JP2003042956A - Data read method and scanner used therefor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a data read method, capable of reading, at a low cost and at a high speed, data of a radiolabeling material included in a sample, for labeling the sample, a labeling material for generating chemiluminescence by bringing into contact with a fluorescent material and/or a chemiluminescent substrate, or the like, and completing quantitative analysis in a short time based on the read data. SOLUTION: In this data read method, a sample 10, having plural sport regions 12 formed mutually separately on a substrate and including selectively the labeling material, is scanned, and the light emitted from the plural spot regions is detected photoelectrically, to thereby generate the data. The method generates the data, by detecting photoelectrically light emitted from a region having a larger width in the direction perpendicular to the main scanning direction than that in the direction perpendicular to the main scanning direction of the spot region.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a data reading method and a scanner used therefor,
More specifically, at low cost and at high speed, a labeling substance that causes chemiluminescence by contacting a radioactive labeling substance, a fluorescent substance, and / or a chemiluminescent substrate labeling a sample contained in the sample, etc. Data can be read, and based on the read data, in a short time,
The present invention relates to a data reading method capable of completing quantitative analysis and a scanner used therefor.

[0002]

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

Further, when irradiated with an electron beam or radiation, it absorbs the energy of the electron beam or radiation,
Accumulation, recording, and then, when excited by using an electromagnetic wave in a specific wavelength range, a stimulable phosphor having a characteristic of emitting a stimulable amount of light according to the amount of energy of an irradiated electron beam or radiation. Used as a material for detecting electron beam or radiation, irradiating a metal or non-metal sample with an electron beam and detecting a diffraction image or transmission image of the sample to analyze elements, analyze the composition of the sample, analyze the structure of the sample, etc. Or to irradiate biological tissue with an electron beam to detect an image of biological tissue using an electron microscope image detection system with an electron microscope or to irradiate a sample with radiation and detect the resulting radiation diffraction image. A radiation diffraction image detection system for performing structural analysis of a sample is known (for example, JP-A-61-51738, JP-A-61-93538, and JP-A-59-59). Such as the 5843 JP).

Unlike the case where a photographic film is used, the system using these stimulable phosphor sheets as a material for detecting an image not only requires a chemical treatment called a developing treatment but also obtains the obtained digital data. By performing the data processing on (1), there is an advantage that the analysis data can be reproduced or the quantitative analysis by the 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 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, hormones, tumor markers, enzymes, antibodies, antigens, abzymes, etc. have been found at different positions on the surface of a carrier such as a slide glass plate and a membrane filter.
Other proteins, nucleic acids, cDNA, DNA, RNA
Such as specific binding substances that can specifically bind to a substance of biological origin and whose base sequence, base length, composition, etc. are known, are dropped using a spotter device, and a large number of independent Then, a spot is formed, and then hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, cDNAs, DNAs, mRNAs, etc. are collected from the living body by extraction, isolation, etc., or, Substances of biological origin that have been subjected to chemical treatment, chemical modification, etc., labeled with a labeling substance such as a fluorescent substance or a dye, can be specifically bound to a specific binding substance by hybridization. The bound microarray is irradiated with excitation light, and light such as fluorescence emitted from a labeling substance such as a fluorescent substance or dye is photoelectrically detected to obtain a substance derived from a living body. Microarray analysis system that analyzes have been developed. According to this microarray analysis system, a large number of spots of specific binding substances are formed at high density at different positions on the surface of a carrier such as a slide glass plate or a membrane filter, and a substance of biological origin labeled with a labeling substance is used. By hybridizing with, there is an advantage that a substance derived from a living body can be analyzed in a short time.

[0008] Further, hormones, tumor markers, enzymes,
Antibodies, antigens, abzymes, other proteins, nucleic acids,
A specific binding substance, such as cDNA, 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. , Multiple independent spots, then hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, cDNA, DN
Substances derived from a living body, such as A and mRNA, which have been collected from the living body by extraction, isolation, etc., or which have been further subjected to chemical treatment, chemical modification, etc., and which have been labeled with radiolabeled substances , By hybridization or the like, to the specific binding substance, the macroarray specifically bound, is brought into close contact with the stimulable phosphor sheet on which the stimulable phosphor layer containing the stimulable phosphor is formed, The photostimulable phosphor layer is exposed to light, and then the photostimulable phosphor layer is irradiated with excitation light, and the photostimulable light emitted from the photostimulable phosphor layer is photoelectrically detected for biochemical analysis. A macroarray analysis system using a radiolabeled substance that generates use data and analyzes a substance derived from a living body has also been developed.

[0009]

Conventionally, in these systems, a label which causes chemiluminescence by bringing a sample contained in a sample into contact with a labeling radioactive labeling substance, a fluorescent substance and / or a chemiluminescent substrate. Scanners used to read data such as substances are
After irradiating the sample with excitation light or contacting the chemiluminescent substrate with the sample at a pixel pitch of several microns to several tens of microns, the light emitted from minute pixels of several microns to several tens of microns of the sample is emitted. Contacting the sample contained in the sample with the radioactive labeling substance, the fluorescent substance, and / or the chemiluminescent substrate, which is configured to detect photoelectrically, and thus has a minute pixel pitch In order to read data such as a labeling substance that causes chemiluminescence, it is necessary to use a highly accurate scanner, which causes a problem of cost.

Further, in this way, with a fine pixel pitch,
When reading data such as a labeling substance that causes chemiluminescence by bringing a sample contained in a sample into contact with a labeling radioactive labeling substance, a fluorescent substance, and / or a chemiluminescent substrate, the reading is necessarily performed. Not only does it take longer and lower throughput,
Further, it took a lot of time to quantitatively analyze the read data, which was not efficient.

Accordingly, the present invention provides chemiluminescence at low cost and at high speed by contacting a sample contained in a sample with a radioactive labeling substance, a fluorescent substance and / or a chemiluminescent substrate which are labeled. It is an object of the present invention to provide a data reading method capable of reading data such as a labeling substance to be read and capable of completing quantitative analysis in a short time based on the read data, and a scanner used therefor.

[0012]

The object of the present invention is to:
At least one-dimensionally spaced apart from each other on the substrate, a sample provided with a plurality of spot-like regions selectively containing a labeling substance is scanned at least in the main scanning direction, and the plurality of samples are scanned. In a data reading method of photoelectrically detecting light emitted from a spot-shaped area to generate data, a width in a direction perpendicular to the main scanning direction is such that the spot-shaped area has the main scanning direction. This is achieved by a method of reading data, characterized in that light emitted from a region larger than a width in a direction perpendicular to the direction is photoelectrically detected to generate data.

According to the present invention, light emitted from a region in which the width in the direction perpendicular to the main scanning direction is larger than the width of the spot-like region in the direction perpendicular to the main scanning direction is photoelectrically detected. Since the data is generated, the light emitted from the one row of spot-like regions can be photoelectrically detected by one main scan to generate the data.
Therefore, the data of the labeling substance labeling the sample contained in the sample can be read at high speed, and the quantitative analysis can be completed in a short time based on the read data.

In a preferred aspect of the present invention, the plurality of spot-shaped areas are two-dimensionally formed so as to be spaced apart from each other, and the plurality of spot-shaped areas are formed in the main scanning direction and the main scanning direction. Scanning in the sub-scanning direction perpendicular to the scanning direction, the light emitted from the labeling substance contained in the plurality of spot-shaped regions is photoelectrically detected, and is configured to generate data. There is.

In a preferred aspect of the present invention, the excitation light is so arranged that the width in the direction perpendicular to the main scanning direction is larger than the length of the spot-shaped region in the direction perpendicular to the main scanning direction. A beam is shaped, the sample is irradiated, the spot-shaped regions are scanned with excitation light to excite the labeling substance, and the labeling substance contained in the spot-shaped regions is excited. It is configured to photoelectrically detect the emitted light to generate data.

According to a preferred embodiment of the present invention, the beam of excitation light is made so that the width in the direction perpendicular to the main scanning direction is larger than the length of the spot-shaped region in the direction perpendicular to the main scanning direction. After shaping, irradiating the sample, scanning the spot-shaped regions with excitation light to excite the labeling substance, and photoelectrically emitting light emitted from the labeling substance contained in the spot-shaped regions. Since it is configured to detect the data and generate the data, the light emitted from one row of spot-like regions by one main scan,
Data can be photoelectrically detected to generate data, and therefore, data of the labeling substance labeling the sample contained in the sample can be read at high speed, and based on the read data, data can be read in a short time. , It becomes possible to complete the quantitative analysis.

In a preferred embodiment of the present invention, the width in the direction perpendicular to the main scanning direction is larger than the width of the spot-like region in the direction perpendicular to the main scanning direction, and the width in the main scanning direction is Is shaped so as to be smaller than the width of the spot-shaped region in the main scanning direction, irradiating the sample with the beam of excitation light, and scanning the plurality of spot-shaped regions with the excitation light. Then, the labeling substance is excited, and light emitted from the labeling substance contained in the plurality of spot-shaped regions is photoelectrically detected to generate data.

According to a preferred embodiment of the present invention, the width in the direction perpendicular to the main scanning direction is larger than the width in the direction perpendicular to the main scanning direction of the spot-like region, and the width in the main scanning direction is the spot. The beam of excitation light is shaped so that it becomes smaller than the width of the region in the main scanning direction, and the sample is irradiated, and the spot-shaped regions are scanned by the excitation light to excite the labeling substance. , The light emitted from the labeling substance contained in the plurality of spot-shaped regions is photoelectrically detected to generate data, so that one line of spots is formed by one main scan. The light emitted from the region of interest can be photoelectrically detected to generate data, and thus the data of the labeled substance labeling the sample contained in the sample can be read at high speed. Read Based on over data, in a short time, it is possible to complete the quantitative analysis.

In a preferred embodiment of the present invention, the plurality of spot-shaped regions are formed by a photostimulable phosphor that is selectively labeled with a radioactive labeling substance.

According to a preferred embodiment of the present invention, the photostimulative light emitted from one row of spot-like regions can be photoelectrically detected by one main scan to generate data. Therefore, it is possible to read the radiation data of the radio-labeled substance labeling the sample contained in the sample at high speed, and it is possible to complete the quantitative analysis in a short time based on the read radiation data. .

[0021] In a preferred aspect of the present invention, the plurality of spot-like regions selectively include at least one kind of fluorescent substance, and the plurality of spot-like regions are provided.
It is configured to scan with excitation light to excite the at least one fluorescent substance, and photoelectrically detect fluorescence emitted from the at least one fluorescent substance to generate data.

According to a preferred embodiment of the present invention, the fluorescence emitted from one row of spot-like regions can be photoelectrically detected by one main scan to generate data, and The fluorescence data of the fluorescent substance labeling the sample contained in the sample can be read at high speed, and the quantitative analysis can be completed in a short time based on the read fluorescence data.

In a further preferred aspect of the present invention, the sample is irradiated with a laser beam, the plurality of spot-shaped regions are scanned with the laser beam, and the sample is emitted from the plurality of spot-shaped regions. the light,
It is configured to photoelectrically detect and generate data.

[0024] In a preferred aspect of the present invention, the plurality of spot-shaped regions selectively include a labeling substance that causes chemiluminescence when brought into contact with a chemiluminescent substrate, and further, in the main scanning direction. The width in the vertical direction is larger than the width of the spot-shaped region in the direction perpendicular to the main scanning direction, and the width in the main scanning direction is smaller than the width of the spot-shaped region in the main scanning direction. Chemiluminescence emitted from the plurality of spot-shaped regions is passed through a spatial filter having an aperture,
It is configured to detect photoelectrically.

According to a preferred embodiment of the present invention, the width in the direction perpendicular to the main scanning direction is larger than the width in the direction perpendicular to the main scanning direction of the spot-shaped region, and the width in the main scanning direction is the spot. Through a spatial filter having an aperture smaller than the width in the main scanning direction of the region
Since the chemiluminescence emitted from a plurality of spot-shaped regions is photoelectrically detected, the chemiluminescence emitted from one row of the spot-shaped regions is photoelectrically detected by one main scan. Chemiluminescence data of a labeling substance that can be detected rapidly to generate data and, therefore, at a high rate, causing chemiluminescence to occur by contacting a sample contained in the sample with a chemiluminescent substrate that is labeled. It can be read, and the quantitative analysis can be completed in a short time based on the read chemiluminescence data.

In a further preferred aspect of the present invention, the light emitted from the plurality of spot-shaped regions is
The spatial filter is configured to focus the light on the aperture.

The object of the present invention is also a sample stage for mounting a sample having a plurality of spot-like regions which are formed at least one-dimensionally apart from each other and selectively contain a labeling substance. , A photodetector that photoelectrically detects light emitted from the plurality of spot-shaped regions and generates data, and relatively moves the photodetector and the sample stage in at least the main scanning direction. A scanning mechanism, the photodetector, the width in the direction perpendicular to the main scanning direction, the light emitted from a region larger than the width of the spot-shaped region in the direction perpendicular to the main scanning direction, Achieved by a scanner characterized by being configured to photoelectrically detect and generate data.

According to the present invention, the photodetector emits light emitted from a region in which the width in the direction perpendicular to the main scanning direction is larger than the width of the spot-like region in the direction perpendicular to the main scanning direction. Since it is configured to detect data photoelectrically and generate data, the scanning mechanism relatively moves the photodetector and the sample stage once in the main scanning direction to form one row. The light emitted from the spot-like areas of the can be photoelectrically detected to generate data, and thus the data of the labeling substance labeling the sample contained in the sample can be read at high speed. Can
Based on the read data, it becomes possible to complete the quantitative analysis in a short time.

In a preferred embodiment of the present invention, the sample includes a plurality of spot-like regions formed two-dimensionally and mutually spaced apart from each other, and the scanning mechanism comprises the main scanning direction and the main scanning direction. It is configured to relatively move the photodetector and the sample stage in a sub-scanning direction perpendicular to the scanning direction.

In a preferred embodiment of the present invention, the scanner further comprises an excitation light source which, together with the photodetector, forms an optical unit and emits excitation light, and the scanning mechanism comprises the optical unit and the sample stage. And at least in the main scanning direction, is configured to move relatively, further, the optical unit, the excitation light emitted from the excitation light source, the beam width in a direction perpendicular to the main scanning direction, , A focusing optical system for shaping the spot-shaped region so as to be larger than a width of the spot-shaped region in a direction perpendicular to the main scanning direction, and condensing the spot-shaped region on the sample, The excitation light shaped by the condensing optical system scans the plurality of spot-shaped areas and detects the light emitted from the plurality of spot-shaped areas. Vessel is configured to photoelectrically detecting.

According to a preferred embodiment of the present invention, the optical unit has a beam width of the excitation light emitted from the excitation light source in a direction perpendicular to the main scanning direction, which is perpendicular to the main scanning direction of the spot-like region. It is equipped with a condensing optical system that shapes the light so that it is larger than the width in the direction, and collects it on the sample.By the excitation light emitted from the excitation light source and shaped by the condensing optical system, multiple spots are formed. Since the photodetector photoelectrically detects the light emitted from the plurality of spot-shaped regions by scanning the region, the excitation light and the sample stage are moved once in the main scanning direction. , The light emitted from the one row of spot-like regions can be photoelectrically detected by the relative movement to generate data, and thus the sample contained in the sample can be detected at high speed. Be a sign That data of the labeled substance can be read, based on the read data, in a short time, it is possible to complete the quantitative analysis.

In a further preferred aspect of the present invention, the condensing optical system sets the excitation light so that the beam width is smaller than the width of the spot-shaped region in the main scanning direction. It is configured to focus on the sample.

In a further preferred aspect of the present invention, the excitation light source is a laser excitation light source.

In another preferred embodiment of the present invention, the excitation light source is an LED light source.

According to another preferred embodiment of the invention,
Since the LED light source is used as the excitation light source, it is possible to read the data of the radio-labeled substance and / or the fluorescent substance that label the sample contained in the sample at low cost and at high speed. Based on the data obtained, it becomes possible to complete the quantitative analysis in a short time.

In a further preferred aspect of the present invention, the optical unit further includes a spectral filter for cutting light emitted from the LED light source and having a wavelength component that does not contribute to excitation of the labeling substance. .

According to a further preferred embodiment of the present invention, the optical unit is provided with a spectral filter for cutting off light of a wavelength component which does not contribute to the excitation of the labeling substance,
Using an inexpensive LED light source, it is possible to read the data of the radiolabeled substance and / or the fluorescent substance labeling the sample contained in the sample as desired, and based on the read data, in a short time, It is possible to complete the quantitative analysis.

In a further preferred aspect of the present invention, the optical unit further includes an excitation light cut filter for cutting excitation light in an optical path of light emitted from the plurality of spot-shaped regions. .

In a preferred embodiment of the present invention, excitation light having a wavelength different from that of the excitation light emitted from the excitation light source of the optical unit is further provided at a position different from the optical unit in the main scanning direction. A second excitation light source that emits light, a second photodetector that photoelectrically detects light emitted from the plurality of spot-shaped regions, and generates data, and a beam width in a direction perpendicular to the main scanning direction. But,
A second shape that shapes the excitation light emitted from the second excitation light source so as to be larger than a width of the spot-shaped region in a direction perpendicular to the main scanning direction and collects the light on the sample. The second optical unit having the condensing optical system is provided.

According to a preferred embodiment of the present invention, a second excitation light having a wavelength different from that of the excitation light emitted from the excitation light source of the optical unit is provided at a position different from the optical unit in the main scanning direction. The excitation light source and the light emitted from the multiple spot-shaped areas are photoelectrically detected,
A second photodetector for generating data and a second excitation light source so that the beam width in the direction perpendicular to the main scanning direction is larger than the width of the spot-shaped region in the direction perpendicular to the main scanning direction. Since the second optical unit that has the second condensing optical system that shapes the excitation light emitted from the and collects it on the sample is efficiently excited by the excitation light of different wavelengths. Even if a sample is selectively labeled with two possible fluorescent substances, it is possible to read the data of the two labeling substances that label the sample contained in the sample at low cost and at high speed. Therefore, the quantitative analysis can be completed in a short time based on the read data.

In a further preferred aspect of the present invention, the second condensing optical system sets the beam width of the excitation light to be smaller than the width of the spot-shaped region in the main scanning direction. In addition, the light is focused on the sample.

In a further preferred aspect of the present invention, the second excitation light source is a laser excitation light source.

In another preferred embodiment of the present invention, the second excitation light source is an LED light source.

According to another preferred embodiment of the invention,
Since the LED light source is used as the second excitation light source,
It is possible to read the data of two kinds of fluorescent substances labeling the sample contained in the sample at low cost and at high speed, and to complete the quantitative analysis in a short time based on the read data. It will be possible.

In a further preferred aspect of the present invention, the second optical unit further comprises the second L unit.
A second spectral filter that cuts light having a wavelength component that does not contribute to the excitation of the labeling substance from the light emitted from the ED light source is provided.

According to a further preferred embodiment of the present invention, since the second optical unit is provided with the second spectral filter for cutting off the light of the wavelength component which does not contribute to the excitation of the labeling substance, an inexpensive LED light source is provided. Can be used to read the fluorescence data of two kinds of fluorescent substances labeling the sample contained in the sample, and the quantitative analysis can be completed in a short time based on the read fluorescence data. It will be possible.

In a further preferred aspect of the present invention, the second optical unit further includes an excitation light cut filter for cutting excitation light in an optical path of light emitted from the plurality of spot-shaped regions. I have it.

[0048] In a preferred aspect of the present invention, the optical unit is further arranged such that a width in a direction perpendicular to the main scanning direction is within the optical path of light emitted from the plurality of spot-shaped regions. A spatial filter having an aperture larger than the width of the spot-shaped region in the direction perpendicular to the main scanning direction and having a width in the main scanning direction smaller than the width of the spot-shaped region in the main scanning direction. .

According to a preferred embodiment of the present invention, the optical unit further includes, in the optical path of the light emitted from the plurality of spot-shaped regions, a spot-shaped region having a width in a direction perpendicular to the main scanning direction. Of the main scanning direction is larger than the width in the direction perpendicular to the main scanning direction, and the width in the main scanning direction is smaller than the width of the spot-shaped region in the main scanning direction. Chemiluminescence emitted from a row of spot-like regions can be photoelectrically detected to generate data,
Therefore, it is possible to read the chemiluminescence data of the labeling substance that causes chemiluminescence by contacting the sample contained in the sample with the labeling chemiluminescence substrate at a high speed. In time, it will be possible to complete the quantitative analysis.

[0050] In a further preferred aspect of the present invention, the optical unit further comprises a condensing optical system for condensing light emitted from the plurality of spot-shaped regions on the aperture of the spatial filter. ing.

[0051]

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

FIG. 1 is a schematic sectional view of a scanner according to a preferred embodiment of the present invention.

In the scanner according to the present embodiment, a specific binding substance such as cDNA is dropped on a slide glass plate to form a large number of spot-shaped regions, which are labeled with a fluorescent substance such as a fluorescent dye. This substance is selectively hybridized with a specific binding substance contained in a large number of spot-like regions, and the fluorescence data of the fluorescent substance carried on the generated microarray can be read. In an aspect, in order to reliably prevent the generation of noise in the data when the excitation light is detected, after the excitation light is irradiated, even if the excitation light is not irradiated, the fluorescent substance is continuously emitted. The fluorescence data is read by photoelectrically detecting the delayed fluorescence.

Therefore, in the present embodiment, the sample emits delayed fluorescence S over a relatively long period of time.
Labeled with YPRO Ruby®.

As shown in FIG. 1, the scanner according to the present embodiment has an optical unit 1 and a sample stage 2 on which a microarray (not shown) as a sample is mounted.
Is equipped with.

As shown in FIG. 1, the optical unit 1
Includes a casing 3, and inside the casing 3, an LED light source 4 that emits excitation light, a convex lens 5, and an LED light source 4
The convex lens 5 is provided with a spectral filter 7 that cuts a wavelength component that does not contribute to the excitation of the fluorescent substance contained in the excitation light 6 formed into a parallel beam, and a convex lens 8 that condenses the excitation light 6. There is.

FIG. 2 is a schematic perspective view of a microarray carrying fluorescence data to be read by the scanner according to this embodiment.

As shown in FIG. 2, the microarray 1
0 is the slide glass plate 11 and the slide glass plate 11
A plurality of regularly formed spot-shaped regions 12 are provided on the top, and each spot-shaped region 12 is formed in a substantially circular shape having a diameter D.

The plurality of spot-like regions 12 are, for example,
It is formed on the slide glass plate 11 as follows.

First, the surface of the slide glass plate 11 is pretreated, and then a sample solution containing a plurality of cDNA binding probes each having a known base sequence and different from each other is put on the slide glass plate 11. Using a potter device, drop in spots.

On the other hand, RNA, which is a sample, was extracted from living cells, and m having poly A at the 3'end was further extracted from RNA.
Extract RNA. When cDNA was synthesized from the thus extracted mRNA having poly A at the end, SYPRO Ruby (registered trademark), which is a labeling substance, was allowed to exist,
Generate target DNA labeled with SYPRO RUBY®.

The solution containing the target DNA thus prepared is gently placed on the surface of the slide glass plate 11 on which the cDNA probe has been dropped, and hybridized.

As a result, the target DNA selectively binds specifically to the cDNA probe, and the spot-like regions 12 are selectively labeled with SYPRO Ruby (registered trademark).

Here, SYPRO Ruby is 473
Since it can be excited most efficiently by a laser having a wavelength of nm, an LED light source having an emission wavelength center at 473 nm is selected as the LED light source 4, and light having a wavelength near 473 nm is selected as the spectral filter 7. Transparent,
A spectral filter having a property of cutting light of other wavelengths is selected.

FIG. 3 is a schematic plan view showing the shape of the bottom wall of the casing 3 which constitutes the optical unit 1.

As shown in FIG. 3, a rectangular aperture 15 is formed on the bottom wall of the casing 3, and the excitation light 6 is irradiated to the microarray 10 via the aperture 15. .

As shown schematically in FIG. 3, the long side L of the excitation light 6 emitted from the LED light source 4 has a diameter D of the spot-like region 12 formed in the microarray 10.
Larger than that, and its short side W is smaller than the diameter D of the spot-shaped region formed in the microarray 10, and is shaped into a rectangular shape by the convex lens 8 and is formed on the microarray 10 via the aperture 15. It is configured to collect light.

The sample stage 2 is moved by an arrow X in FIG. 1 by a sample stage scanning mechanism (not shown).
It is configured to be movable in the main scanning direction indicated by and in the sub-scanning direction perpendicular to the paper surface. Therefore, by only moving the sample stage 2 once in the main scanning direction indicated by the arrow X in FIG. One row of spot-like regions 1 of the microarray 10 placed on the sample stage 2
2 through the aperture 15 by the convex lens 8,
Scanning is performed by the excitation light 6 shaped into a rectangular shape, the fluorescent substance contained in the spot-shaped region 12 is excited, and fluorescence is emitted.

As shown in FIG. 1, the fluorescent substance contained in the microarray 10 which is a sample is further emitted into the casing 3 of the optical unit 1, passes through the aperture 15, and enters the optical unit 1. Fluorescent 9
A convex lens 16 for condensing light, a spectral filter 17 having a property of cutting light having a wavelength of the excitation light 6 and transmitting light having a wavelength longer than that of the excitation light, and detecting fluorescent light 9 photoelectrically to obtain analog data. A photomultiplier 18 for generating

Here, SYPRO Ruby is 473
Since it can be efficiently excited by a laser having a wavelength of nm, a spectral filter having a property of cutting light having a wavelength of 473 nm and transmitting light having a wavelength longer than 473 nm is selected as the spectral filter 17. ing.

The analog data generated by the photomultiplier 18 is input to the A / D converter 19,
It is digitized by the A / D converter 19 and output to the data processing device 20.

FIG. 4 is a block diagram showing the control system, input system, detection system, and drive system of the scanner according to the preferred embodiment of the present invention.

As shown in FIG. 4, the scanner control system according to this embodiment includes a control unit 25 for controlling the operation of the entire scanner, and the scanner input system includes a keyboard 26.

As shown in FIG. 4, the detection system of the scanner according to this embodiment includes a photomultiplier 18, and the drive system of the scanner includes the sample stage 2 and the sample stage 2.
, A sample stage scanning mechanism 2 for moving in a main scanning direction indicated by an arrow X and a sub scanning direction perpendicular to the paper surface.
Equipped with 7.

The control unit 25 is configured to turn on / off the LED excitation light source 4 and the photomultiplier 18.

The scanner according to this embodiment configured as described above reads the data of the fluorescent substance carried by the microarray 10 and generates digital data as follows.

First, SYPRO RUBY (registered trademark)
A plurality of spot-like regions 12 selectively labeled by
The microarray on which is formed is placed on the sample stage 2 by the user.

Then, the keyboard 2 is set by the user.
When the reading start signal is input to 6, the reading start signal is output to the control unit 25, and the control unit 25 activates the LED light source 4,
Excitation holes 6 having an emission wavelength center at 473 nm are emitted.

The excitation light 6 emitted from the LED light source 4 is
After being made into a parallel beam by the convex lens 5, it is incident on the spectral filter 7.

The spectral filter 7 is an S for labeling the sample.
Does not contribute to excitation of YPRO RUBY (registered trademark) 4
SYPRO cuts light with wavelength components near 73 nm
Since it has a property of transmitting light having a wavelength near 473 nm that can efficiently excite RUBY, only light having a wavelength near 473 nm passes through the spectral filter 7 and enters the convex lens 8.

The exciting light 6 has a long side L larger than the diameter D of the spot-like region 12 formed in the microarray 10 and a short side W thereof due to the convex lens 8 in the spot-like region formed in the microarray 10. Via a rectangular aperture 15 formed in the bottom wall of the casing 3 so as to be smaller than the diameter D of 12 through a rectangular shape.
Microarray 10 mounted on the sample stage 2
Is focused.

In the present embodiment, the excitation light 6 has the longer side L larger than the diameter D of the spot-like region 12 formed on the microarray 10 and the short side W formed on the microarray 10 by the convex lens 8. The sample stage 2 is shaped into a rectangular shape so as to be smaller than the diameter D of the formed spot-shaped region 12, and the sample stage 2 is first moved by the sample stage scanning mechanism 16 in FIG.
1 is moved in the main scanning direction, the sample stage 2 is moved once in the main scanning direction indicated by an arrow X in FIG. By scanning with the excitation light 6, it is possible to excite the fluorescent substance labeling the sample contained in the one row of spot-like regions.

When the excitation light 6 is irradiated, the fluorescent substance labeling the sample contained in each spot-shaped region is excited and the fluorescence 9 is emitted.

The fluorescent light 9 emitted from the fluorescent substance labeling the sample contained in each spot-shaped region passes through the aperture 15 and enters the convex lens 16 provided in the optical unit 1.

The fluorescent light 9 is condensed by the convex lens 16 and enters the spectral filter 17.

The spectral filter 17 is a SYPRO RUB.
473 nm used to excite Y®
Of SYPRO RUBY has a wavelength longer than 473 nm used to excite SYPRORUBY. Therefore, the light of the wavelength of 473 nm used for exciting SYPRO RUBY is cut, and SYPRO R
Only the fluorescence 9 emitted from UBY (registered trademark) passes through the spectral filter 17 and enters the photomultiplier 18.

However, when the excitation light 6 cannot be completely cut by the spectral filter 17, the excitation light 6 which is not cut by the spectral filter 17 is used.
However, since the photomultiplier 18 photoelectrically detects and noise is generated in the data, in the present embodiment, the photomultiplier 18 is controlled by the control unit 25 while the excitation light 6 is being irradiated. Fluorescence emitted from the fluorescent substance 9 which is kept in the off state
The photomultiplier 18 is not detected.

When the predetermined irradiation time elapses, the control unit 25 turns off the LED light source 4 and
The photomultiplier 18 is turned on.

As a result, after the LED light source 4 is turned off, the SYPRO RU which is subsequently labeling the sample
Delayed fluorescent light 9 emitted from BY (registered trademark) is collected by a convex lens 16 through an aperture 15 of the optical unit 1, transmitted through a spectral filter 17, and photoelectrically detected by a photomultiplier 18. , Analog data is generated.

The analog data generated by the photomultiplier 18 is input to the A / D converter 19,
It is digitized by the A / D converter 19 and output to the data processing device 20.

In this manner, the control unit 25 controls the ON / OFF of the LED light source 4 and the photomultiplier 18, and the sample stage scanning mechanism 2
The sample stage 2 is moved in the main scanning direction indicated by the arrow X in FIG. 1 by 7, and the one row of spot-like regions 12 formed on the microarray 10 is scanned by the excitation light 6 to label the sample. SYPRO
RUBY (registered trademark) is excited, and the emitted delayed fluorescence 9 is photoelectrically detected by the photomultiplier 18, and SYPRO labeling the sample contained in the spot-like region 12 of the first row. When the fluorescence data of RUBY is read, the LED light source 4 and the photomultiplier 18 are turned off, and the sample stage scanning mechanism 27
As a result, the sample stage 2 is moved in the sub-scanning direction by a distance equal to the interval between the spot-like regions 12 adjacent to each other in the sub-scanning direction perpendicular to the paper surface in FIG.

Next, while the LED light source 4 is on / off controlled, the sample stage 2 is moved by the sample stage scanning mechanism 27 in the direction opposite to the direction indicated by the arrow X in FIG. The spot-shaped region 12 in the second row is scanned by the excitation light 6, and SYPRO RUBY (registered trademark) labeling the sample contained in the spot-shaped region 12 is excited by the excitation light 6. The emitted delayed fluorescent light 9 excites SYPRO RUBY included in the spot-like regions 12 of the first row formed in the microarray 10,
Just like the delayed fluorescence 9 emitted, the photomultiplier 18 photoelectrically detects and generates analog data, and the A / D converter 19 digitizes and outputs it to the data processing device 20. To be done.

By repeating the same operation, the n rows of spot-like regions 12 formed on the microarray 10 are scanned by the excitation light 6 shaped into a rectangular shape, and the sample contained in the spot-like regions 12 is labeled. Doing SYPRO R
The delayed fluorescence 9 emitted from uby (registered trademark) is photoelectrically detected by the photomultiplier 18, and
Analog data is generated, digitized by the A / D converter 19, and output to the data processing device 20.

According to this embodiment, the long side of the excitation light 6 emitted from the LED light source 4 is in the microarray 10.
Larger than the diameter D of the spot-like region 12 formed in
The short side is shaped into a rectangular shape so that it is smaller than the diameter D of the spot-like region 12 formed in the microarray 10, and is condensed on the microarray 10 via the aperture 15 to form the microarray 10. Since it is configured to excite the fluorescent substance contained in the plurality of spot-shaped regions 12 formed, the sample stage 2
1 is moved once in the main scanning direction indicated by arrow X in FIG. 1, so that one row of spot-like regions 12 formed on the microarray 10 is scanned by the excitation light 6 and is included in the spot-like regions 12. The fluorescent substance contained in the sample can be excited, and thus, the data of the fluorescent substance labeling the sample contained in the sample can be read at high speed.

Further, according to the present embodiment, since it is not necessary to focus the excitation light on the minute area on the sample, the LED light source 4 can be used as the excitation light source, and therefore at low cost and It becomes possible to read the data of the fluorescent substance labeling the sample contained in the sample at high speed.

In this embodiment, the control unit 25 controls the ON / OFF of the LED light source 4 and the photomultiplier 18, and after the LED light source 4 is turned off, the sample is labeled SYPRO.
Since the photomultiplier 18 photoelectrically detects the delayed fluorescence 9 emitted from RUBY (registered trademark), the photomultiplier 18
It is possible to reliably prevent the noise caused by detecting the excitation light 6 from being generated in the data.

FIG. 5 is a schematic sectional view of a scanner according to another preferred embodiment of the present invention.

As shown in FIG. 5, the scanner according to this embodiment comprises a first optical unit 30, a second optical unit 31, and a sample stage 32. And the second optical unit 3
1 in the main scanning direction indicated by arrow X in FIG.
They are provided separately from each other.

As shown in FIG. 4, the first optical unit 30 has an LED light source 34 and a convex lens 3 inside a casing 33, just like the optical unit 1 shown in FIG.
5, an optical system for irradiating the sample with the excitation light 36 configured by the spectral filter 37 and the convex lens 38, and detection optics for detecting fluorescence 39 configured by the convex lens 40, the spectral filter 41, and the photomultiplier 42. It has a system.

As shown in FIG. 5, the second optical unit 31 has an LED light source 54 and a convex lens 5 inside a casing 53, just like the optical unit 1 shown in FIG.
5, an optical system for irradiating the sample with the excitation light 56 composed of the spectral filter 57 and the convex lens 58, and detection optics for detecting the fluorescence 59 composed of the convex lens 60, the spectral filter 61 and the photomultiplier 62. It has a system.

FIG. 6 is a schematic perspective view of a biochemical analysis unit carrying fluorescence data to be read by the scanner according to this embodiment.

As shown in FIG. 6, the biochemical analysis unit 70 includes a substrate 71 made of aluminum.
The substrate 71 is regularly formed with through holes filled with an absorptive material such as nylon 6 to form a plurality of dot-shaped absorptive regions 72.

Although not shown exactly in FIG. 6, in this embodiment, 50 / adhesive regions 72 each having a substantially circular adsorbing region 72 having a diameter of about 100 square millimeters / min.
The dots are formed on the substrate 71 with a density of square centimeters.

Fluorescence data is recorded in the plurality of dot-shaped absorptive regions 72 of the biochemical analysis unit 70, for example, as follows.

First, a sample solution containing a plurality of different DNA probes whose base sequences are known is dropped onto a plurality of absorptive regions 72 using a spotter device.

On the other hand, RNA, which is a sample, was extracted from living cells, and m having poly A at the 3'end was further extracted from RNA.
Extract RNA. When the cDNA thus synthesized is synthesized from the mRNA having poly A at the terminal, Cy3 (registered trademark) as a labeling substance is allowed to be present to generate the first target DNA labeled with Cy3.

On the other hand, RNA as a sample is extracted from living cells, and mRNA having poly A at the 3'end is extracted from RNA. When the cDNA thus synthesized is synthesized from the mRNA having poly A at the end, Cy5 (registered trademark), which is a labeling substance, is allowed to exist and Cy5 is added.
To produce a second target DNA labeled by.

The first target DN thus prepared
A and the second target DNA are mixed, and the mixed solution is gently placed on the surface of the substrate 71 to form a plurality of absorptive regions 72.
It hybridizes to the cDNA probe which is the specific binding substance dropped onto the.

As a result, the target DNA selectively and specifically binds to the cDNA probe, and a plurality of dot-shaped absorptive regions 72 are formed in Cy3 (registered trademark) and Cy.
5 (registered trademark).

Here, Cy3 (registered trademark) is 532n.
Since light having a wavelength of m can be most efficiently excited, an LED light source having an emission wavelength center at 532 nm is selected as the LED light source 34, and light having a wavelength near 532 nm is selected as the spectral filter 37. A spectral filter having a property of transmitting light and cutting light of other wavelengths is selected. Further, as the spectral filter 41,
A spectral filter having a property of cutting light having a wavelength of 532 nm and transmitting light having a wavelength longer than 532 nm is selected.

On the other hand, Cy5 (registered trademark) has 6
Since it can be excited most efficiently by light having a wavelength of 35 nm, the LED light source 54 has a wavelength of 635 nm.
An LED light source having an emission wavelength center is selected as the spectral filter 57, and a spectral filter having a property of transmitting light having a wavelength near 635 nm and cutting light having other wavelengths is selected as the spectral filter 57. Further, as the spectral filter 61, a spectral filter having a property of cutting light having a wavelength of 635 nm and transmitting light having a wavelength longer than 635 nm is selected.

FIG. 7 is a schematic plan view showing the shape of the bottom wall of the casing 33 which constitutes the first optical unit 30.

As shown in FIG. 7, a rectangular aperture 45 is formed on the bottom wall of the casing 33 of the first optical unit 30, and the biochemical analysis unit 70 is excited through the aperture 45. The light 36 is configured to be emitted.

As shown schematically in FIG. 7, the excitation light 3
6, the long side L is larger than the diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70, and the short side W is formed in the biochemical analysis unit 70. The convex lens 38 shapes the rectangular shape so as to be smaller than the diameter D of each of the plurality of absorptive regions 72,
The light is focused on the biochemical analysis unit 70 via the aperture 45 formed on the bottom wall of the casing 33.

An aperture 65 exactly the same as the aperture 45 is formed on the bottom wall of the casing 53 constituting the second optical unit 31, and the long side L of the aperture 45 is used for biochemical analysis. It is larger than the diameter D of each of the plurality of absorptive regions 72 formed in the unit 70, and its short side W is larger than the diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70. The excitation light 36 shaped into a rectangular shape so as to be small is configured to irradiate the biochemical analysis unit 70.

The sample stage 32 is configured to be movable by the sample stage scanning mechanism (not shown) in the main scanning direction indicated by the arrow X in FIG. 5 and the sub-scanning direction perpendicular to the paper surface. By moving the sample stage 32 once in the main scanning direction indicated by the arrow X in FIG. 5, the absorptive region 72 of one row of the biochemical analysis unit 70 placed on the sample stage 32 is removed. , And is scanned by the excitation light 36 shaped into a rectangular shape through the aperture 45, and the excitation light 56 shaped into a rectangular shape via the aperture 65.
The fluorescent substance contained in the absorptive region 72 is excited by the scanning with the fluorescent substance to emit fluorescence.

The analog data generated by the photomultipliers 42 and 62 is input to the A / D converter 75 and digitized by the A / D converter 75.
It is output to the data processing device 76.

The control system, input system, detection system, and drive system of the scanner according to this embodiment have exactly the same construction as in FIG.

The scanner according to the present embodiment configured as described above reads the data of the fluorescent substance carried by the biochemical analysis unit 70 and produces digital data as follows.

First, the biochemical analysis unit 70, which is a sample, is placed on the sample stage 32 by the user.

Then, the LED light source 34 of the first optical unit 30 is activated by the user, and the LED light source 3
Excitation light 36 having an emission wavelength center from 4 to 532 nm
Is emitted.

The excitation light 36 is made into a parallel beam by the convex lens 35, and then enters the spectral filter 37.

The spectral filter 37 cuts light having a wavelength component that does not contribute to excitation of Cy3 (registered trademark) labeling the sample, and transmits light having a wavelength near 532 nm that can efficiently excite Cy3. 532n because it has
Only light having a wavelength in the vicinity of m passes through the spectral filter 37 and enters the convex lens 38.

The long side L of the excitation light 36 is larger than the diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70 by the convex lens 38, and the short side W thereof is generated. To be smaller than the diameter D of each of the plurality of absorptive regions 72 formed in the chemical analysis unit 70,
The light is focused on the biochemical analysis unit 70 via the rectangular aperture 45 formed in the bottom wall of the casing 33, which is shaped like a rectangle.

On the other hand, the sample stage 32 is moved by the sample stage drive mechanism 27 in FIG.
Since it is moved in the main scanning direction shown by, the excitation light 36 shaped into a rectangular shape is irradiated through the aperture 45 to the microarray mounted on the sample stage 32.

Also in this embodiment, the excitation light 36 has a long side L larger than each diameter of the absorptive regions 72 formed in the biochemical analysis unit 70 and a short side W thereof.
Absorptive region 72 formed in the biochemical analysis unit 70
The sample stage 32 is shaped in a rectangular shape so as to be smaller than the diameter of each sample, and the sample stage 32 is moved in the main scanning direction indicated by an arrow X in FIG. Stage 32
5 is moved once in the main scanning direction indicated by arrow X in FIG. 5, so that one row of the absorptive regions 72 formed in the biochemical analysis unit 70 is passed through the rectangular aperture 45. The fluorescent substance contained in the absorptive region 72 can be excited by scanning with the excitation light 36 shaped into a rectangular shape.

When the excitation light 36 is irradiated, Cy3 (registered trademark) contained in the absorptive region 72 is excited and fluorescence 39 is emitted.

The fluorescence 39 emitted from Cy3 contained in the absorptive region 72 passes through the aperture 45 and enters the convex lens 40 provided in the first optical unit 30.

The fluorescent light 39 is condensed by the convex lens 40 and enters the spectral filter 41.

The spectral filter 41 cuts the light of 532 nm used for exciting Cy3, and cuts the light of 532 nm.
Has the property of transmitting light with a longer wavelength than
The fluorescence 39 emitted from 3 (R) has a wavelength longer than 532 nm used to excite Cy3, and thus was used to excite Cy3 53.
Only the fluorescence 39 emitted from Cy3 after the light of the wavelength of 2 nm is cut is transmitted through the spectral filter 41 and is incident on the photomultiplier 42, which is photoelectrically detected by the photomultiplier 42 and converted into analog data. Is generated.

The analog data generated by the photomultiplier 42 is input to the A / D converter 75,
It is digitized by the A / D converter 75, output to the data processing device 76, and stored in a memory (not shown).

In this way, the first-row absorptive region 72 formed in the biochemical analysis unit 70 is scanned by the excitation light 36, and Cy3 (registered trademark) contained in the absorptive region 72 is excited. The emitted fluorescence 39 is photoelectrically detected by the photomultiplier 42, and the generated analog data is digitized by the A / D converter 75, and the memory of the data processing device 76 (not shown). LED light source 34 and photomultiplier 42 are turned off and the sample stage 32 is
It is further sent to the second optical unit 31 by the sample stage drive mechanism 27.

In the control unit 25, the sample stage 32 is the casing 5 of the second optical unit 31.
The LED light source 54 is activated at the timing when the LED light source 54 is moved below the aperture 65 formed in FIG.

As a result, the LE of the second optical unit 31 is
Excitation light 56 having an emission wavelength center at 635 nm is emitted from the D light source 54, is made into a parallel beam by the convex lens 55, and is then incident on the spectral filter 57.

The spectral filter 57 has a property of cutting light having a wavelength component that does not contribute to the excitation of Cy5 (registered trademark) labeling the sample and transmitting light having a wavelength near 635 nm that can efficiently excite Cy5. Has 635n
Only light having a wavelength near m is transmitted through the spectral filter 57 and is incident on the convex lens 58.

The long side L of the excitation light 56 is larger than the diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70 by the convex lens 58, and the short side W thereof is generated. To be smaller than the diameter D of each of the plurality of absorptive regions 72 formed in the chemical analysis unit 70,
The light is focused on the biochemical analysis unit 70 via a rectangular aperture 65 formed in the bottom wall of the casing 53 and shaped into a rectangle.

Also in the second optical unit 31, the excitation light 56 is exactly the same as in the first optical unit 30.
The long side L thereof is larger than the diameter of each of the absorptive regions 72 formed in the biochemical analysis unit 70, and the short side W thereof.
Is shaped into a rectangular shape so as to be smaller than the diameter of each of the absorptive regions 72 formed in the biochemical analysis unit 70, and the sample stage 32 is moved by the sample stage scanning mechanism 27 in FIG. , The sample stage 3 is moved in the main scanning direction indicated by the arrow X.
2 in the main scanning direction indicated by arrow X in FIG.
By moving it once, the biochemical analysis unit 70
The one row of the absorptive regions 72 formed on the substrate is excited by the excitation light 56 shaped into a rectangular shape through the rectangular aperture 65.
The fluorescent substance contained in the absorptive region 72 can be excited by scanning with.

When irradiated with the excitation light 36, Cy5 (registered trademark) contained in the absorptive region 72 is excited and fluorescence 59 is emitted.

The fluorescence 39 emitted from Cy5 contained in the absorptive region 72 passes through the aperture 65 and enters the convex lens 60 provided in the second optical unit 31.

The fluorescent light 59 is condensed by the convex lens 60 and enters the spectral filter 61.

The spectral filter 61 cuts the light of 635 nm used to excite Cy5, and cuts it to 635 nm.
Has the property of transmitting light with a longer wavelength than
The fluorescence 59 emitted from 5 (R) has a wavelength longer than the 635 nm used to excite Cy5, and thus was used to excite Cy5 63.
Only the fluorescence 59 emitted from Cy5 with the light of the wavelength of 5 nm cut is transmitted through the spectral filter 61 and is incident on the photomultiplier 62, which is photoelectrically detected by the photomultiplier 62 and converted into analog data. Is generated.

The analog data generated by the photomultiplier 52 is input to the A / D converter 75,
The data is digitized by the A / D converter 75 and output to the data processing device 76.

In this way, the first-row absorptive region 72 formed in the biochemical analysis unit 70 is scanned by the excitation light 56, and Cy5 (registered trademark) contained in the absorptive region 72 is excited. The emitted fluorescence 59 is photoelectrically detected by the photomultiplier 62, and the generated analog data is digitized by the A / D converter 75, and the memory (not shown) of the data processing device 76. When stored in, the LED light source 54 and the photomultiplier 62 are turned off, and the sample stage scanning mechanism 27 causes the sample stage 32 to move the space between the spot-like regions adjacent to each other in the sub-scanning direction perpendicular to the paper surface in FIG. Is moved a distance equal to.

Next, the LED of the second optical unit 31
The light source 54 is activated again and the sample stage 32 is moved by the sample stage scanning mechanism 27.
In FIG. 5, the absorptive region 72 of the second row formed in the biochemical analysis unit 70 by being moved in the direction opposite to the direction indicated by the arrow X is the LE of the second optical unit 31.
Cy5 (registered trademark) included in the absorptive region 72 scanned by the excitation light 56 emitted from the D light source 54
However, the fluorescence 59 excited and emitted by the excitation light 56 excites Cy5 contained in the absorptive region 72 of the first row formed in the biochemical analysis unit 70 and emitted. In exactly the same manner as the fluorescence 59, it is photoelectrically detected by the photomultiplier 62, analog data is generated, digitized by the A / D converter 75, and output to the data processing device 76.

In this way, the absorptive region 72 of the second row formed in the biochemical analysis unit 70 is scanned by the excitation light 56 emitted from the LED light source 54 of the second optical unit 31, and the absorptive region is obtained. Cy5 (registered trademark) contained in 72 is excited, and the emitted fluorescence 59 is photoelectrically detected by the photomultiplier 62, and the generated analog data is detected by the A / D converter 75.
Once digitized and stored in memory (not shown) of data processor 76, LED light source 54 and photomultiplier 62 are turned off and sample stage scanning mechanism 27 causes sample stage 32 to move to the first optical unit. Sent to 30.

The sample stage 32 is the aperture 4 formed in the casing 33 of the first optical unit 30.
5, the control unit 25 activates the LED light source 34 of the first optical unit 30 again, and the sample stage 32 is moved by the sample stage scanning mechanism 27 in FIG. The absorptive region 72 of the second row, which is moved in the direction opposite to the direction indicated by the arrow X and is formed in the biochemical analysis unit 70, is the LED of the first optical unit 30.
Cy3 (registered trademark) included in the absorptive region 72 scanned by the excitation light 36 emitted from the light source 34
Is excited by the excitation light 36 and emitted fluorescence 3
9 is excited by Cy3 contained in the absorptive region 72 of the first row formed in the biochemical analysis unit 70, and is exactly the same as the emitted fluorescence 39. Is detected, analog data is generated, digitized by the A / D converter 75, and output to the data processing device 76.

In this way, the absorptive area 72 of the second row formed in the biochemical analysis unit 70 is scanned by the excitation light 36 emitted from the LED light source 34 of the first optical unit 30, and the absorptive area is obtained. Cy3 (registered trademark) contained in 72 is excited, and the emitted fluorescence 39 is photoelectrically detected by the photomultiplier 42, and the generated analog data is detected by the A / D converter 75.
When digitized and stored in the memory (not shown) of the data processing device 76, the LED light source 34 and the photomultiplier 42 are turned off, and the sample stage scanning mechanism 27 causes the sub-scanning perpendicular to the paper surface in FIG. It is moved by a distance equal to the spacing between the spot-like areas adjacent in the direction.

By repeating the same operation, the m rows of absorptive regions 72 formed in the biochemical analysis unit 70 are excited by the excitation light 36 and the second light emitted from the LED light source 34 of the first optical unit 30. Fluorescence 3 emitted from Cy3 (registered trademark) and Cy5 (registered trademark) which are scanned by the excitation light 56 emitted from the LED light source 54 of the optical unit 31 and label the sample contained in the absorptive region 72.
9 and fluorescence 59 are photoelectrically detected by the photomultiplier 42 and the photomultiplier 62 to generate analog data, which are digitized by the A / D converter 75 and output to the data processing device 76. , Are stored in a memory (not shown).

According to the present embodiment, the long side L of the excitation light 36 emitted from the LED light source 34 is larger than the diameter D of the absorptive region 72 formed in the biochemical analysis unit 70. The rectangular aperture 45 formed in the bottom wall of the casing 33 is shaped into a rectangle so that the short side W is smaller than the diameter D of the absorptive region 72 formed in the biochemical analysis unit 70. Via, the fluorescent substance contained in the plurality of absorptive regions 72 formed on the biochemical analysis unit 70 and condensed on the biochemical analysis unit 70 is excited and emitted from the LED light source 54. The excitation light 56 has a long side L larger than the diameter D of the absorptive region 72 formed in the biochemical analysis unit 70, and a short side W thereof formed in the biochemical analysis unit 70. From the diameter D of the elastic region 72 Since the fluorescent substance contained in the plurality of absorptive regions 72 formed in the biochemical analysis unit 70 is excited so that the fluorescent substance is shaped into a rectangular shape so as to be small, the sample stage 32 is , Fig. 5
In the main scanning direction indicated by the arrow X, the one row of absorptive regions 72 formed in the biochemical analysis unit 70 is moved to the excitation light 36 and the excitation light 5
6 can excite the fluorescent substance contained in the adsorptive region 72, and therefore, it becomes possible to read the data of the fluorescent substance labeling the sample contained in the sample at high speed. .

Further, according to the present embodiment, since it is not necessary to focus the excitation light on the minute area on the sample, the LED light sources 34 and 54 can be used as the excitation light source, and therefore the cost can be reduced. Moreover, it becomes possible to read the data of the fluorescent substance labeling the sample contained in the sample at high speed.

Furthermore, when different target DNAs are labeled with two kinds of fluorescent substances and selectively bound to the probe DNAs and the generated fluorescence data is read, the excitation light sources having different wavelengths are switched. However, it is necessary to excite, which causes an increase in the cost of the scanner. According to the present embodiment, the first optical unit 30 and the second optical unit 31 are separated from each other in the main scanning direction and arranged side by side. Then, the sample stage 32 is attached to the first optical unit 3
0 and the second optical unit 31 are only moved in the main scanning direction and the sub-scanning direction, and Cy3
Since different target DNAs are labeled with Cy5 (registered trademark) and selectively bound to the probe DNAs and the generated fluorescence data is read, it is included in the sample at low cost and at high speed. It becomes possible to read the data of the fluorescent substance labeling the prepared sample.

FIG. 8 is a schematic sectional view of a scanner according to another preferred embodiment of the present invention.

As shown in FIG. 8, the scanner according to this embodiment includes an optical unit 80 and a sample stage 8
1 is provided, and a large number of stimulable phosphor layer regions are configured to be able to read the radiation data carried by the dot-shaped stimulable phosphor sheet.

FIG. 9 is a schematic perspective view of the stimulable phosphor sheet.

As shown in FIG. 9, the stimulable phosphor sheet 82 is provided with a support 83 made of oxygen-free copper, and the stimulable fluorescent material is provided in through holes regularly formed in the support 83. The body is filled to form a plurality of dot-shaped photostimulable phosphor layer regions 84.

Although not shown accurately in FIG. 9, in this embodiment, a substantially circular stimulable phosphor layer region 84 having a diameter of about 100 square millimeters is formed.
At a density of 50 pieces / square centimeter, on the support 83,
It is formed in a dot shape.

Radiation data is recorded in the stimulable phosphor layer region 84 of the stimulable phosphor sheet 82 in the following manner, for example.

First, using a spotter device, a sample solution containing a plurality of different cDNA probes having known base sequences was placed in a plurality of absorptive regions 72 of the biochemical analysis unit 70 shown in FIG. , Is dropped.

On the other hand, RNA, which is a sample, was extracted from living cells, and m having poly A at the 3'end was further extracted from RNA.
Extract RNA. When a cDNA is synthesized from the thus extracted mRNA having poly A at its end, a radioactive labeling substance is allowed to be present to generate a probe DNA labeled with the radioactive labeling substance.

The probe DNA labeled with the radioactive labeling substance thus obtained is adjusted to a predetermined solution, and the substrate 71
The sample is gently placed on the surface of, and selectively hybridized with the cDNA contained in the plurality of absorptive regions 72.

Next, the biochemical analysis unit 70 thus obtained is added to the stimulable phosphor sheet 82 shown in FIG.
A plurality of stimulable phosphor layer regions 84 are provided in each of the absorptive regions 72 formed in the biochemical analysis unit 70.
The radiolabeled substances contained in the plurality of absorptive regions 72 formed in the biochemical analysis unit 70 are released by being superposed so as to face each other and kept in a close contact state for a predetermined time. The stimulable phosphor layer region 84 is exposed to radiation (β rays), and the radiation data is recorded on the stimulable phosphor sheet 82.

As shown in FIG. 8, in this embodiment, the optical unit 80 includes a laser diode 86 which emits a laser beam 85 having a wavelength of 635 nm and a laser beam 85 which is emitted from the laser diode 86. The stimulable fluorescent light formed on the stimulable phosphor sheet 82 by cutting the light in the wavelength region of the laser light 85, which is the excitation light, and the convex lens 87 that collects light on the stimulable phosphor sheet placed on The photostimulable phosphor contained in the body layer region 84 is excited by the laser beam 85 and emitted, and the photostimulable phosphor 88 is emitted.
An excitation light cut filter 89 having a property of transmitting only the light in the wavelength range and a photomultiplier 90 for photoelectrically detecting the stimulated emission light 88 are provided.

FIG. 10 is a schematic plan view showing a state where the stimulable phosphor sheet 82 is irradiated with the laser light 85.

As shown in FIG. 10, the convex lens 87
Is the laser light 85 emitted from the laser diode 86.
On the stimulable phosphor sheet 82, the long side L is larger than the diameter D of the stimulable phosphor layer region 84, and the short side W is smaller than the diameter D of the stimulable phosphor layer region 84. It is configured to collect light in a rectangular shape.

The scanner according to the present embodiment having the above-described structure is constructed as follows, and the stimulable phosphor sheet 8 is used.
2. Read the radiation data carried by 2.

First, the stimulable phosphor sheet 82 is placed on the sample stage 81 by the user.

Then, the laser diode 86 is activated, and the laser diode 86 emits the laser light 85 having a wavelength of 635 nm.

The laser light 85 is projected by the convex lens 87.
The long side L is larger than the diameter D of the stimulable phosphor layer region 84, and the short side W is smaller than the diameter D of the stimulable phosphor layer region 84. The light is focused on the phosphor sheet 82.

On the other hand, the sample stage 81 is moved in the main scanning direction indicated by arrow X in FIG. 8 by the sample stage scanning mechanism (not shown). By moving the photostimulable phosphor layer region 84 for one row formed in the stimulable phosphor sheet 82 by the laser light 85 once by moving the photostimulable phosphor in the main scanning direction shown by The stimulable phosphor contained in the layer region 84 can be excited.

Upon irradiation with the laser beam 85, the stimulable phosphor contained in the stimulable phosphor layer region 84 is excited and the stimulable light 88 is emitted.

The photostimulable light 88 excited by the laser light 85 and emitted from the photostimulable phosphor contained in the photostimulable phosphor layer region 84 enters the excitation light cut filter 89.

Since the excitation light cut filter 89 has a property of cutting off the light in the wavelength range of the laser light 85 which is the excitation light and transmitting only the light in the wavelength range of the stimulated emission light 88, the laser light 85 The light in the wavelength range is cut off, and only the photostimulable light 88 emitted from the photostimulable phosphor contained in the photostimulable phosphor layer region 84 enters the photomultiplier 90, and the photomultiplier 90 Are detected photoelectrically and generate analog data.

The analog data generated by the photomultiplier 90 is digitized by the A / D converter 91 and output to the data processing device 92.

The sample stage 81 is moved by the sample stage scanning mechanism (not shown) in the main scanning direction indicated by the arrow X in FIG. 8 to form a row of bright lines formed on the stimulable phosphor sheet 82. Exhaust Phosphor Layer Area 84
Is scanned by the laser light 85, the stimulable phosphor contained in the stimulable phosphor layer region 84 is excited, and the emitted stimulable light 88 is photoelectrically converted by the photomultiplier 90. When the radiation data detected and read in the stimulable phosphor layer region 84 of the first row is read,
When the laser diode 86 is turned off, the sample stage scanning mechanism causes the sample stage 81 to move a distance equal to the distance between the photostimulable phosphor layer regions 84 adjacent to each other in the sub-scanning direction perpendicular to the paper surface in FIG. It is moved in the scanning direction.

Then, the laser diode 86 is turned on, and the sample stage 81 is moved by the sample stage scanning mechanism in the direction opposite to the direction indicated by the arrow X in FIG. 8 to form on the stimulable phosphor sheet 82. The stimulable phosphor layer region 84 in the second row thus formed is irradiated with the laser beam 85.
The stimulable phosphor 88 contained in the stimulable phosphor layer region 84 is excited by the stimulable phosphor 88 and emitted.
Of the photomultiplier 9 in exactly the same manner as the photostimulable light 88 emitted from the photostimulable phosphor layer region 84 in the first row.
0 is photoelectrically detected to generate analog data, which is digitized by the A / D converter 91 and output to the data processing device 92.

By repeating the same operation, the stimulable phosphor layer region 84 of the k-th row formed on the stimulable phosphor sheet 82 is formed.
The photostimulable light 88 emitted from the photostimulable phosphor contained in
It is photoelectrically detected by the photomultiplier 90 to generate analog data, which is digitized by the A / D converter 91 and output to the data processing device 92.

According to this embodiment, the laser light 85 emitted from the laser diode 86 of the optical unit 80 is
The convex lens 87 irradiates a rectangular region whose long side L is larger than the diameter D of the stimulable phosphor layer region 84 and whose short side W is smaller than the diameter D of the stimulable phosphor layer region 84. Then, since the light is condensed on the stimulable phosphor sheet 82, it is formed on the stimulable phosphor sheet 82 by moving the sample stage 81 once in the main scanning direction indicated by an arrow X in FIG. One row of the stimulable phosphor layer area 84 can be scanned with the laser light 85 to excite the stimulable phosphor contained in the stimulable phosphor layer area 84, and therefore high speed Thus, it becomes possible to read the radiation data carried by the plurality of stimulable phosphor layer regions 84 of the stimulable phosphor sheet.

FIG. 11 is a schematic sectional view of a scanner according to still another preferred embodiment of the present invention.

The scanner according to the present embodiment is constructed so that the chemiluminescence data recorded in the biochemical analysis unit 70 shown in FIG. 6 can be read.

As shown in FIG. 11, the scanner according to the present embodiment comprises an optical unit 95 and a sample stage 96, and the sample stage 96 is provided with a sample stage scanning mechanism (not shown) in FIG. , And is configured to be movable in the main scanning direction indicated by the arrow X and the sub scanning direction perpendicular to the paper surface.

As shown in FIG. 11, the optical unit 9
5 includes a cooled CCD camera 97 and a dark box 98, an imaging lens 99 is provided in the dark box 98, and a spatial filter 100 is formed on the upper wall of the dark box 98.

A pair of slits 101, 101 are formed on the opposite side walls of the dark box 98, and the sample stage 96
Through the slit formed in the dark box 98
It is configured to be able to pass inside.

The chemiluminescence data is recorded in the biochemical analysis unit 70 shown in FIG. 6 as follows, for example.

First, a sample solution containing a plurality of different DNA probes whose base sequences are known is dropped onto a plurality of absorptive regions 72 formed in the biochemical analysis unit 70 using a spotter device. It

On the other hand, RNA, which is a sample, was extracted from living cells, and m having poly A at the 3'end was further extracted from RNA.
Extract RNA. When cDNA is synthesized from the thus extracted mRNA having poly A at its end, a labeling substance that causes chemiluminescence by contact with a chemiluminescent substrate is present, and chemiluminescence is generated by contacting with the chemiluminescent substrate. Target DNA labeled with the labeling substance is generated.

The thus-prepared solution containing the target DNA was gently placed on the surface of the substrate 71 and dropped onto the plurality of absorptive regions 72 as the specific binding substance cDN.
Hybridize to A probe.

As a result, the target DNA selectively and specifically binds to the cDNA probe, and the plurality of dot-shaped absorptive regions 72 are brought into contact with the chemiluminescent substrate by the labeling substance which causes chemiluminescence. , Selectively labeled.

FIG. 12 is a schematic front view of the spatial filter 100.

As shown in FIG. 12, the spatial filter 1
00 is constituted by a rectangular aperture 102 formed on the upper side wall 102 of the dark box 98, and the rectangular aperture 103 has a plurality of absorptive regions whose long sides L are formed in the biochemical analysis unit 70. 72 is larger than each diameter D, and the short side W thereof is the biochemical analysis unit 70.
It is formed on the upper side wall 102 of the dark box 98 so as to be smaller than the diameter D of each of the plurality of absorptive regions 72 formed in.

The scanner according to the present embodiment configured as described above reads the chemiluminescence data carried by the biochemical analysis unit 70 as follows.

First, on the sample stage 96, the chemiluminescent substrate is brought into contact with the labeling substance contained in the large number of dot-shaped absorptive regions 72 formed in the biochemical analysis unit 70 to emit chemiluminescence. The biochemical analysis unit 70 in operation is placed.

The sample stage scanning mechanism (not shown) moves the sample stage 96 into the dark box 98,
Chemiluminescence 105 emitted from one of the dot-shaped absorptive regions 72 formed in the biochemical analysis unit 70.
However, upon entering the imaging lens 99, the chemiluminescence 105 becomes
An image is formed on the photocathode of the cooled CCD camera 97 via the spatial filter 100.

The CCD (not shown) of the cooled CCD camera 97 receives the light of the image thus formed on the photocathode and stores it in the form of electric charge.

After a predetermined exposure time, the cooled CCD
The analog data accumulated in the CCD of the camera 97 in the form of electric charge is transferred to the A / D converter 106, digitized, and output to the data processing device 107.

In the present embodiment, the spatial filter 10
0 is constituted by a rectangular aperture 103 formed on the upper side wall 102 of the dark box 98, and the long side L of the rectangular aperture 103 has a biochemical analysis unit 7
0 is larger than the diameter D of each of the plurality of absorptive regions 72 formed in 0, and its short side W is smaller than the diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70. Since it is formed on the upper side wall 102 of the dark box 98 as shown in FIG.
By moving once in the main scanning direction indicated by the arrow X, the chemiluminescence 105 emitted from one row of the absorptive regions 72 formed in the biochemical analysis unit 70 is photoelectrically converted by the cooling CCD camera 97. Detection is performed to generate analog data, and the A / D converter 106 can generate digital data.

A sample stage scanning mechanism (not shown) moves the sample stage 96 in the main scanning direction indicated by the arrow X in FIG. 11 to form one line of the unit formed in the biochemical analysis unit 70. The chemiluminescence 105 emitted from the adsorptive region 72 is cooled by the cooled CCD camera 9.
When the chemiluminescence data detected photoelectrically and recorded in the absorptive region 72 of the first row is read by 7, the sample stage scanning mechanism causes the sample stage 96 to move vertically to the paper surface in FIG. It is moved in the sub-scanning direction by a distance equal to the distance between the adsorbing regions 72 adjacent in the sub-scanning direction.

Then, the sample stage 96 is changed to the one shown in FIG.
In, the chemiluminescence 105 emitted from the absorptive region 72 in the second row formed in the biochemical analysis unit 70 is moved in the direction opposite to the direction indicated by the arrow X.
Just like the chemiluminescence 105 emitted from the absorptive region 72 of the row, photoelectrically detected by the cooled CCD camera 97, analog data is generated and digitized by the A / D converter 106. And output to the data processing device 107.

By repeating the same operation, the chemiluminescence 105 emitted from the dot-shaped absorptive region 72 formed in the biochemical analysis unit 70 is cooled by the CCD camera 97.
Are photoelectrically detected by, to generate analog data, which are digitized by the A / D converter 106 and output to the data processing device 107.

According to this embodiment, the spatial filter 100
Is composed of a rectangular aperture 103 formed on the upper side wall 102 of the dark box 98, and the long side L of the rectangular aperture 103 has a plurality of adsorptive properties formed in the biochemical analysis unit 70. Diameter D of each of the regions 72
Is shorter than that of the biochemical analysis unit 7
Since the sample stage 96 is formed on the upper side wall 102 of the dark box 98 so as to be smaller than the diameter D of each of the plurality of absorptive regions 72 formed in 0, the sample stage 96 is indicated by an arrow X in FIG. The chemiluminescence 105 emitted from one row of the absorptive regions 72 formed in the biochemical analysis unit 70 by moving once in the main scanning direction,
The cooled CCD camera 97 can photoelectrically detect and generate analog data, and the A / D converter 106 can generate digital data. Therefore, chemiluminescence data can be read at high speed. Become.

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

For example, in the embodiment shown in FIGS. 1 to 4, a plurality of spot-shaped regions 12 are two-dimensionally formed on the surface of the slide glass plate 11, but a plurality of spot-shaped regions 12 are formed. It is not always necessary that the region 12 is formed two-dimensionally, and the plurality of spot-like regions 12 may be formed at least one-dimensionally on the surface of the slide glass plate 11.

In the embodiment shown in FIGS. 5 to 7 and the embodiments shown in FIGS. 10 and 11, a plurality of absorptive regions 72 are provided on the substrate 71 of the biochemical analysis unit 70. Although it is formed two-dimensionally, it is not always necessary that the plurality of absorptive regions 72 be formed two-dimensionally, and the plurality of absorptive regions 72 are formed on the substrate 71 of the biochemical analysis unit 70. In addition, it may be formed at least one-dimensionally.

Further, in the embodiment shown in FIGS. 8 to 10, a plurality of stimulable phosphor layer regions 84 are two-dimensionally formed on the support 83 of the stimulable phosphor sheet 82. However, it is not always necessary that the plurality of stimulable phosphor layer regions 84 are two-dimensionally formed on the support body 83 of the stimulable phosphor sheet 82, and at least one-dimensionally formed. Just do it.

Further, in the embodiment shown in FIGS. 1 to 4, the long side L of the excitation light 6 is larger than the diameter D of the spot-like region 12 formed in the microarray 10, and the short side thereof. W is shaped into a rectangular shape so as to be smaller than the diameter D of the spot-like region 12 formed in the microarray 10, and the W is irradiated onto the microarray 10.
In the embodiment shown in FIGS. 5 to 7, the excitation lights 36 and 56 have the long side L of the biochemical analysis unit 7.
The diameter is larger than the diameter D of the absorptive area 72 formed in 0, and the short side W is smaller than the diameter D of the absorptive area 72 formed in the biochemical analysis unit 70. Although shaped and irradiated on the biochemical analysis unit 70, the length in the direction perpendicular to the main scanning direction is formed on the spot-like region 12 formed on the microarray 10 and the biochemical analysis unit 70. Diameter D of the adsorptive area 72
It suffices that the excitation lights 6, 36, 56 be shaped so as to be larger than the above, and the excitation lights 6, 36, 56 can be shaped in a rectangular shape as well. However, it is not always necessary to shape the spot-shaped regions 12 formed in the microarray 10 and the absorptive regions 72 formed in the biochemical analysis unit 70 to be smaller than the diameter D.

Further, in the embodiment shown in FIGS. 1 to 4, the optical unit 1 is provided with the aperture 15, and in the embodiment shown in FIGS. 5 to 7,
First optical unit 30 and second optical unit 31
Are provided with apertures 45 and 65, respectively, but the optical unit 1, the first optical unit 30, and the second optical unit 31 have apertures 45, 6 and 6, respectively.
It is not always necessary to have 5.

Further, in the embodiment shown in FIGS. 8 to 10, the laser light 85 emitted from the laser diode 86 is placed on the stimulable phosphor sheet 82 and the long side L thereof is stimulable fluorescence. Larger than the diameter D of the body layer region 84,
The short side W is condensed into a rectangular shape smaller than the diameter D of the stimulable phosphor layer region 84, but the length in the direction perpendicular to the main scanning direction is the stimulable phosphor layer region 84. Of the stimulable phosphor sheet 8 so that the laser light 85 becomes larger than the diameter D of
It suffices that the laser beam 85 is focused in a rectangular shape so that the short side W of the laser beam 85 is smaller than the diameter D of the stimulable phosphor layer region 84. , Laser light 8
It is not always necessary that 5 is focused.

In the embodiment shown in FIGS. 11 and 12, the rectangular aperture 103 constituting the spatial filter 100 has a plurality of long sides L formed in the biochemical analysis unit 70. The diameter of the dark box 98 is larger than the diameter D of each of the absorptive regions 72, and the short side W thereof is smaller than the diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70. Although formed on the upper side wall 102, the length in the direction perpendicular to the main scanning direction is
It is sufficient that the aperture 103 is formed so as to be larger than the diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70.
It is also possible to form the aperture 103 with a rectangular shape.
It is not always necessary that the short side W of W is formed so as to be smaller than the diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70.

Furthermore, in the embodiment shown in FIGS. 1 to 4, the delayed fluorescence 9 emitted from the fluorescent substance is detected photoelectrically by the photomultiplier 18 after the irradiation of the excitation light 6 is completed. But delayed fluorescence 9
Is not necessarily detected, and the fluorescence emitted from the fluorescent substance may be photoelectrically detected when the excitation light 6 is irradiated.

Further, in the embodiment shown in FIGS. 5 to 7, the fluorescence 39, 59 emitted from the fluorescent substance when the excitation light 36, 56 is irradiated is converted into the photomultipliers 42, 62. However, delayed fluorescence emitted from the fluorescent substance may be detected photoelectrically after the irradiation of the excitation lights 36 and 56 is completed.

Further, in the embodiment shown in FIGS. 8 to 10, the laser light 85 emitted from the laser diode 86 is placed on the stimulable phosphor sheet 82 and the long side L thereof is stimulable fluorescence. Larger than the diameter D of the body layer region 84,
The short side W is condensed into a rectangular shape smaller than the diameter D of the stimulable phosphor layer region 84, and the long side L is on the bottom wall of the optical unit 80, and the stimulable phosphor layer. A rectangular aperture, which is larger than the diameter D of the region 84 and whose short side W is smaller than the diameter D of the stimulable phosphor layer region 84, is formed so that the laser beam 85 is focused on the aperture. Good.

In the embodiment shown in FIGS. 11 and 12, the sample stage 96 is conveyed in the dark box 98 via the slits 101, 101 formed in the opposite side walls of the dark box 98. However, the long side L of the bottom wall of the dark box 98 is larger than the diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70, and the short side W thereof is formed. , The diameter D of each of the plurality of absorptive regions 72 formed in the biochemical analysis unit 70
It is also possible to form a smaller aperture and allow the chemiluminescence 105 to enter the imaging lens 99 through the aperture.

Further, in the embodiment shown in FIGS. 1 to 4, the LED light source 4 is used as the excitation light source, and in the embodiment shown in FIGS. 5 to 7, the LED light source is used as the excitation light source. 34 and 54 are used, and in the embodiment shown in FIGS. 8 to 10, a laser diode 86 is used as the excitation light source, but instead of these, a halogen lamp is used as the excitation light source. It is also possible to use a spectral filter to cut wavelength components that do not contribute to excitation.

Further, in the embodiment shown in FIGS. 1 to 4, a sample solution containing cDNA probes, which are a plurality of different specific binding substances having known base sequences, is placed on the slide glass plate 11. Drop regularly, SY
Although the target DNA labeled with PRO RUBY (registered trademark) is hybridized with a cDNA probe, the fluorescent data recorded in the selectively labeled spot-like regions 12 is read by SYPRO Ruby (registered trademark). A biochemical analysis unit 7 shown in FIG.
0 onto a plurality of absorptive regions 72 and SYPRO RU
Target DNA labeled with BY (registered trademark)
To the SYP
The RO Ruby (registered trademark) may read the fluorescence data recorded in the selectively labeled adsorptive region 72.

Further, in the embodiment shown in FIGS. 8 to 10, the radiation data recorded in the plurality of absorptive regions 72 formed in the biochemical analysis unit 70 are
It is configured to be transferred to a plurality of dot-shaped stimulable phosphor layer regions 84 formed on the stimulable phosphor sheet 82 and read the radiation data recorded in the plurality of stimulable phosphor layer regions 84. However, the radiation data recorded in the plurality of absorptive regions 72 formed in the biochemical analysis unit 70 is transferred to the stimulable phosphor layer uniformly formed on the surface of the support 83, and the brightness is increased. It can also be configured to read the radiation data recorded in the exhaustive phosphor layer.

Further, in the embodiment shown in FIGS. 8 to 10, the radiation data recorded in the plurality of absorptive regions 72 formed in the biochemical analysis unit 70 is stored in the stimulable phosphor sheet 82. It is configured to transfer the formed dot-shaped stimulable phosphor layer regions 84 to read the radiation data recorded in the plurality of stimulable phosphor layer regions 84, but form a membrane filter. A target solution labeled with a radioactive labeling substance by regularly dropping a sample solution containing cDNA probes, which are different specific binding substances with known base sequences, on a substrate formed of a possible porous material. DNA is hybridized with a cDNA probe, and the porous substrate is selectively labeled with a radioactive labeling substance to record radiation data. The recorded radiation data is transferred to a plurality of dot-shaped stimulable phosphor layer areas 84 formed on the stimulable phosphor sheet 82, and the radiation recorded in the plurality of stimulable phosphor layer areas 84 is recorded. It can also be configured to read data.

Further, in the embodiment shown in FIGS. 5 to 7, the first optical unit 30 and the second optical unit 31 are provided and labeled with two kinds of fluorescent substances having different excitation wavelengths. Although the data of the sample is read, the sample is labeled with three or more kinds of fluorescent substances having different excitation wavelengths, and three or more kinds of LED light sources each having a different emission wavelength center of the emitted excitation light are provided. The optical units may be arranged side by side in the main scanning direction to read the fluorescence data.

[0217]

INDUSTRIAL APPLICABILITY According to the present invention, chemiluminescence can be obtained at low cost and at high speed by bringing a sample contained in a sample into contact with a radioactive labeling substance, a fluorescent substance, and / or a chemiluminescent substrate which are labeled. It is possible to provide a data reading method that can read data such as a labeling substance that causes the above, and can complete quantitative analysis in a short time based on the read data, and a scanner used therefor.

[Brief description of drawings]

FIG. 1 is a schematic cross-sectional view of a scanner according to a preferred embodiment of the present invention.

FIG. 2 is a schematic perspective view of a microarray carrying fluorescence data to be read by the scanner according to the present embodiment.

FIG. 3 is a schematic plan view showing a shape of a bottom wall of a casing which constitutes the optical unit.

FIG. 4 is a block diagram showing a control system, an input system, a detection system, and a drive system of the scanner according to the preferred embodiment of the present invention.

FIG. 5 is a schematic cross-sectional view of a scanner according to another preferred embodiment of the present invention.

FIG. 6 is a schematic perspective view of a biochemical analysis unit carrying fluorescence data to be read by a scanner according to another preferred embodiment of the present invention.

FIG. 7 is a schematic plan view showing the shape of the bottom wall of the casing that constitutes the first optical unit of the scanner according to another preferred embodiment of the present invention.

FIG. 8 is a schematic cross-sectional view of a scanner according to another preferred embodiment of the present invention.

FIG. 9 is a schematic perspective view of a stimulable phosphor sheet.

FIG. 10 is a schematic plan view showing a state in which laser light is irradiated onto the stimulable phosphor sheet.

FIG. 11 is a schematic sectional view of a scanner according to still another preferred embodiment of the present invention.

FIG. 12 is a schematic front view of a spatial filter.

[Explanation of symbols]

1 Optical unit 2 sample stage 3 casing 4 LED light source 5 convex lens 6 Excitation light 7 Spectral filter 8 convex lens 9 fluorescence 10 microarray 11 Slide glass plate 12 spot-shaped areas 15 Aperture 16 convex lens 17 Spectral filter 18 Photomultiplier 19 A / D converter 20 Data processing device 25 control unit 26 keyboard 27 Sample stage scanning mechanism 30 First optical unit 31 Second optical unit 32 sample stages 33 casing 34 LED light source 35 convex lens 36 Excitation light 37 Spectral filter 38 Convex lens 39 fluorescence 40 convex lens 41 Spectral filter 42 Photomultiplier 45 aperture 53 casing 54 LED light source 55 Convex lens 56 Excitation light 57 Spectral filter 58 Convex lens 59 Aperture 60 convex lens 61 Spectral filter 62 Photomultiplier 65 Aperture 70 Biochemical analysis unit 71 board 72 Adsorbable area 74 A / D converter 75 Data processing device 80 Optical unit 81 sample stage 82 Accumulative phosphor sheet 83 Support 84 Photostimulable phosphor layer region 85 laser light 86 Laser diode 87 Convex lens 88 bright light 89 Excitation light cut filter 90 Photomultiplier 91 A / D converter 92 Data processing device 95 Optical unit 96 sample stage 97 Cooled CCD camera 98 dark box 99 Imaging lens 100 spatial filters 101 slit 102 Upper wall of dark box 103 aperture 105 chemiluminescence 106 A / D converter 107 data processing device

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Claims (25)

[Claims] 1. A sample having a plurality of spot-like regions formed on a substrate at least one-dimensionally spaced apart from each other and selectively containing a labeling substance is scanned at least in the main scanning direction. In the data reading method of photoelectrically detecting light emitted from the plurality of spot-shaped areas to generate data, the width in the direction perpendicular to the main scanning direction is the spot-shaped areas. The method for reading data, characterized in that light emitted from a region larger than the width in the direction perpendicular to the main scanning direction is photoelectrically detected to generate data. 2. The plurality of spot-shaped regions are two-dimensionally formed so as to be spaced apart from each other, and the plurality of spot-shaped regions are sub-scanned perpendicularly to the main scanning direction and the main scanning direction. 2. The data according to claim 1, wherein the light emitted from the labeling substance contained in the plurality of spot-shaped areas is photoelectrically detected by scanning in the direction to generate data. How to read. 3. The beam of excitation light is shaped such that the width in the direction perpendicular to the main scanning direction is larger than the length of the spot-shaped region in the direction perpendicular to the main scanning direction, The sample is irradiated, the plurality of spot-shaped regions are scanned with excitation light to excite the labeling substance, and the light emitted from the labeling substance contained in the plurality of spot-shaped regions is photoelectrically converted. 3. The data reading method according to claim 1, wherein the data is generated by detecting the data. 4. The width in the direction perpendicular to the main scanning direction is larger than the width of the spot-shaped region in the direction perpendicular to the main scanning direction, and the width in the main scanning direction is the spot-shaped region. To be smaller than the width in the main scanning direction, the beam of excitation light is shaped, the sample is irradiated, the spot-like regions are scanned with the excitation light, and the labeling substance is excited. 4. The data reading method according to claim 3, wherein the light emitted from the labeling substance contained in the plurality of spot-shaped regions is photoelectrically detected to generate data. 5. The data reading according to claim 3, wherein the plurality of spot-shaped regions are formed by a photostimulable phosphor that is selectively labeled with a radioactive labeling substance. Method. 6. The plurality of spot-like regions selectively include at least one kind of fluorescent substance, and the plurality of spot-like regions are scanned with excitation light to obtain the at least one kind of fluorescent substance. The method for reading data according to claim 3 or 4, wherein the fluorescence emitted from the at least one fluorescent substance is photoelectrically detected to generate data. 7. The sample is irradiated with a laser beam, the plurality of spot-shaped regions are scanned with the laser beam, and light emitted from the plurality of spot-shaped regions is photoelectrically detected. The data reading method according to any one of claims 3 to 6, wherein the data is generated. 8. The plurality of spot-shaped regions selectively include a labeling substance that causes chemiluminescence when brought into contact with a chemiluminescent substrate, and further, a width in a direction perpendicular to the main scanning direction is: Greater than the width of the spot-shaped region in the direction perpendicular to the main scanning direction, the width in the main scanning direction is through a spatial filter having an aperture smaller than the width of the spot-shaped region in the main scanning direction. The method for reading data according to claim 1 or 2, wherein chemiluminescence emitted from the plurality of spot-shaped regions is detected photoelectrically. 9. The data reading method according to claim 8, wherein the chemiluminescence emitted from the plurality of spot-shaped regions is condensed on the aperture of the spatial filter. 10. A sample stage, on which a sample having a plurality of spot-shaped regions selectively containing a labeling substance, which is formed at least one-dimensionally apart from each other, is placed, and the plurality of spot-shaped regions. Photoelectrically detecting the light emitted from the region of, and a photodetector for generating data, and a scanning mechanism for relatively moving the photodetector and the sample stage in at least the main scanning direction, The photodetector photoelectrically detects light emitted from a region whose width in a direction perpendicular to the main scanning direction is larger than a width of the spot-shaped region in a direction perpendicular to the main scanning direction. , A scanner configured to generate data. 11. The sample comprises a plurality of spot-like regions formed two-dimensionally and spaced apart from each other,
11. The scanning mechanism is configured to relatively move the photodetector and the sample stage in the main scanning direction and a sub-scanning direction perpendicular to the main scanning direction. Scanner as described in. 12. The photodetector further comprises an excitation light source that forms an optical unit and emits excitation light, and the scanning mechanism relatively positions the optical unit and the sample stage in at least a main scanning direction. The optical unit is configured to move the excitation light emitted from the excitation light source, and the excitation light emitted from the excitation light source has a beam width in a direction perpendicular to the main scanning direction. Excitation light emitted from the excitation light source and shaped by the condensing optical system, the condensing optical system shaping and condensing on the sample so as to be larger than the width in the direction perpendicular to the direction. Is configured to scan the plurality of spot-shaped areas, and the photodetector photoelectrically detects light emitted from the plurality of spot-shaped areas. The scanner according to claim 10 or 11, which is used as a signature. 13. The condensing optical system condenses the excitation light on the sample such that the beam width is smaller than the width of the spot-shaped region in the main scanning direction. 13. The scanner according to claim 12, characterized in that 14. The pumping light source is constituted by a laser pumping light source.
Scanner as described in. 15. The scanner according to claim 12, wherein the excitation light source is an LED light source. 16. The optical unit further comprises the L
16. The scanner according to claim 15, further comprising a spectral filter that cuts light having a wavelength component that does not contribute to the excitation of the labeling substance from the light emitted from the ED light source. 17. The optical unit further comprises an excitation light cut filter for cutting excitation light in an optical path of light emitted from the plurality of spot-shaped regions. 16. The scanner according to any one of 16. 18. A second pumping light source that emits pumping light having a wavelength different from that of the pumping light emitted from the pumping light source of the optical unit, at a position different from the optical unit with respect to the main scanning direction. A second photodetector that photoelectrically detects light emitted from the plurality of spot-shaped areas and generates data, and a beam width in a direction perpendicular to the main scanning direction is the spot-shaped areas. Second condensing optical system that shapes the excitation light emitted from the second excitation light source so as to be larger than the width in the direction perpendicular to the main scanning direction, and condenses it on the sample. 2. A second optical unit comprising: is provided.
18. The scanner according to any one of 2 to 17. 19. The second condensing optical system condenses the excitation light on the sample such that the beam width is smaller than the width of the spot-shaped region in the main scanning direction. 19. The scanner according to claim 18, wherein: 20. The scanner according to claim 18, wherein the second excitation light source is a laser excitation light source. 21. The second excitation light source is constituted by an LED light source.
9. The scanner according to item 9. 22. The second optical unit further comprises:
22. The scanner according to claim 21, further comprising a second spectral filter that cuts light having a wavelength component that does not contribute to the excitation of the labeling substance from the light emitted from the second LED light source. 23. The second optical unit further comprises:
23. The scanner according to claim 18, further comprising an excitation light cut filter that cuts the excitation light, in the optical path of the light emitted from the plurality of spot-shaped areas. 24. The optical unit further includes, in the optical path of the light emitted from the plurality of spot-shaped regions, a width in a direction perpendicular to the main-scanning direction, the main-scanning of the spot-shaped regions. 11. A spatial filter having an aperture larger than a width in a direction perpendicular to the direction and having a width in the main scanning direction smaller than a width of the spot-shaped region in the main scanning direction.
Or the scanner according to item 11. 25. The optical unit further comprises a condensing optical system that condenses the light emitted from the plurality of spot-shaped regions on the aperture of the spatial filter. 24. The scanner according to 24.