JP2003088399A - Hybridization method and device and unit for biochemical analysis - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hybridization device, and to provide a method for repeatably and simply executing hybridization with the hybridization device. SOLUTION: This hybridization device is characterized by comprising a sliding member for sliding a unit for biochemical analysis, a hybridization tank, a washing treatment tank, a hybridization solution tank, a probe solution chip which can supply a probe solution containing a labeled organism-derived substance into the hybridization tank, a washing solution tank, a hybridization solution recovery tank, a washing solution recovery tank, a means for vibrating the unit for the biochemical analysis, and a lifting mechanism for the unit for the biochemical analysis, wherein the sliding member can be moved between the hybridization tank and the washing treatment tank, and the unit for the biochemical analysis is received in the hybridization tank or the washing treatment tank.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hybridization method and apparatus and a biochemical analysis unit. More specifically, it is a high-performance hybridization apparatus that can perform hybridization easily and reproducibly. The present invention relates to a hybridization method and device and a biochemical analysis unit.

[0002]

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

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

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

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

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

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

[0008]

In a microarray analysis system or a macroarray analysis system, a solution containing a specific binding substance is dropped at different positions on the surface of a biochemical analysis unit such as a membrane filter, and a large number of A specific substance contained in the spot-like region is a biological substance labeled with a radioactive substance, a fluorescent substance, or a labeling substance that causes chemiluminescence when contacted with a chemiluminescent substrate. By hybridizing with the binding substance, the specific binding substance is selectively labeled, and the stimulable phosphor layer of the stimulable phosphor sheet is changed by the radioactive labeling substance selectively contained in a large number of spot-shaped regions. Exposed, the exposed photostimulable phosphor layer, scanned by excitation light, to excite the photostimulable phosphor contained in the photostimulable phosphor layer, Photostimulated photostimulable light emitted from the photostimulable phosphor is generated photoelectrically to generate data for biochemical analysis, or a large number of spot-shaped regions are scanned with excitation light to form a large number of spot-shaped regions. Exciting the fluorescent substance selectively contained, photoelectrically detecting the fluorescence emitted from the fluorescent substance, to generate biochemical analysis data, or
It is required to generate data for biochemical analysis by contacting a chemiluminescent substrate with a labeling substance selectively contained in many spot-like regions and photoelectrically detecting chemiluminescence emitted from the labeling substance. Has been done.

In the case of hybridizing a specific binding substance with a substance of biological origin, conventionally, an experimenter manually performed biochemistry such as a membrane filter in which a large number of spot-shaped regions containing the specific binding substance were formed. The analysis unit is placed in a hybridization bag, and a substance derived from a living body labeled with a labeling substance that causes chemiluminescence by contacting with a radioactive labeling substance, a fluorescent substance, or a chemiluminescent substrate is placed in the hybridization bag. Add a hybridization solution containing the product, and apply vibration to the hybridization bag to move the substance of biological origin by convection or diffusion to hybridize the specific binding substance and the substance of biological origin. Remove from hybridization bag and fill with wash solution Placed in the vessel for cleaning was generally.

However, the experimenter manually puts the unit for biochemical analysis in the hybridization bag, adds the hybridization solution, and vibrates the hybridization bag so that the specific binding substance and the biological origin can be obtained. When the biochemical analysis unit is hybridized and the unit for biochemical analysis is taken out from the hybridization bag and placed in a container filled with a washing solution for washing, the results of the hybridization vary depending on the experimenter and the reproducibility is reproducible. However, there is a problem in that the reproducibility may decrease even if the same experimenter.

[0011] Therefore, an object of the present invention is to provide a hybridization method and apparatus and a biochemical analysis unit which can perform hybridization easily with good reproducibility.

[0012]

The object of the present invention is to:
A biochemical analysis in which a plurality of absorptive regions containing a specific binding substance having a known structure or property are formed apart from each other, and at least three sides of the substrate are attached to a rigid frame body. The upper part of the frame of the unit for
The hybridization chamber is held by a biochemical analysis unit holding member that is movable in a substantially horizontal direction along the guide means and has an elevating mechanism, and the elevating mechanism lowers the biochemical analysis unit to obtain a hybridization tank. The biochemical analysis unit is repeatedly moved relative to the hybridization solution in the up-and-down direction, and pre-hybridization is performed to perform the pre-hybridization. A probe solution containing a substance of biological origin labeled with a labeling substance was supplied to the hybridization solution contained in the tank, and the biochemical analysis unit was added to the hybridization solution to which the probe solution was added. Repeatedly move up and down relative to the solution. By performing the hybridization, by the elevating mechanism, the biochemical analysis unit is raised, taken out from the hybridization tank, the biochemical analysis unit holding member is moved along the guide means, By the elevating mechanism, the biochemical analysis unit is lowered, immersed in a cleaning solution contained in a cleaning treatment tank, the biochemical analysis unit, with respect to the cleaning solution, repeatedly in the vertical direction, A hybridization method, wherein the biochemical analysis unit is relatively moved to perform a cleaning process, and the biochemical analysis unit is raised by the elevating mechanism and taken out from the cleaning process tank. Achieved by

According to the present invention, a plurality of absorptive regions containing a specific binding substance having a known structure or characteristic are formed so as to be spaced apart from each other, and at least three sides of the substrate are
The upper part of the frame of the biochemical analysis unit attached to the rigid frame can be moved in a substantially horizontal direction along the guide means, and by the biochemical analysis unit holding member equipped with a lifting mechanism, Hold it, lower the biochemical analysis unit by the elevating mechanism, and immerse it in the hybridization solution contained in the hybridization tank.
The biochemical analysis unit is repeatedly moved relative to the hybridization solution in the up and down direction to perform prehybridization, and the hybridization solution contained in the hybridization tank is labeled with a labeling substance. The probe solution containing the substance derived from the living body was supplied, and the biochemical analysis unit was repeatedly moved relative to the hybridization solution in the vertical direction relative to the solution to which the probe solution was added. Hybridization is carried out, the biochemical analysis unit is raised by the elevating mechanism, taken out from the hybridization tank, and along the guide means,
The biochemical analysis unit holding member is moved, and the elevating mechanism lowers the biochemical analysis unit to immerse it in the cleaning solution contained in the cleaning treatment tank. Repeatedly moving up and down, relative to each other to perform the cleaning process of the biochemical analysis unit, and the elevating mechanism raises the biochemical analysis unit to remove it from the cleaning process tank. Therefore, the hybridization solution, the probe solution containing the substance derived from the living body labeled with the labeling substance is added to the hybridization solution, and the prepared solution and the washing solution are all prepared in the biochemical analysis unit. Both sides of the absorptive area should be in uniform contact, and therefore substances of biological origin should be included in the absorptive area and hybridize. It is possible to significantly improve the probability of encountering a heterologous binding substance, and even if a substance of biological origin that should not be bound originally is hybridized to the specific binding substance in the hybridization step. The substance derived from the living body that should not be bound to the specific binding substance can be effectively stripped and removed, so that the efficiency of hybridization can be significantly improved and It is possible to significantly reduce the time required.

Further, according to the present invention, by simply holding the upper portion of the frame of the biochemical analysis unit by the biochemical analysis unit holding member, a plurality of adsorption units of the biochemical analysis unit are automatically held. The specific binding substance contained in the active region can be selectively hybridized with the substance of biological origin which is labeled with the labeling substance and contained in the hybridization solution, and the biochemical analysis unit can be washed. Therefore, it is possible for the experimenter to significantly improve the reproducibility of the hybridization without causing the hybridization result to vary, and to realize the significant labor saving.

Further, according to this embodiment, since the biochemical analysis unit has at least three sides of the substrate attached to the frame having rigidity, the biochemical analysis unit is extremely thin and Even when it is difficult to handle, it is extremely easy to use the biologically-derived substances contained in the hybridization solution, which are labeled with the specific binding substances contained in the multiple absorptive regions of the biochemical analysis unit. It becomes possible to selectively hybridize the substance of (4) and wash the unit for biochemical analysis.

[0016] In a preferred aspect of the present invention, the biochemical analysis unit holding member is provided with a vibration mechanism for vertically vibrating the biochemical analysis unit held by the biochemical analysis unit holding member. By the vibration mechanism, the biochemical analysis unit is vertically vibrated in the hybridization solution, in the hybridization solution in which the probe solution is added, and in the washing solution. Is configured to let.

According to a preferred embodiment of the present invention, the biochemical analysis unit holding member is provided with a vibration mechanism for vertically vibrating the biochemical analysis unit held by the biochemical analysis unit holding member, By vibrating mechanism, biochemical analysis unit in the hybridization solution,
Since the probe solution is added to the hybridization solution and the washing solution is configured to vibrate vertically, the probe solution is added to the hybridization solution and the hybridization solution. , The prepared solution and the washing solution are uniformly in contact with both surfaces of all the absorptive regions of the biochemical analysis unit, respectively. Therefore, the substance derived from the living body is hybridized in the absorptive region. It is possible to significantly improve the probability of encountering a specific binding substance to be bound, and in the hybridization step, a substance derived from a living body that should not be bound originally is hybridized to the specific binding substance. Even if the substance of biological origin that should not be bound to the specific binding substance,
Since it can be effectively peeled and removed, the efficiency of hybridization can be significantly improved, and the time required for hybridization can be significantly shortened.

In another preferred embodiment of the present invention, a first vibrating mechanism for vertically vibrating the hybridization tank and a second vibrating mechanism for vertically vibrating the washing treatment tank are provided. The first vibration mechanism vibrates the hybridization tank in the vertical direction, and the second vibration mechanism vibrates the washing processing tank in the vertical direction.

According to another preferred embodiment of the invention,
A first vibrating mechanism for vertically vibrating the hybridization tank and a second vibrating mechanism for vertically vibrating the washing treatment tank are provided, and the first vibrating mechanism vertically vibrates the hybridization tank. Since the cleaning treatment tank is vibrated in the vertical direction by the second vibrating mechanism, the probe solution is added to the hybridization solution and the hybridization solution to prepare the solution and the cleaning solution. Respectively uniformly contact both surfaces of all the adsorptive regions of the biochemical analysis unit, and therefore the substance of biological origin encounters the specific binding substance to be hybridized contained in the adsorptive region. It makes it possible to improve the probability significantly, and it should not be bound by nature in the process of hybridization. Even if the body-derived substance is hybridized to the specific binding substance, the biological substance that should not have been bound to the specific binding substance can be effectively peeled off and removed. The efficiency of hybridization can be significantly improved, and the time required for hybridization can be significantly shortened.

In a preferred embodiment of the present invention, the biochemical analysis unit is moved by the elevating mechanism before the biochemical analysis unit is dipped in a hybridization solution contained in a hybridization tank. By descending and immersing in the pretreatment liquid contained in the pretreatment tank, the biochemical analysis unit is repeatedly moved relative to the pretreatment liquid in the up-and-down direction repeatedly and by the elevating mechanism. , Raising the biochemical analysis unit, taking out from the pretreatment tank, moving the attachment member along the guide means, and lowering the biochemical analysis unit by the elevating mechanism, It is configured to be immersed in the hybridization solution contained in the hybridization tank.

A preferred embodiment of the invention makes it possible to automate the pretreatment in addition to prehybridization, hybridization and washing.

In a further preferred aspect of the present invention, the cleaning solution is discharged from the cleaning processing tank, and a new cleaning solution is supplied to the cleaning processing layer to clean the biochemical analysis unit. It is configured to repeat.

The above object of the present invention also includes a substrate in which a plurality of absorptive regions containing a specific binding substance having a known structure or property are formed apart from each other, and at least three sides of the substrate are rigid. A biochemical analysis unit holding means capable of holding the upper side of the frame of the biochemical analysis unit attached to the frame having a biochemical analysis unit, and movable in a substantially horizontal direction along the guide means; And a hybridization treatment tank in which the hybridization is performed, a washing treatment tank in which the washing treatment of the biochemical analysis unit is performed, and a hybridization solution, and a hybridization treatment tank capable of supplying the hybridization solution. A hybridization solution tank and a probe containing a biological substance labeled with a labeling substance. A probe solution chip that contains a solution and can supply a probe solution to the hybridization tank; a cleaning solution tank that contains a cleaning solution and can supply a cleaning solution to the cleaning treatment tank; A hybridization solution recovery tank capable of recovering the probe solution added to the hybridization solution, a cleaning solution recovery tank capable of recovering the cleaning solution from the cleaning treatment tank, and the biochemical analysis unit holding means The biochemical analysis unit thus prepared, the hybridization solution contained in the hybridization tank, the probe solution is added to the hybridization solution, and the solution contained in the hybridization tank and the washing treatment tank. Vertical direction with respect to the cleaning solution The biochemical analysis unit holding means is configured to be movable between the hybridization tank and the washing treatment tank along the guide means. , The biochemical analysis unit holding means,
An elevating mechanism for elevating and lowering the biochemical analysis unit is provided, wherein the elevating mechanism accommodates the biochemical analysis unit in the hybridization tank or the cleaning treatment tank, and the hybridization tank or the cleaning treatment tank. From the above, the biochemical analysis unit can be taken out, and the biochemical analysis unit can be moved up and down.

According to the present invention, the hybridization apparatus includes a substrate having a plurality of absorptive regions containing a specific binding substance having a known structure or property, which are separated from each other, and at least three sides of the substrate are provided. , A biochemical analysis unit holding means capable of holding the upper side of the frame of the biochemical analysis unit attached to the rigid frame, and moving in a substantially horizontal direction along the guide means; A hybridization tank for carrying out hybridization and hybridization, a washing tank for washing the biochemical analysis unit, and a hybridization solution containing a hybridization solution and capable of supplying the hybridization solution to the hybridization tank. Contains a solution tank and a substance of biological origin labeled with a labeling substance The probe solution chip that contains the lobe solution and can supply the probe solution to the hybridization tank, the washing solution tank that contains the cleaning solution and can supply the cleaning solution to the cleaning treatment tank, and the hybridization solution from the hybridization tank In addition, a hybridization solution recovery tank capable of recovering the solution to which the probe solution has been added, a cleaning solution recovery tank capable of recovering the cleaning solution from the cleaning treatment tank, and a biochemical analysis unit holding means The analysis unit is placed above and below the hybridization solution contained in the hybridization tank, the probe solution added to the hybridization solution, and the solution contained in the hybridization tank and the washing solution contained in the washing treatment tank. Direction, repeat, move relative The biochemical analysis unit holding means is configured to be movable between the hybridization tank and the cleaning treatment tank along the guide means, and the biochemical analysis unit holding means is provided with a vibrating means. Equipped with an elevating mechanism that elevates and lowers the analysis unit.The elevating mechanism stores the biochemical analysis unit in the hybridization tank or the washing treatment tank, and removes the biochemical analysis unit from the hybridization tank or the washing treatment tank. As described above, since the biochemical analysis unit is configured to be movable up and down, the biochemical analysis unit held by the biochemical analysis unit holding means is shaken by the vibrating means. The probe solution is added to the hybridization solution and the hybridization solution, and the hybridization is performed. A solution in which the probe solution is added to the hybridization solution and the hybridization solution by repeatedly moving the solution contained in the tank and the cleaning solution contained in the cleaning treatment tank in the vertical direction. The washing solution and the washing solution, respectively, can be uniformly contacted with both surfaces of all the adsorptive regions of the biochemical analysis unit, so that the substance of biological origin should be hybridized to the adsorptive regions. It is possible to significantly improve the probability of encountering a specific binding substance, and even if a substance of biological origin that should not be bound originally is hybridized to the specific binding substance in the hybridization step. , Effectively exfoliates and removes substances of biological origin that should not have been bound to specific binding substances Consists, the efficiency of hybridization can be greatly improved, it is possible to greatly reduce the time required for hybridization.

Further, according to the present invention, by simply holding the upper part of the frame of the biochemical analysis unit by the biochemical analysis unit holding means, a plurality of adsorption units of the biochemical analysis unit are automatically held. The specific binding substance contained in the active region can be selectively hybridized with the substance of biological origin which is labeled with the labeling substance and contained in the hybridization solution, and the biochemical analysis unit can be washed. Therefore, it is possible for the experimenter to significantly improve the reproducibility of the hybridization without causing the hybridization result to vary, and to realize the significant labor saving.

Furthermore, according to the present invention, since the biochemical analysis unit has at least three sides of the substrate attached to the frame having rigidity, the biochemical analysis unit is extremely thin and handles itself. Even if it is difficult to do so, it is extremely easy to label the specific binding substance contained in the plurality of absorptive regions of the biochemical analysis unit with the labeling substance and The substances can be selectively hybridized and the biochemical analysis unit can be washed.

[0027] In a preferred aspect of the present invention, the vibrating means is provided in the biochemical analysis unit holding means, and is configured to vertically vibrate the biochemical analysis unit. .

According to a preferred embodiment of the present invention, the vibrating means is provided in the biochemical analysis unit holding means and is configured to vibrate the biochemical analysis unit in the vertical direction. By vibrating the biochemical analysis unit in the hybridization solution, the solution in which the probe solution is added to the hybridization solution, and the washing solution by the vibrating means, the hybridization solution is vertically vibrated. The probe solution added to the hybridization solution and the washing solution can be uniformly contacted with both surfaces of all the absorptive regions of the biochemical analysis unit, respectively. Greatly increases the probability of encountering a specific binding substance contained in the adsorptive region and to be hybridized In addition, the substance of biological origin which should not be bound originally should be bound to the specific binding substance in the hybridization step even if it is hybridized to the specific binding substance. Effectively exfoliate substances that were not living,
Since it can be removed, the efficiency of hybridization can be significantly improved, and the time required for hybridization can be significantly shortened.

In another preferred embodiment of the present invention, the hybridization apparatus further comprises a vibrating table to which the hybridization tank and the washing treatment tank are attached, and the vibrating means includes the vibrating table.
It is configured to vibrate in the vertical direction.

According to another preferred embodiment of the invention,
The hybridization apparatus further includes a vibrating table to which a hybridization tank and a washing treatment tank are attached, and the vibrating means is configured to vibrate the vibrating table in the vertical direction. By vibrating the vibrating table in the vertical direction, the hybridization solution, the solution in which the probe solution was added to the hybridization solution, and the washing solution were respectively applied to both sides of all the absorptive regions of the biochemical analysis unit. It is possible to make uniform contact, and therefore, it is possible to significantly improve the probability that a substance derived from a living body encounters a specific binding substance contained in the adsorptive region to be hybridized, and hybridization is performed. In the process of, the substance of biological origin that should not be bound originally is
Even if it is hybridized to the specific binding substance, the substance derived from the living body that should not be bound to the specific binding substance can be effectively peeled off and removed, thereby improving the efficiency of hybridization. It can be significantly improved, and the time required for hybridization can be significantly reduced.

In another preferred embodiment of the present invention, the hybridization apparatus further comprises a first vibrating table to which the hybridization tank is attached and a second vibrating table to which the washing treatment tank is attached. The vibrating means includes a first vibrating means that vibrates the first vibrating table in the vertical direction, and a second vibrating means that vibrates the second vibrating table in the vertical direction. ing.

According to another preferred embodiment of the invention,
The hybridization apparatus further includes a first vibrating table to which a hybridization tank is attached and a second vibrating table to which a cleaning treatment tank is attached, and the vibrating means moves the first vibrating table up and down. Since the first vibrating means for vibrating in the vertical direction and the second vibrating means for vertically vibrating the second vibrating table are provided, the first vibrating means
The probe solution is added to the hybridization solution and the hybridization solution by vertically vibrating the first vibrating table and vertically vibrating the second vibrating table by the second vibrating means. Solution and washing solution, respectively, can be uniformly contacted with both surfaces of all the adsorptive regions of the biochemical analysis unit, so that the substance of biological origin is hybridized to the adsorptive regions. It is possible to significantly improve the probability of encountering a specific binding substance to be bound, and in the hybridization step, a substance derived from a living body that should not be bound originally is hybridized to the specific binding substance. Even if it is possible to effectively exfoliate and remove substances of biological origin that should not have been bound to specific binding substances? , The efficiency of hybridization can be greatly improved, it is possible to greatly reduce the time required for hybridization.

In a preferred embodiment of the present invention, with respect to the moving direction of the biochemical analysis unit holding means,
On the upstream side of the hybridization tank, the biochemical analysis unit is provided with a biochemical analysis unit setting section for holding the biochemical analysis unit in the biochemical analysis unit holding means, and the moving direction of the biochemical analysis unit holding means. On the other hand, on the downstream side of the cleaning treatment tank, the biochemical analysis unit is detached from the biochemical analysis unit holding means, and a biochemical analysis unit extraction section is provided, and the biochemical analysis unit is provided. Holding means is configured to be movable along the guide means among the biochemical analysis unit setting section, the hybridization tank, the washing treatment tank, and the biochemical analysis unit removal section.

A preferred embodiment of the present invention makes it possible to automate the pretreatment in addition to prehybridization, hybridization and washing.

[0035] In a preferred aspect of the present invention, a pretreatment tank for performing pretreatment is provided upstream of the hybridization tank with respect to the moving direction of the biochemical analysis unit holding means, and a pretreatment tank. A pretreatment liquid tank that contains a liquid and can supply the pretreatment liquid to the pretreatment layer; and a pretreatment liquid recovery tank that can collect the pretreatment liquid from the pretreatment liquid tank, and the biochemical analysis Unit holding means is configured to be movable along the guide means among the pretreatment tank, the hybridization tank, and the washing treatment tank, and the vibrating means is further provided for the biochemical analysis. The biochemical analysis unit held by the unit holding means is repeatedly movable in the vertical direction relative to the pretreatment liquid stored in the pretreatment tank.

According to a preferred embodiment of the present invention, the vibrating means further comprises a biochemical analysis unit held by the biochemical analysis unit holding means with respect to the pretreatment liquid contained in the pretreatment tank. Since it is configured to be repeatedly movable in the vertical direction repeatedly, the pretreatment liquid can be uniformly contacted with both surfaces of all the absorptive regions of the biochemical analysis unit. It is possible to significantly improve the efficiency of pretreatment.

[0037] In a preferred aspect of the present invention, the vibrating means is provided in the biochemical analysis unit holding means, and is configured to vibrate the biochemical analysis unit in the vertical direction. .

According to a preferred embodiment of the present invention, the biochemical analysis unit is vertically moved by vibrating means.
By vibrating, the pretreatment solution, hybridization solution, hybridization solution, probe solution added solution and washing solution are evenly contacted to both sides of all absorptive regions of the biochemical analysis unit. Therefore, it is possible to significantly improve the pretreatment efficiency, and it is possible to significantly increase the probability that a substance derived from a living body encounters a specific binding substance contained in the adsorptive region and to be hybridized. In addition, the substance of biological origin which should not be bound originally should be bound to the specific binding substance in the hybridization step even if it is hybridized to the specific binding substance. The substance of biological origin that was not
Since it can be effectively peeled and removed, the efficiency of hybridization can be significantly improved, and the time required for hybridization can be significantly shortened.

In another preferred embodiment of the present invention, the hybridization apparatus further comprises a vibrating table to which the pretreatment bath, the hybridization bath and the washing treatment bath are attached, and the vibrating means comprises:
The vibrating table is configured to vibrate vertically.

According to another preferred embodiment of the present invention,
By vibrating the vibrating table in the vertical direction by the vibrating means, the pretreatment solution, the hybridization solution,
The hybridization solution can be uniformly contacted with the probe solution-added solution and the washing solution, respectively, on both sides of all the absorptive regions of the biochemical analysis unit, thus significantly improving the pretreatment efficiency. It is possible to improve the probability that the substance derived from the living body will meet with the specific binding substance contained in the adsorptive region and to be hybridized. In the process, even if the biological substance that should not be bound originally is hybridized to the specific binding substance, the biological substance that should not be bound to the specific binding substance is effectively peeled off. And can be removed, the efficiency of hybridization can be greatly improved. It is possible to greatly reduce the time required.

In another preferred embodiment of the present invention, the hybridization apparatus further comprises a first vibrating table to which the pretreatment tank is attached and a second vibrating table to which the hybridization tank is attached. A third vibrating table to which the cleaning tank is attached, wherein the vibrating means vibrates the first vibrating table in the vertical direction, and the second vibrating table. A second vibrating means for vibrating the table in the vertical direction and the third vibrating table,
A third vibrating means for vibrating vertically is provided.

According to another preferred embodiment of the present invention,
The first vibrating means vibrates the first vibrating table in the vertical direction, and the second vibrating means causes the second vibrating table to vibrate.
The probe is added to the pretreatment liquid, the hybridization solution, and the hybridization solution by vertically vibrating and vertically vibrating the third vibrating table by the third vibrating means. The washing solution can be brought into uniform contact with both surfaces of all the absorptive regions of the biochemical analysis unit, and therefore the pretreatment efficiency can be significantly improved and the biological material However, it is possible to significantly improve the probability of encountering a specific binding substance contained in the adsorptive region and to be hybridized, and, in the step of hybridization, it is originally derived from a living body that should not be bound. Substances of biological origin that should not be bound to a specific binding substance even if the substance is hybridized to the specific binding substance , Effectively detached, because it is possible to remove, the efficiency of hybridization can be greatly improved, it is possible to greatly reduce the time required for hybridization.

In a preferred embodiment of the present invention, with respect to the moving direction of the biochemical analysis unit holding means,
On the upstream side of the pretreatment tank, the biochemical analysis unit is provided with a biochemical analysis unit setting unit for holding the biochemical analysis unit holding unit, and the moving direction of the biochemical analysis unit holding unit. On the other hand, on the downstream side of the cleaning treatment tank, the biochemical analysis unit,
The biochemical analysis unit holding means is provided with a biochemical analysis unit removing section that is removed from the biochemical analysis unit holding means, and the biochemical analysis unit holding means is along the guide means. It is configured to be movable among the pretreatment tank, the hybridization tank, the washing tank, and the biochemical analysis unit take-out section.

In a preferred embodiment of the present invention, the hybridization device further comprises a radiation sensor for detecting the concentration of the radiolabeled substance contained in the washing solution contained in the washing treatment tank.

According to a preferred embodiment of the present invention, the hybridization apparatus further comprises a radiation sensor for detecting the concentration of the radioactive labeling substance contained in the washing solution contained in the washing treatment tank. When a biologically-derived substance labeled with a substance is hybridized with a specific binding substance, the end point of washing is determined by detecting the concentration of the radiolabeled substance contained in the washing solution during the washing process. Further, it becomes possible to collect and manage a solution containing a radiolabeled substance at a predetermined concentration or higher separately from a solution having a radiolabeled substance concentration lower than the predetermined concentration.

In a preferred embodiment of the present invention, the substance derived from a living body is at least one selected from the group consisting of a radiolabeling substance, a fluorescent substance and a labeling substance which produces chemiluminescence by contacting with a chemiluminescent substrate. It is labeled with the labeling substance.

In the present invention, the fact that the substance derived from the living body is labeled with a fluorescent substance means that the substance is labeled with a fluorescent dye, and that the enzyme is bound to the labeled sample and then the enzyme is used as a fluorescent substrate. When the fluorescent substance is brought into contact with the fluorescent substance to emit fluorescence, the fluorescent substance is labeled with the obtained fluorescent substance.

The object of the present invention is also provided with a substrate capable of forming a plurality of spot-shaped regions containing a specific binding substance, which are spaced apart from each other, and at least three sides of the substrate are attached to a rigid frame body. It is achieved by a biochemical analysis unit characterized by the above.

According to the present invention, the biochemical analysis unit comprises a substrate capable of forming a plurality of spot-like regions containing a specific binding substance, separated from each other, and at least three sides of the substrate have rigidity. Because it is attached to the frame,
It is easy to handle, and when the specific binding substance is dropped on the substrate to form multiple spot-shaped regions containing the specific binding substance, the specific binding substance contained in the multiple spot-shaped regions is Also, when hybridizing a substance of biological origin contained in a hybridization solution,
It will be possible to easily automate it, and it will be possible to realize significant labor savings, and it will be possible to generate highly reliable data for biochemical analysis by eliminating variations among experimenters. .

In a preferred embodiment of the present invention, the frame has at least two positioning through holes.

According to a preferred embodiment of the present invention, since at least two positioning through-holes are formed in the frame of the biochemical analysis unit, the biochemical analysis unit can be accurately positioned to achieve a unique position. The binding substance can be dropped on a desired position on the substrate, and the spotting device can be easily automated.

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

In another preferred aspect of the present invention, a plurality of absorptive regions containing an absorptive material are formed on the substrate of the biochemical analysis unit so as to be separated from each other.

According to another preferred embodiment of the invention,
Since a plurality of absorptive regions containing an absorptive material are formed on the substrate of the biochemical analysis unit so as to be separated from each other,
By dropping the specific binding substance on the plurality of absorptive regions formed on the substrate, the size and distribution of the spot-shaped region containing the specific binding substance can be accurately controlled, and therefore, It becomes possible to generate biochemical analysis data with excellent quantitativeness.

In a further preferred aspect of the present invention, the plurality of absorptive regions of the biochemical analysis unit are:
The substrate is formed by filling an adsorptive material in holes formed so as to be separated from each other.

In a further preferred aspect of the present invention, the plurality of absorptive regions of the biochemical analysis unit are:
The substrate is formed by filling an adsorptive material in through holes formed so as to be separated from each other.

In a further preferred aspect of the present invention, the plurality of absorptive regions of the biochemical analysis unit have an absorptive film containing an absorptive material in a plurality of through holes formed in the substrate. Is press-fitted and formed.

According to a further preferred embodiment of the present invention, the biochemical analysis is simply performed by press-fitting the adsorptive film containing the adsorptive material into the plurality of through holes formed in the substrate of the biochemical analysis unit. Since it is possible to form a plurality of absorptive regions in the medical unit, it becomes possible to manufacture the biochemical analysis unit very easily.

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

[0060] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is formed with 50 or more absorptive regions.

[0061] 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.

[0063] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is provided with 1000
The absorptive region described above is formed.

[0064] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is provided with 5000
The absorptive region described above is formed.

[0065] In a further preferred aspect of the present invention, the substrate of the biochemical analysis unit is provided with 1000
Zero or more of the absorptive regions are formed.

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

In a preferred aspect of the present invention, each of the plurality of absorptive regions of the biochemical analysis unit has a size of less than 5 mm 2.

[0069] In a further preferred aspect of the present invention, each of the plurality of absorptive regions of the biochemical analysis unit has a size of less than 1 mm 2.

[0070] In a further preferred aspect of the present invention, each of the plurality of absorptive regions of the biochemical analysis unit has a size of less than 0.5 mm 2.

[0071] In a further preferred aspect of the present invention, each of the plurality of absorptive regions of the biochemical analysis unit has a size of less than 0.1 mm 2.

[0072] In a further preferred aspect of the present invention, each of the plurality of absorptive regions of the biochemical analysis unit has a size of less than 0.05 mm 2.

In a further preferred aspect of the present invention, each of the plurality of absorptive regions of the biochemical analysis unit has a size of less than 0.01 mm 2.

[0074] In a preferred aspect of the present invention, the plurality of absorptive regions are formed on the substrate of the biochemical analysis unit at a density of 10 or more per cm 2.

[0075] In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the substrate of the biochemical analysis unit at a density of 50 or more per cm 2.

In a further preferred aspect of the present invention, the plurality of absorptive regions are formed on the substrate of the biochemical analysis unit at a density of 100 or more per cm 2.

[0077] In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the substrate of the biochemical analysis unit at a density of 500 or more per cm 2.

[0078] In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the substrate of the biochemical analysis unit at a density of 1,000 or more per cm 2.

[0079] In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the substrate of the biochemical analysis unit at a density of 5000 or more per cm 2.

In a further preferred aspect of the present invention, the plurality of absorptive regions are formed on the substrate of the biochemical analysis unit at a density of 10,000 or more per cm 2.

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

[0082] In a preferred aspect of the present invention, the plurality of through holes are formed in the substrate of the biochemical analysis unit in a substantially circular shape.

In another preferred aspect of the present invention, the plurality of through holes are formed in a substantially rectangular shape in the substrate of the biochemical analysis unit.

In a preferred aspect of the present invention, the substrate of the biochemical analysis unit has a property of attenuating radiation.

According to a further preferred embodiment of the present invention, since the substrate of the biochemical analysis unit has a property of attenuating radiation, a plurality of absorptive regions are provided on the substrate of the biochemical analysis unit. Even when formed at a high density, it is possible to bind specifically to a substance of biological origin to multiple absorptive regions of the biochemical analysis unit, and it is known that the base sequence, base length, composition, etc. are known. Specific binding substance adsorbed in a plurality of adsorptive regions, a substance of biological origin labeled with a radiolabeling substance is hybridized and selectively labeled, The biochemical analysis unit and the stimulable phosphor sheet are superposed on each other, and a plurality of stimuli formed on the support of the stimulable phosphor sheet by the radioactive labeling substance selectively contained in the plurality of absorptive regions. Fluorescent substance To effectively prevent the electron beam (β-ray) emitted from the radiolabeled substance contained in each adsorptive region from scattering in the substrate of the biochemical analysis unit when exposing the region. Therefore, the electron beam (β-ray) emitted from the radio-labeled substance contained in each adsorptive region is applied to the corresponding stimulable phosphor layer region,
Since it becomes possible to selectively expose the corresponding photostimulable phosphor layer region to light, scanning a plurality of dot-shaped photostimulable phosphor layer regions exposed by the radioactive labeling substance with excitation light. Then, by photoelectrically detecting the photostimulable light emitted from the plurality of photostimulable phosphor layer regions, it becomes possible to generate data for biochemical analysis with high resolution and high quantitativeness. .

In a preferred aspect of the present invention, when the substrate of the biochemical analysis unit is exposed to radiation by a distance equal to the distance between the adjacent absorptive regions, the radiation is Energy of 1/5
It has the following property of damping.

In a further preferred aspect of the present invention, when the substrate of the biochemical analysis unit transmits radiation through the substrate by a distance equal to the distance between the adjacent absorptive regions, The energy of radiation
It has the property of being attenuated to 1/10 or less.

In a further preferred aspect of the present invention, when the substrate of the biochemical analysis unit transmits radiation through the substrate by a distance equal to the distance between the adjacent absorptive regions, The energy of radiation
It has the property of being attenuated to 1/50 or less.

In a further preferred aspect of the present invention, when the substrate of the biochemical analysis unit has radiation transmitted through the substrate by a distance equal to the distance between the adjacent absorptive regions, The energy of radiation
It has the property of being attenuated to 1/100 or less.

In a further preferred aspect of the present invention, when the substrate of the biochemical analysis unit transmits radiation through the substrate by a distance equal to the distance between the adjacent absorptive regions, The energy of radiation
It has the property of being attenuated to 1/500 or less.

In a further preferred aspect of the present invention, when radiation is transmitted through the substrate by a distance equal to the distance between adjacent absorptive regions of the substrate of the biochemical analysis unit, The energy of radiation
It has the property of being attenuated to 1/1000 or less.

In a preferred aspect of the present invention, the substrate of the biochemical analysis unit has a property of attenuating light.

According to a preferred embodiment of the present invention, since the substrate of the biochemical analysis unit has a property of attenuating light, the absorptive region is densely formed on the substrate of the biochemical analysis unit. A substance derived from a living body, which is labeled with a labeling substance that causes chemiluminescence by contacting a specific binding substance that has been formed and is adsorbed in the adsorptive region with a fluorescent substance and / or a chemiluminescent substrate, is selectively used. Even when hybridized, a large number of absorptive regions are irradiated with excitation light to excite fluorescent substances selectively contained in a large number of absorptive regions, and the emitted fluorescence is photoelectrically detected. In doing so, it is possible to effectively prevent the fluorescence emitted from each adsorbent from being scattered within the substrate and being mixed with the fluorescence emitted from the adjacent adsorbent regions. Emitted from It is possible to effectively prevent chemiluminescence from scattering within the substrate and mixing with chemiluminescence emitted from adjacent adsorbent regions, thus detecting fluorescence or chemiluminescence photoelectrically. Therefore, it becomes possible to generate biochemical analysis data with excellent quantification.

[0094] In a preferred aspect of the present invention, when the substrate of the biochemical analysis unit receives light through the substrate by a distance equal to the distance between the adsorbing regions adjacent to each other, Has the property of attenuating the energy of 1/5 or less.

[0095] In a further preferred aspect of the present invention, when the substrate of the biochemical analysis unit transmits light through the substrate by a distance equal to the distance between the adjacent absorptive regions, 1/10 of the energy of light
It has the following property of damping.

[0096] In a further preferred aspect of the present invention, when the substrate of the biochemical analysis unit transmits light through the substrate by a distance equal to the distance between the adjacent absorptive regions, 1/50 the energy of light
It has the following property of damping.

In a further preferred aspect of the present invention, when light is transmitted through the substrate by a distance equal to the distance between the adjacent absorptive regions of the substrate of the biochemical analysis unit, 1/10 of the energy of light
It has the property of being attenuated to 0 or less.

In a further preferred aspect of the present invention, when the substrate of the biochemical analysis unit transmits light through the substrate by a distance equal to the distance between the adjacent absorptive regions, 1/50 the energy of light
It has the property of being attenuated to 0 or less.

In a further preferred aspect of the present invention, when the substrate of the biochemical analysis unit transmits light through the substrate by a distance equal to the distance between the adjacent absorptive regions, 1/10 of the energy of light
It has the property of being attenuated to 00 or less.

In the present invention, the material for forming the substrate of the biochemical analysis unit preferably has a property of attenuating radiation and / or light, but is not particularly limited, and it is not limited to inorganic materials. Either a compound material or an organic compound material can be used, and a metal material, a ceramic material or a plastic material is 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 used to form the substrate of the biochemical analysis unit, and a polymer compound that can be preferably used is, for example, Polyolefin such as polyethylene and polypropylene; acrylic resin such as polymethylmethacrylate, butyl acrylate / methylmethacrylate copolymer; polyacrylonitrile; polyvinyl chloride; polyvinylidene chloride; polyvinylidene fluoride; polytetrafluoroethylene; polychlorotrifluoroethylene; Polycarbonate; Polyester such as polyethylene naphthalate and polyethylene terephthalate; Nylon such as Nylon 6, Nylon 6,6, Nylon 4, 10; Polyimide; Polysulfone; Polyphenyl Nsarufaido; phenolic resins such as novolak; silicon resins such as polydiphenylsiloxane epoxy resin; polyurethane; polystyrene;
Butadiene-styrene copolymer; polysaccharides such as cellulose, cellulose acetate, nitrocellulose, starch, calcium alginate, and hydroxypropylmethylcellulose; chitin; chitosan; sumac; polyamide such as gelatin, collagen and keratin, and copolymerization of these polymer compounds Examples include coalescing. These may be composite materials, and may be filled with metal oxide particles, glass fibers, or the like, if desired, or may be used by blending with an organic compound material.

Generally, the higher the specific gravity is, the higher the radiation attenuating ability is. Therefore, the substrate of the biochemical analysis unit is preferably formed 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 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. Fine particles of a material different from the material forming the substrate of the biochemical analysis unit are used as the light scatterer, and pigments or dyes are used as the light absorber.

In the present invention, a porous material or a fibrous material is preferably used as the absorptive material for forming the absorptive region or the absorptive substrate of the biochemical analysis unit. The absorptive region or the absorptive substrate can be formed by using the porous material and the fiber material together.

In the present invention, the porous material used to form the adsorptive region of the biochemical analysis unit or the adsorptive substrate 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 absorptive region or the absorptive substrate of the biochemical analysis unit is not particularly limited, but it is a carbon material such as activated carbon or a membrane. A material capable of forming a filter is preferably used. Specifically, nylons such as nylon 6, nylon 6,6, nylon 4,10; nitrocellulose, cellulose acetate,
Cellulose derivatives such as cellulose acetate butyrate; collagen; alginic acid, calcium alginate, alginic acid /
Alginic acids such as 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. .

In the present invention, the inorganic porous material used to form the adsorptive region or the adsorptive substrate of the biochemical analysis unit is not particularly limited, but preferably, for example, platinum, Examples thereof include metals such as gold, iron, 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 fibrous material used for forming the absorptive region or the absorptive substrate of the biochemical analysis unit is not particularly limited, but preferably, for example, nylon 6 or nylon. Nylons such as 6,6 and nylon 4,10, nitrocellulose,
Examples thereof include cellulose derivatives such as cellulose acetate and cellulose butyrate.

In the present invention, the absorptive region of the biochemical analysis unit is subjected to oxidation treatment such as electrolytic treatment, plasma treatment and arc discharge; primer treatment using silane coupling agent, titanium coupling agent and the like; surfactant. It can also be formed by surface treatment such as treatment.

[0111]

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

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

As shown in FIG. 1, the biochemical analysis unit 1 according to this embodiment is formed of an absorptive substrate 2 formed of nylon 6 and a material having rigidity such as metal or plastic. , Two plate members 3 and 3 each having a rectangular opening 3a are formed, the two plate members 3 and 3 are fixed with an adhesive to form a frame body 4, and the frame body 4 is formed. Plate members 3 and 3 constituting
The peripheral region of the biochemical analysis unit 1 is sandwiched between the two.

As shown in FIG. 1, the frame body 4 of the biochemical analysis unit 1 is provided with two circular positioning through holes 5a and 5b.

In the biochemical analysis, a plurality of different cDNAs having known base sequences as different specific binding substances are provided at predetermined positions on the adsorptive substrate 2 of the biochemical analysis unit 1 separated from each other. , Using a spotting device, is dropped.

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

As shown in FIG. 2, the spotting device comprises a spotting head 9 equipped with an injector for injecting a solution of a specific binding substance toward the biochemical analysis unit 1, and the spotting head 9 comprises The drive mechanism 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 drive mechanism of the spotting device is attached to the frame 11 fixed to the substrate 10 on which the biochemical analysis unit 1 on which the specific binding substance is to be dropped is placed.

As shown in FIG. 2, a sub-scanning pulse motor 12 and a pair of rails 13, 13 are provided on the frame 11.
2 are fixed, and a substrate 14 that is movable on the frame 11 along the pair of rails 13 and 13 in the sub-scanning direction indicated by the arrow Y in FIG. 2 is further provided.

A threaded hole (not shown) is formed in the movable substrate 14, and a threaded rod 15 rotated by the sub-scanning pulse motor 12 is formed in this hole. Engaged.

A main scanning pulse motor 16 is provided on the movable substrate 14, and the main scanning pulse motor 16 is capable of intermittently driving the endless belt 17 at a predetermined pitch.

The spotting head 9 of the spotting device is fixed to the endless belt 17, and when the endless belt 17 is driven by the main scanning pulse motor 16, it moves in the main scanning direction indicated by the arrow X in FIG. It is configured to be moved.

In FIG. 2, 18 is a linear encoder for detecting the position of the spotting head 9 in the main scanning direction, and 19 is a slit of the linear encoder 18.

As shown in FIG. 2, on the substrate 10 of the spotting device, two spots are provided at positions corresponding to the two positioning through holes 5a and 5b formed in the frame body 4 of the biochemical analysis unit 1. The two positioning pins 20a, 20b are provided upright, and the two positioning pins 20a, 20b formed on the substrate 10 of the spotting device are inserted so as to be inserted into the corresponding positioning through holes 5a, 5b. The chemical analysis unit 1 is mounted on the substrate 10 of the spotting device.
By placing it on top, it is guaranteed that the biochemical analysis unit 11 is always placed at approximately the same position on the substrate 10 of the spotting device.

FIG. 3 is a block diagram showing the control system, input system, drive system and detection system of the spotting device.

As shown in FIG. 3, the control system of the spotting device has a control unit 25 for controlling the operation of the entire spotting device, and the input system of the spotting device has a keyboard 26.

The drive system of the spotting device is provided with a main scanning pulse motor 16 and a sub-scanning pulse motor 12, and the detection system of the spotting device is a linear encoder 18 for detecting the position of the spotting head 9 in the main scanning direction. A rotary encoder 17 for detecting the rotation amount of the rod 15 is provided.

With the spotting device having the above-described structure, the unique sites such as cDNA are placed at predetermined positions separated from each other on the absorptive substrate 2 of the biochemical analysis unit 1 according to this embodiment as follows. The binding substance is dripped.

First, the two positioning pins 20a, 20b formed on the substrate 10 of the spotting device are inserted into the corresponding two through holes 5a, 5b for positioning of the biochemical analysis unit 1, respectively. Then, the biochemical analysis unit 1 is placed on the substrate 10 of the spotting device.

Next, the specific binding substance is dropped on the absorptive substrate 2, and the dropping data regarding the number and density of the spot-like regions formed is input to the keyboard 26.

In the present embodiment, the spot-like region of the specific binding substance having a size of about 10,000 square millimeters of about 10,000 has a density of about 5000 cells / square centimeter, and the adsorptivity of the biochemical analysis unit 1 is high. The specific binding substance is dropped onto the adsorptive substrate 2 of the biochemical analysis unit 1 so as to be formed on the substrate 2.

The drop data input to the keyboard 26 is input to the control unit 25, and when the control unit 25 receives the drop data, it moves the spotting head 9 to the position where the specific binding substance should be dropped. Drive pulses to be applied to the main scanning pulse motor 16 and the sub scanning pulse motor 12 are calculated, and the driving pulse data is stored in a memory (not shown).

In the present embodiment, the specific binding substance is dropped on the adsorptive substrate 2 of the biochemical analysis unit 1 at a constant interval. In order to move the spotting head 9 to the position where the binding substance should be dropped, the main scanning pulse motor 1
6 and the driving pulse to be applied to the sub-scanning pulse motor 12 are as follows.
Secondly, it is the same as the drive pulse to be applied to the main scanning pulse motor 16 and the sub scanning pulse motor 12 in order to move the spotting head 9 to the position where the specific binding substance should be dropped. Therefore, first, A drive pulse to be given to the main scanning pulse motor 16 and the sub-scanning pulse motor 12 in order to move the spotting head 9 to the position where the specific binding substance should be dropped, and the position where the specific binding substance should be dropped first. From the second,
It suffices to calculate the drive pulse to be given to the main scanning pulse motor 16 and the sub scanning pulse motor 12 in order to move the spotting head 9 to the position where the specific binding substance should be dropped, and store it in the memory. is there.

The driving pulse to be applied to the main scanning pulse motor 16 and the sub scanning pulse motor 12 in order to move the spotting head 9 to the position where the specific binding substance should be dropped is calculated, and the driving pulse data is stored in the memory. Then, the control unit 25 gives a predetermined driving pulse to the main scanning pulse motor 16 and the sub scanning pulse motor 12 based on the driving pulse data stored in the memory to intermittently move the spotting head 9, When the spotting head 9 reaches the position where the specific binding substance should be dropped, a driving stop signal is output to the main scanning pulse motor 16 and the sub scanning pulse motor 12 to stop the spotting head 9 and Output a drop signal to the injector,
A specific binding substance is ejected.

In the second and subsequent steps, when the spotting head 9 is moved to the position where the specific binding substance should be dropped, the spotting head 9 moves in the main scanning direction indicated by arrow X and the sub-scanning direction indicated by arrow Y. In each direction, it is moved at a constant pitch.

Similarly, the spotting head 9 is intermittently moved by the main scanning pulse motor 16 and the sub-scanning pulse motor 12, and the spotting head 9 is placed on the absorptive substrate 2 of the biochemical analysis unit 1 according to the input dropping data. To
A predetermined specific binding substance is dropped in sequence.

FIG. 4 is a schematic perspective view of a hybridization apparatus according to a preferred embodiment of the present invention.

As shown in FIG. 4, the hybridization apparatus according to the present embodiment comprises a biochemical analysis unit setting section 30a for setting the biochemical analysis unit 1 in the hybridization apparatus and a biochemical analysis unit 1. A pretreatment unit 30b for moistening the
The specific binding substance dropped on the adsorptive substrate 2 of the biochemical analysis unit 1 is brought into contact with a hybridization solution to carry out prehybridization, and further,
A probe solution containing a substance of biological origin labeled with a labeling substance is added to the hybridization solution and brought into contact with the specific binding substance dropped on the adsorptive substrate 2 of the biochemical analysis unit 1 to carry out hybridization. A hybridization unit 30c that performs the cleaning process, and a cleaning process unit 30d that executes the cleaning process of the biochemical analysis unit 1,
The biochemical analysis unit 1 is provided with a biochemical analysis unit take-out section 30e for taking out the biochemical analysis unit 1 from the hybridization apparatus.

As shown in FIG. 4, the hybridization apparatus according to the present embodiment comprises a biochemical analysis unit setting section 30a, a pretreatment section 30b, a hybridization section 30c, a washing treatment section 30d, and a biochemical analysis unit. A pair of guide rails 31, 31 extending between the take-out portions 30e are provided.

The pair of guide rails 31 are respectively provided with
A slidable slide member 32 is attached by a motor (not shown), and a rod 33 is attached to each slide member 32. Each rod 33 is attached to the slide member 32 so as to be vertically movable between an upper standby position and a lower processing position. A gripping member 34 that can grip and grip one side of the frame body 4 of the biochemical analysis unit 1 is attached to the tip end portion of the rod 33 attached to each slide member 32.

As shown in FIG. 4, in the pretreatment section 30b of the hybridization apparatus, the pretreatment liquid tank 35a for containing the pretreatment liquid and the pretreatment for executing the pretreatment of the biochemical analysis unit 1 are performed. Tank 35b, pretreatment liquid recovery tank 35c for collecting pretreatment liquid, and pretreatment liquid tank 35a
To the pretreatment bath 35b, the pretreatment liquid supply tube 35d for supplying the pretreatment liquid, and the pretreatment bath 3 after completion of the pretreatment.
A pretreatment liquid recovery tube 35e for recovering the pretreatment liquid is provided in the pretreatment liquid recovery tank 35c from 5b, and the pretreatment liquid supply tube 35d and the pretreatment liquid recovery tube 3 are provided.
Valves 35f and 35g are provided in 5e, respectively.

As shown in FIG. 4, in the hybridization section 30c of the hybridization device, a hybridization solution tank 36a containing a hybridization solution and a probe solution containing a substance of biological origin labeled with a labeling substance are provided. A probe solution chip 36b to be housed, a hybridization tank 36c in which pre-hybridization and hybridization are performed, a hybridization solution recovery tank 36d for recovering a solution in which the probe solution is added to the hybridization solution, and a hybridization solution. A hybridization solution supply tube 36e for supplying a hybridization solution from the tank 36a to the hybridization tank 36c,
From the probe solution chip 36b to the hybridization tank 36c, a probe solution supply tube 36f for supplying the probe solution, and after completion of hybridization, from the hybridization tank 36c to the hybridization solution recovery tank 36d, to the hybridization solution, A hybridization solution collection tube 36g for collecting the solution to which the solution has been added is provided, and valves 36h, 36i, and 36j are provided to the hybridization solution supply tube 36e, the probe solution supply tube 36f, and the hybridization solution collection tube 36g, respectively. Is provided.

As shown in FIG. 4, in the washing processing section 30d of the hybridization apparatus, a washing solution tank 37a containing a washing solution and a washing treatment tank 37b for performing the washing treatment of the biochemical analysis unit 1 are carried out. A cleaning solution recovery tank 37c for recovering the cleaning solution; a cleaning solution supply tube 37d for supplying the cleaning solution from the cleaning solution tank 37a to the cleaning processing tank 37b; and a cleaning processing tank 37b for cleaning after completion of the cleaning processing. The solution recovery tank 37c is provided with a cleaning solution recovery tube 37e for recovering the cleaning solution, and the cleaning solution supply tube 37d and the cleaning solution recovery tube 37e are provided with valves 37f and 37g, respectively.

The washing processing section 30d of the hybridization apparatus is further provided with a radiation sensor 40 for detecting the concentration of the radioactive labeling substance contained in the washing solution. The radiation sensor 40 is located at the detection position in the washing treatment tank 37b. And a standby position retracted from the cleaning processing tank 37b.

As shown in FIG. 4, the pretreatment bath 35b,
Hybridization tank 36c and washing treatment layer 37
b are vibrating tables 41 and 4 which can vibrate in the vertical direction, respectively.
It is provided on 2, 43.

The inside of the hybridization apparatus is controlled at a predetermined temperature by a temperature controller (not shown).

FIG. 5 is a block diagram of a control system, a detection system, a drive system and an input system of the hybridization apparatus according to the preferred embodiment of the present invention.

As shown in FIG. 5, the control system of the hybridization apparatus according to the present embodiment comprises a control unit 50 for controlling the operation of the entire hybridization apparatus, and the detection system of the hybridization apparatus has a washing treatment layer. A radiation sensor 40 for detecting the concentration of the radioactive labeling substance contained in the cleaning solution in 37b is provided.

As shown in FIG. 5, the drive system of the hybridization apparatus according to this embodiment includes a slide member motor 51 for moving the pair of slide members 32, 32 along the guide rails 31, 31. A rod motor 52 that vertically moves the rod 33 attached to each slide member 32, a first vibration motor 55 that vertically vibrates the vibration table 41 provided in the pretreatment unit 30b, and hybridization. A second vibration motor 56 for vertically vibrating the vibrating table 42 provided in 30c, and a vibrating table 43 provided in the cleaning processing unit 30d.
A third vibration motor 57 that vibrates in the vertical direction, and a radiation sensor motor 58 that moves the radiation sensor 40 between a detection position in the cleaning processing tank 37b and a standby position retracted from the cleaning processing tank 37b. Pretreatment liquid supply tube 35
The first valve opening / closing means 61 for opening / closing the valve 35f provided in d and the second valve opening / closing means 62 for opening / closing the valve 35g provided in the pretreatment liquid recovery tube 35e.
A third valve opening / closing means 63 for opening / closing a valve 36h provided on the hybridization solution supply tube 36e, and a fourth valve opening / closing means 64 for opening / closing a valve 36i provided on the probe solution supply tube 36f.
A fifth valve opening / closing means 65 for opening / closing a valve 36j provided in the hybridization solution collecting tube 36g, a sixth valve opening / closing means 66 for opening / closing a valve 37f provided in the washing solution supply tube 37d, and a washing operation. A seventh valve opening / closing means 67 for opening / closing a valve 37g provided on the solution recovery tube 37e is provided.

As shown in FIG. 5, the input system of the hybridization apparatus according to this embodiment has a keyboard 68.

The hybridization apparatus according to the present embodiment configured as described above is as follows.
The specific binding substance dropped on the adsorptive substrate 2 of the biochemical analysis unit 1 is selectively hybridized with the substance of biological origin labeled with the labeling substance.

First, the hybridization solution is prepared and housed in the hybridization solution tank 36a, the cleaning solution is adjusted, and the cleaning solution tank 37 is prepared.
It is housed in a.

On the other hand, a probe solution containing a substance of biological origin labeled with a labeling substance is prepared and housed in the probe solution chip 36b.

When a specific binding substance such as cDNA is selectively labeled with a radioactive labeling substance, a probe solution containing a substance derived from a living body, which is a probe labeled with the radioactive labeling substance, is prepared, and a probe solution chip is prepared. It is accommodated in 36b.

On the other hand, by using a labeling substance that causes chemiluminescence by contacting with a chemiluminescent substrate, the cDNA is
In the case of selectively labeling a specific binding substance such as, a probe solution containing a substance derived from a living organism, which is a probe labeled with a labeling substance that causes chemiluminescence by contacting with a chemiluminescent substrate, is prepared, It is housed in the probe solution chip 36b.

Further, in the case of selectively labeling a specific binding substance such as cDNA with a fluorescent substance such as a fluorescent dye, a probe containing a substance derived from a living body which is a probe labeled with a fluorescent substance such as a fluorescent dye. A solution is prepared and housed in the probe solution chip 36b.

[0157] 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 by contact with a chemiluminescent substrate, and a living body labeled with a fluorescent substance such as a fluorescent dye Of the substances derived from the living body, a probe solution containing two or more living body-derived substances can be prepared and housed in the probe solution chip. In the present embodiment, the substance derived from the living body labeled with the radioactive labeling substance is used. A probe solution containing a substance of biological origin labeled with a fluorescent substance is prepared and housed in the probe solution chip 36b.

In the hybridization, first, the pair of slide members 32 are held by the biochemical analysis unit set portion 30a, and the specific binding substance such as cDNA is dropped on the adsorptive substrate 2. One side of the frame body 4 of the unit 1 for use has a pair of slide members 32.
Further, the biochemical analysis unit 1 is clamped by the gripping member 34 attached to the tip of the rod 33 that is movably mounted in the vertical direction, and the biochemical analysis unit 1 is set in the hybridization apparatus.

When the biochemical analysis unit 1 is set, the rod 33 of each slide member 32 is held at the upper standby position.

Then, a hybridization start signal is input to the keyboard 68.

In this embodiment, when the substance of biological origin contained in the hybridization solution is labeled with the radioactive labeling substance, at the same time, the radiolabel signal is input to the keyboard 68 by the user. .

The hybridization start signal input to the keyboard 68 is sent to the control unit 50.
In response to the hybridization start signal, the control unit 50 outputs a drive signal to the slide member motor 51.

As a result, the slide member motor 51 is driven, and each slide member 32 is moved by the gripping member 34.
Along with the biochemical analysis unit 1 in which one side portion of the frame body 4 is sandwiched, it is moved along the guide rail 31 from the biochemical analysis unit setting section 30a toward the pretreatment section 30b.

When the biochemical analysis unit sandwiched by the grasping member 34 reaches above the opening of the pretreatment tank 35b, the control unit 50 outputs a drive stop signal to the slide member motor 51 to cause a pair of slides. Member 3
Stop 2.

Then, the control unit 50 outputs a descending signal to the rod motor 52 to move the rod 33 to
From the upper standby position, the lower processing position is lowered.

As a result, the biochemical analysis unit 1 is housed in the pretreatment bath 35b.

The biochemical analysis unit 1 comprises the pretreatment tank 35.
When housed in b, the control unit 50 outputs a valve opening signal to the first valve opening / closing means 61,
Valve 35f provided on the pretreatment liquid supply tube 35d
And the pretreatment liquid is supplied from the pretreatment liquid tank 35a to the pretreatment tank 35b.

The predetermined amount of the pretreatment liquid is stored in the pretreatment liquid tank 3
When supplied to the pretreatment tank 35b from the pretreatment liquid supply tube 35d from the 5a, the control unit 50
Outputs a valve closing signal to the first valve opening / closing means 61 to close the valve 35f provided in the pretreatment liquid supply tube 35d.

Next, the control unit 50 outputs a drive signal to the first vibration motor 55 to vibrate the vibrating table 41 having the pretreatment tank 35b on its upper surface in the vertical direction.

As a result, the biochemical analysis unit 1 and the pretreatment liquid contained in the pretreatment tank 35b relatively move in the vertical direction, and the pretreatment liquid is forcibly flowed, and the biochemical analysis is performed. The pretreatment liquid comes into uniform contact with the treatment unit 1 to uniformly wet the entire surface of the biochemical analysis unit 1.

In this embodiment, since the biochemical analysis unit 1 is provided with the frame body 4, the side portion of the frame body 4 opposed to the one side portion of the frame body 4 held by the gripping member 34 is The pretreatment liquid is stirred, and the biochemical analysis unit 1 and the pretreatment liquid can be brought into contact with each other more uniformly.

After the first vibration motor 55 is driven,
When a predetermined time has passed, the control unit 50
Outputs a drive stop signal to the first vibration motor 55,
The driving of the first vibration motor 55 is stopped, and then a rising signal is output to the rod motor 52 to move the rod 33 to the upper standby position.

When the rod 33 moves to the standby position, the control unit 50 outputs a valve opening signal to the second valve opening / closing means 62, and the pretreatment liquid recovery tube 35
The valve 35g provided in e is opened, and the pretreatment liquid stored in the pretreatment tank 35b is transferred to the pretreatment liquid recovery tube 35e.
The pretreatment liquid collecting tank 35c collects the liquid through the above, and outputs a drive signal to the slide member motor 51.

As a result, the slide member motor 51 is driven and each slide member 32 is moved by the gripping member 34.
Along with the biochemical analysis unit 1 in which one side portion of the frame body 4 is sandwiched, the frame body 4 is moved along the guide rail 31 from the pretreatment unit 30b toward the hybridization unit 30c.

When the biochemical analysis unit sandwiched by the gripping member 34 reaches above the opening of the hybridization tank 36b, the control unit 50
A drive stop signal is output to the slide member motor 51 to stop the pair of slide members 32.

Then, the control unit 50 outputs a descending signal to the rod motor 52 to move the rod 33 to
From the upper standby position, the lower processing position is lowered.

As a result, the biochemical analysis unit 1 is housed in the hybridization tank 36b.

When the biochemical analysis unit 1 is housed in the hybridization tank 36b, the control unit 50 outputs a valve opening signal to the third valve opening / closing means 63 to the hybridization solution supply tube 36e. The valve 36h provided is opened to supply the hybridization solution from the hybridization solution tank 36a to the hybridization tank 36b.

When a predetermined amount of hybridization solution is supplied from the hybridization solution tank 36a to the hybridization tank 36b through the hybridization solution supply tube 36e,
The control unit 50 includes the third valve opening / closing means 6
A valve closing signal is output to 3 to close the valve 36h provided in the hybridization solution supply tube 36e.

Next, the control unit 50 outputs a drive signal to the second vibrating motor 56 to vibrate the vibrating table 42 on the upper surface of which the hybridization tank 36b is provided in the vertical direction.

As a result, the biochemical analysis unit 1 and the hybridization solution accommodated in the hybridization 36b relatively move in the vertical direction, and the hybridization solution is forcibly flowed for biochemical analysis. Pre-hybridization is performed by bringing the hybridization solution into uniform contact with the specific binding substance that has been dropped onto the adsorptive substrate 2 of the unit 1.

In this embodiment, since the biochemical analysis unit 1 is provided with the frame body 4, the side portion of the frame body 4 opposed to the one side portion of the frame body 4 held by the gripping member 34 allows The hybridization solution is stirred, and the biochemical analysis unit 1 and the hybridization solution can be brought into contact with each other more uniformly.

After the second vibration motor 56 is driven,
When a predetermined time has passed, the control unit 50
Outputs a valve opening signal to the fourth valve opening / closing means 64 to open the valve 36i provided in the probe solution supply tube 36f to supply the probe solution from the probe solution chip 36b to the hybridization tank 36b.

When a predetermined amount of probe solution is supplied from the probe solution chip 36b to the hybridization tank 36b via the probe solution supply tube 36f, the control unit 50 causes the fourth valve opening / closing means 64 to open the valve. A closing signal is output to close the valve 36i provided on the probe solution supply tube 36f.

As a result, the hybridization tank 36
A probe solution containing a substance of biological origin labeled with a radioactive labeling substance and a substance of biological origin labeled with a fluorescent substance is added to the hybridization solution housed in b.

Next, the control unit 50 outputs a drive signal to the second vibrating motor 56 to vibrate the vibrating table 42 on the upper surface of which the hybridization tank 36b is provided in the vertical direction.

As a result, the probe solution was added to the biochemical analysis unit 1 and the hybridization solution contained in the hybridization 36b, and the prepared solution moved relatively in the vertical direction, The probe solution is added to the hybridization solution,
The prepared solution is forcibly flowed, dropped onto the adsorptive substrate 2 of the biochemical analysis unit 1, and evenly contacts the adsorbed specific binding substance to form a specific binding substance and a probe solution. The contained biological material is selectively hybridized.

In this embodiment, since the biochemical analysis unit 1 is provided with the frame body 4, the side portion of the frame body 4 opposed to the one side portion of the frame body 4 held by the gripping member 34 is The probe solution is added to the hybridization solution, the prepared solution is stirred, and the biochemical analysis unit 1 and the probe solution are added to the hybridization solution to make the prepared solution more uniform. It is possible to make contact.

After the second vibration motor 56 is driven,
When a predetermined time has passed, the control unit 50
Outputs a drive stop signal to the second vibration motor 56,
The driving of the second vibration motor 56 is stopped, and then a rising signal is output to the rod motor 52 to move the rod 33 to the upper standby position.

When the rod 33 moves to the standby position, the control unit 50 outputs a valve opening signal to the fifth valve opening / closing means 65 to open the valve 36j provided in the hybridization solution collecting tube 36g, and the hybridization is performed. The probe solution is added to the hybridization solution contained in the bath 36b, and the prepared solution is recovered in the hybridization solution recovery tank 36d through the hybridization solution recovery tube 36g, and at the same time, the slide member motor is driven. The drive signal is output to 51.

As a result, the slide member motor 51 is driven and each slide member 32 is moved by the gripping member 34.
Along with the biochemical analysis unit 1 in which one side portion of the frame body 4 is sandwiched, the frame body 4 is moved along the guide rail 31 from the hybridization section 30c toward the washing processing section 30d.

When the biochemical analysis unit sandwiched by the gripping member 34 reaches above the opening of the cleaning treatment tank 37b, the control unit 50 outputs a drive stop signal to the slide member motor 51 to cause a pair of slides. The member 32 is stopped.

Then, the control unit 50 outputs a descending signal to the rod motor 52 to move the rod 33 to
From the upper standby position, the lower processing position is lowered.

As a result, the biochemical analysis unit 1 is housed in the cleaning treatment tank 37b.

The biochemical analysis unit 1 is used in the cleaning treatment tank 3
When housed in 7b, the control unit 50
A valve opening signal is output to the sixth valve opening / closing means 66, and the valve 3 provided in the cleaning solution supply tube 37d is output.
7f is opened, and the cleaning solution is supplied from the cleaning solution tank 37a,
It is supplied to the cleaning treatment tank 37b.

A predetermined amount of cleaning solution is stored in the cleaning solution tank 3
When supplied to the cleaning treatment tank 37b from the cleaning solution supply tube 7d from the cleaning unit 7a, the control unit 5
0 outputs a valve closing signal to the sixth valve opening / closing means 66 to close the valve 37f provided in the cleaning solution supply tube 37d.

Next, the control unit 50 outputs a drive signal to the third vibration motor 58 to vibrate the vibrating table 43 having the cleaning processing tank 37b provided on the upper surface thereof in the vertical direction.

As a result, the biochemical analysis unit 1 and the cleaning solution accommodated in the cleaning treatment tank 37b relatively move in the vertical direction, and the cleaning solution is forced to flow, and the biochemical analysis unit The cleaning solution is brought into uniform contact with the cleaning liquid 1, and the entire surface of the biochemical analysis unit 1 is cleaned with the cleaning solution.

In this embodiment, since the biochemical analysis unit 1 is provided with the frame body 4, the side portion of the frame body 4 opposed to the one side portion of the frame body 4 held by the gripping member 34 is The cleaning solution is agitated, and the biochemical analysis unit 1 and the cleaning solution can be brought into contact with each other more uniformly.

After the third vibration motor 58 is driven,
When a predetermined time has passed, the control unit 50
Outputs a drive stop signal to the third vibration motor 58,
The driving of the third vibration motor 58 is stopped, and then a rising signal is output to the rod motor 52 to move the rod 33 to the upper standby position.

When the radiation indicator signal is input from the keyboard 68, when the rod 33 moves to the standby position, the control unit 50 outputs a detection instruction signal to the radiation sensor motor 58 to cause the radiation sensor 40 to move.
The cleaning processing tank 37b is moved from the standby position retracted from the cleaning processing tank 37b to a detection position in the cleaning processing tank 37b.
The concentration of the radiolabel substance contained in the washing solution contained in the container is detected.

The detection signal of the radiation sensor 40 is output to the control unit 50, and the control unit 5
0 compares the concentration of the radioactive labeling substance in the cleaning solution with the reference concentration of the radioactive labeling substance stored in the memory (not shown) based on the detection signal input from the radiation sensor 40.

As a result, when the concentration of the radioactive labeling substance in the washing solution exceeds the standard concentration of the radioactive labeling substance,
Since it is recognized that the biochemical analysis unit 1 is not sufficiently washed and a new washing solution needs to be supplied into the washing treatment layer 37d to continue the washing operation, the control unit 50 uses the seventh valve. A valve opening signal is output to the opening / closing means 67 to open the valve 37g provided in the cleaning solution recovery tube 37e to recover the cleaning solution contained in the cleaning treatment layer 37d into the cleaning solution recovery tank 37c.

When the cleaning solution contained in the cleaning treatment layer 37d is recovered in the cleaning solution recovery tank 37c via the cleaning solution recovery tube 37e, the control unit 50 causes the seventh valve opening / closing means 67 to operate. To the cleaning solution recovery tube 37e and outputs a downward signal to the rod motor 52 to lower the rod 33 from the upper standby position to the lower processing position. Let

As a result, the biochemical analysis unit 1 is housed again in the cleaning treatment tank 37b.

The biochemical analysis unit 1 is used in the cleaning treatment tank 3
When housed in 7b, the control unit 50
A valve opening signal is output to the sixth valve opening / closing means 66, and the valve 3 provided in the cleaning solution supply tube 37d is output.
7f is opened again, and a new cleaning solution is supplied from the cleaning solution tank 37a to the cleaning processing tank 37b.

A predetermined amount of cleaning solution is stored in the cleaning solution tank 3
When supplied to the cleaning treatment tank 37b from the cleaning solution supply tube 7d from the cleaning unit 7a, the control unit 5
0 outputs a valve closing signal to the sixth valve opening / closing means 66 to close the valve 37f provided in the cleaning solution supply tube 37d.

Next, the control unit 50 outputs a drive signal to the third vibrating motor 58 to vibrate the vibrating table 43 provided with the cleaning processing tank 37b on its upper surface in the vertical direction.

As a result, the biochemical analysis unit 1 and the cleaning solution accommodated in the cleaning treatment tank 37b relatively move in the vertical direction, and the cleaning solution is forced to flow, and the biochemical analysis unit 1 The cleaning solution is brought into uniform contact with the cleaning liquid 1, and the entire surface of the biochemical analysis unit 1 is cleaned with the cleaning solution.

After the third vibration motor 58 is driven,
When a predetermined time has passed, the control unit 50
Outputs a drive stop signal to the third vibration motor 58,
The driving of the third vibration motor 58 is stopped, and then a rising signal is output to the rod motor 52 to move the rod 33 to the upper standby position.

When the rod 33 moves to the standby position, the control unit 50 outputs a detection instruction signal to the radiation sensor motor 58 to move the radiation sensor 40 from the standby position retracted from the cleaning processing bath 37b to the cleaning processing bath. 37
It is moved to a detection position in b, and the concentration of the radiolabeled substance contained in the cleaning solution contained in the cleaning treatment tank 37b is detected.

The detection signal of the radiation sensor 40 is output to the control unit 50, and the control unit 5
0 compares the concentration of the radioactive labeling substance in the cleaning solution with the reference concentration of the radioactive labeling substance stored in the memory (not shown) based on the detection signal input from the radiation sensor 40.

As a result, when the concentration of the radioactive labeling substance in the washing solution exceeds the standard concentration of the radioactive labeling substance,
The washing of the biochemical analysis unit 1 is not yet sufficient,
It is recognized that it is necessary to supply a new cleaning solution into the cleaning treatment layer 37d and continue the cleaning operation.
The control unit 50 includes the seventh valve opening / closing means 6
A valve opening signal is output to 7 to open the valve 37g provided in the cleaning solution recovery tube 37e, and the cleaning treatment layer 3
The cleaning solution stored in 7d is collected in the cleaning solution recovery tank 37c.

When the cleaning solution contained in the cleaning treatment layer 37d is recovered in the cleaning solution recovery tank 37c via the cleaning solution recovery tube 37e, the control unit 50 causes the seventh valve opening / closing means 67 to operate. To the cleaning solution recovery tube 37e and outputs a downward signal to the rod motor 52 to lower the rod 33 from the upper standby position to the lower processing position. Let

As a result, the biochemical analysis unit 1 is housed again in the cleaning treatment tank 37b.

The biochemical analysis unit 1 is used in the cleaning treatment tank 3
When housed in 7b, the control unit 50
A valve opening signal is output to the sixth valve opening / closing means 66, and the valve 3 provided in the cleaning solution supply tube 37d is output.
7f is opened again, and a new cleaning solution is supplied from the cleaning solution tank 37a to the cleaning processing tank 37b.

A predetermined amount of cleaning solution is stored in the cleaning solution tank 3
When supplied to the cleaning treatment tank 37b from the cleaning solution supply tube 7d from the cleaning unit 7a, the control unit 5
0 outputs a valve closing signal to the sixth valve opening / closing means 66 to close the valve 37f provided in the cleaning solution supply tube 37d.

Next, the control unit 50 outputs a drive signal to the third vibration motor 58 to vibrate the vibrating table 43 having the cleaning processing tank 37b on its upper surface in the vertical direction.

As a result, the biochemical analysis unit 1 and the cleaning solution accommodated in the cleaning treatment tank 37b relatively move in the vertical direction, and the cleaning solution is forced to flow, and the biochemical analysis unit The cleaning solution is brought into uniform contact with the cleaning liquid 1, and the entire surface of the biochemical analysis unit 1 is cleaned with the cleaning solution.

After the third vibration motor 58 is driven,
When a predetermined time has passed, the control unit 50
Outputs a drive stop signal to the third vibration motor 58,
The driving of the third vibration motor 58 is stopped, and then a rising signal is output to the rod motor 52 to move the rod 33 to the upper standby position.

When the rod 33 moves to the standby position, the control unit 50 outputs a detection instruction signal to the radiation sensor motor 58 to move the radiation sensor 40 from the standby position retracted from the cleaning treatment tank 37b to the cleaning treatment tank. 37
It is moved to a detection position in b, and the concentration of the radiolabeled substance contained in the cleaning solution contained in the cleaning treatment tank 37b is detected.

The detection signal of the radiation sensor 40 is output to the control unit 50, and the control unit 5
0 compares the concentration of the radioactive labeling substance in the cleaning solution with the reference concentration of the radioactive labeling substance stored in the memory (not shown) based on the detection signal input from the radiation sensor 40.

As a result, when the concentration of the radioactive labeling substance in the washing solution exceeds the standard concentration of the radioactive labeling substance,
Since it is recognized that the biochemical analysis unit 1 is not sufficiently washed and a new washing solution needs to be supplied into the washing treatment layer 37d to continue the washing operation, the control unit 50 uses the seventh valve. A valve opening signal is output to the opening / closing means 67 to open the valve 37g provided in the cleaning solution recovery tube 37e to recover the cleaning solution contained in the cleaning treatment layer 37d into the cleaning solution recovery tank 37c.

When the cleaning solution contained in the cleaning treatment layer 37d is recovered in the cleaning solution recovery tank 37c via the cleaning solution recovery tube 37e, the control unit 50 causes the seventh valve opening / closing means 67 to operate. To the cleaning solution recovery tube 37e and outputs a downward signal to the rod motor 52 to lower the rod 33 from the upper standby position to the lower processing position. Let

As a result, the biochemical analysis unit 1 is housed again in the cleaning treatment tank 37b.

The biochemical analysis unit 1 is used in the cleaning treatment tank 3
When housed in 7b, the control unit 50
A valve opening signal is output to the sixth valve opening / closing means 66, and the valve 3 provided in the cleaning solution supply tube 37d is output.
7f is opened again, and a new cleaning solution is supplied from the cleaning solution tank 37a to the cleaning processing tank 37b.

A predetermined amount of cleaning solution is stored in the cleaning solution tank 3
When supplied to the cleaning treatment tank 37b from the cleaning solution supply tube 7d from the cleaning unit 7a, the control unit 5
0 outputs a valve closing signal to the sixth valve opening / closing means 66 to close the valve 37f provided in the cleaning solution supply tube 37d.

Next, the control unit 50 outputs a drive signal to the third vibration motor 58 to vibrate the vibrating table 43 having the cleaning processing tank 37b on its upper surface in the vertical direction.

As a result, the biochemical analysis unit 1 and the cleaning solution accommodated in the cleaning treatment tank 37b relatively move in the vertical direction, and the cleaning solution is forced to flow, and the biochemical analysis unit The cleaning solution is brought into uniform contact with the cleaning liquid 1, and the entire surface of the biochemical analysis unit 1 is cleaned with the cleaning solution.

After the third vibration motor 58 is driven,
When a predetermined time has passed, the control unit 50
Outputs a drive stop signal to the third vibration motor 58,
The driving of the third vibration motor 58 is stopped, and then a rising signal is output to the rod motor 52 to move the rod 33 to the upper standby position.

When the rod 33 moves to the standby position, the control unit 50 outputs a detection instruction signal to the radiation sensor motor 58 to move the radiation sensor 40 from the standby position retracted from the cleaning treatment tank 37b to the cleaning treatment tank. 37
It is moved to a detection position in b, and the concentration of the radiolabeled substance contained in the cleaning solution contained in the cleaning treatment tank 37b is detected.

The detection signal of the radiation sensor 40 is output to the control unit 50, and the control unit 5
0 compares the concentration of the radioactive labeling substance in the cleaning solution with the reference concentration of the radioactive labeling substance stored in the memory (not shown) based on the detection signal input from the radiation sensor 40.

Thus, until the concentration of the radioactive labeling substance in the washing solution drops below the standard concentration of the radioactive labeling substance,
When the washing with the washing solution is repeated and the concentration of the radioactive labeling substance in the washing solution decreases to the standard concentration of the radioactive labeling substance or less, the control unit 50 determines that the washing is completed, and the seventh valve opening / closing means 67. A valve opening signal is output to open the valve 37g provided in the cleaning solution recovery tube 37e to recover the cleaning solution contained in the cleaning treatment layer 37d into the cleaning solution recovery tank 37c, and slide the slide member. A drive signal is output to the motor 51.

As a result, the slide member motor 51 is driven, and each slide member 32 is moved by the gripping member 34.
Along with the biochemical analysis unit 1 in which one side portion of the frame body 4 is sandwiched, along with the guide rail 31, the cleaning processing unit 30d
From, it is moved toward the biochemical analysis unit extraction section 30e.

Here, in this embodiment, since the substance of biological origin contained in the probe solution is labeled with the radioactive labeling substance, the radiation sensor 40 detects the concentration of the radioactive labeling substance in the washing solution. Then, the washing solution is repeatedly washed until the concentration of the radiolabeled substance in the wash solution falls below the radiolabeled substance standard concentration, but the substance of biological origin contained in the probe solution is changed by the radiolabeled substance. When not labeled, the cleaning operation is completed when the control unit 50 determines that the cleaning solution has been injected and the cleaning has been performed a predetermined number of times.

The biochemical analysis unit clamped by the gripping member 34 is used as the biochemical analysis unit take-out section 30.
When sent to e, the biochemical analysis unit 1 is taken out from the hybridization device.

Thus, the biochemical analysis unit 1 records the radiation data of the radioactive labeling substance as the labeling substance and the fluorescence data of the fluorescent substance such as the fluorescent dye. The fluorescence data recorded in the biochemical analysis unit 1 is read by a scanner described later to generate biochemical analysis data.

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 70 according to the present embodiment has a large number of substantially circular through holes 7.
3 includes a nickel-made support 71 that is regularly formed, and a stimulable phosphor is embedded in a large number of through holes 73 formed in the support 71 to form a large number of stimulable phosphor layers. The area 72 is formed in a dot shape.

A large number of through holes 73 are formed in the support 71 in the same pattern as the spot-like region of the specific binding substance formed on the absorptive substrate 2 of the biochemical analysis unit 1, and each stimulable substance is formed. The phosphor layer region 72 is formed to have the same size as the spot-like region of the specific binding substance formed on the adsorptive substrate 2 of the biochemical analysis unit 1.

Therefore, although not shown exactly in FIG. 6, there are about 10,000 photostimulable phosphor layer regions 72 having a size of about 0.01 mm 2 and a density of about 5000 / cm 2. The dots are formed on the support 71 of the stimulable phosphor sheet 70 in the same regular pattern as the spot-like region of the specific binding substance formed on the adsorptive substrate 2 of the biochemical analysis unit 1. ing.

Further, in the present embodiment, the support 71
Surface and stimulable phosphor layer region 7 formed in a dot shape
The support 71 is placed so that the surface of
The stimulable phosphor is embedded in the through hole 73 formed in the above to form the stimulable phosphor sheet 70.

FIG. 7 shows a large number of stimulable phosphor sheets 70 formed by the radioactive labeling substance contained in the spot-like regions of the specific binding substance formed on the adsorptive substrate 2 of the biochemical analysis unit 1. FIG. 9 is a schematic cross-sectional view showing a method of exposing the dot-shaped stimulable phosphor layer region 72 of FIG.

As shown in FIG. 7, upon exposure, each of the spot-like regions 6 of the specific binding substance formed on the adsorptive substrate 2 of the biochemical analysis unit 1 is transferred to the stimulable phosphor sheet 70. The stimulable phosphor sheet 70 is superposed on the biochemical analysis unit 1 so as to exactly face the corresponding dot-shaped stimulable phosphor layer region 72 formed.

In this way, by holding the biochemical analysis unit 1 and the stimulable phosphor sheet 70 in a superposed state for a predetermined time, the radioactive labeling substance contained in the spot-shaped region 6 causes accumulation. A large number of dot-shaped stimulable phosphor layer regions 72 formed on the phosphor sheet 70 are exposed.

Thus, the radiation data of the radioactive labeling substance is recorded in the large number of dot-shaped stimulable phosphor layer regions 72 formed on the stimulable phosphor sheet 70.

In FIG. 8, the radiation data recorded on the stimulable phosphor sheet 70 is read to generate biochemical analysis data, and at the same time the fluorescence data recorded on the biochemical analysis unit 1 is read to obtain the raw data. FIG. 9 is a schematic perspective view of a scanner that generates data for chemical analysis, and FIG. 9 is a schematic perspective view showing details near the photomultiplier of the scanner shown in FIG. 8.

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 72 formed on the stimulable phosphor sheet 70. The fluorescent data such as the fluorescent dye recorded on the first absorptive substrate 2 can be read.

As shown in FIG. 8, the scanner according to the present embodiment includes a first laser excitation light source 81 which emits a laser beam 84 having a wavelength of 640 nm and a second laser excitation laser which emits a laser beam 84 having a wavelength of 532 nm. Excitation light source 82 and 47
It is provided with a third laser excitation light source 83 which emits a laser beam 84 having a wavelength of 3 nm.

In the present embodiment, the first laser excitation light source 81 is composed of a semiconductor laser light source, and the second laser excitation light source 82 and the third laser excitation light source 83.
Is composed of a second harmonic generation element.

The laser light 84 generated by the first laser excitation light source 81 is collimated by the collimator lens 85 and then reflected by the mirror 86. First
In the optical path of the laser light 84 emitted from the laser excitation light source 81 and reflected by the mirror 86, a first dichroic mirror 87 that transmits the laser light 4 of 640 nm and reflects light of a wavelength of 532 nm and 532 nm or more A second dichroic mirror 88 that transmits light of a wavelength and reflects light of a wavelength of 473 nm is provided.
Laser light 84 generated by the laser excitation light source 81
Passes through the first dichroic mirror 87 and the second dichroic mirror 88 and enters the mirror 89.

On the other hand, the laser beam 84 generated from the second laser excitation light source 82 is passed by the collimator lens 90.
After being made into parallel light, it is reflected by the first dichroic mirror 87, its direction is changed by 90 degrees, and
The light passes through the dichroic mirror 88 and enters the mirror 89.

The laser light 84 generated from the third laser excitation light source 83 is made into parallel light by the collimator lens 91, and then the second dichroic mirror 8 is used.
After being reflected by 8 and changing its direction by 90 degrees,
It is incident on the mirror 89.

The laser beam 84 incident on the mirror 89 is reflected by the mirror 89 and further incident on the mirror 92 and reflected.

Laser light 8 reflected by mirror 92
A perforated mirror 94 formed by a concave mirror having a hole 93 formed in the central portion is arranged in the optical path of No. 4, and the laser light 84 reflected by the mirror 92 passes through the hole 93 of the perforated mirror 94. It passes through and enters the concave mirror 98.

Laser light 84 incident on the concave mirror 98
Is reflected by the concave mirror 98, and the optical head 9
It is incident on 5.

The optical head 95 is provided with a mirror 96 and an aspherical lens 97. The laser light 84 incident on the optical head 95 is reflected by the mirror 96, and the glass plate of the stage 100 is reflected by the aspherical lens 97. 101
It is incident on the stimulable phosphor sheet 70 placed on the top or the biochemical analysis unit 1.

A laser beam 84 is applied to the stimulable phosphor sheet 70.
Is incident, the dot-shaped photostimulable phosphor layer region 72 formed on the support 71 of the stimulable phosphor sheet 70 is excited, the photostimulable light 105 is emitted, and the biochemical analysis unit 1 is irradiated. When the laser light 84 is incident, the fluorescent substance such as the fluorescent dye contained in the spot-like region 6 is excited and the fluorescence 105 is emitted.

The photostimulable light 105 emitted from the dot-shaped photostimulable phosphor layer region 72 of the stimulable phosphor sheet 70 or the fluorescence 105 emitted from the spot-shaped region 6 of the biochemical analysis unit 1 is The aspherical lens 97 provided in the head 95 focuses the light on a mirror 96, reflects the laser light 84 on the same side as the optical path of the laser light 84, collimates the light, and makes the light incident on a concave mirror 98.

The photostimulable light 105 or fluorescence 105 that has entered the concave mirror 98 is reflected by the concave mirror 98 and enters the perforated mirror 94.

The photostimulable light 105 incident on the perforated mirror 94.
Alternatively, as shown in FIG. 9, the fluorescent light 105 is reflected downward by a perforated mirror 94 formed by a concave mirror, enters the filter unit 108, cuts light of a predetermined wavelength, and photomultiplies. Prior 1
It is incident on 10 and is detected photoelectrically.

As shown in FIG. 9, the filter unit 108 includes four filter members 111a, 151b, and 1b.
The filter unit 10 includes 51c and 151d.
8 is configured to be movable in the left-right direction in FIG. 9 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 1
11a includes a filter 112a, and the filter 112a
Is used when the fluorescent substance contained in the spot-like region 6 formed on the absorptive substrate 2 of the biochemical analysis unit 1 is excited by using the first laser excitation light source 81 and the fluorescence 105 is read. 640nm which is a filter member
It has a property of cutting off light having a wavelength of, and transmitting light having a wavelength longer than 640 nm.

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

As shown in FIG. 11, the filter member 1
11b includes a filter 112b, and the filter 112b
Is used when the fluorescent material contained in the spot-like region 6 formed on the adsorptive substrate 2 of the biochemical analysis unit 1 is excited by using the second laser excitation light source 82 and the fluorescence 105 is read. 532nm which is a filter member
It has a property of cutting off light having a wavelength of, and transmitting light having a wavelength longer than 532 nm.

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

As shown in FIG. 12, the filter member 1
11c includes a filter 112c, and the filter 112c
When the fluorescence 105 is read by exciting the fluorescent substance contained in the spot-like region 6 formed on the absorptive substrate 2 of the biochemical analysis unit 1 using the third laser excitation light source 83 It is a filter member used, 473n
It has a property of cutting off light having a wavelength of m and transmitting light having a wavelength longer than 473 nm.

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

As shown in FIG. 13, the filter member 1
11d includes a filter 112d, and the filter 112d
Is emitted from the stimulable phosphor layer area 72 by exciting the dot-shaped stimulable phosphor layer area 72 formed on the stimulable phosphor sheet 70 using the first laser excitation light source 81. This is a filter used when reading the stimulated emission light 105 that has been emitted from the photostimulable phosphor layer region 72.
It has a property of transmitting only the light of the wavelength range of 05 and cutting the light of the wavelength of 640 nm.

Therefore, depending on the laser excitation light source to be used, the filter members 111a, 151b, 151c,
By selectively positioning 151d in front of the photomultiplier 110, the photomultiplier 11
0 can photoelectrically detect only the light to be detected.

The photomultiplier 110 photoelectrically detects the stimulated emission 105, and the generated analog data is output to the A / D converter 113, digitized, and output to the data processing unit 114. It

FIG. 14 is a schematic plan view of the scanning mechanism of the optical head 95. In FIG. 14, for simplification, the optical system except the optical head 95 and the optical paths of the laser beam 84 and the fluorescent light 105 or the stimulating light 105 are omitted.

As shown in FIG. 14, the optical head 95
The scanning mechanism that scans the substrate includes a substrate 120.
Above the sub-scanning pulse motor 121 and the pair of rails 12
2, 62 are fixed, and a substrate 123 which is movable in the sub-scanning direction indicated by arrow Y in FIG. 14 is further provided on the substrate 120.

A threaded hole (not shown) is formed in the movable substrate 123, and a threaded rod 124 rotated by the sub-scanning pulse motor 121 is formed in this hole. Engaged.

A main scanning stepping motor 125 is provided on the movable substrate 123, and the main scanning stepping motor 125 has endless belts 126 formed adjacent to each other on the absorptive substrate 2 of the biochemical analysis unit 1. Intermittently at a pitch equal to the distance between the spot-shaped regions 6, that is, at a pitch equal to the distance between adjacent dot-shaped stimulable phosphor layer regions 72 formed on the stimulable phosphor sheet 70. It is configured to be drivable.

The optical head 95 includes the endless belt 12
6 is fixed, and the main scanning stepping motor 125
When the endless belt 126 is driven by, the endless belt 126 is moved in the main scanning direction indicated by an arrow X in FIG. In FIG. 14, 67 is a linear encoder that detects the position of the optical head 95 in the main scanning direction, and 128 is the linear encoder 12
7 slits.

Therefore, the main scanning stepping motor 1
25, the endless belt 126 is intermittently driven in the main scanning direction, and when scanning of one line is completed, the substrate 123 is intermittently moved in the sub scanning direction by the sub scanning pulse motor 121. In FIG. 14, the optical head 95 is moved in the main scanning direction indicated by the arrow X and in the sub-scanning direction indicated by the arrow Y, and all the dot-like shapes formed on the stimulable phosphor sheet 70 by the laser light 84 are moved. The entire surface of the photostimulable phosphor layer region 72 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.

As shown in FIG. 15, the control system of the scanner is a control unit 1 for controlling the entire scanner.
In addition, the input system of the scanner is provided with a keyboard 131 that is operated by the user and can input various instruction signals.

As shown in FIG. 15, the scanner drive system includes a main scanning stepping motor 125 for intermittently moving the optical head 95 in the main scanning direction, and an optical head 95.
Of the sub-scanning pulse motor 121 that intermittently moves the filter in the sub-scanning direction, and the four filter members 111a, 151b, 1
A filter unit motor 132 for moving the filter unit 108 including 51c and 151d is provided.

The control unit 130 selectively outputs a drive signal to the first laser excitation light source 81, the second laser excitation light source 82 or the third laser excitation light source 83, and also outputs a drive signal to the filter unit motor 132. It is configured to output.

Further, as shown in FIG. 15, the detection system of the scanner comprises a photomultiplier 110 and a linear encoder 127 for detecting the position of the optical head 95 in the main scanning direction.

In the present embodiment, the control unit 130, in accordance with the position detection signal of the optical head 95 inputted from the linear encoder 127, the first laser excitation light source 81, the second laser excitation light source 82 or the third laser excitation light source 82. The laser excitation light source 83 is configured to be turned on / off.

The scanner according to the present embodiment configured as described above is recorded in a large number of dot-shaped stimulable phosphor layer regions 72 formed on the stimulable phosphor sheet 70 as follows. The radiation data obtained is read and biochemical analysis data is generated.

First, the stimulable phosphor sheet 70 is placed on the glass plate 101 of the stage 100.

Next, the keyboard 1 is set by the user.
An instruction signal for scanning a large number of dot-shaped photostimulable phosphor layer regions 72 formed on the stimulable phosphor sheet 70 with a laser beam 84 is input to 31.

The instruction signal input to the keyboard 131 is input to the control unit 130, and the control unit 130 outputs a drive signal to the filter unit motor 132 in accordance with the instruction signal to move the filter unit 108 and activate it. 640 nm, which transmits only the light in the wavelength range of the photostimulable light 105 emitted from the luminescent phosphor.
Filter 112d having a property of cutting off light of wavelength
The filter member 111d provided with is placed in the optical path of the photostimulable light 105.

Further, the control unit 130 is
A drive signal is output to the main scanning stepping motor 125,
The optical head 95 is moved in the main scanning direction, and based on the position detection signal of the optical head 95 input from the linear encoder 127, the first dot-shaped stimulable phosphor layer region 7 is formed.
2, the optical head 9 is placed at a position where the laser beam 84 can be irradiated.
When it is confirmed that 5 has moved, a stop signal is output to the main scanning stepping motor 125, and a drive signal is output to the first laser excitation light source 81 to activate the first laser excitation light source 81. , Laser light 84 having a wavelength of 640 nm is emitted.

The laser light 84 emitted from the first laser excitation light source 81 is made into parallel light by the collimator lens 85, and then enters the mirror 86 and is reflected.

Laser light 8 reflected by mirror 86
4 passes through the first dichroic mirror 87 and the second dichroic mirror 88, and enters the mirror 89.

The laser beam 84 incident on the mirror 89 is reflected by the mirror 89 and further incident on the mirror 92 and reflected.

Laser light 8 reflected by mirror 92
4 passes through the hole 93 of the perforated mirror 94 and enters the concave mirror 98.

Laser light 84 incident on the concave mirror 98
Is reflected by the concave mirror 98, and the optical head 9
It is incident on 5.

Laser light 84 incident on the optical head 95
Is reflected by the mirror 96 and is condensed by the aspherical lens 97 onto the first dot-shaped stimulable phosphor layer region 72 of the stimulable phosphor sheet 70 placed on the glass plate 101 of the stage 100. It

As a result, the stimulable phosphor contained in the first dot-shaped stimulable phosphor layer area 72 formed on the stimulable phosphor sheet 70 is excited by the laser beam 84 to generate the first stimulable phosphor. Photostimulable light 105 is emitted from the photostimulable phosphor layer region 72 of FIG.

At this time, since the support 71 of the stimulable phosphor sheet 70 is made of nickel, the laser light 84 is scattered inside the support 71 and the first stimulable phosphor layer region 72 is formed. To excite the stimulable phosphor contained in the adjacent stimulable phosphor layer region 72, and effectively prevent the accumulated radiation energy from being emitted in the form of stimulable light 105. In addition, the stimulable light 105 emitted from the first stimulable phosphor layer region 72 is transferred to the support 71.
It is possible to effectively prevent the light from being scattered inside and not being detected by the photomultiplier 110.

The photostimulable light 105 emitted from the first dot-shaped photostimulable phosphor region 12 is collected by the aspherical lens 97 provided in the optical head 95, and the laser light 84 of the laser light 84 is reflected by the mirror 96. The light is reflected on the same side as the optical path, becomes parallel light, and enters the concave mirror 98.

Photostimulation 105 incident on the concave mirror 98
Is reflected by the concave mirror 98 and enters the perforated mirror 94.

Photostimulation 105 incident on the perforated mirror 94
Is reflected downward by the perforated mirror 94 formed by the concave mirror and enters the filter 112d of the filter unit 108, as shown in FIG.

The filter 112d transmits only the light in the wavelength range of the photostimulable light 105 emitted from the photostimulable phosphor,
Since it has the property of cutting light with a wavelength of 0 nm,
Photostimulation light 1 emitted from the dot-shaped photostimulable phosphor layer region 72 in which the excitation light having a wavelength of 640 nm is cut
Only light in the 05 wavelength range passes through the filter 112d,
It is detected photoelectrically by the photomultiplier 110.

The analog data generated by being detected photoelectrically by the photomultiplier 110 is A / D.
The data is digitized by the converter 113 and output to the data processing device 114.

After the first laser excitation light source 81 is turned on, when a predetermined time, for example, several microseconds elapses, the control unit 130 causes the first laser excitation light source 81 to move.
And outputs a drive stop signal to the first laser excitation light source 81
Driving of the main scanning stepping motor 125 is stopped and the optical head 95 is
It is moved by a pitch equal to the distance between adjacent dot-shaped stimulable phosphor layer regions 72 formed on the stimulable phosphor sheet 70.

On the basis of the position detection signal of the optical head 95 input from the linear encoder 127, the optical head 9
5 is moved by one pitch equal to the distance between the adjacent dot-shaped stimulable phosphor layer regions 72, and the laser beam 84 emitted from the first laser excitation light source 81 is transferred to the stimulable phosphor sheet 70. When it is confirmed that the formed second dot-shaped stimulable phosphor layer region 72 has moved to a position where it can be irradiated, the control unit 130 outputs a drive signal to the first laser excitation light source 81. Then, the first laser excitation light source 81 is turned on, and the laser beam 84 causes the photostimulable phosphor layer region 72 formed in the second dot-shaped photostimulable phosphor layer 72 to be stimulated. Excitable fluorescent substance.

Similarly, the laser light 84 emitted from the first laser excitation light source 81 for a predetermined time is used as the second dot-shaped stimulable phosphor layer on the stimulable phosphor sheet 70. The region 72 is irradiated and the stimulable phosphor contained in the second stimulable phosphor layer region 72 is excited,
Photostimulable light 1 emitted from the second photostimulable phosphor layer region 72
05 was photoelectrically detected by the photomultiplier 110 to generate analog data, digitized by the A / D converter 113, and recorded in the second stimulable phosphor layer region 72. When the biochemical analysis data is generated from the radiation data, the control unit 130 outputs an OFF signal to the first laser excitation light source 81 to turn off the first laser excitation light source 81 and perform main scanning stepping. A drive signal is output to the motor 125 to move the optical head 95 by one pitch equal to the distance between the adjacent dot-shaped stimulable phosphor layer regions 72.

In this way, the first laser excitation light source 81 is repeatedly turned on and off in synchronization with the intermittent movement of the optical head 95, and the optical head 95 is detected based on the position detection signal of the optical head 95 input from the linear encoder 127. 95 is
When it is confirmed that the scanning by the laser beam 84 of the dot-shaped stimulable phosphor layer region 72 of the first line has been completed after being moved by one line in the main scanning direction, the control unit 130 A drive signal is output to the scanning stepping motor 125 to return the optical head 95 to its original position, and a drive signal is output to the sub-scanning pulse motor 121 to move the movable substrate 123 in the sub-scanning direction.
Move only one line.

Based on the position detection signal of the optical head 95 input from the linear encoder 127, the optical head 9
5 is returned to its original position and the movable substrate 123
However, when it is confirmed that the line has been moved by one line in the sub-scanning direction, the control unit 130 sequentially moves to the dot-shaped stimulable phosphor layer region 72 of the first line,
Laser light 84 emitted from the first laser excitation light source 81
The dot-shaped photostimulable phosphor layer region 72 of the second line is sequentially irradiated with laser light 84 emitted from the first laser excitation light source 81 in the same manner as the irradiation of Of the photostimulable phosphor layer region 72, the photostimulable phosphor 105 is emitted from the photostimulable phosphor layer region 15 by exciting the photostimulable phosphor contained in the photostimulable phosphor layer region 72.
To be detected photoelectrically.

The analog data photoelectrically detected and generated by the photomultiplier 110 is converted into analog data.
Biochemical analysis data is generated from the radiation data output to the converter 113, digitized, and recorded in each dot-shaped stimulable phosphor layer region 72.

In this way, the large number of dot-shaped photostimulable phosphor layer regions 72 formed on the stimulable phosphor sheet 70 are all scanned by the laser light 84 emitted from the first laser excitation light source 81, and a large number of them are scanned. The stimulable phosphor contained in the dot-shaped stimulable phosphor layer region 72 of is excited,
The emitted photostimulable light 105 is the photomultiplier 11
The analog data photoelectrically detected and generated by 0 are digitized by the A / D converter 113, and biochemical analysis is performed from the radiation data recorded in each dot-shaped stimulable phosphor layer region 72. When the usage data is generated, the control unit 130 outputs a drive stop signal to the first laser excitation light source 81, and the drive of the first laser excitation light source 81 is stopped.

On the other hand, when the fluorescence data of the fluorescent substance recorded in the large number of spot-like regions 6 formed on the absorptive substrate 2 of the biochemical analysis unit 1 is read to generate digital data for biochemical analysis, First, the user sets the biochemical analysis unit 1 on the glass plate 101 of the stage 100.

Next, the keyboard 1 is selected by the user.
The type of the fluorescent substance that is the labeling substance is specified and an instruction signal indicating that the fluorescence data should be read is input to 31.

The instruction signal input to the keyboard 131 is input to the control unit 130, and when the control unit 130 receives the instruction signal, it follows the table stored in the memory (not shown).
The laser excitation light source to be used is determined, and which of the filters 112a, 152b, 152c, 152d is to be located in the optical path of the fluorescent light 105 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 derived from a living body
Is used and is input to the keyboard 131, the control unit 130 selects the second laser excitation light source 82, selects the filter 112b, and outputs a drive signal to the filter unit motor 132. To move the filter unit 108 to 532n
A filter member 111b provided with a filter 112b having a property of cutting light having a wavelength of m and transmitting light having a wavelength longer than 532 nm is located in the optical path of the fluorescence 105 to be emitted from the biochemical analysis unit 1. Let

Further, the control unit 130 is
A drive signal is output to the main scanning stepping motor 125,
The optical head 95 is moved in the main scanning direction, and based on the position detection signal of the optical head 95 input from the linear encoder, a large number of spot-shaped regions 6 formed on the absorptive substrate 2 of the biochemical analysis unit 1 are detected. When it is confirmed that the optical head 95 has reached the position where the laser beam 84 can be irradiated to the first spot-shaped region 6, a stop signal is output to the main scanning stepping motor 125 and the second scanning is performed.
A driving signal is output to the laser excitation light source 82 to activate the second laser excitation light source 82 to emit the laser light 84 having a wavelength of 532 nm.

The laser light 84 emitted from the second laser excitation light source 82 is made into parallel light by the collimator lens 90, and then enters the first dichroic mirror 87 and is reflected.

The laser beam 84 reflected by the first dichroic mirror 87 passes through the second dichroic mirror 88 and enters the mirror 89.

The laser beam 84 incident on the mirror 89 is reflected by the mirror 89 and further incident on the mirror 92 to be reflected.

Laser light 8 reflected by mirror 92
4 passes through the hole 93 of the perforated mirror 94 and enters the concave mirror 98.

Laser light 84 incident on the concave mirror 98
Is reflected by the concave mirror 98, and the optical head 9
It is incident on 5.

Laser light 84 incident on the optical head 95
Is reflected by the mirror 96 and is condensed by the aspherical lens 97 on the biochemical analysis unit 1 mounted on the glass plate 101 of the stage 100.

As a result, the laser beam 84 excites a fluorescent substance such as a fluorescent dye contained in the first spot-shaped region 6 of the biochemical analysis unit 1, for example, rhodamine to emit fluorescence.

The fluorescence 105 emitted from rhodamine is
The light is condensed by the aspherical lens 97 provided in the optical head 95, reflected by the mirror 96 to the same side as the optical path of the laser light 84, and made into parallel light, which is a concave mirror 98.
Incident on.

The fluorescent light 105 that has entered the concave mirror 98 is
The perforated mirror 94 is reflected by the concave mirror 98.
Incident on.

Fluorescent light 105 incident on the perforated mirror 94
Is reflected downward by the perforated mirror 94 formed by the concave mirror, and enters the filter 112b of the filter unit 108, as shown in FIG.

Since the filter 112b 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 1
Only light in the 05 wavelength range passes through the filter 112b,
It is detected photoelectrically by the photomultiplier 110.

The analog signal photoelectrically detected and generated by the photomultiplier 110 is output to the A / D converter 113 and converted into a digital signal.
It is output to the data processing device 114.

After the second laser excitation light source 82 is turned on, when a predetermined time, for example, several microseconds elapses, the control unit 130 causes the second laser excitation light source 82 to turn on.
And outputs a drive stop signal to the second laser excitation light source 82.
Driving of the main scanning stepping motor 125 is stopped and the optical head 95 is
The biochemical analysis unit 1 is moved by a pitch equal to the distance between adjacent spot-like regions 6 formed on the absorptive substrate 2.

On the basis of the position detection signal of the optical head 95 input from the linear encoder 127, the optical head 9
The laser beam 84 emitted from the second laser excitation light source 82 is moved by one pitch equal to the distance between the adjacent spot-like regions 6 formed on the adsorptive substrate 2 of the biochemical analysis unit 1 and the second laser excitation light source 82. When it is confirmed that the second spot-shaped region 6 formed on the adsorptive substrate 2 of the biochemical analysis unit 1 can be irradiated with the laser beam, the control unit 130 causes the second laser excitation light source to move. A drive signal is output to 82, the second laser excitation light source 82 is turned on, and the laser beam 84 is included in the second spot-shaped region 6 formed on the absorptive substrate 2 of the biochemical analysis unit 1. Excited fluorescent substances, such as rhodamine.

Similarly, the laser beam 84 is irradiated onto the second spot-shaped region 6 formed on the absorptive substrate 2 of the biochemical analysis unit 1 for a predetermined time, and the second spot-shaped region 6 is irradiated. When the fluorescence 105 emitted from the photomultiplier 110 is photoelectrically detected by the photomultiplier 110 to generate analog data, the control unit 1
30 outputs an off signal to the second laser excitation light source 82 to turn off the second laser excitation light source 82, and
A drive signal is output to the main scanning stepping motor 125 to move the optical head 95 by one pitch equal to the distance between the adjacent spot-like regions 6 formed on the absorptive substrate 2 of the biochemical analysis unit 1. Let

Thus, the first laser excitation light source 81 is repeatedly turned on and off in synchronization with the intermittent movement of the optical head 95, and the optical signal is detected based on the position detection signal of the optical head 95 inputted from the linear encoder 127. Head 95
Is moved by one line in the main scanning direction, and when it is confirmed that all the spot-like regions 6 on the first line of the biochemical analysis unit 1 are scanned by the laser beam 84, the control unit 130 outputs a drive signal to the main scanning stepping motor 125, and the optical head 9
5 is returned to its original position, and a drive signal is output to the sub-scanning pulse motor 121 to move the movable substrate 123.
Is moved by one line in the sub-scanning direction.

On the basis of the position detection signal of the optical head 95 input from the linear encoder 127, the optical head 9
5 is returned to its original position and the movable substrate 123
However, when it is confirmed that the line has been moved by one line in the sub-scanning direction, the control unit 130 causes the spot-shaped region of the first line formed on the absorptive substrate 2 of the biochemical analysis unit 1 to be formed. 6 is sequentially irradiated with the laser beam 84 emitted from the second laser excitation light source 82, in exactly the same manner as the spot shape of the second line formed on the absorptive substrate 2 of the biochemical analysis unit 1. The fluorescence 105 emitted from the spot-shaped region 6 by exciting the rhodamine contained in the region 6 is sequentially converted into the photomultiplier 110.
To detect photoelectrically.

The analog data photoelectrically detected and generated by the photomultiplier 110 is converted into analog data.
The data is converted into digital data by the converter 113 and sent to the data processing device 114.

Thus, the entire surface of the biochemical analysis unit 1 is scanned by the laser beam 84 emitted from the second laser excitation light source 82, and a large number of the adsorbent substrates 2 of the biochemical analysis unit 1 are formed. Rhodamine contained in the spot-like region 6 is excited and emitted fluorescence 105
Is photoelectrically detected by the photomultiplier 110, and the generated analog data is converted into the A / D converter 11
3 is converted into digital data and sent to the data processing device 114, the control unit 13
From 0, a drive stop signal is output to the second laser excitation light source 82, and the drive of the second laser excitation light source 82 is stopped.

As described above, a large number of spot-shaped regions 6 formed on the absorptive substrate 2 of the biochemical analysis unit 1
Data for biochemical analysis is generated based on the radiation data and the fluorescence data recorded in.

According to this embodiment, the biochemical analysis unit 1 is provided with the frame 4 made of a material having rigidity. Therefore, the biochemical analysis unit 1 is extremely thin and handles itself. Even if it is difficult to do so, it is very easy to drop the specific binding substance on the absorptive substrate 2 so that a large number of spot-shaped regions 6 are formed as desired.
Can be formed, and it becomes extremely easy to selectively hybridize the substance of biological origin to the specific binding substance contained in the spot-shaped region 6.

Further, according to this embodiment, pretreatment, prehybridization, hybridization and washing are automatically carried out only by sandwiching the biochemical analysis unit 1 between the gripping members 34, and the biochemical analysis is performed. Since the substance of biological origin is selectively hybridized with the specific binding substance contained in the large number of spot-like regions 6 of the medical unit 1, the substance is sent to the biochemical analysis unit extraction unit 30e. Even if they are different, the result of hybridization does not vary, the reproducibility of hybridization can be significantly improved, and significant labor saving can be realized.

Further, according to this embodiment, the gripping member 3
4, the biochemical analysis unit 1 held in
The pretreatment layer 35 in a state where it is completely immersed in a hybridization solution or a solution prepared by adding a probe solution containing a substance of biological origin labeled with a labeling substance to the hybridization solution or a washing solution.
b, since the vertical vibration is applied to the hybridization layer 36b or the washing treatment tank 37b, the pretreatment liquid, the hybridization solution, and the hybridization solution are derived from a living body labeled with a labeling substance. The solution prepared by adding the probe solution containing the substance or the washing solution uniformly contacts all the spot-like regions 6 formed in the biochemical analysis unit 1 from both sides, so that the substance of biological origin Since the probability of encountering the specific binding substance contained in the spot-like region 6 to be hybridized can be significantly improved, the efficiency of hybridization can be significantly improved, which is required for hybridization. It is possible to significantly reduce the time.

Further, according to this embodiment, the radiation sensor 40 detects the concentration of the radioactive labeling substance contained in the cleaning solution, and the concentration of the radioactive labeling substance in the cleaning solution is equal to or lower than the reference concentration of the radioactive labeling substance. Since it is configured to repeat the cleaning with the cleaning solution until it decreases to
It is possible to accurately determine the end point of cleaning.

FIG. 16 is a schematic perspective view of a biochemical analysis unit according to another preferred embodiment of the present invention.

As shown in FIG. 16, the biochemical analysis unit 141 according to this embodiment includes a substrate 142 formed of aluminum and having a large number of substantially circular through holes 143 formed therein at a high density. And a large number of through holes 1
Nylon 6 is filled inside 43 to form a large number of dot-shaped absorptive regions 144.

Although not shown accurately in FIG. 16, in the present embodiment, a substantially circular through hole 143 having a size of about 10,000 square millimeters of about 10,000 is provided.
It is regularly formed on the substrate 142 at a density of about 5000 pieces / square centimeter. Absorptive area 144
Is formed by filling a large number of through holes 143 with nylon 6 so that the surface thereof is located at the same height as the surface of the substrate 142.

As shown in FIG. 16, in the peripheral region of the substrate 142, two plate members 145 each formed of a material having rigidity such as metal or plastic and having a rectangular opening 145a are formed. 145
The frame body 146 is formed by being fixed with an adhesive, and the peripheral region of the substrate 142 is sandwiched between the two plate members 145 and 145.

As shown in FIG. 16, the frame body 146 of the biochemical analysis unit 1 is provided with two circular positioning through holes 147a and 147b.

In the biochemical analysis unit 141 according to this embodiment having the above-described structure, in the biochemical analysis, a large number of absorptive regions 144 formed on the substrate 142 of the biochemical analysis unit 141 are formed. For example, as specific binding substances, a plurality of cDNAs having different known base sequences are dropped using the spotting device shown in FIGS. 2 and 3.

At the time of dropping the specific binding substance, the specific binding substance is dropped on the adsorptive substrate 2, and instead of the dropping data on the number and density of spot-like regions formed, the biochemical analysis unit 141 is used. The position data of the absorptive regions 144 regarding the number and density of the absorptive regions 144 formed on the substrate 142 of FIG.
In the same manner as in the above-mentioned embodiment, except that a specific binding substance such as cDNA is dropped according to the position data of 1., cDNA or the like is attached to the absorptive region 144 formed on the substrate 142 of the biochemical analysis unit 141. Specific binding substance is dripped.

The biochemical analysis unit 141 in which a specific binding substance is dropped on a large number of absorptive regions 144 is sent to the hybridization apparatus shown in FIGS. 4 and 5, and is carried out in exactly the same manner as in the above embodiment. Thus, the specific binding substance adsorbed on the large number of absorptive regions 144 is selectively hybridized with the substance of biological origin labeled with a radioactive labeling substance and the substance of biological origin labeled with a fluorescent substance. .

Thus, the biochemical analysis unit 141
The radiation data of the radioactive labeling substance which is the labeling substance and the fluorescence data of the fluorescent substance such as the fluorescent dye are recorded in.
The fluorescence data recorded in the biochemical analysis unit 141 are shown in FIGS.
The data is read by the scanner shown in FIG. 1 to generate biochemical analysis data.

On the other hand, the radiation data of the radiolabeled substance is
The radiation data transferred to the stimulable phosphor layer area 72 of the stimulable phosphor sheet 70 and transferred to the stimulable phosphor layer area 72 of the stimulable phosphor sheet 70 shown in FIG. In exactly the same manner as the embodiment, the data for biochemical analysis is generated by being read by the scanner shown in FIGS. 8 to 15.

FIG. 17 shows a large number of dot-shaped stimulants formed on the stimulable phosphor sheet 70 by the radioactive labeling substance contained in the large number of absorptive regions 144 formed in the biochemical analysis unit 141. FIG. 6 is a schematic cross-sectional view showing a method of exposing the phosphor layer region 72.

As shown in FIG. 17, at the time of exposure, each of the absorptive regions 144 formed on the substrate 142 of the biochemical analysis unit 141 has a corresponding dot shape formed on the stimulable phosphor sheet 70. The stimulable phosphor sheet 70 is superposed on the biochemical analysis unit 1 so as to exactly face the stimulable phosphor layer region 72 of FIG.

In the present embodiment, in the biochemical analysis unit 141, nylon 6 is filled in a large number of through holes 143 formed in the aluminum substrate 142,
Since it is formed, it hardly expands or contracts even when subjected to a treatment with a liquid such as hybridization, and therefore, the substrate 1 of the biochemical analysis unit 141 is
Each of the large number of absorptive regions 144 formed on the storage layer 42 exactly opposes the corresponding dot-shaped stimulable phosphor layer region 72 formed on the stimulable phosphor sheet 15 so that the stimulable fluorescent substance is formed. Body sheet 70 and biochemical analysis unit 1
41 and the dot-shaped stimulable phosphor layer region 7
2 can be exposed.

In this way, each of the large number of absorptive regions 144 formed on the substrate 142 of the biochemical analysis unit 141 over a predetermined time is stored in the stimulable phosphor sheet 7.
By stacking the biochemical analysis unit 141 and the stimulable phosphor sheet 70 so as to face the corresponding dot-shaped stimulable phosphor layer region 72 formed in 0, the biochemical analysis unit 141 Of the dot-shaped stimulable phosphor layer region 7 formed on the stimulable phosphor sheet 70 by the radioactive labeling substance contained in the absorptive region 144 of
2 is exposed.

At this time, an electron beam (β-ray) is emitted from the radiolabeled substance adsorbed in the adsorptive region 144 of the biochemical analysis unit 141.
The absorptive region 144 of 41 is formed on the substrate 142 made of aluminum having a property of attenuating radiation,
Since they are spaced apart from each other and are formed in a dot shape, the electron beam (β-ray) emitted from each absorptive region 144 is scattered in the substrate 142 of the biochemical analysis unit 141, and adjacent absorptive substances are adsorbed. Electron beam (β-ray) emitted from region 144
It can be effectively prevented from being mixed with the photostimulable phosphor layer region 72 opposed to the adsorbing region 144 adjacent to the adsorbent region 144. The stimulable phosphor layer region 72 has a plurality of through holes 73 formed in the nickel support 71 having a property of attenuating radiation, and the stimulable phosphor is embedded in the through holes 73.
Since it is formed, the electron beam (β-ray) emitted from each absorptive region 144 is scattered inside the support 71 of the stimulable phosphor sheet 70, and is scattered in the opposing stimulable phosphor layer region 72. It becomes possible to effectively prevent the light from entering the adjacent photostimulable phosphor layer regions 72, and therefore, the electron beam (β-ray) emitted from the radiolabel substance contained in the adsorptive region 144. Can be selectively made incident on the stimulable phosphor layer region 72 facing the adsorptive region 144, and an electron beam (β-ray) emitted from the radiolabel substance contained in the adsorptive region 144. But adjacent adsorbent regions 1
It is possible to reliably prevent the photostimulable phosphor from being exposed by being incident on the photostimulable phosphor layer region 72 to be exposed by the electron beam emitted from 44.

Thus, the radiation data of the radioactive labeling substance is recorded in a large number of dot-shaped stimulable phosphor layer regions 72 formed on the stimulable phosphor sheet 70, and the recorded radiation data is the same as that of the above embodiment. In exactly the same manner, the data shown in FIGS. 8 to 15 is read and biochemical analysis data is generated.

According to the present embodiment, the plurality of absorptive regions 144 of the biochemical analysis unit 141 are further provided with a plurality of through holes 143 formed in the aluminum substrate 142.
Nylon 6 is filled and formed inside, and since there is an aluminum substrate 142 having a property of attenuating light between adjacent adsorbing regions 144, the adsorbing region 144 is It is possible to reliably prevent the fluorescent substance contained in the fluorescent substance 105 from being excited and mixed with the emitted fluorescent substance 105 from being excited by the fluorescent substance contained in the adsorbing regions 144 adjacent to each other. Therefore, it becomes possible to effectively prevent the noise caused by the scattering of the fluorescence 105 from being generated in the biochemical analysis data, and the biochemical analysis data excellent in quantification can be obtained. Can be generated.

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

For example, in the above-described embodiment, the biochemical analysis unit 1 in which one side portion of the frame 4 is held by the gripping member 34 is installed in the pretreatment tank 35b, the hybridization tank 36b, and the cleaning treatment tank 37b. And then the pretreatment liquid, the hybridization solution, and the washing solution are stored in the pretreatment tank 35b and the hybridization tank 36.
b, the pretreatment liquid, which is supplied into the cleaning treatment tank 37b,
Pretreatment tank 3 with hybridization solution and washing solution
5b, hybridization tank 36b, washing treatment tank 3
After supplying the biochemical analysis unit 1 into the pretreatment tank 35b, the hybridization tank 36b, and the washing processing tank 37b, the biochemical analysis unit 1 may be housed in the pretreatment tank 35b.

In the above embodiment, the pair of plate members 3 and 3 and the plate members 145 and 145 are respectively
The frame members 4 and 146 are fixed by an adhesive to form the frame members 4 and 146.
It is not always necessary to fix 145 using an adhesive, and the pair of plate members 3 and 3 and plate members 145 and 145 are fixed by any method to form the frame bodies 4 and 146. You can

Furthermore, in the embodiment shown in FIG. 1, the four sides of the absorptive substrate 2 of the biochemical analysis unit 1 are
It is sandwiched by the frame 4, and in the embodiment shown in FIG. 16, the four sides of the substrate 142 of the biochemical analysis unit 141 are configured to be sandwiched by the frame 146. From the viewpoint of facilitating the handling of the units 1 and 141, the four sides of the adsorptive substrate 2 of the biochemical analysis unit 1 are sandwiched by the frame body 4, and the four sides of the substrate 142 of the biochemical analysis unit 141 are It is not always necessary that the frame body 146 be sandwiched between the frame body 146 and the frame body 146.
The biochemical analysis units 1 and 141 can be configured such that at least three sides of 2 are sandwiched by the frame bodies 4 and 146.

Further, in the above-mentioned embodiment, one side portion of the frame body 4 of the biochemical analysis unit 1 is sandwiched by the holding member 34 of the hybridization device. You may make it hold | maintain one side part of the frame 4 of the unit 1 by another method.

Further, in the above embodiment, the rod 33 which is movable in the vertical direction is attached to the slide member 32, and the rod motor 52 moves the rod 33 up and down to pretreat the biochemical analysis unit 1. It is housed in the bath 35b, the hybridization bath 36b and the washing bath 37b and taken out from the pretreatment bath 35b, the hybridization bath 36b and the washing bath 37b. The unit 1 can be housed in the pretreatment bath 35b, the hybridization bath 36b and the washing treatment bath 37b, and taken out from the pretreatment bath 35b, the hybridization bath 36b and the washing treatment bath 37b.

Further, in the above-described embodiment, the vibrating table 41 having the pretreatment tank 35b mounted on the upper surface thereof, the vibrating table 42 having the hybridization tank 36b mounted on the upper surface thereof, and the cleaning treatment tank mounted on the upper surface thereof. The vibration table 43 to which the 37b is attached is attached to the first vibration motor 55,
The second vibrating motor 56 and the third vibrating motor 56 are used to vibrate vertically, but the biochemical analysis unit 1, the pretreatment solution, the hybridization solution, the hybridization solution, and the probe solution are used. Is added,
It suffices that the prepared solution or the cleaning solution is configured to be relatively moved in the vertical direction, and the first vibration motor 55, the second vibration motor 56 and the third vibration motor 56 Instead of the motor 56, a mechanism for vertically vibrating the holding member 34 holding one side portion of the frame body 4 of the biochemical analysis unit 1 may be provided.

Further, in the above embodiment, the pretreatment bath 35b, the hybridization bath 36b, and the washing treatment bath 37b are respectively provided with independent vibrating tables 41, 42, and 4.
3, the vibration table 41, 42, 43 is independently vibrated in the vertical direction by the first vibration motor 55, the second vibration motor 56, and the third vibration motor 57. However, the pretreatment tank 35b, the hybridization tank 3
6b and the cleaning treatment tank 37b may be attached to the upper surface of a common base, and the base may be vibrated in the vertical direction by a vibration motor.

Further, in the above-mentioned embodiment, the hybridization device is composed of a pair of guide rails 31,3.
The biochemical analysis unit 1 is provided between the biochemical analysis unit setting unit 30a, the pretreatment unit 30b, the hybridization unit 30c, the washing treatment unit 30d, and the biochemical analysis unit removal unit 30e. It is only necessary to have a means for guiding the biochemical analysis unit 1 when moving it, and it is not always necessary to have the pair of guide rails 31, 31.

Further, in the above-mentioned embodiment, the hybridization apparatus is provided with the radiation sensor 40 for detecting the concentration of the radiolabeled substance contained in the washing solution contained in the washing treatment tank 37b. Sensor 4
It is not always necessary to have 0.

Furthermore, in the above-mentioned embodiment, the hybridization device is a single washing solution recovery tank 3
7c is provided, but two or more cleaning solution recovery tanks are provided, and the cleaning solution is recovered in different cleaning solution recovery tanks depending on the concentration of the radiolabeled substance contained in the cleaning solution. You can also

Further, in the embodiment shown in FIG. 1, two circular positioning through holes 5a and 5b are formed in the frame body 4 of the biochemical analysis unit 1 and shown in FIG. In the embodiment, the biochemical analysis unit 14
Two circular positioning through-holes 1 are provided in one frame body 146.
Although 47a and 147b are formed, positioning through holes 5a and 5b are formed in the frame body 4 of the biochemical analysis unit 1, and the frame body 146 of the biochemical analysis unit 141 is formed.
It is not always necessary to form the positioning through holes 147a and 147b.

Further, in the embodiment shown in FIGS. 1 to 15, the absorptive substrate 2 of the biochemical analysis unit 1 is provided with the spot-like region 6 having a size of about 10,000 and about 0.01 mm 2. The specific binding substance is dropped so as to be formed according to a regular pattern at a density of about 5000 pieces / square centimeter, but the number and size of the spot-like regions 6 are arbitrary depending on the purpose. Can be selected, preferably 10
The spot-like regions 6 having a size of less than 5 square millimeters are formed on the absorptive substrate 2 at a density of 10 pieces / square centimeter or more.

Further, in the embodiment shown in FIGS. 1 to 15, the absorptive substrate 2 of the biochemical analysis unit 1 is used.
Then, the specific binding substance is dropped so that the spot-like regions 6 having a size of about 0.01 mm 2 of about 10000 are formed at a density of about 5000 pieces / cm 2 according to a regular pattern. However, the specific binding substance is adsorbed on the substrate 2 so that the spot-like regions 6 are formed according to a regular pattern.
Dropping on top is not necessary.

Furthermore, in the embodiment shown in FIG. 1, the absorptive substrate 2 of the biochemical analysis unit 1 is made of nylon 6, but the absorptive substrate 2 of the biochemical analysis unit 1 is , Porous materials capable of forming a membrane filter other than nylon 6, for example, nylons such as nylon 6,6, nylon 4,10; nitrocellulose, cellulose acetate, Cellulose derivatives such as cellulose acetate butyrate; collagen; alginates such as alginic acid, calcium alginate, alginic acid / polylysine polyion complex; polyolefins such as polyethylene and polypropylene; polyvinyl chloride; polyvinylidene chloride; polyvinylidene fluoride, polytetrafluoride, etc. of Rifuruoraido or copolymers thereof or complex, or a porous carbon material such as activated carbon, adsorptive substrate 2 of the biochemical analysis unit 1
It is also possible to form platinum, gold, iron, silver,
Metals such as nickel and aluminum; metal oxides such as alumina, silica, titania, zeolite; metal salts such as hydroxyapatite and calcium sulfate, inorganic porous materials such as composites thereof, or bundles of multiple fibers for biochemistry The absorptive substrate 2 of the analysis unit 1 may be formed.

In the embodiment shown in FIG. 16, the substrate 142 of the biochemical analysis unit 141 has a substantially circular absorptive region 144 having a size of about 10,000, about 0.01 mm 2. Although it is formed according to a regular pattern with a density of about 5000 pieces / square centimeter, it is not always necessary to form the absorptive region 144 in a substantially circular shape, and it may be formed in any shape such as a rectangular shape. You can

Further, in the embodiment shown in FIG. 16, the substrate 142 of the biochemical analysis unit 141 is
The number of the absorptive regions 144 is about 10,000, and the substantially circular absorptive regions 144 having a size of about 0.01 mm 2 are formed in a regular pattern at a density of about 5000 pieces / cm 2. The size and the size can be arbitrarily selected depending on the purpose, and preferably, 10 or more absorptive regions 144 having a size of less than 5 mm 2 are formed on the substrate 142 at a density of 10 pieces / cm 2 or more. It is formed.

Further, in the embodiment shown in FIG. 16, the substrate 142 of the biochemical analysis unit 141 is provided with a substantially circular absorptive region 144 having a size of about 10,000 and about 0.01 mm 2. Although it is formed according to a regular pattern at a density of about 5000 pieces / square centimeter, it is not always necessary to form the absorptive regions 144 according to the regular pattern.

Further, in the embodiment shown in FIG. 16, the biochemical analysis unit 141 is formed by filling nylon 6 inside a large number of through holes 143 formed in a substrate 142 made of aluminum. The biochemical analysis unit 14 has a large number of absorptive regions 144
It is not always necessary that the first absorptive region 144 is formed of nylon 6, and a porous material other than nylon 6 capable of forming a membrane filter, for example,
Nylons such as nylon 6,6 and nylon 4,10;
Cellulose derivatives such as nitrocellulose, cellulose acetate, cellulose butyrate acetate; collagen; alginic acid,
Alginic acids such as calcium alginate, alginic acid / polylysine polyion complex; polyolefins such as polyethylene and polypropylene; polyvinyl chloride; polyvinylidene chloride; polyvinylidene fluoride,
The biochemical analysis unit 141 is composed of a polyfluoride such as polytetrafluoride, a copolymer or complex thereof, or a porous carbon material such as activated carbon.
Of the absorptive region 144 can be formed, and further,
Metals such as platinum, gold, iron, silver, nickel and aluminum; metal oxides such as alumina, silica, titania and zeolite; metal salts such as hydroxyapatite and calcium sulfate; inorganic porous materials such as composites thereof; Unit 14 for biochemical analysis by a bundle of fibers
One absorptive region 144 may be formed.

Further, in the embodiment shown in FIG. 16, the biochemical analysis unit 141 includes an aluminum substrate 142, but the biochemical analysis unit 14
It is not absolutely necessary that the first substrate 142 is made of aluminum, but other materials may be used.
Can also be formed. Biochemical analysis unit 141
The substrate 142 of is preferably formed of a material having a property of attenuating radiation and / or light, but the material is not particularly limited and may be a biochemical material such as an inorganic compound material or an organic compound material. The substrate 142 of the analysis unit 141 can also be formed, and metal materials, ceramic materials or plastic materials are particularly preferably used. Examples of the inorganic compound material that can be preferably used to form the substrate 142 of the biochemical analysis unit 141 include gold and the like.
Metals such as silver, copper, zinc, aluminum, titanium, tantalum, chromium, iron, nickel, cobalt, lead, tin and selenium; alloys such as brass, stainless steel and bronze; silicon, amorphous silicon, glass, quartz, silicon carbide, Examples thereof include silicon materials such as 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. Further, a polymer compound is preferably used as the organic compound material that can be preferably used for forming the substrate 142 of the biochemical analysis unit 141, and a preferable polymer compound is, for example, polyethylene or polypropylene. Polyolefin; acrylic resin such as polymethylmethacrylate, butyl acrylate / methylmethacrylate copolymer; polyacrylonitrile; polyvinyl chloride; polyvinylidene chloride; polyvinylidene fluoride; polytetrafluoroethylene; polychlorotrifluoroethylene; polycarbonate; polyethylene naphthalate Polyester such as polyethylene terephthalate; nylon 6, nylon 6,6, nylon 4,10, etc .; polyimide; polysulfone; polyphenylene sulfa De; phenolic resins such as novolak; silicon resins such as polydiphenylsiloxane epoxy resin; polyurethane; polystyrene;
Butadiene-styrene copolymer; polysaccharides such as cellulose, cellulose acetate, nitrocellulose, starch, calcium alginate, and hydroxypropylmethylcellulose; chitin; chitosan; sumac; polyamide such as gelatin, collagen and keratin, and copolymerization of these polymer compounds Examples include coalescing. These may be composite materials, and may be filled with metal oxide particles, glass fibers, or the like, if desired, or may be used by blending with an organic compound material.

Further, in the embodiment shown in FIG. 16, a large number of absorptive regions 144 of the biochemical analysis unit 141 are provided inside the large number of through holes 143 formed in the aluminum substrate 142. Filled with 6,
Although formed, the adsorptive film containing the adsorptive material is press-fitted into the large number of through holes 143 formed in the substrate 142,
Many absorptive regions 144 of the biochemical analysis unit 141
Can also be formed.

Furthermore, in the embodiment shown in FIG. 16, a large number of absorptive regions 144 of the biochemical analysis unit 141 are provided with nylon inside a large number of through holes 143 formed in the aluminum substrate 142. Filled with 6,
Although it is formed, it is also possible to form an absorptive region separated from each other by adhering a porous plate having a large number of through holes to at least one surface of the absorptive substrate formed of an absorptive material. .

In the above embodiment, a plurality of c
Although DNA is used, the specific binding substance usable in the present invention is not limited to cDNA,
Cell, virus, hormone, tumor marker, enzyme, antibody, antigen, abzyme, other protein, nucleic acid, c
Any specific binding substance capable of specifically binding to a substance of biological origin such as DNA, DNA, RNA, etc. and having known base sequence, base length, composition, etc. is used as the specific binding substance of the present invention. can do.

Further, in the above-mentioned embodiment, a hybridization solution containing a substance of biological origin labeled with a radioactive labeling substance and a substance of biological origin labeled with a fluorescent substance such as a fluorescent dye is prepared, and the adsorptive region 4 is prepared. Although it is hybridized with the specific binding substance dropped on the, the substance derived from the living body does not necessarily need to be labeled with a fluorescent substance such as a radiolabeling substance and a fluorescent dye, and a radiolabeling substance, a fluorescent substance And a labeling substance that produces chemiluminescence when brought into contact with a chemiluminescent substrate.

[0380]

According to the present invention, reproducibility is high and
It is possible to easily provide a hybridization method and device capable of performing hybridization, and a biochemical analysis unit.

[Brief description of drawings]

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

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

FIG. 3 is a block diagram showing a control system, an input system, a drive system and a detection system of the spotting device.

FIG. 4 is a schematic perspective view of a hybridization device according to a preferred embodiment of the present invention.

FIG. 5 is a block diagram of a control system, a detection system, a drive system and an input system of the hybridization apparatus according to the preferred embodiment of the present invention.

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

FIG. 7 is a photostimulable film formed on a stimulable phosphor sheet by a radiolabel substance contained in a spot-like region of a specific binding substance formed on an adsorptive substrate of a biochemical analysis unit. It is a schematic sectional drawing which shows the method of exposing a fluorescent substance layer area | region.

FIG. 8 is a diagram showing the radiation data recorded on the stimulable phosphor sheet to generate biochemical analysis data and the fluorescence data recorded on the biochemical analysis unit to read the biochemical analysis data. 3 is a schematic perspective view of a scanner that generates analysis data. FIG.

9 is a schematic perspective view showing details near the photomultiplier of the scanner shown in FIG. 8;

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 according to another preferred embodiment of the present invention.

FIG. 17 shows a large number of dot-shaped stimulable phosphors formed on a stimulable phosphor sheet by a radioactive labeling 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.

[Explanation of symbols]

1 Biochemical Analysis Unit 2 Adsorbent Substrate 3 Plate Member 3a Plate Member Opening 4 Frames 5a, 5b Positioning Through Hole 6 Spot Area 10 Substrate 11 Frame 12 Sub-scanning Pulse Motor 13 Rail 14 Movable Substrate 15 Rod 16 Main-scanning pulse motor 17 Endless belt 18 Linear encoder 19 Linear encoder slits 20a, 20b Positioning pin 25 Control unit 26 Keyboard 30a Biochemical analysis unit setting section 30b Pretreatment section 30c Hybridization section 30d Washing section 30e Raw Unit for chemical analysis 31 Guide rail 32 Slide member 33 Rod 34 Gripping member 35a Pretreatment liquid tank 35b Pretreatment tank 35c Pretreatment liquid recovery tank 35d Pretreatment liquid supply tube 35e Pretreatment liquid recovery tube 35 f, 35g valve 36a hybridization solution tank 36b probe solution chip 36c hybridization tank 36d hybridization solution recovery tank 36e hybridization solution supply tube 36f probe solution supply tube 36g hybridization solution recovery tube 36h, 36i, 36j valve 37a washing solution tank 37b Cleaning treatment tank 37c Cleaning solution recovery tank 37d Cleaning solution supply tube 37e Cleaning solution recovery tube 37f, 37g Valve 40 Radiation sensor 41, 42, 43 Shaking table 50 Control unit 51 Slide member motor 52 Rod motor 55 First vibration motor 56 second vibration motor 57 third vibration motor 58 radiation sensor motor 61 first valve opening / closing means 62 second valve Opening / closing means 63 Third valve opening / closing means 64 Fourth valve opening / closing means 65 Fifth valve opening / closing means 66 Sixth valve opening / closing means 67 Seventh valve opening / closing means 68 Keyboard 70 Storage phosphor sheet 71 Support 72 Bright Exhaust Phosphor Layer Region 73 Through Hole 81 First Laser Excitation Light Source 82 Second Laser Excitation Light Source 83 Third Laser Excitation Light Source 84 Laser Light 85 Collimator Lens 86 Mirror 87 First Dichroic Mirror 88 Second Dichroic Mirror 89 Mirror 90 Collimator lens 91 Collimator lens 92 Mirror 93 Perforated mirror hole 94 Perforated mirror 95 Optical head 96 Mirror 97 Aspherical lens 98 Concave mirror 100 Stage 101 Glass plate 105 Fluorescent or stimulated light 108 Filter unit 110 Photomultiplier 111a, 11 1b, 111c, 111d Filter member 112a, 112b, 112c, 112d Filter 113 A / D converter 114 Data processing device 120 Substrate 121 Sub scanning pulse motor 122 Pair of rails 123 Movable substrate 124 Rod 125 Main scanning stepping motor 126 Endless Belt 127 Linear encoder 128 Linear encoder slit 130 Control unit 131 Keyboard 132 Filter unit Motor 141 Biochemical analysis unit 142 Substrate 143 Through hole 144 Adsorbable area 145 Plate member 145a Plate member opening 146 Frame body 147a, 147b Positioning Through hole

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) // C12N 15/09 C12N 15/00 AF term (reference) 2G043 AA01 BA16 CA03 DA01 DA02 DA05 EA01 FA06 GA07 GB19 GB21 HA01 HA02 HA03 HA15 JA02 KA02 KA05 KA09 LA02 NA05 4B024 AA11 CA09 HA14 4B029 AA07 AA23 CC10 FA10 FA12 GA03 GB02 4B063 QA01 QA18 QA19 QQ42 QQ52 QR56 QS34 QS39 QX02 QX07

Claims (28)

[Claims] 1. A substrate, wherein a plurality of absorptive regions containing a specific binding substance having a known structure or characteristic are separated from each other, and at least three sides of the substrate are attached to a rigid frame body. The upper and lower parts of the frame of the biochemical analysis unit thus obtained are held by a biochemical analysis unit holding member that is movable in a substantially horizontal direction along the guide means and that has an elevating mechanism. By lowering the biochemical analysis unit and immersing it in the hybridization solution contained in the hybridization tank, and repeating the biochemical analysis unit with respect to the hybridization solution in the vertical direction. To perform prehybridization,
The probe solution containing a substance of biological origin labeled with a labeling substance is supplied to the hybridization solution housed in the hybridization tank, and the biochemical analysis unit is added to the hybridization solution, and the probe solution is With respect to the added solution, it is repeatedly moved in the vertical direction relative to each other to perform hybridization, and the biochemical analysis unit is raised by the elevating mechanism and taken out from the hybridization tank, The biochemical analysis unit holding member is moved along the guide means, the biochemical analysis unit is lowered by the elevating mechanism, and the biochemical analysis unit holding member is dipped in the cleaning solution housed in the cleaning treatment tank. Repeat the chemical analysis unit with respect to the cleaning solution vertically. Is moved to perform a cleaning process of the biochemical analysis unit, by the lifting mechanism,
A hybridization method, wherein the biochemical analysis unit is raised and taken out from the washing treatment tank. 2. The biochemical analysis unit holding member,
The biochemical analysis unit held by the biochemical analysis unit holding member is provided with a vibration mechanism for vertically vibrating the biochemical analysis unit in the hybridization solution by the vibration mechanism. 2. The hybridization method according to claim 1, wherein the hybridization solution is vibrated vertically in the solution to which the probe solution is added and in the washing solution. 3. A first vibrating mechanism for vertically vibrating the hybridization tank, and a second vibrating mechanism for vertically vibrating the washing treatment tank are provided, and the first vibrating mechanism is used to The hybridization method according to claim 1, wherein the hybridization tank is vibrated in the vertical direction, and the washing processing tank is vibrated in the vertical direction by the second vibrating mechanism. 4. A pretreatment tank is prepared by lowering the biochemical analysis unit by the elevating mechanism before immersing the biochemical analysis unit in the hybridization solution contained in the hybridization tank. The biochemical analysis unit is repeatedly moved relative to the pretreatment liquid in the up-down direction by being dipped in the pretreatment liquid stored in the biochemical analysis unit. And the biochemical analysis unit holding member is moved along the guide means, and the biochemical analysis unit is lowered by the elevating mechanism. The hive according to any one of claims 1 to 3, wherein the hive is immersed in a hybridization solution housed in How to redistribute. 5. The cleaning solution is discharged from the cleaning processing tank, a new cleaning solution is supplied to the cleaning processing layer, and the cleaning processing of the biochemical analysis unit is repeated. The hybridization method according to any one of 1 to 4. 6. The substance derived from a living body is labeled with at least one labeling substance selected from the group consisting of a radioactive labeling substance, a fluorescent substance, and a labeling substance that causes chemiluminescence by contacting with a chemiluminescent substrate. The hybridization method according to any one of claims 1 to 5, characterized in that: 7. A substrate, wherein a plurality of absorptive regions containing a specific binding substance having a known structure or property are formed apart from each other, and at least three sides of the substrate are attached to a rigid frame body. Pre-hybridization and hybridization are performed with the biochemical analysis unit holding means that can hold the upper side of the frame of the biochemical analysis unit that has been moved and that can move in a substantially horizontal direction along the guide means. A hybridization tank, a washing treatment tank for washing the biochemical analysis unit, a hybridization solution tank containing a hybridization solution and capable of supplying the hybridization solution to the hybridization tank, and a label. A probe solution containing a substance of biological origin labeled with a substance is contained, A probe solution chip capable of supplying the probe solution to the hybridization tank, a cleaning solution tank capable of containing the cleaning solution and supplying the cleaning solution to the cleaning treatment tank, and a probe solution to the hybridization solution from the hybridization tank. A hybridization solution recovery tank capable of recovering the added solution, a cleaning solution recovery tank capable of recovering the cleaning solution from the cleaning treatment tank, and a biochemical analysis holding unit held by the biochemical analysis unit holding means. The unit is a hybridization solution contained in the hybridization tank, a probe solution is added to the hybridization solution, and a solution contained in the hybridization tank and a cleaning solution contained in the cleaning treatment tank are added. Repeatedly move up and down, relatively The biochemical analysis unit holding means is configured to be movable between the hybridization tank and the washing treatment tank along the guide means, and the biochemical analysis unit is provided. The holding means includes an elevating mechanism for elevating and lowering the biochemical analysis unit, the elevating mechanism stores the biochemical analysis unit in the hybridization tank or the washing treatment tank, and the hybridization tank or A hybridization apparatus, wherein the biochemical analysis unit is configured to be movable up and down so that the biochemical analysis unit can be taken out of the cleaning treatment tank. 8. The vibrating means is provided in the biochemical analysis unit holding means, and is configured to vibrate the biochemical analysis unit in the vertical direction. The hybridization device according to 1. 9. A vibration table to which the hybridization tank and the washing processing tank are attached,
The hybridization apparatus according to claim 7, wherein the vibrating unit is configured to vibrate the vibrating table in the vertical direction. 10. The vibrating means further comprises a first vibrating table to which the hybridization tank is attached and a second vibrating table to which the cleaning treatment tank is attached.
The first vibrating means for vertically vibrating the first vibrating table, and the second vibrating means for vertically vibrating the second vibrating table are provided. 7. The hybridization device according to 7. 11. A biochemistry for causing the biochemical analysis unit holding means to hold the biochemical analysis unit on the upstream side of the hybridization tank with respect to the moving direction of the biochemical analysis unit holding means. With the analysis unit setting unit, the biochemical analysis unit from the biochemical analysis unit holding means on the downstream side of the cleaning treatment tank with respect to the moving direction of the biochemical analysis unit holding means. A biochemical analysis unit withdrawing part, which is removed and taken out, wherein the biochemical analysis unit holding means is along the guide means, the biochemical analysis unit setting part, the hybridization tank,
The hybridization apparatus according to any one of claims 7 to 10, wherein the hybridization apparatus is configured to be movable between the washing treatment tank and the biochemical analysis unit take-out section. 12. A pretreatment bath for performing pretreatment and a pretreatment liquid are housed upstream of the hybridization bath with respect to the moving direction of the biochemical analysis unit holding means, and the pretreatment liquid is stored in the pretreatment bath. A pretreatment liquid tank capable of supplying a pretreatment liquid to the treatment layer, and a pretreatment liquid recovery tank capable of recovering the pretreatment liquid from the pretreatment liquid tank, wherein the biochemical analysis unit holding means is Along the guide means, the pretreatment tank, the hybridization tank, and the washing treatment tank are configured to be movable, and the vibrating means is further held by the biochemical analysis unit holding means. 8. The biochemical analysis unit is configured to be repeatedly movable in the vertical direction relative to the pretreatment liquid contained in the pretreatment tank.
The hybridization device according to 1. 13. The vibrating means is provided in the biochemical analysis unit holding means, and is configured to vibrate the biochemical analysis unit in a vertical direction. The hybridization device according to 1. 14. A vibrating table to which the pretreatment tank, the hybridization tank, and the cleaning treatment tank are attached, and the vibrating means is configured to vibrate the vibrating table in a vertical direction. The hybridization device according to claim 12, wherein 15. A first vibrating table to which the pretreatment tank is attached, a second vibrating table to which the hybridization tank is attached, and a third vibrating table to which the cleaning treatment tank is attached. And a second vibrating means for vibrating the first vibrating table in a vertical direction, and a second vibrating table vibrating the second vibrating table in a vertical direction. And a third vibrating means for vertically vibrating the third vibrating table.
The hybridization device according to 1. 16. A biochemistry for causing the biochemical analysis unit holding means to hold the biochemical analysis unit on the upstream side of the pretreatment tank with respect to the moving direction of the biochemical analysis unit holding means. With the analysis unit setting unit, the biochemical analysis unit from the biochemical analysis unit holding means on the downstream side of the cleaning treatment tank with respect to the moving direction of the biochemical analysis unit holding means. A biochemical analysis unit withdrawing section that is removed and taken out, wherein the biochemical analysis unit holding means is along the guide means, the biochemical analysis unit setting section, the pretreatment tank, the hybridization tank, 16. The structure according to claim 12, wherein the cleaning treatment tank and the biochemical analysis unit take-out section are movable. The hybridization apparatus according to any one of items. 17. The method according to claim 7, further comprising a radiation sensor for detecting the concentration of the radioactive labeling substance contained in the cleaning solution contained in the cleaning treatment tank.
6. The hybridization device according to item 6. 18. The substance derived from a living body is labeled with at least one labeling substance selected from the group consisting of a radioactive labeling substance, a fluorescent substance, and a labeling substance which causes chemiluminescence by contacting with a chemiluminescent substrate. The hybridization apparatus according to any one of claims 7 to 17, characterized in that: 19. A substrate, which is capable of forming a plurality of spot-shaped regions containing a specific binding substance, separated from each other, and at least three sides of the substrate are attached to a frame body having rigidity. A biochemical analysis unit. 20. The biochemical analysis unit according to claim 19, wherein at least two positioning through holes are formed in the frame body. 21. The biochemical analysis unit according to claim 19, wherein the substrate is made of an adsorptive material. 22. The biochemical analysis unit according to claim 19 or 20, wherein a plurality of absorptive regions containing an absorptive material are formed on the substrate so as to be separated from each other. 23. The absorptive region is formed by filling an absorptive material in holes formed in the substrate so as to be spaced apart from each other. Biochemical analysis unit. 24. The biochemical analysis unit according to claim 22, wherein 10 or more absorptive regions are formed on the substrate. 25. Each of the plurality of absorptive regions,
The unit for biochemical analysis according to any one of claims 22 to 24, which has a size of less than 5 mm 2. 26. The biochemical analysis according to any one of claims 22 to 25, wherein the plurality of absorptive regions are formed on the substrate at a density of 5 pieces / square centimeter or more. unit. 27. The adsorbent material according to claim 21, wherein the adsorbent material is a porous carbon material or a porous material capable of forming a membrane filter.
The unit for biochemical analysis according to the item. 28. The biochemical analysis unit according to claim 21, wherein the adsorptive material is a fiber material.