JP2002168871A - Sample carrier - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sample carrier which can set samples to a sample stage so that a sample face is always positioned to the same position of the sample stage without requiring highly accurate machining. SOLUTION: The sample carrier 21 to be set to the sample stage 20 with holding samples 22 includes a frame body 50 formed by machining one plate-like member, opening parts 51, 52, 53, 54 and 55 which are formed to the frame body and in which samples can be stored, a plurality of plate members 60, 61, 62, 63, 64 and 65 mounted to a surface of the frame body at both sides of the opening parts, pressing members 51a, 52a, 53a, 54a and 55a which can press samples stored in the opening parts to the plate members. The plate members partly projecting above the opening parts can support the samples stored in the opening parts by surfaces thereof. The surface of the frame body at the side where the plate members of both side parts are mounted via the opening parts is placed and set to the stage.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sample carrier for holding a sample, and more particularly, to a method in which a sample surface is always fixed to a sample stage without requiring high-precision processing. A sample carrier that can set a sample on the sample stage so that it is located at the same position, in particular, it can hold multiple samples and does not require high-precision processing, and the sample surface of all samples Relates to a sample carrier capable of setting a sample on a sample stage so as to be located at the same position with respect to the sample stage.

[0002]

2. Description of the Related Art When irradiated with radiation, the energy of the radiation is absorbed, stored, recorded, and then excited using electromagnetic waves in a specific wavelength range. A stimulable phosphor having a characteristic of emitting a stimulating amount of radiated light is used as a radiation detecting material, and a substance provided with a radioactive label is administered to an organism, and then the organism or a tissue of the organism is treated. Partly as a sample,
This sample is superimposed on a stimulable phosphor sheet provided with a stimulable phosphor layer for a certain period of time, whereby radiation energy is accumulated and recorded on the stimulable phosphor, and thereafter, the stimulable phosphor is stimulated by electromagnetic waves. Scans the stimulable phosphor layer to excite the stimulable phosphor, photoelectrically detects the stimulable light emitted from the stimulable phosphor, generates a digital image signal, and performs image processing. An autoradiography detection system configured to reproduce an image on display means such as a CRT or a recording material such as a photographic film is known (for example, Japanese Patent Publication No. 1-60784, Japanese Patent Publication No. No. 60782, Japanese Patent Publication No. 4-3952).

An autoradiography detection system using a stimulable phosphor sheet as a material for detecting an image, unlike the case of using a photographic film, not only does not require a chemical treatment called a development process, but also obtains an obtained image. By performing image processing on image data, there is an advantage that an image can be reproduced or quantitative analysis can be performed by a computer as desired.

[0004] On the other hand, a fluorescence detection system using a fluorescent substance as a labeling substance instead of a radioactive labeling substance in an autoradiography system is known. According to this system, by reading a fluorescent image, gene sequence, gene expression level, separation and identification of protein, or evaluation of molecular weight and characteristics can be performed. After adding a fluorescent dye to the solution containing the fragments,
A plurality of DNA fragments are electrophoresed on a gel support, or a plurality of DNA fragments are placed on a gel support containing a fluorescent dye.
After the NA fragment is subjected to electrophoresis, or a plurality of DNA fragments are subjected to electrophoresis on a gel support, the gel support is immersed in a solution containing a fluorescent dye, etc. By labeling, exciting a fluorescent dye with excitation light, and detecting the generated fluorescence, an image is generated, and the distribution of DNA on the gel support is detected. After electrophoresis on a support, the DNA is denaturated, and then at least a part of the denatured DNA fragment is transferred onto a transfer support such as nitrocellulose by Southern blotting to obtain the desired DNA. A probe prepared by labeling DNA or RNA complementary to the DNA to be labeled with a fluorescent dye and a denatured DNA fragment is hybridized, and the probe DNA
Alternatively, only the DNA fragment complementary to the probe RNA is selectively labeled, and the excitation light excites the fluorescent dye,
By detecting the generated fluorescence, an image can be generated and the distribution of the target DNA on the transfer support can be detected. Further, a DNA probe complementary to the DNA containing the target gene labeled with the labeling substance is prepared, hybridized with the DNA on the transcription support, and the enzyme is reacted with the complementary DNA labeled with the labeling substance. After binding, it is brought into contact with a fluorescent substrate to convert the fluorescent substrate into a fluorescent substance that emits fluorescence, and the excitation light excites the generated fluorescent substance and detects the generated fluorescence to generate an image. However, the distribution of the target DNA on the transcription support can also be detected. This fluorescence detection system has an advantage that a gene sequence or the like can be easily detected without using a radioactive substance.

[0005] In recent years, hormones, tumor markers, enzymes, antibodies, antigens, and the like have been placed at different positions on the surface of a carrier such as a slide glass plate, a membrane filter, or a gel support.
Abzyme, other proteins, nucleic acids, cDNA, D
NA, RNA, etc., can be specifically bound to a substance derived from a living body, and a specific binding substance whose base sequence, base length, composition, etc. are known is dropped using a spotter device,
Form a number of independent spots, followed by hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, cDNA, DNA, mRNA
Such as, extraction, isolation, etc., collected from a living body, or, furthermore, a chemical substance, a biologically-derived substance that has been subjected to a treatment such as chemical modification, and is labeled with a labeling substance such as a fluorescent substance or a dye. Microarrays that irradiate excitation light to microarrays that have hybridized substances that have been hybridized, and that photoelectrically detect light such as fluorescence emitted from fluorescent substances, dyes, and other labeled substances, and analyze biologically derived substances Detection systems have been developed. According to this microarray detection system, a large number of specific binding substance spots are formed at different positions on a carrier surface such as a slide glass plate or a membrane filter at a high density, and a biological substance labeled with a labeling substance is formed. Is advantageous in that a substance derived from a living body can be analyzed in a short time.

[0006] In addition, hormones, tumor markers, enzymes, and the like can be located at different positions on the surface of a carrier such as a membrane filter.
Antibodies, antigens, abzymes, other proteins, nucleic acids,
Using a spotter, a specific binding substance that can specifically bind to a substance derived from a living body, such as cDNA, DNA, or RNA, and has a known base sequence, base length, or composition, is dropped using a spotter device. Form a number of independent spots, followed by hormones, tumor markers, enzymes, antibodies, antigens, abzymes, other proteins, nucleic acids, cDNAs, DNs
A, mRNA, etc., a substance derived from a living body that has been collected from a living body by extraction, isolation, or the like, or that has been further subjected to a chemical treatment, a chemical modification, or the like, and that has been labeled with a radioactive labeling substance. The macroarray hybridized with the above is brought into close contact with the stimulable phosphor sheet on which the stimulable phosphor layer containing the stimulable phosphor is formed, and the stimulable phosphor layer is exposed, and then the luminescent phosphor layer is exposed. A macroarray detection system using a radioactive labeling substance that irradiates the stimulable phosphor layer with excitation light, photoelectrically detects the stimulable phosphor emitted from the stimulable phosphor layer, and analyzes substances derived from living organisms Has also been developed.

[0007]

In a microarray detection system, a sample is scanned with excitation light to excite a labeling substance such as a fluorescent substance, and to photoelectrically detect fluorescence emitted from the fluorescent substance. Therefore, data for biochemical analysis such as image data and luminescence amount data of the labeling substance are generated, and in order to enable high-precision detection, the sample surface must be positioned with respect to the sample stage. Therefore, it is required to set a sample on a sample stage so that the sample is always located at the same position, and a setting with high accuracy of usually 10 to 20 microns is required.

Therefore, the surface of the sample carrier holding the sample and the surface of the sample carrier placed on the sample stage always have a certain relationship.
It is necessary to process the sample carrier with high accuracy, and there is a problem that the manufacturing cost of the sample carrier increases.

In particular, in order to efficiently generate data for biochemical analysis, a microarray sample having a plurality of slide glass plates as carriers is simultaneously held on a sample carrier and excited by excitation light. In such a case, it is proposed that scanning is performed, so that the surface of the sample carrier holding all the samples and the surface of the sample carrier mounted on the sample stage have a certain relationship. It is extremely difficult to process the sample carrier, and when setting the sample carrier on the sample stage, it is necessary to make adjustments so that all sample surfaces are located at the same position with respect to the sample stage. And there is a problem that it is extremely complicated.

Therefore, the present invention provides a method of setting a sample on a sample stage such that the sample surface is always located at the same position with respect to the sample stage without requiring high-precision processing. It is intended to provide a sample carrier that can be used.

[0011] Another object of the present invention is to hold a plurality of samples, and without requiring high-precision processing, the sample surfaces of all the samples are located at the same position with respect to the sample stage. The purpose of the present invention is to provide a sample carrier on which a sample can be set on a sample stage.

[0012]

SUMMARY OF THE INVENTION The object of the present invention is as follows.
A sample carrier that holds a sample and is set on a sample stage, wherein the frame body is formed by processing one plate-shaped member, and at least one opening formed in the frame body and capable of containing a sample. And a portion of the frame body attached to a surface of the frame body on both sides of the at least one opening, a portion of which protrudes over the at least one opening and is received at the surface in the at least one opening. A plurality of plate members capable of supporting a sample, and a sample housed in the at least one opening is provided with a pressing member capable of pressing the sample toward the plate member, and the at least one opening of the frame body is provided. The surface on the side where the plate member was attached on both sides sandwiched was placed on the sample stage and configured to be set on the sample stage. It is achieved by the sample carrier, wherein the door.

According to the invention, the sample carrier comprises one
A frame formed by processing a plurality of plate-like members, at least one opening formed in the frame, and capable of containing a sample; and one of the openings attached to the surface of the frame on both sides of the opening. A plurality of plate members projecting over the at least one opening, the surface of which is capable of supporting a sample contained in the at least one opening; The sample housed in the at least one opening is pressed by the pressing member onto the surface of the plate member attached to the surface of the frame body, so that the sample is The surface on the side where the plate members on both sides sandwiching at least one opening of the frame body made by processing one plate-shaped member are supported by the surface of the member, It is placed on the sample stage,
Since it is configured to be set on the sample stage, the position of the surface of the sample supported on the surface of the plate member and the position of the surface of the frame placed on the sample stage are always in the same plane. Therefore, after setting on the sample stage, the sample is always moved relative to the sample stage without the complicated operation of adjusting the position of the sample carrier and the sample held on the sample carrier in the height direction. With the same positional relationship, it is possible to set.

Further, according to the present invention, the sample can be always moved to the sample stage by the same process with respect to the sample stage simply by forming the frame body by processing one plate-shaped member and attaching the plate member to the surface thereof. Since it can be set in a positional relationship, the cost of the sample carrier can be significantly reduced.

In a preferred embodiment of the present invention, the sample contained in the at least one opening is pressed against one inner wall of the at least one opening,
A press alignment member capable of aligning the sample is provided along the other opposing inner wall of the at least one opening.

In a further preferred aspect of the present invention, the pressing member is formed by a leaf spring.

In a further preferred aspect of the present invention, the leaf spring has an L-shape, and a bent portion thereof is configured to be able to abut on the sample accommodated in the at least one opening.

According to a further preferred embodiment of the present invention, the sample is irradiated with excitation light, a fluorescent substance contained in the sample is excited, and the emitted fluorescence is detected to generate data for biochemical analysis. In this case, it is possible to reliably prevent the light reflected by the leaf spring from generating noise in data.

In a further preferred aspect of the present invention, the pressing and aligning member is formed by a leaf spring.

In a further preferred aspect of the present invention, the at least one opening has a rectangular shape, the plurality of plate members have a rectangular shape, and the plate member has a rectangular shape on a side of the at least one opening. A side region projects over the at least one opening along an inner wall of the at least one opening, and a surface of the side region can support a sample contained in the at least one opening. Is configured.

According to a further preferred embodiment of the present invention, at least one opening has a rectangular shape,
A plurality of plate members having a rectangular shape, a side region on a side of at least one opening of the plate member protruding along at least one opening along an inner wall portion of the at least one opening;
Since the sample accommodated in the at least one opening can be supported on the surface of the side region, the sample can be reliably supported by the surface of the side region of the plate member.

In a further preferred aspect of the present invention, the frame body has two or more openings.

According to a further preferred embodiment of the present invention, a plurality of samples are always placed in the same positional relationship with respect to the sample stage without the complicated operation of adjusting the position of the sample carrier. Since the setting can be performed, data for biochemical analysis can be efficiently generated.

[0024]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below in detail with reference to the accompanying drawings.

FIG. 1 shows a data for biochemical analysis by exciting a labeling substance contained in a sample held by a sample carrier and detecting light emitted from the labeling substance according to a preferred embodiment of the present invention. FIG. 2 is a schematic perspective view of a data generation device that generates the data.

As shown in FIG. 1, the data generating apparatus comprises a first laser excitation light source 1 for emitting a laser beam 4 having a wavelength of 640 nm, and a second laser excitation light source 2 for emitting a laser beam 4 having a wavelength of 532 nm. And a third laser excitation light source 3 that emits laser light 4 having a wavelength of 473 nm. In this embodiment, the first laser excitation light source is
The second laser excitation light source 2 and the third laser excitation light source 3 are each configured by a semiconductor laser light source, and are configured by a second harmonic generation (Second Harmonic Generation) element.

The laser light 4 generated by the first laser excitation light source 1 is collimated by a collimator lens 5 and then reflected by a mirror 6. In the optical path of the laser light 4 emitted from the first laser excitation light source 1 and reflected by the mirror 6, the first dichroic mirrors 7 and 532nm transmitting the 640nm laser light 4 and reflecting the 532nm wavelength light are provided. A second dichroic mirror 8 that transmits light having the above wavelength and reflects light having a wavelength of 473 nm is provided. The laser light 4 generated by the first laser excitation light source 1 is used as a first dichroic mirror. The light passes through 7 and the second dichroic mirror 8 and enters the optical head 15.

On the other hand, the laser light 4 generated from the second laser excitation light source 2 is collimated by the collimator lens 9 and then reflected by the first dichroic mirror 7 to change its direction by 90 degrees. Then, the light passes through the second dichroic mirror 8 and enters the optical head 15.

The laser light 4 generated from the third laser excitation light source 3 is collimated by the collimator lens 10 and then reflected by the second dichroic mirror 8 to change its direction by 90 degrees. After that, the light enters the optical head 15.

The optical head 15 includes a mirror 16, a perforated mirror 18 having a hole 17 formed in the center thereof, and a lens 19. The laser beam 4 incident on the optical head 15 is Reflected and perforated mirror 18
The sample carrier 21 set on the sample stage 20 through the hole 17 and the lens 19 formed in
Incident on top. The sample stage 20 is configured to be movable in the XY directions in FIG. 1 by a scanning mechanism (not shown).

In this embodiment, the sample carrier 2
Reference numeral 1 denotes a data generation device which uses a slide glass plate as a carrier and is capable of holding five microarrays formed on the slide glass plate in which a large number of spots of a sample selectively labeled with a fluorescent dye are provided. The five microarrays held in the sample carrier 21 are sequentially scanned by the laser light 4 to excite the fluorescent dye, and the fluorescence emitted from the fluorescent dye is photoelectrically detected, so that the microarray is used for biochemical analysis. Is generated.

Further, in this embodiment, the data generating apparatus uses a gel support as a carrier instead of the sample carrier 21 and a large number of spots of a sample selectively labeled with a fluorescent dye are formed on the gel support. 1 that is formed in
Alternatively, a sample carrier holding a plurality of microarrays is set on a sample stage 20, and a microarray using a gel support as a carrier is scanned by a laser beam 4 to excite a fluorescent dye and to emit fluorescence emitted from the fluorescent dye. A membrane filter configured to be capable of photoelectrically detecting and generating data for biochemical analysis, and having a large number of spots of a sample selectively labeled with a radioactive label instead of the sample carrier 21. A carrier such as a stimulable phosphor layer containing a stimulable phosphor layer is brought into close contact with the stimulable phosphor sheet, and the position information of the radiolabeled substance obtained by exposing the stimulable phosphor layer. The sample carrier holding the stimulable phosphor sheet on which is recorded is set on the sample stage 20, and the stimulable phosphor layer of the stimulable phosphor sheet is Scanning with the laser light 4 to excite the stimulable phosphor, photoelectrically detect the stimulable light emitted from the stimulable phosphor, and generate data for biochemical analysis. ing.

A microarray using a slide glass plate as a carrier is produced, for example, as follows.

First, the surface of the slide glass plate was
Pretreated with an L-lysine solution or the like, and then, at a predetermined position on the surface of the slide glass plate, cDNAs, which are a plurality of specific binding substances having different base sequences and different from each other.
Is dropped using a spotter device.

On the other hand, mRNA as a specimen is extracted from living cells, and RNA having poly A at the 3 ′ end is extracted from the mRNA. When synthesizing cDNA from the RNA having poly A at the end thus extracted, Cy-5 (registered trademark) which is a labeling substance is present to generate a probe DNA labeled with Cy-5.

The probe DNA labeled with Cy-5 thus obtained is prepared into a predetermined solution, and gently placed on the surface of a slide glass onto which cDNA as a specific binding substance has been dropped, and hybridized.

When a gel support is used as a carrier, a microarray is similarly produced.

FIG. 2 is a schematic perspective view of the microarray 22 thus obtained. In FIG. 2, reference numeral 23 denotes the dropped cDNA.

On the other hand, in the stimulable phosphor layer of the stimulable phosphor sheet, position information of the radioactive labeling substance is recorded, for example, as follows.

The surface of a carrier such as a membrane filter is pre-treated, and cDNAs, which are a plurality of specific binding substances whose base sequences are different from each other, are deposited at predetermined positions on the surface of the carrier such as a membrane filter. Use the device to drip.

On the other hand, mRNA as a specimen is extracted from living cells, and RNA having poly A at the 3 ′ end is extracted from the mRNA. When synthesizing cDNA from the RNA having poly A at the terminal thus extracted, a radiolabeled substance is present to generate a probe DNA labeled with the radiolabeled substance.

The probe DNA labeled with the radiolabeled substance thus obtained is adjusted to a predetermined solution, and is gently placed on the surface of a carrier such as a membrane filter onto which cDNA as a specific binding substance has been dropped, and hybridized. .

Next, the stimulable phosphor layer formed on the stimulable phosphor sheet is superimposed on the surface of a carrier such as a membrane filter on which the hybridized sample is formed, and is kept in close contact for a predetermined time. By doing so, at least part of the radiation emitted from the radiolabeled substance on the carrier such as a membrane filter is absorbed by the stimulable phosphor layer formed on the stimulable phosphor sheet, and the position information of the radiolabeled substance is obtained. Is recorded in the stimulable phosphor layer.

When the laser beam 4 is incident on the sample 22 from the optical head 15, when the sample 22 is a microarray, the fluorescent material is excited by the laser beam 4 to emit fluorescence. However, in the case of a stimulable phosphor sheet, the stimulable phosphor contained in the stimulable phosphor layer is excited to emit stimulable phosphor.

The fluorescence or stimulating light 25 emitted from the sample 22 is converted into parallel light by the lens 19 of the optical head 15, reflected by the perforated mirror 18, and
Any one of the filters 28a, 28a, 28b, 28c, 28d of the filter unit 27 having four filters 28a, 28b, 28c, 28d.
The light is incident on 28b, 28c, 28d.

The filter unit 27 is configured to be movable in the left-right direction in FIG. 1 by a motor (not shown), and predetermined filters 28a, 28b, 28c, 28d are provided depending on the type of laser excitation light source used. , Or in the optical path of the fluorescent or stimulating light 25.

Here, the filter 28a is a filter used when the first laser excitation light source 1 is used to excite the fluorescent substance contained in the sample 22 and read the fluorescence, and has a wavelength of 640 nm. Cut the light, 640n
It has the property of transmitting light having a wavelength longer than m.

The filter 28b is a filter used to excite the fluorescent dye contained in the sample 22 by using the second laser excitation light source 2 and to read the fluorescence. 532nm
It has the property of transmitting light with a longer wavelength than that.

Further, the filter 28c is a filter used to excite the fluorescent dye contained in the sample 22 by using the third laser excitation light source 3 and to read out the fluorescence. And cut 473n
It has the property of transmitting light having a wavelength longer than m.

When the sample 22 is a stimulable phosphor sheet, the filter 28d uses the first laser excitation light source 1 to excite the stimulable phosphor contained in the stimulable phosphor sheet. A filter used to read the stimulable light emitted from the stimulable phosphor, and transmits only light in the wavelength region of the stimulable light emitted from the stimulable phosphor;
It has the property of cutting light having a wavelength of 0 nm.

Therefore, these filters 28a, 28a, and 28a are used in accordance with the type of laser excitation light source to be used, that is, the type of sample and the type of fluorescent substance that labels the sample.
By selectively using 8b, 28c, 28d,
It becomes possible to cut off light in a wavelength region that becomes noise.

The filter 28a of the filter unit 27,
After passing through 28b and 28c and cutting light in a predetermined wavelength range, the fluorescence or stimulating light 25 enters a mirror 29, is reflected, and is condensed by a lens 30.

The lens 19 and the lens 30 constitute a confocal optical system. As described above, the confocal optical system is employed because, when the sample 22 is a microarray using a slide glass plate as a carrier, the fluorescence emitted from a minute spot-shaped sample formed on the slide glass plate is used. To
This is to enable reading at a high S / N ratio.

A confocal switching member 31 is provided at the focal point of the lens 30.

FIG. 3 is a schematic front view of the confocal switching member 31.

As shown in FIG. 3, the confocal switching member 31 has a plate shape and has three pinholes 3 having different diameters.
2a, 32b and 32c are formed.

The pinhole 32a having the smallest diameter is arranged in the optical path of the fluorescent light emitted from the microarray when the sample 22 is a microarray using a slide glass plate as a carrier. Reference numeral 32c denotes a sample arranged in the optical path of the fluorescence emitted from the gel support when the sample 22 is a microarray using the gel support as a carrier.

Further, a pinhole 32b having an intermediate diameter is provided.
In the case where the sample 22 is a stimulable phosphor sheet, the sample 22 is arranged on the optical path of the stimulable light emitted from the stimulable phosphor layer.

As described above, at the focal position of the lens 30,
By providing the confocal switching member 31, when the sample 22 is a microarray using a slide glass plate as a carrier,
The pinhole 32a having the smallest diameter is positioned in the optical path of the fluorescent light. When the sample 22 is a microarray using a slide glass plate as a carrier, the fluorescent dye is excited by the laser light 4 so that the fluorescent light is Since the light is emitted from the surface of the slide glass plate and the light emitting point is almost constant in the depth direction, it is necessary to form an image on the pinhole 32a having a small diameter using a confocal optical system in order to improve the S / N ratio. Is desirable.

In contrast, when the sample 22 is a microarray using a gel support as a carrier, the pinhole 32c having the largest diameter is located in the optical path of the fluorescence because the sample 22 is a gel support. In the case of a microarray using as a carrier, when the fluorescent dye is excited by the laser light 4, the fluorescent dye is distributed in the depth direction of the gel support, and the emission point fluctuates in the depth direction. So
With a confocal optical system, an image cannot be formed on a pinhole having a small diameter.
This is because, when the fluorescence emitted from the sample is cut off and the fluorescence is photoelectrically detected, a sufficient signal intensity cannot be obtained, so that it is necessary to use the pinhole 32c having a large diameter.

On the other hand, when the sample 22 is a stimulable phosphor sheet, the pinhole 32b having an intermediate diameter is positioned in the optical path of the stimulable phosphor by the laser light 4. When the stimulable phosphor contained in the layer is excited, the emission points of the stimulable phosphor are distributed in the depth direction of the stimulable phosphor layer, and the emission points fluctuate in the depth direction. Due to the optical system, it is not possible to form an image on a pinhole with a small diameter, and if a pinhole with a small diameter is used, the photostimulable light emitted from the sample is cut off, and the photostimulable light is detected Although a sufficient signal intensity cannot be obtained, the distribution in the depth direction of the light-emitting points and the fluctuation in the depth direction of the light-emitting points are not as large as those of the microarray using the gel support as a carrier. This is because it is desirable to use the hole 32b.

The fluorescence or stimulating light that has passed through the confocal switching member 31 is photoelectrically detected by the photomultiplier 33, and analog data is generated.

The analog data generated by the photomultiplier 33 is converted into digital data by the A / D converter 34 and sent to the data processing device 35.

FIG. 4 is a block diagram showing a detection system, a drive system, an input system, and a control system of the data generator.

As shown in FIG. 4, the detection system of the data generation device includes a carrier sensor 40 for detecting the type of carrier holding the sample 22 set on the sample stage 20, and the drive system of the data generation device is Unit motor 41 for moving the filter unit 27
And a switching member motor 42 for moving the confocal switching member 31.

The input system of the data generating device has a keyboard 43, and the control system of the data generating device has a control unit 45.

FIG. 5 is a schematic perspective view of the sample carrier 21 according to a preferred embodiment of the present invention, and is a drawing of the sample carrier 21 viewed from the back side, that is, from the side mounted on the sample stage 20. .

As shown in FIG. 5, the sample carrier 21 has a frame body 50 formed by processing one plate-like member, and the sample body 22 is set inside the frame body 50. 5 possible openings 5
1, 52, 53, 54 and 55 are formed.

Plate members 60, 61, 62, 63, 64, 65 each having a rectangular shape are provided on the surface of the frame body 50 on both sides of each of the openings 51, 52, 53, 54, 55, respectively.
The side regions on the side of the openings 51, 52, 53, 54, 55 are placed on the openings 51, 52, 53, 54, 55 along the longitudinal direction of the openings 51, 52, 53, 54, 55. It is mounted so as to protrude.

As shown in FIG. 5, each opening 51, 5
L-shaped leaf springs 5 are provided in 2, 53, 54 and 55.
1 a, 52 a, 53 a, 54 a, 55 a are attached to the back side of the sample carrier 21 so that a spring force can be applied.
Each of the openings 51, 52, 5
The leaf springs 51b, 5b align the sample 22 set in 3, 54, 55 along the other opposing inner wall.
2b, 53b, 54b and 55b are attached.

The sample carrier 21 includes a frame 50
Are placed on the sample stage 20 and set on the sample stage 20.

When a microarray using a slide glass plate as a carrier as the sample 22 is set on the sample carrier 21, the sample 22 is placed in the direction indicated by the arrow A in FIG. 53, 5
4, 55.

One inner wall of each of the openings 51, 52, 53, 54, 55 is provided with a leaf spring 51b, 52b, 53b, 5b.
4b and 55b are attached, the sample 22
Are aligned along the other opposing inner wall in each of the openings 51, 52, 53, 54, 55.

At the same time, the openings 51, 52, 53, 5
The bent portions of the L-shaped leaf springs 51a, 52a, 53a, 54a, and 55a abut on the sample 22 inserted into the sample springs 4 and 55, and the leaf springs 51a, 52a, 53a and 54
Due to the spring force of the openings a, 55a, the side regions on the opening 51, 52, 53, 54, 55 side respectively extend along the longitudinal direction of the openings 51, 52, 53, 54, 55. , Plate members 60, 6 attached to project over openings 51, 52, 53, 54, 55.
1, 62, 63, 64, and 65 are urged to the surface and held on the sample carrier 21.

The sample carrier 21 according to the present embodiment
In the above, the plate members 60, 6
1, 62, 63, 64, 65 have their openings 51, 5
The side regions on the 2, 53, 54, 55 side are the openings 51, 5
Along the longitudinal direction of 2, 53, 54, 55
1, 52, 53, 54, 55 so as to protrude above the sample 22, and the leaf springs 51 a, 52 a, 5
The spring members 3a, 54a, and 55a are configured to be urged against the surfaces of the plate members 60, 61, 62, 63, 64, and 65, respectively, and held on the sample carrier 21.

On the other hand, the sample carrier 21 has a frame 50 made by processing one plate-like member.
Are placed on the sample stage 20 and set on the sample stage 20.

Therefore, the surface of the plate member 60, 61, 62, 63, 64, 65 on which the sample 22 is supported, and the sample carrier 21 are placed on the sample stage 20.
The surfaces supported by are always in the same plane, so that the five samples 22 are always moved relative to the sample stage 20 without the complicated operation of adjusting the position of the sample carrier 21. With the same positional relationship, it is possible to set.

Further, the frame body 50 is simply made by processing one plate-like member, and the plate members 60, 61, 62, 63,
By simply mounting the 64 and 65 on the surface of the frame body 50, the five samples 22 can always be set in the same positional relationship with respect to the sample stage 20, so that the cost of the sample carrier 21 is greatly reduced. It becomes possible to reduce to.

When the sample 22 is a microarray using a slide glass plate as a carrier, the data generator configured as described above scans the entire surface of the sample 22 with the laser beam 4 as follows. Then, the fluorescent dye that selectively labels the sample is excited, and the fluorescence emitted from the fluorescent dye is photoelectrically detected to generate digital data for biochemical analysis.

First, five microarrays using a slide glass plate as a sample 22 as a carrier are placed in the openings 51, 52, 53, 54, 55 of the sample carrier 21 in the direction shown by the arrow A in FIG. Is inserted into.

The openings 51, 5 and 5 of the sample carrier 21
A leaf spring 51 is provided on one of the inner wall portions of 2, 53, 54, 55.
Since b, 52b, 53b, 54b, and 55b are attached, the sample 22 has respective openings 51,
Within 52,53,54,55, they are aligned along the other opposing inner wall.

At the same time, the openings 51, 52, 53, 5
The tops of the L-shaped leaf springs 51a, 52a, 53a, 54a, 55a abut against the sample 22 inserted in the insides 4, 55, and the leaf springs 51a, 52a, 53a, 54a,
With the spring force of 55a, the sample 22 respectively
The side regions on the side of the openings 51, 52, 53, 54, 55 are placed on the openings 51, 52, 53, 54, 55 along the longitudinal direction of the openings 51, 52, 53, 54, 55. The plate members 60, 61, 6 attached so as to protrude
It is urged against the surfaces of 2, 63, 64 and 65 and held on the sample carrier 21.

Here, plate members 60, 61, 62, 63, 64, 65 are provided on the surface of the frame body 50 with the openings 5.
The side regions on the 1, 52, 53, 54, 55 side are the openings 5
Along the longitudinal direction of 1, 52, 53, 54, 55, it protrudes above the openings 51, 52, 53, 54, 55,
Attached, the sample 22 includes leaf springs 51a, 52
a, 53a, 54a, and 55a are configured to be urged against the surfaces of the plate members 60, 61, 62, 63, 64, and 65, respectively, and held on the sample carrier 21 by the spring force of the sample carriers 21. The carrier 21 has a frame body 50 formed by processing one plate-like member.
Are placed on the sample stage 20 and set on the sample stage 20, so that the plate member 60 on which the sample 22 is supported on its surface,
The surfaces of the sample carriers 21, 62, 63, 64, 65 and the surface on which the sample carrier 21 is supported by the sample stage 20 are always in the same plane.
One and five samples 22 can be easily adjusted without complicated operations of adjusting the position of each sample 22 in the height direction.
Can always be set to the sample stage 20 with the same positional relationship.

In this way, when the sample carrier 21 on which the five microarrays each having the slide glass plate as the sample 22 as a carrier is set is set on the sample stage 20, the type of the sample carrier 21 is detected by the carrier sensor 40. The carrier detection signal is output to the control unit 45.

Upon receiving the carrier detection signal from the carrier sensor 40, the control unit 45 outputs a drive signal to the switching member motor 42 based on the carrier detection signal, and causes the confocal switching member 31 to rotate the pinhole having the smallest diameter. 32a is moved so as to be located in the optical path.

Then, when the operator inputs the type of the fluorescent substance as the labeling substance and the start signal to the keyboard 43, the keyboard 43 outputs an instruction signal to the control unit 45.

For example, the type of fluorescent substance is Cy-
When 5 (registered trademark) is input, the control unit 45 outputs a drive signal to the filter unit motor 41 in accordance with the input instruction signal, moves the filter unit 27, and cuts light having a wavelength of 640 nm. Then, a filter 28a having a property of transmitting light having a wavelength longer than 640 nm is located in the optical path, and a drive signal is output to the first laser excitation light source 1 to be turned on.

The laser light 4 emitted from the first laser excitation light source 1 is converted into parallel light by a collimator lens 5, then reflected by a mirror 6, and is reflected by a first dichroic mirror 7 and a second dichroic mirror. 8 and enter the optical head 15.

The laser beam 4 incident on the optical head 15 is
The sample 22 reflected by the mirror 16, passes through the hole 17 formed in the perforated mirror 18, is condensed by the lens 19, and is set on the sample stage 20.
Is incident on the microarray.

The sample stage 20 is moved in the X and Y directions in FIG. 1 by a scanning mechanism (not shown), so that the five samples 22 set on the sample carrier 21 by the laser beam 4, ,
The entire surface of the five microarrays is sequentially scanned.

When the laser beam 4 is irradiated, the probe D
The fluorescent dye that labels NA, for example Cy-5, is excited and emits fluorescence. When a slide glass plate is used as a carrier of the microarray, the fluorescent dye is distributed only on the surface of the slide glass plate, and thus fluorescence is emitted only from the surface of the slide glass plate.

The fluorescent light emitted from the surface of the slide glass plate is converted into parallel light by the lens 19, reflected by the perforated mirror 18, and enters the filter unit 27.

The filter unit 27 includes a filter 28a
Is moved so as to be located in the optical path, the fluorescent light enters the filter 28a, the light having a wavelength of 640 nm is cut, and only the light having a wavelength longer than 640 nm is transmitted.

The fluorescent light transmitted through the filter 28a is reflected by the mirror 29 and is imaged by the lens 30.

Prior to the irradiation of the laser beam 4, the confocal switching member 31 is moved so that the pinhole 32a having the smallest diameter is located in the optical path, so that the fluorescent light is focused on the pinhole 32a. , Photomultiplier 33
Is detected photoelectrically, and analog data is generated.

As described above, the fluorescence emitted from the fluorescent dye on the surface of the slide glass plate is guided to the photomultiplier 33 using the confocal optical system, and is photoelectrically detected. Can be minimized.

The analog data generated by the photo multiplier 33 is converted into digital data by the A / D converter 34 and sent to the data processing device 35.

According to this embodiment, the plate members 60, 61, 62, 63, 64, 65 are provided on the surface of the frame body 50.
The side regions on the side of the openings 51, 52, 53, 54, 55 are placed on the openings 51, 52, 53, 54, 55 along the longitudinal direction of the openings 51, 52, 53, 54, 55. The sample 22 is mounted so as to project, and the leaf spring 5
By the spring force of 1a, 52a, 53a, 54a, 55a, the plate members 60, 61, 62, 63, 64,
65 and is configured to be held by the sample carrier 21 while the sample carrier 21
Is configured such that both side portions 50a and 50b of the frame body 50 formed by processing one plate-like member are placed on the sample stage 20 and set on the sample stage 20. , The plate members 60, 61, 62, 63, 6 on which the sample 22 is supported
4, 65 and the surface on which the sample carrier 21 is supported by the sample stage 20 are always in the same plane, so that after setting on the sample stage 20, the sample carrier 21 and each sample 2
It is possible to always set the five samples 22 on the sample stage 20 in the same positional relationship without the need for complicated operation of adjusting the position in the height direction of 2.

Further, according to the present embodiment, the frame body 50 is simply formed by processing one plate-like member, and
By simply mounting the 0, 61, 62, 63, 64, 65 on the surface of the frame body 50, the five samples 22 can always be set on the sample stage 20 in the same positional relationship. , Sample carrier 2
1 can be greatly reduced.

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

For example, in the above embodiment, five openings 51, 52, 53, 54, 55 are formed in the frame body 50 of the sample carrier 21, and the sample carrier 21 uses a slide glass plate as a carrier. Although it is configured to be able to hold five microarrays, the number of openings formed in the frame body 50, that is, the number of microarrays that can hold the sample carrier 21, can be arbitrarily determined. It is not limited.

Further, in the above embodiment, the bent portion comes into contact with the sample 22, and the sample 22 is biased toward the plate members 60, 61, 62, 63, 64, 65. L-shaped leaf springs 51a, 5a
2a, 53a, 54a and 55a are the sample carriers 2
1, the leaf springs 51a, 52a, 53
It is not always necessary that a, 54a and 55a have an L shape, and any leaf spring can be used as long as it is not in a positional relationship parallel to the sample 22.

In the above embodiment, the sample carrier 21 is in contact with the sample 22,
Are urged toward the plate members 60, 61, 62, 63, 64, 65 in the form of leaf springs 51a, 52a, 53a, 54a,
55a, the sample carrier 21 transfers the sample 22 to the plate members 60, 61, 62, 63, 64, 6
It is only necessary to provide a member capable of urging toward 5,
It is not always necessary to provide the leaf springs 51a, 52a, 53a, 54a, 55a.

Further, in the above embodiment, the sample carrier 21 has the openings 51, 52, 53, 54,
55 is attached to one of the inner walls, and each of the openings 51, 5
Sample 22 set in 2, 53, 54, 55
5 is arranged along the other opposing inner wall.
Although 1b, 52b, 53b, 54b, and 55b are provided, it is not always necessary to provide the leaf springs 51b, 52b, 53b, 54b, and 55b.

In the above embodiment, each opening 5 formed in the frame body 50 of the sample carrier 21 is formed.
On the surface of the frame body 50 on both sides of 1, 52, 53, 54, 55, rectangular plate members 60, 61, 62, 6
3, 64, 65 have openings 51, 52,
The side regions on the 53, 54, 55 side are the openings 51, 52,
Along the longitudinal direction of 53, 54, 55, openings 51, 5
2, 53, 54, 55 are mounted so as to protrude therefrom, but the plate members 60, 61, 62, 63, 64, 6
It is not necessary for the plate member 5 to have a rectangular shape, and the plate members 60, 61, 62, 63, 64, 65 need only be configured so that the surface thereof can support the sample 22. , Plate members 60, 61, 62, 63, 6
The side regions on the sides of the openings 51, 52, 53, 54, 55 of 4, 65 are arranged along the longitudinal direction of the openings 51, 52, 53, 54, 55, so that the openings 51, 52, 53, 54, It is not necessary to be mounted so as to protrude above 55.

[0106]

According to the present invention, the sample is set on the sample stage so that the sample surface is always located at the same position with respect to the sample stage without requiring high-precision processing. It is possible to provide a sample carrier that can be used.

Further, according to the present invention, a plurality of samples can be held, and the sample surfaces of all the samples are located at the same position with respect to the sample stage without requiring high-precision processing. Thus, it is possible to provide a sample carrier on which a sample can be set on a sample stage.

[Brief description of the drawings]

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a diagram showing a configuration for exciting a labeling substance contained in a sample held in a sample carrier according to a preferred embodiment of the present invention, detecting light emitted from the labeling substance, and performing a biochemical analysis. FIG. 2 is a schematic perspective view of a data generation device that generates data.

FIG. 2 is a schematic perspective view of a microarray.

FIG. 3 is a schematic front view of a confocal switching member.

FIG. 4 is a block diagram showing a detection system, a drive system, an input system, and a control system of the data generation device.

FIG. 5 is a schematic perspective view of a sample carrier according to a preferred embodiment of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 1st laser excitation light source 2 2nd laser excitation light source 3 3rd laser excitation light source 4 laser beam 5 collimator lens 6 mirror 7 1st dichroic mirror 8 2nd dichroic mirror 9 collimator lens 10 collimator lens 15 optical head Reference Signs List 16 mirror 17 hole 18 perforated mirror 19 lens 20 sample stage 21 sample carrier 22 sample 23 dropped cDNA 25 fluorescence or stimulating light 27 filter unit 28a, 28b, 28c, 28d filter 29 mirror 30 lens 31 confocal switching member 32a, 32b, 32c Pinhole 33 Photomultiplier 34 A / D converter 35 Image data processing device 40 Carrier sensor 41 Filter unit motor 42 Switching member motor 43 Keyboard 4 Control unit 50 Frame body 51, 52, 53, 54, 55 Opening 51a, 52a, 53a, 54a, 55a Leaf spring 51b, 52b, 53b, 54b, 55b Leaf spring 60, 61, 62, 63, 64, 65 Element

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) G01N 27/447 G01N 33/566 33/53 37/00 102 33/566 1/28 W 37/00 102 27 / 26 325A F-term (Reference) 2G043 AA03 BA16 CA03 DA02 DA05 DA06 EA01 FA02 FA06 GA02 GA04 GA07 GB18 GB19 HA01 HA02 HA09 HA15 JA02 KA02 KA05 LA02 MA04 NA05 2G057 AA04 AB01 AB04 AC01 BA03 BB01 2G058 AA09 CC09 CC09 CC09 CC09 CC16 DD03 DD12 DD13 EE07 EE11 FF03 FF12 GG01 GG03 HH02 HH06 JJ02 JJ07 JJ11 JJ13 JJ22 JJ30 KK02 LL04 MM09

Claims (7)

[Claims] 1. A sample carrier which holds a sample and is set on a sample stage, wherein the frame is formed by processing a single plate-like member, and the sample is formed on the frame and can accommodate a sample. At least one opening and attached to a surface of the frame body on opposite sides of the at least one opening, a portion of which protrudes over the at least one opening and at which surface the at least one opening A plurality of plate members capable of supporting the sample accommodated in the portion, and a sample accommodated in the at least one opening, and a pressing member capable of pressing the sample toward the plate member; The surfaces on both sides of the one opening on which the plate member is attached are placed on the sample stage and set on the sample stage. A sample carrier characterized in that: 2. A sample accommodated in the at least one opening is pressed against one inner wall of the at least one opening along the other opposite inner wall of the at least one opening. The sample carrier according to claim 1, further comprising a pressing and aligning member capable of aligning the sample. 3. The sample carrier according to claim 1, wherein the pressing member is formed by a leaf spring. 4. The apparatus according to claim 3, wherein the leaf spring has an L-shape, and a bent portion thereof is configured to be able to abut on the sample accommodated in the at least one opening. Sample carrier. 5. The sample carrier according to claim 1, wherein the pressing and aligning member is formed by a leaf spring. 6. The at least one opening has a rectangular shape, the plurality of plate members have a rectangular shape, and a side region of the plate member on the side of the at least one opening has the at least one opening. Protruding above the at least one opening along the inner wall of the one opening, and configured to support a sample accommodated in the at least one opening on a surface of the side region. Claim 1
6. The sample carrier according to any one of items 5 to 5. 7. The sample carrier according to claim 1, wherein two or more openings are formed in the frame body.