JP2008298516A - Dna chip processor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a DNA chip processor capable of keeping the hermetically sealed state of a section in which a DNA chip is housed though constituted so as to easily open and close the opening of a plate. <P>SOLUTION: The DNA chip processor is composed of a plate 3 having a plurality of sections 2 in which a plurality of DNA chips 1 are respectively housed, an hermetic seal material 5 for hermetically closing the opening of the plate 3, a temperature adjusting mechanism 10 capable of holding the liquid 4 held in the sections 2 to a set temperature, a cover 6 for fixing the plate 3 and the hermetic seal material 5, a moving mechanism 7 for moving the cover 6 in a horizontal or vertical direction with respect to the plate 3 and a pressing mechanism 9 for pressing the cover 6 to the plate 3 under predetermined pressure. A space 8 is provided to the contact part with the opening of the plate 3 of the cover 6. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an apparatus for hybridizing and washing a DNA chip.

  In recent years, a new analysis method or methodology called DNA microarray method (DNA chip method) that enables collective expression analysis of a large number of genes has been developed and attracts attention. All of these methods are nucleic acid detection and quantification methods based on nucleic acid-nucleic acid hybridization reactions, and a method is used in which a large number of DNA fragments are aligned and immobilized on a flat substrate called a microarray or chip. There is a big feature in the point. As a specific method of using the microarray method, for example, a sample obtained by labeling a gene expressed in a cell to be studied with a fluorescent dye or the like is hybridized on a flat base piece, and complementary nucleic acids (DNA or RNA) are bound to each other. There is a method in which the portion is labeled with a fluorescent dye or the like and then read at high speed with a high resolution analyzer. Thus, the amount of each gene in the sample can be quickly estimated. With the introduction of this new method, it has become possible to reduce the amount of reaction sample and to analyze and quantify the reaction sample in a large amount, quickly and systematically with high reproducibility.

  In addition to the above-described planar base piece, for example, a polymer gel in which a probe that functions as a probe for a substance to be inspected is immobilized has a microarray. A DNA chip (DNA microarray) having a structure in which a fixed polymer gel is held is known. As an example, there is disclosed a DNA microarray (fiber type DNA microarray) in which holes are formed of hollow fibers (see, for example, Patent Document 1).

  Also, a DNA chip processing apparatus is disclosed that can handle a large amount of DNA chips in a simple manner and efficiently with respect to hybridization and washing treatment of the fiber-type DNA microarray (see, for example, Patent Document 2). .

  Here, processing steps (hybridization step, washing step) of the conventional DNA chip processing apparatus will be described with reference to FIG. The DNA microarray 101 is inserted into the compartment 102 of the hybridization and washing plate (hereinafter referred to as plate 103). Next, after injecting the specimen 104 from the opening of the plate 103, each compartment is sealed with an adhesive film 105 to prevent evaporation of internal liquid and contamination. Next, in order to fix the plate 103, the cover part 106 is arranged on the upper part of the plate 103, and the plate 103 is firmly fixed by the cover part set screw 107. Thereafter, the hybridization step is started under predetermined conditions (temperature, time, etc.).

  When the execution time of the hybridization process is completed, the washing process is started. In the cleaning process, the nozzle 108 is moved to a predetermined position in each section 102 by the moving mechanism 109 of the cleaning liquid injection nozzle and the cleaning liquid suction nozzle (hereinafter referred to as the nozzle 108), and the nozzle 108 is lowered at that position. The adhesive film 105 is punctured by the nozzle 108 through the film puncture port 110, and cleaning liquid injection and suction are performed.

Here, the cleaning liquid switching valve 112 that selects the cleaning liquid, the cleaning liquid pump 113 that sucks and discharges the cleaning liquid, the suction and discharge switching valve 114 that can select the suction and discharge, and the cleaning liquid are controlled to a predetermined temperature from the cleaning liquid bottle 111 containing the cleaning liquid. Using the heat exchange unit 115, a cleaning liquid having a predetermined temperature is injected from the nozzle 108 into each section of the plate 103. Further, the waste liquid sucked from the plate 103 is sucked by the waste liquid pump 116 and collected in the waste liquid bottle 117.
JP 2001-133453 A JP 2006-3349 A

  However, in the conventional configuration, in order to seal the compartment in which the DNA chip is stored so that water vapor generated at the time of hybridization does not escape to the outside, a cover part is arranged on the upper part of the plate, and the plate is fixed with a cover part set screw. Since it is fixed, the opening of the plate cannot be easily opened and closed.

  The present invention solves the above-described conventional problems, and provides a DNA chip processing apparatus capable of maintaining the hermetically sealed compartment in which the DNA chip is housed while being configured to easily open and close the opening of the plate. For the purpose.

  In order to solve the conventional problems, a DNA chip processing apparatus of the present invention includes a plate having a plurality of compartments in which each of a plurality of DNA chips is accommodated, a sealing material that seals the plate opening, A temperature adjusting mechanism capable of holding the liquid held in the compartment at a set temperature; a cover portion for fixing the plate and the sealing material; and a moving mechanism for moving the cover portion horizontally or vertically with respect to the plate. And a pressing mechanism that presses the cover portion against the plate with a predetermined pressure, and a space is provided in a portion of the cover portion that contacts the opening of the plate.

  In the DNA chip processing apparatus, the cover unit further includes a cleaning liquid injection nozzle for injecting a cleaning liquid, a cleaning liquid suction nozzle for sucking the cleaning liquid, a cleaning liquid injection nozzle for injecting the cleaning liquid, and a cleaning liquid suction nozzle for sucking the cleaning liquid. It is characterized by that.

  Further, in the DNA chip processing apparatus, the space of the cover part is characterized in that it has a volume larger than at least a volume in which the air in the compartment expands due to a temperature rise.

  Furthermore, in the DNA chip processing apparatus, the cover part is provided with an air port for allowing air in the space of the cover part to pass therethrough.

  Furthermore, the DNA chip processing apparatus is characterized in that the moving mechanism is provided with a control unit for matching the opening of the plate and the space of the cover.

  Further, in the DNA chip processing apparatus, the sealing material is extendable and contractible.

  According to the DNA chip processing apparatus of the present invention, it is possible to prevent the water vapor generated in the compartment containing the DNA chip from leaking outside during hybridization while facilitating the opening and closing of the plate and the cover.

  Hereinafter, embodiments of the DNA chip processing apparatus of the present invention will be described in detail with reference to the drawings.

(Embodiment 1)
FIG. 1 is a cross-sectional view of the DNA chip processing apparatus according to the first embodiment of the present invention, FIG. 2 is a detailed view of the cover of the DNA chip processing apparatus according to the first embodiment of the present invention, and FIG. The plate block diagram of the DNA chip processing apparatus in the 1st Embodiment of this invention is each shown. 3A is a top view of the plate 3, and FIG. 3B is a cross-sectional view of the plate 3.

  In FIG. 1, the DNA chip processing apparatus of the present invention contains a DNA chip 1, a compartment 2 into which a liquid specimen 4 is injected, a plate 3 having a plurality of compartments 2, and a compartment 2 disposed on the plate 3. , A cover portion 6 disposed on the plate 3, a moving mechanism 7 for moving the cover portion 6 up and down, a pressing mechanism 9 for pressing the cover portion 6 against the plate 3, and a heater for heating the plate 3. 10. Further, the cover 6 has a space 8 and an air port 11. Further, a nozzle 52 is disposed at a predetermined position of the cover portion 6.

  Here, a description of the hybridization process using the DNA chip processing apparatus will be given with reference to FIGS. 1, 2, and 3. FIG. In FIG. 1, the DNA chip 1 is inserted into a plate 3 for performing hybridization and washing having a plurality of compartments 2 in which a plurality of DNA chips 1 are accommodated, and the specimen 4 is inserted from the opening of each compartment. inject. Next, the film 5 for preventing contamination of the specimen is attached to the cover portion 6 for fixing the plate 3.

  Here, regarding the mounting of the film 5 on the cover portion 6, for example, in FIG. 2, the film mounting portion 50 is provided in a portion where the plate 3 and the cover portion 6 are in contact with the cover portion 6. To put. The film 5 has a size that can cover the range 53 excluding the nozzle 52, and the film mounting unit 50 can mount a film of that size.

  Next, in the operation of the apparatus before the start of hybridization, the cover unit 6 is moved to a position where the entire plate 3 can be sealed by the moving mechanism 7 that moves the cover unit 6 horizontally or vertically with respect to the plate 3. At this time, the cover 6 is moved so that the space 8 of the cover provided corresponding to each section 2 of the plate 3 coincides with the opening 61 of each section 2 of the plate 3.

  Here, it is better to position the cover unit 6 when moving it by providing a reference position. For example, in a configuration in which the cover unit 6 and the nozzle 52 are integrated as shown in FIG. Each section of the plate 3 is arranged at a relative position from the nozzle storage section 60 shown in FIG. 3, so that the position at which the space 8 of the cover section is provided is also determined. The space 8 of the cover part can be easily matched.

  In addition, each section of the plate 3 is securely sealed using a pressing mechanism 9 that presses the cover portion 6 against the plate 3 and a moving mechanism 7 of the cover portion. For example, the predetermined pressing force is realized by moving the cover portion by a predetermined distance in the direction perpendicular to the plate by the moving mechanism 7 and using the force of the spring provided in the pressing mechanism 9.

  In this way, hybridization can be performed with this apparatus. Further, since the cover 6 and the film 5 are moved in conjunction with each other by the moving mechanism 7, the opening of the plate 3 can be easily opened and closed, and the nozzle 52 punctures the film 5 during the cleaning operation. Therefore, stable cleaning performance can be realized.

  While the hybridization is being performed, the plate 3 is hermetically sealed, and the temperature is controlled by the heater 10 so as to reach a predetermined temperature. However, during the hybridization, the internal temperature in each section of the plate 3 increases. Since the internal air expands and the internal pressure rises, the film 5 is pushed up by the volume of the expanded air. Since the volume of the expanded air can be released to the space 8 of the cover portion, the increase in internal pressure in each section of the plate 3 can be reduced.

  This prevents the specimen 4 from evaporating due to a gap generated between the cover 6 and the plate 3 due to an increase in internal pressure in each section of the plate 3, thereby reducing the amount of the specimen. 2 can ensure the uniformity of the reaction conditions of each DNA chip 1 and the specimen 4 housed in 2.

Further, the volume of the space 8 in the cover part needs to be provided at least by the volume of air that expands due to a temperature change during hybridization. For example, assuming that the room temperature is T ₁ , the hybridization execution temperature T ₂ , the height of the air-existing portion of each section of the plate 3 is h 1, and the height of the space 8 of the cover portion is h 2, h 2 from Charles' law Is obtained from the following equation.

  However, the area of the space 8 of the cover part and the area of the opening of each section of the plate 3 are the same, and the specimen 4 is injected up to the height h3. Further, during the execution of hybridization, air is passed through so that the pressure balance between the pressure in the space 8 of the cover portion and the internal pressure of each section of the plate 3 is not balanced while the opening of the plate 3 is closed with the film 5. An air port 11 is provided. By doing so, the increase in internal pressure in each section of the plate 3 can be easily released to the space 8 of the cover portion.

  The film 5 can be sufficiently expanded and contracted with changes in the internal pressure of each section of the plate 3, and for example, polyolefin or the like is used.

  As described above, according to the first embodiment, since the cover portion is provided with a space serving as a pressure relief portion due to thermal expansion of the specimen, the cover portion is kept sealed without being screwed, and the specimen is evaporated to the outside. Can be prevented.

  The DNA chip processing apparatus according to the present invention can easily open and close the opening of the plate in which the DNA chip is housed, and further has the effect of preventing evaporation of the sample in the plate during hybridization. It is useful as a gene analyzer that can be processed quickly.

Configuration diagram of DNA chip processing in the first embodiment of the present invention Detailed view of the cover of the DNA chip processing apparatus in the first embodiment of the present invention Plate configuration diagram of the DNA chip processing apparatus in the first embodiment of the present invention Configuration diagram of conventional DNA chip processing apparatus

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 DNA chip 2 Compartment 3 Plate 4 Specimen 5 Film 6 Cover part 7 Movement mechanism 8 Cover part space 9 Pressing mechanism 10 Heater 11 Air port 50 Film mounting part 50a Film mounting range 51 Insertion port 52 Nozzle 53 Cleaning liquid bottle 54 Cleaning liquid switching valve 55 Cleaning liquid pump 56 Suction / discharge switching valve 57 Heat exchange unit 58 Exhaust pump 59 Waste liquid bottle 60 Nozzle storage part 61 Opening part 101 DNA microarray 102 Partition 103 Plate 104 Sample 105 Adhesive film 106 Cover part 107 Set screw 108 Nozzle 109 Moving mechanism 110 Film puncture Mouth 111 Cleaning liquid bottle 112 Cleaning liquid switching valve 113 Cleaning liquid pump 114 Suction / discharge switching valve 115 Heat exchange unit 116 Exhaust pump 117 Waste liquid bottle

Claims (6)

A plate having a plurality of compartments each accommodating a plurality of DNA chips;
A sealing material for sealing the plate opening;
A temperature adjustment mechanism capable of holding the liquid held in the compartment at a set temperature;
A cover portion for fixing the plate and the sealing material;
A moving mechanism for moving the cover part horizontally or vertically with respect to the plate;
A pressing mechanism that presses the cover portion against the plate with a predetermined pressure;
A space is provided in a portion of the cover that contacts the opening of the plate.
DNA chip processing equipment. A cleaning liquid injection nozzle for injecting the cleaning liquid;
A cleaning liquid suction nozzle for sucking the cleaning liquid;
The cover portion further includes a cleaning liquid injection nozzle for injecting the cleaning liquid and a cleaning liquid suction nozzle for sucking the cleaning liquid.
The DNA chip processing apparatus according to claim 1. The space of the cover part is
At least a volume larger than the volume in which the air in the compartment expands due to a temperature rise,
The DNA chip processing apparatus according to claim 1. The cover part is
An air port that allows air in the space of the cover portion to pass through;
The DNA chip processing apparatus according to claim 1. In the moving mechanism,
A control unit for matching the opening of the plate and the space of the cover unit;
The DNA chip processing apparatus according to claim 1. The sealing material is extensible.
The DNA chip processing apparatus according to claim 1.

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