JP2003014748A - Composite material sheet for analyzing organism-related substance - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composite material sheet for analyzing organism-related substance that makes the high-accuracy and high-efficiency detection of a substance to be detected possible. SOLUTION: The composite material sheet is constituted of partition walls which finely divide the flat surface of a sheet in two-dimensional directions and a plurality of areas divided by the partition walls. In addition, an adsorptive material is arranged in the upper parts of the areas and phosphor layers containing an accumulating phosphor are arranged in the lower parts of the areas.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a composite material sheet which is advantageously used for analysis of various bio-related substances based on a biochemical specific binding reaction, a method for detecting and analyzing bio-related substances using the same, and The present invention relates to a radiation image information reading device used for it.

[0002]

2. Description of the Related Art In recent years, analytical tools called macroarrays and microarrays have been widely used to perform gene analysis in the fields of biology and medicine. All of them are analytical tools for detecting and analyzing nucleic acids such as DNA and RNA or fragments thereof or their duplicates by utilizing hybridization which is a kind of biochemical specific binding reaction. The former macro array is composed of a porous sheet made of polyamide resin or the like, and detection and analysis using the macro array encloses a large number of nucleic acid fragments (probe molecules) such as DNA fragments in the pores of the porous sheet. Thus, the sample nucleic acid fragment fixed in this manner and labeled with a radioactive substance such as radioisotope (RI) is used as an analysis target (target molecule). On the other hand, the latter microarray consists of a solid-phase carrier such as a surface-treated slide glass, and its detection analysis is usually carried out by immobilizing a probe molecule on the surface of the solid-phase carrier and using a sample nucleic acid fragment labeled with a fluorescent substance as a target molecule. Performed using. However, the use of the name of macro array and the use of name of micro array are not always made strictly strictly.

Gene analysis using a macro array is advantageous in that it can be easily carried out by utilizing conventional autoradiography technology.

Nuclear such as DNA using the above macro array
The acid analysis is usually carried out by the following method. (1) First, regarding a plurality of nucleic acid fragments, a large number of single strands
Nucleic acid fragment (probe molecule; usually its base sequence is known
Is used) and an aqueous solution containing each of them is prepared.
On the macro array using a spotter with high density and
Sequential spotting in the shape of a trick allows probe molecules
Attached so that it entangles with the pores at the spotting position of the porous sheet
To form a large number of dot-shaped probe molecule spots.
Let (2) Next, the nucleic acid fragment sample to be analyzed is radioactively
Element (RI:³²P, ³³Release prepared by labeling with P etc.)
Liquid-labeled single-stranded nucleic acid fragment sample is applied to this macroarray.
In contact with each other in phase (eg radioactive with a particular container)
Immerse the macroarray in an aqueous solution of labeled nucleic acid fragment sample
The target molecule to be detected as a probe molecule.
Hybridize and bind and immobilize. Ie the nucleus
It also has a base sequence complementary to the probe molecule in the acid fragment sample.
One target molecule is complementary to the spot probe molecule
(Hybridize) (3) Then, do not hybridize from the macro array.
Wash away the radioactively labeled nucleic acid fragment sample. (4) The washed macro array is used as a radiosensitive photographic film
Using the autoradiography,
Detecting radiation from radiolabeled target molecules
Binds the target molecule to each probe molecule by
Get information (whether or not there is a bond, strength, etc.) (5) Base arrangement of probe molecule bound to target molecule
If the columns are known, by using the principle of complementarity
Determine the base sequence of at least part of the target molecule
be able to. Alternatively, the expression, mutation,
Simultaneous analysis of multiple genes such as polymorphism
You can

In the conventional autoradiography for radiolabeled biological samples and biopolymers, a stimulable phosphor sheet (imaging plate or radiographic image) has been used instead of the method using a radiographic film. A radiation image recording / reproducing method using a conversion panel) has been developed. This radiation image recording / reproducing method absorbs and stores a part of radiation energy when irradiated with radiation such as X-rays, and then accumulates radiation energy when irradiated with electromagnetic waves (excitation light) such as visible light and infrared rays. It uses a stimulable phosphor (eg, stimulable phosphor) that has the property of emitting light in accordance with the above conditions. A sheet-shaped stimulable phosphor sheet containing a stimulable phosphor is used to transmit an analyte. Or, the radiation image information of the subject is once accumulated and recorded by irradiating the radiation emitted from the subject, and then the sheet is scanned with excitation light such as laser light and sequentially emitted as emission light (stimulated emission light). Then, the emitted light is photoelectrically read to obtain an electric image signal (digital signal), and then the obtained digital signal is visualized as it is or after various signal processing. Or play with such consists of saving in a suitable recording medium.

[0006] Autoradiography using the above-described radiation image recording / reproducing method using a stimulable phosphor sheet can obtain a radiation image with high sensitivity even if the radiation dose from a radioactive substance labeled sample is extremely small. It has become an important autoradiography technology at present because it has many advantages such as that image information can be obtained as a digital signal to facilitate image processing and storage.

As a method for measuring radiation from a radiolabeled target molecule, a method using the above-mentioned stimulable phosphor sheet has already been proposed. For example, Human Mole
cular Genetics, 1999, Vol.8, No.9, 1715-1722,
DNA fragments (probe molecules) are fixed on the surface of the porous sheet as a large number of spots, and a radiolabeled DNA fragment sample having complementarity with this DNA fragment is hybridized on the porous sheet, and then this It is described that target molecules can be detected by stacking a porous sheet and a stimulable phosphor sheet and performing autoradiography.

However, the porous sheet used as the macro array has the following problems.
When spotting and immobilizing the probe molecule solution on the porous sheet,
The attachment region (spot) of the probe molecule is likely to spread in the plane direction of the porous sheet, so that the binding immobilization region of the target molecule hybridized with the probe molecule also spreads. In many cases, unhybridized target molecules remain attached to between the spots on the porous sheet. Each of these causes noise in the work of detecting the radiation from the radiolabeled target molecule. Moreover, the scattering of radiation from the target molecule also increases noise. That is, if the distance between adjacent spots is shortened, the influence of both cannot be ignored in quantitative data, and as a result, highly accurate analysis cannot be performed. On the other hand, if an attempt is made to suppress noise and increase the resolution, the spot density (number per unit area) cannot be made too high.

[0009]

Even when autoradiography is carried out using a combination of the above-mentioned composite material sheet and stimulable phosphor sheet, the amount of radiolabeled sample is small and is released from the sample. Since the radiation such as electron beam is weak and the radiation is easily scattered, the composite material sheet to which the radiolabeled sample is bound and fixed and the stimulable phosphor sheet are brought into intimate contact with each other and exposed (radiation energy Is required to be absorbed and accumulated in the stimulable phosphor sheet). The present applicant has studied on further improving the accuracy of radiation image information obtained by this autoradiography, and as a result, by integrating the adsorptive material of the composite material sheet and the phosphor layer of the stimulable phosphor sheet. , And found that it is possible to obtain radiation image information with further improved resolution by increasing the adhesion between the two.

It is an object of the present invention to provide a composite material sheet for analyzing a biological substance, which enables highly accurate and highly efficient detection of a substance to be detected. Another object of the present invention is to provide a method for detecting and analyzing a biological substance that enables highly accurate and highly efficient detection of a substance to be detected. Further, the present invention is to provide a radiation image information reading device capable of obtaining radiation image information with high sensitivity and high image quality from the composite material sheet.

[0011]

DISCLOSURE OF THE INVENTION The present invention comprises a partition wall that subdivides a sheet plane in a two-dimensional direction, and a plurality of regions partitioned by the partition wall, and one surface side of each region. In the composite material sheet, the absorptive material is arranged in the part, and the phosphor layer containing the stimulable phosphor is arranged in the part on the other surface side.

According to the present invention, the storage is also performed on one side of a composite material sheet composed of partition walls that subdivide the sheet plane in the two-dimensional direction and an adsorptive material disposed in each region partitioned by the partition walls. There is also a composite material sheet provided with a phosphor layer containing a fluorescent substance.

The present invention further comprises attaching a large number of probe molecules to the adsorptive material of the above composite material sheet,
A step of bringing this into contact with a biologically relevant substance of a sample labeled with a radioactive substance in a liquid phase and immobilizing the radioactively labeled sample to the probe molecule by a biochemical specific binding reaction; unfixed from the composite material sheet The step of removing the radioactively labeled sample of the above; the step of irradiating the surface of the phosphor layer of the composite material sheet with an erasing light to erase the radiation energy that has been absorbed and accumulated; Of adsorbing and accumulating radiation energy emitted from the radioactively labeled sample on the adjacent phosphor layer; emission light emitted from the phosphor layer by irradiating excitation light on the surface of the phosphor layer having absorbed and accumulated radiation energy And photoelectrically converting to obtain an electric image signal; and a process of processing the electric image signal to detect binding information of the radiolabeled sample to the probe molecule. There is also a detection method for analyzing biological substances having.

In the present invention, a large number of single-stranded probe nucleic acid fragments are attached and fixed to the adsorptive material of the above composite material sheet, and then a single-stranded nucleic acid labeled with a radioactive substance or a fragment sample thereof is sampled. In a liquid phase to bind and immobilize the radiolabeled nucleic acid or fragment sample thereof to the probe nucleic acid fragment by hybridization; a step of removing unfixed nucleic acid or fragment sample thereof from the composite material sheet A step of irradiating the surface of the phosphor layer of the composite material sheet with an erasing light to erase the absorbed and accumulated radiation energy; a radiolabeled nucleic acid or fragment sample thereof fixed and bound to the adsorptive material of the composite material sheet A step of absorbing and accumulating radiation energy emitted from the phosphor layer in an adjacent phosphor layer; a surface of the phosphor layer absorbing and accumulating the radiation energy The emission light emitted from the phosphor layer is irradiated with excitation light is condensed, obtaining a electrical image signal by photoelectric conversion into; and processes the said electrical image signal,
There is also a method for detecting and analyzing a complementary nucleic acid, which comprises a step of detecting binding information of a nucleic acid or a sample of fragments thereof to a probe nucleic acid fragment.

The present invention further provides a composite material sheet in which radiation energy from a radiolabeled sample fixed to the adsorptive material of the composite material sheet is absorbed and accumulated in an adjacent phosphor layer in the plane direction thereof. Conveying means for moving the phosphor layer side up; Optics for irradiating the phosphor layer surface of the composite material sheet with excitation light in a spot shape corresponding to the region of the adsorptive material in a direction different from the moving direction. There is also a radiation image information reading apparatus provided with a reading means including a system; and a photodetector for photoelectrically detecting the emitted light emitted from the excitation light irradiation portion of the phosphor layer.

In the detection and analysis method of the present invention, the biological substance to be detected is a substance directly collected from the living body by extraction, isolation, or the like, which is further subjected to chemical treatment or chemical modification. , And a replica obtained by utilizing a replication technique such as a PCR method of these substances derived from the living body, and a typical example thereof is a polynucleotide (DN
A, RNA), nucleic acids such as peptide nucleic acids (PNA) or fragments thereof; antigens, antibodies, tumor markers, enzymes, abzymes, hormones and other proteins.

Further, the biochemical specific binding reaction which can be used in the present invention includes the hybridization caused by the complementarity of the above-mentioned nucleotide sequences, and the immunospecific binding such as the antigen-antibody reaction. Protein-specific binding based on the three-dimensional structure between proteins is also included.

Preferred embodiments of the composite material sheet of the present invention are as follows. (1) A composite material sheet in which a waterproof layer is provided on one side or both sides of a phosphor layer. (2) The average density of the partition walls is 0.6 g / cm ³ or more,
A composite material sheet in which the average density of the adsorbent material is 1.0 g / cm ³ or less (however, the relationship of the average density of partition walls> the average density of the adsorbent material is satisfied).

(3) A composite material sheet in which partition walls are formed of metal, plastic and / or ceramic glass. (4) A composite material sheet in which the adsorbent material is a porous organic polymer substance structure. (5) A composite material sheet in which the weight per unit area of the stimulable phosphor in the phosphor layer is in the range of 10 to 140 g / m ² .

(6) A composite material sheet in which the average area of the openings of the regions partitioned by the partition walls is in the range of 0.001 to ⁵ mm ² . (7) The average value of the number of existing areas per unit area of the area partitioned by the partition walls in the sheet is 10 to 10,000 / cm ^2.
Material sheet in the range of. (8) A composite material sheet in which the surface of the adsorptive material on the side opposite to the phosphor layer is set back toward the inside of the sheet with respect to the surface of the partition wall in contact with the surface.

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION The composite material sheet of the present invention has partition walls for subdividing the sheet in the plane direction, and an absorptive material arranged in a region partitioned by the partition walls, and further accumulates. It has a phosphor layer containing a fluorescent substance.

The structure of the composite material sheet of the present invention will be described with reference to the accompanying drawings. FIG. 1 is a perspective view schematically showing an example of the composite material sheet of the present invention, and FIG. 2 is an enlarged partial sectional view taken along the line I-I in FIG.

1 and 2, the composite material sheet
Is a partition wall 11 and a region 12 surrounded by the partition wall 11 (hatched portion).
Minutes) and. The area 12 is a minute through hole.
The adsorptive material 13 is placed on the upper side of each region 12.
And a phosphor layer 14 containing a stimulable phosphor in the lower part.
Are arranged. The area of the opening of region 12 is generally
Is 5 mm²Less than, preferably 1 mm²Less than, more
Preferably 0.5 mm ²Less, more preferably 0.1 m
m²Is less than. And preferably 0.001 mm²Since
Top, and particularly preferably 0.01 mm²That is all.
The thickness of the composite material sheet is generally 100 to 500.
It is in the range of 0 μm.

In the present invention, a porous material or a fibrous material is preferably used as the absorptive material forming the absorptive region. The porous material may be either an organic material or an inorganic material, or may be an organic / inorganic composite. In the present invention, the organic porous material used to form the adsorptive region is not particularly limited, but a carbon material such as activated carbon or a material capable of forming a membrane filter is preferably used. Specifically, nylon 6,
Nylons such as nylon 6,6 and nylon 4,10,
Cellulose derivatives such as nitrocellulose, cellulose acetate, cellulose butyrate acetate, collagen, alginic acid,
Calcium alginate, alginic acids such as alginic acid / polylysine polyion complex, polyolefins such as polyethylene and polypropylene, polyvinyl chloride, polyvinylidene chloride, polyvinylidene fluoride,
Examples thereof include polyfluorides such as polytetrafluoride, and copolymers or composites thereof.

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

In the present invention, the fiber material used for forming the adsorptive region is not particularly limited, but for example, nylons such as nylon 6, nylon 6,6, nylon 4,10, etc., Examples thereof include cellulose derivatives such as nitrocellulose, cellulose acetate, and cellulose acetate butyrate. In the present invention, the adsorptive region is
Electrolytic treatment, plasma treatment, oxidation treatment such as arc discharge,
It can also be formed by a surface treatment such as a primer treatment using a silane coupling agent or a titanium coupling agent or a surfactant treatment.

The front surface of the adsorbent material 13 (phosphor layer 14
As shown in FIG. 2, it is desirable that the surface not contacting with the inner surface of the partition wall 11 is recessed toward the inside of the sheet with respect to the surface of the partition wall 11 adjacent to the surface. With such a configuration, the probe molecule solution can be easily spotted on the adsorbent material, and once the probe molecule solution is spotted, it does not flow out to the partition wall surface or to other adsorbent materials. Can be prevented. The thickness of the adsorbent material 13 is generally 100-5.
It is in the range of 000 μm.

In the phosphor layer 14, the weight per unit area of the stimulable phosphor is generally in the range of 10 to 140 g / m ² , and preferably in the range of 50 to 100 g / m ² . The layer thickness is generally in the range of 5 to 50 μm. As a result, 90% or more of the electron beam from the radioisotope (RI) can be absorbed in the phosphor layer, so that the electron beam energy from the sample can be effectively used without lowering the resolution of the radiation image. It can be absorbed and accumulated in the layer. In addition, since the phosphor layer 14 is provided in each region 12 adjacent to the adsorptive material 13, scattering of radiation from target molecules bonded and fixed to each adsorptive material can be effectively performed by the partition wall. In addition to being able to prevent it, exposure can be performed efficiently.

The number of regions 12 in the plane of the sheet is generally 50 / cm ² or more, preferably 100 / cm ^2.
cm ² or more, more preferably 500 pieces / cm ² or more, further preferably 1000 pieces / cm ² or more, preferably 100,000 pieces / cm ² or less, and particularly preferably 10,000 pieces / cm ² or less. All of these do not necessarily have to be provided at equal intervals as shown in FIG. 1, and a plurality of regions may be formed for each block by dividing into some blocks.

In order to shield the radiation such as the electron beam from the radioactively labeled sample more effectively, the average density of the partition walls 11 is generally 0.6 g / cm ³ or more, preferably 1 to 20 g / cm ^3. It is in the range of cm ³ , and particularly preferably in the range of 2 to 10 g / cm ³ . Transmission distance of the electron beam is inversely proportional to the density of the material, radioactive material ³²
In the case of general RI such as P, ³³ P, ³⁵ S, and ¹⁴ C, by setting the average density of the partition walls within this range, the electron beams from the RI of the sample in each region are shielded by the partition walls. Thus, it is possible to prevent the resolution of the radiation image from being deteriorated due to the transmission and scattering of the electron beam.

In order to effectively immobilize the probe molecule such as nucleic acid or its fragment or synthetic oligonucleotide, the average density of the adsorptive material 13 is generally 1.0 g.
/ Cm ³ or less, preferably 0.5 g / cm ³ or less,
And preferably at least 0.1 g / cm ³ (however,
The average density of the adsorbent material is smaller than the average density of the partition wall).

The adsorbent material 13 generally has a porosity (volume ratio) in the range of 10 to 90%, and the average pore diameter of the fine pores constituting the void is in the range of 0.1 to 50 μm.

FIG. 3 is an enlarged partial sectional view schematically showing another example of the composite material sheet of the present invention. In FIG.
The composite material sheet has a partition wall 11 and a region 12 surrounded by the partition wall 11, an adsorbent material 13 is disposed on an upper portion of each region 12, and a stimulable phosphor is disposed on a lower portion thereof. A phosphor layer 14 containing the phosphor layer 14 is disposed, and further, the adsorbent material 13
And a phosphor layer 14 are provided with a waterproof layer 15, and a waterproof layer 16 is provided also on the entire surface of the sheet on the phosphor layer side.

Waterproof layers 15 and 16 are formed on both surfaces of the phosphor layer 14.
By providing, it is possible to prevent the phosphor layer from being adversely affected by the aqueous solution such as deterioration in the operation of spotting the probe molecule or fixing the target molecule. The waterproof layer 16 may be provided only on each surface of the phosphor layer 14 instead of on the entire surface of the sheet, or only one of the waterproof layers 15 and 16 may be provided.

4 to 6 are enlarged partial sectional views schematically showing another example of the composite material sheet of the present invention. In FIG. 4, the composite material sheet has a partition wall 11 and an adsorptive material 13 arranged in each region 12 surrounded by the partition wall 11,
Then, a phosphor layer 17 containing a stimulable phosphor is provided on the entire one surface of the sheet.

In FIG. 5, the composite material sheet is the partition wall 1.
1 and the adsorptive material 13 arranged in each region 12 surrounded by the partition walls 11, and in order on one side of the sheet,
The waterproof layer 18, the phosphor layer 17 containing a stimulable phosphor, and the waterproof layer 16 are provided.

In FIG. 6, the composite material sheet is the partition wall 1.
1 and the adsorptive material 13 disposed in each region 12 surrounded by the partition walls 11, and a waterproof layer 18 and a phosphor layer 1 containing a stimulable phosphor in this order on the entire one surface of the sheet.
7, and a waterproof layer 16 are further provided, and a phosphor layer 17 is further provided.
The side surface of the is provided with a waterproof edging 19.

By providing the waterproof layers 16, 17 and the edge sticking 19 on both surfaces and side surfaces of the phosphor layer 17, as described above, the phosphor layer can be protected from the aqueous solution of the probe molecule and the target molecule. Only one of the waterproof layers 16 and 17 may be attached.

In the present invention, the arrangement of the regions 12 and the shape of the openings defined by the partition walls 11 are not limited to the lattice-like arrangement and the circular openings shown in FIG. The arrangement, shape, etc. of can be appropriately changed.

FIG. 7 is a top view showing another example of the arrangement of the regions 12. In FIG. 7, the regions 12 are arranged so as to be displaced from each other in adjacent columns.

8 and 9 are top views showing examples of other shapes of the opening of the region 12. As shown in FIG. In FIG. 8, the opening of the area 12 is a quadrangle. In FIG. 9, the opening of region 12 is triangular. Alternatively, the regions 12 may be randomly arranged, and the openings thereof may be elliptical or polygonal such as hexagonal. Further, it is possible to form the elongated rectangular adsorptive material region in a stripe shape and partition the partition wall only in one-dimensional direction by the partition wall.

The composite material sheet of the present invention can be manufactured, for example, by using the following method. First, a substrate provided with a large number of through holes is prepared. The material of the substrate is preferably one that can enhance the strength as a composite material sheet, for example, nickel, metal such as nickel alloy, polyamide resin, aramid resin, polyethylene terephthalate resin, polyolefin resin (eg, polyethylene resin, Examples thereof include organic materials such as polypropylene resin) and ceramic materials such as alumina, zirconia, magnesia, and quartz.
Alternatively, a composite material in which metal or ceramic particles are mixed with an organic substance can be used.

The substrate can be produced, for example, when the substrate material is metal, by electrodeposition of the metal on the mold by electroforming. When the substrate material is an organic material, an organic polymer sheet is produced by applying and drying a coating solution in which an organic material is dissolved, and then performing laser processing using lithography such as dry etching, or LIGA process, excimer laser, etc. It can be manufactured by etching using the method. When the substrate material is ceramic, it can be produced by pressing the slurry of the ceramic raw material into a sheet-shaped molded body and then subjecting this molded body to an etching treatment such as a laser processing method.

Then, the adsorbent material-forming material is dissolved or dispersed in a suitable solvent to prepare a solution or dispersion of the material, which is then injected into each hole of the substrate and dried to obtain Micropores can be formed during the formation of the dry film to make it porous. As the material for forming the adsorptive material,
For example, cellulose derivatives such as cellulose acetate and nitrocellulose; polyamides (nylons) such as 6-nylon and 6,6-nylon; fluorine-based polymers such as polytetrafluoroethylene and polyvinylidene fluoride; and polyvinyl chloride, polycarbonate, Examples thereof include organic polymer materials composed of polysulfone and polyether sulfone; and inorganic materials such as ceramics. If desired, these materials can be used together. In the case of polyamide such as nylon, water shrinks the polymer. Therefore, after applying a non-aqueous solution and drying to form a film, the film is immersed in an aqueous solution to form fine pores in the film. In the case of ceramic, a dispersion is prepared using a ceramic raw material in which desired fine pores are formed in advance. Subsequently, the stimulable phosphor is dispersed and dissolved in a suitable organic solvent together with a binder to prepare a dispersion liquid, which is poured into each hole of the substrate and dried to obtain an adsorbent material in each hole. A phosphor layer is formed on top.

As the stimulable phosphor, 400 to 900n
300 to 500 n by irradiation with excitation light in the wavelength range of m
A stimulable phosphor that exhibits stimulated emission in the wavelength range of m is preferable. An example of such a stimulable phosphor is disclosed in JP-A-2-193.
The details are described in Japanese Patent Laid-Open No. 100 and Japanese Patent Laid-Open No. 4-310900. As a preferable stimulable phosphor,
Alkaline earth metal halide phosphors activated by europium or cerium (eg BaFB
Examples thereof include r: Eu, BaF (Br, I): Eu), and cerium-activated rare earth oxyhalide-based phosphors.

Of these, the rare earth activated alkaline earth metal fluorohalide stimulable phosphor represented by the basic composition formula: M ^II FX: zLn ... (I) is particularly preferable. However, M ^II is B
represents at least one alkaline earth metal selected from the group consisting of a, Sr and Ca, and Ln represents Ce, Pr, S
m, Eu, Tb, Dy, Ho, Nd, Er, Tm and Y
Represents at least one rare earth element selected from the group consisting of b. X represents at least one halogen selected from the group consisting of Cl, Br and I. z is 0 <z ≦ 0.2
Represents a number within the range.

As M ^II in the above basic composition formula (I),
It is preferable that Ba accounts for more than half. Ln is preferably Eu or Ce. Further, in the basic composition formula (I), it appears as F: X = 1: 1 in the notation, but this shows that it has a BaFX type crystal structure, and the stoichiometric composition of the final composition is shown. It does not indicate the composition. In general, a state in which a large number of F ⁺ (X ⁻ ) centers, which are vacancy points of X ⁻ ions, are generated in the BaFX crystal is preferable in order to enhance the photostimulation efficiency for light of 600 to 700 nm. At this time, F is often slightly over X.

Although omitted in the basic composition formula (I), the following additives may be added to the basic composition formula (I), if necessary. bA, wN ^I , xN ^II , yN ^III where A represents a metal oxide such as Al ₂ O ₃ , SiO ₂ and ZrO ₂ . In preventing sintering between M ^II FX particles, it is preferable to use an average particle size of the primary particles has low reactivity with M ^II FX in the following ultrafine particles 0.1 [mu] m. N ^I represents a compound of at least one alkali metal selected from the group consisting of Li, Na, K, Rb and Cs, N ^II represents a compound of an alkaline earth metal consisting of Mg and / or Be, and N ^III is Al, Ga, In,
It represents a compound of at least one trivalent metal selected from the group consisting of Tl, Sc, Y, La, Gd and Lu. As these metal compounds, it is preferable to use halides as described in JP-A-59-75200, but it is not limited thereto.

Further, b, w, x and y are respectively M ^II
It is the amount of addition when the number of moles of FX is 1, and is 0.
≦ b ≦ 0.5, 0 ≦ w ≦ 2, 0 ≦ x ≦ 0.3, 0 ≦ y ≦
It represents a numerical value within each range of 0.3. These figures do not represent the elemental ratios contained in the final composition with respect to additives that are reduced by firing and subsequent cleaning treatments. In addition, some of the above compounds may remain as the compounds just added in the final composition,
^Some react with or are incorporated into ^II FX.

In addition to the above basic composition formula (I), Z may be described in JP-A-55-12145, if necessary.
n and Cd compounds; TiO ₂ , BeO, MgO, C which are metal oxides described in JP-A-55-160078.
aO, SrO, BaO, ZnO, Y ₂ O ₃ , La ₂ O ₃ , I
n ₂ O ₃ , GeO ₂ , SnO ₂ , Nb ₂ O ₅ , Ta ₂ O ₅ , Th
O ₂ ; Zr and Sc compounds described in JP-A-56-116777; B compound described in JP-A-57-23673; As described in JP-A-57-23675.
And Si compounds; tetrafluoroboric acid compounds described in JP-A-59-27980; JP-A-59-4728.
Hexafluorosilicic acid, hexafluorotitanic acid, and hexafluorozirconic acid monovalent or divalent salts described in JP-A No. 9-58; V, Cr described in JP-A-59-56480; Mn, F
Compounds of transition metals such as e, Co and Ni may be added. Further, in the present invention, not only the phosphor containing the above-mentioned additive, but any substance having a composition which is basically regarded as a rare earth activated alkaline earth metal fluorohalide stimulable phosphor. May be

The rare earth activated alkaline earth metal fluorohalide stimulable phosphor represented by the above basic composition formula (I) usually has an aspect ratio in the range of 1/1 to 5/1. . The stimulable phosphor particles used in the phosphor layer according to the present invention are columnar or needle-shaped phosphor particles having an aspect ratio in the range of 2/1 to 5/1. And the median diameter (Dm) of the particle size is 0.1 to 10 μm (preferably, 0.
5 to 2 μm), and when the standard deviation of the particle size distribution is σ, σ / Dm is 50% or less (preferably,
40% or less). Further, the shape of the particles includes a rectangular parallelepiped type, an octahedral type, a tetrahedral type and an intermediate polyhedral type of these, and among them, the tetrahedral type is preferable. However, as long as the stimulable phosphor particles satisfy the above aspect ratio, particle size, and particle size distribution, they can be used for the composite material sheet even if they are not necessarily of the tetradecahedral type.

The ratio of the binder to the phosphor in the above dispersion is usually set to a value in the range of 1: 1 to 1: 100 (weight ratio). This ratio is in particular 1: 8 to 1:40
It is preferably in the range of (weight ratio). Various kinds of resin materials are known for the binder that dispersively supports the stimulable phosphor particles, and also in the formation of the phosphor layer according to the present invention, any of these known binder resins may be used as the center. The resin material can be appropriately selected and used.

In this way, it is possible to manufacture a composite material sheet in which each hole of a substrate having through holes as shown in FIGS. 1 and 2 is filled with an adsorbent material and a phosphor layer.

Furthermore, as shown in FIG. 3, a waterproof layer may be provided on one side or both sides of the phosphor layer. The waterproof layer is for preventing the phosphor layer from being adversely affected by the aqueous solution such as deterioration when the probe molecule solution is spotted or the target molecule solution is fixed. In particular, the waterproof layer to be located on the surface side of the composite material sheet is preferably transparent so that it hardly affects the incidence of excitation light and the emission of emitted light, and a physical layer applied from the outside. It is desirable to be chemically stable and have high physical strength so that the composite sheet can be adequately protected from impact and chemical influences. As the waterproof layer, polymethylmethacrylate, one formed by applying a solution prepared by dissolving an organic polymer substance such as an organic solvent-soluble fluororesin in a suitable solvent onto the phosphor layer, Alternatively, a film in which an organic polymer film such as polyethylene terephthalate is separately formed and provided on the surface of the phosphor layer with an appropriate adhesive is used. The layer thickness of the waterproof layer is generally in the range of 1 to 10 μm.

Alternatively, for the composite material sheet, two sheets of partition wall supports having a large number of through holes are prepared, and a sheet in which an adsorbent material layer and, if desired, a waterproof layer are laminated on the phosphor layer is formed separately. The sheet can also be manufactured by using a method of sandwiching this sheet between two partition wall supports and press-bonding the sheet with heat or a solvent.

In the composite material sheet having the structure shown in FIGS. 4 to 6, after the adsorbent material is formed in each hole of the substrate as described above, the phosphor layer and optionally the waterproof layer are formed on one surface thereof. Can be manufactured by coating and forming, or by bonding a separately formed phosphor layer and waterproof layer with an adhesive. In this case, the phosphor layer is not only composed of a stimulable phosphor and a binder containing and supporting it in a dispersed state, but also composed of only aggregates of the phosphor without containing a binder, Alternatively, it may be a phosphor layer in which a polymer substance is impregnated in the gap between the aggregates of the phosphor.

For example, the phosphor layer may be formed by a vapor deposition method such as a vapor deposition method. When the phosphor layer is formed by a vapor deposition method, a particularly preferable stimulable phosphor is an alkali metal halide stimulable phosphor represented by the following basic composition formula (II).

M ^I X · aM ^II X ′ ₂ · bM ^III X ″ ₃ : zA (II) where M ^I is at least one alkali metal selected from the group consisting of Li, Na, K, Rb and Cs. Represents
M ^II is Be, Mg, Ca, Sr, Ba, Ni, Cu, Z
represents at least one alkaline earth metal or divalent metal selected from the group consisting of n and Cd, M ^III is Sc,
Y, La, Ce, Pr, Nd, Pm, Sm, Eu, G
d, Tb, Dy, Ho, Er, Tm, Yb, Lu, A
represents at least one rare earth element or trivalent metal selected from the group consisting of 1, Ga and In, and A represents Y, C
e, Pr, Nd, Sm, Eu, Gd, Tb, Dy, H
o, Er, Tm, Yb, Lu, Na, Mg, Cu, A
It represents at least one rare earth element or metal selected from the group consisting of g, Tl and Bi. X, X ′ and X ″ each represent at least one halogen selected from the group consisting of F, Cl, Br and I. a, b and z represent 0 ≦ a <0.5 and 0 ≦ b <, respectively. 0.5, 0 ≦ z <
It represents a numerical value within the range of 0.2.

It is preferable that M ^I in the above basic composition formula (II) contains at least Cs. X preferably contains at least Br. It is particularly preferable that A is Eu or Bi. Further, in the basic composition formula (II), if necessary, aluminum oxide,
A metal oxide such as silicon dioxide or zirconium oxide may be added as an additive in an amount of 0.5 mol or less with respect to 1 mol of M ^I.

In the case of the electron beam evaporation method which is a typical method of the vapor deposition method, first, the evaporation source made of the above-mentioned stimulable phosphor and the substrate of the object to be evaporated are set in the evaporation apparatus, Exhaust the inside of the device. The evaporation source is preferably in the form of tablets by pressure compression. At this time, Ar gas, N
You may introduce inert gas, such as e gas. Next, an electron beam is generated from an electron gun in an acceleration voltage range of 1.5 to 5.0 kV, and the evaporation source is irradiated with the electron beam to deposit a stimulable phosphor on the surface of the substrate. Vapor deposition rate is generally 0.1 to 1000 μm
/ Minute, preferably in the range of 1 to 100 μm / minute. The electron beam irradiation may be divided into a plurality of times, or different phosphors may be co-deposited by using a plurality of electron guns. It is also possible to form the phosphor layer at the same time as synthesizing the phosphor on the support using the phosphor raw material. Further, the material to be vapor-deposited may be cooled or heated at the time of vapor deposition, or the phosphor layer may be heat-treated after the vapor deposition is completed. This makes it possible to obtain a phosphor layer which is composed of only the stimulable phosphor and has voids (cracks) between the columnar crystals of the stimulable phosphor.

A method for detecting and analyzing a biological substance of the present invention using the above-mentioned composite material sheet will be described below.

As the probe molecule fixed to the adsorptive material of the composite material sheet of the present invention, for example, various polynucleotides and oligonucleotides which can be conventionally used as the probe molecule of the macro array can be used. For example, cDNA (complementary DNA synthesized using mRNA as a template), part of cDNA, PC such as EST
A polynucleotide prepared by amplification by the R method ("P
CR products ”), and synthetic oligonucleotides. Further, it may be an artificial nucleic acid obtained by converting a phosphodiester bond of DNA into a peptide bond, that is, a peptide nucleic acid (PNA), or a derivative thereof. Further, proteins capable of producing biochemical specific binding such as antigens and antibodies can also be used.

Specific combinations of the probe molecule and the target molecule (sample) include DNA (DNA or its fragment, or oligo DNA) and DNA, and DNA and RN.
A, PNA and DNA or RNA, PNA and PNA, antigen and antibody, avidin and biotin, and the like.

In the following, the probe molecule and the target molecule are fragments of nucleic acid such as DNA and RNA, and
And the case of using the composite material sheet shown in FIG. 3 will be specifically described.

First, a plurality of types of aqueous solutions containing a large number of single-stranded nucleic acid fragments (usually, one whose nucleotide sequence is known) are used, a spotter or the like is used, and the composite material sheet of FIGS. The probe molecules are fixed so as to be entangled with the fine pores of the adsorbent material 13 by being spotted on the regions 12 on the adsorbent material side.

Then, the single-stranded nucleic acid fragment of the target molecule is subjected to RI using a hybridization container or the like.
By immersing this composite material sheet in an aqueous solution of a radiolabeled target molecule prepared by labeling with (for example, ³² P, ³³ P), the radiolabeled target molecule is bound and immobilized on the probe molecule in the composite material sheet by hybridization. To do. Then, the target molecules that have not hybridized are removed from the composite material sheet by washing or the like.

Next, the surface of the composite material sheet on the phosphor layer side is irradiated with erase light by using an erase light source such as a sodium lamp, a fluorescent lamp, an infrared lamp, etc. Releases and removes the energy of natural radiation that may be present and radiation that may remain from previous use.

This composite material sheet is then passed through, for example, 0-3.
Autoradiography is carried out by exposing the sample by allowing it to stand at 0 ° C. for a certain period of time (eg, 1 to 120 hours).
Radiation energy emitted from the radio-labeled target molecule in each adjacent adsorbent material is absorbed and accumulated in each phosphor layer of the composite material sheet. By this autoradiography operation, the phosphor layer as a whole holds information regarding the position and amount of the target molecule, or the binding with the probe molecule, as radiation image information.

Next, on the composite material sheet on which the radiation image information is accumulated and recorded, the image information reading operation is performed by using the radiation image information reading device of the present invention.

FIG. 10 is a schematic block diagram showing an example of the radiation image information reading apparatus of the present invention, and FIG.
It is sectional drawing along the -I line. In FIG. 10, the radiation image information reading apparatus corresponds to a region 12 of the composite material sheet 20 in which the composite material sheet 20 is placed and conveyed in the arrow Y direction, and the scanning belt 30 is substantially parallel to the surface of the sheet 20. Laser light source 21 for emitting excitation light L in a spot shape
The excitation light L, which is provided on the optical path of the excitation light L and is arranged at an angle of 45 degrees with respect to the optical system 22 including a collimator lens and a toric lens that make the excitation light L a parallel beam, is arranged at an angle of 45 degrees. A dichroic mirror 23 that is set to reflect and transmit the emitted light M, and a gradient index lens array that collects the excitation light L in a linear shape extending along the arrow X direction on the sheet 20 (a large number of refractive indexes This is a lens in which distributed lenses are arranged, and is hereinafter referred to as a first SELFOC lens array) 24, and a second light for converging the emitted light (stimulated emitted light) M emitted from the sheet 20 on the line sensor 27. The SELFOC lens array 25 and the emission light M transmitted through the SELFOC lens array 25 are slightly mixed, and the excitation light L reflected on the surface of the sheet 20 is cut and the emission light M is transmitted. The excitation light cut filter 26, a line sensor 27 in which a large number of photoelectric conversion elements 28 for receiving and photoelectrically converting the emitted light M transmitted through the excitation light cut filter 26 are arranged, and a signal Q output from the line sensor 27 is output to the sheet 10. The image information reading means 29 which outputs the electric image signal S by performing the arithmetic processing corresponding to the part of FIG.

The laser light source 21 is arranged in the arrow X direction, and emits light in the visible region having a wavelength of 630 to 690 nm in a plurality of spots along the arrow X direction. The SELFOC lens array 25 acts on the light-receiving surface of the line sensor 27 to form an emission area of the emission light M on the surface of the sheet 20 as an image surface for forming an image with a size of 1: 1.

The line sensor 27 has a structure in which a large number (for example, 1000 or more) of photoelectric conversion elements (CCDs, charge-coupled elements) 28 are arranged in a direction orthogonal to the arrow Y direction. Each of the plurality of photoelectric conversion elements 28 has a length of 100 μm.
× It has a light receiving surface of about 100 μm in width,
Corresponds to the pixel. Each light receiving surface has a composite material sheet 20.
The emitted light M emitted from the surface of each phosphor layer 14 is received.

The composite material sheet 20 placed on the scanning belt 30 with the phosphor layer 14 side facing up is the scanning belt 30.
Is moved in the arrow Y direction, and is conveyed in the arrow Y direction. The conveying speed of the sheet 20 is equal to the moving speed of the belt 30, and the moving speed of the belt 30 is input to the image reading unit 29.

On the other hand, the spot-shaped excitation light L emitted from the laser light source 21 substantially perpendicularly to the surface of the sheet 20.
Is made into a vertical beam by an optical system 22 including a collimator lens and a toric lens provided on the optical path, and a plurality of spots are formed on the surface of the sheet 20 along the direction of arrow X corresponding to the region 12 of the composite material sheet 20. It is irradiated in a shape.

Excitation of the spot-shaped excitation light L vertically incident on the sheet 20 causes the intensity corresponding to the radiation image information accumulated and recorded from the phosphor layer 14 of the sheet 20 which is the condensing region of the excitation light L. The emitted light M is emitted.

The emitted light M is collimated by the first SELFOC lens array 24, passes through the dichroic mirror 23, and then passes through the second SELFOC lens array 2.
5, the excitation light L is condensed on the light-receiving surface of each photoelectric conversion element 28 that constitutes the line sensor 27 arranged right above the condensing area.

At this time, the excitation light L reflected by the surface of the sheet 20 which is slightly mixed with the emitted light M transmitted through the second SELFOC lens array 25 is cut by the excitation light cut filter 27.

The emitted light M received by each photoelectric conversion element 28 is photoelectrically converted, and each signal S obtained by photoelectric conversion is input to the image information reading means 29. Each signal S is processed by the image information reading means 29 in accordance with the moving speed of the scanning belt 30 corresponding to the part of the sheet 20, and is output as image data to an image processing device (not shown).

The radiation image information reading apparatus used in the present invention is not limited to the embodiment shown in FIGS. 10 and 11, and the light source, the condensing optical system between the light source and the composite material sheet, the sheet. The optical system between the line sensor and the line sensor and the line sensor can each adopt various known configurations.

The laser light source may have a linear light source, and a fluorescent lamp, a cold cathode fluorescent lamp, an LED (light emitting diode) array, or the like can also be used. The excitation light emitted from the line light source may be continuously emitted, or may be pulsed light in which emission and stop are repeated. From the viewpoint of noise reduction, pulsed light with high output is preferable. Alternatively, the pulsed light may be emitted in conformity with the moving speed of the region 12 of the composite material sheet 20 and the scanning belt 30.

As the line sensor, an amorphous silicon sensor, a CCD sensor, a CCD with a back illuminator, a MOS image sensor or the like can be used. Further, the line sensor is not limited to one in which the photoelectric conversion elements are arranged in one row, and may be one in which two or three rows are arranged.

In the above embodiment, the optical system between the sheet and the line sensor is set to the 1: 1 image forming system in order to simplify the description, but a scaling optical system may be used. However, it is preferable to use an equal-magnification or magnifying optical system in order to enhance the light collection efficiency.

In the above embodiment, the device is made compact by adopting a structure in which the optical path of the excitation light L and the optical path of the emitted light M partially overlap with each other.
It is also possible to adopt a configuration in which the optical paths of are completely different.

Further, in the above-mentioned mode, the composite material sheet is moved for reading, but the sheet may be left stationary and the line sensor may be moved along the surface of the sheet.

Alternatively, the structure further comprises an image processing device for performing various signal processing on the image data signal output from the image information reading means, and the radiation remaining on the composite material sheet before and after reading. It is also possible to employ a configuration further including an erasing unit for appropriately releasing energy.

Based on the radiation image information obtained as a visible image or digital data, the probe molecule to which the radiolabeled target molecule is bound complementarily is detected,
By identifying, the base sequence of the target molecule can be determined. In addition, the expression, mutation,
Polymorphism and the like can be analyzed simultaneously for many samples.

[0087]

EXAMPLES Example 1 (1) Fabrication of Substrate Stainless steel was electrodeposited on a mold by electroforming to fabricate a substrate having a large number of through holes. The substrate has a size of 40 mm × 60 mm, a thickness of 0.2 mm, the total number of holes is 2,400, and the density of holes is 100 / cm.
^{Was 2} . The opening of each hole was circular, and its area was 0.07 mm ² . The average density of the substrate is 8.8 g /
It was cm ³ .

(2) Formation of adsorbent material 15% by weight of nylon 6 and 83% by weight of formic acid and 2% by weight
Was added to water and mixed at room temperature for 3 hours, then mixed and dissolved at 50 ° C. for 1 hour, and then cooled to room temperature to prepare a polymer solution. This polymer solution was injected into each through hole of the substrate and then dried to form a film on the lower half of each hole. Next, the substrate was immersed in an aqueous formic acid solution (20% by weight of formic acid) to form a large number of fine pores in the film to make it porous.

(3) Formation of Phosphor Layer A stimulable phosphor particle (BaF (Br,
I): Eu) and a thermoplastic high molecular weight polyester resin are dispersed in an organic solvent at a weight ratio of 5: 1 to obtain a phosphor dispersion liquid, and the phosphor dispersion liquid is applied to each through hole of the substrate. After the injection, it was dried to form a phosphor layer on the upper half of each hole.

(4) Formation of Waterproof Layer A transparent polyethylene terephthalate film (thickness: 6 μm, polyester-based on one side is formed on the phosphor layer side surface of the substrate in which the through holes are filled with the adsorbent material and the phosphor layer. An adhesive layer (having a layer thickness of 1.5 μm) was overlaid with the adhesive layer on the lower side and heat-pressed to form a waterproof layer.

Thus, FIGS. 1 and 3 (however, the waterproof layer 15 is not provided) having the waterproof layer on one side, which is composed of the stainless steel partition wall, the polyamide (nylon 6) adsorbent material and the phosphor layer filling region. A composite material sheet having the configuration schematically shown in was obtained.

(5) Evaluation of Composite Material Sheet A single-stranded nucleic acid fragment (probe molecule) was fixed to the polyamide adsorbent material of the composite material sheet by spotting according to a conventional method, and then this composite material sheet was treated with the probe molecule. Hybridization was carried out by immersing in a solution of a sample in which a single-stranded nucleic acid fragment (target molecule) having a complementarity with was radioactively labeled. The composite sheet was removed from the aqueous solution, washed with water and dried. Next, the surface of the composite material sheet facing the phosphor layer was irradiated with a fluorescent lamp to erase the accumulated radiation energy. Then, an autoradiography operation was performed at room temperature. Figure 1 for this composite material sheet
When a radiation image was read using the radiation image information reading device shown in FIG. 0 and FIG. 11, a region of the adsorbent material of the composite material sheet (a region where the radiolabeled target molecule was bound and fixed to the probe molecule by hybridization) The radiographic image of was obtained with high resolution and high sensitivity.

[0093]

EFFECTS OF THE INVENTION By using the composite material sheet of the present invention for the analysis of a bio-related substance utilizing a biochemical specific binding reaction, probe molecules such as nucleic acid fragments are selectively spot-immobilized on the adsorptive material. Therefore, the diffusion of the probe molecule at the time of spotting can be prevented. Further, it is possible to prevent diffusion of radiolabeled target molecules and non-specific attachment which are likely to occur during analysis work. As a result, noise in the radiation image obtained by autoradiography can be reduced, and a radiation image with high resolution can be obtained. Further, the partition walls can effectively prevent the scattering of radiation from the target molecules, which also improves the resolution of the radiation image.

Moreover, since the adsorptive material of the composite material sheet and the phosphor layer are integrated in a laminated state, it is not necessary to superimpose with the stimulable phosphor sheet during autoradiography operation. In addition, since the radiation from the target molecule is almost directly incident on the phosphor layer, it is possible to obtain a radiation image with higher resolution.

Therefore, according to the present invention, it is possible to remarkably improve the accuracy of detection and analysis of biologically relevant substances. Further, the composite material sheet of the present invention can increase the number of regions of the adsorptive material corresponding to conventional spots per unit area, and can achieve higher density than conventional porous sheets.

[Brief description of drawings]

FIG. 1 is a schematic perspective view showing an example of the configuration of a composite material sheet of the present invention.

FIG. 2 is an enlarged partial sectional view taken along line I-I in FIG.

FIG. 3 is an enlarged partial sectional view showing another example of the configuration of the composite material sheet of the present invention.

FIG. 4 is an enlarged partial cross-sectional view showing another example of the configuration of the composite material sheet of the present invention.

FIG. 5 is an enlarged partial sectional view showing another example of the constitution of the composite material sheet of the present invention.

FIG. 6 is an enlarged partial sectional view showing another example of the configuration of the composite material sheet of the present invention.

FIG. 7 is a top view showing another example of arrangement of regions.

FIG. 8 is a top view showing an example of another shape of the opening of the area.

FIG. 9 is a top view showing another example of the shape of the opening of the area.

FIG. 10 is a configuration diagram showing an example of a radiation image information reading apparatus of the present invention.

11 is a cross-sectional view taken along line I-I in FIG.

[Explanation of symbols]

11 Partition 12 Region 13 Adsorbent Material 14, 17 Phosphor Layers 15, 16, 18 Waterproof Layer 19 Edge Adhesion 20 Composite Material Sheet 21 Laser Light Source 22 Optical System 23 Composed of Collimator Lens and Toric Lens 23 Dichroic Mirror 24, 25 Selfoc Lens Array 26 Excitation light cut filter 27 Line sensor 28 Photoelectric conversion element 29 Image information reading means 30 Scan belt L Excitation light M Emission light S Signal

Front page continuation (51) Int.Cl. ⁷ Identification code FI theme code (reference) G01N 33/566 G01N 33/566 5C072 33/60 33/60 A 37/00 102 37/00 102 G01T 1/00 G01T 1 / 00 B G21K 4/00 G21K 4/00 L H04N 1/04 H04N 1/04 EF Term (reference) 2G045 AA35 DA12 DA13 DA14 FA11 FA29 FB02 FB09 FB12 HA16 HA20 JA01 2G054 AB07 BB20 CA22 EA03 EA10 EB01 FA04 FA50 FA02 FA50 FA02 GA10 GB02 GE01 2G083 AA03 CC02 CC04 DD12 EE03 4B029 AA07 AA21 AA23 BB20 CC03 CC08 CC10 CC11 FA15 4B063 QA01 QA18 QQ42 QQ52 QR56 QR84 QS28 QS34 QS36 QS39 QX07 5C072 AA01 CA04 NA05 CA06 CA05 CA06 CA05 CA06 CA02 CA06 CA05 CA06 CA05 CA06 CA05 CA06 CA05 CA06 CA05 CA06 CA02 CA06 CA05 CA06 CA02 CA06 CA05 CA06 CA02 CA06 CA05 CA06 CA02 CA05 CA06 CA05 CA06 CA06 CA05 CA06 CA02 CA05 CA06 CA06 CA02 CA05 CA06 CA05 CA06 CA02 CA05 CA06 CA02 CA05 CA06 CA02 CA06 CA02 CA06 CA02 CA05 CA 05 CA 06 CA 02 CA 06 CA 02 CA 05 CA 05

Claims (22)

[Claims] 1. A partition wall which divides a sheet plane into two-dimensional directions, and a plurality of regions partitioned by the partition wall, and an adsorbent material is disposed on one surface side portion in each region. And a phosphor layer containing a stimulable phosphor is disposed on the other surface side portion of the composite material sheet. 2. The composite material sheet according to claim 1, wherein a waterproof layer is provided on one side or both sides of the phosphor layer. 3. The average density of the partition walls is 0.6 g / cm ³ or more, and the average density of the adsorbent material is 1.0 g / cm ³ or less (where, average density of partition walls> average density of adsorbent material). (The relationship of 1) is satisfied) The composite material sheet according to claim 1 or 2. 4. The composite material sheet according to claim 3, wherein the partition wall is formed of a metal, an organic material and / or a ceramic glass. 5. The composite material sheet according to claim 3, wherein the adsorbent material is a porous organic polymer substance structure. 6. The composite material sheet according to claim 1, wherein the weight per unit area of the stimulable phosphor in the phosphor layer is in the range of 10 to 140 g / m ² . 7. The composite material sheet according to claim 1, wherein an average value of the areas of the openings of the regions partitioned by the partition walls is in the range of 0.001 to ⁵ mm ² . 8. The average value of the number of existing areas per unit area of a region partitioned by partition walls in the sheet is 10 to 10.
The composite material sheet according to any one of claims 1 to 7, which is in a range of 000 pieces / cm ² . 9. The method according to claim 1, wherein the surface of the adsorptive material on the side opposite to the phosphor layer is set back toward the inside of the sheet with respect to the surface of the partition wall in contact with the surface. Composite material sheet. 10. A stimulable phosphor is provided on one surface of a composite material sheet composed of partition walls that subdivide a sheet plane in a two-dimensional direction, and an adsorbent material arranged in each region partitioned by the partition walls. A composite material sheet additionally provided with a phosphor layer containing. 11. The composite material sheet according to claim 10, wherein a waterproof layer is provided on one side or both sides of the phosphor layer. 12. The partition walls have an average density of 0.6 g / cm ³ or more and the adsorptive material has an average density of 1.0 g / cm ³ or less (wherein, the partition wall average density> the adsorptive material average density). (The relationship of 1) is satisfied) The composite material sheet according to claim 10 or 11. 13. The composite material sheet according to claim 12, wherein the partition wall is formed of a metal, an organic substance and / or a ceramic glass. 14. The composite material sheet according to claim 12, wherein the adsorbent material is a porous organic polymer material structure. 15. The composite material sheet according to claim 10, wherein an average value of the areas of the openings of the regions partitioned by the partition walls is in the range of 0.001 to ⁵ mm ² . 16. An average value of the number of existing areas per unit area of a region partitioned by partition walls in the sheet is 10 to 1
The composite material sheet according to any one of claims 10 to 15, which is in a range of 0000 pieces / cm ² . 17. The surface of the adsorptive material on the side opposite to the surface of the phosphor layer is set back toward the inside of the sheet with respect to the surface of the partition wall in contact with the surface. 7. The composite material sheet according to. 18. The composite material sheet according to claim 10, wherein the weight per unit area of the stimulable phosphor in the phosphor layer is in the range of 10 to 140 g / m ² . 19. A biological-related sample of a sample labeled with a radioactive substance after a large number of probe molecules are adhered and fixed to the adsorptive material of the composite material sheet according to any one of claims 1 to 18. A step of contacting a substance in a liquid phase to immobilize the radiolabeled sample on the probe molecule by a biochemical specific binding reaction; a step of removing an unimmobilized radiolabeled sample from the composite material sheet; the complex The step of irradiating the surface of the phosphor layer of the material sheet with an erasing light to erase the radiation energy that has been absorbed and accumulated; the radiation energy emitted from the radiolabeled sample bonded and fixed to the adsorptive material of the composite material sheet, A step of absorbing and accumulating in an adjacent phosphor layer; irradiating excitation light to the surface of the phosphor layer that has absorbed and accumulated radiation energy to collect emitted light emitted from the phosphor layer and perform photoelectric conversion Converting to obtain an electrical image signal;
Then, a method for detecting and analyzing a bio-related substance, comprising a step of processing the electrical image signal to detect binding information of the radiolabeled sample to the probe molecule. 20. A large number of single-stranded probe nucleic acid fragments are attached and fixed to the adsorptive material of the composite material sheet according to any one of claims 1 to 18, and then labeled with a radioactive substance. Contacting the single-stranded nucleic acid or fragment sample thereof in a liquid phase to bind and immobilize the radiolabeled nucleic acid or fragment sample to the probe nucleic acid fragment by hybridization; unfixed from the composite material sheet A step of removing a nucleic acid or a fragment sample thereof;
Irradiating the surface of the phosphor layer of the composite material sheet with erasing light,
Erasing the absorbed and accumulated radiation energy;
A step of absorbing and accumulating radiation energy emitted from a radiolabeled nucleic acid or fragment sample thereof fixed and bound to the adsorbent material of the composite material sheet in an adjacent phosphor layer;
The surface of the phosphor layer that has absorbed and accumulated radiation energy is irradiated with excitation light to collect the emitted light emitted from the phosphor layer,
A method for detecting and analyzing a complementary nucleic acid, comprising a step of photoelectrically converting to obtain an electric image signal; and a step of processing the electric image signal to detect binding information of a nucleic acid to a probe nucleic acid fragment or a sample of the fragment thereof. 21. Radiation energy from a radiolabeled sample bound and fixed to an adsorbent material of a composite material sheet according to any one of claims 1 to 18 is absorbed and accumulated in an adjacent phosphor layer. Conveying means for moving the composite material sheet in its plane direction; irradiating the phosphor layer surface of the composite material sheet with excitation light in a spot shape corresponding to the region of the adsorptive material in a direction different from the moving direction. A radiation image information reading device comprising an optical system; and a reading unit including a photodetector for photoelectrically detecting the emitted light emitted from the excitation light irradiation portion of the phosphor layer. 22. The photodetector is a line sensor which linearly arranges a plurality of photoelectric conversion elements for receiving emitted light one-dimensionally and performing photoelectric conversion, and the reading means is the line sensor. The output from the sensor is sequentially read according to the movement of the composite material sheet, and the radiation energy information of the radiolabeled sample is obtained as an electric image signal.
The radiation image information reading device described in 1.