaped region 3 is effectively prevented from being mixed with the absorptive substrate 2 of the biochemical analysis unit 1.
In addition, even when formed in a high density, the stimulable phosphor layer regions 92 to be exposed by the radioactive labeling substance contained in each of the spot-shaped regions 3 are included in the adjacent spot-shaped regions 3. Electron beam (β-ray) emitted from labeling substance
By this, it is possible to prevent noise caused by exposure from being generated in the data for biochemical analysis,
It becomes possible to greatly improve the quantitativeness of biochemical analysis.

The present invention is not limited to the above embodiments, and various modifications can be made within the scope of the invention described in the claims, and these are also included in the scope of the present invention. It goes without saying that it is a thing.

For example, in the above-described embodiment, a plurality of cDNAs having different known base sequences are used as the specific binding substance, but the specific binding substance usable in the present invention is not limited to the cDNA. Hormones, tumor markers, enzymes, antibodies, antigens,
Abzyme, other proteins, nucleic acids, cDNA, D
All specific binding substances, such as NA and RNA, which can be specifically bound to a substance of biological origin and whose base sequence, base length, composition, etc. are known, should be used as the specific binding substance of the present invention. You can

In the above-mentioned embodiment, the substance of biological origin labeled with a radioactive labeling substance or a fluorescent substance is hybridized with the specific binding substance. It is not always necessary to hybridize, and a substance derived from a living body can be specifically bound to a specific binding substance by a reaction such as an antigen-antibody reaction or a receptor / ligand instead of hybridization.

Furthermore, in the above-mentioned embodiment, the biochemical analysis unit 1 is provided with an adsorptive substrate formed of nylon 6, and a solution containing a specific binding substance is dropped onto the adsorptive substrate 2, Although a large number of spot regions 3 are formed so as to be separated from each other, a large number of through holes or concave portions are formed at a distance from each other on a substrate made of metal or the like, and nylon 6 is formed in the through holes or concave portions formed on the substrate. It is also possible to form a large number of adsorbent regions by filling with the above-mentioned solution and to drop a solution containing a specific binding substance into the large number of adsorbent regions to form a large number of spot regions 3.

Further, in the above-mentioned embodiment, the biochemical analysis unit 1 includes the absorptive substrate formed of nylon 6, but it is not always necessary to form the absorptive substrate by nylon 6. Nylon 6 can also be used to form an absorptive region in a large number of through holes or recesses formed in a substrate made of metal or the like and spaced from each other.
It is not always necessary to form the absorptive region by the above, and the absorptive substrate 2 or the absorptive region can be formed by another absorptive material. As the adsorptive material for forming the adsorptive substrate 2 or the adsorptive region of the biochemical analysis unit 1, a porous material or a fibrous material is preferably used. The absorptive substrate 2 or the absorptive region of the analysis unit 1 can also be formed. The porous material used to form the absorptive substrate 2 or the absorptive region of the biochemical analysis unit 1 may be an organic material, an inorganic material, or an organic / inorganic composite. The organic porous material used to form the adsorptive substrate 2 or the adsorptive region of the biochemical analysis unit 1 is not particularly limited, but forms a carbon porous material such as activated carbon or a membrane filter. Possible porous materials are preferably used. Specifically, nylons such as nylon 6, nylon 6,6 and nylon 4,10; cellulose derivatives such as nitrocellulose, cellulose acetate, cellulose butyrate acetate; collagen; alginic acid, calcium alginate, alginic acid / polylysine polyion complex, etc. Examples thereof include alginic acids; polyolefins such as polyethylene and polypropylene; polyvinyl chloride; polyvinylidene chloride; polyvinylidene fluoride, polyfluorides such as polytetrafluoride, and copolymers or composites thereof. The inorganic porous material used to form the absorptive substrate 2 or the absorptive region of the biochemical analysis unit 1 is not particularly limited, but preferably, for example, platinum, gold, iron, silver. ,
Examples thereof include metals such as nickel and aluminum; metal oxides such as alumina, silica, titania and zeolite; metal salts such as hydroxyapatite and calcium sulfate, and composites thereof. The fibrous material used to form the absorptive substrate 2 or the absorptive region of the biochemical analysis unit 1 is not particularly limited, but preferably nylon 6, nylon 6,6, nylon, for example. Nylons such as 4,10, nitrocellulose,
Examples thereof include cellulose derivatives such as cellulose acetate and cellulose butyrate.

Further, in the above embodiment, 192
The spot-shaped areas 3 of 00 having a size of about 0.07 mm 2 are regularly formed in a matrix of 120 columns × 160 rows on the absorptive substrate 2 of the biochemical analysis unit 1. The number and size of the spot-shaped regions 3 can be arbitrarily selected according to the purpose,
Preferably, 10 or more spot-like regions 3 are 10 /
The spot-like region 3 is formed on the absorptive substrate 2 of the biochemical analysis unit 1 with a density of not less than square centimeters.
It is formed to a size of less than 5 mm 2.

In the embodiment described above, a large number of substantially circular spot areas 3 are formed on the absorptive substrate 2 of the biochemical analysis unit 1, and in the embodiment shown in FIGS. 14 and 15, , Stimulable phosphor sheet 80
A substantially circular stimulable phosphor layer region 82 is formed on the support 81 of FIG. 16 and is formed on the support 91 of the stimulable phosphor sheet 90 in the embodiment shown in FIGS. 16 and 17. A large number of substantially circular recesses are filled with stimulable phosphors,
Although a large number of stimulable phosphor layer regions 92 are formed, the shapes of the spot-shaped regions 3 and the stimulable phosphor layer regions 82, 92 are not limited to a substantially circular shape, and they may be rectangular or the like. It can also be formed.

Further, in the above embodiment, the spacer 15 is made of stainless steel whose surface is covered with an insulating layer (not shown), but the spacer 15 is not necessarily made of stainless steel. Not necessary. The spacer 15 is preferably formed of a material having a property of attenuating radiation energy, but the material used for forming the spacer 15 is not particularly limited, and an inorganic compound material,
Any organic compound material can be used, with metallic, ceramic or plastic materials being particularly preferred. Examples of the inorganic compound material that can be used to form the spacer 15 and can attenuate the radiation energy include gold, silver, copper,
Zinc, aluminum, titanium, tantalum, chromium, iron,
Metals such as nickel, cobalt, lead, tin and selenium; alloys such as brass, stainless steel and bronze; silicon materials such as silicon, amorphous silicon, glass, quartz, silicon carbide and silicon nitride; aluminum oxide, magnesium oxide, zirconium oxide, etc. Metal oxides of the above; inorganic salts such as tungsten carbide, calcium carbonate, calcium sulfate, hydroxyapatite, gallium arsenide and the like. These may have any structure in a polycrystalline sintered body such as single crystal, amorphous, or ceramic. As the organic compound material that can be used to form the spacer 15 and can attenuate the radiation energy, polymer compounds are preferably used. For example, polyolefin such as polyethylene or polypropylene; polymethylmethacrylate, butylacrylate /
Acrylic resins such as methylmethacrylate copolymers; polyacrylonitrile; polyvinyl chloride; polyvinylidene chloride; polyvinylidene fluoride; polytetrafluoroethylene; polychlorotrifluoroethylene; polycarbonate; polyesters such as polyethylene naphthalate and polyethylene terephthalate; nylon 6 Polyamide; Polysulfone; Polyphenylene sulfide; Silicon resin such as polydiphenylsiloxane; Phenolic resin such as novolac; Epoxy resin; Polyurethane; Polystyrene; Butadiene-styrene copolymer; Cellulose Polysaccharides such as cellulose acetate, nitrocellulose, starch, calcium alginate, hydroxypropylmethylcellulose; ; Chitosan; lacquer; gelatin, collagen, copolymers of polyamides and these high molecular compounds, such as keratin, and the like.
These may be a composite material, if necessary, can be filled with metal oxide particles or glass fiber,
It is also possible to blend and use an organic compound material.

In the above embodiment, the spacer 15 is made of stainless steel whose surface is covered with an insulating layer (not shown).
It is not always necessary to cover the surface of 5 with an insulating layer, the spacer 15 itself may be formed of a material having an insulating property, and further, the spacer 15 may not have an insulating property.

[0183]

EFFECTS OF THE INVENTION According to the present invention, a plurality of spot-like regions containing a specific binding substance capable of specifically binding to a substance of biological origin and having a known base sequence, base length, composition, etc. are formed. The biochemical analysis unit obtained by forming a plurality of spot-shaped regions on the carrier surface with high density and selectively labeling the multiple spot-shaped regions with a radioactive labeling substance is brought into close contact with the stimulable phosphor layer to produce a luminescent material. Exposing the exhaustive phosphor layer with a radioactive labeling substance,
Irradiating the stimulable phosphor layer with excitation light and photoelectrically detecting the stimulable light emitted from the stimulable phosphor layer to generate biochemical analysis data and analyze substances derived from living organisms. Even when
Exposure of the stimulable phosphor layer of the stimulable phosphor sheet that can prevent noise due to scattering of electron beams (β rays) emitted from radiolabeled substances in the data for biochemical analysis It becomes possible to provide a method, a biochemical analysis unit used for the method, and a stimulable phosphor sheet.

[Brief description of drawings]

FIG. 1 is a schematic perspective view of a biochemical analysis unit according to a preferred embodiment of the present invention.

FIG. 2 is a schematic front view of a spotting device.

FIG. 3 is a schematic vertical sectional view of a hybridization reaction container.

FIG. 4 is a schematic perspective view of a stimulable phosphor sheet according to a preferred embodiment of the present invention.

FIG. 5 is a graph showing the luminescence formed on the support of the stimulable phosphor sheet by the radioactive labeling substance contained in the large number of spot-like regions formed on the absorptive substrate of the biochemical analysis unit. It is a schematic sectional drawing which shows the method of exposing an exhaustive fluorescent substance layer.

FIG. 6 is a schematic perspective view showing an example of a scanner.

FIG. 7 is a schematic perspective view showing details of the vicinity of the photomultiplier of the scanner shown in FIG.

8 is a schematic cross-sectional view taken along the line AA of FIG.

9 is a cross-sectional view taken along the line BB of FIG.

10 is a cross-sectional view taken along the line CC of FIG.

11 is a cross-sectional view taken along the line DD of FIG.

FIG. 12 is a schematic plan view of a scanning mechanism of an optical head.

FIG. 13 is a block diagram showing a control system, an input system and a drive system of the scanner shown in FIG.

FIG. 14 is a schematic perspective view of a stimulable phosphor sheet according to another preferred embodiment of the present invention.

FIG. 15 is a view of supporting the stimulable phosphor sheet shown in FIG. 14 by a radiolabel substance contained in a large number of spot-like regions formed on the absorptive substrate of the biochemical analysis unit. It is a schematic sectional drawing which shows the method of exposing many photostimulable fluorescent substance layers formed in the body.

FIG. 16 is a schematic perspective view of a stimulable phosphor sheet according to another preferred embodiment of the present invention.

FIG. 17 is a view of supporting the stimulable phosphor sheet shown in FIG. 16 by a radiolabel substance contained in a large number of spot-shaped regions formed on the absorptive substrate of the biochemical analysis unit. It is a schematic sectional drawing which shows the method of exposing many photostimulable fluorescent substance layers formed in the body.

[Explanation of symbols]

1 Biochemical analysis unit 2 Adsorbent substrate 3 spot-shaped areas 4 electrodes 5 Spotting device 6 injectors 7 CCD camera 8 Hybridization reaction container 9 Hybridization reaction solution 10 Storage phosphor sheet 11 Support 12 Photostimulable phosphor layer 14 electrodes 15 Spacer 16 Spacer through hole 17 DC power supply 21 First laser excitation light source 22 Second laser excitation light source 23 Third Laser Excitation Light Source 24 laser light 25 Collimator lens 26 mirror 27 First Dichroic Mirror 28 Second dichroic mirror 29 mirror 30 collimator lens 31 Collimator lens 32 mirror 33 holes for the perforated mirror 34 perforated mirror 35 Optical head 36 mirror 37 Aspherical lens 38 concave mirror 40 stages 41 glass plate 45 Fluorescence or stimulated emission 48 filter units 50 Photomultiplier 51a, 51b, 51c, 51d filter member 52a, 52b, 52c, 52d filters 53 A / D converter 54 Data processing device 60 substrates 61 Sub-scanning pulse motor 62 a pair of rails 63 Movable substrate 64 rod 65 Main scanning pulse motor 66 endless belt 67 Linear encoder 70 Control unit 71 keyboard 72 Filter unit motor 80 Phosphor sheet 81 Support 82 Photostimulable phosphor layer region 90 Storage phosphor sheet 91 Support 92 Photostimulable phosphor layer region

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) G01T 1/00 G01T 1/00 B 4B029 1/29 1/29 D G03B 42/02 G03B 42/02 B G21K 4/00 G21K 4/00 NF term (reference) 2G043 AA01 BA16 DA02 DA06 EA01 FA01 FA06 GA07 GB01 GB11 GB12 GB16 HA01 HA02 HA03 HA15 JA02 KA02 KA05 KA09 LA02 LA03 MA16 NA05 2G045 DA12 DA13 DA14 DA36 FA08 FA03 FB02 FB02 FB02 FB02 FB02 AA03 AA09 BB03 CC03 CC04 CC09 CC10 DD16 EE02 2G088 EE27 FF05 GG10 GG25 JJ05 JJ30 JJ32 KK32 KK35 LL09 LL11 LL12 2H013 AB02 AC01 4B029 AA07 BB01 BB15 BB20 CC03 CC08 FA12

Claims (20)

[Claims] 1. A specific binding substance having a known structure or property is dropped on one surface, and a substance of biological origin labeled with a radiolabeling substance is specifically bound to the specific binding substance, A plurality of spot-shaped regions are formed apart from each other, and on the other surface, a biochemical analysis unit in which an electrode is provided, and at least one of the biochemical analysis units corresponding to the plurality of spot-shaped regions In the area of the surface, the stimulable phosphor layer is provided, and on the other surface, the stimulable phosphor sheet provided with the electrodes is opposed to each other, and the biochemical analysis unit is negative, Apply an electric field so that the stimulable phosphor sheet becomes positive,
A method for exposing a stimulable phosphor layer of a stimulable phosphor sheet, which comprises exposing the stimulable phosphor layer with the radioactive labeling substance. 2. The higher the electric field, the larger the distance between the one surface of the biochemical analysis unit and the stimulable phosphor layer of the stimulable phosphor sheet is set, 2. The photostimulable phosphor layer is exposed to light.
The method for exposing the stimulable phosphor layer of the stimulable phosphor sheet according to item 1. 3. Between the one surface of the biochemical analysis unit and the stimulable phosphor layer of the stimulable phosphor sheet, at least the surface thereof has an insulating property and is separated from each other. The stimulable phosphor is provided with a spacer having a plurality of through-holes so that the plurality of spot-shaped regions respectively face the stimulable phosphor layer through the through-holes. The method for exposing a stimulable phosphor layer of a stimulable phosphor sheet according to claim 1, wherein the layer is exposed. 4. The method for exposing a stimulable phosphor layer of a stimulable phosphor sheet according to claim 2, wherein the spacer is formed of a material that attenuates radiation energy. 5. A material having a property of attenuating radiation energy to 1/5 or less when radiation passes through the spacer by a distance equal to a distance between adjacent through holes. The method for exposing a stimulable phosphor layer of a stimulable phosphor sheet according to claim 4, wherein the stimulable phosphor layer is formed. 6. The stimulable phosphor of the stimulable phosphor sheet according to claim 5, wherein the spacer is formed of a material selected from the group consisting of a metal material, a ceramic material and a plastic material. Layer exposure method. 7. The higher the electric field, the thicker the spacer, the one side of the biochemical analysis unit, and the photostimulable phosphor layer of the stimulable phosphor sheet. 7. The method for exposing a stimulable phosphor layer of a stimulable phosphor sheet according to claim 3, wherein the stimulable phosphor layer is interposed between the stimulable phosphor layer and the stimulable phosphor layer. 8. A plurality of stimulable phosphor layer regions are separated from each other only in a region of one surface of the stimulable phosphor sheet that faces the plurality of spot-shaped regions of the biochemical analysis unit. The method of exposing a stimulable phosphor layer of a stimulable phosphor sheet according to claim 1, wherein the stimulable phosphor layer is exposed to light. 9. The spacers are interposed so that the plurality of spot-shaped regions and the plurality of stimulable phosphor layer regions respectively face each other through the through holes, and the plurality of bright regions are provided. The method of exposing the stimulable phosphor layer of the stimulable phosphor sheet according to claim 8, wherein the stimulable phosphor layer region is exposed. 10. The stimulable phosphor sheet according to claim 1, wherein the stimulable phosphor layer is formed on substantially the entire surface of the stimulable phosphor sheet. Method for exposing photostimulable phosphor layer. 11. A plurality of absorptive regions made of an absorptive material are formed on the one surface of the biochemical analysis unit so as to be spaced apart from each other, and the plurality of spot-shaped regions are a plurality of the absorptive regions. The method for exposing a stimulable phosphor layer of a stimulable phosphor sheet according to claim 1, wherein the stimulable phosphor layer is formed in a region. 12. The photostimulable phosphor layer of the stimulable phosphor sheet according to claim 1, wherein the biochemical analysis unit is formed of an adsorptive material. Exposure method. 13. The adsorptive material comprises a porous material or a fibrous material.
The method for exposing the stimulable phosphor layer of the stimulable phosphor sheet according to item 1. 14. A specific binding substance having a known structure or characteristic is dropped on one surface, and a substance of biological origin labeled with a radiolabeling substance is specifically bound to form a plurality of spot-shaped regions. A biochemical analysis unit, characterized in that it is formed so as to be separated from each other, and an electrode is provided on the other surface. 15. The biochemical analysis unit according to claim 14, wherein substantially the whole of the unit is formed of an adsorptive material. 16. A method according to claim 1, wherein only the plurality of spot-shaped regions are formed of an adsorptive material.
The unit for biochemical analysis according to item 5. 17. The adsorptive material comprises a porous material or a fibrous material.
The biochemical analysis unit described in. 18. A stimulable phosphor sheet characterized in that a stimulable phosphor layer is formed on at least a region to be exposed by a radiolabel substance on one surface and an electrode is provided on the other surface. . 19. The plurality of stimulable phosphor layer regions are formed separately from each other only in a region of the one surface to be exposed by the radiolabel substance. Stimulable phosphor sheet of. 20. The stimulable phosphor sheet according to claim 18, wherein the stimulable phosphor layer is formed on substantially the entire surface of the stimulable phosphor sheet.