JP2003042911A - Method and device for spotting specific bonding substance - Google Patents

Abstract

PROBLEM TO BE SOLVED: To effectively prevent chemiluminescence and/or fluorescence emitted from adjacent spot-like areas from mixing together, so as to generate data for biochemical analysis excellent in quantitativeness, when preventing effectively an electron beam (β-ray) emitted from a radioactive labelled substance contained in the adjacent spot-like regions from being mixed together, or when detecting photoelectrically the chemiluminescence and/or the fluorescence emitted from the adjacent spot-like regions to generate the data for the biochemical analysis. SOLUTION: In this spotting method, a plurality of holes 3 are formed separatedly each other in a substrate 2 of a biochemical analyzing unit 1, having a property capable of attenuating a radiation and/or light, and a solution containing a specific bonding substance is spotted in the adsorptive areas 4 formed inside the plural holes respectively. Evaporation of the solution containing the specific bonding substance spotted in the plural adsorptive areas is promoted forcibly by an evaporation promoting means 8, in the method.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a spotting method and apparatus, and more specifically, it is capable of specifically binding to a substance derived from a living body and has a base sequence, a base length, a composition and the like. A known specific binding substance is spotted on a carrier to form a high density of spot-like regions on the carrier, and the specific binding substance contained in the spot-like region is labeled with a radiolabeling substance from a living body. The biochemical analysis unit obtained by selectively binding the substance and selectively labeling it is brought into close contact with the stimulable phosphor layer, and the stimulable phosphor layer is exposed to a radiolabeled substance to produce a luminescent material. 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, adjacent spots are also used. Emitted from radiolabeled substances contained in Specific binding substance that effectively prevents the mixed electron beams (β-rays) from mixing with each other and can specifically bind to a substance of biological origin, and whose base sequence, base length, composition, etc. are known A label substance which forms chemiluminescence by forming a spot-shaped region on the carrier at a high density on a carrier and bringing a specific binding substance contained in the spot-shaped region into contact with a chemiluminescent substrate. For biochemical analysis, a substance of biological origin labeled with a fluorescent substance is specifically bound and selectively labeled, and chemiluminescence and / or fluorescence emitted from a spot-like region is photoelectrically detected. Even when generating data, chemiluminescence emitted from adjacent spot-like regions and / or
Further, the present invention relates to a spotting method and apparatus capable of effectively preventing mixing of fluorescence and generating biochemical analysis data with excellent quantitativeness.

[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.

Further, in recent years, hormones, tumor markers, enzymes, antibodies, antigens, abzymes, etc. have been found at different positions on the surface of a carrier such as a slide glass plate and a membrane filter.
Other proteins, nucleic acids, cDNA, DNA, RNA
For example, using a spotter device, a specific binding substance that can specifically bind to a substance of biological origin and whose base sequence, base length, composition, etc. is known is spotted, and a large number of independent Forming a spot, and then collected from the living body by extraction, isolation, etc. of hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, cDNA, DNA, mRNA, etc., 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 labeling substance such as a fluorescent substance or a dye, can be subjected to a specific binding substance by hybridization or the like. A microarray analysis system that analyzes substances derived from living organisms by irradiating excitation light to the microarrays that have been mechanically bound and photoelectrically detecting light such as fluorescence emitted from labeling substances such as fluorescent substances and dyes Being developed. 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 a substance of biological origin labeled with a labeling substance is used. By hybridizing with, there is an advantage that a substance derived from a living body can be analyzed in a short time.

[0007] Further, hormones, tumor markers, enzymes,
Antibodies, antigens, abzymes, other proteins, nucleic acids,
Spot specific binding substances, such as cDNA, DNA, and RNA, that can be specifically bound to substances of biological origin and whose base sequence, base length, composition, etc., are known, using a spotter device. Forming a large number of independent spots,
Next, hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, cDNA
A, DNA, mRNA, etc., by extraction, isolation, etc.
A substance derived from a living body that has been collected from a living body, or has been further subjected to chemical treatment, chemical modification, or the like,
A macroarray in which a substance labeled with a radioactive labeling substance is specifically bound to a specific binding substance by hybridization or the like, and a stimulable phosphor layer containing a stimulable phosphor is formed to accumulate. The stimulable phosphor layer is exposed by exposing it to the stimulable phosphor layer by exposing the stimulable phosphor layer to light by exposing the stimulable phosphor layer in close contact with the phosphor sheet. A macroarray analysis system using a radiolabeled substance has also been developed, which is used to generate biochemical analysis data by detecting it in order to analyze biogenic substances.

[0008]

However, in the macroarray analysis system, when a solution containing a specific binding substance is spotted on a carrier such as a membrane filter, the carrier itself has hygroscopicity. Therefore, the solution containing the spotted specific binding substance cannot permeate the inside of the carrier to form spot-shaped regions partitioned from each other as desired, and as a result, the biological substance labeled with the radiolabeled substance cannot be formed. The derived substance is selectively and specifically bound to a specific binding substance contained in the spot-like region by hybridization or the like,
When the stimulable phosphor layer containing the stimulable phosphor is brought into close contact with the stimulable phosphor sheet, and when the stimulable phosphor layer is exposed, a radioactive labeling substance contained in each spot-shaped region Since it is inevitable that the electron beams (β-rays) emitted from the mixture will be mixed and enter the region of the stimulable phosphor layer to be exposed by the radiolabel substance contained in the adjacent spot-shaped regions. , Irradiating the exposed photostimulable phosphor layer with excitation light and photoelectrically detecting the photostimulable light emitted from the photostimulable phosphor layer to generate biochemical analysis data. There was a problem that biochemical analysis data with excellent properties could not be generated.

Further, a specific binding substance is spotted at different positions on the surface of a carrier such as a membrane filter to form spot-like regions, and the specific binding substances contained in the plurality of spot-like regions are subjected to chemiluminescence. A substance of biological origin, which is labeled with a labeling substance or a fluorescent substance that produces chemiluminescence when brought into contact with a substrate, is specifically bound by hybridization or the like, selectively labeled, and contained in the spot-like region. Even when chemiluminescence emitted from a labeled substance or fluorescence emitted from a fluorescent substance is photoelectrically detected to generate data for biochemical analysis, spot-shaped regions partitioned from each other can be formed as desired. Since it cannot be formed, chemiluminescence or fluorescence emitted from adjacent spot-like regions are mixed, and therefore, There is a problem that can not be generated excellent biochemical analysis data on the amount of.

Therefore, according to the present invention, a specific binding substance capable of specifically binding to a substance of biological origin and having a known base sequence, base length, composition, etc. is spotted on a carrier,
The spot-like regions are formed on the carrier at a high density, and the specific binding substance contained in the spot-like regions is specifically bound to the substance of biological origin labeled with a radiolabeling substance to selectively label it. The unit for biochemical analysis obtained in this manner is brought into close contact with the stimulable phosphor layer, and the stimulable phosphor layer is exposed by a radioactive labeling substance, and the stimulable phosphor layer is irradiated with excitation light, Electrons emitted from radiolabeled substances contained in adjacent spot-shaped regions are also detected when photoelectrically detecting photostimulable light emitted from the photostimulable phosphor layer to generate biochemical analysis data. Of a specific binding substance that effectively prevents the mixing of radiation (β-rays), can specifically bind to a substance of biological origin, and has a known base sequence, base length, composition, etc. Spot on the carrier with high density. The specific binding substance contained in the spot-shaped region is specifically bound to a substance derived from a living body labeled with a labeling substance and / or a fluorescent substance that causes chemiluminescence by contacting with a chemiluminescent substrate. By selectively labeling, and photoelectrically detecting chemiluminescence and / or fluorescence emitted from the spot-like region,
Even when biochemical analysis data is generated, it is possible to effectively prevent mixing of chemiluminescence and / or fluorescence emitted from adjacent spot-like regions, and highly accurate biochemical analysis data. It is an object of the present invention to provide a spotting method and device capable of generating

[0011]

The object of the present invention is to:
A plurality of holes are formed in the substrate of the biochemical analysis unit having a property of attenuating radiation and / or light so as to be spaced apart from each other, and the absorptive regions formed in the plurality of holes are unique to the absorptive regions respectively formed. A spotting method for spotting a solution containing a specific binding substance, which comprises forcibly promoting the evaporation of the solution containing the specific binding substance spotted on the plurality of adsorptive regions. This is achieved by the spotting method.

According to the present invention, the absorptive region for spotting the solution containing the specific binding substance is formed in the plurality of holes formed in the substrate of the biochemical analysis unit so as to be separated from each other. Therefore, it is possible to effectively prevent the solution containing the spotted specific binding substance from reaching the adsorbing regions adjacent to each other. Therefore, the substance derived from the living body labeled with the radiolabeled substance can be hybridized, etc. The biochemical analysis unit selectively and specifically bound to the specific binding substance contained in the plurality of absorptive regions forms a stimulable phosphor layer containing a stimulable phosphor. When the photostimulable phosphor layer is exposed by being brought into close contact with the stimulable phosphor sheet, electron beams (β-rays) emitted from the radioactive labeling substance contained in each absorptive region are mixed,
The exposed stimulable phosphor can be effectively prevented from being incident on the region of the stimulable phosphor layer to be exposed by the radioactive labeling substance contained in the adjacent adsorptive region. By irradiating the layer with excitation light and photoelectrically detecting the photostimulable light emitted from the photostimulable phosphor layer, it becomes possible to generate biochemical analysis data with excellent quantitativeness.

Further, according to the present invention, the absorptive region for spotting the solution containing the specific binding substance is formed in the plurality of holes formed on the substrate of the biochemical analysis unit so as to be separated from each other. Therefore, the solution containing the spotted specific binding substance can be effectively prevented from reaching the adsorbing regions adjacent to each other, and thus the specific binding substance contained in the plurality of adsorbing regions can be A substance of biological origin labeled with a labeling substance or a fluorescent substance that produces chemiluminescence when brought into contact with a chemiluminescent substrate is specifically bound by hybridization or the like, and selectively labeled to form an adsorptive region. If the chemiluminescence emitted from the contained labeling substance or the fluorescence emitted from the fluorescent substance is photoelectrically detected to generate biochemical analysis data, they are adjacent to each other. Since it is possible to effectively prevent the chemiluminescence or fluorescence emitted from the adsorptive region from being mixed, it is possible to quantitatively detect the chemiluminescence or fluorescence emitted from the adsorptive region by photoelectric detection. It becomes possible to generate excellent biochemical analysis data.

Further, according to the present invention, the substrate of the biochemical analysis unit is formed of a material having a property of attenuating radiation, so that the electron beam emitted from the radiolabeled substance contained in each adsorptive region is formed. It is possible to effectively prevent the (β-rays) from being scattered in the substrate, and therefore, the electron beams (β-rays) emitted from the radio-labeled substances contained in each adsorptive region are mixed with each other and are adjacent to each other. The exposed stimulable phosphor layer can be effectively prevented from being incident on the region of the stimulable phosphor layer to be exposed by the radiolabeled substance contained in the adsorbing region that fits. It is possible to generate biochemical analysis data with excellent quantification by irradiating the stimulative light on the photosensitizer and photoelectrically detecting the photostimulable light emitted from the stimulable phosphor layer.

Further, according to the present invention, by forming the substrate of the biochemical analysis unit with a material having a property of attenuating light, chemiluminescence or fluorescence emitted from each adsorptive region is scattered within the substrate. Can be effectively prevented, and therefore chemiluminescence or fluorescence emitted from each adsorptive region can be effectively prevented from being mixed with chemiluminescence or fluorescence emitted from the adjacent adsorptive regions. Therefore, it is possible to generate biochemical analysis data having excellent quantitativeness by photoelectrically detecting chemiluminescence or fluorescence emitted from the adsorptive region.

Further, according to the present invention, the solution containing the specific binding substance is configured to be forcedly promoted to evaporate the solution containing the specific binding substance spotted on the plurality of adsorptive regions. The solution containing the specific binding substance spotted in the adsorptive region permeates into the adsorptive region by forcibly promoting the evaporation of the solution containing the specific binding substance on the side opposite to the spotted side. It is possible to effectively prevent the specific binding substance from being adsorbed within a predetermined range from the surface of the spotted adsorptive region, and thus, the specific binding substance can be labeled with the radiolabeling substance. A biochemical analysis unit in which a substance derived from a living body is selectively and specifically bound to a specific binding substance contained in a plurality of absorptive regions by hybridization or the like, When the stimulable phosphor layer is exposed by contacting it with the stimulable phosphor sheet on which the stimulable phosphor layer containing the stimulable phosphor is formed, an electron beam (β-ray) emits a stimulable phosphor layer. Since the electron beam (β-ray) emitted from only the area within a predetermined range from the surface of the absorptive area adjacent to the body layer can be effectively prevented from being absorbed by the substrate, The electron beam emitted from the contained radiolabeled substance (β
Line) allows the stimulable phosphor layer of the stimulable phosphor sheet to be exposed as desired, and allows the specific binding substance contained in the plurality of adsorptive regions to come into contact with the chemiluminescent substrate. A labeling substance contained in the adsorptive region by selectively binding to a substance of biological origin labeled with a labeling substance or a fluorescent substance that causes chemiluminescence by being specifically bound by hybridization. Chemoluminescence or fluorescence emitted from a fluorescent substance is detected photoelectrically to generate biochemical analysis data, the chemiluminescence or fluorescence is within a predetermined range from the surface of the adsorptive region. Chemiluminescence or fluorescence can be effectively prevented from being emitted from only the region and absorbed by the substrate, so that chemiluminescence or fluorescence can be detected photoelectrically with high sensitivity. Door becomes possible, therefore,
It becomes possible to generate highly quantitative biochemical analysis data.

Further, when a plurality of absorptive regions of the biochemical analysis unit are formed by press-fitting an absorptive film containing an absorptive material into a plurality of holes formed in the substrate, or when the substrate is a substrate. Is adhered to the absorptive substrate formed of the absorptive material and is formed by the absorptive substrate in the plurality of holes of the substrate, the absorptive material exists between the adjacent absorptive regions. In the case where the specific binding substance is included, the present invention is configured to forcibly promote evaporation of the solution containing the specific binding substance spotted on the plurality of adsorptive regions. By forcibly promoting the evaporation of the solution containing the specific binding substance on the side opposite to the side where the solution is spotted, the solution containing the specific binding substance spotted on the adsorptive region is separated from the adjacent adsorptive regions. Existing in between It can be effectively prevented from penetrating into the adsorptive material, and therefore, a substance of biological origin labeled with a radiolabeled substance can be specifically contained in a plurality of adsorptive regions by hybridization or the like. To the binding substance, selectively, the biochemical analysis unit that is specifically bound, is brought into close contact with the stimulable phosphor sheet on which the stimulable phosphor layer containing the stimulable phosphor is formed,
When exposing the photostimulable phosphor layer, the electron beams (β-rays) emitted from the radiolabeled substances contained in each adsorptive region are mixed, and the radiolabeled substances contained in the adjacent adsorptive regions are mixed. Since it becomes possible to effectively prevent the light from entering the region of the stimulable phosphor layer that is to be exposed, the exposed stimulable phosphor layer is irradiated with excitation light, and the stimulable fluorescent layer is exposed. By photoelectrically detecting the photostimulable light emitted from the body layer, it becomes possible to generate highly quantitative data for biochemical analysis, as well as specific binding contained in multiple absorptive regions. A substance of biological origin labeled with a labeling substance or a fluorescent substance that produces chemiluminescence by contacting a substance with a chemiluminescent substrate is specifically bound by hybridization or the like, selectively labeled, and adsorbed. In the sex area The chemiluminescence emitted from the labeled substance or the fluorescence emitted from the fluorescent substance is detected photoelectrically to generate data for biochemical analysis. Since it is possible to effectively prevent the fluorescence from mixing together, the chemiluminescence or fluorescence emitted from the adsorptive region is photoelectrically detected to generate highly quantitative biochemical analysis data. It becomes possible to do.

In a preferred embodiment of the present invention, a spotting head for spotting a solution containing a specific binding substance and the substrate of the biochemical analysis unit are provided.
A solution containing a specific binding substance is spotted from the spotting head while relatively moving in two dimensions.

In a preferred embodiment of the present invention, the plurality of absorptive regions on which the solution containing the specific binding substance is spotted are blown with air whose temperature and humidity are controlled, to thereby cause the plurality of absorptive regions to be adsorbed. It is configured to forcibly promote evaporation of the solution containing the specific binding substance spotted on.

[0021] In a further preferred aspect of the present invention, the plurality of absorptive regions on which the solution containing the specific binding substance is spotted have a temperature of 40 ° C or higher and a humidity of 50%.
The following air is blown to force the evaporation of the solution containing the specific binding substance spotted on the plurality of absorptive regions to be forcibly promoted.

[0021] In a further preferred aspect of the present invention, air is blown onto the plurality of absorptive regions on which the solution containing the specific binding substance is spotted at a rate of 0.1 m / sec to 10 m / sec. , Is configured to forcibly promote the evaporation of the solution containing the specific binding substance spotted on the plurality of adsorptive regions.

In a preferred embodiment of the present invention, the plurality of absorptive regions on which the solution containing the specific binding substance has been spotted are heated by infrared rays to cause the specific binding spots on the plurality of absorptive regions. It is configured to forcefully promote evaporation of the solution containing the substance.

In a further preferred aspect of the present invention, the plurality of absorptive regions on which the solution containing the specific binding substance is spotted are heated by infrared rays having a wavelength of 1 μm to 30 μm to obtain a plurality of the absorptive regions. It is configured to forcibly promote evaporation of the solution containing the specific binding substance spotted on.

In the case of heating by infrared rays to accelerate evaporation, efficient heating can be achieved by using radiation in the energy wavelength range that promotes interatomic motion of the heat receiver, that is, the infrared activity standard range. Since the vibration due to energy irradiation has a unique frequency depending on the molecular structure of the heat receiver, the optimal infrared frequency depends on the molecular structure of the heat receiver, but For evaporation, it is preferable to use an infrared source that emits infrared rays having a wavelength of 1 μm to 30 μm.

[0025] In a preferred embodiment of the present invention, the plurality of absorptive regions on which the solution containing the specific binding substance is spotted are heated by microwaves to be spotted on the plurality of absorptive regions. It is configured to forcibly promote the evaporation of the solution containing the chemically bound substance.

Also in the case of heating by microwaves to promote evaporation, in the same manner as in the case of heating by infrared rays to promote evaporation, the microwaves are heated in accordance with the natural frequency of the heat receiver. The wavelength can be determined.

In a preferred embodiment of the present invention, the plurality of absorptive regions on which the solution containing the specific binding substance is spotted are heated by a high frequency wave to cause the specific binding spots on the plurality of absorptive regions. It is configured to forcefully promote evaporation of the solution containing the substance.

A further preferred embodiment of the invention has a frequency of 2 to 20 megacycles, 800
To a high frequency having an electric field strength of 2000 V / cm,
A solution containing a specific binding substance spotted on the plurality of adsorptive regions is heated by outputting the output of 1 to 100 kW · hr to heat the plurality of adsorptive regions on which the solution containing the specific binding substance is spotted. Is configured to force the evaporation of the.

In a preferred embodiment of the present invention, the plurality of absorptive regions on which the solution containing a specific binding substance is spotted are brought into contact with a heating substrate whose temperature is controlled to heat the plurality of absorptive regions. It is configured to forcibly promote evaporation of the solution containing the specific binding substance spotted on the area.

The object of the present invention is also to provide a holding means for holding a biochemical analysis unit having a substrate in which a plurality of absorptive regions are formed apart from each other, and the raw material held by the holding means. At least one spotting head for spotting a solution containing a specific binding substance on the plurality of absorptive regions of the chemical analysis unit, and on the opposite side of the at least one spotting head with respect to the biochemical analysis unit. And a spotting device for a specific binding substance, comprising evaporation promoting means for forcibly promoting evaporation of a solution containing the specific binding substance spotted on the plurality of absorptive regions.

According to the present invention, the spotting device for the specific binding substance has a holding means for holding a biochemical analysis unit having a substrate in which a plurality of absorptive regions are formed apart from each other, and a holding means. At least one spotting head for spotting a solution containing a specific binding substance on a plurality of absorptive regions of the biochemical analysis unit held in the column, and at least one spotting head opposite to the biochemical analysis unit. On the side, since the evaporation promoting means for forcibly promoting the evaporation of the solution containing the specific binding substance spotted on the plurality of adsorptive regions is provided, the solution containing the specific binding substance is spotted by the evaporation promoting means. Specific spots on the adsorptive region by forcing the evaporation of the solution containing the specific binding substance on the opposite side The solution containing the binding substance is effectively prevented from penetrating inside the adsorptive region, and the specific binding substance is selectively introduced within a predetermined range from the surface of the spotted adsorptive region. Therefore, the substance of biological origin that can be adsorbed and is labeled with a radiolabeled substance is selectively and specifically bound to a specific binding substance contained in a plurality of adsorptive regions by hybridization or the like. The biochemical analysis unit is attached to the stimulable phosphor sheet containing the stimulable phosphor, and the stimulable phosphor layer is exposed to the electron beam ( Beta rays are emitted only from a region within a predetermined range from the surface of the absorptive region adjacent to the stimulable phosphor layer, and electron beams (β rays) are effectively prevented from being absorbed by the substrate. Can be included in the adsorptive area The stimulable phosphor layer of the stimulable phosphor sheet can be exposed as desired by the electron beam (β-ray) emitted from the radioactive labeling substance, and the stimulable phosphor layer can be contained in a plurality of absorptive regions. To the specific binding substance, a substance of biological origin labeled with a labeling substance or a fluorescent substance that produces chemiluminescence by contacting with a chemiluminescent substrate is specifically bound by hybridization or the like, and selectively. When chemiluminescence emitted from the labeling substance contained in the adsorptive region or fluorescence emitted from the fluorescent substance is photoelectrically detected to generate biochemical analysis data, the chemiluminescence or fluorescence is Since it is possible to effectively prevent chemiluminescence or fluorescence from being absorbed by the substrate, which is released only from a region within a predetermined range from the surface of the adsorptive region, high sensitivity and Scientific luminescence or fluorescence can be detected photoelectrically, and thus highly quantitative biochemical analysis data can be generated.

Furthermore, when a plurality of absorptive regions of the biochemical analysis unit are formed by press-fitting an absorptive film containing an absorptive material into a plurality of holes formed in the substrate, or when the substrate is a substrate. Is adhered to the absorptive substrate formed of the absorptive material and is formed by the absorptive substrate in the plurality of holes of the substrate, the absorptive material exists between the adjacent absorptive regions. In this case, according to the present invention, the evaporation promoting means can forcibly promote the evaporation of the solution containing the specific binding substance spotted on the plurality of adsorptive regions. The solution containing the specific binding substance on the side opposite to the side where the solution containing It is possible to effectively prevent the permeation into the adsorptive material existing between the regions, and therefore, the substance of biological origin labeled with the radiolabeled substance is transferred to the multiple adsorptive regions by hybridization or the like. The biochemical analysis unit selectively and specifically bound to the contained specific binding substance is adhered to the stimulable phosphor sheet on which the stimulable phosphor layer containing the stimulable phosphor is formed. Then, when exposing the stimulable phosphor layer, the electron beams (β-rays) emitted from the radiolabeled substance contained in each adsorptive region were mixed and included in the adjacent adsorptive regions. Since it becomes possible to effectively prevent the radioactive labeling substance from entering the region of the stimulable phosphor layer to be exposed, the exposed stimulable phosphor layer is irradiated with excitation light to emit light. Bright emission from the photostimulable phosphor layer It is possible to generate biochemical analysis data with excellent quantification by photosensitivity detection, and to contact the chemiluminescent substrate with specific binding substances contained in multiple adsorptive regions. A substance of biological origin labeled with a labeling substance or a fluorescent substance that causes chemiluminescence by
It is specifically bound by hybridization or the like and selectively labeled, and the chemiluminescence emitted from the labeling substance contained in the adsorptive region or the fluorescence emitted from the fluorescent substance is photoelectrically detected to produce When generating data for chemical analysis, it is possible to effectively prevent the chemiluminescence or fluorescence emitted from adjacent adsorbing regions from being mixed with each other. Therefore, chemiluminescence emitted from the adsorbing regions can be effectively prevented. Alternatively, by photoelectrically detecting fluorescence, it becomes possible to generate biochemical analysis data with excellent quantitativeness.

In a preferred embodiment of the present invention, the spotting device for specific binding substances comprises one spotting head, and the spotting head and the substrate of the biochemical analysis unit are two-dimensionally relative to each other. From the spotting head while moving the
A solution containing a specific binding substance is spotted on the plurality of absorptive regions.

In a preferred embodiment of the present invention, the spotting device for the specific binding substance further comprises a scanning mechanism for moving the holding means two-dimensionally with respect to the spotting head.

[0035] In a preferred aspect of the present invention, the spotting device for the specific binding substance has a plurality of spots arranged in the same pattern as the plurality of absorptive regions formed on the substrate of the biochemical analysis unit. Equipped with a spotting head.

In a preferred embodiment of the present invention, the spotting head comprises an ink jet injector for ejecting a solution containing a specific binding substance.

In another preferred embodiment of the present invention, the spotting head comprises a dropping pin for dropping a solution containing a specific binding substance.

[0038] In a preferred aspect of the present invention, the evaporation promoting means injects temperature and humidity controlled air toward the plurality of absorptive regions on which the solution containing the specific binding substance is spotted. It is composed of air injection means.

[0039] In a further preferred aspect of the present invention, the air injecting means is configured to inject air having a temperature of 40 ° C or higher and a humidity of 50% or lower.

[0040] In a further preferred aspect of the present invention, the air injecting means is 0.1 m / sec to 10 m / sec.
It is configured to inject air at a rate of seconds.

In a preferred embodiment of the present invention, the evaporation promoting means is constituted by an infrared source which emits infrared rays.

[0042] In a further preferred aspect of the present invention, the infrared source is configured to emit infrared light having a wavelength of 1 µm to 30 µm.

In a preferred embodiment of the present invention, the evaporation promoting means is constituted by a microwave heating means.

In a preferred embodiment of the present invention, the evaporation promoting means is constituted by high frequency heating means.

In a further preferred aspect of the present invention, the high frequency heating means outputs a high frequency having a frequency of 2 to 20 megacycles and an electric field strength of 800 to 2000 V / cm, and a power of 1 to 100 kW · hr. It is configured to output with.

[0046] In a preferred aspect of the present invention, the evaporation promoting means is constituted by a heating substrate which is contactable with the biochemical analysis unit held by the holding means and whose temperature is controlled.

In a preferred aspect of the present invention, the plurality of absorptive regions are formed by filling an absorptive material into the plurality of holes formed in the substrate.

[0048] In a further preferred aspect of the present invention, each of the plurality of holes formed in the substrate is:
It is composed of a through hole.

In another preferred embodiment of the present invention, each of the plurality of holes formed in the substrate is
It is composed of a recess.

[0050] In a further preferred aspect of the present invention, each of the plurality of holes formed in the substrate is:
The plurality of absorptive regions are formed by through holes, and an absorptive film containing an absorptive material is press-fitted into the plurality of through holes formed in the substrate.

[0051] In a preferred aspect of the present invention, the biochemical analysis unit includes an absorptive substrate formed of an absorptive material, and the substrate is brought into close contact with the absorptive substrate to form the aforesaid substrate. The absorptive region of the biochemical analysis unit is formed by the absorptive substrate in the plurality of holes.

In a further preferred aspect of the present invention, the substrate is adhered to both surfaces of the absorptive substrate.

According to a further preferred embodiment of the present invention, since the substrates are adhered to both sides of the absorptive substrate,
The strength of the biochemical analysis unit is improved, and the biochemical analysis unit can be easily handled.

In a preferred aspect of the present invention, the substrate of the biochemical analysis unit is exposed to radiation and / or a distance equal to the distance between the adsorbing regions adjacent to each other.
Alternatively, it has a property of attenuating the energy of radiation and / or energy to 1/5 or less when light passes through the substrate.

[0055] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is arranged such that radiation and / or light penetrates through the substrate by a distance equal to a distance between the adjacent absorptive regions. In doing so, it has the property of attenuating radiation and / or energy to 1/10 or less.

[0056] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is arranged such that radiation and / or light penetrates through the substrate by a distance equal to a distance between the adjacent absorptive regions. In doing so, it has the property of attenuating radiation and / or energy to 1/50 or less.

In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit transmits radiation and / or light through the substrate by a distance equal to the distance between the adjacent absorptive regions. In doing so, it has a property of attenuating the radiation and / or the energy to 1/100 or less.

In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is arranged such that radiation and / or light is transmitted through the substrate by a distance equal to a distance between adjacent absorptive regions. In doing so, it has the property of attenuating radiation and / or energy to 1/500 or less.

[0059] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is arranged such that radiation and / or light penetrates through the substrate by a distance equal to a distance between the adjacent absorptive regions. In doing so, it has the property of attenuating radiation and / or energy to 1/1000 or less.

In the present invention, the material for forming the substrate of the biochemical analysis unit is not particularly limited as long as it has a property of attenuating radiation and / or light, and an inorganic compound Both materials and organic compound materials can be used, but metal materials, ceramic materials or plastic materials are preferably used.

In the present invention, inorganic compound materials that can be preferably used for forming the substrate of the biochemical analysis unit include, for example, gold, silver, copper, zinc,
Metals such as aluminum, titanium, tantalum, chromium, iron, 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. Metal oxides such as aluminum oxide, magnesium oxide and zirconium oxide; inorganic salts such as tungsten carbide, calcium carbonate, calcium sulfate, hydroxyapatite and gallium arsenide. 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 the organic compound material that can be preferably used for forming the substrate of the biochemical analysis unit, and a polymer compound that can be preferably used is, for example, Polyolefins such as polyethylene and 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.

Generally, the higher the specific gravity is, the higher the radiation attenuating ability is. Therefore, the substrate of the biochemical analysis unit is preferably made of a compound material or a composite material having a specific gravity of 1.0 g / cm ³ or more, Specific gravity is 1.5g / c
It is particularly preferable that it is formed of a compound material or a composite material of m ³ or more and 23 g / cm ³ or less.

Generally, the greater the light scattering and / or absorption, the higher the light attenuating ability. Therefore, the substrate of the biochemical analysis unit should have an absorbance of 0.3 or more per cm of thickness. Is preferable, and it is more preferable if the absorbance per 1 cm of thickness is 1 or more. Here, for the absorbance, an integrating sphere is placed immediately after the plate body having a thickness of Tcm,
The transmitted light amount A at the wavelength of the probe light or the emission light used for measurement is measured by a spectrophotometer, and A /
It is obtained by calculating T. In the present invention, in order to improve the light attenuating ability, a light scatterer or a light absorber may be contained in the substrate of the biochemical analysis unit. As the light scatterer, fine particles of a material different from the material forming the substrate of the biochemical analysis unit are used,
A pigment or dye is used as the light absorber.

In a preferred aspect of the present invention, the plurality of absorptive regions are regularly formed on the substrate of the biochemical analysis unit.

In a preferred aspect of the present invention, each of the plurality of absorptive regions is formed in a substantially circular shape.

[0067] In another preferred aspect of the present invention, each of the plurality of absorptive regions of the biochemical analysis unit is formed in a substantially rectangular shape.

In a preferred aspect of the present invention, 10 or more absorptive regions are formed on the substrate of the biochemical analysis unit.

[0069] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is formed with 50 or more absorptive regions.

[0070] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is formed with 100 or more absorptive regions.

In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is formed with 500 or more absorptive regions.

In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is provided with 1000
The above-mentioned absorptive region is formed.

In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is provided with 5000
The above-mentioned absorptive region is formed.

[0074] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is provided with 1000
Zero or more absorptive regions are formed.

[0075] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is provided with 5000
Zero or more absorptive regions are formed.

In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is provided with 1000
00 or more absorptive regions are formed.

[0077] In a preferred aspect of the present invention, the absorptive region of the biochemical analysis unit has a size of less than 5 mm 2.

[0078] In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is 1 or more.
It has a size of less than a square millimeter.

In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is:
It has a size of less than 0.5 mm 2.

[0080] In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is:
It has a size of less than 0.1 mm 2.

In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is:
It has a size of less than 0.05 mm 2.

[0082] In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is:
It has a size of less than 0.01 mm 2.

In the present invention, the density of the absorptive region formed on the substrate of the biochemical analysis unit is determined by the material of the substrate, the thickness of the substrate and the type of electron beam emitted from the radiolabeled substance or the fluorescent substance. It is determined according to the wavelength of the fluorescent light emitted.

[0084] In a preferred aspect of the present invention, the number of the absorptive regions of the biochemical analysis unit is 10 /
The substrate is formed with a density of not less than square centimeter.

[0085] In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is 5 or more.
It is formed on the substrate with a density of 0 pieces / square centimeter or more.

In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is 1
It is formed on the substrate with a density of 00 pieces / square centimeter or more.

In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is 5 or more.
It is formed on the substrate with a density of 00 pieces / square centimeter or more.

In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is 1
It is formed on the substrate at a density of 000 pieces / square centimeter or more.

In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is 5
It is formed on the substrate at a density of 000 pieces / square centimeter or more.

In a further preferred aspect of the present invention, the absorptive region of the biochemical analysis unit is 1
It is formed on the substrate at a density of 0000 pieces / square centimeter or more.

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

In the present invention, the porous material used for forming the adsorptive region 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 is not particularly limited, but a carbon porous material such as activated carbon or a porous material capable of forming a membrane filter. Are preferably used. As the porous material capable of forming the membrane filter, 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 acids such as alginic acid / polylysine polyion complex; polyolefins such as polyethylene and polypropylene; polyvinyl chloride; polyvinylidene chloride; polyfluoride such as polyvinylidene fluoride and polytetrafluoride; and copolymers or composites thereof. Can be mentioned.

In the present invention, the inorganic porous material used to form the adsorptive region is not particularly limited, but preferably, for example, platinum, gold, iron,
Examples thereof include metals such as silver, nickel and aluminum; metal oxides such as alumina, silica, titania and zeolite; metal salts such as hydroxyapatite and calcium sulfate, and complexes thereof.

In the present invention, the fiber material used for forming the adsorptive region is not particularly limited, but preferably, for example, nylon 6, nylon 6,6, nylon 4,10, etc. Examples include nylons, cellulose derivatives such as nitrocellulose, cellulose acetate, and cellulose acetate butyrate.

In the present invention, the adsorptive region is subjected to an electrolytic treatment, a plasma treatment, an oxidation treatment such as an arc discharge; a primer treatment using a silane coupling agent, a titanium coupling agent or the like; a surface treatment such as a surfactant treatment. It can also be formed.

[0097]

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 in which a solution containing a specific binding substance is spotted by the spotting method of the specific binding substance according to a preferred embodiment of the present invention.

As shown in FIG. 1, the biochemical analysis unit 1 according to the present embodiment is a substrate formed of flexible aluminum and having a large number of substantially circular through holes 3 formed at a high density. Nylon 6 is filled inside the large number of through holes 3 to form the absorptive region 4.

Although not shown exactly in FIG. 1, in the present embodiment, there are about 5,000 through holes 3 having a size of about 10,000 square millimeters of about 10,000.
It is regularly formed on the substrate 2 with a density of square centimeters.

FIG. 2 is a schematic vertical sectional view of a spotting device according to a preferred embodiment of the present invention.

As shown in FIG. 2, the spotting device according to this embodiment comprises a frame 5 holding the biochemical analysis unit 1 and an injector 6 for injecting a solution containing a specific binding substance such as cDNA. Further, the spotting head 7 and an air jetting device 8 which is arranged on the opposite side of the frame 5 from the spotting head 7 and jets air whose temperature and humidity are controlled are provided.

In the present embodiment, the air whose temperature is 40 ° C. or higher and whose humidity is controlled to 50% or lower is 0.1 m / min.
It is configured to be jetted from the air jetting device 8 at a speed of 2 to 10 m / sec.

As shown in FIG. 2, in the injector 6 of the spotting head 7 and the air injection device 8, the tip of the injector 6 and the air injection port of the air injection device 8 face each other via the frame 5. Is fixed as.

The frame 5 is for biochemical analysis held by the frame 5 in a main scanning direction indicated by an arrow X in FIG. 2 and a sub-scanning direction orthogonal to the main scanning direction by a scanning mechanism (not shown). The unit 1 is configured to be intermittently movable at a pitch equal to the distance between the adsorbing regions 4 adjacent to each other.

FIG. 3 is a block diagram showing a control system, a detection system, a drive system and an input system of the spotting device according to the preferred embodiment of the present invention.

As shown in FIG. 3, the control system of the spotting device according to the present embodiment includes a control unit 10 for controlling the operation of the entire spotting device, and the detection system of the spotting device has a main scanning direction and a sub-scanning direction. A position detecting means 11 for detecting the position of the frame 5 in the direction is provided. As the position detecting means 11,
A linear encoder or the like is used.

As shown in FIG. 3, the drive system of the spotting device according to the present embodiment is a main scanning pulse motor for moving the injector 6 of the spotting head 7, the air jetting device 8 and the frame 5 in the main scanning direction. 12
And a sub-scanning pulse motor 13 for moving the frame 5 in the sub-scanning direction, and an input system of the spotting device has a keyboard 14 for inputting various signals and data.

The spotting device according to the present embodiment having the above-described structure has the absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1 as follows.
Then, a solution containing a specific binding substance is spotted.

First, the operator sets the biochemical analysis unit 1 on the frame 5.

Next, by the operator, the keyboard 13 is used for data on the pattern of the large number of absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1, that is, the distance between the adjacent absorptive regions 4 is 1 Data such as the number of absorptive areas 4 included in a row and the number of rows of the absorptive area 4 are input, and a start signal is input.

The data input to the keyboard 13 and the start signal are output to the control unit 10, and the control unit 10 stores the input data in a memory (not shown), and according to the input data, Required to move the frame 5 in the main scanning direction until the first absorptive region 4 of the biochemical analysis unit 1 set on the frame 5 reaches a position facing the injector 6 and the air injection device 8. The initial drive pulse is calculated and the frame 5 is
The drive pulse required to move in the main scanning direction by the distance between the adsorbing regions 4 adjacent to each other in the biochemical analysis unit 1 set in the frame 5 is calculated, and then the main scanning pulse motor 12 is initially driven. A drive signal is output together with the pulse.

When receiving the drive signal and the initial drive pulse,
The main scanning pulse motor 12 moves the frame in the main scanning direction according to the initial drive pulse.

Based on the position detection signal input from the position detection means 11, the first absorptive region 4 of the biochemical analysis unit 1 set in the frame 5 is moved to the injector 6
When it is determined that the position has reached the position facing the air injection device 8, the control unit 10 outputs a drive signal to the injector 6.

As a result, the solution containing the specific binding substance is jetted from the injector 6 toward the first absorptive region 4 of the biochemical analysis unit 1 set in the frame 5.

After outputting the drive signal to the injector 6, the control unit 10 outputs the drive signal to the air injection device 8 at a predetermined timing.

As a result, the temperature is 4
Air whose humidity is controlled to 50% or less at 0 ° C or higher,
Toward the surface opposite to the surface on which the solution containing the specific binding substance of the first adsorptive region 4 of the biochemical analysis unit 1 is spotted at a speed of 0.1 m / sec to 10 m / sec, Is jetted.

FIG. 4 is a schematic enlarged sectional view showing the absorptive region 4 of the biochemical analysis unit 1 on which the solution containing the specific binding substance is spotted from the injector 6 of the spotting head 7.

As shown in FIG. 4, the solution 6a containing the specific binding substance spotted from the injector 6 penetrates into the first adsorptive region formed by the nylon 6 having adsorptivity. On the surface of the first adsorptive region 4 on the opposite side of the formed surface, from the air injection device 8,
Since the air 8a whose temperature is 40 ° C. or higher and whose humidity is controlled to 50% or less is blown, the solution 6a containing the specific binding substance is prevented from permeating, and the specific binding substance is separated from the spotted surface by a predetermined amount. It is selectively adsorbed in the area of the range.

When a solution containing a specific binding substance is spotted on the first adsorptive region 4 of the biochemical analysis unit 1 set on the frame 5, the control unit 11
To the main scanning pulse motor 12 together with the drive pulse,
Output drive signal.

As a result, the first biochemical analysis unit 1
The frame 5 is moved until the second absorptive region 4 adjacent to the absorptive region 4 reaches a position facing the injector 6 and the air injecting device 8.
When reaching a position facing the injector 6 and the air injection device 8, the solution 6a containing the specific binding substance is spotted on the first adsorptive region 4, in exactly the same manner,
From the injector 6, a solution 6a containing a specific binding substance
Is ejected toward the second adsorptive region 4 of the biochemical analysis unit 1, and thereafter, the air 8a is ejected from the air ejecting device 8 at a predetermined timing.

Similarly, when the solution 6a containing the specific binding substance is spotted on the large number of absorptive regions 4 forming one row, the control unit 10 outputs a drive signal to the main scanning pulse motor 12. Then, after returning the frame 5 to the original position, for the biochemical analysis based on the data on the pattern of the large number of absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1 stored in the memory. The drive pulse required to move the frame 5 in the sub-scanning direction by the distance between the rows of the adsorbing regions 4 adjacent to each other formed in the unit 1 is calculated, and the sub-scanning pulse motor 13 outputs the drive pulse together with the drive pulse. , Output the drive signal, in the sub-scanning direction,
The frame 5 is moved by the distance between the rows of the adjacent absorptive regions 4 formed in the biochemical analysis unit 1.

The control unit 10 includes the main scanning pulse motor 12, the injector 6 and the air injection device 8 in exactly the same manner as spotting the solution 6a containing the specific binding substance on the absorptive region 4 in the first row. By controlling, the solution 6a containing the specific binding substance is spotted on the absorptive region 4 of the second row of the biochemical analysis unit 1.

The solution 6a containing the specific binding substance was spotted on the absorptive regions 4 in the first and second rows of the biochemical analysis unit 1 in exactly the same manner as in the frame 5
The solution 6a containing the specific binding substance is spotted on all the absorptive regions 4 of the biochemical analysis unit 1 set to.

In this way, when the solution 6a containing the specific binding substance is spotted on all the absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1, a large number of adsorptions of the biochemical analysis unit 1 are carried out. In the specific binding substance contained in the sex region 4, the substance derived from the living body labeled with the labeling substance is
Optionally hybridized.

FIG. 5 is a schematic vertical sectional view of the hybridization container.

As shown in FIG. 5, the hybridization container 15 has a rectangular cross section, and contains a hybridization solution 16 containing a substance derived from a living body which is a probe labeled with a labeling substance. .

In the case of selectively labeling a specific binding substance such as cDNA with a radiolabeling substance, a hybridization solution 16 containing a substance derived from a living body which is a probe labeled with the radiolabeling substance is prepared,
It is housed in the hybridization container 15.

On the other hand, by using a labeling substance that produces chemiluminescence by contacting with a chemiluminescent substrate, the cDNA is
In the case of selectively labeling a specific binding substance such as, a hybridization solution 16 containing a substance derived from a living body, which is a probe labeled with a labeling substance that causes chemiluminescence by contacting with a chemiluminescent substrate, is prepared. And is housed in the hybridization container 15.

Furthermore, in the case of selectively labeling a specific binding substance such as cDNA with a fluorescent substance such as a fluorescent dye, a high-molecular substance containing a probe which is a probe labeled with a fluorescent substance such as a fluorescent dye is used. A hybridization solution 16 is prepared and housed in the hybridization container 15.

[0131] A substance derived from a living body labeled with a radioactive labeling substance, a substance derived from a living body labeled with a labeling substance that causes chemiluminescence when brought into contact with a chemiluminescent substrate, and a living body labeled with a fluorescent substance such as a fluorescent dye It is also possible to prepare a hybridization solution 16 containing two or more kinds of substances derived from a living body among the substances derived from the living body and store the hybridization solution 16 in the hybridization container 15. In the present embodiment, the hybridization solution 16 is labeled with a radioactive labeling substance. A hybridization solution 16 containing a biogenic substance and a biogenic substance labeled with a fluorescent substance is prepared and housed in a hybridization container 15.

For hybridization, cD
The biochemical analysis unit 1 in which a specific binding substance such as NA is adsorbed on a large number of absorptive regions 4 is inserted into the hybridization container 15.

As a result, the specific binding substance adsorbed on the large number of adsorptive regions 4 is selectively separated from the biologically-derived substance labeled with the radioactive labeling substance and the biologically-derived substance labeled with the fluorescent substance. , Hybridized.

In this way, the radiation data of the radioactive labeling substance as the labeling substance and the fluorescence data of the fluorescent substance are recorded in a large number of absorptive regions 4 of the biochemical analysis unit 1.
The fluorescence data recorded in the absorptive region 4 is read by a scanner described later, and biochemical analysis data is generated.

On the other hand, the radiation data of the radiolabeled substance is
The radiation data transferred to the stimulable phosphor sheet and transferred to the stimulable phosphor sheet is read by a scanner described later to generate biochemical analysis data.

FIG. 6 is a schematic perspective view of the stimulable phosphor sheet.

As shown in FIG. 6, the stimulable phosphor sheet 17 is provided with a nickel support 19 in which a large number of substantially circular through holes 18 are regularly formed, and is formed on the support 19. A stimulable phosphor is embedded in the large number of through holes 18, and a large number of stimulable phosphor layer regions 20 are formed in a dot shape.

The large number of through holes 18 are formed in the support 19 in the same pattern as the large number of absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1, and each stimulable phosphor layer region. 20 is formed to have the same size as the absorptive region 4 formed on the substrate 2 of the biochemical analysis unit 1.

Therefore, although not shown exactly in FIG. 6, there is about 5 of the substantially circular stimulable phosphor layer region 20 having a size of about 0.01 square millimeter of about 10,000.
The support 19 of the stimulable phosphor sheet 17 has a density of 000 / square centimeter and the same regular pattern as the large number of absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1, It is formed in a dot shape.

In the present embodiment, the support 19
Surface and dot-shaped stimulable phosphor layer region 2
Support 19 so that the surface of 0 is located at the same height.
The stimulable phosphor is embedded in the through-hole 18 formed in 1. to form the stimulable phosphor sheet 17.

FIG. 7 shows a large number of dot-shaped stimulants formed on the stimulable phosphor sheet 17 by the radioactive labeling substance contained in the large number of absorptive regions 4 formed in the biochemical analysis unit 1. FIG. 6 is a schematic cross-sectional view showing a method of exposing the phosphor layer region 20.

As shown in FIG. 7, upon exposure,
The numerous absorptive regions 4 formed in the biochemical analysis unit 1 face the many dot-shaped stimulable phosphor layer regions 20 formed on the support 19 of the stimulable phosphor sheet 17. The stimulable phosphor sheet 17 and the biochemical analysis unit 1 are superposed.

In this embodiment, the biochemical analysis unit 1 is formed by filling nylon 6 into a large number of through holes 3 formed in the aluminum substrate 2, so that hybridization etc. Even when it is treated with a liquid, it hardly expands or contracts. Therefore, the large number of absorptive regions 4 formed in the biochemical analysis unit 1 are formed in a large number of dot shapes formed in the stimulable phosphor sheet 17. The stimulable phosphor layer region 20 of the above is easily and surely overlapped with the stimulable phosphor sheet 17 and the biochemical analysis unit 1 so as to exactly face each other, and the dot-shaped stimulable phosphor is formed. It is possible to expose the layer region 20.

Thus, over a predetermined time, each of a large number of dot-shaped stimulable phosphor layer regions 20 formed on the stimulable phosphor sheet 17 and a large number of adsorption formed on the biochemical analysis unit 1. By facing the absorptive region 4, a large number of dot-shaped stimulable phosphor layer regions 20 formed on the stimulable phosphor sheet 17 are exposed by the radioactive labeling substance contained in the absorptive region 4.

At this time, an electron beam is emitted from the radioactive labeling substance adsorbed on the adsorbing region 4, but the adsorbing region 4 of the biochemical analysis unit 1 is separated from the substrate 2 formed of aluminum. Aluminum which has a property of attenuating radiation is formed around each of the absorptive regions 4 in the form of dots, and further, a large number of dots of the stimulable phosphor sheet 17 are stimulable. A phosphor layer region 20 is formed by embedding a stimulable phosphor in a plurality of through holes 18 formed in a nickel support 19 having a property of attenuating radiation, and each stimulable phosphor is formed. Since the support 19 made of nickel having a property of attenuating the radiation exists around the layer region 20, the electron beam emitted from the radiolabel substance contained in the adsorptive region 4 is scattered. Therefore, all the electron beams emitted from the radiolabeled substance contained in the adsorptive region 4 enter the stimulable phosphor layer region 20 facing the adsorptive region 4. Thus, it is possible to reliably prevent the light from entering the stimulable phosphor layer region 20 to be exposed by the electron beam emitted from the adsorbing regions 4 adjacent to each other.

Furthermore, in this embodiment, the cDNA
A specific binding substance such as is selectively adsorbed in a region within a predetermined range from the surface of each adsorptive region 4 of the biochemical analysis unit 1, so that the radiolabeled substance is also incorporated in the biochemical analysis unit. 1 exists in a region within a predetermined range from the surface of each absorptive region 4, and therefore the electron beam (β-ray) has a predetermined amount from the surface of the absorptive region 4 adjacent to the stimulable phosphor layer region 20. A part of the electron beam (β-ray) is emitted from only the region within the range and the electron beam (β-ray) is emitted from the deep portion of the adsorptive region 4, and the biochemical analysis unit 1
The photostimulable phosphor layer region 20 is absorbed by the substrate 2 or the like.
Since it can be effectively prevented from being incident on the stimulable fluorescent substance, the stimulable phosphor is generated by the electron beam (β-ray) emitted from the radiolabeled substance contained in the adsorptive region 4 of the biochemical analysis unit 1. Photostimulable phosphor layer region 2 of sheet 17
It is possible to expose 0 as desired.

In this way, the radiation data of the radiolabeled substance is recorded in the large number of dot-shaped stimulable phosphor layer regions 20 formed on the support 19 of the stimulable phosphor sheet 17.

FIG. 8 shows radiation data of radiolabeled substances recorded in a large number of dot-shaped stimulable phosphor layer regions 20 formed on the stimulable phosphor sheet 17, and a large number of units of the biochemical analysis unit 1. FIG. 9 is a schematic perspective view of a scanner according to a preferred embodiment of the present invention, which reads fluorescence data such as a fluorescent dye recorded in the absorptive region 4 to generate biochemical analysis data. 2 is a schematic perspective view showing details of the scanner of FIG.

The scanner according to this embodiment is a unit for radiation data and biochemical analysis of radiolabeled substances recorded in a large number of dot-shaped stimulable phosphor layer regions 20 formed on the stimulable phosphor sheet 17. It is configured to be able to read fluorescence data such as a fluorescent dye recorded in a large number of absorptive regions 4 of one laser beam 24 having a wavelength of 640 nm.
And a second laser excitation light source 22 for emitting a laser light 24 having a wavelength of 532 nm.
And a third laser excitation light source 23 that emits laser light 24 having a wavelength of 473 nm.

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 22 and the 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. First
In the optical path of the laser light 24 emitted from the laser excitation light source 21 and reflected by the mirror 26, the first dichroic mirror 27 that transmits the laser light 4 of 640 nm and reflects the light of 532 nm wavelength and the 532 nm or longer A second dichroic mirror 28 that transmits light of a wavelength and reflects light of a wavelength of 473 nm is provided.
Laser light 24 generated by the laser excitation light source 21 of
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, it is reflected by the first dichroic mirror 27, its direction is changed by 90 degrees, and
The light passes through the dichroic mirror 28 and enters 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 the second dichroic mirror 2 is used.
After being reflected by 8 and changing its direction by 90 degrees,
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.

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 light 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 17 placed on 41 or the biochemical analysis unit 1.

A laser beam 24 is applied to the stimulable phosphor sheet 17.
Is incident, a large number of dot-shaped photostimulable phosphor layer regions 20 formed on the support 19 of the stimulable phosphor sheet 17 are excited to emit photostimulable light 45, and the biochemical analysis unit is also used. When the laser light 24 is incident on 1, the fluorescent substance such as the fluorescent dye contained in the large number of the absorptive regions 4 is excited, and the fluorescence 45 is emitted.

Photostimulable light 45 emitted from a large number of dot-shaped stimulable phosphor layer regions 20 of the stimulable phosphor sheet 17 or fluorescence emitted from a large number of absorptive regions 4 of the biochemical analysis unit 1. 45 is condensed on a mirror 36 by an aspherical lens 37 provided in the optical head 35, reflected on the same side as the optical path of the laser beam 24 by the mirror 36, becomes parallel light, and is reflected by a concave mirror 38. Incident.

The photostimulable light 45 or the fluorescent light 45 incident on 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 and enters 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. 9, 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. 8 by a motor (not shown).

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

As shown in FIG. 10, the filter member 5
1a includes a filter 52a, and the filter 52a includes a first
Is a filter member used when exciting a fluorescent substance contained in a large number of absorptive regions 4 formed in the biochemical analysis unit 1 by using the laser excitation light source 21 of FIG. Cut the light of 640 nm wavelength,
It has a property of transmitting light having a wavelength longer than 640 nm.

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

As shown in FIG. 11, the filter member 5
1b includes a filter 52b, and the filter 52b includes a second
Is a filter member used when exciting a fluorescent substance contained in a large number of absorptive regions 4 formed in the biochemical analysis unit 1 by using the laser excitation light source 22 and reading the fluorescence 45. Cuts light with a wavelength of 532 nm,
It has a property of transmitting light having a wavelength longer than 532 nm.

FIG. 12 is a sectional view taken along the line CC of FIG.

As shown in FIG. 12, the filter member 5
1c includes a filter 52c, and the filter 52c includes a third filter 52c.
Is a filter member used when the fluorescent substance contained in the large number of absorptive regions 4 formed in the biochemical analysis unit 1 is excited by using the laser excitation light source 23 of FIG. , 473 nm is cut off, and light with a wavelength longer than 473 nm is transmitted.

FIG. 13 is a sectional view taken along the line DD of FIG.

As shown in FIG. 13, 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
7. A large number of dot-shaped stimulable phosphor layer regions 2 formed in 7
It is a filter used when 0 is excited to read the photostimulable light 45 emitted from the photostimulable phosphor layer region 20, and the photostimulable light 45 emitted from the photostimulable phosphor layer region 20.
Has a property of transmitting only the light in the wavelength range of, 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. 8, the optical head 35 is configured to be movable in the main scanning direction indicated by arrow X and the sub-scanning direction indicated by arrow Y in FIG. The entire surface of the biochemical analysis unit 1 is configured to be scanned by the laser light 24.

FIG. 14 is a schematic plan view of the scanning mechanism of the optical head. In FIG. 14, for simplification, the optical system except the optical head 35, the laser light 24, and the fluorescent light 4 are shown.
The optical path of 5 or stimulated emission 45 is omitted.

As shown in FIG. 14, 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.
14 are fixed, and the substrate 6 which is 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 stepping motor 65 is provided on the movable substrate 63, and the main scanning stepping motor 65 connects the endless belt 66 to the adjacent through holes 3 formed in the biochemical analysis unit 1, that is, the through holes 3. It is configured such that it can be driven intermittently at a pitch equal to the distance between adjacent dot-shaped stimulable phosphor layer regions 20 formed on the stimulable phosphor sheet 17. The optical head 35 is fixed to the endless belt 66, and when the endless belt 66 is driven by the main scanning stepping motor 65, the optical head 35 is moved in the main scanning direction indicated by an arrow X in FIG. Has been done. In FIG.
67 is a linear encoder for detecting the position of the optical head 35 in the main scanning direction, and 68 is a slit of the linear encoder 67.

Therefore, the main scanning stepping motor 6
5, the endless belt 66 is intermittently driven in the main scanning direction, and when scanning of one line is completed, the substrate 63 is intermittently moved in the sub scanning direction by the sub scanning pulse motor 61. The optical head 35 is
In FIG. 14, all the dot-shaped photostimulable phosphors formed on the stimulable phosphor sheet 17 by the laser light 24 are moved in the main scanning direction indicated by the arrow X and the sub-scanning direction indicated by the arrow Y. The entire surface of the layer region 20 or the biochemical analysis unit 1 is scanned.

FIG. 15 is a block diagram showing the control system, input system, drive system and detection system of the scanner according to the preferred embodiment of the present invention.

As shown in FIG. 15, the control system of the scanner is a control unit 7 for controlling the entire scanner.
0, a data processing device 54, and a memory 55, and the input system of the scanner is provided with a keyboard 71 which is operated by a user and can input various instruction signals.

As shown in FIG. 15, the drive system of the scanner intermittently moves the optical head 35 in the main scanning direction, and the main scanning stepping motor 65, and intermittently moves the optical head 35 in the sub scanning direction. Sub-scanning pulse motor 6
1 and 4 filter members 51a, 51b, 51c, 5
A filter unit motor 72 for moving the filter unit 48 including 1d 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.

Further, as shown in FIG. 15, the detection system of the scanner comprises a photomultiplier 50 and a linear encoder 67 for detecting the position of the optical head 35 in the main scanning direction.

In the present embodiment, the control unit 70 controls the first laser pumping light source 21, the second laser pumping light source 22, or the third laser pumping light source 22 according to the position detection signal of the optical head 35 input from the linear encoder 67. The laser excitation light source 23 is configured to be on / off controllable.

The scanner configured as described above uses a large number of dot-shaped dots by the radiolabel substance contained in the large number of absorptive regions 4 formed in the biochemical analysis unit 1 in the following manner. The stimulable phosphor layer region 20 is exposed, and the radiation data of the radiolabeled substance recorded on the stimulable phosphor sheet 17 is read to generate biochemical analysis data.

First, the stimulable phosphor sheet 17 is placed on the glass plate 41 of the stage 40.

[0187] Next, the user operates the keyboard 7
An instruction signal for scanning a large number of dot-shaped stimulable phosphor layer regions 20 formed on the stimulable phosphor sheet 17 with a laser beam 24 is input to the first column.

The instruction signal input to the keyboard 71 is
Input to the control unit 70, the control unit 70 outputs a drive signal to the filter unit motor 72 according to the instruction signal, and the filter unit 4
Photostimulable light 45 emitted from the photostimulable phosphor by moving 8
The filter member 51d provided with the filter 52d having the property of transmitting only the light in the wavelength range of 640 nm and cutting the light of the wavelength of 640 nm is positioned in the optical path of the stimulated emission light 45.

Further, the control unit 70 outputs a drive signal to the main scanning stepping motor 65 to move the optical head 35 in the main scanning direction, and based on the position detection signal of the optical head 35 input from the linear encoder, A position where the first dot-shaped stimulable phosphor layer region 20 among the many dot-shaped stimulable phosphor layer regions 20 formed on the stimulable phosphor sheet 17 can be irradiated with the laser beam 24. When it is confirmed that the optical head 35 has reached,
A stop signal is output to the main scanning stepping motor 65, and a drive signal is output to the first laser excitation light source 21 to activate the first laser excitation light source 21, and 640 nm
The laser light 24 of the wavelength is 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 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
4 passes through the hole 33 of the perforated mirror 34 and enters the concave mirror 38.

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 onto the first dot-shaped stimulable phosphor layer region 20 of the stimulable phosphor sheet 17 placed on the glass plate 41 of the stage 40. To be done.

As a result, the stimulable phosphor contained in the first dot-shaped stimulable phosphor layer region 20 formed on the stimulable phosphor sheet 17 is excited by the laser beam 24 to generate the first stimulable phosphor. Photostimulation light 45 is emitted from the photostimulable phosphor layer region 20 of FIG.

The photostimulable light 45 emitted from the first dot-shaped photostimulable phosphor region 15 is collected by the aspherical lens 37 provided in the optical head 35, and the laser light 24 is reflected by the mirror 36. The light is reflected on the same side as the optical path, becomes parallel light, and enters the concave mirror 38.

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

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

The filter 52d transmits only the light in the wavelength region of the photostimulable light 45 emitted from the photostimulable phosphor, and emits 640n.
Since it has the property of cutting off the light of wavelength m, the light of wavelength 640 nm which is the excitation light is cut off, and the wavelength of photostimulable light 45 emitted from the dot-shaped photostimulable phosphor layer region 20. Only the light in the region passes through the filter 52d and is photoelectrically detected by the photomultiplier 50.

The analog signal photoelectrically detected by the photomultiplier 50 and generated is output to the A / D converter 53, converted into a digital signal, and output to the data processing device 54.

When a predetermined time, for example, several microseconds elapses after the first laser excitation light source 21 is turned on, the control unit 70 outputs a drive stop signal to the first laser excitation light source 21, The drive of the first laser excitation light source 21 is stopped, and a drive signal is output to the main scanning stepping motor 65 so that the optical head 35 is activated by the adjacent dot-shaped stimulants formed on the stimulable phosphor sheet 17. It is moved by a pitch equal to the distance between the luminescent phosphor layer regions 20.

Based on the position detection signal of the optical head 35 input from the linear encoder 67, the optical head 35
Is moved by one pitch equal to the distance between the adjacent dot-shaped stimulable phosphor layer regions 20 to form the laser light 24 emitted from the first laser excitation light source 21 on the stimulable phosphor sheet 17. When it is confirmed that the second dot-shaped stimulable phosphor layer region 20 has been moved to a position where it can be irradiated, the control unit 70 outputs a drive signal to the first laser excitation light source 21. The stimulability contained in the second dot-shaped stimulable phosphor layer region 20 formed on the stimulable phosphor sheet 17 is turned on by turning on the first laser excitation light source 21. Excite the phosphor.

Similarly, the laser light 24 is applied to the second dot-shaped stimulable phosphor layer area 20 formed on the stimulable phosphor sheet 17 for a predetermined time, and the second stimulable phosphor layer 20 is irradiated. The stimulable phosphor contained in the stimulable phosphor layer region 20 is excited, and the stimulable light 45 emitted from the second stimulable phosphor layer region 20 is converted by the photomultiplier 50 into
When photoelectrically detected and analog data is generated,
The control unit 70 includes the first laser excitation light source 2
1 to turn off the first laser excitation light source 21, and the main scanning stepping motor 65
Then, a drive signal is output to set the optical head 35 to a distance equal to the distance between adjacent dot-shaped stimulable phosphor layer regions 20.
Move only the pitch.

Thus, the first laser excitation light source 21 is repeatedly turned on and off in synchronization with the intermittent movement of the optical head 35, and the optical head 35 is detected based on the position detection signal of the optical head 35 input from the linear encoder 67. 35 is moved by one line in the main scanning direction, and when it is confirmed that the scanning of the dot-shaped stimulable phosphor layer region 20 of the first line by the laser beam 24 is completed, the control unit 70 Outputs a drive signal to the main scanning stepping motor 65 to return the optical head 35 to its original position and outputs a drive signal to the sub scanning pulse motor 61 to move the movable substrate 63 to the sub scanning direction. Then, move only one line.

Based on the position detection signal of the optical head 35 input from the linear encoder 67, the optical head 35
Is returned to its original position, and the movable substrate 63 is
When it is confirmed that the line has been moved by one line in the sub-scanning direction, the control unit 70 sequentially applies the first laser excitation to the dot-shaped stimulable phosphor layer region 20 on the first line. Laser light emitted from the first laser excitation light source 21 is sequentially applied to the dot-shaped photostimulable phosphor layer region 20 of the second line in the same manner as the irradiation of the laser light 24 emitted from the light source 21. 24 to irradiate 24 to excite the stimulable phosphor contained in the dot-shaped stimulable phosphor layer region 20 to sequentially emit stimulable light 45 emitted from the stimulable phosphor layer region 20. , The photomultiplier 50 is detected photoelectrically.

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.

In this way, the large number of dot-shaped photostimulable phosphor layer regions 20 formed on the stimulable phosphor sheet 17 are all scanned by the laser light 24 emitted from the first laser excitation light source 21, and a large number of them are scanned. When the stimulable phosphor contained in the dot-shaped stimulable phosphor layer region 20 is excited,
The emitted photostimulable light 45 is photoelectrically detected by the photomultiplier 50, and the generated analog data is converted into digital data by the A / D converter 53 and sent to the data processing device 54. A drive stop signal is output from the control unit 70 to the first laser excitation light source 21, and the drive of the first laser excitation light source 21 is stopped.

On the other hand, when the fluorescence data of the fluorescent substance recorded in the many absorptive regions 4 formed in the biochemical analysis unit 1 is read to generate the biochemical analysis digital data, first, the operator The biochemical analysis unit 1 is set on the glass plate 41 of the stage 40.

Next, the operator specifies on the keyboard 71 the type of the fluorescent substance as the labeling substance and inputs an instruction signal to the effect that the fluorescent data should be read.

The instruction signal input to the keyboard 71 is
When the control unit 70 receives the instruction signal, the control unit 70 determines the laser excitation light source to be used according to the table stored in the memory (not shown), and the filter 52.
Which of a, 52b, and 52c is to be positioned in the optical path of the fluorescent light 45 is determined.

For example, Rhodamine (registered trademark) that can be most efficiently excited by a laser having a wavelength of 532 nm as a fluorescent substance for labeling a substance of biological origin
Is used and is input to the keyboard 71, the control unit 70 selects the second laser excitation light source 22, selects the filter 52b, and outputs a drive signal to the filter unit motor 72. Then, the filter unit 48 is moved to cut the light having the wavelength of 532 nm, and the filter member 51b having the property of transmitting the light having the wavelength longer than 532 nm is emitted from the biochemical analysis unit 1. It is located in the optical path of the fluorescent light 45 to be formed.

Further, the control unit 70 outputs a drive signal to the main scanning stepping motor 65 to move the optical head 35 in the main scanning direction, and based on the position detection signal of the optical head 35 input from the linear encoder, When it is confirmed that the optical head 35 has reached the position where the laser beam 24 can be irradiated to the first absorptive region 4 among the many absorptive regions 4 formed in the biochemical analysis unit 1. , A stop signal is output to the main scanning stepping motor 65, and a drive signal is output to the second laser excitation light source 22 to activate the second laser excitation light source 22,
A laser beam 24 having a wavelength of 532 nm is emitted.

The laser light 24 emitted from the second laser excitation light source 22 is made into parallel light by the collimator lens 30, and then enters the first dichroic mirror 27 and is reflected.

The laser beam 24 reflected by the first dichroic mirror 27 passes through the second dichroic mirror 28 and enters the mirror 29.

The laser light 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 beam 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 biochemical analysis unit 1 mounted on the glass plate 41 of the stage 40.

As a result, the laser beam 24 excites a fluorescent substance such as a fluorescent dye contained in the first adsorptive region 4 of the biochemical analysis unit 1, for example, rhodamine, and emits fluorescence.

Here, in the biochemical analysis unit 1 according to this embodiment, a large number of absorptive regions 4 are filled with nylon 6 in a large number of through holes 3 formed in the substrate 2 made of aluminum. Thus, since the aluminum substrate 2 having the property of attenuating light is present between the adjacent adsorbing regions 4, the fluorescent substance contained in the adsorbing regions 4 is excited. Therefore, it is possible to reliably prevent the fluorescence 45 emitted from the fluorescent substance from being mixed with the emitted fluorescence 45 due to the excitation of the fluorescent substance contained in the adsorbing regions 4 adjacent to each other.

Furthermore, in this embodiment, the cDNA
Since a specific binding substance such as is selectively adsorbed within a predetermined range from the surface of each adsorptive region 4 of the biochemical analysis unit 1, the fluorescent substance is also absorbed in the biochemical analysis unit 1. Exists in a region within a predetermined range from the surface of each absorptive region 4, and therefore, the fluorescence 45 is emitted only from a region within a predetermined range from the surface of the absorptive region 4 of the biochemical analysis unit 1, It is possible to effectively prevent a part of the fluorescence from being undetected by being absorbed by the biochemical analysis unit 1 substrate 2 as in the case where the fluorescence is emitted from the deep part of the absorptive region 4. Therefore, the fluorescence emitted from the fluorescent substance contained in the adsorptive region 4 of the biochemical analysis unit 1 can be guided to the photomultiplier 50 and detected photoelectrically as desired. It will be possible.

The fluorescent light 45 emitted from rhodamine is condensed by the aspherical lens 37 provided in the optical head 35, reflected by the mirror 36 on the same side as the optical path of the laser light 24, and made into parallel light. , Enters the concave mirror 38.

The fluorescent light 45 which has entered the concave mirror 38 is reflected by the concave mirror 38 and enters the perforated mirror 34.

Fluorescent light 45 that has entered the perforated mirror 34 is
The perforated mirror 34 formed by the concave mirror reflects the light downward as shown in FIG. 8 and makes it incident on the filter 52b of the filter unit 48.

Since the filter 52b has a property of cutting light having a wavelength of 532 nm and transmitting light having a wavelength longer than 532 nm, light having a wavelength of 532 nm, which is excitation light, is cut and emitted from rhodamine. Fluorescence 45
Only the light in the wavelength range of 1 passes through the filter 52b and is photoelectrically detected by the photomultiplier 50.

The analog signal photoelectrically detected by the photomultiplier 50 and generated is output to the A / D converter 53, converted into a digital signal, and output to the data processing device 54.

After the second laser excitation light source 22 is turned on, when a predetermined time, for example, several microseconds has elapsed, the control unit 70 outputs a drive stop signal to the second laser excitation light source 22, The drive of the second laser excitation light source 22 is stopped, and a drive signal is output to the main scanning stepping motor 65 to move the optical head 35 to the adsorbing regions 4 adjacent to each other formed in the biochemical analysis unit 1.
Move by a pitch equal to the distance between.

On the basis of the position detection signal of the optical head 35 input from the linear encoder 67, the optical head 35
Is moved by one pitch equal to the distance between the adjacent absorptive regions 4 formed in the biochemical analysis unit 1,
Laser light 24 emitted from the second laser excitation light source 22
Is confirmed to have moved to a position where the second absorptive region 4 formed in the biochemical analysis unit 1 can be irradiated, the control unit 70 sends a drive signal to the second laser excitation light source 22. Output the second laser excitation light source 2
2 is turned on, and the laser beam 24 excites the fluorescent substance, for example, rhodamine, contained in the second absorptive region 4 formed in the biochemical analysis unit 1.

Similarly, the laser beam 24 is irradiated to the second absorptive region 4 formed in the biochemical analysis unit 1 for a predetermined time, and the fluorescence 45 emitted from the second absorptive region 4 is emitted. However, with the photomultiplier 50,
When photoelectrically detected and analog data is generated,
The control unit 70 includes the second laser excitation light source 2
2 to turn off the second laser excitation light source 22 and to output the main scanning stepping motor 65.
Then, a drive signal is output to move the optical head 35 by one pitch equal to the distance between the adsorbing regions 4 adjacent to each other formed in the biochemical analysis unit 1.

Thus, the first laser excitation light source 21 is repeatedly turned on and off in synchronization with the intermittent movement of the optical head 35, and the optical head 35 is detected based on the position detection signal of the optical head 35 input from the linear encoder 67. 35 is moved by one line in the main scanning direction, and when it is confirmed that all the absorptive regions 4 on the first line of the biochemical analysis unit 1 are scanned by the laser beam 24, control is performed. The unit 70 includes the main scanning stepping motor 6
5, a drive signal is output to return the optical head 35 to the original position, and a drive signal is output to the sub-scanning pulse motor 61 to move the movable substrate 63 in the sub-scanning direction.
Move only one line.

On the basis of the position detection signal of the optical head 35 input from the linear encoder 67, the optical head 35
Is returned to its original position, and the movable substrate 63 is
When it is confirmed that the line has been moved by one line in the sub-scanning direction, the control unit 70 causes the absorptive region 4 of the first line formed in the biochemical analysis unit 1 to be detected.
In the same manner as irradiating the laser beam 24 emitted from the second laser excitation light source 22 in sequence, the absorptive region 4 of the second line formed in the biochemical analysis unit 1
Of the fluorescence 45 emitted from the adsorptive region 4 by exciting the rhodamine contained in the photomultiplier 5 sequentially.
0 causes photoelectric detection.

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.

In this way, all the absorptive regions 4 formed in the biochemical analysis unit 1 are scanned by the laser light 24 emitted from the second laser excitation light source 22 and formed in the biochemical analysis unit 1. A large number of absorptive areas 4
Rhodamine contained in is excited and the emitted fluorescence 45 is photoelectrically detected by the photomultiplier 50, and the generated analog data is converted into digital data by the A / D converter 53. When sent to the data processing device 54, the control unit 70
Then, the drive stop signal is output to the second laser excitation light source 22, and the drive of the second laser excitation light source 22 is stopped.

According to this embodiment, in each of the absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1,
After spotting the solution containing the specific binding substance from the injector 6, air is sprayed on the surface of the first adsorptive region 4 on the opposite side of the surface on which the solution containing the specific binding substance is spotted, at a predetermined timing. Since the jetting device 8 is configured to blow air whose temperature is 40 ° C. or higher and whose humidity is controlled to 50% or less, permeation of the solution containing the specific binding substance is hindered, and the specific binding substance is The radiolabeled substance, which is selectively adsorbed within a predetermined range from the spotted surface and therefore labels the substance of biological origin that has hybridized with the specific binding substance, is also included in the biochemical analysis unit 1. Since each of the absorptive regions 4 of the biochemical analysis unit 1 exists in a region within a predetermined range from the surface of the absorptive region 4, the radioactive labeling substance selectively contained in a large number of the absorptive regions 4 of the biochemical analysis unit 1 causes accumulation fluorescence When exposing a large number of stimulable phosphor layer regions 20 of the sheet 17, electron beams (β-rays) are within a predetermined range from the surface of the absorptive region 4 adjacent to the stimulable phosphor layer regions 20. A part of the electron beam (β-ray) is absorbed by the biochemical analysis unit 1 substrate 2 as in the case where the electron beam (β-ray) is emitted only from the deep part of the adsorptive region 4. It is possible to effectively prevent the light from entering the stimulable phosphor layer region 20 by, for example, and therefore release from the radiolabeled substance contained in the absorptive region 4 of the biochemical analysis unit 1. The stimulable phosphor layer region 20 of the stimulable phosphor sheet 17 is irradiated with the generated electron beam (β-ray).
Can be exposed as desired, and the exposed photostimulable phosphor layer region 20 is scanned with a laser beam 24 to photoelectrically emit photostimulable light 45 emitted from the photostimulable phosphor. It is possible to generate biochemical analysis data with excellent quantification by performing the detection.

Further, according to this embodiment, after the solution containing the specific binding substance is spotted from the injector 6 on each of the absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1, the predetermined region is determined. At the timing of, the temperature of the surface of the first absorptive region 4 opposite to the surface on which the solution containing the specific binding substance is spotted is changed by the
Since it is configured to blow air whose humidity is controlled to be 50% or less at 0 ° C. or higher, the solution containing the specific binding substance is prevented from permeating, and the specific binding substance can be separated from the spotted surface by a predetermined amount. The fluorescent substance which is selectively adsorbed in the region of the range and therefore labels the substance derived from the living body which is hybridized with the specific binding substance is also the surface of each adsorptive region 4 of the biochemical analysis unit 1. Since it exists in the region of a predetermined range from, when the fluorescent substance contained in the absorptive region 4 is excited by the laser beam 24, the fluorescence is emitted from each of the absorptive regions 4 of the biochemical analysis unit 1. It is released only from the area within a predetermined range from the surface, and the adsorptive area 4
It is possible to effectively prevent a part of the fluorescence from being undetected by being absorbed by the biochemical analysis unit 1 substrate 2 as in the case where the fluorescence is emitted from the deep part of the. From the above, the fluorescence emitted from the fluorescent substance contained in the adsorptive region 4 of the biochemical analysis unit 1 was guided to the photomultiplier 50 as desired, and photoelectrically detected to provide excellent quantitativeness. It becomes possible to generate data for biochemical analysis.

FIG. 16 is a schematic perspective view of a biochemical analysis unit in which a solution containing a specific binding substance is spotted by a spotting method according to another preferred embodiment of the present invention.

As shown in FIG. 16, the biochemical analysis unit 80 according to this embodiment has an adsorptive film 83 made of nylon 6 and a large number of substantially circular through holes 82.
Is provided with a dot-shaped aluminum substrate 81 having a regular pattern, and the absorptive film 83 is disposed in a large number of through holes 82 formed in the substrate 81 by a calendering device (not shown). Is press-fitted by
A large number of absorptive regions 84 are regularly formed in a dot shape corresponding to the large numbers of through holes 82 formed in the substrate 81.

Although not shown exactly in FIG. 16, the approximately circular absorptive regions 84 having a size of about 0.01 mm 2 of about 10000 are regularly arranged at a density of about 5000 pieces / cm 2. It is formed in the biochemical analysis unit 80.

In this embodiment, the absorptive film 83 is pressed into the substrate 81 so that the surface of the absorptive region 84 and the surface of the substrate 81 are located at the same height, and the biochemical analysis unit is formed. 80 is formed.

FIG. 17 is a schematic vertical sectional view of a spotting device according to another preferred embodiment of the present invention.

As shown in FIG. 17, the spotting apparatus according to the present embodiment comprises a biochemical analysis unit 80.
And a spotting head 87 having an injector 86 for injecting a solution containing a specific binding substance such as cDNA, and a frame 85 for holding the same. The spotting head 87 is arranged on the side opposite to the spotting head 87 with respect to the frame 85 and emits infrared rays. An infrared lamp 88 is provided.

In this embodiment, the infrared lamp 88 is used.
Is configured to emit infrared light having a wavelength of 1 μm to 30 μm.

As shown in FIG. 17, the injector 86 of the spotting head 87 and the infrared lamp 88.
Is fixed such that the tip end portion of the injector 86 and the infrared emission surface of the infrared lamp 88 face each other via the frame 85.

Similar to the spotting device shown in FIG. 2, in the present embodiment, the frame 85 has a main scanning pulse motor (not shown) and a sub-scanning pulse motor (not shown). In the main scanning direction indicated by the arrow X and the sub-scanning direction orthogonal to the main scanning direction,
At a pitch equal to the distance between adjacent absorptive regions 84 of the biochemical analysis unit 80 held by the frame 85,
It is configured to be able to move intermittently.

In the present embodiment, when the absorptive region 84 formed on the biochemical analysis unit 80 held by the frame 85 is moved to a position facing the tip of the injector 86 and the infrared lamp 88, From the injector 86, the solution containing the specific binding substance is transferred to the adsorptive region 8
4, the solution containing the specific binding substance is injected from the injector 86, and then the infrared lamp 88 is activated at a predetermined timing so that the infrared ray changes the specific binding substance in the adsorptive region 4. It is configured such that the containing solution is irradiated to the surface opposite to the spotted surface.

FIG. 18 shows the absorptive region 84 of the biochemical analysis unit 80 in which the solution containing the specific binding substance is spotted from the injector 86 of the spotting head 87.
FIG.

As shown in FIG. 18, a large number of absorptive regions 84 of the biochemical analysis unit 80 according to this embodiment.
Is formed by press-fitting the absorptive film 83 into a large number of through holes 82 of the substrate 81.
Since the absorptive film 83 exists between 4 and 4, the solution 86a containing the specific binding substance spotted from the injector 6 passes through the absorptive region 84 formed by the absorptive nylon 6. , The solution 86a containing the specific binding substance may penetrate into the absorptive film 83 located between the adjacent absorptive regions 84, and the solution 86a containing the specific binding substance may reach the absorptive film 83 located between the adjacent absorptive regions 84. When it penetrates, the substance of biological origin labeled with a radioactive labeling substance is hybridized, and then the stimulable phosphor layer of the stimulable phosphor sheet is exposed by the radioactive labeling substance contained in the adsorptive region 84. At this time, the electron beam (β-ray) emitted from the radioactive labeling substance passes through the adsorptive film 83 and enters the adsorbing regions 84 adjacent to each other, and the radioactive labeling substance contained in the adsorbing regions 84 adjacent to each other. Incident on the region of the stimulable phosphor layer to be exposed by exposure, the exposed stimulable phosphor layer is scanned by excitation light, the stimulable light emitted from the stimulable phosphor layer The biochemical analysis data obtained by photoelectrically detecting 45 significantly deteriorates the quantification property, and the biological substance labeled with a labeling substance or a fluorescent substance that causes chemiluminescence by contacting with a chemiluminescent substrate is used. When the substances are hybridized and the chemiluminescence or fluorescence emitted from the adsorptive region 84 is photoelectrically detected to generate biochemical analysis data, the chemiluminescence or fluorescence emitted from the labeling substance is adsorbed. Of the biochemical analysis data generated by being incident on the adsorbing regions 84 adjacent to each other through the permeable film 83 and being mixed with chemiluminescence or fluorescence emitted from the adsorbing regions 84 adjacent to each other. It may decrease significantly.

However, in the present embodiment, the solution 86a containing the specific binding substance is spotted from the injector 86 on each of the absorptive regions 84 formed on the substrate 81 of the biochemical analysis unit 80, and then predetermined. The infrared lamp 88 irradiates the surface of the absorptive region 84 on the opposite side of the surface on which the solution 86a containing the specific binding substance is spotted with the infrared light 88a to heat the same. From this, the solution 86a containing the specific binding substance is prevented from permeating the inside of the adsorptive region 84 to reach the adsorptive film 83 between the adjacent adsorptive regions 84, and the specific binding substance is spotted. Radioactivity labeling a substance of biological origin that is selectively adsorbed within a predetermined range from the surface and is therefore hybridized with a specific binding substance.識物 quality also, biochemical analysis unit 8
0 exists in a region within a predetermined range from the surface of each absorptive region 84 of 0. Therefore, the stimulable fluorescent substance is generated by the radioactive labeling substance selectively contained in a large number of absorptive regions 84 of the biochemical analysis unit 80. When exposing a large number of stimulable phosphor layer regions 20 of the sheet 17, electron beams (β-rays) are within a predetermined range from the surface of the absorptive region 84 adjacent to the stimulable phosphor layer regions 20. Adsorbed regions 8 adjacent to each other, which are discharged from only
As in the case where an electron beam (β-ray) is emitted from the portion of the adsorptive film 83 between 4 and 4, a part of the electron beam (β-ray) passes through the adsorptive film 83 and is adjacent to the adsorbent film. It is possible to effectively prevent the light from entering the region 84, and therefore the electron beam (β-ray) emitted from the radio-labeled substance contained in the adsorptive region 84 of the biochemical analysis unit 80 causes accumulation. The photostimulable phosphor layer region 20 of the phosphor sheet 17 can be exposed as desired, and the exposed photostimulable phosphor layer region 20 is scanned with a laser beam 24,
By photoelectrically detecting the photostimulable light 45 emitted from the photostimulable phosphor, it becomes possible to generate biochemical analysis data having excellent quantitativeness.

Further, according to this embodiment, after the solution 86a containing the specific binding substance is spotted from the injector 86 on each of the absorptive regions 84 formed on the substrate 81 of the biochemical analysis unit 80, The infrared lamp 88 irradiates the surface of the absorptive region 84 opposite to the surface on which the solution 86a containing the specific binding substance is spotted with the infrared light 88a at a predetermined timing, and is heated. Therefore, the solution containing the specific binding substance 86
a is prevented from penetrating inside the absorptive region 84 and reaching the absorptive film 83 between the adjacent absorptive regions 84, and the specific binding substance is within a predetermined range from the spotted surface. In addition, the fluorescent substance that is selectively adsorbed and thus labels the substance of biological origin that has hybridized with the specific binding substance is within a predetermined range from the surface of each absorptive region 84 of the biochemical analysis unit 80. Since the fluorescent substance contained in the absorptive region 84 is excited by the laser light 24 because it exists in the region, the fluorescence is predetermined from the surface of each absorptive region 84 of the biochemical analysis unit 80. In the case where fluorescence is emitted only from the region within the range and the fluorescence is emitted from the adsorptive film 83 located between the adjacent adsorptive regions 84, the fluorescence passes through the adsorptive film 83 and is adjacent to each other. Enter the adsorptive area 84 However, it is possible to effectively prevent the fluorescence emitted from the adsorbing regions 84 adjacent to each other from being mixed with each other. Therefore, the fluorescent substance contained in the adsorbing regions 84 of the biochemical analysis unit 80 is emitted. Fluorescence
As desired, it is possible to lead to the photomultiplier 50 and photoelectrically detect it to generate biochemical analysis data excellent in quantification.

FIG. 19 is a schematic sectional view of a biochemical analysis unit in which a solution containing a specific binding substance is spotted by a spotting method according to another preferred embodiment of the present invention.

As shown in FIG. 19, the biochemical analysis unit 90 according to this embodiment has an absorptive substrate 91 made of nylon 6 and a large number of substantially circular through holes 9.
Two aluminum substrates 93 on which 2 is regularly formed
Is equipped with.

As shown in FIG. 19, two substrates 93 are provided.
Is adhered to both sides of the absorptive substrate 91, and a large number of absorptive regions 94 are formed by the absorptive substrate 91 located inside the through hole 92 formed in the substrate 93.

Although not shown exactly in FIG. 19, the approximately circular adsorbent regions 94 having a size of about 0.01 mm 2 of about 10,000 are regularly arranged at a density of about 5000 pieces / cm 2. It is formed in the biochemical analysis unit 90.

FIG. 20 is a schematic vertical sectional view of a spotting device according to another preferred embodiment of the present invention.

As shown in FIG. 20, the spotting apparatus according to the present embodiment comprises a biochemical analysis unit 90.
And a spotting head 97 having an injector 96 for injecting a solution containing a specific binding substance such as cDNA, and a frame 95 for holding A microwave irradiation device 98 for emitting light is provided.

As shown in FIG. 20, the injector 96 of the spotting head 97 and the microwave irradiation device 98 are arranged so that the tip of the injector 96 and the microwave irradiation device 98 face each other via the frame 95. It is fixed to.

In this embodiment, the frame 95 is indicated by an arrow X in FIG. 20 by a main scanning pulse motor (not shown) and a sub scanning pulse motor (not shown) in the same manner as in the above embodiment. The main scanning direction and the sub-scanning direction orthogonal to the main scanning direction are intermittently movable at a pitch equal to the distance between the adsorbing regions 94 adjacent to each other of the biochemical analysis unit 90 held by the frame 95. When the absorptive region 94 formed in the biochemical analysis unit 90 held by the frame 95 is moved to a position facing the tip of the injector 96 and the microwave irradiation device 98, respectively, From the injector 96, the solution containing the specific binding substance is ejected toward the adsorptive region 94, and after the ejection of the solution containing the specific binding substance, a predetermined value is given. At a timing, the surface of the absorptive region 94 opposite to the surface on which the solution containing the specific binding substance is spotted is irradiated with microwaves from the microwave irradiation device 98 and heated. There is.

Therefore, according to this embodiment, the solution containing the specific binding substance is prevented from penetrating to the absorptive substrate 91 between the adjacent absorptive regions 94, and the specific binding substance is spotted. Since the substance is selectively adsorbed in a region within a predetermined range from the surface of the adsorbed region 94, the radiolabeled substance labeling the substance of biological origin hybridized with the specific binding substance is also biochemically analyzed. Unit 90
Of the absorptive region 94 of the biochemical analysis unit 90, and therefore, the stimulable fluorescent substance is selectively contained in the large number of absorptive regions 94 of the biochemical analysis unit 90. When exposing a large number of stimulable phosphor layer regions 20 of the sheet 17, electron beams (β-rays) are within a predetermined range from the surface of the absorptive region 94 adjacent to the stimulable phosphor layer regions 20. As in the case where the electron beam (β-ray) is emitted from only the adsorbent substrate 91 between adjacent adsorbent regions 94, a part of the electron beam (β-ray) is emitted from the adsorbent substrate. It can be effectively prevented from entering through the 91 to the adjacent absorptive regions 94, and thus,
The stimulable phosphor layer region 20 of the stimulable phosphor sheet 17 is generated by the electron beam (β-ray) emitted from the radioactive labeling substance contained in the adsorptive region 94 of the biochemical analysis unit 90.
Can be exposed as desired, and the exposed photostimulable phosphor layer region 20 is scanned with a laser beam 24 to photoelectrically emit photostimulable light 45 emitted from the photostimulable phosphor. It is possible to generate biochemical analysis data with excellent quantification by performing the detection.

Further, according to this embodiment, the solution containing the specific binding substance is prevented from penetrating to the absorptive substrate 91 between the adjacent absorptive regions 94, and the specific binding substance is spotted. The fluorescent substance labeling the substance of biological origin hybridized with the specific binding substance is also used for biochemical analysis because it is selectively adsorbed within a predetermined range from the surface of the adsorbed region 94. When the fluorescent substance contained in the adsorptive region 94 is excited by the laser light 24, the fluorescence exists in the region within a predetermined range from the surface of each adsorptive region 94 of the unit 90. From the surface of each adsorptive area 94 of the analysis unit 90, only the area within a predetermined range is released, and the adsorbent areas 94 adjacent to each other are adsorbed.
As in the case where fluorescence is emitted from the absorptive substrate 91 located between the two, the fluorescent light passes through the absorptive substrate 91 and is incident on the adjacent absorptive regions 94, and the adjacent absorptive regions 94 are adjacent to each other.
It is possible to effectively prevent mixing with fluorescence emitted from the biochemical analysis unit 90.
The fluorescence emitted from the fluorescent substance contained in the absorptive region 94 is guided to the photomultiplier 50 as desired, and photoelectrically detected to generate biochemical analysis data having excellent quantitativeness. It will be possible.

FIG. 21 is a schematic vertical sectional view of a spotting device according to still another preferred embodiment of the present invention.

As shown in FIG. 21, in the spotting device according to this embodiment, the heating substrate 108 on which the temperature is controlled and the biochemical analysis unit 1 is placed, and the cDNA.
And a spotting head 107 having an injector 106 for injecting a solution containing a specific binding substance such as A.

In this embodiment, the heating substrate 108 is held stationary and the spotting head 107 is
21, a biochemical analysis unit 1 or 80 placed on the heating substrate 108 in the main scanning direction indicated by arrow X and the sub-scanning direction orthogonal to the main scanning direction in FIG. 21 by a scanning mechanism (not shown). , 90 adjacent to each other in the absorptive region 4 at a pitch equal to the distance between the absorptive regions 4 so as to be movable intermittently. In FIG. 21, the biochemical analysis unit 1 is shown for convenience of description.

In the present embodiment, the tip of the injector 106 of the spotting head 107 has the biochemical analysis units 1, 80 mounted on the heating substrate 108.
When moved to a position facing each of the absorptive regions 4 formed in 90, the solution containing the specific binding substance is injected from the injector 106 into the biochemical analysis units 1, 80,
It is jetted toward 90 absorptive regions 4, 84, 94.

Therefore, according to this embodiment, the surface of the absorptive regions 4, 84 and 94 on the opposite side of the surface on which the solution containing the specific binding substance is spotted is heated by the heating substrate 108. The solution containing the specific binding substance is prevented from penetrating into a deep portion of the adsorptive region 4, or the adsorptive film 83 and the adsorptive substrate 91 located between the adjacent adsorptive regions 84 and 94. The specific binding substance is selectively adsorbed within a predetermined area from the spotted surface, and therefore, the radiolabeled substance labeling the substance of biological origin hybridized with the specific binding substance is also included. , The biochemical analysis units 1, 80, 90 are present within a predetermined range from the surface of each absorptive region 4, 84, 94 of the biochemical analysis units 1, 80, 90.
The stimulable phosphor sheet 17 is provided by the radioactive labeling substance selectively contained in the large number of 90 absorptive regions 1, 84, 94.
When a large number of stimulable phosphor layer regions 20 are exposed, electron beams (β rays) are within a predetermined range from the surface of the absorptive regions 4, 84, 94 adjacent to the stimulable phosphor layer regions 20. Of the electron beam (β
It is said that a part of the electron beam (β-ray) is not incident on the stimulable phosphor layer region 20 because it is absorbed by the biochemical analysis unit 1 substrate 2 as in the case where the (ray) is emitted. This can be effectively prevented, and the adsorbing regions 8 adjacent to each other can be prevented.
The adsorptive film 83 and the adsorptive substrate 91 which are located between
As in the case where the electron beam (β-ray) is emitted from the part of, the part of the electron beam (β-ray) passes through the absorptive film 83 and the absorptive substrate 91, and the adjacent absorptive regions 84, Can be effectively prevented from entering 94, and therefore
The stimulable phosphor layer region 20 of the stimulable phosphor sheet 17 is generated by the electron beam (β-ray) emitted from the radioactive labeling substance contained in the adsorptive region 84 of the biochemical analysis unit 80.
Can be exposed as desired, and the exposed photostimulable phosphor layer region 20 is scanned with a laser beam 24 to photoelectrically emit photostimulable light 45 emitted from the photostimulable phosphor. It is possible to generate biochemical analysis data with excellent quantification by performing the detection.

Further, according to this embodiment, the surfaces of the absorptive regions 4, 84, 94 on the opposite side of the surface on which the solution containing the specific binding substance is spotted are heated by the heating substrate 108. , A solution containing a specific binding substance is located in a deep portion of the adsorptive regions 4, 84, 94 or between the adsorbent regions 84, 94 adjacent to each other,
The specific binding substance is prevented from penetrating to the adsorptive substrate 91, and the specific binding substance is selectively adsorbed within a predetermined area from the spotted surface, and therefore, the biological substance hybridized with the specific binding substance. Since the fluorescent substance labeling the substance of origin is also present in the region within a predetermined range from the surface of each of the absorptive regions 4, 84, 94 of the biochemical analysis units 1, 80, 90, the laser light When the fluorescent substance contained in the absorptive regions 4, 84, 94 is excited by 24, the fluorescence is within a predetermined range from the surface of each absorptive region 84 of the biochemical analysis unit 1, 80. As in the case where the fluorescence is emitted only from the deep region of the adsorptive region 4, a part of the fluorescence is absorbed by the substrates 2 and 83 of the biochemical analysis unit 1 and 80, That it will not be detected It is possible to effectively prevent,
Further, as in the case where the fluorescence is emitted from the absorptive film 83 and the absorptive substrate 91 located between the adjacent absorptive regions 84 and 94, the fluorescence passes through the absorptive film 83 and the absorptive substrate 91. Therefore, it is possible to effectively prevent the fluorescent light emitted from the adjacent absorptive regions 84, 94 from being incident on the adjacent absorptive regions 84, 94 and being mixed with each other, and thus the biochemical analysis units 1, 80. , 90 absorptive regions 4, 84,
Fluorescence emitted from the fluorescent substance contained in 94 can be guided to the photomultiplier 50 as desired and photoelectrically detected to generate biochemical analysis data with excellent quantitativeness. Become.

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-mentioned 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

Further, in the above-mentioned embodiment, the spotting device is provided with the air injection device 8, the infrared lamp 88, the microwave irradiation device 98 or the heating substrate 108, but the spotting device is the biochemical analysis unit 1, It suffices if a means for forcibly promoting the evaporation of the solution containing the specific binding substance spotted on the plurality of absorptive regions 4, 84, 94 formed on 80, 90 is provided, the air injection device 8, infrared rays. A high-frequency heating device may be used instead of the lamp 88, the microwave irradiation device 98, or the heating substrate 108. When using a high frequency heating device, use a high frequency heating device capable of outputting a high frequency having a frequency of 2 to 20 megacycles and an electric field strength of 800 to 2000 V / cm with an output of 1 to 100 kW · hr. Is preferred.

Furthermore, in the embodiment shown in FIGS. 2, 17 and 20, the spotting heads 7, 87,
97, the air injection device 8, the infrared lamp 88, and the microwave irradiation device 98 are held stationary, and the frames 5, 85, 95 are configured to be movable in the main scanning direction and the sub scanning direction. , 85, 95 stationary, spotting heads 7, 87, 9
7, the air injection device 8, the infrared lamp 88, and the microwave irradiation device 98 can be configured to be movable in the main scanning direction and the sub scanning direction.
95 is moved in the main scanning direction or the sub scanning direction, and the spotting heads 7, 87, 97, the air ejecting device 8, the infrared lamp 88, and the microwave irradiation device 98 are moved in the sub scanning direction or the main scanning direction. May be.

In the embodiment shown in FIGS. 2, 17, and 20, the solution containing the specific binding substance was spotted from the injectors 6, 86, 96 of the spotting heads 7, 87, 97, respectively. After that, at a predetermined timing, air is jetted from the air jetting device 8 or infrared rays are emitted from the infrared lamp 88 to the absorptive regions 4, 84 and 94 where the solution containing the specific binding substance is spotted. Alternatively, the microwave is irradiated from the microwave irradiation device 98, but the air is uniformly irradiated from the air injection device 8 or the infrared light is uniformly irradiated from the infrared lamp 88. Alternatively, each of the biochemical analysis units 1, 80, 90 which are uniformly irradiated with microwaves from the microwave irradiation device 98. The wearing region 4,84,94, injector 6,8 spotting head 7,87,97
From 6, 96, a solution containing a specific binding substance may be spotted.

Furthermore, in the above-mentioned embodiment, from the injectors 6, 86, 96 of the single spotting heads 7, 87, 97 to the biochemical analysis units 1, 80,
In the plurality of absorptive regions 4, 84, 94 formed in 90,
The biochemical analysis units 1, 80, 9 are configured to sequentially spot a solution containing a specific binding substance.
The same number of dropping pins as the absorptive regions 4, 84, 94 formed in 0 are provided in the same pattern as the absorptive regions 4, 84, 94 formed in the biochemical analysis units 1, 80, 90, A solution containing a specific binding substance may be simultaneously spotted on a large number of absorptive regions 4, 84, 94, or a plurality of dropping pins may be provided to provide a predetermined number of absorptive regions 4, 84, 94. A solution containing a specific binding substance may be spotted every 94th.

Further, in the embodiment shown in FIG. 1, the biochemical analysis unit 1 is formed by filling the inside of a large number of through holes 3 formed in the substrate 2 made of aluminum with nylon 6. In the embodiment shown in FIG. 16, the biochemical analysis unit 80 includes the absorptive membrane 8 formed of nylon 6.
3 has a large number of absorptive regions 84 formed by being press-fitted into a large number of through holes 82 formed in a substrate 81 made of aluminum, and in the embodiment shown in FIG. 19, for biochemical analysis. The unit 90 includes an absorptive substrate 91 formed of nylon 6 and two aluminum substrates 93 that are adhered to both surfaces thereof and have a large number of through holes 92 formed therein. Adsorbent substrate 9
1, the absorptive region 94 is formed, but the absorptive regions 4, 84 of the biochemical analysis units 1, 80, 90,
It is not always necessary for 94 to be formed of nylon 6, and instead of nylon 6, a porous material capable of forming another membrane filter, for example, nylons such as nylon 6,6, nylon 4,10, etc. Cellulose derivatives such as nitrocellulose, cellulose acetate and cellulose butyrate acetate; Collagen; Alginic acids such as alginic acid, calcium alginate, alginic acid / polylysine polyion complex; Polyolefins such as polyethylene and polypropylene; Polyvinyl chloride; Polyvinylidene chloride; Polyfluoride The biochemical analysis unit 1, including polyfluoride such as vinylidene and polytetrafluoride, or a copolymer or complex thereof,
It is also possible to form 80, 90 adsorptive regions 4, 84, 94, and further, a carbon porous material such as activated carbon or a metal such as platinum, gold, iron, silver, nickel, aluminum; alumina, silica, titania. , A metal oxide such as zeolite; a metal salt such as hydroxyapatite or calcium sulfate, or an inorganic porous material such as a complex thereof, or a bundle of a plurality of fibers, the biochemical analysis unit 1,
The absorptive regions 4, 84, 94 of 80, 90 may be formed.

Further, in the above-mentioned embodiment, the biochemical analysis units 1, 80, 90 are all provided with the aluminum substrates 2, 81, 93, but the biochemical analysis units 1, 80, 90 90 substrates 2, 81, 93
It is not always necessary to form it with aluminum, and the biochemical analysis units 1, 80, 90 have the substrates 2, 8
1 and 93 are preferably formed of a material having a property of attenuating radiation and light, but the material is not particularly limited, and either an inorganic compound material or an organic compound material may be used. In particular, metallic materials, ceramic materials or plastic materials are preferably used. Biochemical analysis unit 1, 80,
Examples of the inorganic compound material that can be preferably used to form the substrates 2, 81, and 93 of 90 include gold, silver, and
Copper, zinc, aluminum, titanium, tantalum, chrome,
Metals such as iron, 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; metal oxides such as aluminum oxide, magnesium oxide and zirconium oxide; tungsten carbide, calcium carbonate, sulfuric acid. Inorganic salts such as calcium, hydroxyapatite and gallium arsenide can be mentioned. These may have any structure in a polycrystalline sintered body such as single crystal, amorphous, or ceramic. Further, as the organic compound material which can be preferably used for forming the substrates 2, 81, 93 of the biochemical analysis units 1, 80, 90, a polymer compound is preferably used, and a preferable polymer compound is, for example, Polyolefins such as polyethylene and polypropylene; acrylic resins such as polymethylmethacrylate and butyl acrylate / methylmethacrylate copolymers; polyacrylonitrile; polyvinyl chloride; polyvinylidene chloride;
Polyvinylidene fluoride; polytetrafluoroethylene;
Polychlorotrifluoroethylene; Polycarbonate;
Polyester such as polyethylene naphthalate and polyethylene terephthalate; nylon 6, nylon 6,6,
Nylon such as nylon 4 and 10; polyimide; polysulfone; polyphenylene sulfide; silicon resin such as polydiphenyl siloxane; phenol resin such as novolac; epoxy resin; polyurethane; polystyrene; butadiene-styrene copolymer; cellulose, cellulose acetate, nitrocellulose Examples include polysaccharides such as starch, calcium alginate, and hydroxypropylmethylcellulose; chitin; chitosan; sumacum; polyamides such as gelatin, collagen, and keratin, and copolymers of these polymer compounds. They are,
A composite material may be used, and if necessary, metal oxide particles, glass fibers and the like may be filled, and an organic compound material may be blended and used.

In the embodiment shown in FIG. 16, the absorptive region 84 of the biochemical analysis unit 80 has an absorptive film 83 formed of nylon 6 formed on an aluminum substrate 81. Although it is formed by press-fitting into the many through-holes 82, it is not always necessary to press-fit the adsorptive film 83 into the many through-holes 82 formed in the substrate 81 using a calendering device. Alternatively, the absorptive film 83 can be press-fitted into the large number of through holes 82 formed in the substrate 81 by using other means such as a hot press device. Instead of press-fitting, the adsorptive film 83 can be sucked by an appropriate method. Membrane 8
3 may be embedded in a large number of through holes 82 formed in the substrate 81 to form a large number of absorptive regions 84.

Further, in the above-mentioned embodiment, the biochemical analysis units 1, 80, 90 are provided with the approximately circular absorptive regions 4, 84, 94 having a size of about 10,000, about 0.01 mm 2. Although it is formed at a density of 5000 pieces / square centimeter and according to a regular pattern, it is not always necessary to form the absorptive regions 4, 84, 94 into a substantially circular shape, and it is not necessary to form an absorptive area such as a rectangular shape. It can be formed into a shape.

Further, in the above-mentioned embodiment, the biochemical analysis units 1, 80, 90 are provided with about 10000.
The substantially circular adsorptive regions 4, 84, 94 having a size of 01 square millimeters have a density of about 5000 pieces / square centimeter and follow a regular pattern.
Although formed, the number and size of the absorptive regions 4, 84, 94 can be arbitrarily selected according to the purpose, and preferably the absorptive region having a size of 10 or more and less than 5 mm 2. Areas 4, 84, 94 are 10 /
It is formed with a density of not less than square centimeters.

Furthermore, in the above-mentioned embodiment, the biochemical analysis units 1, 80, 90 are provided with approximately 10,000 absorptive regions 4, 84, 94 having a substantially circular shape having a size of approximately 0.01 mm 2 of approximately 10,000. The absorptive regions 4, 84 and 94 are formed at a density of 5000 pieces / square centimeter and according to a regular pattern.
Forming according to a regular pattern is not necessary.

In the above embodiment, the hybridizing liquid 16 containing the substance of biological origin labeled with the radioactive labeling substance and the substance of biological origin labeled with the fluorescent substance is prepared, and the absorptive regions 4, 84, Although it is hybridized to the specific binding substance dropped on 94, it is not always necessary that the substance derived from the living body is labeled with a radioactive substance such as a radiolabeling substance and a fluorescent dye. It may be labeled with at least one labeling substance selected from the group consisting of labeling substances that produce chemiluminescence when brought into contact with a substance and a chemiluminescent substrate.

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

Further, in the above-described embodiment, the scanner shown in FIGS. 8 to 15 is used to record in a large number of dot-shaped stimulable phosphor layer regions 12 formed on the stimulable phosphor sheet 10. The radiological data of the radiolabeled substance and the fluorescence data of the fluorescent substance such as the fluorescent dye recorded in the absorptive region 4 of the biochemical analysis unit 1 are read,
Although the data for biochemical analysis is generated, it is not always necessary to read the radiation data of the radiolabeled substance and the fluorescence data of the fluorescent substance by one scanner. The radiation data of the radiolabeled substance and the fluorescence data of the fluorescent substance are not necessarily required. May be read by a separate scanner to generate biochemical analysis data.

In the above embodiment, the control unit 70 controls the first laser excitation light source 21 to be turned on / off in synchronization with the intermittent movement of the optical head 35. However, in the main scanning direction, If the moving speed of the optical head 35 in the main scanning direction is determined so that the laser light 24 moves quickly between the adjacent dot-shaped stimulable phosphor layer regions 12, the first laser excitation light source 21 Is maintained in the ON state, and the optical head 35 is simply moved intermittently to provide a large number of dot-shaped stimulable phosphor layer regions 12
Can be sequentially scanned with the laser light 24 to photoelectrically detect the photostimulable light 45 emitted from the dot-shaped photostimulable phosphor layer region 12 to generate biochemical analysis data. .

The scanner shown in FIGS. 8 to 15 includes a first laser excitation light source 21, a second laser excitation light source 22 and a third laser excitation light source 23, but three laser excitation light sources are used. It is not always necessary to have a light source.

Further, in the scanner shown in FIGS. 8 to 15, the scanner is a laser beam 24 having a wavelength of 640 nm.
And a second laser excitation light source 22 for emitting a laser light 24 having a wavelength of 532 nm.
And a third laser excitation light source 23 that emits a laser light 24 having a wavelength of 473 nm.
It is not always necessary to use a laser excitation light source, instead of a laser excitation light source, an LED light source can be used as an excitation light source, and furthermore, a halogen lamp is used as an excitation light source, and a spectral filter does not contribute to excitation. The wavelength component may be cut.

In the above embodiment, the optical head 3 is moved by the scanning mechanism in the main scanning direction indicated by arrow X and the sub-scanning direction indicated by arrow Y in FIG.
5 is moved to scan all dot-shaped stimulable phosphor layer regions 12 of the stimulable phosphor sheet 10 or all absorptive regions 4 of the biochemical analysis unit 1 with the laser light 24, Although a fluorescent substance such as a stimulable phosphor or a fluorescent dye is excited, the optical head 35 is maintained in a stationary state, and the stage 40 in FIG.
By moving in the main scanning direction indicated by arrow X and the sub-scanning direction indicated by arrow Y, all dot-shaped stimulable phosphor layer regions 12 or biochemistry of the stimulable phosphor sheet 10 are moved by the laser beam 24. All the absorptive regions 4 of the analysis unit 1 may be scanned to excite a fluorescent substance such as a stimulable phosphor or a fluorescent dye,
14, the optical head 35 is moved in the main scanning direction indicated by arrow X or the sub-scanning direction indicated by arrow Y, and the stage 40 is indicated by the sub-scanning direction indicated by arrow Y or arrow X. It can also be moved in the main scanning direction.

Further, in the scanner shown in FIGS. 8 to 15, the photomultiplier 50 is used as the photodetector to photoelectrically detect fluorescence or stimulated emission. Is a photomultiplier 5 as long as it can detect fluorescence or stimulated emission photoelectrically.
Not only 0, but other photodetectors such as photodiodes, line CCDs, and two-dimensional CCDs can also be used.

[0287]

INDUSTRIAL APPLICABILITY According to the present invention, 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. is spotted on a carrier, and spotted. Area is formed on the carrier at a high density, and the substance of biological origin labeled with the radiolabeling substance is specifically bound to the specific binding substance contained in the spot-shaped region to selectively label it. The unit for biochemical analysis obtained as described above is brought into close contact with the stimulable phosphor layer, and the stimulable phosphor layer is exposed to a radioactive labeling substance, and the stimulable phosphor layer is irradiated with excitation light,
Electrons emitted from radiolabeled substances contained in adjacent spot-shaped regions are also detected when photoelectrically detecting photostimulable light emitted from the photostimulable phosphor layer to generate biochemical analysis data. Of a specific binding substance that effectively prevents the mixing of radiation (β-rays), can specifically bind to a substance of biological origin, and has a known base sequence, base length, composition, etc. And / or a labeling substance for forming chemiluminescence by contacting a specific binding substance contained in the spot-like region with a chemiluminescent substrate A substance derived from a living body that is labeled with a fluorescent substance is specifically bound and selectively labeled, and chemiluminescence and / or fluorescence emitted from a spot-like region is photoelectrically detected to obtain data for biochemical analysis. Generate In the case of the spotting, it is possible to effectively prevent the chemiluminescence and / or the fluorescence emitted from the adjacent spot-like regions from being mixed with each other, and to generate the biochemical analysis data with excellent quantitativeness. It becomes possible to provide methods and apparatus.

[Brief description of drawings]

FIG. 1 is a schematic perspective view of a biochemical analysis unit in which a solution containing a specific binding substance is spotted by a spotting method for a specific binding substance according to a preferred embodiment of the present invention.

FIG. 2 is a schematic vertical sectional view of a spotting device according to a preferred embodiment of the present invention.

FIG. 3 is a block diagram showing a control system, a detection system, a drive system and an input system of a spotting device according to a preferred embodiment of the present invention.

FIG. 4 is a schematic enlarged cross-sectional view showing an absorptive region of a biochemical analysis unit in which a solution containing a specific binding substance is spotted from an injector of a spotting head.

FIG. 5 is a schematic vertical cross-sectional view of a hybridization container.

FIG. 6 is a schematic perspective view of a stimulable phosphor sheet.

FIG. 7 shows a large number of dot-shaped stimulable phosphors formed on a stimulable phosphor sheet by a radiolabel substance contained in a large number of absorptive regions formed in a biochemical analysis unit. FIG. 7 is a schematic cross-sectional view showing a method of exposing a layer region.

FIG. 8 is a schematic perspective view showing an example of a scanner.

FIG. 9 is a schematic perspective view showing details of a scanner near the photomultiplier.

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

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

FIG. 12 is a schematic cross-sectional view taken along the line CC of FIG.

FIG. 13 is a schematic cross-sectional view taken along the line DD of FIG.

FIG. 14 is a schematic plan view of a scanning mechanism of an optical head.

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

FIG. 16 is a schematic perspective view of a biochemical analysis unit on which a solution containing a specific binding substance is spotted by a spotting method according to another preferred embodiment of the present invention.

FIG. 17 is a schematic vertical sectional view of a spotting device according to another preferred embodiment of the present invention.

FIG. 18 is a schematic enlarged cross-sectional view showing an absorptive region of a biochemical analysis unit in which a solution containing a specific binding substance is spotted from an injector of a spotting head.

FIG. 19 is a schematic perspective view of a unit for biochemical analysis in which a solution containing a specific binding substance is spotted by a spotting method according to another preferred embodiment of the present invention.

FIG. 20 is a schematic vertical cross-sectional view of a spotting device according to another preferred embodiment of the present invention.

FIG. 21 is a schematic vertical sectional view of a spotting device according to still another preferred embodiment of the present invention.

[Explanation of symbols]

1 Biochemical analysis unit 2 substrates 3 through holes 4 Adsorbable area 5 frames 6 injectors 6a Solution containing specific binding substance 7 spotting head 8 Air injection device 8a air 10 control unit 11 Position detection means 12 Main scanning pulse motor 13 Sub-scanning pulse motor 14 keyboard 15 Hybridization container 16 Hybridization solution 17 Storage phosphor sheet 18 through holes 19 Support 20 Photostimulable phosphor layer region 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 stepping motor 66 endless belt 67 Linear encoder 68 Linear encoder slit 70 Control unit 71 keyboard 72 Filter unit motor 80 Biochemical analysis unit 81 substrate 82 through hole 83 Adsorbent membrane 84 Adsorbable area 85 frames 86 injector 86a Solution containing specific binding substance 87 Spotting head 88 infrared lamp 88a infrared 90 Biochemical analysis unit 91 Adsorbent substrate 92 Through hole 93 substrate 94 Adsorbable area 95 frames 96 injector 97 spotting head 98 Microwave irradiation device 106 injector 107 spotting head 108 heating substrate

   ─────────────────────────────────────────────────── ─── Continued front page    F-term (reference) 2G052 AB20 AD06 AD26 CA04 EB01                       EB11 JA09 JA11 JA13                 2G083 AA03 AA09 CC03 CC04 CC10                       DD17                 2G088 EE27 FF05 GG10 GG13 GG17                       HH06 HH08 JJ05 JJ23 JJ25                       JJ30 LL12 LL13

Claims (35)

[Claims] 1. A plurality of holes are formed in a substrate of a biochemical analysis unit having a property of attenuating radiation and / or light so as to be separated from each other, and the adsorption formed in each of the plurality of holes. A spotting method for spotting a solution containing a specific binding substance on a specific region, comprising forcibly promoting evaporation of a solution containing the specific binding substance spotted on the plurality of adsorptive regions. A method for spotting a specific binding substance. 2. A specific binding spotted on the plurality of absorptive regions by blowing air whose temperature and humidity are controlled to the plurality of absorptive regions on which the solution containing the specific binding substance is spotted. The method for spotting a specific binding substance according to claim 1, wherein evaporation of a solution containing the substance is forcibly promoted. 3. An air having a temperature of 40 ° C. or higher and a humidity of 50% or less is blown to the plurality of absorptive regions on which the solution containing a specific binding substance is spotted to blow the plurality of absorptive regions to the plurality of absorptive regions. The spotting method for a specific binding substance according to claim 2, wherein evaporation of a solution containing the spotted specific binding substance is forcedly promoted. 4. The solution containing the specific binding substance is spotted with a solution containing 0.1 m / sec to 10 m / sec.
2. The uniqueness according to claim 1, wherein air is blown at a velocity of m / sec to forcibly promote evaporation of the solution containing the specific binding substance spotted on the plurality of adsorptive regions. Method for spotting chemically bound substances. 5. The plurality of adsorptive regions on which the solution containing the specific binding substance is spotted are heated by infrared rays to evaporate the solution containing the specific binding substance spotted on the plurality of adsorptive regions. The spotting method for a specific binding substance according to claim 1, wherein the spotting is forcedly promoted. 6. The specific binding substance spotted on the plurality of absorptive regions by heating the plurality of absorptive regions on which the solution containing the specific binding substance is spotted by infrared rays having a wavelength of 1 μm to 30 μm. The method for spotting a specific binding substance according to claim 5, which comprises forcibly promoting the evaporation of the solution containing 7. The evaporation of the solution containing the specific binding substance spotted on the plurality of adsorptive regions by heating the plurality of adsorptive regions spotted with the solution containing the specific binding substance by microwaves. The method for spotting a specific binding substance according to claim 1, wherein the spotting is forcedly promoted. 8. The plurality of absorptive regions on which the solution containing a specific binding substance is spotted are heated by high frequency to evaporate the solution containing the specific binding substance spotted on the plurality of absorptive regions. The spotting method for a specific binding substance according to claim 1, wherein the spotting is forcedly promoted. 9. A solution containing a specific binding substance is spotted by outputting a high frequency having a frequency of 2 to 20 megacycles and an electric field strength of 800 to 2000 V / cm at an output of 1 to 100 kW · hr. 9. The specificity according to claim 8, wherein the plurality of absorptive regions thus formed are heated to forcibly promote evaporation of the solution containing the specific binding substance spotted on the plurality of absorptive regions. A method for spotting a binding substance. 10. The specific adsorptive regions spotted on the plurality of adsorptive regions are heated by bringing the plurality of adsorptive regions on which a solution containing a specific binding substance is spotted into contact with a temperature-controlled heating substrate. The method for spotting a specific binding substance according to claim 1, wherein evaporation of the solution containing the binding substance is forcibly promoted. 11. The absorptive region of the biochemical analysis unit is formed by filling an absorptive material into the plurality of holes formed in the substrate. 11. The method for spotting a specific binding substance according to any one of 1 to 10. 12. The plurality of holes are respectively formed by through holes, and the absorptive region of the biochemical analysis unit is provided with an absorptive material in the plurality of through holes formed in the substrate. The method for spotting a specific binding substance according to claim 11, wherein the adsorptive membrane containing the film is formed by press-fitting. 13. The biochemical analysis unit comprises an absorptive substrate formed of an absorptive material, and the substrate is brought into close contact with the absorptive substrate so that the absorptive substances in the plurality of holes of the substrate are adsorbed. The specific binding substance spotting method according to any one of claims 1 to 10, wherein the absorptive region of the biochemical analysis unit is formed by a biocompatible substrate. 14. The radiation and / or the radiation of the substrate of the biochemical analysis unit, and / or when the radiation and / or the light penetrates through the substrate by a distance equal to the distance between the adjacent absorptive regions. 2. The property of attenuating the energy of 1 to ⅕ or less.
14. The method for spotting a specific binding substance according to any one of 1 to 13. 15. The specific binding substance according to claim 14, wherein the substrate of the biochemical analysis unit is formed of a material selected from the group consisting of a metal material, a ceramic material and a plastic material. Spotting method. 16. The specific binding substance according to claim 1, wherein 10 or more of the absorptive regions are formed on the substrate of the biochemical analysis unit. Spotting method. 17. The peculiar claim according to claim 1, wherein each of the absorptive regions of the biochemical analysis unit has a size of less than 5 mm 2. Method for spotting chemically bound substances. 18. The absorptive region is formed on the substrate of the biochemical analysis unit at a density of at least 10 pieces / square centimeter, and any one of claims 1 to 17 is provided. Method for spotting specific binding substance of. 19. The bioadhesive region of the biochemical analysis unit is formed of a carbon material or a porous material capable of forming a membrane filter. The method for spotting a specific binding substance according to 1. 20. The specific according to any one of claims 1 to 18, wherein the plurality of absorptive regions of the biochemical analysis unit are formed by a plurality of fiber bundles. A method for spotting a binding substance. 21. A holding means for holding a biochemical analysis unit having a substrate in which a plurality of absorptive regions are formed apart from each other, and the biochemical analysis unit held by the holding means. At least one spotting head for spotting a solution containing a specific binding substance on a plurality of absorptive regions, and the biochemical analysis unit,
Specific binding provided on the opposite side of the at least one spotting head by evaporation promoting means for forcibly promoting evaporation of the solution containing the specific binding substance spotted on the plurality of adsorptive regions. Material spotting device. 22. One spotting head,
While relatively moving the spotting head and the substrate of the biochemical analysis unit two-dimensionally,
22. The spotting device for a specific binding substance according to claim 21, wherein a solution containing the specific binding substance is spotted on the plurality of absorptive regions from the spotting head. 23. The spotting device for a specific binding substance according to claim 22, further comprising a scanning mechanism for moving said holding means two-dimensionally with respect to said spotting head. 24. The plurality of spotting heads arranged in the same pattern as the plurality of absorptive regions formed on the substrate of the biochemical analysis unit. Specific binding substance spotting device. 25. The spotting device for a specific binding substance according to claim 21, wherein the spotting head includes an inkjet injector for ejecting a solution containing the specific binding substance. . 26. The spotting device for a specific binding substance according to claim 21, wherein the spotting head has a dropping pin for dropping a solution containing the specific binding substance. . 27. The evaporation promoting means is constituted by an air injection means for injecting air of which temperature and humidity are controlled, toward the plurality of absorptive regions on which the solution containing the specific binding substance is spotted. 2. The method according to claim 2, wherein
27. A spotting device for a specific binding substance according to any one of 1 to 26. 28. The spotting of a specific binding substance according to claim 27, wherein the air injecting means is configured to inject air having a temperature of 40 ° C. or higher and a humidity of 50% or lower. apparatus. 29. The specific binding substance according to claim 27 or 28, wherein the air jetting means is configured to jet air at a velocity of 0.1 m / sec to 10 m / sec. Spotting device. 30. The evaporation promoting means is constituted by an infrared source which emits infrared rays.
27. A spotting device for a specific binding substance according to any one of 1 to 26. 31. The infrared source is 1 .mu.m to 30 .mu.m.
31. The specific binding substance spotting device according to claim 30, which is configured to emit infrared light having a wavelength of m. 32. The specific binding substance spotting device according to claim 21, wherein the evaporation promoting means is constituted by a microwave heating means. 33. The spotting device for a specific binding substance according to claim 21, wherein the evaporation promoting means is constituted by a high frequency heating means. 34. The high frequency heating means is 2 to 20.
800-2000V with megacycle frequency
A high frequency with an electric field strength of 1 / 100k / cm
34. The spotting device for a specific binding substance according to claim 33, which is configured to be capable of outputting W · hr. 35. The evaporation promoting means is constituted by a heating substrate whose temperature is controlled so that it can contact the biochemical analysis unit held by the holding means. A spotting device for the specific binding substance according to claim 1.