JP2004357698A - Treatment apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a treatment apparatus with a comparatively simple structure, having a stirring means with simple structure, for stirring liquid to be treated on a sheet-like substrate on which the object to be treated is adhered. <P>SOLUTION: The treatment apparatus allows treatment of the object S by a treating liquid R present on the adhering face P1 of the sheet-like substrate P on which the object S is adhered. The treatment apparatus is provided with a treating section on which the substrate P is installed, a stirring member 3 which has a flat face 31 and installed on the countering position to the adhered face P1 with a space and a displacement means which displaces the stirring member 3 to the face direction of the adhered face P1. The treatment apparatus has a distance regulating means 5 which keeps the gap distance h1 of the prescribed gap constant, and the displacement of the stirring member 3 by the actuation of the displacement means comprises the displacement with a gap constant distance h1. The treatment apparatus stirs the treating liquid R in a state filling the gap with the treating liquid R and then displacing the stirring member 3 by operating the displacing means. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a processing device.

  For example, when performing a process such as hybridization for nucleic acids (RNA, DNA), a nucleic acid (object to be treated) is attached to a plate (support), and a treatment solution is supplied to the nucleic acid (contact). Processing) is performed.

  As a method of bringing the nucleic acid into contact with the treatment liquid, the treatment liquid is dropped on each support, and further, a developing member is overlapped thereon, and the treatment liquid is filled in a gap formed therebetween. By developing, the nucleic acid is brought into contact with the treatment liquid.

  In the conventional processing apparatus, a cover plate (development member) 560 is superimposed on a microarray M which is a plate (support) P to which an object to be processed is attached, and a gap 569 formed between the microarray M and The processing liquid for processing the object to be processed is developed (for example, see Patent Document 1). Note that the code used here is the code described in Patent Document 1.

  As described above, in the above-described sample processing apparatus, when processing a plurality of microarrays (plates), the processing liquid is individually dropped onto each microarray using a dispenser or the like, and the processing is performed on the cover plate (development member). The liquid was developing. However, since there is no means for stirring (agitation) the developed processing solution, there is a problem that stirring cannot be performed sufficiently and unevenness occurs in the processing solution. That is, there was a problem that there was no means for stirring the treatment solution over the entire nucleic acid attached to the plate.

JP-A-2003-57245

  An object of the present invention is to provide a processing apparatus which has a relatively simple structure and has a stirring means for stirring a processing liquid existing on a plate-like support to which an object to be processed is attached with a simple structure. is there.

Such an object is achieved by the present invention described in the following (1) to (8).
(1) A processing apparatus for processing an object to be processed by a processing liquid existing on an attachment surface of a plate-shaped support to which the object is attached,
A processing unit in which the support is installed,
A stirrer having a flat surface opposed to the adhesion surface with a gap therebetween,
Displacing means for displacing the stirring member in the plane direction of the adhesion surface,
A processing apparatus, wherein the stirring member is displaced by the operation of the displacement means in a state where the processing liquid is filled in the gap, and the processing liquid is stirred.

  (2) The processing apparatus according to (1), wherein the stirring member reciprocates at least on the attachment surface by the operation of the displacement unit.

  (3) The processing apparatus according to (1) or (2), further including a distance regulating unit that keeps a gap distance of the gap constant.

  (4) The processing apparatus according to (3), wherein the distance regulating unit is provided near an edge of the plane, and is configured by a spacer that abuts inside the processing unit and keeps the gap distance constant.

  (5) The processing apparatus according to (3), wherein the distance regulating unit is provided near an edge of the plane, and is configured by a spacer that abuts on the support to keep the gap distance constant.

  (6) The processing apparatus according to (4) or (5), wherein the plane has a substantially quadrangular shape, and the spacer is provided at least at four corners of the plane.

(7) the distance restricting means includes a projecting portion projecting from the stirring member in parallel with the plane;
The processing apparatus according to (3), further including a contact portion formed on the processing unit side and contacting the protruding portion.

  (8) The processing apparatus according to any one of (1) to (7), wherein at least a portion of the stirring member for stirring the processing liquid has hydrophilicity.

  ADVANTAGE OF THE INVENTION According to this invention, the processing liquid which exists on the plate-shaped support body to which the to-be-processed object was adhered can be stirred with a comparatively simple structure.

  Further, according to the present invention, the processing liquid can be uniformly and reliably stirred with a small amount of the processing liquid with respect to the processing target adhered to the support.

Hereinafter, a processing apparatus of the present invention will be described in detail based on preferred embodiments shown in the accompanying drawings.
<First embodiment>
In the following, a nucleic acid (DNA, cDNA, RNA, etc.) is represented as an example of the object to be treated, and a microarray (DNA chip) in which the nucleic acid (nucleic acid fragment) is attached to a plate (support) in a scattered manner. A case in which the processing apparatus of the present invention is applied to a microarray processing apparatus for processing the above will be described.

  In addition, as an example of the treatment liquid (reaction liquid), a nucleic acid (for example, mRNA, DNA, or the like) collected from a subject or a nucleic acid (for example, cDNA or the like) synthesized based on this nucleic acid is labeled (for example, a dye, a fluorescent light, or the like). A liquid containing a substance (probe) labeled with a substance, a radioactive substance, or the like (hereinafter, referred to as a “probe liquid”) will be described as a representative.

  The treatment referred to herein preferably refers to hybridization of the nucleic acid adhered to the plate in a scattered manner with the nucleic acid or probe contained in the probe solution.

  1 is an overall configuration diagram showing a first embodiment of the processing apparatus of the present invention, FIG. 2 is a cross-sectional view taken along line AA in FIG. 1, and FIG. 3 is a cross-sectional view taken along line BB in FIG. It is a bottom view (Y) of X) and the stirring member with which the processing apparatus in FIG. 1 is provided. In the following, for convenience of explanation, the upper side of FIG. 1 (also in FIGS. 2 and 3) is referred to as “upper” or “upper”, and the lower side is referred to as “lower” or “lower”. The left side is called “left” or “left”, and the right side is called “right” or “right”. However, the nucleic acids in FIG. 1 (similarly in FIGS. 2, 3, 4, and 5) are exaggerated for the sake of description.

  The processing apparatus 1 shown in FIG. 1 is present on an attachment surface P1 of a plate-like plate (support) P (microarray M) on which nucleic acids (objects to be treated) S are attached (scattered). This is a processing apparatus for processing a nucleic acid S with a probe liquid (processing liquid) R. The processing apparatus 1 has a processing unit 2 on which a plate P is installed, a flat surface 31 opposed to an attachment surface P1 via a gap, a stirring member 3 for stirring the probe liquid R, and a stirring member. And a displacement means 4 for displacing 3 in the plane direction of the attachment surface P1.

  In the processing apparatus 1 of the present invention, it is preferable that the processing apparatus 1 is housed in a hermetically sealed airtight tank (not shown) and the processing is performed in an environment in which temperature and humidity are controlled.

  Further, according to the processing apparatus 1, the nucleic acid S can be reacted with the probe solution R, and the nucleic acid S can be treated with various liquids. From the reaction results of the nucleic acid S, for example, mutation analysis of gene DNA (nucleic acid), polymorphism analysis, base sequence analysis, expression analysis (presence / absence), and diagnosis of various diseases based on these are performed. It can be suitably performed. Hereinafter, the configuration of each unit will be described.

  The processing unit 2 has a bottom plate 21 formed on the upper surface so that one or more plates P can be installed (placed).

  The stirring member 3 has a main body 32 on which a flat surface 31 is formed. Further, the stirring member 3 is placed (placed) on the bottom plate 21 (attachment surface P1) such that the flat surface 31 is arranged to face the attachment surface P1 on the bottom plate 21 with a gap therebetween, and The probe liquid R filled in is stirred.

  The displacement unit 4 has a moving mechanism 41 that moves (displaces) the stirring member 3 in the plane direction of the attachment surface P1. The movement mechanism 41 has an air cylinder 411 as a movement drive source, and a connection member 412 that connects the stirring member 3 and the air cylinder 411. The air cylinder 411 is fixed to, for example, a part of the processing apparatus 1. The connection member 412 is connected to the air cylinder 411 coaxially with the longitudinal axis of the air cylinder 411. The connection member 412 connects (connects) the stirring member 3 and the air cylinder 411 such that the expansion / contraction direction of the air cylinder 411 (the direction in which the air cylinder 411 is drawn in and pushed out) is parallel to the plane 31.

  In the present embodiment, the stirring member 3 and the connection member 412 are configured as separate members, but may be configured to be integrally formed.

  In the illustrated configuration, the air cylinder 411 is used as the moving drive source, but the invention is not particularly limited to the air cylinder. For example, a motor drive, a gear mechanism, or the like may be used.

  Further, the stirring member 3 is drawn in or pushed out by the operation of the air cylinder 411 (moving mechanism 41), so that the stirring member 3 reciprocates on the bottom plate 21. Since the probe liquid stirred by the stirring member 3 is present on the attachment surface P1, the range in which the stirring member 3 reciprocates is at least sufficient as long as it is on the attachment surface P1.

  The processing apparatus 1 includes a distance regulating unit 5 that keeps a constant gap distance h1 between the plane 31 and the attachment surface P1.

  The distance regulating means 5 is constituted by a spacer 51 for keeping the gap distance h1 constant. The spacer 51 is formed near the edge of the flat surface 31 so as to contact the bottom plate 21 (inside the processing unit 2). The spacer 51 has a function of holding the plane member 31 and the attachment surface P1 such that the stirring member 3 is superimposed on the microarray M so that the plane 31 and the attachment surface P1 are substantially parallel to each other without being inclined with respect to the other. It is. That is, the spacer 51 has a function of keeping the gap distance h1 almost constant.

  Further, as shown in FIG. 3 (Y), the plane 31 has a substantially rectangular shape (square shape), and in the present embodiment, the four spacers 51 are respectively provided near the edges of the plane 31, particularly, It is provided in the four corners. Each spacer 51 is set to have substantially the same thickness. With such a configuration, the gap distance h1 can be maintained more easily and accurately.

  In the present embodiment, the plane 31 and the spacer 51 are configured as separate members, but they may be integrally formed.

  It is preferable that each spacer 51 has a substantially fan-like shape in plan view. Thereby, the air bubbles in the probe liquid R can be better discharged from the gap between the flat surface 31 and the attachment surface P1.

  The configuration of the spacer 51 is not limited to the illustrated one as long as it can regulate the gap between the flat surface 31 and the adhesion surface P1, that is, can maintain the gap distance h1 substantially constant. . For example, it is possible to adopt a configuration in which a plurality of spacers 51 are provided near the edge of the plane 31. For example, when five or more spacers 51 are provided, it is preferable to provide them at least at four corners of the plane 31 as in the present embodiment.

  In such a processing apparatus 1, the stirrer 3 reciprocates and adheres by the operation of the moving mechanism 41 (displacement means 4) in a state where the probe liquid R is filled in the gap (liquid passage portion) with the gap distance h1. The probe liquid R on the surface P1 is uniformly stirred. That is, the stirring member 3 reciprocated by the operation of the moving mechanism 41 causes the probe liquid R existing on the attachment surface P1 to flow. By this flow, the probe present in the probe solution R spreads over the entirety of the attachment surface P1, so that the probe can reliably react with the nucleic acid S on the attachment surface P1.

  In addition, since the stirring member 3 (the flat surface 31) is configured to stir the probe liquid R in this manner, the flat surface 31 of the stirring member 3 is changed according to the area (area) of the probe liquid R on the plate P. By appropriately setting the area (position), the probe liquid R can be more efficiently stirred and the drying of the probe liquid R can be suppressed.

  Further, for example, when air bubbles exist between the stirring member 3 (the flat surface 31) and the probe liquid R, the air bubbles are pushed out by the reciprocating movement of the stirring member 3, so that the probe can be more efficiently used. The liquid R can be stirred.

  Next, a preferable surface state of the stirring member 3 will be described. It is preferable that at least the portion of the stirring member 3 for stirring the probe liquid R has a hydrophilic property. That is, it is preferable that the stirring member 3 itself is made of a material having hydrophilicity, or that the surface thereof is subjected to a hydrophilic treatment. Here, hydrophilicity means that the contact angle with water is preferably 40 degrees or less, more preferably about 1 to 30 degrees.

  The fact that the portion of the stirring member 3 that comes into contact with the probe liquid R has hydrophilicity is effective in stirring the probe liquid R even when the amount is small. That is, as shown in FIG. 3, the meniscus J formed by the probe liquid R attached to the stirring member 3 moves (reciprocates) together with the stirring member 3 so that the probe liquid R flows and is stirred. . This indicates that hydrophilicity is important for making the meniscus J to some extent effective.

  Further, since the stirring member 3 is located at the position where the gap distance h1 is maintained by the spacer 51 (distance regulating means 5), the reciprocation of the stirring member 3 by the operation of the moving mechanism 41 makes the gap distance h1 constant. The reciprocation is maintained. Thus, the stirring member 3 can stir the probe liquid R on the attachment surface P1 under uniform conditions. Here, the uniform condition means that the stirring member 3 does not intermittently separate from the probe solution, does not interfere with the nucleic acid S, or the like.

  The ratio h1 / h2 of the gap distance h1 to the depth h2 of the probe liquid R excluding the meniscus J on the plate P is not particularly limited, but is preferably 0.7 to 1.5, and 0.85. More preferably, it is .about.1.2. When the ratio h1 / h2 exceeds the upper limit, when the hydrophilicity of the stirring member 3 is not sufficient, the meniscus J is difficult to be properly formed, or the stirring member 3 continuously stirs the probe liquid R. It may not be possible or the stirring efficiency may decrease. If the ratio h1 / h2 is less than the lower limit, the distance between the stirring member 3 and the attachment surface P1 becomes short, so that the stirring member 3 may interfere with the nucleic acid S depending on the movement accuracy of the stirring member 3. There is.

  In this embodiment, the stirring member 3 may develop the probe liquid R supplied to the attachment surface P1 on the attachment surface P1. The spacer 51 makes it possible to accurately adjust the amount of the probe solution R supplied to the nucleic acid S on the attachment surface P1, and to uniformly spread the probe solution R on the nucleic acid S. . As a result, an accurate reaction result of the nucleic acid S can be obtained.

<Second embodiment>
FIG. 4 is an overall configuration diagram showing a second embodiment of the processing apparatus of the present invention, and FIG. 5 is a sectional view taken along line AA in FIG. 4 and 5 are referred to as "up" or "upper", the lower side is referred to as "lower" or "lower", and the left side of FIG. 4 is referred to as "left" or "left". The right side is called "right" or "right side."

  Hereinafter, a second embodiment of the processing apparatus of the present invention will be described with reference to these drawings, but the description will focus on differences from the above-described first embodiment, and description of similar items will be omitted.

  The processing apparatus 1 'of this embodiment shown in FIG. 4 is the same as the first embodiment except that the configuration of the distance regulating means is different.

  The distance restricting means 5 ′ has a protruding portion 52 protruding from the main body 32 and a contact portion 53 formed on the processing unit 2 side, with which the protruding portions 52 abut. The protruding portions 52 are formed so as to protrude from the main body 32 in directions opposite to each other in a direction parallel to the plane 31 and substantially perpendicular to the direction of reciprocation of the stirring member 3 by the operation of the moving mechanism 41. The contact portions 53 are respectively formed on the bottom plate 21 in a direction perpendicular to the bottom plate 21 so as to contact the outer peripheral surfaces of the protruding portions 52 so that the gap between the flat surface 31 and the attachment surface P1 keeps the gap distance h1. I have. Note that the distance regulating means 5 'may be formed on the main body 32 so that the protruding portions 52 are opposite to each other as in the present embodiment, or one of the protruding portions 52 formed. Only the protrusion 52 may be formed on the main body 32.

  In the present embodiment, the main body 32 and the protruding portion 52 are configured as separate members, but they may be integrally formed.

<Third embodiment>
7 is an overall configuration diagram showing a third embodiment of the processing apparatus of the present invention, FIG. 8 is a cross-sectional view taken along line AA in FIG. 7 (X), and a lower surface of a stirring member provided in the processing apparatus in FIG. FIG. In the following, for convenience of description, the upper side of FIG. 7 (also in FIG. 8) is referred to as “upper” or “upper”, and the lower side is referred to as “lower” or “lower”.

  Hereinafter, a third embodiment of the processing apparatus of the present invention will be described with reference to these drawings, but the description will focus on differences from the above-described first embodiment, and description of similar items will be omitted.

  The processing apparatus 1 of the present embodiment shown in FIG. 7 is the same as the first embodiment except that the shape of the distance regulating means is different.

  The distance regulating means 5A is constituted by a spacer 54 for keeping the gap distance h1 constant (see FIGS. 7 and 8). Each spacer 54 is formed so as to protrude from each of the edges 311 and 312 of the plane 31 toward the plate P, and the lower surface 541 is in contact with the plate P (the same surface as the attachment surface P1) (FIG. 8). As shown in FIG. 8 (Y), each spacer 54 has an elongated shape in plan view, and its width (length indicated by w in FIG. 8) is substantially constant.

  The sum of the width of the plane 31 (length indicated by u1 in FIG. 8 (Y)) and the width of each spacer 54 (length indicated by w in FIG. 8 (Y)) is the width of the plate P ( It is preferably equal to or slightly smaller than (X) in FIG. 8 and the length indicated by u2).

  Thereby, when the stirring member 3 reciprocates, it is possible to reliably prevent the spacer 54 from falling off from above the plate P, and thus, it is possible to reliably keep the gap distance h1 constant.

  With such a configuration, since the plate P is pressed against the bottom plate 21 of the processing unit 2 by the spacer 54 (stirring member 3), it is possible to prevent the plate P from floating (separating) from the bottom plate 21, and The gap distance h1 can be maintained more easily and accurately.

  In the present embodiment, the main body 32 of the stirring member 3 and the spacer 54 are not limited to being integrally formed (see FIG. 8 (X)), and may be formed of separate members. Good.

  Now, an example of displacement of the stirring member 3 due to operation of the displacement means 4 will be described with reference to FIG. FIG. 6 is a diagram in which the displacement of the stirring member 3 by the operation of the displacement means 4 on the attachment surface P1 is indicated by an arrow.

  As shown in FIG. 6A, the displacement of the stirring member 3 due to the operation of the displacement means 4 on the attachment surface P1 is performed on the attachment surface P1 along the longitudinal direction of the plate P as shown in FIG. It may reciprocate.

  If only a mechanism for reciprocating the stirring member 3 in a direction substantially perpendicular to the longitudinal direction is provided, as shown in FIG. 6B, the displacement of the stirring member 3 It may reciprocate in a direction substantially perpendicular to the longitudinal direction.

  If each mechanism for reciprocating the stirring member 3 in the longitudinal direction and a direction substantially perpendicular to the longitudinal direction is provided, the operation of each mechanism is appropriately combined as shown in FIG. 6C. Alternatively, the displacement of the stirring member 3 may be a displacement obtained by combining the direction of the arrow in FIG. 6A and the direction of the arrow in FIG. 6B.

  Similarly, as shown in FIG. 6D, the displacement of the stirring member 3 may be a displacement along the edge of the plate P.

  Similarly, as shown in FIG. 6E, the displacement of the stirring member 3 may be a displacement that reciprocates in a direction substantially perpendicular to the longitudinal direction and also reciprocates in the longitudinal direction. .

  If a mechanism for rotating the stirring member 3 in a state where the plane 31 and the attachment surface P1 are parallel to each other is provided, the displacement of the stirring member 3 may be a rotating displacement as shown in FIG. .

  If the mechanism for reciprocating the stirring member 3 in the longitudinal direction and the mechanism for rotating the stirring member 3 are provided, as shown in FIG. 6 (g), the displacement of the stirring member 3 is changed while rotating in the longitudinal direction. The displacement may be such that it reciprocates.

  The processing apparatus of the present invention has been described with reference to the illustrated embodiment. However, the present invention is not limited to this, and each unit constituting the processing apparatus may have any configuration capable of exhibiting the same function. Can be replaced by Further, an arbitrary component may be added.

  Further, the spacer of the first embodiment may be formed (provided) over substantially the entire length of the planar edge of the stirring member like the spacer of the third embodiment.

Further, the spacers of the third embodiment may be formed (provided) at the four corners of the plane of the stirring member like the spacers of the first embodiment.
In addition, the edge of the plane of the stirring member may be rounded.

1 is an overall configuration diagram illustrating a first embodiment of a processing apparatus according to the present invention. FIG. 2 is a sectional view taken along line AA in FIG. 1. FIG. 2 is a cross-sectional view (X) taken along line BB in FIG. 1 and a bottom view (Y) of a stirring member provided in the processing apparatus in FIG. 1. FIG. 4 is an overall configuration diagram illustrating a second embodiment of the processing apparatus of the present invention. FIG. 5 is a sectional view taken along line AA in FIG. 4. It is the figure which showed the displacement of the stirring member by operation | movement of the displacement means on the adhesion surface P1 with the arrow. FIG. 6 is an overall configuration diagram showing a third embodiment of the processing apparatus of the present invention. FIG. 8 is a cross-sectional view taken along line AA in FIG. 7 (X) and a bottom view (Y) of a stirring member provided in the processing apparatus in FIG. 7.

Explanation of reference numerals

DESCRIPTION OF SYMBOLS 1 Processing apparatus 1 'Processing apparatus 2 Processing part 21 Bottom plate 3 Stirring member 31 Flat surface 311 Edge 312 Edge 32 Main body 4 Displacement means 41 Moving mechanism 411 Air cylinder 412 Connection member 5 Distance regulating means 5' Distance regulating means 5A Distance regulating means 51 Spacer 52 Projecting part 53 Contact part 54 Spacer 541 Lower surface h1 Gap distance h2 Depth w Width u1 Width u2 Width J Meniscus M Microarray P plate P1 Attachment surface R Probe solution S Nucleic acid

Claims (8)

A processing apparatus for processing the object to be processed, by a processing liquid present on an attachment surface of a plate-shaped support to which the object is attached,
A processing unit in which the support is installed,
A stirrer having a flat surface opposed to the adhesion surface with a gap therebetween,
Displacing means for displacing the stirring member in the plane direction of the adhesion surface,
A processing apparatus, wherein the stirring member is displaced by the operation of the displacement means in a state where the processing liquid is filled in the gap, and the processing liquid is stirred.   The processing apparatus according to claim 1, wherein the stirring member reciprocates at least on the attachment surface by the operation of the displacement unit.   The processing apparatus according to claim 1, further comprising a distance regulating unit that keeps a gap distance of the gap constant.   4. The processing apparatus according to claim 3, wherein the distance regulating unit is provided near an edge of the plane, and is configured by a spacer that abuts inside the processing unit and keeps the gap distance constant. 5.   4. The processing apparatus according to claim 3, wherein the distance regulating unit is provided near an edge of the plane, and is configured by a spacer that abuts on the support and keeps the gap distance constant. 5.   The processing apparatus according to claim 4, wherein the plane has a substantially quadrangular shape, and the spacer is provided at least at four corners of the plane. The distance restricting means, a protrusion protruding from the stirring member parallel to the plane,
The processing apparatus according to claim 3, further comprising: a contact portion formed on the processing unit side and contacting the protruding portion. The processing apparatus according to claim 1, wherein at least a portion of the stirring member that stirs the processing liquid has hydrophilicity.

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