JP2003057247A - Treatment apparatus for object to be treated - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a treatment apparatus for an object to be treated, in which an operation for treating the object to be treated, such as nucleic acid is performed easily, and in which labor and time required for the operation can be reduced. SOLUTION: A microarray treatment apparatus (the treatment apparatus for the object to be treated) 1 shown in the Figure comprises an apparatus body 2, equipped with two airtightly sealable treatment tanks (reaction tanks) 3, 3, a personal computer 110 and a total of four treatment units 30 which are housed (installed) inside the treatment tanks 3, 3 so as to be freely detachable. The apparatus body 2 is provided with a horizontal stage 2a and a vertical stage 2b. A tip installation part 21, a probe-liquid-housing container installation part 22, a container installation part 23 and the treatment tanks 3, 3 are installed at the horizontal stage 2a. A probe-liquid supply means (a reaction- liquid supply means) 6 is installed at the vertical stage 2b. A supply circuit 7, a discharge circuit 8 and a temperature-regulating means 9 are mainly installed at the inside of the apparatus body 2.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus for treating an object to be treated.

[0002]

2. Description of the Related Art For example, when processing such as hybridization for nucleic acid (RNA, DNA),
Nucleic acid (object to be treated) is attached to a slide glass (support), and a reaction solution is supplied (contacted) to the nucleic acid.
Processing is done.

In this case, specifically, the following operation is performed. <1> First, by supplying (dripping) the reaction solution onto the slide glass, further overlaying the cover glass (cover member) on this, and developing the reaction solution in the gap formed between them. , Contact the nucleic acid with the reaction solution. <2> Next, the periphery of the cover glass is hermetically sealed with a sealing material. <3> Next, a slide glass on which the cover glasses are stacked (hereinafter referred to as “slide glass with a cover glass”).
Say ) Is housed in, for example, a closed container, and each closed container is placed in a heating tank (heating tank). Then, the nucleic acid and the reaction solution are reacted while being heated. <4> After completion of the reaction, the slide glass with the cover glass is taken out from the inside of the closed container, and further the cover glass is removed from the slide glass. <5> Next, the excess reaction liquid remaining on the slide glass is removed. <6> Then, the reaction result of the nucleic acid is analyzed. That is, by reacting with a reaction solution, for example, a nucleic acid labeled with coloring, fluorescence, radioactivity or the like is analyzed.

However, such a nucleic acid processing operation is
It is very complicated and requires time and effort.
Further, in particular, the step <2> requires a skilled technique.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to easily process an object to be processed, such as nucleic acid, and to reduce the labor and time required for the operation. Is to provide a processing device.

[0006]

These objects are achieved by the present invention described in (1) to (23) below.

(1) An apparatus for treating an object to be treated, which has a treatment tank which is capable of being hermetically sealed and has a treatment section for placing an object to be treated therein, wherein the treatment tank comprises a main body portion having a concave portion, A lid provided displaceably with respect to the main body,
A lid opening / closing mechanism that applies pressure to the lid body to press the lid body against the body portion while the lid body is moved toward and away from the body portion; However, the lid body has an inner member having an inner surface that is joined to the main body portion, and a reinforcing member for applying the pressure by the lid body opening / closing mechanism evenly and unevenly. apparatus.

(2) The treatment device for an object to be treated according to (1), wherein the reinforcing member is fixed to the inner member and is displaced integrally with the inner member.

(3) The treatment device for an object to be treated according to (1) or (2), wherein the reinforcing member has a plate shape and is installed so as to cover at least the outer surface side of the inner member.

(4) The treatment device for an object to be treated according to any one of (1) to (3), wherein the reinforcing member is made of a material having a hardness higher than that of the constituent material of the inner member.

(5) The apparatus for processing an object to be processed according to (4), wherein the high hardness material is a metal material.

(6) The processing apparatus according to any one of (1) to (5), wherein the lid is rotatably provided with respect to the main body.

(7) The lid body is slidably provided with respect to the main body portion.
The processing device for a processed object according to any one of 1.

(8) The lid opening / closing mechanism includes a carrying mechanism for carrying the lid between an upper position of the main body and a retracted position shifted from the upper position, and a moving direction of the lid. And a moving direction changing mechanism for changing the moving direction changing mechanism from the side of the main body to the upper position so as to be substantially parallel to the upper edge of the main body by the transport mechanism. The treatment device for an object to be treated according to (7), which is configured to change a moving direction of the transported lid body toward a direction toward the main body portion.

(9) The lid opening / closing mechanism includes a carriage that moves between an upper position of the main body and a retracted position shifted from the upper position, and a plate for suspending the lid by the carriage. The upper end of the plate is rotatably supported by the carriage and the lower end of the plate is rotatably supported by the at least one link plate, and an attractive force for attracting the cover to the carriage. And an attracting member for inclining the link plate with respect to the carriage, and allowing downward movement of the lid toward the main body when the carriage moves forward from the retracted position to the upper position. A first stopper for restricting the forward movement, and the first stopper restricts the forward movement of the lid body, and then the carrier. The processing apparatus for processing an object according to (7) or (8) above, wherein the link plate is erected by the forward movement of the lid and pressure is applied so as to press the lid against the main body. .

(10) The processing tank according to any one of the above (1) to (9), further comprising a sealing member that hermetically seals the inside of the processing tank in a state where the lid body covers the recess. Processing equipment for processing.

(11) The above-mentioned (10), wherein the sealing member is installed at an upper edge portion of the main body portion, and the lid body is in pressure contact with the sealing member in a state in which the recess is closed. A processing device for an object.

(12) The sealing member is installed at a lower edge portion of the lid, and the lid covers the recess,
The treatment device for an object to be treated according to (10), which is in pressure contact with an upper edge portion of the main body portion.

(13) The apparatus for treating an object to be treated according to any one of the above (1) to (12), which has a temperature adjusting means for adjusting the temperature of the processing section.

(14) When a reaction liquid capable of reacting with the object to be treated is supplied to the objects to be treated and they are reacted with each other, the temperature adjusting means heats the treatment section while the treatment object is treated. (1) for reacting an object with the reaction solution
3) The processing device for the processed object according to 3).

(15) The apparatus for treating an object to be treated according to the above (13) or (14), wherein the temperature adjusting means is configured to adjust the temperature of the processing section from at least two directions.

(16) A plurality of processing units are provided, and the temperature adjusting means is configured so that different temperature adjusting conditions can be set between the first set of processing units and the second set of processing units. The apparatus for processing an object to be processed according to any one of (13) to (15).

(17) Treatment of the object to be treated according to any one of the above (1) to (16), which has a reaction solution supply means for supplying a reaction solution capable of reacting with the object to be treated to the object to be treated. apparatus.

(18) The above (1) having a moisturizing liquid supply means for supplying a moisturizing liquid for maintaining the humidity in the processing tank.
An apparatus for processing an object to be processed according to any one of (1) to (17).

(19) The apparatus for treating an object to be treated according to any one of the above (1) to (18), which has a cleaning liquid supply means for supplying a cleaning liquid for cleaning the object to be treated.

(20) The apparatus for treating an object to be treated according to any one of the above (1) to (19), which has a draining means for draining the liquid from the treatment tank.

(21) The apparatus for treating an object to be treated according to any one of the above (1) to (20), which has a gas supply means for supplying a gas for drying the object to be treated.

(22) The apparatus for treating an object to be treated according to any one of the above (1) to (21), which has a control means for controlling the operation of each part of the treatment apparatus.

(23) The apparatus for treating an object to be treated according to any one of (1) to (22), wherein the object to be treated is a nucleic acid.

[0030]

BEST MODE FOR CARRYING OUT THE INVENTION A processing apparatus for an object to be processed according to the present invention will be described below in detail with reference to the preferred embodiments shown in the accompanying drawings.

In the following, as an example of the object to be treated,
A macroarray processing apparatus for processing microarrays (DNA chips) in which nucleic acids (DNA, cDNA, RNA, etc.) are represented, and the nucleic acids (nucleic acid fragments) are attached to a plate (plate-shaped support) in a scattered manner, A case where the processing apparatus for a processed object of the present invention is applied will be described.

As an example of the reaction solution, a nucleic acid (eg, mRNA, DNA, etc.) collected from a subject, or
A liquid (hereinafter, referred to as “probe liquid”) containing a substance obtained by labeling (for example, labeling with a dye, a fluorescent substance, a radioactive substance, etc.) that has been synthesized based on this nucleic acid (for example, cDNA) is described as a representative example. To do.

<First Embodiment> FIG. 1 is an overall configuration diagram showing a first embodiment in the case where the apparatus for processing an object to be processed according to the present invention is applied to a microarray processing apparatus.

In the following description, in FIG. 1, the upper side is "upper" or "upper end", the lower side is "lower" or "lower end", the left front side of the paper is "front", and the right rear side of the paper is "rear". ".

A microarray processing apparatus 1 (hereinafter, simply referred to as "apparatus 1") shown in FIG. 1 is an apparatus main body 2 having two processing tanks (reaction tanks) 3 and a control for controlling the operation of each part. It has a personal computer (hereinafter referred to as “PC”) 110 that constitutes a part of the means 10, and a total of four processing units 30 that are detachably housed (installed) in each processing tank 3. .

According to this apparatus 1, the nucleic acid (object to be treated) S
The nucleic acid S can be treated with various liquids and the like while reacting with the probe liquid (reaction liquid) R. Then, from the reaction result of the nucleic acid S, for example, the gene DNA
(Nucleic acid) mutation analysis, polymorphism analysis, nucleotide sequence analysis, expression analysis (presence or absence of presence), and further, based on these, various diseases can be suitably diagnosed.

The configuration of each part will be described below. First, the processing unit 30 will be described with reference to FIGS. Since each processing unit 30 has the same configuration, one unit will be described below as a representative.

FIG. 2 is an exploded perspective view (a part of which is omitted) of the processing unit, FIG. 3 is a plan view showing a part of a processing tab included in the processing unit, and FIG. 3 is a sectional view taken along line AA in FIG. 3, FIG. 5 is a sectional view taken along line BB in FIG. 3, and FIG. 6 is a sectional view showing an operating state of the processing unit.

2 to 6, the upper side is referred to as "upper" or "upper end", the lower side is referred to as "lower" or "lower end", and the right front side of the paper surface in FIG. 2 is referred to. The "front side" and the back side on the left side of the paper are called "rear side".

The processing unit 30, as shown in FIG.
It has a processing tab 40 for accommodating a plate P to which nucleic acid S is attached (hereinafter referred to as “microarray M”), and a cover cassette 50 detachably installed on this processing tab 40.

The processing tab 40 has a tray shape (box shape) as a whole, and is composed of a bottom portion 41 and a side wall portion 42 provided upright along the edge portion of the bottom portion 41.

Further, a plurality of (three in the present embodiment) frame-shaped partition walls 43 are erected on the bottom portion 41, whereby spaces 431 and partition walls are provided inside each partition wall 43. A space 421 is formed in a portion surrounded by the portion 43 and the side wall portion 42.
And are defined.

A microarray M is housed in each space 431. Then, in these spaces 431, the nucleic acid S reacts with the probe solution R,
Various processes such as cleaning with the cleaning liquid W and drying with the gas G are performed. That is, in the present embodiment, the space (processing space) 431 and the plate P constitute the processing unit 300 that processes the nucleic acid (object to be processed) S.

The volume (capacity) of the space 431 is appropriately set depending on the size of the microarray M (plate P) and the like, and is not particularly limited, but it is usually preferable to be about 3 to 10 mL.

In the space 421, the processing unit 3
A moisturizing liquid H for maintaining the humidity in 0 (processing tank 3) is supplied. That is, in the present embodiment, the moisturizing liquid H is supplied around each processing section 300.

Each partition wall portion 43 has a processing tab 40 (the partition wall portion 43 and the bottom portion 4) on the left side in FIGS. 2 and 3.
A first supply path 451 is formed by penetrating 1) in the thickness direction. The cleaning liquid W, the gas G, and the like are supplied into the space 431 through the respective first supply paths 451.

In addition, the bottom portion 41 located inside each partition wall portion 43 has a side opposite to the first supply passage 451 (see FIGS. 2 and 3).
The slopes 432 are formed on the right side of the center, and the slopes 43 are formed.
Grooves 436 are formed at positions where 2 is the deepest.

Further, in the vicinity of the center of each groove 436, a first discharge passage 461 is formed penetrating the processing tab 40 (bottom portion 41) in the thickness direction. This allows
From each space 431, the cleaning liquid W after use,
Excessive probe liquid R and the like (hereinafter collectively referred to as “waste liquid”) is promptly transferred to the processing unit 30 (processing tank 3) via the slope 432, the groove 436, and the first discharge passage 461. It can be discharged (drainage) to the outside.

A plurality of notches are formed inside each partition wall 43 so as to surround the microarray M in a state where the microarray M is housed in the space 431.

Specifically, a pair of large notches 433a and 433b are provided on the upper and lower sides on the left side in FIG. 3, and notches 434 are provided at the four corners.
a to 434d also have notches 43 around the beveled surface 432.
5a to 435e are respectively formed.

These large notches 433a, 433b,
And notches 434a to 434d and 435a to 435.
By providing e, as shown by the arrow in FIG. 3, the waste liquid can be transferred more quickly and reliably from the upper surface (front side of the paper surface in FIG. 3) side of the microarray M to the lower surface side (back side of the paper surface in FIG. 3). You can

From the inside of the space 431, the microarray M
The large notch 433 is used when taking out the microarray M or storing (installing) the microarray M in the space 431.
By inserting a thumb and an index finger into a and 433b, respectively, the operation can be performed more easily and reliably.

A second supply passage 471 and a second discharge passage 481 communicating with the space 421 are formed in the bottom portion 41 so as to penetrate the bottom portion 41 in the thickness direction. The moisturizing liquid H or the like can be supplied into the space 421 via the second supply passage 471, and the used moisturizing liquid H or the like is discharged from the space 421 via the second discharge passage 481 (drainage liquid). can do.

On the lower surface of the bottom portion 41 (the lower surface in FIGS. 4 and 5), leg portions 44 are formed along the edges of the bottom portion 41.
In addition, the projections 45, 45, 45, 46, 4 having a substantially cylindrical shape
6, 46, 47 and 48 are formed so as to project downward, respectively.

A first supply passage 451 is provided inside each protrusion 45, and a first discharge passage 461 is provided inside each protrusion 46.
However, inside the protrusion 47, the second supply path 471 is
Inside the protrusion 48, the second discharge passages 481 are continuously formed.

In the state where the processing unit 30 is housed (installed) in the processing tank 3, the leg portion 44 of the processing tab 40 is inserted into the groove 36 of the processing tank 3 which will be described later. The base 35 of the processing tank 3 described below is inserted into the inner portion of the leg portion 44, whereby the processing tab 40 (processing unit 30) is fixed in the processing tank 3.

A cover cassette 50 is detachably attached to the upper portion of the processing tab 40. By mounting the cover cassette 50 on the processing tab 40, the internal space of the processing unit 30 is kept relatively airtight.

As shown in FIG. 2, the cover cassette 50 includes a frame 500 and slide doors 540 and 550.
And a cover plate (cover member) 560.

The frame 500 includes a first member 510 and a second member 52 sequentially installed on the first member 510.
0 and a third member 530.
The five members 510, 520 and 530 are connected to each other by, for example, screws.

The first member 510 is a member constituting the main part of the frame 500. Spaces 511 that open to the upper surface and the lower surface (upper and lower surfaces in FIG. 3) are formed in the first member 510 at positions corresponding to the respective spaces 431 of the processing tab 40, and form a frame shape as a whole. ing.

The pair of inner wall surfaces 5 facing each space 511
A first guide groove 512a and a second guide groove 512b are formed in each of 12, 512. An end of a first shaft 563 of a cover plate 560, which will be described later, is inserted into each first guide groove 512a, while a second shaft 564 of the cover plate 560 is inserted into each second guide groove 512b.
The ends of are inserted respectively.

Further, as shown in FIG. 6, the first member 510 is
An engaging portion 513 is formed along the edge of the lower end of the engaging portion 513. With the cover cassette 50 attached to the processing tab 40, the engaging portion 513 engages with the upper edge of the side wall portion 42 of the processing tab 40. As a result, the cover cassette 50 is fixed and positioned on the processing tab 40.

A second member 520 is installed above the first member 510. The second member 520 is formed of a flat plate-like member, and recesses 521 are formed in the first member 510 at positions corresponding to the spaces 511.

An opening 522 is formed at the bottom of each recess 521 on the right side in FIG. Through these openings 522, a slide door 55, which will be described later, is provided.
The hooks 053 of 0 respectively protrude downward.

Each opening 522 is a portion which substantially constitutes the window 50a of the cover cassette 50 (see FIG. 6). Cover cassette 50 on processing tab 40
When the operation of supplying the probe liquid R to the nucleic acid S is performed with the attached, the operation can be performed through these windows 50a.

The third member 53 is provided on the upper part of the second member 520.
0 is set. The third member 530 is also made of a flat plate member, and an opening 531 is formed at a position corresponding to each recess 521 of the second member 520. Through these openings 531, an operation knob 542 of the slide door 540 and an operation knob 552 of the slide door 550, which will be described later, respectively project upward.

The opening area of each opening 531 is the second
It is set smaller than the opening area of each recess 521 of the member 520. Therefore, the third member 530 is replaced by the second member 520.
In the state of being joined to each other, a slide space 521a is formed between each recess 521 and the third member 530. In these slide spaces 521a, a door body 541 of the slide door 540 and a door body 55 of the slide door 550 are provided.
1 and 1 are installed so as to be slidable (horizontal movement).

The slide door 540 is used for the cover cassette 50.
Which is a member that opens and closes the window portion 50a of the flat door body 5
41, and a plate-piece-shaped operation knob 542 that is formed to project upward from the door body 541.

The door body 541 is located in the slide space 521a, and the operation knob 542 projects upward through the opening 531 of the third member 530. Operating knob 5
When the operation of sliding 42 is performed, the door main body 541
Slides with respect to the frame 500.

A groove 543 into which the door body 551 of the slide door 550 is inserted is formed in the lower portion of the door body 541. The slide door 540 can be omitted if necessary.

The slide door 550 is also the slide door 54.
It has the same function as 0 and has a flat door body 551.
And a plate piece-shaped operation knob 552 that is formed to project upward from the door body 551. When the operation knob 552 is slid, the door body 551 slides with respect to the frame 500.

Further, the door body 551 has an operation knob 55.
A hook 553 protruding downward is formed on the side opposite to 2 (right side in FIGS. 2 and 6). This hook 5
53 is composed of two plate-shaped leg portions, and a hook groove 553a with which the first shaft 563 of the cover plate 560 can be engaged is formed between these leg portions.

The cover plate 560 is a member for supplying the probe liquid R onto the microarray M and then superimposing the probe liquid R on the microarray M to spread the probe liquid R into the gap formed between them. As a result, the nucleic acid S and the probe liquid R can be brought into uniform contact with each other while using the minimum necessary amount (trace amount) of the probe liquid R. Therefore, there is an advantage that the valuable probe liquid R is not wasted.

As will be described later, the reaction between the nucleic acid S and the probe solution R is carried out by the cover plate 5 on the microarray M.
It is performed in the state where 60 is piled up.

The cover plate 560 has a cover plate main body 561, a pair of side wall portions 562 and 562 provided upright from the cover plate main body 561, a first shaft 563 and a second shaft 564.

The cover plate main body 561 is formed of a flat plate-like member, and in a state of being superposed on the macro array M,
It has a size (size) that can include the attachment region of the nucleic acid S.

Further, the first shaft 563 and the second shaft 564
Are each formed of a rod-shaped member, and each of the pair of side wall parts 5
It is installed so as to penetrate through 62 and 562. Then, both ends of the first shaft 563 are respectively connected to the first member 51.
0 of the first guide groove 512a, both ends of the second shaft 564 are respectively inserted into the respective second guide grooves 512b of the first member 510, whereby the cover plate 560 is moved to the first guide groove 512a.
It is supported by the member 510 (frame 500).

In this state, the central portion of the first shaft 563 is engaged with the hook groove 553a of the slide door 550. When the sliding door 550 is slid with respect to the frame 500 by these engaging actions,
With the movement of the slide door 550, the cover plate 560 also moves. At this time, the cover plate 5
The movement of 60 is guided (restricted) by each first guide groove 512a and each second guide groove 512b.

Each part of such a processing unit 30 is preferably made of a non-metallic material. This allows
It is possible to suitably prevent the reaction of the nucleic acid S and the probe liquid R from being inhibited by the mixing of metal ions in the probe liquid R.

Specifically, the constituent material of each part of the processing unit 30 is, for example, polyvinyl chloride, polyethylene, polypropylene, polystyrene, polycarbonate, acrylic resin, acrylonitrile-butadiene-styrene copolymer, polyethylene terephthalate, or the like. Various resin materials such as polyester, butadiene-styrene copolymer, polyamide, polyether sulfone and polysulfone can be mentioned, and one kind or a combination of two or more kinds thereof can be used.

Next, the apparatus main body 2 will be described with reference to FIGS. 1, 7 and 8. FIG. 7 is a perspective view showing the structure of the processing tank, and FIG. 8 is a schematic view showing the internal structure of the apparatus main body. Note that FIG. 8 shows only one of the two processing tanks.

In the following description, in FIG. 7, the upper side is "upper" or "upper end", the lower side is "lower" or "lower end", the left front side of the paper is "front", and the right rear side of the paper is "rear". ".

The apparatus main body 2 shown in FIG. 1 is provided with a horizontal stage 2a at the front and a vertical stage 2b at the rear.
The horizontal stage 2a is provided with a chip setting unit 21, a probe liquid storage container setting unit 22, a container setting unit 23, and two treatment tanks 3 and 3 that can be sealed, and the vertical stage 2b.
Is provided with a probe liquid supply means (reaction liquid supply means) 6.

Inside the apparatus main body 2, mainly, a supply circuit 7, a discharge circuit 8, a temperature adjusting means 9, a member forming a part of the control means 10, and an operation of each part. A power supply unit (not shown) that supplies necessary electric power is provided.

<Chip Setting Section 21> Chip Setting Section 21
Is a place where a plurality of chips (tubular members) mounted on the nozzle 612 of the dispensing device 61, which will be described later, are installed.

This chip setting section 21 is used for the horizontal stage 2
It is composed of a plurality of holes (recesses) 211 formed on the upper surface (the upper surface in FIG. 1) of a. A chip can be placed in each hole 211 in an upright state.

As described above, since a plurality of chips can be set in the chip setting section 21, when a plurality of different probe liquids R are used in a single processing operation of the microarray M, each of them is used. The tip used for each probe liquid R can be replaced. As a result, it is possible to prevent contamination (contamination) of the other probe liquid R with one probe liquid R, and it is possible to perform accurate processing on each nucleic acid S.

<Probe Liquid Storage Container Installation Unit 22> The probe liquid storage container installation unit 22 is a place where a plurality of containers in which the probe liquid R is stored are installed.

The probe liquid storage container installation section 22 is composed of a plurality of holes (recesses) 221 formed on the upper surface (upper surface in FIG. 1) of the horizontal stage 2a. Each hole 221
Each of the containers can be installed upright.

A lid 222 with a heater is rotatably installed in the probe liquid storage container installation section 22.
The heater-attached cover 222 is formed of a flat plate-like member, and is provided with all the holes 22 in a state of being in contact with the horizontal stage 2a.
1 can be covered, and airtightness is maintained with each container installed in the hole 221.

The heater (not shown) provided in the heater cover 222 constitutes a part of the temperature adjusting means 9 described later.

On the inner surface (lower surface in FIG. 1) of the heater cover 222, a sealing member (not shown) made of an elastic material such as silicone rubber is provided along the vicinity of the edge. ) Is installed. As a result, the heater-equipped lid 22
It is possible to improve airtightness in the state where 2 is in contact with the horizontal stage 2a.

As the operation (rotation) mechanism of the lid 222 with the heater, for example, a mechanism similar to the operation mechanism of the lid 37 in the processing tank 3 described later can be adopted.

<Container Setting Section 23> The container setting section 23 is a place for setting a plurality of containers 72a to 72h described later.

This container setting section 23 is used for the horizontal stage 2a.
Is formed of a plurality of holes (recesses) 231 formed on the upper surface (the upper surface in FIG. 1). Each of the containers 72a to 72h can be installed in each hole 231 in an upright state.

<Treatment Tank 3> As shown in FIG. 7, each treatment tank 3 has a main body portion 32 having a treatment unit housing portion (recess) 31, and is rotatable (displaceable) with respect to the main body portion 32. ) Is provided, and each processing unit storage section 31 is configured to be able to store (install) two processing units 30 each.

That is, a total of four processing units 30 can be installed in the apparatus body 2, and in the apparatus body 2,
Up to 12 microarrays M can be processed simultaneously.

Since each processing tank 3 has the same structure, only one of them will be described below as a representative.

As shown in FIG. 7, the main body 32 has a tray shape (box shape) as a whole, and a bottom portion 33,
It is composed of a side wall portion 34 standing upright along the edge portion of the bottom portion 33.

On the bottom portion 33, two bases 35, 35 having a substantially rectangular parallelepiped shape are integrally formed with the bottom portion 33. In other words, the bottom portion 33 is provided with the groove 36,
As a result, the bases 35, 35 are formed.

Communication holes 351, 351, 351, 352, 352, 352, are formed in these bases 35, respectively.
353 and 354 are formed to penetrate the bottom portion 33 (base 35) in the thickness direction.

At the lower end of each communication hole 351, there is an end of a tube forming each of downstream branch lines 74a to 74c described later, and at the lower end of the communication hole 353 is a downstream branch line 74d described later. The end portion of the tube that constitutes the
The ends of the tubes forming a to 81c are connected to the lower end of the communication hole 354, and the ends of the tubes forming the branch line 81d described later are connected to each other (see FIG. 8).

Two processing units 30 are installed in the processing unit housing section 31. At this time, the leg portion 44 of the processing tab 40 is inserted into the groove 36, in other words, the base 35 is inserted inside the leg portion 44 of the processing tab 40, whereby each processing tab 40 (processing Unit 30)
Are fixed to the main body 32, respectively.

At this time, the projections 45 are inserted into the communication holes 351 so that the communication holes 351 and the first supply passages 45 can be connected.
1, the protrusion 47 is inserted into the communication hole 353,
The communication hole 353 and the second supply passage 471 are communicated with each other, the projections 46 are inserted into the communication holes 352, the communication holes 352 and the first discharge passages 461 are communicated with each other, and the communication holes 354 are projected. Part 4
8 is inserted, and the communication hole 354 and the second discharge passage 481 communicate with each other.

Further, an O-ring (not shown) made of an elastic material is installed on the inner peripheral portion of each of the communication holes 351 to 354, whereby each of the communication holes 351 to 354 is provided. In the state in which each of the protrusions 45 to 48 is inserted, the connection between them is made liquid-tight.

In this embodiment, each processing unit 3
Although 0 is removable from the processing tank 3, it may be fixed to the processing tank 3. That is,
Each processing tab 40 is the bottom portion 33 (base 35) of the processing tank 3.
It may be fixed to (fixed to), or the same configuration as the processing tab 40 may be formed on the bottom portion 33 (base 35).

At the upper edge of the side wall 34, a sealing member 341 made of an elastic material is installed so as to surround the opening of the processing unit housing 31. When the processing unit housing 31 is closed by the lid 37 (the processing tank 3 is closed), the lid 37 is in pressure contact with the sealing member 341. Thereby, the processing tank 3 can be hermetically sealed.

Examples of such elastic materials (constituting materials of the sealing member 341 and the O-ring) include various rubber materials such as silicone rubber and fluororubber, styrene type, polyolefin type, polyvinyl chloride type, Various thermoplastic elastomers such as polyurethane type and polyester type are listed, and one kind or a combination of two or more kinds of them can be used.

The lid 37 is made of a flat plate-like member, and a shaft 371 is integrally formed with the lid 37 behind the lid 37. On the other hand, a bearing (not shown) is formed integrally with the main body 32 at the rear of the main body 32 (side wall 34). By inserting and supporting the shaft 371 in the bearing, the lid 37 is rotatably installed with respect to the main body 32.

On the right side of the shaft 371 in FIG. 7, there is a gear.
372 is attached. Further, in the rear of the processing tank 3,
A motor 38 is installed, and a gear (gear) 382 is attached to a rotating shaft 381 thereof. These gears 372
And 382 are in mesh with each other.

When the motor 38 (rotating shaft 381) is rotated backward (clockwise) in FIG. 7, the gear 382 is rotated in the same direction accordingly. At this time, the gear 372 that meshes with the gear 382 rotates forward (counterclockwise) in FIG.
The shaft 371 also rotates in the same direction as the gear 372. As a result, the lid 37 rotates so as to approach the main body 32, and eventually the lid 37 comes into contact with the main body 32, and the processing tank 3 is closed.

Further, from this state, by rotating the motor 38 in the same direction, pressure (pressing force) such that the lid 37 is pressed against the main body 32 is applied.

On the other hand, the motor 38 (rotating shaft 381) is shown in FIG.
When it is rotated forward (clockwise), the lid 37 is rotated so as to be separated from the main body 32, and the processing tank 3 is opened, contrary to the above.

That is, in this embodiment, the shaft 37 is mainly used.
1, the gear 372, the motor 38 and the gear 382,
A lid opening / closing mechanism 3A is configured.

In the lid opening / closing mechanism 3A, as described above, the lid 37 is rotated (approximated and separated) with respect to the main body 32, and the lid 37 is moved to the processing unit accommodating portion 3A.
It has a function of applying pressure so that the lid 37 is pressed against the main body 32 from the state in which 1 is closed.
The lid opening / closing mechanism 3A ensures the airtightness of the inside of the processing tank 3 in the closed state.

Thus, according to the lid opening / closing mechanism 3A,
Using a single drive source, the opening / closing movement of the lid 37 and the pressing movement of the main body 32 can be performed.

As shown in FIG. 7, the lid 37 has an inner member 37a having an inner surface (lower surface in FIG. 7) joined to the main body 32, and a reinforcing member fixed to the inner member 37a. 37b, and these inner member 37a and reinforcing member 37
b is configured to integrally rotate (displace).

The reinforcing member 37b is composed of a plate-shaped member, and is disposed on the outer surface side of the inner member 37a (in this embodiment, as shown in FIG.
It is installed so as to cover the upper middle and side surfaces.

The reinforcing member 37b is the lid opening / closing mechanism 3A.
The pressing force is applied to the entire lid 37 almost uniformly, and is made of a material having a hardness higher than that of the constituent material of the inner member 37a.

With the lid 37 having such a structure, the airtightness of the inside of the processing tank 3 is more surely secured in the closed state.

As the constituent material of the reinforcing member 37b,
For example, aluminum, iron, nickel, stainless steel,
Various metal materials such as copper, brass, aluminum, titanium, or alloys containing at least one of them can be used.

In the lid 37 of the present invention, only the reinforcing member 37b is made of the metal material,
Compared with the case where the entire lid 37 is made of a metal material, it is possible to prevent (suppress) an excessive increase in the weight of the entire lid 37. For this reason, the lid opening / closing mechanism 3A can exert its function without using a large-sized motor (large output) as the motor 38. That is, according to the present invention, it is possible to contribute to downsizing of the lid opening / closing mechanism 3A, and further to downsizing of the microarray processing apparatus 1.

As shown in FIGS. 7 and 8, the lid 37 is provided with an open / close sensor 373 for detecting the open / closed state of the processing bath 3.

The lid 37 is not rotatably attached to the main body 32 (rotating type) but is, for example, slidably attached to the main body 32 ( (Sliding type) and the like.

Further, in this embodiment, the sealing member 341 is used.
Is installed at the upper edge of the side wall 34 (main body 32), but the installation position (installation location) of the sealing member 341 is not limited to this. The sealing member 341 is, for example, the lid 37.
7 may be installed on the inner surface (the lower surface in FIG. 7) along the vicinity of its edge, or may be installed on both the side wall portion 34 (main body portion 32) and the lid 37.

<Probe Liquid Supply Means 6> The probe liquid supply means (reaction liquid supply means) 6 is mainly composed of nucleic acid (object to be treated).
It has a function of supplying a probe liquid (reaction liquid) R capable of reacting with S to a nucleic acid (subject to be treated) S, and as shown in FIG. The moving mechanism 62 is movable in the dimensional direction.

The dispensing device 61 is a device capable of sucking and discharging a liquid, and is provided with a dispensing pump 611 and a nozzle 612 which is provided at the lower end portion (tip portion) of the dispensing pump 611 and on which a tubular tip can be mounted. ing.

The dispensing pump 611 can be constituted by, for example, a piston type pump, a syringe type (plunger type) pump, or the like.

The moving mechanism 62 is an x-axis direction moving mechanism 62 capable of moving the dispensing device 61 in the x-axis direction (horizontal direction in FIG. 1).
a, a y-axis direction moving mechanism 62b capable of moving the dispensing device 61 in the y-axis direction (front-back direction in FIG. 1), and the dispensing device 61 z
The z-axis direction moving mechanism 62c is movable in the axial direction (vertical direction in FIG. 1), and the dispensing device 61 is fixed to a member constituting the z-axis direction moving mechanism 62c.

Further, as shown in FIG. 1, a rod-shaped operating member (engaging member) 63 is installed at the lower end of the member forming the z-axis direction moving mechanism 62c. Moving mechanism 62
Thus, the operation member 63 can be moved to perform the slide operation of the slide door 540 and the slide door 550.

The slide operation of the slide door 540 and the slide door 550 is performed in place of the operation member 63.
Alternatively, the nozzle 612 of the dispensing device 61 may be used.

<Supply Circuit 7> The supply circuit 7 is a circuit for supplying various liquids (cleaning liquid W, moisturizing liquid H, flushing liquid F) and gas G into the processing tank 3 (processing unit 30). Is.

This supply circuit 7 is, as shown in FIG.
Main supply line 70 and upstream branch lines 71a to 71h
And downstream side branch lines 74a to 74d and a drain line 76.

The main supply line 70 constitutes a main part of the supply circuit 7, and in the middle of the main supply line 70, the pump 7 is arranged in order from the upstream side.
8 and a three-way valve 79 are provided. The main supply line 70 is bifurcated toward the two processing tanks 3 and 3 in the three-way valve 79, and the branched main supply line 70 is further divided into two bases inside each processing tank 3. It is bifurcated toward 35, 35.

The upstream side of the main supply line 70 is connected to one end (downstream end) of each of the upstream branch lines 71a to 71h. Containers 72a to 72h are connected to the other ends (upstream ends) of these upstream side branch lines 71a to 71h, respectively.

In this embodiment, the cleaning liquid W is filled in each of the containers 72a to 72e.
The moisturizing liquid H is filled in f, the flushing liquid F is filled in the container 72g, and the gas G is filled in the container 72h.

Further, each upstream side branch line 71a to 71h
Upstream valves 73a to 73h capable of opening and closing those flow paths are provided in the middle of the above.

On the other hand, one end (upstream end) of each of the downstream branch lines 74a to 74d and one end (upstream end) of the drain line 76 are connected to the downstream side of the main supply line 70.

The other ends (downstream ends) of the downstream branch lines 74a to 74c are connected to the communication holes 351 of the base 35, respectively, and the other ends (downstream ends) of the downstream branch lines 74d.
Are connected to the communication holes 353 of the base 35. Further, the other end (downstream end) of the drain line 76 is connected in the middle of a main discharge line 80 described later.

Further, each of the downstream side branch lines 74a to 74
In the middle of d and the drain line 76, the downstream valves 75a to 75a capable of opening and closing those flow paths, respectively.
5d and 77 are provided.

In such a structure, each container 72a ...
72e, each upstream side branch lines 71a to 71e, each upstream side valve 73a to 73e, part of the main supply line 70, a pump 78, a three-way valve 79, each downstream side branch line 74a to.
The cleaning liquid supply means 7W for supplying the cleaning liquid W for cleaning the nucleic acid (object to be processed) S is configured by the 74c and the downstream valves 75a to 75c.

Further, the container 72f and the upstream branch line 71
f, upstream valve 73f, part of main supply line 70, pump 78, three-way valve 79, downstream branch line 74d,
Also, the processing unit 30 is controlled by the downstream valve 75d.
A moisturizing liquid supply means 7H for supplying the moisturizing liquid H for maintaining the humidity in the (treatment tank 3) is configured.

The container 72h and the upstream branch line 71
h, upstream valve 73h, part of main supply line 70, pump 78, three-way valve 79, each downstream branch line 74a
To 74c and the downstream valves 75a to 75c constitute a gas supply means 7G for supplying a gas G for drying the nucleic acid (object to be processed) S.

Further, the container 72g and the upstream branch line 7
1g, upstream valve 73g, part of main supply line 70,
Pump 78, three-way valve 79, each downstream branch line 74
a-74d, 76 and each downstream valve 75a-75
d, 77, the processing tank 3 (each space 431, 421),
Flushing liquid supply means 7F for supplying the flushing liquid F for cleaning the inside of the supply circuit 7 and the discharge circuit 8.
Is configured.

As shown in FIG. 8, when the processing unit 30 is housed in the processing tank 3, the inside of each space 431 (processing tank 3), the cleaning liquid supply means 7W, the gas supply means 7G and the flushing liquid supply means. Space connected to 7F and space 42
The inside of 1 (processing tank 3) is connected to the moisturizing liquid supply means 7H and the flushing liquid supply means 7F.

Specifically, each protrusion 45 is inserted into each communication hole 351 and each communication hole 351 communicates with each first supply passage 451. The cleaning liquid supply means 7W, the gas supply means 7G and the flow path (internal space) of the flushing liquid 7F are in communication with each other.

In addition, the protrusion 47 is inserted into the communication hole 353, the communication hole 353 and the second supply passage 471 communicate with each other,
As a result, the space 421 communicates with the moisturizing liquid supply unit 7H and the flow path (internal space) of the flushing liquid 7F.

Further, as described above, the cleaning liquid supply means 7
W, the moisturizing liquid supply unit 7H, the gas supply unit 7G, and the flushing liquid supply unit 7F are configured to share some of them (a part of the main supply line 70, the pump 78, the three-way valve 79, etc.). . As a result, the circuit configuration can be simplified, and the device body 2 (the entire device 1) can be simplified and downsized.

In the present invention, the cleaning liquid supply means 7W,
Any two or three of the moisturizing liquid supply unit 7H, the gas supply unit 7G, and the flushing liquid supply unit 7F may be configured to share some of them, and each unit respectively , May be provided separately (independently).

The cleaning liquid W, the moisturizing liquid H, the gas G, and the flushing liquid F will be described below.

The washing solution W is mainly composed of the nucleic acid S and the probe solution R.
It is used to wash away the excess probe solution R after reacting with and is preferably one that does not affect the reaction result of the nucleic acid S. For example, citrate buffer solution, phosphate buffer solution It is preferable to mainly use a buffer solution such as a borate buffer solution. The cleaning solution W mainly containing such a buffer solution has an advantage that it has poor reactivity with the probe and that damage to the nucleic acid S can be made extremely small.

In the washing liquid W, if necessary, for example, sodium dodecyl sulfate, dextran sulfate and Tw are added.
Various additives such as a surfactant such as een-20, NP-40 and Triton X-100 may be added.

The cleaning liquids W filled in the respective containers 72a to 72e may all be under the same conditions, or at least one may be under different conditions. When the conditions of the cleaning liquid W are changed, for example, one or more of composition, concentration, temperature, etc. may be appropriately changed.

For example, the container 72a is filled with the cleaning liquid Wa, and the container 72b is filled with the cleaning liquid W under a condition different from that of the cleaning liquid Wa.
If b is filled, the valves 73a and 73b are switched, that is, the containers 72a and 72b are switched, so that the cleaning liquid W (the cleaning liquid Wa and the cleaning liquid Wb) under different conditions can be easily transferred to the nucleic acid S. Supply against
The nucleic acid S can be washed.

Therefore, by setting the conditions of the cleaning liquid W to be filled in the respective containers 72a to 72e to be different conditions, in the present embodiment, the nucleic acid (object to be treated) S is treated by the cleaning liquid W of five different conditions. Cleaning can be performed.

The moisturizing liquid H maintains the humidity in the processing unit 30 (processing tank 3), whereby the liquid components in the probe liquid R are evaporated when the nucleic acid S reacts with the probe liquid R, for example. Is for preventing (suppressing). The moisturizing liquid H is not particularly limited, but examples thereof include distilled water, ion-exchanged water, ultrapure water, and various water such as RO water. The cleaning liquid W may be used as it is as the moisturizing liquid H.

The gas G is used to dry the nucleic acid (object to be treated) S after the completion of various treatments. This gas G
Examples thereof include air, an inert gas such as nitrogen, argon and helium.

The flushing liquid F is used in the processing tank 3 (each space 4
31, 421), the supply circuit 7 and the discharge circuit 8 are used for cleaning. The flushing liquid F is not particularly limited, but examples thereof include various water such as distilled water, ion-exchanged water, ultrapure water, and RO water.

<Discharging circuit 8> Discharging circuit (drainage means)
Reference numeral 8 is a circuit for discharging (draining) waste liquid (for example, excess probe liquid R, cleaning liquid W after use, moisturizing liquid H after use, etc.) from the inside of the processing unit 30 (processing tank 3). .

This discharge circuit 8 is, as shown in FIG.
It has a main discharge line 80 and branch lines 81a to 81d.

One end (upstream end) of each branch line 81a to 81c is connected to each communication hole 352 of the base 35, and one end (upstream end) of the branch line 81d is connected to the base 35.
Is connected to the communication hole 354.

As shown in FIG. 8, when the processing unit 30 is housed in the processing tank 3, the respective spaces 431 and 421 and the discharging circuit (drainage means) 8 are connected to each other. There is.

Specifically, each protrusion 46 is formed in each communication hole 352.
However, the protrusions 48 are inserted into the communication holes 354, and the communication holes 352 and the first discharge paths 461 are connected to each other by the communication holes 354.
And the second discharge path 481 communicate with each other, whereby the spaces 431 and 421 communicate with the flow path (internal space) of the discharge circuit (discharge means) 8.

The other ends (downstream ends) of the respective branch lines 81a to 81d are connected to the main discharge line 80 which constitutes the main part of the discharge circuit 8, and in the middle of the main discharge line 80. , The drain line 76 joins (is connected).

The four main discharge lines 80 extending from each base 35 are merged into one in the manifold 83 installed outside the processing tank 3 to form one main discharge line 80 at the end. Is connected to a waste liquid collection container 85.

Further, valves 82a to 82d are installed in the middle of the respective branch lines 81a to 81d, and a pump 84 is provided on the downstream side of the main discharge line 80 (between the manifold 83 and the waste liquid recovery container 85). Is installed.

A liquid amount sensor (waste liquid amount detecting means) 86 for monitoring the collected amount (retained amount) of the waste liquid is installed near the waste liquid collecting container 85. In the present embodiment, these waste liquid collection container 85 and liquid amount sensor 86 are provided.
Is installed in the waste liquid recovery unit 800, and this waste liquid recovery unit 800 is installed outside the apparatus main body 2 as shown in FIG. The waste liquid collection container 85 and the liquid amount sensor 86 may be installed (built in) inside the apparatus main body 2.

The discharge circuit 8 and the supply circuit 7 are configured by connecting a plurality of flexible tubes. Examples of constituent materials of these tubes include polyvinyl chloride, polyethylene, polypropylene, polyester, ethylene-vinyl acetate copolymer, polytetrafluoroethylene (PTFE), and tetrafluoroethylene-perfluoroalkyl vinyl ether polymer (PFA). Various kinds of resin materials such as fluorine-based resins can be used, and one kind or a combination of two or more kinds of them can be used (for example, as a laminate having two or more layers).

The constituent materials of the respective containers 72a to 72h and the waste liquid recovery container 85 are, for example, polyvinyl chloride, polyethylene, polypropylene,
Polystyrene, polycarbonate, acrylic resin, acrylonitrile-butadiene-styrene copolymer, polyester such as polyethylene terephthalate, butadiene-
Examples include various resin materials such as styrene copolymer, polyamide, polyether sulfone and polysulfone, and various glass materials.

Further, each upstream valve 73a to 73h, each downstream valve 75a to 75d, 77, each valve 82a to.
The 82d and the three-way valve 79 can be respectively configured to be driven by various drive sources such as an electromagnetic motor, a solenoid, or a cylinder (hydraulic pressure or pneumatic pressure).

<Temperature Adjusting Unit 9> The temperature adjusting unit 9 adjusts the temperature of each part of the apparatus main body 2. As shown in FIGS. 1 and 8, the temperature adjusting means 9 includes a first temperature adjusting unit 91, a second temperature adjusting unit 92, a third temperature adjusting unit 93, and a fourth temperature adjusting unit 94.
And have.

The first temperature adjusting unit 91 and the second temperature adjusting unit 92 respectively adjust the temperature of each processing section 300.

The first temperature adjusting unit 91 is provided in the main body 32 (bottom 33) of the processing bath 3, while the second temperature adjusting unit 92 is provided in the lid 37 of the processing bath 3.

That is, in this embodiment, the first temperature adjusting unit 91 and the second temperature adjusting unit 92
The temperature of each processing unit 30 (each processing unit 300) can be adjusted in the vertical direction (two directions).

The temperature of each processing section 300 may be adjusted not only in the vertical direction but also in another direction (for example, lateral direction).

The first temperature adjusting unit 91 is provided with a Peltier element 91 provided at a predetermined distance (predetermined interval).
1a and 911b and temperature sensors 912a and 912b respectively installed near them, and each processing unit 30
The temperature of the nucleic acid S and the reaction liquid R can be adjusted by heating and / or cooling 0.

On the other hand, the second temperature adjusting unit 92 includes a heater 921a provided at a predetermined distance (predetermined interval),
It has 921b and temperature sensors 922a and 922b respectively installed in the vicinity thereof, and by heating each processing unit 300, the temperatures of the nucleic acid S and the probe liquid R can be adjusted.

As described above, in the processing tank 3, the Peltier elements 911a and 911b and the heaters 921a and 921 are used.
By providing b separately from each other, between the first processing unit 300 and the second processing unit 300 among the plurality of processing units 300, that is, different for each processing unit 30. It is configured so that temperature adjustment conditions can be set. In the present embodiment, different temperature adjustment conditions can be set in each of the four processing units 30.

The temperature adjustment conditions include, for example, temperature, rate of temperature increase, rate of temperature decrease, heating (heating) time, temperature history pattern, etc. One or more of these are used in combination. be able to.

In the second temperature adjusting unit 92, a Peltier element may be used instead of the heater.

The third temperature adjusting unit 93 adjusts the temperature of the probe liquid storage container installation section 22.

As shown in FIG. 1, the third temperature adjusting unit 93 includes a Peltier element 931 installed below the probe liquid storage container installation section 22 (inside the apparatus main body 2).
By having the temperature sensor 932 installed in the vicinity thereof and heating and / or cooling the probe liquid storage container installation part 22, the temperature of the probe liquid R can be adjusted.

The fourth temperature adjusting unit 94 is for adjusting the temperature of the container installation section 23. The fourth temperature adjusting unit 94 includes a plurality (five in the present embodiment) of heaters 941a to 941d and 941f provided in a lower portion (inside the apparatus body 2) at a position corresponding to the predetermined hole 231.
Temperature sensors 942a to 942 installed near them
d and 942f, the temperature of the liquid (or gas) filled in the container can be adjusted by heating the container installed in the predetermined hole 231.

In this embodiment, the containers 72a to 72d and 72f are installed in the predetermined (five) holes 231.

In the fourth temperature adjusting unit 94, a Peltier element may be used instead of the heater.

<Control Means 10> The control means 10 controls the operation of each part of the apparatus main body 2 (apparatus 1).

This control means 10 is, as shown in FIG.
A personal computer 110 and a CP installed inside the apparatus main body 2
It has a U board 120, a device control board 130, a temperature control board 140, an I / O board (input / output board) 150, and a relay board 160.

The personal computer 110 is a monitor (display means) 1
11 and a keyboard (input means) 112. The personal computer 110 is electrically connected to the apparatus main body 2 via the CPU board 120.

The CPU board 120 is provided with a memory (storage unit) 121 in which predetermined programs, tables, etc. are recorded, and controls the probe liquid supply means 6 (dispensing device 61, moving mechanism 62), motor 38, etc. Device control board 130 and Peltier elements 911a, 911b, 93
1 and heaters 921a, 921b, 941a to 941
d, the temperature control board 140 for controlling 941f, and I /
Relay boards 160 are electrically connected to each other via O-boards 150.

Further, on the relay board 160, each upstream valve 73a to 73h and each downstream valve 75a to 75h.
d, 77, the valves 82a to 82d, the three-way valve 79, and the pumps 78, 84 are electrically connected to each other, and control the energization of these.

Further, on the CPU board 120, the respective temperature sensors 912a, 912b, 922a, 922b, 93.
2, 942a to 942d, 942f, open / close sensor 373
And the liquid amount sensor 86 are electrically connected to each other,
Information (detection signal) from these is input to the CPU board 120 at any time.

A power supply unit (not shown) is electrically connected to the CPU board 120, and power is supplied to each unit that requires power supply.

Hereinafter, the control of each part of the apparatus main body 2 performed by the CPU board 120 via the apparatus control board 130, the temperature control board 140 and the I / O board 150 will be simply referred to as "control of the control means 10". .

Further, although the personal computer 110 is provided outside the apparatus main body 2 in this embodiment, a configuration corresponding to the personal computer 110 may be incorporated in the apparatus main body 2.

Next, an example of the method of use and the operation of the microarray processing apparatus 1 will be described.

[1] First, the operator (measuring person) has a container 72 filled with the cleaning liquid W (cleaning liquids Wa to We).
a to 72e, a container 72f filled with the moisturizing liquid H, a container 72g filled with the flushing liquid F, and a container 72h filled with the gas G are prepared.

Next, the containers 72a to 72h are installed in the predetermined holes 231 of the container installation section 23, and the respective upstream side branch lines 71a to 71h (cleaning liquid supply means 7W, moisturizing liquid supply means 7H, gas supply means). 7G and flushing liquid supply means 7F).

As shown in FIG. 8, in this embodiment, each of the containers 72a to 72d and 72f can be heated (the temperature can be adjusted).

[2] Next, the operator turns on the power switch (not shown) of the apparatus main body 2. As a result, the Peltier elements 911a and 911b and the heaters 921a and 921a and 9
21b is operated, and the processing tank 3 (processing unit housing 3
1) Preliminarily heat (heat) each processing unit 30 installed in each to a predetermined temperature (for example, about 25 to 30 ° C.).
To do.

At this time, the heaters 941a to 941
d, 941f, respectively, to activate the cleaning liquids Wa to Wd.
The moisturizing liquid H is heated (heated) to a predetermined temperature.

[3] Next, the operator selects the personal computer 110.
The power switch (not shown) is turned on. This allows
The program recorded in the memory 121 is executed.

Then, the operator operates the keyboard 112 according to the display screen displayed on the monitor 111,
Information such as various processing conditions in the processing of the microarray M and selection (setting) of the cleaning liquid W (Wa to We) to be used is input. In the present embodiment, the cleaning liquids Wa to Wd are used.
Set to use.

[4] Next, when the operator operates the keyboard 112 according to the display screen of the monitor 111, the apparatus main body 2 performs the priming process.

First, the upstream valves 73a to 73d, 7
3f to 73g and the downstream valve 77 are opened, and the pump 78 is operated. As a result, each cleaning liquid Wa
~ Wd, the moisturizing liquid H, and the flushing liquid F are introduced into the upstream branch lines 71a to 71d, 71f to 71g, respectively.

Then, when the pump 78 is rotated a predetermined number of times, the valves 73a to 73d, 73f to 73g and the downstream valve 77 are closed, and the pump 78 is stopped. Thereby, each upstream side branch line 71a-7
1d and 71f to 71g respectively have respective valves 73a.
~ 73d, 73f ~ 73g position, cleaning liquid Wa ~ W
d, the moisturizing liquid H and the flushing liquid F are introduced.

[5] Next, when the operator operates the keyboard 112 according to the display screen of the monitor 111, the apparatus main body 2 brings the processing tank 3 into an open state.

First, when the motor 38 is rotated by the control of the control means 10 so that the rotation direction of the rotary shaft 381 is forward (counterclockwise) in FIG. 7, the gear 382 moves in the same direction accordingly. Rotate. At this time, the gear 372 meshing with the gear 382 rotates backward (clockwise) in FIG. 7, and the shaft 371 also rotates in the same direction as the gear 372. As a result, the lid 37 is rotated so as to be separated from the main body 32, and the processing tank 3 is opened.

[6] Next, the operator selects each processing unit 3 installed in the processing tank 3 (processing unit housing 31).
The cover cassettes 50 of 0 are removed. In addition,
In this state, each processing tab 40 is installed in the processing tank 3.

Then, the operator stores (installs) a predetermined number of microarrays M in the spaces 431 of the processing tabs 40, respectively.

Then, the operator mounts the cover cassette 50 on each processing tab 40. At this time, each window portion 50a of each cover cassette 50 is preferably in the closed state (the state shown in FIG. 6A).

[7] Next, when the operator operates the keyboard 112 according to the display screen of the monitor 111, the apparatus main body 2 causes the reaction processing of the nucleic acid S and the probe liquid R, the nucleic acid S.
The washing process and the drying process of the nucleic acid S are sequentially performed.

[7-1] Reaction of Nucleic Acid S with Probe Solution R First, the moving mechanism 62 of the probe solution supply means 6 is operated. By this moving mechanism 62, the operating member 63 is moved to be brought into contact with the operating knob 542 of the slide door 540 from the right side in FIG. When the operating member 63 is moved to the left side in FIG. 6 from this state, the slide door 540 moves in the same direction, whereby the window 50a is opened (see FIG. 6).
(State shown in (B)).

Next, the moving mechanism 62 moves the dispensing device 61 closer to above the chip installed in the predetermined hole 211 of the chip installation section 21, and mounts the chip on the nozzle 612.

Next, the pipetting device 61 having such a tip mounted thereon is moved by the moving mechanism 62, and the probe liquid R is introduced into the tip from the container installed in the predetermined hole 221 of the probe liquid storage container installation part 22. Aspirate into.

When a double-stranded nucleic acid such as DNA or cDNA is used as the probe, the probe solution R is, for example, 65% before being sucked into the chip. After heating (warming) to about 95 ° C, the probe is preferably single-stranded by, for example, rapidly cooling to about 4 to 10 ° C or cooling to about 20 to 30 ° C. As a result, in the reaction between the nucleic acid S and the probe liquid R, this reaction can be performed more quickly and accurately.

Also, heating (warming) of the probe liquid R
Is preferably performed in a state in which the probe liquid storage container installation portion 22 (each hole 221) is covered by the heater-equipped lid 222 and the airtightness of each container is maintained. Thereby, the evaporation of the liquid component in the probe liquid R can be prevented more reliably.

After that, the dispensing mechanism 6 is moved by the moving mechanism 62.
1 is moved to insert the tip portion (lower end portion) of the chip into the inside of the processing unit 30 through the open window portion 50a and position it near the upper portion of the microarray M. In this state, the probe solution R in the chip is discharged to supply the probe solution R to the nucleic acid S.

[0218] Next, the moving mechanism 62 moves the dispensing device 61 to above the tip setting section 21. And
The used chip is removed from the nozzle 612 by, for example, a chip removing means (not shown), and the chip setting unit 2
It is re-installed (returned) in the predetermined hole 211 of No. 1.

The used chips may be separately disposed in a chip discarding unit and discarded in this chip discarding unit.

Then, the operating member 63 is moved by the moving mechanism 62, and the operating knob 552 of the slide door 550 is moved.
6 is contacted from the left side in FIG. From this state, when the operation member 63 is moved rightward in FIG. 6, the operation knob 55
2 comes into contact with the door body 541 of the slide door 540, and the slide door 550 and the slide door 540 are integrally formed as shown in FIG.
Move to the middle right. As a result, the window 50a is closed (the state shown in FIG. 6C).

The center portion of the first shaft 563 of the cover plate 560 is engaged with the hook 553 of the slide door 550, and the cover plate 560 moves to the right side in FIG. 6 as the slide door 550 moves. Move toward. At this time, the cover plate 560 has the cover plate body 561 shown in FIG.
From the left side in the middle, the microarray M (plate P) is approached in sequence, and almost at the same time when the window portion 50a is closed,
Superposed on the microarray M. As a result, the probe liquid R is uniformly spread in the gap formed between the cover plate main body 561 (cover plate 560) and the microarray M, and the nucleic acid S and the probe liquid R can be brought into uniform contact with each other. .

The above operation is repeated to supply the probe liquid R to each microarray M (nucleic acid S).

Further, in parallel with this step, each processing tab 4
The moisturizing liquid H is supplied to each of the spaces 421 of 0.

Specifically, the upstream valve 73f, the three-way valve 79 and the downstream valve 75d are opened and the pump 78 is operated.

As a result, a predetermined amount of the moisturizing liquid H is transferred from the container 72f through the upstream branch line 71f, the main supply line 70, the downstream branch line 74d, the communication hole 353 and the second supply passage 471. , Into each space 421.

The supply amount of the moisturizing liquid H is not particularly limited, but it is preferably about 5.0 to 10.0 mL, for example.

First, by the control of the control means 10,
When the motor 38 is rotated so that the rotation direction of the rotation shaft 381 is rearward (clockwise) in FIG. 7, the gear 382 accordingly rotates in the same direction. At this time, this gear 38
The gear 372 meshing with 2 is the front (counterclockwise) in FIG.
The shaft 371 also rotates in the same direction as the gear 372.
As a result, the lid body 37 rotates so as to approach the main body portion 32, and eventually comes into contact with the upper edge portion of the main body portion 32, and the processing tank 3 is closed.

At this time, the lid 37 is pressure-bonded to the sealing member 341, and the processing bath 3 is hermetically sealed (sealed).

Further, from this state, by rotating the motor 38 in the same direction, pressure (pressing force) such that the lid 37 is pressed against the main body 32 is applied.

Then, the control means 10 controls so that the temperature of each Peltier element 911a, 911b and each heater 921a, 921b rises. As a result, the internal temperature of each processing unit 30 rises, and along with this, each processing unit 3
00 temperature rises. That is, the nucleic acid S and the probe liquid R are heated in each processing unit 300.

While maintaining this heating state, the nucleic acid S and the probe solution R are reacted. Nucleic acid S and probe solution R
By carrying out the reaction while heating, this reaction can proceed efficiently (accurately) and the reaction time can be shortened.

The heating temperature (heating temperature) is not particularly limited, but is preferably about 45 to 75 ° C., more preferably about 50 to 70 ° C., for example. If the heating temperature is too low, the nucleic acid S and the probe solution R may not be able to react sufficiently. on the other hand,
If the heating temperature is set too high, the probe may be thermally decomposed depending on the type of the probe in the probe liquid R, which may lead to a decrease in the analysis accuracy.

Further, due to this heating, the temperature inside the processing tank 3 also rises. As a result, the pressure in the processing tank 3 gradually increases as the air in the processing tank 3 expands and the moisturizing liquid H evaporates. At this time, the lid 37
Is pressed against the main body 32 by the lid opening / closing mechanism 3A, so that the processing tank 3 can be kept closed against the force of pushing up the lid 37 due to the pressure increase in the processing tank 3. .

The heating time (heating time) is appropriately set depending on the heating temperature and the like and is not particularly limited, but is preferably about 2 to 20 hours, for example, 16 to 1
It is more preferable that the time is about 8 hours. If the heating time is too short, the nucleic acid S and the probe solution R may not be able to react sufficiently. On the other hand, even if you lengthen the heating time,
No further increase in the effect is observed, and depending on the heating temperature or the like, the probe in the probe liquid R may be thermally decomposed, leading to a decrease in analysis accuracy.

As described above, the moisturizing liquid H is supplied to the periphery of each processing section 300 (in each space 421) and the humidity is appropriately maintained, so that the reaction between the nucleic acid S and the probe liquid R occurs. At this time, evaporation of the liquid component in the probe liquid R due to the temperature rise of each processing unit 300 is preferably prevented (suppressed).

Also, in this embodiment, each processing unit 3
Since the temperature of 0 (each processing unit 300) can be heated (adjusted) from the vertical direction, the temperature in the processing tank 3 can be made more uniform. Thereby, the humidity in each processing unit 30 (processing tank 3) can be kept more uniform, and the above effect can be further improved.

The humidity at this time is, for example,
It is preferably about 45 to 80% RH.

Further, the control means 10 controls the Peltier elements 911a and 911b and the heaters 921a and 921b.
By appropriately controlling the operation of each processing unit 30
With the microarrays M installed therein as one set, different temperature adjustment conditions can be set between the sets.
Therefore, for example, different types of microarrays M are prepared for the probe liquids R collected and prepared from the same subject.
When it is desired to perform different inspections by using, such an inspection can be performed simultaneously, which is advantageous.

[7-2] Washing of nucleic acid S Next, when a predetermined heating time has elapsed, the heaters 921a and 921b are stopped by the control of the control means 10 and the motor 38 is moved forward (counterclockwise) in FIG. Rotate around). As a result, the processing tank 3 is opened in the same manner as described above.

The opening of the processing tank 3 may be performed after the lid 37 is cooled to a predetermined temperature (for example, about 25 to 30 ° C.).

Then, the moving mechanism 62 of the probe liquid supply means 6 is operated. The operation member 63 is moved by the moving mechanism 62, and the operation knob 552 of the slide door 550 is moved.
The right side in FIG. From this state, when the operation member 63 is moved toward the left side in FIG. 6, the slide door 5
50 moves in the same direction. At this time, the slide door 550
The hook 553 of the first plate 5 of the cover plate 560.
The central portion of 63 is engaged, and the cover plate 560 is also shown in FIG.
After moving toward the middle left side, the state shown in FIG. That is, from the microarray M to the cover plate 5
Separate 60 (remove).

By repeating this operation, the cover plate 560 is separated from each microarray M.

At this time, each Peltier element 911
The heating by a and 911b is continued. In other words, the operation of separating the cover plate 560 from the microarray M is preferably performed while maintaining the temperature of each processing unit 300 at a relatively high temperature. This gives, for example,
The nucleic acid S is the cover plate body 5 of the cover plate 560.
Even when it is in contact with 61, it is possible to prevent (suppress) the probe that has reacted with the nucleic acid S, the label of this probe, or the nucleic acid S itself from adhering (migrating) to the cover plate body 561. Then, when analyzing the reaction result of the nucleic acid S, it is possible to prevent (suppress) the decrease of the analysis accuracy.

At the same time as or before the start of the operation, the upstream side valve 73a, the three-way valve 79 and the downstream side valves 75a to 75c are opened by the control of the control means 10, and the pump 78 is turned on. Operate. Thereby, the cleaning liquid Wa is transferred through the upstream branch line 71a, the main supply line 70, the downstream branch lines 74a to 74c, the communication holes 351 and the first supply passage 451.
Supply into each space 431.

That is, the operation of separating the cover plate 560 from the microarray M is performed while supplying the cleaning liquid Wa. As a result, the microarray M
At the site where the nucleic acid S is attached (the site where the object to be processed S of the processing section 300 is installed), rapid drying due to contact of the probe liquid (reaction liquid) R with air is prevented (suppressed), and the unreacted probe It is possible to preferably prevent (suppress) the precipitation of (unnecessary probe). Therefore, the excess probe liquid R can be washed out more efficiently, and as a result,
When the reaction result of the nucleic acid S is analyzed, the analysis accuracy can be improved.

It should be noted that a predetermined amount of cleaning liquid W is placed in each space 431.
When a is supplied, the upstream valve 73a and the three-way valve 79
And the downstream valves 75a to 75c are closed, and the pump 78 is stopped.

The predetermined amount (supply amount) of the cleaning liquid Wa is, for example, preferably about 50 to 200 times, and more preferably about 100 to 150 times the supply amount of the probe liquid R.

As described above, the microarray M
The operation of separating the cover plate 560 from is preferably performed at a relatively high temperature. Therefore, as the cleaning liquid Wa, one having a temperature (for example, about 40 to 70 ° C.) at which the temperature of each processing unit 300 at the start of the operation can be prevented (suppressed) from abruptly decreasing. It is preferable to use one having a temperature of about 45 to 65 ° C.

Next, when the operation of separating the cover plate 560 from all the microarrays M is completed, the valves 82a to 82c are opened and the pump 84 is operated.
As a result, the waste liquid in each space 431 (cleaning liquid W after use)
a and the surplus probe liquid R) to the respective first discharge paths 46
1, transferred through the communication holes 352, the branch lines 81a to 81c, and the main discharge line 80, and collected in the waste liquid collection container 85. That is, drainage is performed from each space 431 (processing tank 3).

After that, when the pump 84 is rotated a predetermined number of times, the valves 82a to 82c are closed and the pump 84 is stopped. This ends the drainage.

In this drainage operation, for example, a bubble sensor capable of detecting bubbles flowing in the flow path of the main discharge line 80 is provided between the manifold 83 and the pump 84, and the bubble sensor The process may be ended based on the information (detection signal), that is, when the bubble sensor detects a bubble.

Then, the upstream valve 73b, the three-way valve 79 and the downstream valves 75a to 75c are opened, and the pump 78 is operated. As a result, the cleaning liquid Wb is transferred via the upstream branch line 71b, the main supply line 70, the downstream branch lines 74a to 74c, the communication holes 351 and the first supply path 451, and supplied into each space 431. To do.

Then, when a predetermined amount of the cleaning liquid Wb is supplied into each space 431, the upstream valve 73b, the three-way valve 79 and the downstream valves 75a to 75c are closed, and the pump 78 is stopped.

Next, the control means 10 controls the Peltier elements 911a and 911b to have a predetermined temperature (for example, 25 to 30 ° C.).
Control). As a result, each processing unit 3
The temperature of 00 is lowered.

Then, each space 431 is processed in the same manner as described above.
Drain the liquid from the inside. Next, in the same manner as described above, after the cleaning liquid Wb is supplied into each space 431, the liquid is drained from each space 431.

It is preferable that the cleaning liquid Wb has, for example, the same composition and concentration as the cleaning liquid Wa and the temperature thereof is about 20 to 30 ° C.

The supply amount of the cleaning liquid Wb is preferably substantially the same as that of the cleaning liquid Wa.

Then, the upstream valve 73c, the three-way valve 79 and the downstream valves 75a to 75c are opened, and the pump 78 is operated. As a result, the cleaning liquid Wc is transferred through the upstream branch line 71c, the main supply line 70, the downstream branch lines 74a to 74c, the communication holes 351 and the first supply path 451, and supplied into each space 431. To do.

After that, when a predetermined amount of cleaning liquid Wc is supplied into each space 431, the upstream valve 73c, the three-way valve 79 and the downstream valves 75a to 75c are closed, and the pump 78 is stopped.

Then, the control means 10 causes the Peltier elements 911a and 911b to have a predetermined temperature (for example, 35 to 45 ° C.).
Control). As a result, each processing unit 3
Increase the temperature of 00.

Then, each space 431 is processed in the same manner as described above.
Drain the liquid from the inside. Next, in the same manner as described above, after the cleaning liquid Wc is supplied into each space 431, the liquid is drained from each space 431.

The concentration of the cleaning liquid Wc (eg, salt concentration, surfactant concentration, etc.) is lower than that of the cleaning liquid Wb, and the temperature thereof is slightly higher than that of the cleaning liquid Wb (eg, It is preferably about 35 to 45 ° C.).

The supply amount of the cleaning liquid Wc is preferably substantially the same as the cleaning liquid Wa.

Next, the upstream valve 73d, the three-way valve 79 and the downstream valves 75a to 75c are opened, and the pump 78 is operated. As a result, the cleaning liquid Wd is transferred through the upstream branch line 71d, the main supply line 70, the downstream branch lines 74a to 74c, the communication holes 351 and the first supply path 451, and supplied into each space 431. To do.

After that, when a predetermined amount of the cleaning liquid Wd is supplied into each space 431, the upstream valve 73d, the three-way valve 79 and the downstream valves 75a to 75c are closed, and the pump 78 is stopped.

Then, the control means 10 causes the Peltier elements 911a and 911b to have a predetermined temperature (for example, 20 to 30 ° C.).
Control). As a result, each processing unit 3
The temperature of 00 is lowered.

Then, each space 431 is processed in the same manner as described above.
Drain the liquid from the inside. Then, in the same manner as described above, after the cleaning liquid Wd is supplied into each space 431, the liquid is drained from each space 431.

The cleaning liquid Wd has a composition different from that of the cleaning liquids Wa to Wc (for example, one containing no surfactant) and the temperature thereof is, for example, 20.
It is preferably about 30 ° C.

The supply amount of the cleaning liquid Wd is preferably substantially the same as that of the cleaning liquid Wa.

As described above, by properly setting and using the conditions of the respective washing solutions Wa to Wd, the washing of the nucleic acid S can be carried out more reliably, that is, the excess probe solution R (unreacted probe) can be further removed. It can be reliably removed from the nucleic acid S. As a result, when the reaction result of the nucleic acid S is analyzed, the accuracy of the analysis can be further improved.

The condition setting of each cleaning liquid Wa to Wd is as follows.
It goes without saying that the present invention is not limited to the above. In the washing treatment of the nucleic acid S, if necessary,
Cleaning liquids under different conditions may be additionally used, or any one of the cleaning liquids Wb to Wd may be omitted.

[7-3] Drying of nucleic acid S Next, the upstream valve 73h, the three-way valve 79 and the downstream valves 75a to 75c are opened and the pump 78 is operated. As a result, the gas G is transferred to the upstream branch line 71.
h, main supply line 70, each downstream side branch line 74a-7
4c, the communication holes 351 and the first supply passage 451 to transfer the respective components into the spaces 431.

By supplying the gas G into each space 431,
In each space 431, the gas G is brought into contact with the nucleic acid S to dry the nucleic acid S.

Then, when a predetermined amount of gas G is supplied into each space 431, the upstream valve 73h, the three-way valve 79 and the downstream valves 75a to 75c are closed, and the pump 78 is stopped.

[0275] In the above-described washing treatment and drying treatment of the nucleic acid S, when the washing liquid W or the gas G supplied into each space 431 is changed (switched), the following may be performed.

For example, when changing the cleaning liquid Wb supplied into each space 431 to the cleaning liquid Wc, first, the upstream valve 73c, the three-way valve 79 and the downstream valve 77 are opened, and the pumps 78 and 84 are operated. To do. This allows
Once the cleaning liquid Wb remaining in the flow path of the main supply line 70
Is transferred through the drain line 76 and the main discharge line 80, and is collected in the waste liquid collection container 85.

Next, after supplying the cleaning liquid Wc that can sufficiently fill the flow path of the main supply line 70, the downstream side valve 77 is closed, the pump 84 is stopped, and each of the downstream side valves 75a to 75c. Is opened to supply the cleaning liquid Wc into each space 431.

In such an operation, the cleaning liquid Wb is replaced with the cleaning liquid W
Not only when changing to c, but also when changing the washing liquid Wa to the washing liquid Wb, changing the washing liquid Wc to the washing liquid Wd, changing the washing liquid Wd to the gas G, and the like. .

Thereby, for example, each of the cleaning liquids Wa to Wd
When the gas G and the gas G are not desired to be mixed with each other, the mixing of these can be suitably reduced (suppressed).

[8] Next, the operator selects each processing unit 3 installed in the processing tank 3 (processing unit housing 31).
The cover cassette 50 of No. 0 is removed, and each microarray M is collected from each space 431 of each processing tab 40. Then, each microarray M is subjected to analysis of the reaction result of the nucleic acid S.

[9] Next, when the operator operates the keyboard 112 according to the display screen of the monitor 111, the apparatus main body 2 performs the flushing process.

First, the upstream valve 73g and the three-way valve 7
9. The downstream valves 75a to 75d and 77 and the valves 82a to 82d are opened, and the pumps 78 and 84 are operated. As a result, the flushing liquid F is passed through the upstream branch line 71g and the main supply line 70, and a part of the flushing liquid F is further treated by the processing tank 3 (each of the spaces 431, 42).
1) The rest is transferred from the drain line 76 directly to the main discharge line 80 via the inside, and the waste liquid recovery container 8
Collect within 5.

Then, when a predetermined amount of flushing liquid F is supplied, the upstream valve 73g is closed. The three-way valve 79, the downstream valves 75a to 75d and 77, and the valves 82a to 82d are kept open, and the pumps 78 and 84 are kept operating. As a result, the flushing liquid F remaining in the supply circuit 7, the processing tank 3 (each of the spaces 431 and 421) and the discharge circuit 8 is transferred and collected in the waste liquid collection container 85. As a result, the inside of the supply circuit 7, the processing tank 3 (each of the spaces 431 and 421) and the discharge circuit 8 are cleaned.

After that, when the pump 78 and the pump 84 are rotated a predetermined number of times, the three-way valve 79, the downstream valves 75a to 75d and 77, and the valves 82a to 82d are closed, and the pumps 78 and 84 are stopped. This allows
The flushing process ends.

The flushing process may be terminated based on the information (detection signal) from the bubble sensor as described above.

[10] Next, the operator selects each processing tab 4
The newly prepared cover cassettes 50 are attached to the respective 0s.

Then, when the operator operates the keyboard 112 according to the display screen of the monitor 111, the apparatus main body 2
In the same manner as described above, the processing tank 3 is closed.

Next, the operator turns off the power switches of the personal computer 110 and the apparatus main body 2 to complete one processing of the microarray M.

In the above steps [1] to [10],
You may make it add an arbitrary process as needed.

<Second Embodiment> Next, a microarray processing apparatus according to the second embodiment will be described.

In the microarray processing apparatus of the second embodiment, mainly the structure of the lid opening / closing mechanism is different, and other than that,
This is the same as the first embodiment.

9 to 11 are schematic views showing the construction of the lid opening / closing mechanism of the second embodiment, respectively. this house,
9 shows a state in which the lid body is in the retracted position, and FIG.
FIG. 11 shows a state in which the lid is being conveyed, and FIG. 11 shows a state in which the lid is in the upper position. FIG. 12 is a side view showing the configuration of the fixed wall in the lid opening / closing mechanism of the second embodiment, and FIG. 13 describes the relationship between the carriage and the rack in the lid opening / closing mechanism of the second embodiment. FIG. 14 is a plan view (partially cut away) of the lid opening / closing mechanism of the second embodiment, and FIG. 15 describes the operation of the lid opening / closing mechanism of the second embodiment. FIG.

In the following description, in FIGS. 9 to 13 and 15, the upper side is "upper" or "upper end", the lower side is "lower" or "lower end", the left side is "front", and the right side is "." In FIG. 14, the upper side is referred to as “front” and the lower side is referred to as “rear”.

The lid opening / closing mechanism of the second embodiment will be described below focusing on the differences from the first embodiment, and the description of the same items will be omitted.

In this embodiment, the lid 37 is made up of the main body 32.
It is slidable (displaceable) with respect to.

The lid opening / closing mechanism 3B of the second embodiment mainly includes a carriage 391 for conveying the lid 37 and the lid 37.
Link plates 392a and 392b that are rotatably connected to the carriage 391 and are connected to suspend the lid body 37 from the carriage 391, and attract the lid body 37 to the carriage 391 in the transport state of the lid body 37. Spring as a member (tensile spring) 3
It has 93 and the 1st stopper 394 which contacts the link plate 392a and raises the link plate 392a.

The link plates 392a, 392b
Of the carriage 391 is set to be longer than the connection distance when the carriage 391 and the lid body 37 are in close contact with each other, and in a steady state, the carriage 391 is in close contact with the pulling force of the spring 393.
And the lid 37 are connected by inclining.

Further, the link plate 392b is indirectly erected in association with the erection of the link plate 392a.

The attracting member (pulling means) is
Instead of the spring 393, an elastic member having elastic force may be used.

As shown in FIG. 12, a carriage 391.
Are fixed walls 395 disposed on the left and right of the main body 32 (see FIG.
In FIG. 11, only the back side of the paper with respect to the main body 32 is shown. ), It is configured to move along the guide groove 395a formed therein.

The guide groove 395a is at a position where the lid 37 shown in FIG. 9 is stored (retracted) behind the main body 32 (hereinafter referred to as "retracted position") and a retracted position shown in FIG. From the upper portion of the main body portion 32 (hereinafter, referred to as “upper position”) that is shifted (moved) in parallel from the above. The link plate 3 is placed in the guide groove 395a.
A roller 396 coaxially arranged on a shaft on the side of the carriage 391 that rotatably supports 92a and 392b is inserted to smoothly move the carriage 391.

9 to 11, the guide groove 395a shown in the drawing engages with the roller 396 mounted on the shafts of the link plates 392a and 392b arranged on the back side of the carriage 391.

The upper position and the retracted position may have a positional relationship such that the upper position and the retracted position are located at both ends of the L-shape, as shown in FIG. The positional relationship may be such that they are located at.

Further, on the fixed wall 395, racks 398a, 398b (FIGS. 9 to 11) with which a pinion gear 397 connected to a motor 38 which is a drive source mounted on a carriage 391 as shown in FIG. 12 meshes. See also) is fixed. Therefore, the drive of the motor 38 allows the carriage 391 to be self-propelled along the guide groove 395a.

The motor 38 mounted on the carriage 391 is preferably a motor with a brake, and when power is not supplied, rotation is stopped and its position can be maintained. It is preferable to use one.

Besides, on the fixed wall 395, the carriage 3
When 91 moves to the upper position, the link plate 3
The first stopper 394 for fixing the link plate 392a is fixed by the contact with 92a. The first stopper 394 may have any shape as long as it promotes the standing of the link plate 392a, but in order to promote a smooth standing operation, it is preferable that the contact surface is a curved surface, and further smooth standing is promoted. For this purpose, it is preferable that the roller be rotatably formed.

Shafts 391a and 391b for rotatably supporting the plate upper ends of the link plates 392a and 392b respectively project to the left and right sides of the carriage 391, and the guide plates are provided outside the link plates 392a and 392b. Roller 396 inserted in groove 395a
Is still rotatably mounted.

Further, a self-propelled motor 38 of the carriage 391 is fixed inside the carriage 391, and the driving force thereof is transmitted to the pinion gear 397 via the gear train 383 and rotated with respect to the rack 398b. By
The carriage 391 runs on its own.

The gear train 383 is arranged so as to rotationally drive a shaft 397a that supports a pair of pinion gears 397 that mesh with a rack 398b formed on the left and right fixed walls 395.

Further, shafts 374 for rotatably supporting the plate lower ends of the link plates 392a and 392b also project to the left and right of the lid 37. Therefore, in the case of this embodiment, the lid 37 is suspended and held by the carriage 391 at four points.

When the lid 371 and the link plates 392a and 392b move forward together with the carriage 391 by the self-propelled movement of the carriage 391 and move to the upper position, the lower end portion of the link plate 392a (the lid 37 The first stopper 394 is fixed to a predetermined position of the fixed wall 395 so that the side (the side that engages with) abuts.

When the lid 37 is moved to the upper position and the direction is changed so that the lid 37 is moved in the pressing direction by the standing of the link plate 392a, the link plate 37 is moved to the upper position. A second stopper 399 for preventing the 392a from standing upright or more is fixed. The second stopper 399 is composed of, for example, a bolt that can move forward and backward, and the stop position can be adjusted appropriately. Usually, this second stopper 399
The position can be fixed with a double nut or the like.

Next, the operation from immediately before the lid opening / closing mechanism 3B presses the lid 37 to the completion thereof will be described with reference to FIG.

In FIG. 15A, the lid 37 is the carriage 3
The state of being suspended from 91 and being conveyed from the retracted position to the upper position is shown.

In this state, the lid 3 is attached to the bottom surface side of the carriage 391 by the spring 393 which is a tension spring.
7 is drawn so as to be in close contact.

Here, the close contact between the carriage 391 and the lid body 37 means that the carriage body 391 and the carriage body 391 do not sway with the movement of the carriage 391 or the bottom surface side of the lid body 37 does not come into contact with the main body portion 32. The state in which the lid 37 and the lid 37 are close to each other does not necessarily require perfect contact. In other words, the close contact between the carriage 391 and the lid body 37 is only required to form a substantially close contact state, and there may be a part that is not in contact.

Also, the link plates 392a, 392b
Are formed longer than the fixed point distance when the carriage 391 and the lid 37 are in close contact with each other. For this reason,
As shown in FIG. 5A, when the spring 393 and the spring 393 are in close contact with each other, the plate lower ends of the link plates 392a and 392b are inclined with respect to the carriage 391 so as to precede the forward movement direction of the carriage 391. It is supposed to do. Note that this state is the same when the carriage 391 is at the retracted position.

FIG. 15B shows the carriage 391 in the upper position. In this state, the fixed wall 3
The carriage 39 is fixed to the first stopper 394 fixed to
The lower end side of the plate 2a is in contact (contact). Therefore, from this position, the lid 37 does not move forward even if the forward movement of the carriage 391 is continued. That is, the lid 37 reaches the position (upper position) where the processing unit housing 31 of the main body 32 can be closed, and the forward movement is stopped.

In this state, the link plate 39
Only the 2a is in contact with the stopper 394, and the forward movement of the carriage 391 itself is not regulated. Therefore, by driving the motor 38, the carriage 391 continues the forward movement.

As described above, the link plate 392a
Since the lower end side of the plate is in contact with the first stopper 394, as shown in FIG.
As shown in FIG. 5 (c), it starts to stand. Further, at this time, the link plate 392b also stands up in association with each other.

The carriage 391 has the guide groove 3
Since the vertical movement of the link plates 392a and 392b is restricted by 95a,
The lid 37 resists the attractive force of the spring 393,
Move down.

Since the movement of the link plate 392a is restricted by the first stopper 394, the lid 3
7 descends almost vertically toward the main body 32.

In this embodiment, the sealing member 375 having the same structure as the sealing member 341 described in the first embodiment.
Is installed on the inner surface (the lower surface in FIG. 11) of the lid 37 along the vicinity of the edge thereof.

Also, the link plates 392a, 392b
The length in the longitudinal direction is crushed until the lid member 37 is pressed by the main body portion 32 and the sealing member 375 is brought into the optimum function state with respect to the carriage 391 whose vertical movement is restricted by the guide groove 395a. The length is set so as to descend to a position where the airtightness of the main body 32 can be secured. Therefore, after the link plates 392a and 392b are erected, the lid body 37 is pushed down by the rigidity of the link plates 392a and 392b and the rigidity of the fixed wall 395 through the carriage 391, so that a stable large pressing force is exerted. Can be secured.

In this way, the link plates 392a, 3
Since 92b performs the same operation and action as the toggle mechanism (power increasing mechanism), the pressing pressure of the lid body 37 is greatly increased as compared with the force of the motor 38.

The movement of the link plate 392a on the lower end side of the plate is restricted by the first stopper 394, and the second stopper 39 of the carriage 391 is also controlled.
By the regulation of the forward movement by 9, the movement is regulated when the upper end side of the plate also stands up substantially vertically.

As a result, the carriage 391 and the lid 37 are separated by the maximum distance determined by the lengths of the link plates 392a and 392b in the longitudinal direction, and the lid 37 is pressed against the main body 32 by the maximum pressing force. Press with. At this time, since the link plates 392a and 392b are erected at a substantially vertical position, even if the force of pushing up the lid 37 due to the pressure increase in the processing tank 3 acts, the link plates 392a and 392b are not pushed down diagonally and maintain the erected state. can do.

Further, by restricting the rising of the link plates 392a, 392b by the second stopper 399,
The conveyance and pressing operation of the lid 37 can be easily and reliably controlled without highly accurately controlling the motor 38 including the forward movement of the carriage 391.

The carriage 391 is a rack 398.
Since it is in a fixed state due to the engagement of b with the pinion gear 397, it is possible to prevent the carriage 391 from moving and the pressing force to the lid 37 from decreasing even if the pressure in the processing tank 3 increases. it can.

Further, as described above, by adding the braking function to the motor 38, the movement of the carriage 391 can be prevented more reliably.

On the other hand, when the lid 37 is removed from the main body 32, the motor 38 of the carriage 391 is rotated in the opposite direction to the forward movement to move the carriage 391 to the retracted position side. Due to the pulling force,
The lid 37 is pulled up. Further, the carriage 391
When is retracted, the state sequentially shifts to the state shown in FIGS. 10 and 9, and the lid 37 can be retracted and stored.

As described above, in this embodiment, the carriage 391, the link plates 392a and 392b, the guide groove 395a, the rollers 396, and the racks 398a and 39 are mainly used.
A transport mechanism that transports the lid 37 is configured between the upper position of the main body 32 and the retracted position by 8b and the like, and mainly includes the link plate 392a, the first stopper 394, and the second stopper.
The stopper 399 constitutes a moving direction changing mechanism that changes the moving direction of the lid 37.

Then, the moving direction changing mechanism is moved by the carrying mechanism so as to be substantially parallel to the upper edge of the main body 32 (as shown in FIG. 15) from the side of the main body 32 to the upper position. The moving direction of the lid 37 conveyed to the main body 32 is changed to the direction toward the main body 32 (downward in FIG. 15).

When the lid 37 is in the retracted position, there is no member constituting the lid opening / closing mechanism 3B above the main body 32, so that another processing operation such as the probe liquid R is performed.
Can be easily and surely supplied (dispensing operation).

In this way, according to the lid opening / closing mechanism 3B,
Using a single drive source, it is possible to perform the transporting movement of the lid 37 between the retracted position and the upper position and the pressing movement to the main body 32.

Further, since the lid 37 has the reinforcing member 37b, it is possible to uniformly apply the pressing force by the lid opening / closing mechanism 3B to the entire lid 37. Therefore, the airtightness of the inside of the processing tank 3 is more reliably ensured in the closed state.

By using a drive mechanism using the racks 398a, 398b, pinion gears 397, etc.,
Even with the small output motor 38, it is possible to realize sufficient conveyance and pressing operation of the large lid 37. That is, according to the present invention, downsizing of the lid opening / closing mechanism 3B, and by extension,
This can contribute to miniaturization of the microarray processing device 1.

In the present embodiment, the link plate 3
92a and 392b are installed on the left and right respectively, for a total of 4
Although the case where the lid body 37 is suspended and pressed by an individual piece is shown, the number of installations and the arrangement position thereof can be appropriately set as long as the lid body 37 can be pressed down in a well-balanced manner. For example, one link plate may be arranged in the central portion of the lid 37, or three link plates may be arranged on each of the left and right sides, for a total of six link plates.

However, considering the pressure balance of the lid body 37, it is desirable to dispose at least one or a pair of link plates in the central portion (the complete central portion of the lid body 37 or the center of both sides of the lid body 37). .

When using a plurality of link plates, in order to easily balance the pressing force of the lid 37, for example, play is provided in the engaging portion between the link plate and the lid 37 other than the central portion. It is preferable that the link plate at the central portion is first pressed, and then the supplementary pressing is performed by another link plate.

The shapes of the carriage, the link plate, the fixed wall, etc. are also examples, and the carriage is at a predetermined position.
The shape can be set as appropriate as long as the lid 37 can be pressed against the main body 32 by the standing motion of the link plate in response to the regulation of the forward movement.

Although the processing apparatus for processing a workpiece of the present invention has been described above with reference to the illustrated embodiments, the present invention is not limited to these, and the constituent elements of the processing apparatus for a processing object have the same functions. It can be replaced with anything that exerts.

The shape of the reinforcing member is not limited to a plate shape, and may be, for example, a frame shape surrounding the outer peripheral portion of the inner member. It may be installed so as to cover the whole.

The reinforcing member need not be provided only for the purpose of substantially uniformly applying pressure (pressing force) by the lid opening / closing mechanism to the lid. That is, the reinforcing member may be provided for other purposes.

Further, the object to be treated may be, for example, living tissue, cells, proteins, lipids, hormones and the like.

As the reaction solution, for example, a staining solution,
It may be a liquid containing a labeled antigen or a labeled antibody.

From the above, the processing apparatus for the object to be processed of the present invention can be applied not only to the microarray processing apparatus but also to a processing apparatus for processing various objects to be processed. In this case, the various processing conditions are not limited to those described above, and can be appropriately set according to, for example, the type of processing object, processing purpose (inspection purpose), and the like.

[0348]

As described above, according to the apparatus for treating an object to be treated of the present invention, the operation of treating an object to be treated such as nucleic acid is easy, and the labor and time required for the operation are reduced. Can contribute to the automation of its implementation.

Further, in the present invention, since the lid body has the reinforcing member, the airtightness of the processing tank during the processing operation of the object to be processed can be ensured more reliably, and the processing of the object to be processed is more accurate. You can do it well.

From the above, by using the apparatus for treating an object to be treated of the present invention, for example, oncogenes, mutant genes, etc. can be searched for more easily and efficiently.

[Brief description of drawings]

FIG. 1 is an overall configuration diagram showing a first embodiment in the case where a treatment device for an object to be treated of the present invention is applied to a microarray treatment device.

FIG. 2 is an exploded perspective view (a part of which is omitted) of the processing unit.

FIG. 3 is a plan view showing a part of a processing tab provided in the processing unit.

FIG. 4 is a sectional view taken along line AA in FIG.

5 is a sectional view taken along line BB in FIG.

FIG. 6 is a cross-sectional view showing an operating state of the processing unit.

FIG. 7 is a perspective view showing a configuration of a processing tank.

FIG. 8 is a schematic diagram showing an internal configuration of the apparatus main body.

FIG. 9 is a schematic diagram showing a configuration of a lid opening / closing mechanism of the second embodiment (showing a state in which the lid is in a retracted position).

FIG. 10 is a schematic diagram showing a configuration of a lid opening / closing mechanism of the second embodiment (showing a state where the lid is being transported).

FIG. 11 is a schematic view showing a configuration of a lid opening / closing mechanism of the second embodiment (showing a state where the lid is at an upper position).

FIG. 12 is a side view showing a configuration of a fixed wall in the lid opening / closing mechanism of the second embodiment.

FIG. 13 is a diagram for explaining the relationship between the carriage and the rack in the lid opening / closing mechanism of the second embodiment.

FIG. 14 is a plan view (partially cut away) of the lid opening / closing mechanism of the second embodiment.

FIG. 15 is a view for explaining the operation of the lid opening / closing mechanism of the second embodiment.

[Explanation of symbols]

1 Microarray processing device 2 device body 2a Horizontal stage 2b vertical stage 21 Chip setting section 211 holes 22 Probe liquid storage container installation section 221 holes 222 Lid with heater 23 Container Installation Department 231 holes 3 treatment tanks 31 Processing unit storage 32 body 33 bottom 34 Side wall 341 sealing member 35 base 351 to 354 communication hole 36 groove 37 Lid 37a Inner member 37b Reinforcement member 371 axis 372 gear 373 Open / close sensor 374 axis 375 sealing member 38 motor 381 rotating shaft 382 gear 383 gear train 391 carriage 391a, 391b axis 392a, 392b Link plate 393 spring 394 First stopper 395 fixed wall 395a guide groove 396 Laura 397 Pinion Gear 397a shaft 398a, 398b rack 399 Second stopper 3A, 3B lid opening / closing mechanism 30 processing units 300 processing unit 40 Processing Tab 41 bottom 42 Side wall 421 space 43 Partition 431 space 432 slope 433a, 433b Large cutout 434a-434d Notch Notches 435a to 435e 436 groove 44 legs 45 Projection 451 First supply path 46 Projection 461 First discharge path 47 Projection 471 Second supply path 48 Projection 481 second discharge path 50 cover cassette 50a window 500 frames 510 First member 511 space 512 inner wall surface 512a First guide groove 512b Second guide groove 513 engagement part 520 Second member 521 recess 521a slide space 522 opening 530 Third member 531 opening 540 sliding door 541 Door body 542 operation knob 543 groove 550 sliding door 551 door body 552 operation knob 553 hook 553a Hook groove 560 cover plate 561 cover plate body 562 Side wall 563 1st axis 564 second axis 6 Probe liquid supply means 61 dispensing device 611 dispensing pump 612 nozzle 62 moving mechanism 62a x-axis direction moving mechanism 62b y-axis direction moving mechanism 62c z-axis movement mechanism 63 Operation member 7 Supply circuit 7W cleaning liquid supply means 7H Moisturizing liquid supply means 7G gas supply means 7F flushing liquid supply means 70 Main supply line 71a-71h Upstream branch line 72a to 72h container 73a-73h upstream valve 74a-74d Downstream branch line 75a-75d Downstream valve 76 drain line 77 Downstream valve 78 pumps 79 three-way valve 8 discharge circuit 80 Main discharge line 81a-81d Branch line 82a-82d valve 83 manifold 84 pumps 85 Waste liquid collection container 86 Liquid level sensor 800 Waste liquid collection section 9 Temperature control means 91 First Temperature Adjustment Unit 911a, 911b Peltier device 912a, 912b Temperature sensor 92 Second temperature adjustment unit 921a, 921b heater 922a, 922b Temperature sensor 93 Third temperature adjustment unit 931 Peltier element 932 Temperature sensor 94 Fourth temperature adjustment unit 941a to 941d, 941f heater 942a to 942d, 942f Temperature sensor 10 Control means 110 personal computer 111 monitor 112 keyboard 120 CPU board 121 memory 130 Device control board 140 Temperature control board 150 I / O board 160 relay board S nucleic acid P plate M microarray R probe solution W (Wa to We) Cleaning liquid H moisturizer F flushing liquid G gas

Continued front page    (72) Inventor Osamu Tanaka             6-22-1, Mure, Mitaka City, Tokyo Aloka             Within the corporation F term (reference) 2G058 AA09 BB02 BB03 BB11 BB15                       BB23 BB27 CC09 EA04 EB01                       EB02 EC03 EC09 ED02 ED35                       FA01 FB03 FB12 FB25 FB28                       GA01 GE02

Claims (23)

[Claims] 1. An apparatus for processing an object to be processed, which has a processing tank that is hermetically sealable and has a processing unit for installing the object to be processed, wherein the processing tank includes a main body having a recess, A lid body that is displaceable with respect to the main body portion, and the lid body is moved toward and away from the main body portion, and the lid body covers the concave portion, and further, the lid body is A lid opening / closing mechanism for applying pressure so as to press it against the main body, wherein the lid has an inner member having an inner surface joined to the main body, and the lid opening / closing mechanism applies the pressure evenly. A treatment device for an object to be treated, comprising: a reinforcing member. 2. The apparatus for treating an object to be processed according to claim 1, wherein the reinforcing member is fixed to the inner member and is displaced integrally with the inner member. 3. The apparatus for treating an object to be treated according to claim 1, wherein the reinforcing member has a plate shape and is installed so as to cover at least an outer surface side of the inner member. 4. The apparatus for treating an object to be treated according to claim 1, wherein the reinforcing member is made of a material having a hardness higher than that of the constituent material of the inner member. 5. The processing apparatus for an object to be processed according to claim 4, wherein the high hardness material is a metal material. 6. The processing apparatus according to claim 1, wherein the lid is rotatably provided with respect to the main body. 7. The processing apparatus for an object to be processed according to claim 1, wherein the lid is slidably provided with respect to the main body. 8. The lid opening / closing mechanism is provided between an upper position of the main body and a retracted position shifted from the upper position.
A transport mechanism for transporting the lid body, and a moving direction changing mechanism for changing the moving direction of the lid body, wherein the moving direction changing mechanism is substantially parallel to the upper edge portion of the main body portion by the transport mechanism. The object to be processed according to claim 7, wherein the movement direction of the lid body conveyed from the side of the main body portion to the upper position is changed to a direction toward the main body portion so that Processing equipment. 9. The lid opening / closing mechanism includes a carriage that moves between an upper position of the main body and a retracted position shifted from the upper position, and a plate for suspending the lid by the carriage. An upper end of the plate is rotatably supported by the carriage, and a lower end of the plate rotatably supports the lid, and at least one link plate, and an attractive force for attracting the lid to the carriage is generated. An attracting member for inclining the link plate with respect to the carriage, and allowing downward movement of the lid toward the main body when the carriage moves forward from the retracted position to the upper position, A first stopper for restricting the forward movement, the first stopper restricts the forward movement of the lid body, and then the carriage By the forward motion, the link plate is erected, the processing unit of the object according to claim 7 or 8 is configured to apply pressure so as to press said lid to said body portion. 10. The object to be processed according to claim 1, wherein the processing tank has a sealing member that hermetically seals the inside of the processing chamber in a state where the lid covers the recess. Processing equipment. 11. The object to be processed according to claim 10, wherein the sealing member is installed at an upper edge portion of the main body portion, and the lid body is pressed against the sealing member in a state in which the concave portion is closed. Object processing equipment. 12. The sealing member according to claim 10, wherein the sealing member is installed at a lower edge portion of the lid body and press-contacts with an upper edge portion of the main body portion in a state where the lid body closes the concave portion. A processing device for an object to be processed. 13. The apparatus for treating an object to be treated according to claim 1, further comprising temperature adjusting means for adjusting the temperature of the processing section. 14. A reaction liquid capable of reacting with the object to be treated,
The object to be treated according to claim 13, wherein the object to be treated and the reaction liquid are reacted while heating the treatment section by the temperature adjusting means when supplying the object to be treated and reacting them. Processing equipment. 15. The apparatus for treating an object to be treated according to claim 13, wherein the temperature adjusting means is configured to adjust the temperature of the processing section from at least two directions. 16. A plurality of the processing units are provided, and the temperature adjusting unit is configured to be able to set different temperature adjustment conditions between the first set of processing units and the second set of processing units. Item 16. The treatment device for an object to be treated according to any one of items 13 to 15. 17. A reaction solution capable of reacting with the object to be treated,
The apparatus for treating an object to be treated according to any one of claims 1 to 16, further comprising a reaction liquid supply means for supplying the object to be treated. 18. A moisturizing liquid supply means for supplying a moisturizing liquid for maintaining the humidity in the processing tank is provided.
7. The processing apparatus for processing the object to be processed according to any one of 7. 19. A cleaning liquid supply means for supplying a cleaning liquid for cleaning the object to be processed.
The processing device for a processed object according to any one of 1. 20. The apparatus for treating an object to be treated according to claim 1, further comprising a draining means for draining the liquid from the treatment tank. 21. The apparatus for treating an object to be treated according to claim 1, further comprising gas supply means for supplying a gas for drying the object to be treated. 22. The processing apparatus for an object to be processed according to claim 1, further comprising control means for controlling the operation of each part of the processing apparatus. 23. The object to be treated is a nucleic acid.
23. An apparatus for treating an object to be treated according to any one of 22 to 22.