JP2003180329A - Automatic hybridization apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an automatic hybridization apparatus to produce a biochemical analysis data in high reproducibility and quantitative accuracy. <P>SOLUTION: The hybridization apparatus is provided with a hybridization reaction chamber 30 enabling the setting of a formed biochemical analysis unit 1, a hybridization solution tank 50b, a washing solution tank 50d to hold a washing solution, a solution injection tube 36, a means for selectively connecting the solution injection tube 36 and solution feeding valve means 51b, 51d, a feeding pump 52 to selectively introduce the washing solution into the hybridization reaction chamber, a liquid crystal display panel 44, and a unit 60 for controlling the solution feeding valve means and the feeding pump. The time necessary for the next operation by the user is calculated by the control unit and displayed on the liquid crystal display panel in real time. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an automatic hybridization device, and more specifically,
The present invention relates to an automatic hybridization device capable of efficiently hybridizing a specific binding substance and a substance derived from a living body, and capable of generating reproducible and highly quantitative biochemical analysis data. Is.

[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 hybridizing the substance of
It is difficult to uniformly contact the hybridization solution with a large number of spot-shaped regions containing the specific binding substance, and therefore the specific binding substance and the substance of biological origin cannot be efficiently hybridized. There was a problem.

Further, 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 biogenic substance are derived. Hybridize the substance of the above, remove the unit for biochemical analysis from the hybridization bag,
When the washing solution is placed in a container filled with a washing solution and washed, it is unavoidable that the results of hybridization vary depending on the experimenter and the reproducibility is deteriorated.
Even the same experimenter has a problem that the reproducibility may decrease.

Therefore, according to the present invention, it is possible to efficiently hybridize a specific binding substance with a substance derived from a living body, and also to generate biochemical analysis data with good reproducibility and excellent quantification. It is an object of the present invention to provide an automatic hybridization device that enables the above.

[0013]

The object of the present invention is to:
Multiple hybridization regions containing specific binding substances with known structures or characteristics are separated from each other, and the hybridization reaction chamber is configured so that the formed unit for biochemical analysis can be set. A hybridization solution tank, a washing solution tank for containing a washing solution, and a solution injection tube having flexibility and connected to a solution injection port formed in the lid of the hybridization reaction chamber. A solution supply valve means for selectively connecting the solution injection tube with the hybridization solution tank or the at least one washing solution tank, and the hybridization solution contained in the hybridization solution tank or the at least One wash melt A supply pump for selectively supplying the cleaning solution contained in the tank into the hybridization reaction chamber, a display unit capable of displaying a message, a control unit for controlling the solution supply valve unit and the supply pump. And an automatic hybridization device characterized in that the control means is configured to calculate the time until the next operation is requested by the user and to display it in real time on the display means. To be done.

According to the present invention, in the automatic hybridization device, a biochemical analysis unit can be set in which a plurality of absorptive regions containing specific binding substances whose structures or characteristics are known are separated from each other. A hybridization reaction chamber configured as described above, a hybridization solution tank containing a hybridization solution, and at least one wash solution tank containing a wash solution, which is flexible and is formed on the lid of the hybridization reaction chamber. A solution injection tube connected to the solution injection port, a solution injection tube, and a hybridization solution tank or at least one washing solution tank, which selectively communicates with each other;
A supply pump for selectively supplying the hybridization solution contained in the hybridization solution tank or the cleaning solution contained in at least one cleaning solution tank into the hybridization reaction chamber, and a display unit capable of displaying a message. And a control means for controlling the solution supply valve means and the supply pump, the biochemical analysis unit is simply set in the hybridization reaction chamber, and
It is possible to hybridize a specific binding substance with a substance derived from a living body, and it is possible to generate biochemical analysis data with good reproducibility and excellent quantification.

Further, according to the present invention, since the control means is configured to calculate the time until the next operation is requested by the user and to display the time on the display means in real time, the user: The time until the next operation is required can be known in real time, so that the necessary operation can be performed without error and when required, and the hybridization can be efficiently performed. ,
Furthermore, it is possible to effectively use the time by executing another operation until the next operation is required, and thus it is possible to significantly improve the efficiency of hybridization.

[0016] In a preferred embodiment of the present invention, the automatic hybridization apparatus has a rocking base that can be rocked around a central axis by a motor, a casing and a lid, and the hybridization reaction chamber is the rocking table. Removably attached to the pedestal.

In a preferred embodiment of the present invention, the automatic hybridization apparatus further comprises a pretreatment liquid tank containing a pretreatment liquid, and the control means comprises the solution injection tube, the pretreatment liquid tank, The hybridization solution tank or the at least one
The solution supply valve means is configured to be controllable so as to selectively communicate with one cleaning solution tank.

According to a preferred embodiment of the present invention, the automatic hybridization apparatus further comprises a pretreatment liquid tank for containing the pretreatment liquid, and the control means has a solution injection tube, a pretreatment liquid tank, and a hybridization. Since the solution supply valve means is configured to be controllable so as to selectively communicate with the solution tank or at least one washing solution tank, the pretreatment can be automated and the hybridization can be performed. It becomes possible to improve efficiency.

In a preferred embodiment of the present invention, the automatic hybridization device further comprises a probe solution chip containing a probe solution containing a substance of biological origin labeled with a labeling substance, and the control means comprises: The solution supply valve means is configured to be controllable so that the solution injection tube and the hybridization solution tank, the probe solution chip, or the at least one washing solution tank are selectively communicated with each other.

According to a preferred embodiment of the present invention, the automatic hybridization device further comprises a probe solution chip containing a probe solution containing a substance of biological origin labeled with a labeling substance, and the control means comprises a solution. Injection tube, hybridization solution tank,
Since the solution supply valve means can be controlled so that the probe solution chip or at least one washing solution tank can be selectively communicated with each other, the biochemical analysis unit can be installed in the hybridization reaction chamber. Pre-hybridization, hybridization, and washing can be performed efficiently just by setting them, and the substance of biological origin contained in the probe solution can be used in multiple adsorption regions of the biochemical analysis unit. It is possible to dramatically improve the probability of encountering the specific binding substance contained in the hybridized protein, and to shorten the time required for hybridization.

In a further preferred aspect of the present invention, the automatic hybridization device further comprises a probe solution chip containing a probe solution, and the control means comprises the solution injection tube, the pretreatment liquid tank, and the pretreatment liquid tank. The solution supply valve means is configured to be controllable so that the hybridization solution tank, the probe solution chip, or the at least one washing solution tank is selectively communicated with each other.

According to a further preferred embodiment of the present invention, the automatic hybridization device further comprises a probe solution chip containing a probe solution, and the control means comprises a solution injection tube, a pretreatment liquid tank, and a hybridization solution. Since the tank, the probe solution chip, or at least one washing solution tank is selectively connected to the solution supply valve means so as to be controllable, the biochemical analysis unit is provided in the hybridization reaction chamber. Pre-treatment, pre-hybridization, hybridization and washing can be performed efficiently just by setting it in the chamber, and the substance of biological origin contained in the probe solution can be stored in the biochemical analysis unit. Hybrid contained in multiple absorptive regions The probability of encountering a phase specific binding substances can be dramatically improved, it is possible to reduce the time required of hybridization.

[0023] In a further preferred aspect of the present invention, the automatic hybridization apparatus further has flexibility, and a solution discharge tube connected to a solution discharge port formed in the lid of the hybridization reaction chamber. And at least one solution recovery tank for recovering the solution contained in the hybridization reaction chamber through the solution discharge tube, and the solution contained in the hybridization reaction chamber with the at least one solution recovery tank. A discharge pump for discharging into the tank is provided, and the control means is configured to control the discharge pump.

[0024] In a further preferred aspect of the present invention, the automatic hybridization apparatus further comprises: a first solution recovery tank and a second solution recovery tank for recovering the solution contained in the hybridization reaction chamber; A solution discharge valve means for selectively communicating the solution discharge tube with the first solution recovery tank or the second solution recovery tank is provided, and the control means has the solution discharge tube and the first solution recovery valve means. The solution discharge valve means is controllable so that the solution recovery tank or the second solution recovery tank is selectively communicated with.

According to a further preferred embodiment of the present invention, the automatic hybridization apparatus further comprises: a first solution recovery tank and a second solution recovery tank for recovering the solution contained in the hybridization reaction chamber; The discharge tube is provided with solution discharge valve means for selectively connecting the first solution recovery tank or the second solution recovery tank to each other, and the control means controls the solution discharge tube and the first solution recovery tank or the first solution recovery tank. Since the solution discharge valve means is configured to be selectively communicated with the second solution recovery tank, the solution having a high concentration of the radioactive labeling substance and the solution having a relatively high concentration of the radioactive labeling substance The low solution can be separated and recovered, and the waste solution containing the radiolabeled substance can be appropriately managed.

[0026] In a further preferred aspect of the present invention, the control means causes the solution having a radiolabeled substance concentration exceeding a predetermined value to be recovered in the first solution recovery tank,
The solution discharge valve means is controllable so that a solution having a radiolabeled substance concentration of a predetermined value or less is recovered in the second solution recovery tank.

According to a further preferred aspect of the present invention, the control means causes the solution having a radiolabeled substance concentration exceeding a predetermined value to be collected in the first solution collecting tank so that the radiolabeled substance concentration is below the predetermined value. The solution discharge valve means is configured to be controllable so that the solution is recovered in the second solution recovery tank, so that the solution having a high concentration of radiolabeled substance and the solution having a relatively low concentration of radiolabeled substance are relatively low. The solution can be separated and recovered, and the waste liquid containing the radiolabeled substance can be appropriately managed.

[0028] In a further preferred aspect of the present invention, the control means supplies the washing solution into the hybridization reaction chamber from the at least one washing solution tank a plurality of times. From the above, the solution supply valve means, the supply pump, and the discharge pump can be controlled so that the cleaning solution is discharged.

[0029] In a further preferred aspect of the present invention, the control means controls the mixed solution of the hybridization solution and the probe solution and the washing solution used for at least the first washing in the first solution recovery tank. The solution discharge valve means is configured to be controllable so as to be recovered.

[0030] In a further preferred aspect of the present invention, the control means controls the mixed solution of the hybridization solution and the probe solution and at least the washing solution used for the first washing in the first solution recovery tank. The solution discharge valve means is controllable so that the pretreatment liquid is recovered in the second solution recovery tank.

[0031] In a further preferred aspect of the present invention, the control means comprises a mixed solution of a hybridization solution and a probe solution, a washing solution used for the first washing and a washing used for the second washing. Solution
The solution discharge valve means so that the pretreatment liquid and the cleaning solution used for the third and subsequent cleanings are recovered in the first solution recovery tank and are recovered in the second solution recovery tank. Is configured to be controllable.

In a further preferred aspect of the present invention, the control means is configured to calculate a date and time at which the user is requested to perform the next operation and display the date and time on the display means.

According to a further preferred embodiment of the present invention, the control means is configured to calculate the date and time when the user is requested to perform the next operation and display the date and time on the display means. You can see if the next operation is required, so when and when you need it
It can be performed without error, hybridization can be performed efficiently, and other operations can be executed before the next operation is required, and time can be effectively used. Therefore, the efficiency of hybridization can be significantly improved.

In a further preferred aspect of the present invention, the control means is configured to display the set prehybridization time, hybridization time and washing time on the display means.

According to a further preferred embodiment of the present invention, the control means is configured to display the set pre-hybridization time, hybridization time and washing time on the display means. It is possible to know the pre-hybridization time, hybridization time and washing time that are currently set, and if these time settings are inappropriate, it is possible to reset them as desired,
Therefore, it becomes possible to carry out hybridization under optimum conditions.

In a further preferred aspect of the present invention, the control means is configured to display the contents of processing being executed on the display means.

According to a further preferred embodiment of the present invention, since the control means is configured to display the contents of the processing being executed on the display means, the user is always asked what kind of processing is currently being performed. It is possible to know what is being carried out and thus it is possible to carry out the hybridization without error.

[0038] In a further preferred aspect of the present invention, at least two small cross-sectional area portions are formed in the hybridization reaction chamber with the central axis interposed therebetween, and between the at least two small cross-sectional area portions. The biochemical analysis unit is settable.

[0039] According to a further preferred embodiment of the present invention, at least two small cross-sectional area portions are formed in the hybridization reaction chamber with the central axis interposed therebetween, and the biochemical reaction is performed between the at least two small cross-sectional area portions. Since the analysis unit is settable, the pretreatment solution, hybridization solution, probe solution or washing solution is injected into the hybridization reaction chamber, the motor is driven, and the rocking table is rocked. Thereby, the pretreatment solution, the hybridization solution, the mixed solution of the hybridization solution and the probe solution, or the washing solution flows in the hybridization reaction chamber across at least two small cross-sectional areas, and thus at least Pretreatment liquid, high when crossing two small cross-section areas Since the redidation solution, the mixed solution of the hybridization solution and the probe solution or the washing solution is stirred and mixed, a pretreatment solution, a hybridization solution, a mixed solution of the hybridization solution and the probe solution, and a washing solution, A plurality of absorptive regions of the biochemical analysis unit can be brought into uniform contact with each other, and the efficiency of pretreatment, prehybridization, hybridization, and washing can be significantly improved, and the probe solution can be used. It is possible to dramatically improve the probability that the substance derived from the living body contained in the biochemical analysis unit will meet the specific binding substance to be hybridized contained in the plurality of adsorptive regions of the biochemical analysis unit. It is possible to reduce the time required.

In a further preferred aspect of the present invention, the lid of the hybridization reaction chamber is provided with at least one unit for holding the biochemical analysis unit set in the hybridization reaction chamber at a predetermined position. A pressing member is formed.

According to a further preferred embodiment of the present invention, the lid of the hybridization reaction chamber is provided with at least one holding member for holding the biochemical analysis unit set in the hybridization reaction chamber at a predetermined position. Since the biochemical analysis unit is formed, the pretreatment solution, the hybridization solution, the mixed solution of the hybridization solution and the probe solution, and the washing solution are kept high while the biochemical analysis unit is held at a predetermined position by the pressing member. It is possible to flow in the hybridization reaction chamber, and thus the pretreatment liquid,
A hybridization solution, a mixed solution of the hybridization solution and the probe solution, and a washing solution, and a plurality of absorptive regions of the biochemical analysis unit are uniformly dispersed.
It is possible to bring them into contact with each other, and it is possible to significantly improve the efficiency of pretreatment, prehybridization, hybridization, and washing, and the substance of biological origin contained in the probe solution can be used as a biochemical analysis unit. The probability of encountering a specific binding substance to be hybridized contained in a plurality of adsorptive regions can be dramatically improved, and the time required for hybridization can be shortened.

[0042] In a further preferred aspect of the present invention, the hybridization reaction chamber is formed with two small cross-sectional area portions.

In a further preferred embodiment of the present invention, said two of said hybridization reaction chambers.
The solution inlet is formed on one side of the two small cross-section areas on the opposite side of the central axis, and the solution injection port is formed on the other side of the two small cross-section areas on the opposite side of the central axis. A discharge port is formed.

According to a further preferred embodiment of the present invention, a solution inlet is formed on one side of the two small cross-sectional area portions of the hybridization reaction chamber on the opposite side of the central axis from the two small cross-sectional area portions. Since the solution discharge port is formed on the opposite side of the central axis to the other of the parts, when the solution injection part is located below the solution discharge part,
The probe solution can be injected from the solution injection part into the hybridization solution in the hybridization reaction chamber, and thus the probe solution and the hybridization solution can be uniformly mixed.

In a further preferred aspect of the present invention, the distance between the casing and the lid of the hybridization reaction chamber is substantially constant, and two narrow portions are formed in the casing and the lid. The two narrow cross-sections form the two small cross-section areas.

According to a further preferred embodiment of the present invention, the distance between the casing and the lid of the hybridization reaction chamber is substantially constant, and two narrow portions are formed in the casing and the lid. Since the two small cross-sectional area portions are formed, when the rocking table is rocked, the pretreatment liquid, the hybridization solution, the mixed solution of the hybridization solution and the probe solution, and the washing solution are separated into two narrow spaces. Across the width, it is flowed, agitated, and mixed homogeneously, thus pretreatment solution, hybridization solution, mixed solution of hybridization solution and probe solution and washing solution, and a plurality of units for biochemical analysis. Can be uniformly contacted with the absorptive region of It is possible to greatly improve the efficiency of lysis and washing, and the substance of biological origin contained in the probe solution is contained in multiple absorptive regions of the biochemical analysis unit and is to be hybridized. The probability of encountering a chemically bound substance can be dramatically improved, and the time required for hybridization can be shortened.

In a further preferred aspect of the present invention, the hybridization reaction chamber between the two small cross-sectional area portions has a substantially rectangular shape having a width slightly larger than the width of the biochemical analysis unit. ing.

[0048] According to a further preferred embodiment of the present invention, the hybridization reaction chamber between the two small cross-sectional area portions has a substantially rectangular shape having a width slightly larger than the width of the biochemical analysis unit. Therefore, the biochemical analysis unit can be held in a substantially rectangular region without providing a pressing member on the lid of the hybridization reaction chamber, and therefore, the biochemical analysis unit can be set to a predetermined size. Since the pretreatment solution, the hybridization solution, the mixed solution of the hybridization solution and the probe solution, and the washing solution can be made to flow in the hybridization reaction chamber while being held at the position of the pretreatment solution, Hybridization solution, mixed solution of hybridization solution and probe solution, and The purified solution and the plurality of absorptive regions of the biochemical analysis unit can be brought into contact with each other uniformly, and the efficiency of pretreatment, prehybridization, hybridization and washing can be significantly improved. At the same time, it is possible to dramatically improve the probability that the substance of biological origin contained in the probe solution encounters the specific binding substance to be hybridized contained in the plurality of adsorptive regions of the biochemical analysis unit. It becomes possible to shorten the time required for hybridization.

[0049] In a further preferred aspect of the present invention, the casing and the lid of the hybridization reaction chamber are formed so as to become gradually narrower toward both ends thereof, whereby the two A small cross-sectional area portion is formed.

According to a further preferred embodiment of the present invention, the casing and the lid of the hybridization reaction chamber are formed so as to become gradually narrower toward both ends thereof, whereby two small cross-sectional areas are provided. Since the part is formed, when the rocking base is rocked, the pretreatment liquid,
Since the hybridization solution, the mixed solution of the hybridization solution and the probe solution, and the washing solution flow toward both ends of the hybridization reaction chamber and are agitated and uniformly mixed, the pretreatment solution, the hybridization solution, and the The mixed solution of the hybridization solution and the probe solution and the washing solution can be brought into contact with a plurality of absorptive regions of the biochemical analysis unit uniformly, and the efficiency of pretreatment, prehybridization, hybridization and washing can be improved. It is possible to improve significantly, and the substance of biological origin contained in the probe solution encounters the specific binding substance to be hybridized contained in the multiple adsorptive regions of the biochemical analysis unit. The probability can be dramatically improved and the hybrid It is possible to shorten the time required for the internalization.

In a further preferred aspect of the present invention, the substance derived from the living body is at least one selected from the group consisting of a radioactive labeling substance, a fluorescent substance and a labeling substance capable of producing chemiluminescence when brought into contact with a chemiluminescent substrate. It is labeled with a species labeling substance.

[0052] In a preferred aspect of the present invention, the biochemical analysis unit includes a substrate in which a plurality of holes are formed apart from each other, and the plurality of absorptive regions are formed in the substrate. The specific material is formed in the adsorptive material filled in the plurality of pores.

In a further preferred aspect of the present invention, the biochemical analysis unit includes a substrate having a plurality of through holes spaced apart from each other, and the plurality of absorptive regions are formed on the substrate. The specific binding substance is contained in the absorptive material filled in the plurality of through-holes thus formed.

[0054] 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 the adsorptive membrane is made to contain a specific binding substance.

In a further preferred aspect of the present invention, the biochemical analysis unit includes a substrate in which a plurality of recesses are formed separately from each other, and the plurality of absorptive regions are formed in the substrate. The specific material is formed in the adsorptive material filled in the plurality of recesses.

[0056] In another preferred aspect of the present invention, the biochemical analysis unit is configured such that an absorptive substrate and a plurality of through holes are formed apart from each other, and at least one surface of the absorptive substrate is formed. A plurality of absorptive regions are formed by adhering a specific binding substance to the absorptive substrates in the plurality of through holes formed in the substrate.

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

According to a preferred embodiment of the present invention, since the substrate of the biochemical analysis unit has a property of attenuating radiation, the biochemical analysis unit has absorptive regions formed at high density. Also in this case, the specific binding substance contained in the plurality of adsorptive regions of the biochemical analysis unit is hybridized with a substance of biological origin labeled with a radioactive labeling substance, selectively labeled, and The chemical analysis unit and the stimulable phosphor sheet are superposed, and a plurality of stimulable substances formed on the support of the stimulable phosphor sheet by the radioactive labeling substance selectively contained in the plurality of absorptive regions. When exposing the phosphor layer area, the electron beam (β-ray) emitted from the radio-labeled substance contained in each adsorptive area is effectively scattered in the substrate of the biochemical analysis unit. Can be prevented , Therefore, each contained in the absorptive regions released from the radioactive labeling substance are electron beam (beta ray)
To the region of the corresponding stimulable phosphor layer to selectively expose only the region of the corresponding stimulable phosphor layer to the exposure, so that it is possible to expose the region exposed to the radioactive labeling substance. The photostimulable phosphor layer is scanned by excitation light, and the photostimulable light emitted from the photostimulable phosphor layer is photoelectrically detected to provide high resolution and quantitative data for biochemical analysis. Can be generated.

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

[0063] 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 a distance between the adjacent absorptive regions, The energy of radiation
It has the property of being attenuated to 1/500 or less.

[0064] 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 a distance between the adjacent absorptive regions, 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 regions are densely formed on the substrate of the biochemical analysis unit. A substance derived from a living body that is labeled with a labeling substance that causes chemiluminescence by forming a specific binding substance contained in a plurality of adsorptive regions and contacting it with a fluorescent substance and / or a chemiluminescent substrate is selectively used. Even when hybridized to, the large number of absorptive regions are irradiated with excitation light to excite the fluorescent substance selectively contained in the large number of absorptive regions, and the emitted fluorescence is photoelectrically converted. At the time of detection, 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 the area 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.

[0067] In a preferred aspect of the present invention, when the substrate of the biochemical analysis unit transmits light in the substrate by a distance equal to a distance between the adsorbing regions adjacent to each other, Has the property of attenuating the energy of 1/5 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 following property of damping.

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 the substrate of the biochemical analysis unit transmits light through the substrate by a distance equal to the distance between the adsorbing regions adjacent to each other, 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.

[0073] In a preferred aspect of the present invention, the biochemical analysis unit is formed with 10 or more absorptive regions.

[0074] In a further preferred aspect of the present invention, the biochemical analysis unit is formed with 50 or more absorptive regions.

[0075] In a further preferred aspect of the present invention, the biochemical analysis unit is formed with 100 or more absorptive regions.

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

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

[0078] In a further preferred aspect of the present invention, the biochemical analysis unit is formed with 5,000 or more absorptive regions.

In a further preferred aspect of the present invention, the biochemical analysis unit is formed with 10,000 or more absorptive regions.

In a further preferred aspect of the present invention, the biochemical analysis unit is formed with 50,000 or more absorptive regions.

In a further preferred aspect of the present invention, the biochemical analysis unit is formed with 100,000 or more absorptive regions.

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.

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.

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.

[0085] 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.

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.

In a preferred embodiment of the present invention, the plurality of absorptive regions are provided in the biochemical analysis unit,
It is formed with a density of 10 pieces / square centimeter or more.

In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in 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 in the biochemical analysis unit at a density of 100 pieces / square centimeter or more.

[0091] In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the biochemical analysis unit at a density of 500 or more per cm 2.

[0092] In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the biochemical analysis unit at a density of 1,000 or more per cm 2.

In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the biochemical analysis unit at a density of 5,000 or more per cm 2.

[0094] In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the biochemical analysis unit at a density of 10,000 or more per cm 2.

[0095] In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the biochemical analysis unit at a density of 50,000 or more per cm 2.

[0096] In a further preferred aspect of the present invention, the plurality of absorptive regions are formed in the biochemical analysis unit at a density of 100,000 per square centimeter or more.

In a preferred embodiment of the present invention, the plurality of absorptive regions are provided in the biochemical analysis unit,
It is formed in a regular pattern.

In a preferred aspect of the present invention, each of the plurality of through holes is formed in the substrate of the biochemical analysis unit in a substantially circular shape.

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, as the inorganic compound material which can be preferably used for forming the substrate of the biochemical analysis unit, 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 and 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 larger 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.

In general, 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 another preferred aspect of the present invention, the biochemical analysis unit comprises an absorptive substrate,
The plurality of absorptive regions are formed by allowing the absorptive substrate to contain a specific binding substance.

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 in which a specific binding substance to which a substance of biological origin is hybridized is dropped by the hybridization apparatus according to a preferred embodiment of the present invention.

As shown in FIG. 1, the biochemical analysis unit 1 according to this embodiment includes a substrate 2 formed of aluminum and having a large number of substantially circular through holes 3 formed therein at a high density. Nylon 6 is filled inside the large number of through holes 3 to form a large number of dot-shaped absorptive regions 4
Are formed.

Although not shown exactly in FIG. 1, in the present embodiment, approximately 500 through-holes 3 of approximately circular shape having a size of approximately 0.01 square millimeter of approximately 10,000 are provided.
Substrate 2 regularly with a density of 0 pieces / cm 2.
Is formed in. The absorptive region 4 has a large number of through holes 3 so that its surface is located at the same height as the surface of the substrate 2.
Nylon 6 is filled inside and formed.

As shown in FIG. 1, the substrate 2 of the biochemical analysis unit 1 is further provided with two circular alignment through holes 5 and 5.

In the biochemical analysis, in a large number of absorptive regions 4 regularly formed in the biochemical analysis unit 1, for example, as a specific binding substance, a plurality of different cDNAs whose base sequences are known are different from each other. Are dropped using a spotting device.

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, 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 5 and 5 formed on the substrate 2 of the biochemical analysis unit 1. Positioning pins 20a, 20b are provided upright and formed on the substrate 10 of the spotting device.
By always placing the biochemical analysis unit 1 on the substrate 10 of the spotting device so that the two positioning pins 20a, 20b are inserted into the corresponding through holes 6a, 6b for positioning, It is guaranteed that the chemical analysis unit 1 is mounted on the substrate 10 of the spotting device at substantially the same position.

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 comprises 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 configured as described above, a specific binding substance such as cDNA is dropped onto the absorptive region 4 of the biochemical analysis unit 1 according to this embodiment as follows.

First, in the biochemical analysis unit 1, the two positioning pins 20a and 20b formed on the substrate 10 of the spotting device have the two corresponding positioning through holes 5 of the biochemical analysis unit 1, respectively. 5 is placed on the substrate 10 of the spotting device so as to be inserted into the inside.

Next, the substrate 2 of the biochemical analysis unit 1
The drop data relating to the position of the absorptive region 4 formed in the above is input to the keyboard 26.

In this embodiment, absorptive regions having a size of about 0.01 square millimeters of about 10,000 are formed on the substrate 2 of the biochemical analysis unit 1 at a density of about 5000 pieces / square centimeter. , The specific binding substance is the absorptive region 4 of the biochemical analysis unit 1.
Then, it is dropped.

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, each of the absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1 is detected. 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 is calculated, and the drive pulse data is
Stored in a memory (not shown).

In this embodiment, a large number of absorptive regions 4 are formed on the substrate 2 of the biochemical analysis unit 1 at regular intervals in a regular pattern.
After the third, in order to move the spotting head 9 to the position of the adsorptive region 4 where the specific binding substance should be dropped, the drive pulse to be given to the main scanning pulse motor 16 and the sub scanning pulse motor 12 is first In order to move the spotting head 9 from the position of the adsorptive region 4 where the specific binding substance should be dropped to the position of the adsorptive region 4 where the specific binding substance should be dropped, a main scanning pulse motor 16 and the sub-scanning pulse motor 12, which is the same as the driving pulse to be applied to the motor 12, and therefore, in order to move the spotting head 9 to the position of the adsorptive region 4 where the specific binding substance should be dropped, From the drive pulse to be applied to the motor 16 and the sub-scanning pulse motor 12, first from the position of the adsorptive region 4 to which the specific binding substance is to be dropped Secondly, 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 of the adsorptive region 4 where the specific binding substance should be dropped is calculated, Suffice it to store in memory.

Adsorbent region 4 onto which a specific binding substance should be dropped
When 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 is calculated and the driving pulse data is stored in the memory, the control unit 2
5 is based on the drive pulse data stored in the memory,
Main scanning pulse motor 16 and sub scanning pulse motor 12
Apply a predetermined drive pulse to the spotting head 9
Is intermittently moved, and when the spotting head 9 reaches the position of the adsorptive region 4 where the specific binding substance should be dropped, a drive stop signal is output to the main scanning pulse motor 16 and the sub scanning pulse motor 12. Then, the spotting head 9 is stopped, a dropping signal is output to the spotting head 9, and the specific binding substance is ejected from the injector.

When the spotting head 9 is moved to the position of the adsorptive region 4 where the specific binding substance should be dropped after the second position, the spotting head 9 is moved by the arrow X.
In the main scanning direction indicated by and the sub-scanning direction indicated by arrow Y, respectively, 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 is formed on the substrate 2 of the biochemical analysis unit 1 according to the input dropping data. A predetermined specific binding substance is successively dropped onto the large number of adsorptive regions 4.

Thus, when the specific binding substance is dropped onto the large number of absorptive regions 4, the biochemical analysis unit 1 becomes
It is taken out from the spotting device and set in the automatic hybridization device.

FIG. 4 is a schematic perspective view of the hybridization reaction chamber.

As shown in FIG. 4, the hybridization reaction chamber 30 has a rectangular casing 31.
And a rectangular lid 32 that is swingably attached around one side edge of the casing 31. When the lid 32 is closed, the hybridization reaction chamber 30 is provided.
Are configured to be watertight.

As shown in FIG. 4, the inside of the hybridization reaction chamber 30 has a rectangular region 33a having a rectangular cross section and a width slightly larger than the width of the biochemical analysis unit 1. On both sides of the rectangular area 33a, a reaction space 33 composed of triangular areas 33b and 33c having a triangular cross section with apexes at both ends is formed.

The lid 32 is provided with six pin-shaped pressing members 34 along the width direction, and when the biochemical analysis unit 1 is set in the casing 31 and the lid 32 is closed, the pressing members are pressed. Biochemical analysis unit 1 housed in hybridization reaction chamber 30 by 34
Are configured to be held in the rectangular area 33a.

As shown in FIG. 4, the triangular region 33b of the lid 32 of the hybridization reaction chamber 30 is shown.
A pretreatment solution, a hybridization solution, a probe solution and a washing solution are introduced into the solution injection port 35 formed near one end of the hybridization reaction chamber 30.
A solution injecting tube 36 for injecting into is attached, while a lid 32 of the hybridization reaction chamber 30 is attached.
The solution discharge port 37 formed in the vicinity of one end of the triangular region 33c for discharging the pretreatment solution, the solution in which the probe solution is added to the hybridization solution, and the washing solution are discharged from the hybridization reaction chamber 30. A tube 38 is attached.

A male screw (not shown) is formed at the tip of the solution injection tube 36, and a male screw is screwed on a female screw (not shown) formed on the inner wall of the solution injection port 35 of the hybridization reaction chamber 30. By combining
A solution injection tube 36 is configured to be attached to the solution injection port 35 of the hybridization reaction chamber 30.

The solution injection tube 36 and the solution discharge tube 38 are both made of a flexible material.

FIG. 5 is a schematic perspective view of an automatic hybridization apparatus according to a preferred embodiment of the present invention.

As shown in FIG. 5, the automatic hybridization apparatus according to this embodiment comprises a hybridization apparatus main body 40 having a thermostat and a personal computer 41.
Is provided with a keyboard 42 and a mouse 43 for inputting various commands and data, and a liquid crystal display panel 44.

FIG. 6 is a schematic perspective view showing details of the hybridization device main body 40, and FIG. 7 is a line A- of FIG.
It is a schematic sectional drawing which followed the A line.

As shown in FIGS. 6 and 7, the hybridization device main body 40 has a swing base plate 47 swingably attached to a base 46 via a shaft 45 provided at a substantially central portion thereof. The hybridization reaction chamber 30 is removably attached to the upper surface of the rocking base 47 so that the central axis 30a thereof is located immediately above the shaft 45.

As shown in FIG. 6, the hybridization apparatus main body 40 further includes a pretreatment liquid tank 50a for containing a pretreatment liquid, a hybridization solution tank 50b for containing a hybridization solution,
A probe solution chip 50c containing a probe solution,
A cleaning solution tank 50d for containing the cleaning solution is provided.

As shown in FIG. 6, the pretreatment liquid tank 5
0a, the hybridization solution tank 50b, the probe solution chip 50c, and the washing solution tank 50d,
Valve 51a, valve 51b, valve 51c, respectively
And a valve 51d, which is connected to the solution injection tube 36, and a pump 52 is provided in the solution injection tube 36 between the hybridization reaction chamber 30 and the valves 51a, 51b, 51c and 51d. ing.

The valve 51a, the valve 51b, the valve 51c and the valve 51d are three-way valves, which are a pretreatment liquid tank 50a, a hybridization solution tank 50b, a probe solution chip 50c and a washing solution tank 50d, respectively. , A first position for connecting the solution injection tube 36, a second position for connecting the atmosphere and the solution injection tube 36, a pretreatment liquid tank 50a, and a hybridization solution tank 50.
b, probe solution chip 50c and cleaning solution tank 5
The third position for blocking the communication between the solution injection tube 36 and 0d and the atmosphere can be selectively taken.

As shown in FIG. 6, the automatic hybridization apparatus according to this embodiment further includes a first solution recovery tank 53 for recovering a solution having a high radiolabeling substance concentration from the hybridization reaction chamber 30.
a and from the hybridization reaction chamber 30,
A second solution recovery tank 53b for recovering a solution having a relatively low radiolabeled substance concentration is provided, and the first solution recovery tank 53a and the second solution recovery tank 53b are respectively provided via a valve 54a and a valve 54b. A pump 55 is provided in the solution discharge tube 38 between the hybridization reaction chamber 30 and the valves 54a and 54b.

Here, the valve 54a and the valve 54b
Are constituted by three-way valves, and are respectively a first solution recovery tank 53a and a second solution recovery tank 53.
b, a first position for connecting the solution discharge tube 38, a second position for connecting the atmosphere and the solution discharge tube 38, a first solution recovery tank 53a, a second solution recovery tank 53b, and the atmosphere. And solution discharge tube 38
The third position for blocking the communication with is selectively formed, and the first solution recovery tank 53a and the second solution recovery tank 53b are each formed of a transparent material. ing.

In this embodiment, the solution obtained by adding the probe solution to the hybridization solution and the washing solution used for the second washing operation are collected in the first solution collecting tank 53a, The solution recovery tank 53b is configured to recover the pretreatment liquid and the cleaning solution used in the third and subsequent cleaning operations.

As shown in FIG. 6, the casing 56a containing the first solution recovery tank 53a comprises a light emitting element 57a and a light receiving element 57b, and is housed in the first solution recovery tank 53a. A first liquid level sensor 57 that detects the liquid level of the solution is provided, while a casing 56b that houses the second solution recovery tank 53b includes a light emitting element 58a and a light receiving element 58b. A second liquid level sensor 58 for detecting the liquid level of the solution contained in the solution recovery tank 18b is provided. Here, when the solution contained in the first solution recovery tank 53a exceeds a predetermined amount and a new hybridization is executed, the first liquid level sensor 57 detects the When the solution cannot be recovered in the solution recovery tank 53a, the light emitting element 57a
When the light emitted from the light emitting element 57a is blocked by the solution contained in the first solution recovery tank 53a and the light emitted from the light emitting element 57a is no longer received by the light receiving element 57b, the liquid level is detected. However, the second liquid level sensor 58 is also provided at a position where the liquid level detection signal can be output.
When the amount of the solution stored in the second solution recovery tank 53b exceeds a predetermined amount and new hybridization is executed, the solution is stored in the second solution recovery tank 53b during the execution of hybridization. When it becomes impossible to collect the light, the light emitted from the light emitting element 58a is blocked by the solution contained in the second solution recovery tank 53b, and the light emitted from the light emitting element 58a is received. It is provided at a position where the liquid level can be detected and a liquid level detection signal can be output when the light is no longer received by 58b.

FIG. 8 shows a control system and a detection system of an automatic hybridization apparatus according to a preferred embodiment of the present invention.
It is a block diagram showing a drive system, an input system, and a display system.

As shown in FIG. 8, the control system of the automatic hybridization apparatus according to this embodiment includes a personal computer 41, and the personal computer 41 controls the operation of the entire personal computer 41. A ROM 61 in which a control program and reference data are stored, an EEPROM 62 for storing various data, and a built-in clock 63.

In this embodiment, the pretreatment liquid tank 5
The pretreatment liquid stored in the hybridization reaction chamber 30 is supplied to the hybridization reaction chamber 30 and the pretreatment time Tw required for performing the pretreatment is changed from the hybridization reaction chamber 30 to the second treatment liquid. Pretreatment liquid discharge time Tw required to discharge into the solution recovery tank 53b
d, the hybridization solution supply time Tpf required to supply the hybridization solution stored in the hybridization solution tank 50b into the hybridization reaction chamber 30, and the probe solution stored in the probe solution chip 50c The probe solution supply time Thf required to supply the solution into the hybridization reaction chamber 30, the solution prepared by adding the probe solution to the hybridization solution is discharged from the hybridization reaction chamber 30 into the first solution recovery tank 53a. Hybridization solution discharge time Thd required to perform the cleaning solution supply, and cleaning solution supply time Tc required to supply the cleaning solution stored in the cleaning solution tank 50d into the hybridization reaction chamber 30. The cleaning solution discharge time Tcd required to discharge the cleaning solution from the hybridization reaction chamber 30 into the first solution recovery tank 53a or the second solution recovery tank 53b is determined in advance and stored in the ROM 61. Also, the pre-hybridization time Tp required for the pre-hybridization, the hybridization time Th required for the hybridization, and the washing time Tc required for the washing operation.
The default value of is predetermined and EEPRO
It is stored in M62.

Further, the detection system of the automatic hybridization apparatus according to this embodiment is the first solution recovery tank 5
A first liquid level sensor 57 for detecting the liquid level of the solution stored in 3a and a second liquid level sensor 58 for detecting the liquid level of the solution stored in the second solution recovery tank 53b. There is.

As shown in FIG. 8, the drive system of the automatic hybridization apparatus according to this embodiment includes a motor 64 for rotating the shaft 45 of the rocking base 47 in both forward and reverse directions.
A pump 52 for injecting the pretreatment liquid, the hybridization solution, the probe solution or the washing solution into the hybridization reaction chamber 30, and the solution or the washing solution in which the probe solution is added to the pretreatment liquid or the hybridization solution, Pump 55 and valve 51 for discharging from the hybridization reaction chamber 30
a, the valve 51b, the valve 51c, and the valve 51d
And a valve 54a and a valve 54b.

As shown in FIG. 8, the input system of the automatic hybridization device is a keyboard 42 and a mouse 4.
3, the display system of the automatic hybridization device is provided with a liquid crystal display panel 44 and a speaker 65 for issuing an alarm.

The hybridization apparatus according to the present embodiment configured as described above is as follows.
The specific binding substance contained in the large number of adsorptive regions 4 of the biochemical analysis unit 1 is selectively hybridized with the substance of biological origin labeled with the labeling substance contained in the probe solution.

First, the pretreatment liquid is prepared and accommodated in the pretreatment liquid tank 50a, the hybridization solution is prepared, and the hybridization solution tank 50 is prepared.
In addition to being stored in b, the cleaning solution is adjusted and stored in the cleaning solution tank 50d.

In the hybridization, first, when the user starts the personal computer 41 and the icon for starting the automatic hybridization software displayed on the screen of the liquid crystal display panel 44 is clicked by the mouse 43, the application is started. The signal is output to the control unit 60 of the personal computer 41, and the control unit 60 activates the automatic hybridization software stored in the ROM 61.

As a result, the first liquid level sensor 57 and the second liquid level sensor 58 are activated, and the liquid level of the solution contained in the first solution recovery tank 53a and the second solution recovery tank The liquid level of the solution contained in 53b is detected.

That is, the solution recovered in the first solution recovery tank 53a exceeds the predetermined amount, and the first liquid level sensor 5
The light emitted from the light emitting element 57a of No. 7 is blocked by the solution recovered in the first solution recovery tank 53a,
When the light emitted from the light emitting element 57a of the first liquid level sensor 57 is not received by the light receiving element 57b, a liquid level detection signal is sent from the first liquid level sensor 57 to the control unit 60 of the personal computer 41. Similarly, the amount of the solution output and the amount of the solution recovered in the second solution recovery tank 53b exceeds a predetermined amount, and the light emitted from the light emitting element 58a of the second liquid level sensor 58 is emitted from the second solution recovery tank 5b.
When the light emitted from the light emitting element 58a of the second liquid level sensor 58 which is blocked by the solution collected in 3a is not received by the light receiving element 58b, the second liquid level sensor 58 outputs the liquid level. The detection signal is output to the control unit 60 of the personal computer 41.

When a liquid level detection signal is input from the first liquid level sensor 57 or the second liquid level sensor 58, it is recovered in the first solution recovery tank 53a or the second solution recovery tank 53b. Solution exceeds a predetermined amount and the first solution recovery tank 53
Since it is recognized that the solution cannot be recovered in the a or the second solution recovery tank 53b, the control unit 60 causes the liquid crystal display panel 44 to display a warning, and also outputs an alarm signal to the speaker 6
Output to 5 to trigger an alarm.

On the other hand, when the liquid level detection signal is not input from the first liquid level sensor 57 or the second liquid level sensor 58, the control unit 60 causes the screen of the liquid crystal display panel 44 to display the main window. Is displayed.

FIG. 9 is a diagram showing the screen of the liquid crystal display panel 44 in which the main window is displayed.

In the present embodiment, when the automatic hybridization software is started, it is determined in advance that E
The default values of the time Tp required for prehybridization, the time Th required for hybridization, and the time required for washing operation Tc stored in the EPROM 62 are read by the control unit 60 and displayed in the main window. Has been done.

In this embodiment, the pre-hybridization time Tp, the hybridization time Th, or the washing time Tc displayed in the main window can be changed when the automatic hybridization software is started. Displays the processing time dialog on the screen of the liquid crystal display panel 44 using the “Settings” menu, and causes the keyboard 42 to
Input the pre-hybridization time Tp, the hybridization time Th or the washing time Tc, or use the mouse 43 to operate the slider in the processing time dialog to change the pre-hybridization time Tp,
Hybridization time Th or washing time Tc
Is reconfigured as desired and is written in the EEPROM 62 so that it can be displayed in the main window when the automatic hybridization software is started.

Next, when the user clicks the "operation SW" in the main window displayed on the screen of the liquid crystal display panel 44 with the mouse 43, a preprocessing start signal is output to the control unit 60. It

Upon receiving the preprocessing start signal, the control unit 60 reads the preprocessing time Tw stored in the EEPROM 62, and based on the preprocessing time Tw,
According to the timing data input from the built-in clock 63,
The scheduled date and time when the preprocessing is completed is calculated.

At the same time, the control unit 60 positions the valve 51a at the first position to bring the pretreatment liquid tank 50a and the solution injection tube 36 into communication with each other, and connects the valves 51b, 51c and 51d to the third position. Position the hybridization solution tank 50
b, probe solution chip 50c and cleaning solution tank 5
The communication between the solution injection tube 36 and 0d and the atmosphere is blocked, and the valve 54a and the valve 54b are connected.
To the second position to remove air and the solution discharge tube 3
Connect with 8.

Next, the control unit 60 outputs a drive signal to the motor 64 to rotate the shaft 45 of the rocking base 47, so that the attachment portion of the solution injection tube 35 to the hybridization reaction chamber 30 causes the hybridization reaction. Solution discharge tube 37 to chamber 30
A drive stop signal is output to the motor 64 to stop the drive of the motor 64 at a timing lower than the mounting portion.

Hybridization Reaction Chamber 30
The attachment portion of the solution injection tube 35 to the solution discharge tube 3 to the hybridization reaction chamber 30
In a state in which it is located below the mounting portion of 7, the rocking table 4
When 7 is stopped, the control unit 60 outputs a drive signal to the pump 52 and, in the main window displayed on the screen of the liquid crystal display panel 44, the fact that the pre-processing is being executed and the pre-processing is completed. The time Tw required for and the scheduled date and time when the preprocessing is completed are displayed.

As a result, the pretreatment liquid contained in the pretreatment liquid tank 50a is injected into the hybridization reaction chamber 30 via the solution injection tube 36.

FIG. 10 shows the hybridization reaction chamber 3 for the pretreatment liquid contained in the pretreatment liquid tank 50a.
It is drawing which shows the screen of a liquid crystal display panel when injection | pouring into 0 is started.

As described above, the liquid crystal display panel 44
In the main window displayed on the screen, the fact that the pre-processing is being executed, the time Tw until the end of the pre-processing, and the scheduled date and time when the pre-processing will be completed are displayed.
It is possible to know the process being executed in the automatic hybridization apparatus, the time required for the process to be completed, and when the process is completed, and therefore it is possible to make the hybridization efficient.

As shown in FIG. 10, in the main window displayed on the screen of the liquid crystal display panel 44, the currently set pre-hybridization time Tp, hybridization time Th and washing time Tc are always displayed. , Is displayed.

Thus, the liquid crystal display panel 44
Since the currently set pre-hybridization time Tp, hybridization time Th, and washing time Tc are always displayed in the main window displayed on the screen, It is possible to know the pre-hybridization time Tp, the hybridization time Th, and the washing time Tc that have been set, and if these time settings are inappropriate, it is possible to reset them as desired. Therefore, it becomes possible to carry out hybridization under optimum conditions.

At this point, since the mounting portion of the solution injection tube 36 to the hybridization reaction chamber 30 is located below the mounting portion of the solution discharge tube 38 to the hybridization reaction chamber 30, the pretreatment liquid is Is the reaction space 33 of the hybridization reaction chamber 30 near the solution injection tube 36.
Housed inside.

When a predetermined amount of the pretreatment liquid is injected into the reaction space 33 of the hybridization reaction chamber 30, the control unit 60 outputs a drive stop signal to the pump 52 to stop the drive of the pump 52. At the same time, a drive signal is output to the motor 64, and the shaft 4 of the rocking base 47 is
5a is alternately rotated in both forward and reverse directions.

As a result, the rocking table 47 is rocked around the shaft 45, and the hybridization reaction chamber 30 attached to the upper surface of the rocking table 47 is rocked around the shaft 45 to carry out the hybridization reaction. Chamber 3
The pretreatment liquid injected into the 0 is uniformly stirred.

After starting the injection of the pretreatment liquid, the control unit 60 constantly waits for the time Tw required to complete the pretreatment in accordance with the time measurement data input from the built-in clock 63.
Is calculated and the time required to complete the preprocessing displayed in the main window displayed on the screen of the liquid crystal display panel 44 is updated.

When the preprocessing time Tw read from the ROM 61 has elapsed after the start of the preprocessing, the control unit 60 outputs a drive stop signal to the motor 64 to stop the rocking of the rocking base 47, and A message indicating that the processing is completed is displayed in the main window displayed on the screen of the liquid crystal display panel 44, and the user is urged to set the biochemical analysis unit 1 in the hybridization reaction chamber 30. Display a message.

Then, the biochemical analysis unit 1 is set by the user to the hybridization reaction chamber 30.
Set inside.

That is, the lid 32 of the hybridization reaction chamber 30 is oscillated around one side edge of the casing 31 and opened, and a specific binding substance such as cDNA is adsorbed on a large number of adsorptive regions 4. The biochemical analysis unit 1 that is present is the hybridization reaction chamber 3
The reaction space 33 is housed in the rectangular region 33a of the reaction space 33 formed in the space 0, and the lid 32 of the hybridization reaction chamber 30 is closed.

When the biochemical analysis unit 1 is set in the hybridization reaction chamber 30, the “operation SW” in the main window displayed on the screen of the liquid crystal display panel 44 by the user uses the mouse 43. Is clicked.

As a result, the prehybridization start signal is output to the control unit 60 of the personal computer 41.

When the pre-hybridization start signal is received, the control unit 60 causes the pre-treatment liquid to be discharged from the hybridization reaction chamber 30 into the second solution recovery tank 53b. Hybridization solution supply time T required to supply the hybridization solution contained in the hybridization solution tank 50b into the hybridization reaction chamber 30.
pdf is read from the ROM 61 and EEPRO
The prehybridization time Tp stored in M62 is read, and the pretreatment liquid discharge time Twd and the hybridization solution supply time Tpf are added to the prehybridization time Tp read from the EEPROM 62, and the The pretreatment liquid is discharged into the second solution recovery tank 53b, the hybridization solution is supplied from the hybridization solution tank 50b to the hybridization reaction chamber 30, pre-hybridization is performed, and pre-hybridization is completed. Then, the time required to inject the probe solution required to inject the probe is calculated.

Next, the control unit 60, based on the time until the probe solution injection calculated in this way,
According to the timing data input from the built-in clock 63,
Calculate the scheduled date and time when pre-hybridization will be completed.

At the same time, the control unit 60 positions the valves 51a, 51b, 51c and 51d in the second position to communicate the atmosphere with the solution injection tube 36 and positions the valve 54b in the first position. , The second solution recovery tank 53b and the solution discharge tube 38 are communicated with each other, and the valve 54a is positioned at the third position so that the first solution recovery tank 53a and the atmosphere are communicated with the solution discharge tube 38. Shut off.

Next, the control unit 60 outputs a drive signal to the pump 55, and the pre-hybridization is being executed in the main window displayed on the screen of the liquid crystal display panel 44. Display the time until the injection of the probe solution is required and the scheduled completion time of prehybridization.

As a result, the pretreatment liquid is discharged from the inside of the hybridization reaction chamber 30 and is discharged into the second solution recovery tank 53b through the solution discharge tube 38.

FIG. 11 is a diagram showing the screen of the liquid crystal display panel when the discharge of the pretreatment liquid contained in the hybridization reaction chamber 30 to the second solution recovery tank 53b is started.

As shown in FIG. 11, in the main window displayed on the screen of the liquid crystal display panel 44, the fact that pre-hybridization is being executed,
Since the time until the prehybridization is completed and the injection of the probe solution is requested and the prehybridization completion date and time are displayed, the user can
Knowing what process is being performed in an automated hybridization device, the time it takes to complete it and when it is completed, and therefore performing other operations during prehybridization Therefore, it is possible to significantly improve the efficiency of hybridization.

When the pretreatment liquid discharge time Twd elapses and the pretreatment liquid contained in the hybridization reaction chamber 30 is discharged into the second solution recovery tank 53b, the control unit 60 causes the valve 54a and The valve 54b is located at the second position, the atmosphere is communicated with the solution discharge tube 38, and the valve 51b is located at the first position.
0b and the solution injection tube 36 are communicated with each other, and the valve 51a, the valves 51c and 51d are located at the third position, and the pretreatment liquid tank 50a, the probe solution tip 50c and the cleaning solution tank 50d, the atmosphere, and the solution The communication with the injection tube 36 is blocked.

Next, the control unit 60 outputs a drive signal to the motor 64 to rotate the shaft 45 of the rocking base 47, so that the attachment portion of the solution injection tube 35 to the hybridization reaction chamber 30 causes the hybridization reaction to occur. Solution discharge tube 37 to chamber 30
A drive stop signal is output to the motor 64 to stop the drive of the motor 64 at a timing lower than the mounting portion.

Hybridization Reaction Chamber 30
The attachment portion of the solution injection tube 35 to the solution discharge tube 3 to the hybridization reaction chamber 30
In a state in which it is located below the mounting portion of 7, the rocking table 4
When 7 is stopped, the control unit 60 outputs a drive signal to the pump 52.

As a result, the hybridization solution contained in the hybridization solution tank 50b is injected into the hybridization reaction chamber 30 through the solution injection tube 36.

At this point, the attachment portion of the solution injection tube 36 to the hybridization reaction chamber 30 is located below the attachment portion of the solution discharge tube 38 to the hybridization reaction chamber 30, so that the hybridization solution Are housed in the reaction space 33 of the hybridization reaction chamber 30 near the solution injection tube 36.

When the hybridization solution supply time Tpf read from the ROM 61 elapses and a predetermined amount of the hybridization solution is injected into the reaction space 33 of the hybridization reaction chamber 30, the control unit 60 drives the pump 52. A stop signal is output to stop the drive of the pump 52, and a drive signal is output to the motor 64 to rotate the shaft 45a of the rocking base 47 alternately in both forward and reverse directions.

As a result, the rocking base 47 is rocked around the shaft 45, and the hybridization reaction chamber 30 attached to the upper surface of the rocking base 47 is rocked around the shaft 45 to carry out the hybridization reaction. Chamber 3
The hybridization solution injected into the 0 is stirred, and the hybridization solution and the many absorptive regions 4 of the biochemical analysis unit 1 are brought into uniform contact with each other, and pre-hybridization is performed.

Here, the hybridization solution injected into the reaction space 33 of the hybridization reaction chamber 30 is first reacted in the reaction space 3 of the hybridization reaction chamber 36 near the solution injection tube 36.
Since it is housed in 3, the hybridization reaction chamber 30 can be rocked to bring the hybridization solution into uniform contact with the large number of absorptive regions 4 of the biochemical analysis unit 1.

FIG. 12 is a schematic cross-sectional view showing the flow of the solution in the reaction space 33 of the hybridization reaction chamber 30.

In this embodiment, the reaction space 33 of the hybridization reaction chamber 30 is provided on both sides of the rectangular area 33a in which the biochemical analysis unit 1 is held.
Since it has the triangular regions 33b and 33c having apexes at both ends, as the rocking base 47 is rocked around the shaft 45, the high space in the reaction space 33 of the hybridization reaction chamber 30 is increased. That the hybridization solution flows as shown by the arrow in FIG. 12 and is stirred and mixed evenly every time it flows into the triangular regions 33b, 33c, thus greatly improving the efficiency of hybridization. Will be possible.

After the start of prehybridization, the control unit 60 constantly calculates the time until the injection of the probe solution is requested according to the timing data input from the built-in clock 63, and the screen of the liquid crystal display panel 44 is displayed. Update the time until the injection of the probe solution displayed in the main window displayed in is required.

Hybridization solution tank 50b
When the pre-hybridization time Tp read from the EEPROM 62 elapses after the hybridization solution stored in the hybridization reaction chamber 30 is supplied to the control unit 60,
The attachment portion of the solution injection tube 36 to the solution discharge tube 3 to the hybridization reaction chamber 30
At a timing below the mounting portion of 8, the drive stop signal is output to the motor 64 to stop the swing of the swing base 47, and the valve 51b is positioned at the third position.
The communication between the hybridization solution tank 50b and the atmosphere and the solution injection tube 36 is blocked.

At the same time, the control unit 60 displays a message indicating that the prehybridization is completed and a message prompting the user to inject the probe solution in the main window displayed on the screen of the liquid crystal display panel 44.

When the message prompting the injection of the probe solution is displayed in the main window displayed on the screen of the liquid crystal display panel 44, the user prepares the probe solution containing the substance of biological origin labeled with the labeling substance. The probe solution chip 50c.

When a specific binding substance such as cDNA is selectively labeled with a radiolabeling substance, a probe solution containing a substance derived from a living body, which is a probe labeled with the radiolabeling substance, is prepared, and a probe solution chip is prepared. It is housed in 50c.

On the other hand, by using a labeling substance that causes chemiluminescence by contacting with a chemiluminescent substrate,
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 50c.

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 50c.

[0216] A substance derived from a living body labeled with a radioactive labeling substance, a substance derived from a living body labeled with a labeling substance that causes chemiluminescence when brought into contact with a chemiluminescent substrate, and a living body labeled with a fluorescent substance such as a fluorescent dye The probe solution chip 50c is prepared by preparing a probe solution containing two or more living body-derived substances among the substances derived from the living body.
In the present embodiment, a probe solution containing a biologically-derived substance labeled with a radioactive labeling substance and a biologically-derived substance labeled with a fluorescent substance is prepared, and is stored in the probe solution chip 50c. Be accommodated.

Next, when the user clicks the "operation SW" in the main window displayed on the screen of the liquid crystal display panel 44 with the mouse 43, a hybridization start signal is output to the control unit 60. It

Upon receiving the hybridization start signal, the control unit 60 reads out the hybridization time Th stored in the EEPROM 62 and the cleaning time Tc required for cleaning, and at the same time the probe solution contained in the probe solution chip 50c
A probe solution supply time Thf required to supply the solution into the hybridization reaction chamber 30 and a solution prepared by adding the probe solution to the hybridization solution are transferred from the hybridization reaction chamber 30 into the first solution recovery tank 53a. The hybridization solution discharge time Thd required to discharge the cleaning solution, the cleaning solution supply time Tcf required to supply the cleaning solution contained in the cleaning solution tank 50d into the hybridization reaction chamber 30, and the cleaning solution The cleaning solution discharge time Tcd required to discharge from the chamber 30 into the first solution recovery tank 53a or the second solution recovery tank 53b is stored in the ROM 6
1, the hybridization solution Th read from the EEPROM 62, the probe solution supply time Thf, the hybridization solution discharge time Thd,
Cleaning solution supply time Tcf and cleaning solution discharge time Tcd
Then, the probe solution is added from the probe solution chip 50c to the hybridization solution contained in the hybridization reaction chamber 30 to carry out the hybridization. After the hybridization is completed, the probe is added to the hybridization solution. The solution prepared by adding the solution is transferred from the hybridization reaction chamber 30 to the first solution recovery tank 53a.
The washing solution is collected in the washing solution tank 50d and supplied into the hybridization reaction chamber 30 a plurality of times to wash the biochemical analysis unit 1. After the washing is completed, The time Tf from the hybridization reaction chamber 30 to the end of cleaning required to collect in the first solution recovery tank 53a or the second solution recovery tank 53b is calculated.

In this embodiment, six times,
The cleaning is configured to be repeated, and the time Tf until the end of cleaning is set to the time from the start of injection into the probe solution to the completion of the sixth cleaning,
The cleaning solution used for the sixth cleaning is configured to remain in the hybridization reaction chamber 30 when the time Tf until the completion of cleaning has elapsed.

Therefore, the time Tf until the end of cleaning is
It is calculated according to the following formula.

Tf = Th + 6 Tc + Thf + Thd + 6
Tcf + 5Tcd In the present embodiment, the cleaning solution used in the first cleaning and the second cleaning and having a high concentration of the radiolabeling substance is the first solution recovery tank 5
The washing solution collected in 3a and used for the third to sixth washings and having a relatively low concentration of the radiolabeling substance is
It is configured to be recovered in the second solution recovery tank 53b.

Then, the control unit 60 calculates the scheduled date and time when the cleaning will end, based on the time Tf until the end of the cleaning thus calculated, according to the time measurement data input from the built-in clock 63.

At the same time, the control unit 60 positions the valve 51c at the first position to communicate the probe solution tip 50c with the solution injection tube 36, and sets the valves 51a, 51b and 51d at the third position. The pretreatment liquid tank 50a, the hybridization solution tank 50b, and the washing solution tank 5.
The communication between the solution injection tube 36 and 0d and the atmosphere is blocked, and the valve 54a and the valve 54b are connected.
To the second position to remove air and the solution discharge tube 3
Connect with 8.

Then, the control unit 60 outputs a drive signal to the motor 64 to rotate the shaft 45 of the rocking base 47, so that the mounting portion of the solution injection tube 35 to the hybridization reaction chamber 30 causes the hybridization reaction. Solution discharge tube 37 to chamber 30
A drive stop signal is output to the motor 64 to stop the drive of the motor 64 at a timing lower than the mounting portion.

Hybridization Reaction Chamber 30
The attachment portion of the solution injection tube 35 to the solution discharge tube 3 to the hybridization reaction chamber 30
In a state in which it is located below the mounting portion of 7, the rocking table 4
When 7 is stopped, the control unit 60 outputs a drive signal to the pump 52.

As a result, the probe solution contained in the probe solution chip 50c is injected into the hybridization reaction chamber 30 via the solution injection tube 36.

At the same time, the control unit 60 displays, in the main window displayed on the screen of the liquid crystal display panel 44, the fact that the hybridization is being executed, the time Tf until the end of washing, and the scheduled date and time of the end of washing.

FIG. 13 is a view showing the screen of the liquid crystal display panel when the injection of the probe solution contained in the probe solution chip 50c into the hybridization reaction chamber 30 is started.

As shown in FIG. 13, in the main window displayed on the screen of the liquid crystal display panel 44, the fact that the hybridization is being performed, the hybridization is completed, and the hybridization solution and the probe solution are mixed. The solution is drained and the wash solution is supplied six times to perform the wash,
The time until the completion of the second cleaning and the scheduled completion date and time of the cleaning are displayed. Therefore, the user can perform the processing executed in the automatic hybridization apparatus, the time required for the processing to be completed, and when the processing is completed. It is possible to know that, and therefore, it is possible to significantly improve the efficiency of hybridization, because other operations can be executed during the execution of hybridization that takes a long time.

At this point, the mounting portion of the solution injection tube 36 to the hybridization reaction chamber 30 is located below the mounting portion of the solution discharge tube 38 to the hybridization reaction chamber 30, so that the probe solution is Is injected into the hybridization solution in the hybridization reaction chamber 30. Therefore, the probe solution and the hybridization solution can be uniformly mixed, and the mixed solution of the hybridization solution and the probe solution can be biochemically mixed. Many absorptive regions 4 of the analysis unit 1
Can be evenly contacted with.

When the probe solution supply time Thf read from the ROM 61 elapses and a predetermined amount of the probe solution is injected into the reaction space 33 of the hybridization reaction chamber 30, the control unit 60 causes the pump 52 to stop driving. Is output to stop the drive of the pump 52, and a drive signal is output to the motor 64 to alternately rotate the shaft 45a of the rocking base 47 in both forward and reverse directions.

As a result, the oscillating table 47 is swung around the shaft 45, and the hybridization reaction chamber 30 attached to the upper surface of the oscillating table 47 is swung around the shaft 45 to allow the hybridization reaction. Chamber 3
The mixed solution of the hybridization solution and the probe solution housed in 0 is agitated, the numerous absorptive regions 4 of the biochemical analysis unit 1 are uniformly contacted, and the hybridization is performed.

In this embodiment, the reaction space 33 of the hybridization reaction chamber 30 is provided on both sides of the rectangular area 33a in which the biochemical analysis unit 1 is held.
Since it has triangular regions 33b and 33c having apexes at both ends, the rocking base 47 is housed in the reaction space 33 of the hybridization reaction chamber 30 as the rocking base 47 is rocked around the shaft 45. The mixed solution of the hybridization solution and the probe solution described above flows as indicated by an arrow in FIG.
Each time it flows into b and 33c, it is agitated and uniformly mixed, so that it hybridizes with the specific binding substance contained in the adsorptive region 4 of the biochemical analysis unit 1. The probability of encountering a substance derived from a living body is dramatically improved, and the efficiency of hybridization can be significantly improved.

After starting the injection of the probe solution, the control unit 60 constantly calculates the time Tf until the end of cleaning in accordance with the time measurement data input from the built-in clock 63, and the main unit displayed on the screen of the liquid crystal display panel 44. The time Tf until the end of cleaning displayed in the window is updated.

The probe solution contained in the probe solution chip 50c is used in the hybridization reaction chamber 3
When the hybridization time Th read from the EEPROM 62 elapses after being supplied to 0, the control unit 60 outputs a drive stop signal to the motor 64 to stop the rocking of the rocking base 47, and the valve 51
a, 51b, 51c and 51d are located at the second position, the atmosphere is communicated with the solution injection tube 36, the valve 54a is located at the first position, and the first solution recovery tank 53a and the solution discharge While communicating with the tube 38, the valve 54b is located at the third position to shut off the communication between the solution discharge tube 38 and the second solution recovery tank 53b and the atmosphere.

Then, the control unit 60 outputs a drive signal to the pump 55.

As a result, the mixed solution of the hybridization solution and the probe solution is discharged from the inside of the hybridization reaction chamber 30, and the solution discharge tube 3
The liquid is recovered in the first solution recovery tank 53a via.

When the hybridization solution discharge time Thd read from the ROM 61 elapses and the mixed solution of the hybridization solution and the probe solution in the hybridization reaction chamber 30 is recovered in the first solution recovery tank 53a, the control is performed. Unit 60
Outputs a drive stop signal to the pump 55,
Stop driving.

Then, the control unit 60 positions the valve 54a and the valve 54b at the second position to communicate the atmosphere with the solution discharge tube 38, and positions the valve 51d at the first position for the cleaning solution. Tank 50
While connecting d and the solution injection tube 38,
The valves 51a, 51b and 51c are positioned at the third position to shut off the communication between the solution injection tube 36 and the pretreatment liquid tank 50a, the hybridization solution tank 50b, the probe solution chip 50c and the atmosphere.

Further, the control unit 60 outputs a drive signal to the motor 64 to rotate the shaft 45 of the rocking base 47, so that the attachment portion of the solution injection tube 36 to the hybridization reaction chamber 30 causes the hybridization reaction. Solution discharge tube 38 to chamber 30
A drive stop signal is output to the motor 64 to stop the drive of the motor 64 at a timing lower than the mounting portion.

Hybridization Reaction Chamber 30
The attachment portion of the solution injection tube 36 to the solution discharge tube 3 to the hybridization reaction chamber 30
In a state in which it is located below the mounting portion of 8, the rocking table 4
When 7 is stopped, the control unit 60 outputs a drive signal to the pump 52.

As a result, the cleaning solution contained in the cleaning solution tank 50d is injected into the hybridization reaction chamber 30 through the solution injection tube 36.

At the same time, the control unit 60 displays in the main window displayed on the screen of the liquid crystal display panel 44 that cleaning is being performed.

FIG. 14 shows the hybridization reaction chamber 3 for the cleaning solution contained in the cleaning solution tank 50d.
It is drawing which shows the screen of a liquid crystal display panel when injection | pouring into 0 is started.

At this point, since the mounting portion of the solution injection tube 36 to the hybridization reaction chamber 30 is located below the mounting portion of the solution discharge tube 38 to the hybridization reaction chamber 30, the washing solution is , The reaction space 33 of the hybridization reaction chamber 30 near the solution injection tube 36
Supplied within.

When the cleaning solution supply time Tcf read from the ROM 61 has elapsed and a predetermined amount of the cleaning solution has been injected into the hybridization reaction chamber 30, the control unit 60 outputs a drive stop signal to the pump 52. , The drive of the pump 52 is stopped, a drive signal is output to the motor 64, and the shaft 45a of the rocking base 47 is
Rotate alternately in both forward and reverse directions.

As a result, the rocking base 47 is rocked around the shaft 45, and the hybridization reaction chamber 30 mounted on the upper surface of the rocking base 47 is rocked around the shaft 45 to carry out the hybridization reaction. Chamber 3
The cleaning solution injected into the 0 is stirred, and the cleaning solution and the many absorptive regions 4 of the biochemical analysis unit 1 are brought into uniform contact with each other to perform cleaning.

Here, via the solution injection tube 36,
The cleaning solution injected into the hybridization reaction chamber 30 firstly has a reaction space 33 in the hybridization reaction chamber 30 near the solution injection tube 36.
Since it is housed inside, the washing solution and the biochemical analysis unit 1 can be brought into uniform contact by rocking the hybridization reaction chamber 30.

In the present embodiment, the reaction space 33 of the hybridization reaction chamber 30 is provided on both sides of the rectangular area 33a in which the biochemical analysis unit 1 is held.
Since it has triangular regions 33b and 33c having apexes at both ends, the rocking base 47 is housed in the reaction space 33 of the hybridization reaction chamber 30 as the rocking base 47 is rocked around the shaft 45. The cleaning solution being
In FIG. 12, it flows as shown by the arrow and is stirred every time it flows into the triangular regions 33b and 33c,
As a result, they can be uniformly mixed, and thus the cleaning efficiency can be significantly improved.

When the cleaning time Tc read from the EEPROM 62 has elapsed, the control unit 60 outputs a drive stop signal to the motor 64 to stop the rocking of the rocking base 47.

Then, the control unit 60 positions the valve 51a, the valve 51b, the valve 51c, and the valve 51d in the second position so that the atmosphere and the solution injection tube 36 communicate with each other, and the valve 54a in the first position. Position, the first solution recovery tank 53a and the solution discharge tube 38 are communicated with each other, and the valve 54b is positioned at the third position so that the second solution recovery tank 53b and the atmosphere and the solution discharge tube 38 are positioned. Cut off communication with.

After that, the control unit 60 outputs a drive signal to the pump 55.

As a result, the washing solution is discharged from the inside of the hybridization reaction chamber 30 and is collected in the first solution collecting tank 53a via the solution discharging tube 38.

The cleaning solution discharge time Tcd read from the ROM 61 has elapsed, and the cleaning solution is removed from the hybridization reaction chamber 30 into the first solution recovery tank 53.
When collected in a, the control unit 60 outputs a drive stop signal to the pump 55 to stop the drive of the pump 55.

Next, the control unit 60 positions the valve 54a and the valve 54b at the second position to communicate the atmosphere with the solution discharge tube 38, and positions the valve 51d at the first position for the cleaning solution. Tank 50
While connecting d and the solution injection tube 36,
The valves 51a, 51b and 51c are positioned at the third position to shut off the communication between the solution injection tube 36 and the pretreatment liquid tank 50a, the hybridization solution tank 50b, the probe solution chip 50c and the atmosphere.

After that, the control unit 60 outputs a drive signal to the motor 64 to rotate the shaft 45 of the rocking base 47 so that the mounting portion of the solution injection tube 36 to the hybridization reaction chamber 30 causes the hybridization reaction to occur. Solution discharge tube 38 to chamber 30
A drive stop signal is output to the motor 64 to stop the drive of the motor 64 at a timing lower than the mounting portion.

Hybridization Reaction Chamber 30
The attachment portion of the solution injection tube 36 to the solution discharge tube 3 to the hybridization reaction chamber 30
In a state in which it is located below the mounting portion of 8, the rocking table 4
When 7 is stopped, the control unit 60 outputs a drive signal to the pump 53.

As a result, the cleaning solution contained in the cleaning solution tank 50d is reinjected into the hybridization reaction chamber 30 via the solution injection tube 36.

When the cleaning solution supply time Tcf read from the ROM 61 elapses and a predetermined amount of cleaning solution is injected into the hybridization reaction chamber 30, the control unit 60 outputs a drive stop signal to the pump 52. , The drive of the pump 52 is stopped, and a drive signal is output to the motor 64 to rotate the shaft 45 of the rocking base 47 alternately in both forward and reverse directions.

As a result, the rocking table 47 is rocked around the shaft 45, and the hybridization reaction chamber 39 attached to the upper surface of the rocking table 47 is rocked around the shaft 45 to carry out the hybridization reaction. Chamber 3
The washing solution injected into the 0 is stirred, the washing solution and the many absorptive regions 4 of the biochemical analysis unit 1 are brought into uniform contact with each other, and the washing is continued.

When the cleaning time Tc read from the EEPROM 62 has elapsed, the control unit 60 outputs a drive stop signal to the motor 64 to stop the rocking of the rocking base 47.

Then, the control unit 60 positions the valve 51a, the valve 51b, the valve 51c and the valve 51d at the second position to bring the atmosphere and the solution injection tube 36 into communication with each other, and the valve 54a at the first position. Position, the first solution recovery tank 53a and the solution discharge tube 38 are communicated with each other, and the valve 54b is positioned at the third position so that the second solution recovery tank 53b and the atmosphere and the solution discharge tube 38 are positioned. Cut off communication with.

Thereafter, the control unit 60 outputs a drive signal to the pump 55.

As a result, the washing solution is discharged from the inside of the hybridization reaction chamber 30 and is collected in the first solution collecting tank 53a via the solution discharging tube 38.

The cleaning solution discharge time Tcf read out from the ROM 61 has elapsed, and the cleaning solution from the hybridization reaction chamber 30 is transferred to the first solution recovery tank 53.
When collected in a, the control unit 60 outputs a drive stop signal to the pump 55 to stop the drive of the pump 55.

Then, the control unit 60 positions the valve 54a and the valve 54b at the second position to communicate the atmosphere with the solution discharge tube 38, and positions the valve 51d at the first position for the cleaning solution. Tank 50
While connecting d and the solution injection tube 36,
The valves 51a, 51b and 51c are positioned at the third position to shut off the communication between the solution injection tube 36 and the pretreatment liquid tank 50a, the hybridization solution tank 50b, the probe solution chip 50c and the atmosphere.

After that, the control unit 60 outputs a drive signal to the motor 64 to rotate the shaft 45 of the rocking base 47 so that the attachment portion of the solution injection tube 36 to the hybridization reaction chamber 30 causes the hybridization reaction to occur. Solution discharge tube 38 to chamber 30
A drive stop signal is output to the motor 64 to stop the drive of the motor 64 at a timing lower than the mounting portion.

Hybridization Reaction Chamber 30
The attachment portion of the solution injection tube 36 to the solution discharge tube 3 to the hybridization reaction chamber 30
In a state in which it is located below the mounting portion of 8, the rocking table 4
When 7 is stopped, the control unit 60 outputs a drive signal to the pump 53.

As a result, the cleaning solution accommodated in the cleaning solution tank 50d is reinjected into the hybridization reaction chamber 30 via the solution injection tube 36.

When the cleaning solution supply time Tcf read from the ROM 61 elapses and a predetermined amount of cleaning solution is injected into the hybridization reaction chamber 30, the control unit 60 outputs a drive stop signal to the pump 52. , The drive of the pump 52 is stopped, and a drive signal is output to the motor 64 to rotate the shaft 45 of the rocking base 47 alternately in both forward and reverse directions.

As a result, the rocking base 47 is rocked around the shaft 45, and the hybridization reaction chamber 39 attached to the upper surface of the rocking base 47 is rocked around the shaft 45 to carry out the hybridization reaction. Chamber 3
The washing solution injected into the 0 is stirred, the washing solution and the many absorptive regions 4 of the biochemical analysis unit 1 are brought into uniform contact with each other, and the washing is continued.

When the cleaning time Tc read from the EEPROM 62 has elapsed, the control unit 60 outputs a drive stop signal to the motor 64 to stop the rocking of the rocking base 47.

Then, the control unit 60 positions the valve 51a, the valve 51b, the valve 51c, and the valve 51d in the second position so that the atmosphere and the solution injection tube 36 communicate with each other, and the valve 54b in the first position. Position, the second solution recovery tank 53b and the solution discharge tube 38 are communicated with each other, and the valve 54a is positioned at the third position so that the first solution recovery tank 53a and the atmosphere, and the solution discharge tube 38. Cut off communication with.

After that, the control unit 60 outputs a drive signal to the pump 55.

As a result, the washing solution is discharged from the inside of the hybridization reaction chamber 30 and is collected in the second solution collecting tank 53b through the solution discharging tube 38.

Here, the cleaning solution used for the third cleaning is recovered in the second solution recovery tank 53b because the cleaning is performed twice and the radioactive label in the cleaning solution is used. This is because the concentration of the substance has dropped to a low value.

From the inside of the hybridization reaction chamber 30 stored in the ROM 61 to the second solution recovery tank 5
When the time required for collecting the cleaning solution elapses in 3b, the control unit 60 outputs a drive stop signal to the pump 55 to stop the drive of the pump 55.

Then, the control unit 60 positions the valve 54a and the valve 54b at the second position to communicate the atmosphere with the solution discharge tube 38, and positions the valve 51d at the first position for the cleaning solution. Tank 50
While connecting d and the solution injection tube 36,
The valves 51a, 51b and 51c are positioned at the third position to shut off the communication between the solution injection tube 36 and the pretreatment liquid tank 50a, the hybridization solution tank 50b, the probe solution chip 50c and the atmosphere.

After that, the control unit 60 outputs a drive signal to the motor 64 to rotate the shaft 45 of the rocking base 47 so that the mounting portion of the solution injection tube 36 to the hybridization reaction chamber 30 causes the hybridization reaction. Solution discharge tube 38 to chamber 30
A drive stop signal is output to the motor 64 to stop the drive of the motor 64 at a timing lower than the mounting portion.

Hybridization Reaction Chamber 30
The attachment portion of the solution injection tube 36 to the solution discharge tube 3 to the hybridization reaction chamber 30
In a state in which it is located below the mounting portion of 8, the rocking table 4
When 7 is stopped, the control unit 60 outputs a drive signal to the pump 53.

As a result, the cleaning solution stored in the cleaning solution tank 50d is reinjected into the hybridization reaction chamber 30 via the solution injection tube 36.

When the cleaning solution supply time Tcf read from the ROM 61 elapses and a predetermined amount of cleaning solution is injected into the hybridization reaction chamber 30, the control unit 60 outputs a drive stop signal to the pump 52. , The drive of the pump 52 is stopped, and a drive signal is output to the motor 64 to rotate the shaft 45 of the rocking base 47 alternately in both forward and reverse directions.

As a result, the rocking base 47 is rocked around the shaft 45, and the hybridization reaction chamber 39 mounted on the upper surface of the rocking base 47 is rocked around the shaft 45 to carry out the hybridization reaction. Chamber 3
The washing solution injected into the 0 is stirred, the washing solution and the many absorptive regions 4 of the biochemical analysis unit 1 are brought into uniform contact with each other, and the washing is continued.

In this way, the washing solution was washed six times.
It is injected into the hybridization reaction chamber 30 and the time T from the completion of the sixth cleaning to the completion of cleaning T
When f has passed, the control unit 60 determines that the valve 51a, the valve 51b, the valve 51c, and the valve 51a.
d to the second position to communicate the atmosphere with the solution injection tube 36, and the valve 54b to the first position to communicate the second solution recovery tank 53b with the solution discharge tube 38. At the same time, the valve 54a is located at the third position to shut off the communication between the solution discharge tube 38 and the first solution recovery tank 53a and the atmosphere.

At the same time, the control unit 60 displays, in the main window displayed on the screen of the liquid crystal display panel 44, a message indicating that the cleaning is completed and a message urging the biochemical analysis unit 1 to be taken out.

On the other hand, when the user clicks the "operation SW" in the main window displayed on the screen of the liquid crystal display panel 44 with the mouse 43, a hybridization completion signal is sent to the control unit. It is output to 60.

Upon receiving the hybridization completion signal, the control unit 60 outputs a drive signal to the pump 55.

As a result, the washing solution remaining in the hybridization reaction chamber 30 and used for the sixth washing was the hybridization reaction chamber 3
From 0, it is discharged through the solution discharge tube 38 into the first solution recovery tank 53a and recovered.

Next, the control unit 60 outputs a drive signal to the motor 64 to rotate the shaft 45 of the rocking base 47 so that the mounting portion of the solution injection tube 35 to the hybridization reaction chamber 30 causes the hybridization reaction to occur. Solution discharge tube 37 to chamber 30
A drive stop signal is output to the motor 64 to stop the drive of the motor 64 at a timing lower than the mounting portion.

As a result, the hybridization reaction chamber 30 is stopped at a position inclined toward the user, and the user can easily put the lid 32 of the hybridization reaction chamber 30 around the one side edge of the casing 31. Then, the hybridization reaction chamber 30 can be opened by swinging it to, and the biochemical analysis unit 1 can be taken out.

In this way, 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 many absorptive regions 4 of the biochemical analysis unit 1. The fluorescence data recorded in the absorptive region 4 is read by a scanner described later, and biochemical analysis data is generated.

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

FIG. 15 is a schematic perspective view of the stimulable phosphor sheet.

As shown in FIG. 15, the stimulable phosphor sheet 70 according to this embodiment includes a nickel support 71 in which a large number of substantially circular through holes 73 are regularly formed. A large number of through holes 73 formed in 71 are filled with a stimulable phosphor, and a large number of stimulable phosphor layer regions 72 are formed in a dot shape.

The large number of through holes 73 are formed in the support 71 in the same pattern as the large number of absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1, and each stimulable phosphor layer region. 72 is formed so as to have the same size as the absorptive region 4 formed on the substrate 2 of the biochemical analysis unit 1.

Therefore, although not shown exactly in FIG. 15, the stimulable phosphor layer regions 72 having a substantially circular shape having a size of about 0.01 square millimeter of about 10,000 have a density of about 5000 pieces / square centimeter. And is formed in a dot shape on the support 71 of the stimulable phosphor sheet 70 by the same regular pattern as the many absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1. There is.

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. The support 71 of the stimulable phosphor sheet 70 has two through-holes 74 for alignment. , 74 are formed at positions corresponding to the two alignment through holes 5 and 5 formed in the substrate 2 of the biochemical analysis unit 1.

FIG. 16 shows the stimulable phosphor contained in the stimulable phosphor layer region 72 formed on the stimulable phosphor sheet 70, and the absorptive region formed on the biochemical analysis unit 1. By the radiolabeled substance selectively contained in 4,
It is a schematic perspective view of the exposure apparatus which exposes.

As shown in FIG. 16, the exposure apparatus for the stimulable phosphor sheet 70 according to the present embodiment is provided with a casing 75 and a lid member 76, and inside the casing 75, the biochemical analysis unit 1 and A substrate 77 on which the stimulable phosphor sheet 70 is placed is provided. The casing 75 and the lid member 76 are made of metal having a property of attenuating radiation.

As shown in FIG. 16, two alignment pins 78a and 78b are provided upright on a substrate 77 of the exposure apparatus.

In exposing the stimulable phosphor layer region 72 formed on the stimulable phosphor sheet 70 to the radioactive labeling substance contained in the absorptive region 4 formed in the biochemical analysis unit 1, First, the user opens the lid member 76 of the exposure apparatus.

Next, the biochemical analysis unit 1 is set by the user to the two positioning pins 78a and 78b formed on the substrate 77 of the exposure apparatus, respectively. Are positioned on the substrate 77 of the exposure apparatus so as to be inserted into the through-holes 5 and 5 for the exposure apparatus, and further, on the surface of the biochemical analysis unit 1, two substrates 77 of the exposure apparatus are erected. The positioning pins 78a, 78b are formed in the support 71 of the stimulable phosphor sheet 70, and the two positioning through holes 7 are formed.
The stimulable phosphor sheet 7 so as to be inserted into
0 is set and the lid member 76 is closed.

FIG. 17 shows a large number of stimulable phosphor layers formed on the stimulable phosphor sheet 70 by the radioactive labeling substance contained in the large number of absorptive regions 4 formed in the biochemical analysis unit 1. FIG. 6 is a schematic cross-sectional view showing a method of exposing a stimulable phosphor contained in a region 72.

As described above, upon exposure, each of the absorptive regions 4 formed on the substrate 2 of the biochemical analysis unit 1 and the photostimulability formed on the support 71 of the stimulable phosphor sheet 70. The biochemical analysis unit 1 and the stimulable phosphor sheet 70 are overlapped in the exposure apparatus so that the phosphor layer regions 72 face each other.

In the present embodiment, since the biochemical analysis unit 1 is formed by filling nylon 6 into a large number of through holes 3 formed in the aluminum substrate 2, hybridization or the like is performed. , Hardly expands or contracts even when subjected to treatment with a liquid, and therefore the absorptive region 4 formed in the biochemical analysis unit 1
Of the stimulable phosphor sheet 70 in the biochemical analysis unit 1 so that each of them accurately faces the corresponding dot-shaped stimulable phosphor layer layer 72 formed in the stimulable phosphor sheet 70. It becomes possible to expose the stimulable phosphor contained in the stimulable phosphor layer region 72 in an overlapping manner.

Thus, each of the absorptive regions 4 formed in the biochemical analysis unit 1 faces the corresponding stimulable phosphor layer region 72 formed in the stimulable phosphor sheet 70 over a predetermined time. As described above, by stacking the biochemical analysis unit 1 and the stimulable phosphor sheet 70 on top of each other, the radiolabeled substance contained in the absorptive region 4 causes a large number of bright spots formed on the stimulable phosphor sheet 70. Exhaust phosphor layer region 72 is exposed.

At this time, an electron beam (β-ray) is emitted from the radiolabeled substance adsorbed in the absorptive region 4, but the absorptive region 4 of the biochemical analysis unit 1 has a property of attenuating radiation. Since the substrate 2 made of aluminum is formed in a dot shape with being separated from each other, the electron beam (β-ray) emitted from each absorptive region 4 is
The photostimulable phosphor layer scattered in the substrate 2 of the biochemical analysis unit 1 and mixed with the electron beam (β-ray) emitted from the adsorbing regions 4 adjacent to each other and facing the adsorbing regions 4 adjacent to each other. A nickel support that can effectively prevent the light from entering the region 72, and that the dot-shaped stimulable phosphor layer region 72 of the stimulable phosphor sheet 70 has a property of attenuating radiation. Many through holes 7 formed in 71
3 is formed by embedding a stimulable phosphor in the inside of 3, and the electron beam (β-ray) emitted from each absorptive region 4 is
It is possible to effectively prevent scattering in the support 71 of the stimulable phosphor sheet 70 and incidence on the stimulable phosphor layer region 72 adjacent to the opposing stimulable phosphor layer region 72. Therefore, the electron beam (β-ray) emitted from the radiolabel substance contained in the absorptive region 4 is selectively incident on the stimulable phosphor layer region 72 facing the absorptive region 4. The electron beam (β-ray) emitted from the radio-labeled substance contained in the adsorptive region 4 can be stimulable fluorescence to be exposed by the electron beam emitted from the adjacent adsorptive region 4. It is possible to reliably prevent the photostimulable phosphor from being exposed to light by entering the body layer region 72.

In this way, a large number of stimulable phosphor layer regions 72 formed on the support 71 of the stimulable phosphor sheet 70,
Radiation data of radiolabeled substances are recorded. FIG.
Reads the radiation data recorded on the stimulable phosphor sheet 70 to generate biochemical analysis data, and reads the fluorescence data recorded on the biochemical analysis unit 1 to obtain the biochemical analysis data. FIG. 19 is a schematic perspective view of a scanner to be generated, and FIG. 19 is a schematic perspective view showing details near the photomultiplier of the scanner shown in FIG. 18.

The scanner according to the present embodiment has a large number of biochemical analysis units 1 and radiation data of radiolabeled substances recorded in a large number of stimulable phosphor layer regions 72 formed on a stimulable phosphor sheet 70. The fluorescent data such as the fluorescent dye recorded in the absorptive region 4 is read.

As shown in FIG. 18, the scanner according to the present embodiment has a first laser excitation light source 81 which emits a laser light 84 having a wavelength of 640 nm and a second laser excitation light source 84 which emits a laser light 84 having a wavelength of 532 nm. Excitation light source 82 and 4
A third laser excitation light source 83 that emits a laser beam 84 having a wavelength of 73 nm is provided.

In this embodiment, the first laser pumping light source 81 is composed of a semiconductor laser light source, and the second laser pumping light source 82 and the third laser pumping light source 83 are used.
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 light 84 generated by 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 beam 84 generated from the third laser excitation light source 83 is collimated by the collimator lens 91, and then the second dichroic mirror 8 is formed.
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 stimulable phosphor layer region 72 formed on the support 71 of the stimulable phosphor sheet 70 is excited, stimulable light 105 is emitted, and the biochemical analysis unit 1 is
When the laser light 84 enters, the fluorescent substance such as the fluorescent dye contained in the absorptive region 4 is excited, and the fluorescence 105 is emitted.

Photostimulable light 105 emitted from the stimulable phosphor layer region 72 of the stimulable phosphor sheet 70 or fluorescence 10 emitted from the absorptive region 4 of the biochemical analysis unit 1.
5 is condensed on the mirror 96 by the aspherical lens 97 provided in the optical head 95, and by the mirror 96,
The laser light 84 is reflected on the same side as the optical path, becomes parallel light, and enters the 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.

Photostimulation 105 incident on the perforated mirror 94
Alternatively, the fluorescent light 105 may be reflected by a perforated mirror 94 formed by a concave mirror, as shown in FIG.
It is reflected downward and enters the filter unit 108,
Light of a predetermined wavelength is cut, enters the photomultiplier 110, and is photoelectrically detected.

As shown in FIG. 19, the filter unit 108 includes four filter members 111a, 151b,
The filter unit 1 is equipped with 151c and 151d.
The motor 08 is configured to be movable in the left-right direction in FIG. 19 by a motor (not shown).

FIG. 20 is a schematic sectional view taken along the line AA of FIG.

As shown in FIG. 20, the filter member 1
11a includes a filter 112a, and the filter 112a
Is a filter used when exciting the fluorescent substance contained in the large number of absorptive regions 4 formed in the biochemical analysis unit 1 using the first laser excitation light source 81 and reading the fluorescence 105. It is a member, and has a property of cutting light having a wavelength of 640 nm and transmitting light having a wavelength longer than 640 nm.

FIG. 21 is a schematic sectional view taken along the line BB of FIG.

As shown in FIG. 21, the filter member 1
11b includes a filter 112b, and the filter 112b
Is a filter used when exciting the fluorescent substance contained in the large number of absorptive regions 4 formed in the biochemical analysis unit 1 using the second laser excitation light source 82 and reading the fluorescence 105. It is a member and has a property of cutting light having a wavelength of 532 nm and transmitting light having a wavelength longer than 532 nm.

FIG. 22 is a schematic sectional view taken along the line CC of FIG.

As shown in FIG. 22, the filter member 1
11c includes a filter 112c, and the filter 112c
Is used when the fluorescent substance contained in the large number of absorptive regions 4 formed in the biochemical analysis unit 1 is excited by using the third laser excitation light source 83 to read the fluorescence 105. It is a filter member, and has a property of cutting light having a wavelength of 473 nm and transmitting light having a wavelength longer than 473 nm.

FIG. 23 is a schematic sectional view taken along the line DD of FIG.

As shown in FIG. 23, the filter member 1
11d includes a filter 112d, and the filter 112d
Uses the first laser excitation light source 81 to excite a large number of stimulable phosphor layer regions 72 formed on the support 71 of the stimulable phosphor sheet 70 to generate a stimulable phosphor layer region 72. Is a filter used when reading the stimulable light 105 emitted from the stimulable phosphor layer region 72, and transmits only the light in the wavelength range of the stimulable light 105 and emits light having a wavelength of 640 nm. It has the property of cutting.

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 photostimulable light 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. 24 is a schematic plan view of the scanning mechanism of the optical head 95. In FIG. 24, for simplification, the optical system except the optical head 95 and the optical paths of the laser light 84 and the fluorescent light 105 or the stimulating light 105 are omitted.

As shown in FIG. 24, 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 that is movable in the sub-scanning direction indicated by arrow Y in FIG. 24 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.

The main scanning stepping motor 125 is provided on the movable substrate 123, and the main scanning stepping motor 125 attaches the endless belt 126 to the adsorbing property of the adjacent dot formed on the biochemical analysis unit 1. The distance between the regions 4, that is, the stimulable phosphor sheet 70
Adjacent dot-shaped stimulable phosphor layer regions 7 formed in
It can be driven intermittently at a pitch equal to the distance between the two. The optical head 95 is the endless belt 1
It is fixed to the main scanning stepping motor 12
When the endless belt 126 is driven by 5,
In FIG. 24, it is configured to move in the main scanning direction indicated by arrow X. In FIG. 24, 67 is
Reference numeral 128 denotes a linear encoder 1 that detects the position of the optical head 95 in the main scanning direction.
27 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. 24, the optical head 95 is moved in the main scanning direction indicated by the arrow X and 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. 25 is a block diagram showing the control system, input system, drive system and detection system of the scanner.

As shown in FIG. 25, the control system of the scanner includes a control unit 130 for controlling the operation of the entire scanner, and the input system of the scanner is
The keyboard 131 that is operated by the user and can input various instruction signals is provided.

As shown in FIG. 25, 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. 25, the detection system of the scanner includes 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 areas 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.

Then, the keyboard 1 is selected 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 to 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 stimulable phosphor layer region 72 is irradiated with the laser beam 84 at a position where it can be irradiated. When it is confirmed that the optical head 95 has moved, the main scanning stepping motor 12
A stop signal is output to 5 and a drive signal is output to the 1st laser excitation light source 81, the 1st laser excitation light source 81 is started, and the laser beam 84 of the 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 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 by the aspherical lens 97, the first stimulable phosphor layer region 7 of the stimulable phosphor sheet 70 placed on the stage 100 glass plate 101.
It is focused on 2.

As a result, the stimulable phosphor contained in the first stimulable phosphor layer region 72 formed on the support 71 of the stimulable phosphor sheet 70 is excited by the laser light 84 to generate the first stimulable phosphor. The stimulable phosphor 105 is emitted from the stimulable phosphor layer region 72 of No. 1.

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 photostimulable phosphor region 12 is collected by the aspherical lens 97 provided in the optical head 95, and the same as the optical path of the laser light 84 by the mirror 96. It is reflected to the side and made into parallel light, and is incident on the concave mirror 98.

The photostimulable light 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 stimulable light 105 emitted from the stimulable phosphor,
Since it has the property of cutting light with a wavelength of 0 nm,
The light of the wavelength of 640 nm which is the excitation light is cut, and only the light of the wavelength range of the photostimulable light 105 emitted from the photostimulable phosphor layer region 72 is transmitted through the filter 112d, and the photomultiplier 110 photoelectrically converts the light. Detected.

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

After the first laser pumping light source 81 is turned on, when a predetermined time, for example, several microseconds has elapsed, the control unit 130 causes the first laser pumping light source 81 to
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
The stimulable phosphor sheet 70 is moved by a pitch equal to the distance between the adjacent dot-shaped stimulable phosphor layer regions 72 formed in the application 71 itself.

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. Second stimulable phosphor layer region 7 formed
2 is confirmed to have moved to a position where irradiation can be performed on the first laser excitation light source 8
1 is turned on to turn on the first laser excitation light source 81, and the laser beam 84 is included in the second stimulable phosphor layer region 72 formed on the stimulable phosphor sheet 70. To excite the stimulable phosphor.

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 formed 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 photostimulable phosphor layer regions 72.

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 based on the position detection signal of the optical head 95 inputted from the linear encoder 127, Optical head 95
Is moved by one line in the main scanning direction, and when it is confirmed that the scanning of the stimulable phosphor layer region 72 of the first line by the laser beam 84 is completed, the control unit 130 causes the main scanning A drive signal is output to the stepping motor 125 to return the optical head 95 to the original position, and a drive signal is output to the sub-scanning pulse motor 121 to move the movable substrate 123 by one line in the sub-scanning direction. Move only minutes.

Based on the position detection signal of the optical head 95 inputted 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 the first laser excitation light source to the stimulable phosphor layer region 72 of the first line. The laser light 84 emitted from the first laser excitation light source 81 is sequentially irradiated to the stimulable phosphor layer region 72 on the second line in the same manner as the irradiation of the laser light 84 emitted from the laser light 81. And the stimulable phosphor layer region 72
The stimulable phosphor contained in the photostimulable phosphor layer region 72 is excited to sequentially cause the photomultiplier 110 to photoelectrically detect the stimulable light 105 emitted from the stimulable phosphor layer region 72.

The analog data generated photoelectrically detected 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 stimulable phosphor layer regions 72 formed on the support 71 of the stimulable phosphor sheet 70 are all scanned by the laser light 84 emitted from the first laser excitation light source 81. The stimulable phosphor contained in the large number of dot-shaped stimulable phosphor layer regions 72 is excited, and the emitted stimulable light 105 is photoelectrically detected by the photomultiplier 110, When the generated analog data is digitized by the A / D converter 113 and biochemical analysis data is generated from the radiation data recorded in each stimulable phosphor layer region 72,
A drive stop signal is output from the control unit 130 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 many absorptive regions 4 formed in the biochemical analysis unit 1 is read to generate the biochemical analysis digital data, first, the user The biochemical analysis unit 1 is set 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, 112b, 112c is used for the fluorescence 105.
To be located in the optical path of.

For example, Rhodamine (registered trademark) which can be most efficiently excited by a laser having a wavelength of 532 nm as a fluorescent substance for labeling a substance of biological origin
Is used and is input to the keyboard 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, the first of the many absorptive regions 4 formed in the biochemical analysis unit 1 is detected. Laser light 8 is applied to the absorptive area 4.
When it is confirmed that the optical head 95 has reached the position where 4 can be irradiated, a stop signal is output to the main scanning stepping motor 125 and a drive signal is output to the second laser excitation light source 82, The second laser excitation light source 82 is activated 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 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 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 adsorptive region 4 of the biochemical analysis unit 1, for example, rhodamine to emit fluorescence.

Here, in the biochemical analysis unit 1 according to the present embodiment, the absorptive regions 4 are adsorbed in a large number of through holes 3 formed on the aluminum substrate 2 so as to be separated from each other. The fluorescent substance contained in the absorptive region 4 is formed by filling the absorptive region 4 with the substrate 2 made of aluminum having a property of attenuating light around the absorptive region 4. It is possible to reliably prevent the fluorescence 105 emitted from the fluorescent substance 105 from being mixed with the fluorescence 105 emitted from the fluorescent substance contained in the adsorbing regions 4 adjacent to each other.

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 incident on 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 absorptive regions 4 formed in the unit 1.

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 adsorbing regions 4 formed adjacent to each other in the biochemical analysis unit 1,
Laser light 84 emitted from the second laser excitation light source 82
Is confirmed to have moved to a position where the second absorptive region 4 formed in the biochemical analysis unit 1 can be irradiated, the control unit 130 sends a drive signal to the second laser excitation light source 82. The second laser excitation light source 82 is turned on to turn on the second laser excitation light source 82, and the laser light 84 causes a fluorescent substance contained in the second absorptive region 4 formed in the biochemical analysis unit 1, for example, rhodamine. To excite.

Similarly, the laser light 84 is irradiated to the second absorptive region 4 formed in the biochemical analysis unit 1 for a predetermined time, and the fluorescence emitted from the second absorptive region 4 is emitted. When 105 is photoelectrically detected by the photomultiplier 110 and analog data is generated, the control unit 130 outputs an off signal to the second laser pumping light source 82 to output the second laser pumping light source. 82 is turned off, and a drive signal is output to the main scanning stepping motor 125 to drive the optical head 95.
The biochemical analysis unit 1 is moved by one pitch that is equal to the distance between the adsorbing regions 4 formed adjacent to each other.

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 based on the position detection signal of the optical head 95 input from the linear encoder 127. , Optical head 9
5 is moved by one line in the main scanning direction, and when it is confirmed that all the absorptive regions 4 on the first line of the biochemical analysis unit 1 are scanned by the laser beam 84, control is performed. The unit 130 outputs a drive signal to the main scanning stepping motor 125, and the optical head 95
Is returned to the 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.

Based on the position detection signal of the optical head 95 inputted 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 advances to the absorptive region 4 of the first line formed in the biochemical analysis unit 1, Exciting the rhodamine contained in the absorptive region 4 of the second line formed in the biochemical analysis unit 1 in exactly the same manner as irradiating the laser beam 84 emitted from the second laser excitation light source 82. And absorptive area 4
The fluorescence 105 emitted from the photomultiplier 110 is sequentially detected photoelectrically by the photomultiplier 110.

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.

In this way, 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 absorptive regions 4 formed in the biochemical analysis unit 1 are formed. Rhodamine contained therein is excited, the emitted fluorescence 105 is photoelectrically detected by the photomultiplier 110, and the generated analog data is converted into digital data by the A / D converter 113, When sent to the data processing device 114, the drive stop signal is output from the control unit 130 to the second laser excitation light source 82, and the drive of the second laser excitation light source 82 is stopped.

As described above, the biochemical analysis data is generated based on the radiation data and the fluorescence data recorded in the absorptive region 4 of the biochemical analysis unit 1.

According to this embodiment, the user simply sets the biochemical analysis unit 1 in the hybridization reaction chamber 30, and the motor 64 causes
The rocking table 47 is rocked around the shaft 45, and the hybridization reaction chamber 30 attached to the upper surface of the rocking table 47 is rocked around the shaft 45 and injected into the hybridization reaction chamber 30. Since the hybridization solution, the mixed solution of the hybridization solution and the probe solution, and the washing solution are agitated, the hybridization solution, the mixed solution of the hybridization solution and the probe solution, and the washing solution are mixed with each other. Pre-hybridization, hybridization and washing can be carried out by uniformly contacting the large number of absorptive regions 4 of the biochemical analysis unit 1 held in the rectangular region 33a of the chamber 30, and thus, Different experimenters It becomes possible to hybridize the specific binding substance and the biological substance with good reproducibility, and it is possible to easily hybridize the specific binding substance and the biological substance even if it takes a long time. Not only will this be possible, but significant labor savings will be possible.

Further, according to this embodiment, the hybridization reaction chamber 30 has triangular regions 33b and 33c having apexes at both ends on both sides of the rectangular region 33a in which the biochemical analysis unit 1 is held. Since the oscillating table 47 is oscillated around the shaft 45, it has the hybridization solution injected into the hybridization reaction chamber 30, a mixed solution of the hybridization solution and the probe solution, and washing. Each time the solution flows into the triangular regions 33b and 33c, the solution is stirred and uniformly mixed, and therefore, the specific binding substance contained in the adsorptive region 4 of the biochemical analysis unit 1 is unique to the specific binding substance. The probability of encountering a biological substance that should hybridize to the chemically bound substance dramatically improves, and It becomes possible to greatly improve the rate, pre-processing, it is possible to greatly improve the efficiency of the pre-hybridization and washing.

Furthermore, according to the present embodiment, the solution injection tube 3 to the hybridization reaction chamber 30
When the attachment part of 6 is located below the attachment part of the solution discharge tube 38 to the hybridization reaction chamber 30, the probe solution is introduced into the hybridization reaction chamber 7 via the solution injection tube 36. Since it is configured to be injected, the probe solution is used in the hybridization reaction chamber 30.
It is injected into the hybridization solution contained therein, thus allowing the probe solution and the hybridization solution to be mixed homogeneously.

According to this embodiment, the prehybridization is completed and the probe is completed for a period of time until the pretreatment is completed and the biochemical analysis unit 1 is required to be set in the hybridization reaction chamber 30. The main window displayed on the screen of the liquid crystal display panel 44 shows the time until the injection of the solution is requested and the time until the hybridization and washing are completed and the biochemical analysis unit 1 is requested to be taken out. The user can know the time until the next operation is requested in real time because it is configured to be updated in real time and displayed in real time. Therefore, it is possible to carry out the necessary operations when and when necessary without error, and Can be executed efficiently, and it is possible to execute other operations and effectively use time until the next operation is requested. It becomes possible to greatly improve the efficiency of hybridization.

Furthermore, according to the present embodiment, the pretreatment is completed, and the prehybridization is completed at the date and time when the biochemical analysis unit 1 is required to be set in the hybridization reaction chamber 30. The liquid crystal display panel 44 indicates the date and time when the injection is requested, and the date and time when the hybridization and washing are completed and the biochemical analysis unit 1 is requested to be taken out.
Configured to be displayed within the main window displayed on the screen, the user can know when the next operation is required and, therefore, the required operation when needed. Can run without error,
Hybridization can be performed efficiently, and it is possible to execute other operations and effectively use time until the next operation is required. It becomes possible to greatly improve the efficiency of hybridization.

Further, according to this embodiment, the currently set pre-hybridization time Tp, hybridization time Th and washing time Tc are always displayed in the main window displayed on the screen of the liquid crystal display panel 44. Since the display is configured to be displayed, the user can know the pre-hybridization time Tp, the hybridization time Th, and the washing time Tc that are currently set, and the setting of these times is inappropriate. In some cases, it is possible to reconfigure as desired, thus allowing hybridization to be performed under optimal conditions.

Further, according to this embodiment, a mixed solution of a hybridization solution having a high concentration of a radiolabeled substance and a probe solution, a washing solution used for the first washing and a washing solution used for the second washing were used. The cleaning solution is discharged into the first solution recovery tank 53a and recovered, and the cleaning solution and the pretreatment solution used for the third to sixth cleaning in which the concentration of the radiolabeled substance is relatively low are Since the second solution recovery tank 53b is configured to be discharged and recovered, it is possible to appropriately manage the waste liquid containing the radioactive labeling substance.

Further, according to the present embodiment, since the contents of the processing currently being executed are displayed in the main window displayed on the screen of the liquid crystal display panel 44, the user can You can always understand what kind of processing is currently being performed,
Therefore, it becomes possible to carry out the hybridization without error.

FIG. 26 is a schematic plan view of a hybridization reaction chamber according to another preferred embodiment of the present invention.

As shown in FIG. 26, the hybridization reaction chamber 140 according to this embodiment includes
The rectangular area 14 has a width slightly larger than that of the biochemical analysis unit 1 and is provided on both sides of a rectangular area 141a having a rectangular cross section in which the biochemical analysis unit 1 is accommodated.
Semicircular region 141b having a diameter equal to the width of 1a, 1
A reaction space 141 having 41c is formed.

Also in this embodiment, FIG. 1 to FIG.
The hybridization reaction chamber 140 is removably attached to the upper surface of the oscillating table 47 of the hybridization apparatus in the same manner as the embodiment shown in FIG. The hybridization solution, the probe solution, and the washing solution are respectively injected, and the rocking table 47 is rocked to execute prehybridization, hybridization, and washing.

FIG. 27 is a schematic cross-sectional view showing the flow of the solution in the reaction space 141 of the hybridization reaction chamber 140.

As shown in FIG. 27, also in this embodiment, the hybridization solution, the mixed solution of the hybridization solution and the probe solution, and the washing solution are in a semicircular shape as the hybridization reaction chamber 140 swings. It flows into the regions 141b and 141c, is agitated, and is uniformly mixed.

Therefore, also in the present embodiment, the probability that the specific binding substance contained in the adsorptive region 4 of the biochemical analysis unit 1 is encountered by the substance derived from the living body to be hybridized with the specific binding substance is determined. It is possible to dramatically improve the efficiency of hybridization, and it is possible to significantly improve the efficiency of prehybridization and washing.

FIG. 28 is a schematic plan view of a hybridization reaction chamber according to another preferred embodiment of the present invention.

As shown in FIG. 28, the hybridization reaction chamber 150 according to this embodiment includes
As a whole, a rectangular region 151a having a rectangular shape and having a width slightly larger than the width of the biochemical analysis unit 1 and having a rectangular cross section in which the biochemical analysis unit 1 is accommodated is formed in the central portion. On both sides of the rectangular area 151a, a reaction space 151 is formed in which two narrow width portions 151b and 151c having a small width are formed.

Also in this embodiment, FIG. 1 to FIG.
The hybridization reaction chamber 150 is detachably attached to the upper surface of the oscillating table 47 of the hybridization apparatus in the same manner as the embodiment shown in FIG. The hybridization solution, the probe solution, and the washing solution are respectively injected, and the rocking table 47 is rocked to execute prehybridization, hybridization, and washing.

FIG. 29 is a schematic cross-sectional view showing the flow of the solution in the reaction space 151 of the hybridization reaction chamber 150.

As shown in FIG. 20, in the present embodiment, the hybridization solution, the mixed solution of the hybridization solution and the probe solution, and the washing solution are moved in the rectangular region as the hybridization reaction chamber 150 rocks. 151a to the narrow portion 151
b, 151c, and flows toward both ends of the hybridization reaction chamber 150, so that the hybridization solution, the mixed solution of the hybridization solution and the probe solution, and the washing solution enter the reaction space 151 in the hybridization reaction chamber 150. When passing through the formed narrow portions 151b and 151c, they are agitated and uniformly mixed.

Therefore, also in the present embodiment, the probability that the specific binding substance contained in the adsorptive region 4 of the biochemical analysis unit 1 is encountered by the substance derived from the living body to be hybridized with the specific binding substance is determined. The efficiency can be dramatically improved, and the efficiency of hybridization can be significantly improved, and the efficiency of pretreatment, prehybridization and washing can be significantly improved.

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 embodiment shown in FIGS. 1 to 25, the reaction space 33 of the hybridization reaction chamber 30 has a rectangular area 33a having a width slightly larger than that of the biochemical analysis unit 1. When,
Triangular areas 33 provided on both sides of the rectangular area 33a
26 b and 33 c, in the embodiment shown in FIG. 26, the reaction space 141 of the hybridization reaction chamber 140 has a rectangular region 141 a having a width slightly larger than the width of the biochemical analysis unit and a rectangular region 141 a. 28. The reaction space 151 of the hybridization reaction chamber 150 is provided in the embodiment shown in FIG. 28, which is provided on both sides of the shape region 141a and has semicircular regions 141b and 141c having a diameter equal to the width of the rectangular region 141a. Is
The biochemical analysis unit 1 has a width slightly larger than that of the biochemical analysis unit 1 and is provided with a rectangular area 151a in which the biochemical analysis unit 1 is housed, and has a rectangular shape as a whole, on both sides of the rectangular area 151a. Two small width narrow portions 151
b, 151c are formed, the reaction chamber 30,
Since the biochemical analysis unit 1 can be held at a predetermined position if the lid 32 of the 140, 150 is provided with the pressing member 34, the rectangular regions 33a, 141a, 151.
It is not always necessary that a has a width slightly larger than the width of the biochemical analysis unit, as long as it can accommodate the biochemical analysis unit 1.

In the embodiment shown in FIGS. 1 to 25, the hybridization reaction chamber 3
The reaction space 33 of 0 has a rectangular area 33a having a width slightly larger than the width of the biochemical analysis unit, and triangular areas 33b and 3b provided on both sides of the rectangular area 10a.
3c and in the embodiment shown in FIG. 26, the reaction space 1 of the hybridization reaction chamber 140
41 denotes a rectangular area 141a having a width slightly larger than the width of the biochemical analysis unit and a rectangular area 141.
28. The reaction space 151 of the hybridization reaction chamber 150 is provided with the semicircular regions 141b and 141c provided on both sides of a and having a diameter equal to the width of the rectangular region 141a. It has a width slightly larger than the width of the biochemical analysis unit 1,
Rectangular area 151 for accommodating the biochemical analysis unit 1
a has a rectangular shape as a whole, and has a rectangular area 15
1a on both sides, two narrower portions 151b, 15
1c is formed, the biochemical analysis unit 1 is configured to be held in the rectangular regions 33a, 141a, 151a, but the reaction space 33 of the hybridization reaction chambers 30, 140, 150 is 141,
151 includes rectangular regions 33a, 141a, 151a, and the biochemical analysis unit 1 is provided with rectangular regions 33a, 14a.
1a, 151a 101a does not necessarily have to be configured to hold the biochemical analysis unit 1 in the reaction spaces 33, 141, 151 of the hybridization reaction chambers 30, 140, 150.
It suffices if it is provided in the substantially central portion of the above, and its shape can be arbitrarily determined, and it is not limited to a rectangular shape and can be formed into an elliptical shape or the like.

Further, in the embodiment shown in FIGS. 1 to 25, the reaction space 33 of the hybridization reaction chamber 30 has a rectangular region 33a having a width slightly larger than the width of the biochemical analysis unit. , Triangular areas 33b provided on both sides of the rectangular area 33a,
33c, and in the embodiment shown in FIG.
The reaction space 141 of the hybridization reaction chamber 140 has a rectangular area 141a having a width slightly larger than the width of the biochemical analysis unit and a rectangular area 14a.
1a, provided with semicircular regions 141b and 141c provided on both sides of the 1a and having a diameter equal to the width of the rectangular region 141a,
In the embodiment shown in FIG. 28, the reaction space 151 of the hybridization reaction chamber 150 has a width slightly larger than the width of the biochemical analysis unit 1, and the biochemical analysis unit 1 is accommodated therein. Rectangular area 1
51a, forming a rectangular shape as a whole, and having two narrow width portions 151b on both sides of the rectangular area 151a,
151c is formed, but the reaction spaces 33, 1 of the hybridization reaction chambers 30, 140, 150 are formed.
41 and 151 are rectangular areas 33a, 141a and 151.
A semicircular region 1 having a diameter equal to the width of the triangular regions 33b and 33c or the rectangular region 141a on both sides of a.
It is not always necessary to provide the two narrow portions 151b and 151c in the rectangular region 151a provided with the biochemical analysis units 1 and 41b. Hybridization reaction chamber 30, 1 in which the analysis unit 1 is to be held
It suffices that a region having a cross-sectional area smaller than the cross-sectional area of the spaces 40, 150 is formed, and the reaction spaces 33, 14 of the hybridization reaction chambers 30, 140, 150 are formed.
If the height of 1, 151 is constant, a region having a width smaller than the width of the region for holding the biochemical analysis unit 1 is formed on both sides of the region for holding the biochemical analysis unit 1. It should have been done.

In the above embodiment, the lid 31 of the hybridization reaction chamber 30 is formed with six pressing members 34, but if the biochemical analysis unit 1 can be held at a predetermined position. , Pressing member 3
The number 4 may be one, and seven or more pressing members 34 may be provided.

Further, in the above-mentioned embodiment, the lid 31 of the hybridization reaction chamber 30 is formed with six pressing members 34, but the rectangular region 33 is formed.
The region of the hybridization reaction chamber 30 in which the biochemical analysis unit 1 is housed can hold the biochemical analysis unit 1, such as a having a size slightly larger than the biochemical analysis unit 1. It is not always necessary to form the pressing member 34 on the lid 31 as long as it has a proper size.

Further, in the above-mentioned embodiment, the hybridization apparatus comprises a mixed solution of the hybridization solution and the probe solution, a washing solution used for the first washing and a washing solution used for the second washing. A first solution recovery tank 53a for recovery and a second solution recovery tank 53b for recovering the pretreatment liquid and the cleaning solution used for the third to sixth cleanings are provided. It is not always necessary to provide two solution recovery tanks, and a pretreatment solution recovery tank for recovering the pretreatment solution, a hybridization solution recovery tank for recovering a mixed solution of the hybridization solution and the probe solution, and a washing solution are not required. A cleaning solution recovery tank may be provided to collect the cleaning solution. The recovery tank, a first cleaning solution recovery tank for collecting the wash solution used in the cleaning solution and the second wash is used for cleaning of the first round, the third
It can be divided into a second washing solution collecting tank for collecting the washing solution used for the sixth to sixth washings, and further, in a single collecting tank, the pretreatment solution and the hybridization solution It is also possible to collect the mixed solution of the probe solution and the washing solution.

Further, in the above-mentioned embodiment, a mixed solution of the hybridization solution and the probe solution, the first
The cleaning solution used for the second cleaning and the cleaning solution used for the second cleaning are stored in the first solution recovery tank 53a.
However, depending on the concentration of the radiolabeled substance, only the cleaning solution used for the first cleaning may be recovered in the first solution recovery tank 53a. Alternatively, the cleaning solution used for the third cleaning may be recovered in the first solution recovery tank 53a.

Further, in the above-mentioned embodiment, the hybridization apparatus includes a mixed solution of the hybridization solution and the probe solution, the washing solution used for the first washing and the washing solution used for the second washing. , The first solution recovery tank 53a is configured to be recovered, but a radiation sensor for detecting the concentration of the radioactive labeling substance in the solution flowing through the solution discharge tube is provided, and the concentration of the radioactive labeling substance in the cleaning solution is set to a predetermined value When the concentration exceeds the predetermined value, it is recovered in the first solution recovery tank 53a, and when the concentration of the radiolabeled substance in the cleaning solution is a predetermined value, the second solution recovery tank 53b is recovered. You can also

Further, in the above-mentioned embodiment, the cleaning is repeated 6 times, but the number of times of cleaning can be arbitrarily determined according to the cleaning efficiency.

Further, in the above-mentioned embodiment, the washing is repeated 6 times, but the concentration of the radioactive labeling substance contained in the washing solution is detected by the radiation sensor, and the radioactivity contained in the washing solution is detected. The cleaning can be terminated when the concentration of the labeling substance becomes equal to or lower than a predetermined value.

Furthermore, in the above embodiment, when the mounting portion of the solution injection tube 36 to the hybridization reaction chamber 30 is located below the mounting portion of the solution discharge tube 38 to the hybridization reaction chamber 30. The pretreatment solution, the hybridization solution, the probe solution and the washing solution are injected into the hybridization reaction chamber 30 from the solution injection tube 36. When the attachment portion of 36 is located below the attachment portion of the solution discharge tube 38 to the hybridization reaction chamber 30, the solution injection tube 36
Therefore, it is not always necessary to inject the pretreatment solution, the hybridization solution, the probe solution and the washing solution into the hybridization reaction chamber 30,
When the hybridization reaction chamber 30 is in a substantially parallel state, the pretreatment liquid, the hybridization solution, the probe solution and the washing solution are supplied from the solution injection tube 36 to the hybridization reaction chamber 30.
It can also be configured to be injected into.

Further, in the above embodiment, the cleaning time is set to be constant, but the cleaning time can be set arbitrarily according to the number of times of cleaning.

Further, in the above embodiment, the default values of the prehybridization time Tp required for prehybridization, the hybridization time Th required for hybridization, and the washing time Tc required for washing operation are determined in advance and E
It is stored in the EPROM 62 and configured so that the user can change them. In addition to the pre-hybridization time Tp, the hybridization time Th and the washing time Tc, the number of washings can also be changed by the user. It can also be configured.

Further, in the above-mentioned embodiment, when the message prompting the injection of the probe solution is displayed in the main window displayed on the screen of the liquid crystal display panel 44, the user-derived biomarker labeled with the labeling substance is displayed. The probe solution containing the substance is prepared and housed in the probe solution chip 50c. However, before starting the personal computer 41, the substance derived from the living body labeled with the labeling substance is Prepare a probe solution containing the probe solution chip 5
It can also be stored in 0c.

Further, in the above-mentioned embodiment, the probe solution is contained in the probe solution chip 50c and is automatically supplied from the probe solution chip 50c into the hybridization reaction chamber 30. The user may manually inject the probe solution into the hybridization reaction chamber 30.

Further, in the above-described embodiment, the hybridization solution is prepared and stored in the hybridization solution tank 50b before the personal computer 41 is started up. But the liquid crystal display panel 44
The hybridization solution may be prepared and stored in the hybridization solution tank 50b when it is displayed in the main window displayed on the screen.

Further, in the above embodiment, prior to starting the personal computer 41, the hybridization solution is prepared and accommodated in the hybridization solution tank 50b, and the hybridization reaction chamber 30 is automatically operated. However, the user may manually inject the hybridization solution into the hybridization reaction chamber 30.

Further, in the above-mentioned embodiment, the automatic hybridization apparatus is provided with the pretreatment tank 50a, but the user may manually inject the pretreatment liquid into the hybridization reaction chamber 30. Alternatively, the pretreatment liquid tank 50a may be omitted.

Further, in the above-mentioned embodiment, the automatic hybridization device is a single washing solution tank 50.
Although d is provided, two or more cleaning solution tanks containing cleaning solutions having different cleaning powers can be provided.

Further, in the above embodiment, the scheduled date and time for completing the pretreatment, the scheduled date and time for completing the prehybridization, and the scheduled date and time for completing the washing are stored in the main window displayed on the screen of the liquid crystal display panel 44. Although it is configured to be displayed, these displays can be omitted.

In the above embodiment, the pre-hybridization time Tp, the hybridization time Th, and the washing time Tc that are currently set are always displayed in the main window displayed on the screen of the liquid crystal display panel 44. Although it is configured to be displayed, these displays can be omitted.

Furthermore, in the above-described embodiment, the operation of the automatic hybridization device is controlled by the personal computer 41. However, a controller is provided in the main body 40 of the automatic hybridization device so that the data input from the personal computer 41 can be processed. Therefore, the controller may be configured to control the operation of the automatic hybridization apparatus.

Further, in the above embodiment, the substrate 2 of the biochemical analysis unit 1 has approximately 5000 absorptive regions 4 each having a substantially circular shape having a size of about 10,000 and a size of about 0.01 mm 2. Although the absorptive region 4 is formed in a regular pattern with a density of square centimeters, it is not always necessary to form the absorptive region 4 in a substantially circular shape, and the absorptive region 4 can be formed in an arbitrary shape such as a rectangular shape.

Further, in the above-mentioned embodiment, the substrate 2 of the biochemical analysis unit 1 has approximately 10,000 approximately 10,000 absorptive regions 4 each having a substantially circular shape and having a size of approximately 0.01 mm 2. Although formed in a regular pattern with a density of square centimeters, the number and size of the absorptive regions 4 are determined according to the purpose.
The adsorbent region 4 is arbitrarily selected and preferably has a size of 10 or more and less than 5 mm 2.
Substrate 2 with a density of 10 or more per square centimeter
Is formed.

In the above-mentioned embodiment, the substrate 2 of the biochemical analysis unit 1 has approximately 5000 approximately 10,000 absorptive regions 4 each having a substantially circular shape having a size of approximately 0.01 mm <2>. The absorptive regions 4 are formed according to a regular pattern with a density of square centimeters and according to a regular pattern.
Forming is not absolutely necessary.

Further, in the above-described embodiment, the biochemical analysis unit 1 has a large number of adsorption holes formed by filling nylon 6 inside the large number of through holes 3 formed in the substrate 2 made of aluminum. However, it is not always necessary that the absorptive region 4 of the biochemical analysis unit 1 is formed of nylon 6, and a porous material capable of forming a membrane filter other than nylon 6, For example, nylons such as nylon 6,6, nylon 4,10; cellulose derivatives such as nitrocellulose, cellulose acetate, cellulose butyrate acetate; 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, or The absorptive region 4 of the biochemical analysis unit 1 can be formed by a porous carbon material such as activated carbon, and further, a metal such as platinum, gold, iron, silver, nickel, aluminum; alumina, silica, titania. , A metal oxide such as zeolite; a metal salt such as hydroxyapatite or calcium sulfate, an inorganic porous material such as a complex thereof, or a bundle of a plurality of fibers forms the adsorptive region 4 of the biochemical analysis unit 1. You may do it.

Further, in the above-mentioned embodiment, the biochemical analysis unit 1 is provided with the substrate 2 made of aluminum, but it is not always necessary to form the substrate 2 of the biochemical analysis unit 1 with aluminum. Alternatively, the substrate 2 can be formed of another material. The substrate 2 of the biochemical analysis unit 1 is preferably formed of a material having a property of attenuating radiation and / or light, but the material is not particularly limited, and it is an inorganic compound material or an organic compound material. With any of the above, the substrate 2 of the biochemical analysis unit 1 can be formed, and a metal material, a ceramic material or a plastic material is particularly preferably used. Examples of the inorganic compound material that can be preferably used to form the substrate 2 of the biochemical analysis unit 1 include gold, silver, and
Copper, zinc, aluminum, titanium, tantalum, chrome,
Metals such as iron, nickel, cobalt, lead, tin and selenium;
Alloys such as brass, stainless steel and bronze; silicon materials such as silicon, amorphous silicon, glass, quartz, silicon carbide and silicon nitride; metal oxides such as aluminum oxide, magnesium oxide and zirconium oxide; tungsten carbide, calcium carbonate, sulfuric acid. Inorganic salts such as calcium, hydroxyapatite and gallium arsenide can be mentioned. These may have any structure in a polycrystalline sintered body such as single crystal, amorphous, or ceramic. Further, as an organic compound material that can be preferably used for forming the substrate 2 of the biochemical analysis unit 1, a polymer compound is preferably used, and a preferable polymer compound is, for example, polyethylene or polypropylene. Polyolefin; acrylic resin such as polymethylmethacrylate, butylacrylate / methylmethacrylate copolymer; polyacrylonitrile;
Polyvinyl chloride; polyvinylidene chloride; polyvinylidene fluoride; polytetrafluoroethylene; polychlorotrifluoroethylene; polycarbonate; polyesters such as polyethylene naphthalate and polyethylene terephthalate; nylon 6, nylon 6,6, nylon 4,1
Nylon such as 0; polyimide; polysulfone; polyphenylene sulfide; silicon resin such as polydiphenylsiloxane; phenol resin such as novolac; epoxy resin; polyurethane; polystyrene; butadiene-
Styrene copolymer; cellulose, cellulose acetate, nitrocellulose, starch, calcium alginate, hydroxypropylmethylcellulose and other polysaccharides; chitin;
Chitosan; lacquer; polyamides such as gelatin, collagen and keratin, and copolymers of these high molecular compounds. 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 above embodiment, the large number of absorptive regions 4 of the biochemical analysis unit 1 are obtained by filling the inside of the large number of through holes 3 formed in the aluminum substrate 2 with nylon 6. , Is formed, at least one surface of the absorptive substrate formed by the absorptive material, the substrate having a large number of through holes are adhered to the absorptive substrate in the large number of through holes of the substrate, A solution containing the specific binding substance may be dropped to form the adsorptive region.

Further, in the above-mentioned embodiment, in the large number of absorptive regions 4 of the biochemical analysis unit 1, nylon 6 is filled inside the large number of through holes 3 formed in the substrate 2 made of aluminum. Although it is formed, the solution containing the specific binding substance may be dropped at positions separated from each other on the adsorptive substrate formed of the adsorptive material to form the adsorptive region.

Furthermore, 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 absorptive region 4 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.

Further, in the above embodiment, the personal computer 41 has a liquid crystal display panel, but a CRT is used instead of the liquid crystal display panel.
Alternatively, other display means such as an organic EL display panel may be provided.

[0448]

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to efficiently hybridize a specific binding substance and a substance derived from a living body, and generate biochemical analysis data with good reproducibility and excellent quantification. It is possible to provide an automatic hybridization device that enables the above.

[Brief description of drawings]

FIG. 1 is a schematic perspective view of a biochemical analysis unit in which a specific binding substance to which a substance of biological origin is hybridized is dropped by a hybridization device 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 reaction chamber.

FIG. 5 is a schematic perspective view of an automatic hybridization device according to a preferred embodiment of the present invention.

FIG. 6 shows a hybridization device body 40.
It is a schematic perspective view which shows the detail of FIG.

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

FIG. 8 is a block diagram showing a control system, a detection system, a drive system, an input system and a display system of the automatic hybridization apparatus according to the preferred embodiment of the present invention.

FIG. 9 is a diagram showing a screen of a liquid crystal display panel on which a main window is displayed.

FIG. 10 is a diagram showing a screen of the liquid crystal display panel when the injection of the pretreatment liquid contained in the pretreatment liquid tank into the hybridization reaction chamber is started.

FIG. 11 is a diagram showing a screen of a liquid crystal display panel when discharge of a pretreatment liquid contained in a hybridization reaction chamber to a second solution recovery tank is started.

FIG. 12 is a schematic cross-sectional view showing the flow of the solution in the reaction space 33 of the hybridization reaction chamber.

FIG. 13 is a view showing a screen of the liquid crystal display panel when the injection of the probe solution contained in the probe solution chip into the hybridization reaction chamber is started.

FIG. 14 is a view showing a screen of the liquid crystal display panel when the injection of the washing solution contained in the washing solution tank into the hybridization reaction chamber is started.

FIG. 15 is a schematic perspective view of a stimulable phosphor sheet.

FIG. 16 is a view showing that the stimulable phosphor contained in the stimulable phosphor layer region formed on the stimulable phosphor sheet is selected as the absorptive region formed on the biochemical analysis unit. FIG. 3 is a schematic perspective view of an exposure apparatus that exposes with a radioactive labeling substance contained therein.

FIG. 17 shows a large number of stimulable phosphor layer regions formed on a stimulable phosphor sheet by a radiolabel substance contained in a large number of absorptive regions formed in a biochemical analysis unit. It is a schematic sectional drawing which shows the method of exposing the stimulable fluorescent substance contained.

FIG. 18 is a diagram showing that the radiation data recorded on the stimulable phosphor sheet is read to generate biochemical analysis data, and at the same time, the fluorescence data recorded on the biochemical analysis unit is read to perform biochemical analysis. 3 is a schematic perspective view of a scanner that generates analysis data. FIG.

FIG. 19 is a schematic perspective view showing details near the photomultiplier of the scanner shown in FIG.

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

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

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

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

FIG. 24 is a schematic plan view of a scanning mechanism of the optical head.

25 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. 26 is a schematic plan view of a hybridization reaction chamber according to another preferred embodiment of the present invention.

FIG. 27 is a schematic cross-sectional view showing a flow of a solution in a reaction space of a hybridization reaction chamber according to another preferred embodiment of the present invention.

FIG. 28 is a schematic plan view of a hybridization reaction chamber according to another preferred embodiment of the present invention.

FIG. 29 is a schematic cross-sectional view showing a flow of a solution in a reaction space of a hybridization reaction chamber according to another preferred embodiment of the present invention.

[Explanation of symbols]

1 Biochemical Analysis Unit 2 Substrate 3 Through Hole 4 Adsorbing Area 5 Positioning Through Hole 9 Spotting Head 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 30 Hybridization reaction chamber 31 Hybridization reaction chamber casing 32 Hybridization reaction chamber lid 33 Reaction space 33a Hybridization reaction chamber rectangular area 33b , 33c Triangular region of hybridization reaction chamber 34 Holding member 35 Solution injection port 36 Solution injection tube 37 Solution discharge port 3 Solution discharge tube 40 Hybridization device main body 41 Personal computer 42 Keyboard 43 Mouse 44 Liquid crystal display panel 45 Shaft substrate shaft 46 Base 47 Swiveling substrate 50a Pretreatment liquid tank 50b Hybridization solution tank 50c Probe solution chip 50d Cleaning solution tank 51a, 51b, 51c, 51d valve 52 pump 53a first solution recovery tank 53b second solution recovery tank 54a, 54b valve 55 pump 56a first solution recovery tank casing 56b second solution recovery tank casing 57 One liquid level sensor 57a Light emitting element 57b Light receiving element 58 Second liquid level sensor 58a Light emitting element 58b Light receiving element 60 Control unit 61 ROM 62 EEPROM 63 Built-in clock 64 Motor 65s Marker 70 stimulable phosphor sheet 71 support 72 stimulable phosphor layer region 73 through hole 74 through hole for alignment 75 exposure device casing 76 exposure device lid member 77 substrates 78a, 78b alignment pin 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 hole Opening mirror hole 94 Opening mirror 95 Optical head 96 Mirror 97 Aspherical lens 98 Concave surface mirror 100 Stage 101 Glass plate 105 Fluorescent or stimulated light 108 Filter unit 110 Photomultipliers 111a, 111b, 111c, 111d Fill Members 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 140 Hybridization reaction chamber 141 Reaction space 141a Rectangular regions 141b, 141c of hybridization reaction chamber Semi-circular region 150 of hybridization reaction chamber 150 Hybridization reaction chamber 151 Reaction space 151a Rectangular regions 151b and 151c of the hybridization reaction chamber The narrow portion of the hybridization reaction chamber

Claims (4)

[Claims] 1. A hybridization reaction chamber configured such that a plurality of absorptive regions containing a specific binding substance having a known structure or characteristic are separated from each other and a biochemical analysis unit formed can be set therein. A hybridization solution tank containing a hybridization solution and at least one cleaning solution tank containing a cleaning solution, which is flexible and is connected to a solution inlet formed in the lid of the hybridization reaction chamber. Solution injection tube, the solution injection tube, and the hybridization solution tank or the at least one washing solution tank, which selectively communicates with each other, and a solution supply valve means and a hybridization solution tank accommodated in the hybridization solution tank. Hybridization solution or at least the above A supply pump for selectively supplying the cleaning solution contained in one cleaning solution tank into the hybridization reaction chamber, a display unit capable of displaying a message, the solution supply valve unit, and the supply pump. And a control unit for controlling the control unit, wherein the control unit is configured to calculate a time until a next operation is requested by the user and display the time on the display unit in real time. Hybridization device. 2. The automatic hybridization apparatus according to claim 1, wherein the control unit is configured to calculate the date and time when the user is requested to perform the next operation and display the date and time on the display unit. . 3. The control unit is configured to display the set pre-hybridization time, hybridization time and washing time on the display unit. Automatic hybridization device. 4. The automatic hybridization according to claim 1, wherein the control means is configured to display the contents of processing being executed on the display means. apparatus.