JP3970796B2 - Liquid transfer device - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a transfer apparatus that is advantageous for use in transferring a target solution, particularly DNA (gene) and protein reagents, onto a substrate in the form of fine dots.
[0002]
[Prior art]
Recently, in the medical field, treatments and drugs using genes (DNA) and proteins have been developed. Research institutions in such technical fields handle what are called DNA chips in which several thousand to several tens of thousands of copies of chemically synthesized different genes are sampled on a base made of glass plates or synthetic resin plates. In addition, what is called a protein chip in which several thousand to tens of thousands of proteins, including antibodies, polypeptide fragments, etc., are pasted on a substrate made of a glass plate or a synthetic resin plate as a sample is handled.
[0003]
The DNA chip and the protein chip are manufactured using an apparatus called an arrayer. The aligner includes a transfer member having a transfer surface formed at the tip of the shaft-shaped main body portion and a groove connected to the transfer surface on the outer periphery of the main body portion. There is one configured so that the liquid can be transferred to a base placed on the work table when the transfer member approaches the work table by moving up and down by an elevating means (for example, Patent Document 1). reference).
[0004]
The above-mentioned arrayer is configured so that a transfer member mounted on the carriage is moved to form about 2500 points of liquid transferred at a pitch of about 0.2 mm in a 10 mm square region set at a predetermined position on the base. Has been. For this reason, the area of the transfer surface in contact with the substrate is extremely small, and therefore the diameter of the tip portion of the transfer member is formed very thin.
[0005]
Further, the transfer device is configured by holding a plurality of transfer members on one holding member so that the liquid can be transferred to the substrate in a short time, and the holding member can be used to stably transfer the liquid. A plurality of held transfer members can be slid in the length direction (axial direction). After the holding member is lowered and the transfer surface of the transfer member comes into contact with the substrate, the holding member is further lowered by a predetermined dimension so that only the weight of the transfer member acts on the transfer surface in contact with the substrate. An excessive force is not applied to the member itself and the transfer surface.
[0006]
[Patent Document 1]
Japanese Patent No. 3037691
[0007]
[Problems to be solved by the invention]
In the above transfer device, when the posture of the transfer member held by the holding member changes every time the holding member is moved up and down, the position of the liquid transferred to the substrate is not stable, so the transfer member holds a stable posture. The transfer member is held through two holes provided on the same axis of the holding member so that the transfer member can slide relative to the holding member. However, the transfer member may fall down due to the fitting tolerance between the hole and the main body, and in this case, it becomes difficult to maintain the pitch of the dots.
[0008]
In order to solve the above problem, it is preferable to reduce the fitting tolerance, but in this case, there is a problem that the smoothness when the transfer member slides in the axial direction (vertical direction) with respect to the holding member is hindered. Arise. In particular, when the liquid is a DNA or protein reagent, it is a fatal defect that impurities are mixed into this reagent, and an oil film of lubricating oil cannot be formed on the sliding surface. Smooth sliding performance at the sliding portion of the transfer member may be hindered to cause sliding failure. In addition, when transferring the reagent to the substrate, the holding member may be used because the humidity of the atmosphere is set high to prevent evaporation of the reagent or an ultrasonic cleaner is used to clean the reagent attached to the transfer member. In some cases, a water film is formed on the sliding portion of the transfer member. For this reason, for example, when dust enters the sliding portion between the holding member and the transfer member, the dust may adhere to the sliding portion and cause sliding failure. When a poor sliding state occurs, there may be a problem that an abnormal state occurs in which the transfer member does not descend even if the holding member is raised, and the relative position with respect to the holding member does not recover.
[0009]
That is, after the holding member is lowered and the transfer member comes into contact with the substrate, the transfer member is raised relative to the holding member as the holding member is further lowered, and then the transfer is performed as the holding member is raised. The member is relatively lowered to restore the initial position. At this time, if a sliding failure occurs between the holding member and the transfer member, the relative movement of the two members is not performed smoothly, and the transfer member is moved. It remains elevated with respect to the holding member and enters an abnormal state.
[0010]
When the transfer member does not slide smoothly with respect to the holding member and an abnormal state occurs, the transfer surface comes into contact with the substrate when the transfer member descends, but the transfer member's own weight acts on the transfer surface. As a result, there is a problem that the transfer of the liquid to the substrate is not stabilized and transfer defects such as blurring occur.
[0011]
An object of the present invention is to provide a liquid transfer device that can transfer a liquid to a substrate reliably by canceling the abnormal state even if the transfer member is in an abnormal state.
[0012]
[Means for Solving the Problems]
In order to solve the above-mentioned problems, a liquid transfer apparatus according to the present invention is a transfer apparatus for transferring a liquid to a base by bringing a transfer member having a shaft-shaped main body and a transfer surface formed at the tip of the main body into contact with the base. In this case, the holding member that slidably holds the transfer member in the axial direction, the driving member that raises and lowers the holding member, and the upper end portion of the transfer member held by the holding member is raised and lowered and lowered. And when the holding member is lowered to the lowering limit by the drive member, the transfer surface of the transfer member contacts the base and the contact with the restriction member is released. When the weight of the transfer member acts to transfer the liquid and the holding member is lifted by the driving member, the upper end of the transfer member held in an abnormal state with respect to the holding member comes into contact with the regulating member and the abnormality occurs. Release state and holding member Regulating member in association with a further increase is also one that is configured so as to increase.
[0013]
In the above-described transfer device, the transfer member that is slidably held by the holding member can be separated from or brought close to the base by moving the holding member up and down by the driving member. Therefore, when the holding member is lowered and the transfer surface formed at the tip of the main body of the transfer member comes into contact with the substrate, the liquid adhering to the transfer surface can be transferred to the substrate.
[0014]
In particular, after the holding member is lowered, the contact of the regulating member with the transfer member is released, and the holding surface is further lowered by further lowering the holding member after the transfer surface of the transfer member comes into contact with the substrate by further lowering the holding member. The holding of the transfer member by the member is released. That is, the transfer member rises relative to the holding member, and the weight of the transfer member acts on the transfer surface. Thereafter, as the holding member moves up, the transfer member is lowered and held relative to the holding member, whereby the transfer member recovers the initial position with respect to the holding member.
[0015]
When a transfer member that does not descend relatively (in an abnormal state) as the holding member rises (abnormal state) occurs, the upper end of the transfer member that is in an abnormal state comes into contact with the regulating member when the holding member is raised. Thus, the abnormal state can be canceled and the position of the transfer member relative to the holding member can be restored to the initial state. Therefore, the transfer member can always come into contact with the substrate in the same manner, and the liquid can be transferred in a stable state. As the holding member further rises, the restricting member rises while maintaining a state in contact with the upper end portion of the transfer member.
[0016]
In the present invention, the components of the liquid are not particularly limited, and any liquid can be used as long as the object can be achieved by transferring the fine dots onto the substrate. Such liquids include, for example, chemically synthesized genes (DNA) or liquid samples (reagents) consisting of copies of genes (chromosomal DNA, cDNA, etc.) artificially produced by genetic recombination methods, as well as antibodies and polypeptides. A liquid sample (reagent) in which various proteins including fragments can be dissolved can be raised. The present invention can be preferably applied when a DNA chip or a protein chip is manufactured by densely transferring such reagents on a substrate and transferring them.
[0017]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, a preferred embodiment of the transfer device will be described with reference to the drawings. FIG. 1 is a diagram illustrating the configuration of the transfer device. FIG. 2 is a view for explaining the relationship between the transfer member and the holding member when transferring to the substrate. FIG. 3 is a diagram illustrating an example of a transfer member. FIG. 4 is a plan view for explaining the configuration of an arrayer equipped with the transfer apparatus according to the present invention. FIG. 5 is a side view of FIG. FIG. 6 is a diagram for explaining a point distribution state when the liquid is transferred to the substrate by the arrayer equipped with the transfer device according to the present invention.
[0018]
Prior to the description of the transfer apparatus according to the present invention, the distribution state of the points 2 where the reagent is transferred to the substrate 1 will be briefly described with reference to FIG. In the figure, the substrate 1 selectively uses a plastic plate or a glass plate, and generally uses a slide glass in many cases. As an example of transferring the liquid (reagent) to the base 1, 2500 dots 2 are formed at a pitch of about 0.2 mm in a 10 mm square area, and 2 × 6 of the areas are created to create one sheet. 30000 points 2 may be formed on the base 1.
[0019]
Note that the pitch of the points 2 and the number of points 2 formed on one substrate 1 are not limited to the above values, and it is required to form them at a smaller pitch and at a higher density. In addition, if the reagent constituting each point 2 is mixed with another adjacent point 2 reagent, the value as a sample is lost. Therefore, it is essential that each point 2 is transferred in an independent state. Further, when analyzing the points 2 formed on the base 1, it is preferable that each point 2 is accurately positioned on the matrix. In the present invention, the position can be accurately formed in a stable state. It is configured as follows.
[0020]
Next, the configuration of the transfer apparatus according to the present embodiment will be described with reference to FIGS. In the figure, a transfer device A includes a holding member 5 that slidably holds a plurality of transfer members 3 formed as shown in FIG. 3, a drive member 6 that moves the holding member 5 up and down, and a regulating member 7. When the holding member 5 is lowered by the driving member 6, the reagent is transferred to the base 1 by the transfer member 3 to form the point 2, and when the holding member 5 is raised, The abnormal state can be canceled by bringing the transfer member 3 in an abnormal state into contact with the regulating member 7.
[0021]
The transfer member 3 has an axial main body 3a and a transfer surface 3b provided at an end of the main body 3a, and a groove 3c is formed in a spiral shape on the outer periphery of the main body 3a. A head 3d having a diameter larger than the diameter of the main body 3a is formed at the upper end of the transfer member 3.
[0022]
The main body 3 a of the transfer member 3 has an appropriate thickness, and the transfer surface 3 b has a size suitable for forming the point 2. The basic shape of the transfer surface 3b is a circle. For example, when the point 2 having a size of 0.2 mm is formed on the substrate 1, the diameter of the transfer surface 3b may be about 0.15 mm. Accordingly, the thickness of the main body 3a has a value sufficiently larger than the diameter of the transfer surface 3b, and the main body 3a and the transfer surface 3b are connected by the tapered portion 3e.
[0023]
In the present invention, whether or not the groove 3c is formed in the transfer member 3 is not particularly limited, and there is no problem even if the groove 3c is not provided. However, in the transfer member 3 of this embodiment, the groove 3c is formed on the outer peripheral portion of the main body 3a including the tapered portion 3e, and the reagent is collected and held when the tip of the transfer member 3 is immersed in the reagent. And a function of replenishing the transfer surface 3b with a reagent.
[0024]
In particular, the groove 3c is formed in a spiral shape on the outer periphery of the main body 3a, and one end thereof is connected to the transfer surface 3b. The length, width, and depth of the groove 3c are not particularly limited, and the volume can be set by appropriately setting these dimensions.
[0025]
The holding member 5 is configured to be able to hold a plurality of transfer members 3 (32 in this embodiment, 32 × 8 × 4) slidably in the axial direction (longitudinal direction of the main body 3a). When transferring the reagent to 1, the support of the weight of the transfer member 3 is released while maintaining the posture of the transfer member 3, thereby allowing the transfer member 3 to act on its own weight on the transfer surface 3b for stable transfer. After the transfer is completed, the transfer member 3 is lifted from the substrate 1.
[0026]
Therefore, as shown in FIG. 2, the holding member 5 has a main body 5a formed in a box shape including an upper side 5b and a bottom side 5c, and a hole 5d formed through the upper side 5b and the bottom side 5c of the main body 5a in the vertical direction. And a concave groove 5e formed corresponding to the hole 5d in the upper side 5b.
[0027]
The hole 5a fits the main body 3a of the transfer member 3 so as to be slidable in the axial direction, and the main body 3a of the transfer member 3 and the hole 5a are formed with a fitting tolerance capable of performing the function. . For example, when the fitting tolerance increases, the main body 3a of the transfer member 3 can easily slide with respect to the hole 5a of the holding member 5, but the transfer member 3 falls down by the gap in the fitting tolerance, and this falls. When the holding member 5 is moved up and down, the pitch of the points 2 formed on the base 1 varies, and when the fitting tolerance is reduced, the gap between the main body 3a and the hole 5a is reduced. Although the accuracy of the pitch of the point 2 is improved, an abnormal state in which the main body 3a is poorly slid with respect to the hole 5a is likely to occur.
[0028]
Further, the head 3d of the transfer member 3 has a diameter larger than the diameter of the main body 3a. The transfer member 3 is fitted into the groove 5e and engaged with the periphery of the hole 5a. And is prevented from dropping from the holding member 5. The head 3d is formed to have a length larger than the depth of the concave groove 5e, and is always in a position protruding from the upper end surface of the holding member 5 when the transfer member 3 is held by the holding member 5. It is configured as follows. Therefore, even when the transfer member 3 is normally held by the holding member 5, the head 3 d of the transfer member 3 comes into contact with the regulating member 7.
[0029]
The holding member 5 is fixed to the elevating member 11 via the stay 10, and is configured so that the elevating member 11 can move up and down along the guide member 13 provided on the frame 12. Therefore, the holding member 5 fixed to the elevating member 11 can be raised and lowered by raising and lowering the elevating member 11 by the driving member 6.
[0030]
In the holding member 5 configured as described above, a plurality of holes 5a are formed, and the transfer member 3 can be held in each hole 5a. That is, the transfer member 3 is detachably fitted to the hole 5a. Therefore, it is not necessary to fit the transfer member 3 to all of the plurality of holes 5a formed in the holding member 5, and one or more transfer members 3 are inserted into the desired hole 5a according to the purpose of transfer. It is possible to arrange.
[0031]
The drive member 6 has a function of driving the holding member 5 up and down, and a mechanism that can exhibit this function can be selectively employed. Examples of such a mechanism include a combination of a reversible motor and a ball screw, and a linear reciprocating mechanism such as an air cylinder.
[0032]
In this embodiment, a mechanism in which a reversible motor and a ball screw are combined is employed. That is, the drive member 6 includes a reversible motor 6a and a ball screw 6b. The ball screw 6b is arranged along the frame 12, and the ball screw 6b and a ball nut (not shown) provided on the elevating member 11 are screwed together, so that the elevating member 11 (holding member 5) according to the rotation direction of the reversible motor 6a. ).
[0033]
When the holding member 5 is raised, the regulating member 7 causes the head 3d of the transfer member 3 held by the holding member 5 to come into contact with the head 3d of the transfer member 3 in an abnormal state to apply a load or force. The load and the force have a function of canceling the abnormal state.
[0034]
In this embodiment, the restricting member 7 stands on the abutting member 7a having an area capable of abutting against all the heads 3d of the plurality of transfer members 3 held by the holding member 5, and the abutting member 7a. And a stopper 7c provided at the tip of the guide bar 7b. The guide bar 7b is fitted into a guide hole provided in the elevating member 11. A bracket 14 is fixed to the frame 12, and a locking portion 14 b that contacts the stopper 7 c and locks the regulating member 7 is provided on the bracket 14.
[0035]
When the holding member 5 is lowered and the transfer surface 3b of the transfer member 3 comes into contact with the base 1, the regulating member 7 is engaged with the stopper 7c so that the contact member 7a stops above the head 3d. The part 14b is set. Therefore, when the transfer member 3 is executing transfer on the substrate 1, no load is applied to the transfer member 3.
[0036]
Further, the restricting member 7 is configured so that the ascending / descending direction is guided by the guide bar 7b and there is no glare. In particular, the restricting member 7 is configured to be able to fall freely, and the lowering limit is set by the engagement of the stopper 7c and the locking portion 14b. For this reason, it is possible for an operator to raise the restricting member 7 while holding the guide bar 7b, thereby opening the space between the abutting member 7a and the holding member 5. It becomes possible to easily attach and detach the transfer member 3 to / from.
[0037]
In the restricting member 7 configured as described above, when the holding member 5 is at a position where it is raised to some extent from the lowering limit, the contact member 7a comes into contact with the head 3d of the transfer member 3 held by the holding member 5, and these When a load is applied to the transfer member 3 and the holding member 5 is lowered from the ascent limit, the restricting member 7 is also lowered along with the lowering, and when the stopper 7c comes into contact with the locking portion 14b, the restricting member 7 The descent stops. At this time, the contact of the contact member 7a with the head 3d of the transfer member 3 is released.
[0038]
As the holding member 5 is lowered, the contact member 7a of the restricting member 7 is lowered while maintaining the contact state of the transfer member 3 with the head 3d, and the stopper 7c of the restricting member 7 is engaged with the locking member 14b. When stopped, the surface of the contact member 7a (the surface that contacts the head 3d of the transfer member 3) and the surface of the head 3d of the transfer member 3 (the surface that contacts the surface of the contact member 7a) When the flatness or parallelism accuracy of the transfer member 3 is high, or when liquid components adhere to both surfaces for some reason, the head 3d of the transfer member 3 adheres to the contact member 7a, and the holding member Even if 5 further descends, the head 3d of the transfer member 3 may not be separated from the contact member 7a.
[0039]
For this reason, the surface of the contact member 7a and the surface of the head 3d of the transfer member 3 or both of them can be grooved so that both surfaces can be in point contact or line contact without being in full contact. It is preferable to configure as described above. By processing the abutting surfaces of the abutting member 7a and the head 3d in this manner, even when both abut, the contact area is increased by interposing an air layer between the opposing surfaces. By reducing the size, the transfer member 3 can be reliably separated from the abutting member 7a when the holding member 5 is lowered.
[0040]
Next, when the transfer device A configured as described above forms the point 2 on the base 1 and the transfer member 3 held by the holding member 5 becomes in an abnormal state, the abnormal state is canceled. The procedure will be described.
[0041]
When the holding member 5 driven by the driving member 6 is raised to the upper limit, the contact member 7a of the regulating member 7 abuts on the head 3d of the transfer member 3 held by the holding member 5, and the regulation The member 7 is pressed downward by the action of the load. In this state, the reagent to be transferred to the substrate 1 is held in the groove 3c of the transfer member 3.
[0042]
When the transfer to the substrate 1 is executed, when the holding member 5 at the ascending limit starts to descend, the transfer member 3 and the regulating member 7 held by the holding member 5 are lowered. During the descending process, the stopper 7c of the regulating member 7 comes into contact with the locking portion 14b provided on the bracket 14 and stops, whereby the load on the regulating member 7 acting on the transfer member 3 is removed. Therefore, the transfer member 3 is slidable in the axial direction of the hole 5 a of the holding member 5.
[0043]
As the holding member 5 is further lowered, the transfer surface 3 b of the transfer member 3 comes into contact with the substrate 1, so that the reagent can be transferred from the transfer surface 3 b to the substrate 1. However, when a plurality of transfer members 3 are held by the holding member 5, even if one transfer member 3 is in contact with the substrate, it is guaranteed that all the transfer members 3 are in contact with the substrate 1 under the same conditions. There is no guarantee that the contact pressure between the transfer surface 3b and the substrate 1 can be secured.
[0044]
For this reason, as shown in FIG. 2, after the transfer surface 3 b of the transfer member 3 comes into contact with the substrate 1, the holding member 5 continues to descend further (the transfer member 3 rises relative to the holding member 5). The head 3 d of the transfer member 3 is lowered to a position separated from the bottom of the concave groove 5 e of the holding member 5 by a distance S. As described above, when the head 3d of the transfer member 3 is detached from the bottom of the concave groove 5e of the holding member 5, the weight of each transfer member 3 acts on the transfer surface 3b. A substantially equal contact pressure can be applied. Therefore, the reagent can be transferred to the substrate 1 under substantially the same conditions.
[0045]
The distance S by which the holding member 5 descends after the transfer member 3 contacts the substrate 1 is not particularly limited, and the plurality of transfer members 3 can guarantee that their own weights act on the transfer surface 3b. Any value is acceptable. In this embodiment, it is set to about 1 mm.
[0046]
Next, the holding member 5 starts to rise from the lowering limit. First, while the holding member 5 is raised by the distance S, the transfer member 3 maintains a state in which the transfer surface 3b is in contact with the substrate 1 (the transfer member 3 is lowered relative to the holding member 5), and the bottom of the recess 5e. Comes into contact with the head 3d, and the holding member 5 and the transfer member 3 rise simultaneously, and the contact of the transfer surface 3b with the base 1 is released.
[0047]
When the transfer member 3 falls down when the reagent is transferred to the substrate 1, the transfer member 3 does not slide smoothly with respect to the holding member 5 when the holding member 5 is raised. May cause sliding failure. In particular, when a reagent is transferred to the substrate 1, there is a risk of mixing with the reagent. Therefore, an oil film may be formed on the sliding surface between the main body 3a of the transfer member 3 and the hole 5d of the holding member 5. If the fitting tolerance between the main body 3a and the hole 5d is made small in order to improve the pitch accuracy of the point 2 formed on the base 1 and not possible, a sliding failure is likely to occur.
[0048]
As described above, the transfer member that has been distorted maintains the state in which the head 3d is detached from the bottom of the concave groove 5e, and an abnormal state has occurred. For example, when an abnormal state occurs in some transfer members 3 among a plurality of transfer members 3 held by the holding member 5, these transfer members 3 have a head 3 d as compared with other transfer members 3. The protruding state will be maintained, and the holding member 5 will rise while maintaining the abnormal state.
[0049]
As the holding member rises, the head 3d of the transfer member 3 collides with the abutting member 7a that has been stopped by the stopper 7c being locked by the locking portion 14b, and a force acts. Therefore, a large force acts on the head 3d of the transfer member 3 in which an abnormal state has occurred due to a collision with the contact member 7a, and the abnormal state is released by dropping into the concave groove 5e by this force.
[0050]
Thereafter, as the holding member 5 is further raised, the regulating member 7 is also raised, and a load is applied to the head 3d of the transfer member 3 held by the holding member 5 substantially evenly, so that the transfer member 3 with respect to the holding member 5 is moved. It becomes possible to hold the posture.
[0051]
As described above, even when the transfer member 3 held by the holding member 5 is in an abnormal state, a mechanically abnormal state is obtained by applying a force to the transfer member 3 in which the abnormal state is generated by the regulating member 7. Can be released, and the holding posture of the transfer member 3 by the holding member 5 is stabilized, so that stable transfer can be realized.
[0052]
Accordingly, when continuously performing a series of operations including the steps of supplying the reagent to the transfer member 3, transferring the transfer member 3 to the substrate 1, and washing the transfer member 3, the individual operations are terminated and the next operation is performed. When the operation is started, the holding member 5 is configured to be retracted to a predetermined height, and the stop position of the contact member 7a is at a position in the middle of the retracted height of the head 3d of the transfer member 3. With this setting, the head 3d of the transfer member 3 can be brought into contact with the contact member 7a when the holding member 5 is raised and lowered for each individual operation. That is, it is possible to cancel the abnormal state that the transfer member 3 generates with respect to the holding member 5 for each operation.
[0053]
Next, an example of the layerer B on which the transfer device A according to this embodiment is mounted will be described with reference to FIGS. In the figure, the layerer B is a work table 21, an X-direction drive member 23 installed in the X direction of the work table 21 to drive the moving table 22 in the X direction, and a Y installed in the Y direction of the work table 21. A direction driving member 24, a carriage 25 driven by the Y direction driving member 24 and traversing in the Y direction, and a transfer device A mounted on the carriage 25 are configured.
[0054]
The work table 21 is designated in advance according to an XY orthogonal coordinate system, and the area 21a where the base 1 is installed, the area 21b where the container 15 containing the reagent is installed, and the area 21c where the ultrasonic cleaning device 16 is installed. The areas 21a to 21c having different functions such as the above are set. In particular, the areas 21a and 21b are set in the movement table 22, and the area 21c is set in the work table 21.
[0055]
A plurality of substrates 1 are arranged in the region 21a. When arranging the board | substrate 1, you may mount and arrange | position directly in the area | region 21a. However, in this embodiment, a positioning member 17a is provided on the moving table 22 corresponding to the region 21a, and the tray 17b can be mounted on the positioning member 17a. The tray 17b is configured such that a plurality of bases 1 can be arranged in preset columns and rows.
[0056]
A container 15 containing a reagent is installed in the region 21b. As the container 15, for example, a so-called microplate having an accommodation portion formed of an 8 × 12 conical depression on the surface is used, and reagents having different personalities are accommodated in the individual depressions.
[0057]
As the ultrasonic cleaning device 16 installed in the region 21c, an ultrasonic cleaner used for general cleaning is used.
[0058]
The X direction driving member 23 has a function of moving the moving table 22 along the X direction. Accordingly, the X-direction drive member 23 is not particularly limited as long as it can satisfy the above functions. In this embodiment, a ball screw is arranged along the X direction, and a moving table 22 is attached to a ball nut screwed to the ball screw, and the ball screw can be driven by a servo motor.
[0059]
The Y-direction drive member 24 has a function of moving the carriage 25 in the Y direction and moving the transfer device A to the range of the regions 21a to 21c in the Y direction. Accordingly, the Y-direction drive member 24 is not particularly limited as long as it can satisfy the above functions. In this embodiment, a ball screw is arranged along the Y direction, and a carriage 25 is attached to a ball nut screwed to the ball screw, and the ball screw can be driven by a servo motor.
[0060]
In the arrayer B configured as described above, the X-direction driving member 23 and the Y-direction driving member 24 installed along the XY direction are driven in synchronization, so that the moving table 22 and the carriage 25 (the transfer device A) are driven. ) Can be moved to the respective work areas 21a to 21c set in the work table 21. Then, after the transfer device A is moved to the desired areas 21a to 21c, the drive member 6 is driven to raise and lower the holding member 5, thereby the transfer member 3 installed in each area 21a to 21c. 15. It is possible to carry out the intended work by approaching either of the ultrasonic cleaning devices 16.
[0061]
Next, the operation of transferring the reagent to the substrate 1 by the transfer device A and the arrayer B configured as described above will be described. First, the base 1 and the container 15 are installed in each of the areas 21a to 21c set on the work table 21 so that the ultrasonic cleaning device 16 can be cleaned.
[0062]
The driving member 6 of the transfer device A is driven to raise the holding member 5. In this state, the X direction driving member 23 and the Y direction driving member 24 are driven to face the container 15. Next, the driving member 6 is driven to lower the holding member 5, the transfer member 3 is inserted into the housing portion of the container 15, and a predetermined amount of reagent is collected and held in the groove 3 c. Thereafter, the driving member 6 is driven to raise the holding member 5, the X direction driving member 23 and the Y direction driving member 24 are driven to face the target substrate 1, and the driving member 6 is driven to hold the holding member 5. The transfer operation is performed on the substrate 1 by lowering and bringing the transfer surface 3b of the transfer member 3 into contact with the substrate 1.
[0063]
When the transfer member 3 performs the transfer of the reagent to the substrate 1 and the transfer member 3 has a sliding failure with respect to the holding member 5 and an abnormal state occurs, as described above, the holding member 5 is raised. The head 3d of the transfer member 3 can collide with the contact member 7a of the restricting member 7 to forcibly cancel the abnormal state.
[0064]
During or after a series of transfer operations on the substrate 1, the holding member 5 is raised to face the ultrasonic cleaning device 16, and is adhered to the outer peripheral surface of the transfer member 3 or remains in the groove 3c. Wash away the reagent. Thereafter, the holding member 5 is moved again to the container 15, and the reagent is sampled on the transfer member 3 in the same manner as described above, facing the accommodating portion other than the already transferred accommodating portion. By repeating such an operation, it is possible to form the points 2 made of a predetermined number of samples on the plurality of substrates 1.
[0065]
For example, in the case of DNA
20 × SSC = 3M NaCl + 0.3M NaCitrate, 0.02 MEDTA (PH 7.0 adjust)
PBS 100 mM Phosphate buffer 0.138M NaCl (PH7.4), 0.0027MKCl
Mouse cDNA (Gene name) mKIAA0054 (5,953 base pairs long)
Reference) DNA Research 9: 179-188 (2002), Okazaki, N, etal
Solution composition
1. DNA was spotted at a final concentration of 100 ng / μl using DNA heat treated at 95 ° C. for 10 minutes at a concentration of 500 μg / ml.
[0066]
2. Diluted solution: 3 × SSC (20 × SSC is an aqueous solution adjusted to PH 7.0 containing 3M NaCl, 0.3NaCitrate, 0.02 MEDTA)
3. Organic solvent: 50% (w / w) DMSO
4). Dye: 0.1% xylene cyanol
Transfer media
Nylon membrane: BiodynB, manufactured by PALL
detection
2,592 spotting attempts were made.
[0067]
It was confirmed by visual observation that no spots were missing.
[0068]
Also for protein
Rabbit IgG I5006 (manufactured by Sigma)
Solution composition
1. Antibody: (2 mg / ml) Final concentration 1 μg / 1 μl
2. Diluted solution: Spotted with PBS (containing 100 mM phosphate buffer (PH7.4) 138 mM NaCl 2.7 mM KCl).
[0069]
3. Organic solvent: 25% (w / w) glycerol
4). Dye: 0.2% xylene cyanol
Transfer media
Slide glass: SDA0031 manufactured by Matsunami Glass Industrial Co., Ltd.
detection
2,592 spotting attempts were made.
[0070]
It was confirmed by visual observation that no spots were missing.
[0071]
【The invention's effect】
As described above in detail, in the transfer device according to the present invention, when a transfer member that does not descend relatively (in an abnormal state) as the holding member rises, an abnormal state occurs when the holding member rises. When the upper end portion of the transfer member comes into contact with the regulating member, the abnormal state can be forcibly released and the position of the transfer member relative to the holding member can be restored to the initial state. Therefore, the liquid can be transferred to the substrate in a stable state.
[0072]
Even when an abnormal state occurs in the transfer member, this abnormal state is acted upon when the transfer member is lowered when the transfer member is raised with respect to the regulating member, particularly the contact member. Since this can be forcibly released, the fitting tolerance between the main body of the transfer member and the hole of the holding member can be reduced. For this reason, since the pitch accuracy of the points when the liquid is transferred to the substrate can be improved, it is possible to improve the reliability with respect to a preset matrix of each point when analyzing the transferred liquid.
[0073]
Also, when the stop position of the restricting member is set to a position lower than the retracting height of the holding member for each individual operation, it is assumed that an abnormal state has occurred in the transfer member for each liquid supply operation, transfer operation, and cleaning operation to the transfer member. Can also cancel this abnormal state.
[0074]
Further, since the restricting member is configured to be able to move up and down, by raising the restricting member, the distance from the holding member can be greatly increased, and the transfer member can be easily exchanged for the holding member by using this distance. Can be done. This means that, for example, a maintenance work, which is an extremely troublesome work in a structure in which the pin is biased by a spring, can be easily realized.
[0075]
Further, by configuring the restricting member so that it can be lifted and lowered by its own weight, even when the transfer member is not evenly arranged with respect to the holding member, uniform transfer can be performed without acting an uneven load. Can be done.
[Brief description of the drawings]
FIG. 1 is a diagram illustrating a configuration of a transfer device.
FIG. 2 is a diagram illustrating a relationship between a transfer member and a holding member when transferring to a substrate.
FIG. 3 is a diagram illustrating an example of a transfer member.
FIG. 4 is a plan view for explaining the configuration of an arrayer equipped with a transfer apparatus according to the present invention.
FIG. 5 is a side view of FIG. 4;
FIG. 6 is a diagram for explaining a point distribution state when a liquid is transferred to a substrate by an arrayer equipped with a transfer device according to the present invention.
[Explanation of symbols]
A Transfer device
B Arrayer
1 foundation
2 points
3 Transfer member
3a body
3b Transfer surface
3c groove
3d head
3e Taper
5 Holding members
5a body
5b Upper side
5c base
5d hole
5e groove
6 Drive member
6a Reversible motor
6b Ball screw
7 Regulatory members
7a Contact member
7b Guide bar
7c stopper
10 stays
11 Lifting member
12 frames
13 Guide member
14 Bracket
14b Locking part
15 containers
16 Ultrasonic cleaning equipment
17a Positioning member
17b tray
21 Work table
21a-21c region
22 Moving table
23 X-direction drive member
24 Y-direction drive member
25 Carriage

Claims (1)

In a transfer device that transfers a liquid onto a base by bringing a transfer member having a shaft-shaped main body and a transfer surface formed at the tip of the main body into contact with the base, holding the transfer member slidably in the axial direction A drive member that raises and lowers the holding member, and a regulating member that comes into contact with the upper end of the transfer member held by the holding member and moves up and down and stops after reaching the lower limit. When the holding member is lowered to the lowering limit by the member, the transfer surface of the transfer member comes into contact with the base, the contact with the regulating member is released, and the weight of the transfer member acts to transfer the liquid, and the driving member When the holding member is raised, the upper end portion of the transfer member held in an abnormal state with respect to the holding member comes into contact with the regulating member to release the abnormal state, and the regulating member also rises as the holding member further rises. Configured to be able to rise A transfer device of a liquid, characterized in that the.

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