JP2001133464A - Microarray chip, method and apparatus for reading microarray chip - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a microarray chip in which correspondence with analytic information representative of conditions concerning to biological analysis is made sure. SOLUTION: A bar code sheet 13 indicating analytic information representative of the type, concentration and reaction time of DNA, being dripped onto a microarray chip 10, in the form of a bar code 14 is attached to the part of a slide glass 11 where cDNA 12 is not placed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a microarray chip used for DNA analysis, immunological analysis, and the like, and a method and an apparatus for reading the microarray chip, and more particularly, to an improvement in the identification of the microarray chip.

[0002]

2. Description of the Related Art In recent years, the technology in the field of genetic engineering has rapidly developed, and the human genome project has been developed with one objective of decoding the base sequence of the human genome, which is thought to reach 100,000. ,Among the,
Enzyme-linked immunosorbent assays and fluorescent antibody assays that utilize antigen-antibody reactions are used for diagnosis and research, and research is underway to search for DNA that is affecting various genetic diseases.
Microarray technology has attracted attention as one of the methods.

[0003] This microarray technology uses a number of different known c-codes that have already been decoded, as shown in FIG.
This is a technique using a microarray chip (also referred to as a DNA chip) in which DNA (an example of a specific binding substance) is preliminarily applied in a matrix form on a chip such as a membrane filter or a slide glass at a high density (interval of several hundred μm or less). For example, DNA extracted from cells of a healthy subject A labeled with fluorescent dye a and D extracted from cells of sample B having a genetic disease, labeled with fluorescent dye b
NA is dropped on this microarray chip with a pipette or the like, and the DNA of each sample is compared with the cD on the microarray chip.
NA is hybridized, and thereafter, each cDAN on this microarray chip is scanned with excitation light for separately exciting each of the fluorescent dyes a and b, and each fluorescence of each cDNA is detected by a photodetector. From this detection result associated with the fluorescence emission position above, it was determined with which cDNA the DNA of each sample was hybridized, and the cDNA hybridized between the two samples was determined.
By comparing DNAs expressed by the above diseases,
Alternatively, it is a technique for identifying a defective DNA, and can be used for gene therapy by associating the disease with the identified DNA.

[0004]

By the way, various DNAs are dropped on the microarray chip in accordance with the purpose of analyzing the results later, and even when the same DNA is dropped, different concentrations and different reaction times are required. Is set, but
Conditions for such biological analysis (dropping DNA
Type, concentration, reaction time, etc.) are mainly set by the experimenter who performs the analysis, and the set analysis information is stored by the experimenter in association with each microarray chip, and later Based on this memory, the experimenter manually input the reading conditions corresponding to each analysis information into the microarray reader.

However, depending on the memory of the experimenter, various types of analysis information may be forgotten, or when the microarray chip is handed over to another experimenter during the experiment, the analysis information and the microarray chip may be lost. May not be able to be reliably delivered in correspondence with each other, and further, there is a possibility that an input error of the correspondence may occur at the stage of inputting the corresponding analysis information to the microarray reader.

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and provides a microarray chip in which the correspondence with analysis information is ensured. It is an object of the present invention to provide a method and an apparatus for reading a microarray chip that reliably associates the obtained image information with the analysis information.

[0007]

The microarray chip according to the present invention is characterized in that the microarray chip itself is attached with analysis information indicating conditions relating to biological analysis, and the microarray chip is associated with the analysis information corresponding to the microarray chip. It is a certainty.

That is, the microarray chip of the present invention is a microarray chip used for biological analysis of a specimen, in which a large number of specific binding substances known in advance are arranged on a flat chip. Analysis information indicating such a condition is attached.

The analysis information is preferably recorded in, for example, a readable optical format or a magnetic format. This is because handling is easy. The optical format may be recorded as, for example, a barcode, and the magnetic format may be recorded on, for example, a magnetic tape.These are attached to the slide glass of the microarray chip, and are attached to the microarray chip. It may be printed directly on the slide glass, but if the bar code sheet or magnetic tape is attached to the slide glass, it is peeled off after use, and a bar code or the like representing new information is used. By affixing the sheet or the like on which is displayed again, the slide glass can be repeatedly used, which is advantageous in recycling.
The recording format may be an optical format, a magnetic format, or a format recorded on an IC chip, for example.

The analysis information itself is not limited to the format attached to the microarray chip. For example, only chip identification information for individually identifying the microarray chip is attached to the microarray chip, and the chip identification information is stored in the LUT (lookup). The analysis information may be indirectly attached to the microarray chip by being associated with the corresponding analysis information by an up-table or the like. In this case, the chip identification information directly attached to the microarray chip is stored in an optical format, magnetic format,
It is preferably recorded in another format.

[0011] Known specific binding substances are substances that are widely involved in living organisms, such as hormones, tumor markers, enzymes, proteins, nucleic acids, antibodies, various substances that can be antigens, and various cDNAs and mRNAs. And a substance capable of immunologically binding or hybridizing with a substance derived from the organism of the specimen, and cDNA is particularly suitable.

The substance derived from the organism of the specimen is a substance representative of a substance capable of immunologically binding or hybridizing with a known specific binding substance placed on a slide glass. Examples of the substance include antibodies, antigens, substrates, DNA, mRNA, etc., and DNA is particularly suitable.

The biological analysis includes, for example, an immunological assay for detecting an antigen or an antibody utilizing a high specificity of an antigen-antibody reaction, a gene analysis using a so-called hybridization, a genetic diagnosis, a biotin- It means analysis utilizing specific binding such as the avidin method.

[0014] The analysis information includes information relating to a specific binding substance such as cDNA which is previously arranged on a slide of a microarray chip (the name of the species or tissue of the specific binding substance, the specific binding substance). Type / combination / location, GeneBank-Symbol, Accession-Number, GeneBa
nk-Name etc.).

The method for reading a microarray chip according to the present invention comprises the steps of: starting from a microarray chip used for biological analysis of a specimen, in which a number of specific binding substances known in advance are arranged on a flat chip; In the method for reading a microarray chip that photoelectrically reads information on the specific binding substance that has been processed according to the conditions related to analysis, the microarray chip according to the above-described microarray chip according to the present invention, that is, the conditions related to biological analysis. Is a microarray chip to which analysis information representing is attached, reads the analysis information attached to the microarray chip, the analysis information obtained by reading, and information by the specific binding substance obtained by reading. Are associated with each other.

In the method of reading a microarray chip according to the present invention, not only the analysis information attached to the microarray chip is read as described above, but further necessary information may be additionally readable.

The microarray chip reading apparatus of the present invention is an apparatus for carrying out the microarray chip reading method of the present invention, and includes a large number of known specific binding substances which are arranged on a flat chip. From a microarray chip used for biological analysis, a microarray chip reading device comprising photoelectric reading means for photoelectrically reading information on the specific binding substance processed according to the conditions related to the biological analysis, The microarray chip is a microarray chip according to the present invention as described above, that is, a microarray chip to which analysis information representing conditions relating to biological analysis is attached, and an attached information reading means for reading the analysis information attached to the microarray chip. Further comprising reading by the attached information reading means. And said analysis information, and is characterized in further comprising a correlation means for associating the information by the specific binding substance obtained by reading by the photoelectric reading means.

As the photoelectric reading means, a photomultiplier (PMT), a CCD, or other known means can be applied. Note that the photoelectric reading means may also function as the attached information reading means.

In the microarray chip reading apparatus of the present invention, in addition to the attached information reading means for reading the analysis information attached to the microarray chip as described above, an attached information recording for additionally writing necessary information in a readable manner. A configuration to which means is added may be adopted. In this case, a pen plotter, a magnetic recording head, or the like can be applied as an attached information recording unit that additionally records necessary information.

[0020]

According to the microarray chip of the present invention, since the analysis information indicating the conditions relating to the biological analysis is attached in an optical form such as a bar code or a magnetic form, the individual microarray chip can be used. The analysis information is securely associated. In other words, according to the conventional microarray chip, since the experimenter relied on the memory of the experimenter, the experimenter forgot the analysis information, or if the experimenter took over the microarray chip to another experimenter during the experiment, There is a possibility that the information and the microarray chip may not be reliably associated with each other and may not be delivered. In addition, at the stage of inputting the corresponding analysis information to the microarray reader, an input error of the correspondence between the microarray chip and the analysis information may occur. However, according to the microarray chip of the present invention, since the analysis information is associated with each microarray chip, even when the experimenter forgets the corresponding analysis information, the analysis information is associated with the microarray chip. By reading the analysis information
Each microarray chip can be reliably associated with analysis information. This makes it possible to appropriately perform subsequent processing (such as quantitative analysis processing of a specific binding substance).

When the microarray chip is handed over to another experimenter during the course of the experiment, the analysis information is attached to the microarray chip. it can. Further, at the stage of inputting the corresponding analysis information to the microarray reader, the analysis information attached to the microarray chip may be input as it is, so that it is possible to prevent the input error of these correspondences from occurring.

According to the method and the apparatus for reading a microarray chip of the present invention, the microarray chip is a microarray chip according to the present invention described above, that is, a microarray chip to which analysis information indicating conditions relating to biological analysis is attached. Yes, by reading the analysis information attached to the microarray chip, and by associating the analysis information obtained by reading with the information on the specific binding substance obtained by reading, the correspondence between each microarray chip and the analysis information Can be ensured.

[0023]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Specific embodiments of a microarray chip and a method and apparatus for reading a microarray chip according to the present invention will be described below with reference to the drawings.

FIG. 1 is a schematic perspective view showing the configuration of an embodiment of the microarray chip of the present invention. The illustrated microarray chip 10 has a large number of known cDNAs 12 arranged on a slide glass 11 in advance. The microarray chip 10 is attached to one end of the slide glass 11 in the longitudinal direction where the cDNAs 12 are not arranged. A bar code sheet 13 on which analysis information indicating the type, concentration, reaction time, and the like of DNA to be dropped from now on is displayed by a bar code 14 is attached.

The large number of cDNAs 12 arranged on the slide glass 11 of the present embodiment are different types of cDNAs, respectively, and are the types of cDNAs 12 combined for examining the presence or absence of a specific genetic disease.

As described above, the microarray chip 1
0, the conditions for the subsequent analysis (D
By attaching analysis information representing NA type, concentration, reaction time, and the like to the microarray chip 10 as a barcode 14, the microarray chip can be used even when an experimenter forgets the corresponding analysis information. 10
By reading the barcode 14 associated with the information, the microarray chip 10 and the analysis information can be reliably associated. This makes it possible to appropriately perform subsequent processing (such as quantitative analysis processing of a specific binding substance).

Also, when the microarray chip 10 is taken over by another experimenter during the course of the experiment, the barcode 14 representing the analysis information is attached to the microarray chip 10. It can be handed over reliably. Further, at the stage of inputting the corresponding analysis information to the microarray reader, the barcode 14 attached to the microarray chip 10 may be directly input using barcode reading means or the like. Can be prevented from occurring.

Although the microarray chip of the present embodiment displays the analysis information by the bar code 13, the microarray chip of the present invention is not limited to this mode, and the analysis information is recorded in a magnetic format. A mode in which a magnetic tape or an IC chip is attached to the slide glass 11 may be used.

FIG. 2 is a diagram showing an embodiment of a reading apparatus for carrying out the method for reading a microarray chip according to the present invention.

The illustrated microarray chip reader 10
0 indicates a number of known cDNAs 1 on the slide glass 11.
2 is a device for photoelectrically reading the hybridization state of each cDNA 12 by photoelectric reading means 20 after hybridization with a microarray chip 10 ′ in which microarrays 2 are arranged in advance according to predetermined analysis conditions. ′
On a portion of the slide glass 11 on which the cDNA 12 is not placed, analysis information 14 ', which is a hybridization condition indicating the type, concentration, reaction time, etc. of the DNA dropped on the microarray chip 10', is magnetically recorded. A tape 13 'is attached, and the reading device 1
00 is the analysis information 1 recorded on the magnetic tape 13 '.
Magnetic head 3 as attached information reading means for reading 4 '
0, the associating means 40 for associating the analysis information 14 'obtained by reading with the magnetic head 30 with the image information P indicating the hybridization state of each cDNA 12 obtained by reading by the photoelectric reading means 20. It is a configuration provided.

Next, the operation of the microarray chip reader 100 of this embodiment will be described.

First, the microarray chip 10 'is subjected to a hybridization process in accordance with the analysis information 14' magnetically recorded on the magnetic tape 13 ', and a part of a large number of arranged cDNAs 12 is hybridized. Hybridized cDN
A12 emits fluorescence. The emitted fluorescent light is photoelectrically read as image information P by the photoelectric reading means 20.

On the other hand, the analysis information 14 ′ recorded on the magnetic tape 13 ′ is read by the magnetic head 30. The analysis information 14 ′ read by the magnetic head 30 and the image information P read by the photoelectric reading means 20 are respectively input to the associating means 40, and the associating means 40 inputs the image information P and the analysis information 14. ′ And
The data is output to an external quantitative analyzer (not shown).

As described above, according to the microarray chip reader 100 of the present embodiment, the microarray chip 1
Since the analysis information 14 'read from 0' and the image information P 'are surely associated with each other, it is possible to prevent an input error in the correspondence between them.

The reading apparatus of this embodiment uses a microarray chip in which the analysis information is recorded on a magnetic tape. However, the reading apparatus shown in FIG. 1 has a format in which the analysis information is recorded in a barcode. A mode using a microarray chip may be used, in which case, a configuration may be adopted in which photoelectric detection means such as a CCD is applied instead of the magnetic head,
Further, the photoelectric reading means 20 may be configured to have the function of the photoelectric detecting means.

[Brief description of the drawings]

FIG. 1 is a perspective view showing one embodiment of a microarray chip of the present invention.

FIG. 2 is a diagram showing one embodiment of a microarray chip reader of the present invention.

FIG. 3 is a diagram showing a conventional microarray chip.

[Explanation of symbols]

 10 Microarray chip 11 Slide glass 12 cDNA 13 Barcode sheet 13 'Magnetic tape 14 Barcode 14' Analysis information 20 PMT 30 Magnetic head 40 Corresponding means 100 Microarray chip reader

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Shu Sato 798 Address Miyagidai, Kaisei-cho, Ashigara-gun, Kanagawa Prefecture Inside (72) Inventor Masashi Hakamada 798 Miyadaidai, Kaisei-cho, Ashigara-gun, Kanagawa Fuji Photo Film In-house F term (reference) 2G043 AA01 BA16 CA03 DA01 DA06 EA01 EA06 EA15 EA17 FA01 LA03 NA02 2G058 AA09 CC14 GA01 GA11 GC02 4B024 AA11 AA19 CA01 CA11 CA12 HA12 4B029 AA07 AA07 BB20 CC03 FA02 QA01 QAQ QQ4 QR32 QR36 QR48 QR51 QR56 QR66 QR84 QS03 QS28 QS33 QS34 QS36 QX02

Claims (6)

[Claims] 1. A microarray chip for use in biological analysis of a specimen, in which a large number of specific binding substances known in advance are arranged on a flat chip, analysis information representing conditions relating to the biological analysis. A microarray chip characterized by the following. 2. The microarray chip is attached with chip identification information for individually identifying the microarray chip, and the chip identification information is associated with the corresponding analysis information, so that the analysis information is stored in the microarray chip. The microarray chip according to claim 1, wherein the microarray chip is attached. 3. The microarray chip according to claim 1, wherein the analysis information or the chip identification information attached to the microarray chip is recorded in a readable optical format. 4. The microarray chip according to claim 1, wherein the analysis information or the chip identification information attached to the microarray chip is recorded in a readable magnetic format. 5. A microarray chip used for biological analysis of a sample, in which a large number of specific binding substances known in advance are arranged on a flat chip, processed according to the conditions relating to the biological analysis. In a reading method of a microarray chip for reading information by the specific binding substance photoelectrically, the microarray chip is the microarray chip according to any one of claims 1 to 4, and is attached to the microarray chip. Reading the analysis information, and associating the analysis information obtained by the reading with the information on the specific binding substance obtained by the reading. 6. A microarray chip used for biological analysis of a sample, in which a large number of specific binding substances known in advance are arranged on a flat chip, and processed according to the conditions relating to the biological analysis. In a microarray chip reader comprising a photoelectric reading means for photoelectrically reading information by the specific binding substance, wherein the microarray chip is the microarray chip according to any one of claims 1 to 4, Further comprising an attached information reading means for reading the analysis information attached to the microarray chip, wherein the analysis information obtained by reading by the attached information reading means and the specific binding obtained by reading by the photoelectric reading means. Microarrays further comprising association means for associating information with substances. Chip reading device.