JP5055617B2 - Dispensing device - Google Patents

Dispensing device Download PDF

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JP5055617B2
JP5055617B2 JP2007139787A JP2007139787A JP5055617B2 JP 5055617 B2 JP5055617 B2 JP 5055617B2 JP 2007139787 A JP2007139787 A JP 2007139787A JP 2007139787 A JP2007139787 A JP 2007139787A JP 5055617 B2 JP5055617 B2 JP 5055617B2
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flow path
capillary
forming member
path forming
dispensing
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JP2008292379A (en
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龍太郎 前田
直樹 市川
壮平 松本
振 楊
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地方独立行政法人 東京都立産業技術研究センター
独立行政法人産業技術総合研究所
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In the present invention, a flow path is formed inside, a reaction such as reaction of liquid injected from the outside is performed, and dispensing is performed using a flow path forming section that can extract the liquid after reaction to the outside. It relates to a dispensing device.

  Currently, in a wide range of fields such as medicine, agriculture, science and pharmacy, for example, separation and extraction of target substances for immune substances such as antibodies and antigens, genetic substances such as DNA and RNA, and recently useful substances such as other medical drugs Or, in order to carry out recovery, processes or operations such as reaction, dispensing, isolation, concentration, stirring, clarification, suspension, dilution and the like are frequently performed.

  Since it is preferable to use a very small amount of liquid for such processing, a micrometer unit flow path and a processing chamber are formed on the chip, and a very small amount of a predetermined liquid is injected into the flow path, for example. Processing such as reaction is performed in a processing chamber of less than 1 μl or several μl, and the liquid is poured out to cause further reaction or to analyze the reaction product. ing.

  In order to handle such a small amount of liquid, for example, a flow path substrate 62 made of PDMS (polydimethylsiloxane) or the like having a groove of a micro flow path 61 as shown in FIG. And a cover 64 made of glass, resin, or the like is pasted to close the top of the microchannel 61.

  In order to inject the liquid into the microchannel 61 formed in this way, the cover 64 is provided with three injection holes 65 in the drawing leading to the microchannel 61, and a nozzle or the like is brought into contact with the injection hole 65. Then, a predetermined liquid required for the reaction is injected from the outside by press-fitting or evacuation or the like, and each liquid is supplied into the reaction chamber 67 through the buffer unit 66. The liquid reacted in the reaction chamber 67 or a substance such as protein produced here is provided at the end of the discharge channel 68 leading to the reaction chamber 67 for inspection by an external inspection device or for further reaction processing. From the pouring hole 69 communicating with the outside, it is poured out through a nozzle or the like brought into contact therewith. The liquid containing the protein or the like extracted here cannot be called a mere liquid, but a liquid containing these various substances is also referred to as a “liquid” for convenience of explanation.

  In order to perform the above operations, for example, a dispensing device 71 as shown in FIG. In addition, the apparatus of the same figure shows the outline | summary of an example of the apparatus which performs a desired reaction etc. using the microchip 70 like Fig.10 (a). In the dispensing device 71 shown in the figure, the microchip 70 as described above is inverted and fixed on a mounting table 72 provided with a flow path, and the mounting table 72 is fixed to a base 73. . The base 73 includes an injection part 74 and a discharge part 75, and allows the liquid from the injection part 74 to be supplied to the injection hole 65 of the microchip 70 and supplied to the discharge part 75 from the extraction hole 69 of the microchip 70. It is possible.

  In addition, a predetermined amount of liquid can be dripped into the injection port 76 provided in the injection unit 74 by a pipette 77 or the like, and a pump 78 is connected to the discharge unit 75 via a discharge pipe 77 to inject into the injection unit 74. The liquid is sucked into the microchip 70, and the liquid that has been processed in the microchip 70 is sucked and discharged to the waste liquid tank 79. In addition, the base 73 may be placed on the temperature control device 80 so that the reaction can be performed under a predetermined temperature condition. In addition, as an apparatus for performing a desired reaction or the like using a microchip, in order to efficiently perform a large number of reactions, for example, a large number of microchannels as shown in FIG. Such a technique is disclosed in, for example, Japanese Patent Laid-Open No. 2006-126011.

  Conventionally, when performing the above-described predetermined work using the microchip as described above, the operator must manually perform the liquid quantification / dispensing operation one by one with the pipette 77 or the like. It was. According to a report from the US National Institute of Occupational Health, this work is done on average 6000 times per person per day, which is hard work for those who actually do it. As a countermeasure, an automatic dispensing device that can automatically perform these operations has been developed.

  Such an automatic dispensing apparatus is disclosed in, for example, Japanese Patent Application Laid-Open No. 2001-13152. In this apparatus, a chip plate having a large number of microwells is disposed above each microwell. A predetermined liquid can be simultaneously supplied from a number of arranged nozzles. In this way, the automatic dispensing device that is usually used supplies liquid from above to a large number of microwells of the chip plate or to the injection holes of the microchip as shown in FIG. 10 (a). It will be.

In addition to the rectangular shape of the microchip as shown in FIG. 10A, for example, a circular shape such as disclosed in JP-A-2006-126010 and JP-A-2005-523728 is radial. It has also been proposed to form a large number of microchannels.
JP 2006-126011 A JP 2001-13152 A JP 2006-126010 A JP 2005-523728 A

  When supplying a liquid to a liquid injection hole of a microchip in which a microchannel is formed in a conventional automatic dispensing device, an apparatus such as that described in Patent Document 2 is used from above the microchip. The nozzle is lowered and dispensing is performed. Furthermore, when the reaction-completed liquid is poured out from the pouring hole, the discharge pipe is lowered from above the pouring hole, brought into close contact with the pouring hole, and sucked by a pump. The exhaust pipe will be raised after completion.

  For this reason, the conventional dispensing device requires a moving space for the nozzle and the discharge pipe above the stage on which the microchip is placed, and a driving device for moving the nozzle is disposed. The height was inevitably high, and the equipment was large. In particular, when the liquid that has been reacted in the reaction chamber of the microchip is dispensed into a microchip equipped with another microchannel, the liquid is discharged from the discharge hole of one microchip to the injection hole of the other microchip. A complicated mechanism that moves while dispensing liquid is required, and this portion of the mechanism is inevitably large.

  This is not only when using a flow path forming member as a microchip in which a flow path having a size of a micrometer unit as described above, but for example, a relatively large flow path whose cross-sectional height or width exceeds 1 mm. The same problem arises when dispensing with the flow path forming member in which is formed.

  Therefore, the present invention automates the dispensing work that has been performed manually, and makes the dispensing device low in height, and can be downsized as a whole, particularly causing the mechanism to be upsized. By reducing the height of the part of the mechanism for dispensing the liquid processed in the flow path forming member into the capillary and further into the flow path in the other flow path forming member, the entire dispensing apparatus is The main object is to provide a flow path forming member that can be reduced in size and a dispensing device that uses the flow path forming member.

  In order to solve the above-described problems, a flow path forming member according to the present invention is a flat flow path forming member formed with a liquid flow path provided with an injecting portion and a dispensing portion. At least one of the injection portion and the extraction portion communicating with the flow passage is opened on a side surface of the flow path forming member, and the injection opening portion of the injection portion opening on the side surface or the extraction opening portion of the extraction portion has the opening A flow path forming member provided with a guide member for guiding a liquid suction capillary in the flow path through the sealing member between the opening and the sealing member of the opening. At least one of the flow path forming member and the capillary gripping device so that the opening of the flow path forming member and the end of the capillary gripped by the capillary gripping device are opposed to each other, and the capillary axis is perpendicular to the surface of the sealing member. One side is movably provided, front By relatively moving at least one of the flow path forming member and the capillary, the capillary end is inserted into the internal flow path through the sealing member while being guided by the guide member. After dispensing a predetermined amount of liquid in the channel into the capillary, a dispensing mechanism for dispensing the liquid in the flow path by repeating the operation of pulling the capillary out by the movement is provided.

  Further, another dispensing apparatus according to the present invention is the above-described dispensing apparatus, wherein the capillary that sucks the predetermined amount of liquid is used as a sealing member in another channel including a sealing member similar to the channel forming member. The predetermined amount of liquid is supplied and dispensed into a flow path inside the other flow path forming member.

  Further, another dispensing apparatus according to the present invention is such that, in the dispensing apparatus, the capillary gripping device is fixed to a capillary moving device, and the capillary moving device grips an unused capillary at a capillary supply position by the capillary gripping device. Then, it moves to the dispensing position, releases the grip of the capillary after supplying and dispensing the liquid into the other flow path, and accumulates the capillary at the used capillary accumulation position. .

  Another dispensing apparatus according to the present invention is the dispensing apparatus, wherein a motor that continuously rotates the disk-shaped flow path forming member and rotates by a predetermined angle is provided in the dispensing apparatus, and the flow path is formed by operating the motor. The liquid in the flow path is moved to the extraction section side by continuous rotation of the member, and the openings of the extraction sections in the plurality of micro flow path constituent sections are discharged by rotation of the flow path forming member by a predetermined angle. It is characterized by rotating to a position.

  Further, another dispensing apparatus according to the present invention includes a pressing tool for pressing the deflection of the flow path forming member in the dispensing apparatus, and the pressing tool has a capillary end gripped by the gripping device in the flow path. A guide for guiding to the opening is provided.

  Since the present invention is configured as described above, it is possible to automate the dispensing work, which has conventionally been a heavy labor by manual work, and to reduce the height of the dispensing apparatus, thereby reducing the overall size. In particular, in the case of a microchannel, the surface force becomes more dominant than gravity, and there is no restriction on handling the solution in the vertical direction. Therefore, as a result of effective dispensing of a planar structure that does not use gravity, the cause of the increase in the size of the mechanism is eliminated, and the liquid reacted in the microchip can be microfluidized in the same or other microchip. By simplifying the mechanism for dispensing into the channel and reducing the size of the entire dispensing device, the cost of the dispensing device can be greatly reduced. It can also contribute to the wider spread of this type of dispensing device.

  The present invention solves the problem of reducing the height of a conventional dispensing device and making it a small-sized dispensing device. A flat flow formed by forming a liquid flow path having an injection portion and a dispensing portion therein. In the path forming member, the extraction portion communicating with an internal flow path is opened in a side surface of the flow path forming member, and an elastic sealing member for sealing the opening is provided in the opening of the extraction portion, and the elastic sealing The member inserts the capillary through the wall of the elastic sealing member from the side surface of the plate-like channel forming member and inserts the capillary into the inner channel, and sucks a predetermined amount of the liquid in the channel into the capillary. The problem is solved by using a flow path forming member configured to seal the wall portion through which the capillary penetrates by self-elasticity when pulled out to the outside. Capillary gripping device can be moved to a position facing the exit The end of the capillary is inserted into the internal flow path through the elastic sealing member by relatively moving at least one of the flow path forming member and the capillary, and the liquid in the flow path is This is achieved by providing a dispensing device having a dispensing mechanism for dispensing the liquid in the flow path by repeating the operation of drawing the capillary into the outside by the movement after a predetermined amount is sucked into the capillary. is there.

  FIG. 1 is an explanatory view of a flow path forming member 1 used in the present invention. As shown in the sectional view of FIG. 1 (c), the flow path of PDMS, acrylic resin, polycarbonate, glass, etc. as in the conventional microchip. A microchannel 5 is formed inside by forming a channel groove 3 having a predetermined planar shape with a depth of micrometer order on the surface of the formation substrate 2 and then providing a cover 4 made of glass, acrylic resin, or the like. In particular, in the case of a flexible flow path forming plate 2 such as PDMS, a substrate 6 made of a highly rigid resin or the like is attached to the back side thereof. In the example shown in the drawing, the flow path forming member 1 is formed in a disk shape similar to a CD disk, and a single micro flow path configuration portion 7 extending in the radial direction from its center is formed, and this is formed on the circumference. In FIG. 9, nine flow path forming members 1 are provided. The flow path forming member according to the present invention is often used as a microchip similar to the conventional one, but in addition to that, considering that it is also used for one having a larger flow path cross section, the flow path forming member This will be described as 1.

  One micro-channel structure 7 shown in FIG. 1A shows an example of a channel structure similar to that shown in FIG. 10A, as shown in FIG. In this example, the cover 4 is provided with injection parts 8 as three injection parts in the drawing that lead to the micro flow path 5, and a nozzle or the like is brought into contact with the injection part 8 to provide a predetermined required for reaction from the outside. Liquids are injected by press-fitting or the like, and each liquid is supplied into the reaction chamber 10 through the buffer unit 9. The liquid reacted in the reaction chamber 10 or a substance such as a protein produced here is provided at the end of the discharge channel 11 leading to the reaction chamber 10 for inspection by an external inspection device or for further reaction processing. In addition, an extraction portion 12 which is a relatively wide microchannel portion is provided. Therefore, the pouring part 12 opens to the opening M on the side surface of the disk-shaped flow path forming member 1.

  The extraction opening 13 formed at the end of the extraction portion 12 is made of an elastic body such as PDMS, and in the illustrated embodiment, the extraction opening 13 is formed by a sealing function portion 15 formed at the center of the elastic sealing member 14 having an arc shape in plan view. It is kept sealed. When the flow path forming plate 2 is made of, for example, a highly rigid resin such as acrylic resin or glass, the elastic sealing member 14 is formed by another member having high elasticity such as PDMS. In this case, for example, FIG. The elastic sealing member 14 as shown in FIG. The elastic sealing member 14 is housed in an elastic sealing member so that the sealing function portion 15 at the center of the elastic sealing member 14 is sealed in contact with the dispensing opening 13 at the end of the dispensing portion 12 as shown in FIG. It is stored in the part 16. Thereby, the elastic sealing member 14 as shown in FIG. 2A is stored in the elastic sealing member storage portion 16 as shown in FIG. 2B in close contact with each other as shown in FIG. .

  As shown in FIG. 1 and FIG. 2, the elastic sealing member 14 has an arc shape. As a result, a space is formed inside the elastic sealing member 14, and a guide member 17 for guiding insertion of a dispensing capillary as will be described later is formed in that portion. Can be provided. In the embodiment shown in FIG. 2, the guide member 17 is formed integrally with the flow path forming plate 2, and the two guides 19 and 19 are opposed to each other so that a guide portion 18 having a predetermined gap is formed. It is arranged. On the mutually opposing surfaces of the guide 19 shown in the figure, an opening M is formed as a trumpet opening outward so that a capillary to be described later can be guided smoothly.

  The elastic sealing member 14 shown in FIG. 2 is made of a material having high elasticity such as PDMS because the flow path forming plate 2 is made of a highly rigid resin such as acrylic resin or polycarbonate, or glass. An example is shown. Further, the guide member 17 is integrally formed with the flow path forming plate 2. However, as shown in FIG. 3A, for example, the guide member 17 may be integrally formed as the same member as the elastic sealing member 13. .

  In the embodiment of FIG. 2, the center of the elastic sealing member 14 is brought into contact with the ends of the two guides 19 and 19 serving as the guide member 17, and the elastic sealing member 14 is accommodated in the guides 19 and 19 and the elastic sealing member. In the example shown in FIG. 3B, the end portions 21 and 21 of the two guides 19 and 19 are arranged away from the elastic sealing member 14 as shown in FIG. However, the elastic sealing member 14 may be freely moved at this portion. Further, in the embodiment shown in FIG. 3A, when the elastic sealing member 14 and the guide member 17 are integrally formed, an example in which the embodiment shown in FIG. 2 is integrated is shown. As shown in 3 (c), an integrated member including the elastic sealing member 14 and the guide portion 18 may be formed in the same manner as the shape of the elastic sealing member storage portion 16.

  When the flow path forming plate 2 is formed of a material having high elasticity such as PDMS, the elastic seal member 14 is integrally formed as an elastic wall that simply closes the dispensing opening 13 as shown in FIG. This portion may be used as the sealing function portion 15. In this case, the guides 19 and 19 can be similarly integrally formed facing each other so as to have the guide portion 18 at the center. At that time, for example, as shown in FIG. 4B, guides 19 facing each other are connected by a film-like connecting portion 26, and liquid PDMS is smoothly flowed to this portion when the two guides 19 and 19 are formed. An accurate guide may be formed by solidification. At this time, the film-like connecting portion 26 seals the guide portion 18, but when the capillary is inserted through this portion as will be described later, the guide portion 18 can penetrate without any particular obstacle. FIG. 4C shows an example in which the guides 19 and 19 in FIG. 4A are all integrally formed without being made independent, and the guide can be easily formed by such molding.

  When the flow path forming member 1 having the above-described configuration is used to extract the liquid reacted in the reaction unit 10 or the liquid containing protein or the like to the outside, for example, as shown in FIG. In the example shown in FIG. 5, the structure of the elastic sealing member 14 and the guide member 17 of the embodiment of FIG. 2 is provided, and the capillary 22 for dispensing is guided between the two guides 19 and 19 of the guide member 17. When being inserted into the guide 18, the guides 19 are guided by the opposing inner surfaces of the guides 19, abut against the outer surface 23 of the sealing function portion 15 of the elastic sealing member 14, and move the sealing function portion 15 from the outer side to the dispensing portion 12 side. Press toward it. At this time, it is important that the reaction part 10 to the sealing function part 15 of the elastic sealing member 14 are filled with the liquid using, for example, centrifugal force so that no bubbles remain inside. Further, when the dispensing capillary 22 is extremely thin, such as several micrometers, the tip of the capillary 22 is difficult to be accurately inserted into the guide portion 18, and therefore, a capillary holding guide 27 is provided for such a case. Alternatively, by fitting the capillary 22 into the capillary holding guide portion 28 formed in the interior or the like, it is possible to perform reliable alignment with the opening M at the tip of the capillary and stable sliding.

  At that time, in order to facilitate the insertion of the capillary 22 into the capillary holding guide portion 28 in the capillary holding guide 27, a capillary receiving surface 29 is provided on the capillary insertion side of the capillary holding guide 27. As a result, the tip of the capillary gripped by the capillary gripping device comes into contact with the capillary receiving surface 29 and is guided to the capillary receiving surface and the surrounding guide wall surface so that it can be easily guided to the capillary holding guide portion 28. To.

  Furthermore, the flow path forming member 1 is not necessarily strictly a flat plate, and may have a deflection of about 500 μm. Even in such a case, in order to reliably guide the tip of the capillary held by the capillary holding device to the opening M of the flow path forming member 1 as described above, for example, a pressing tool 30 as shown in FIG. Can do. The holding tool 30 shown in the figure has a fitting hole for fitting the tip to the center support portion of the table that rotates the flow path forming member 1, and the capillary holding guide as shown in FIG. 5A on the other end side. A capillary holding guide 27 having a portion 28 is integrally provided. By using such a pressing tool 30, the flow path forming member placed on the table in the state shown in FIG. 5C is pressed from above, and the opening of the flow path in the flow path forming member 1 is predetermined. In this state, the tip of the capillary gripped by the capillary gripping device is guided by the capillary receiving surface 29 and the surrounding guide surface and guided to the capillary holding guide portion 28, and thereafter the same as in FIG. According to the aspect, the capillary tip can be reliably guided to the opening.

  The state in which the capillary 22 is inserted from the opening M and the seal function unit 15 is pressed is shown in cross-sectional views in FIGS. 6A and 6B, and the capillary 22 is guided by the capillary holding guide 27 as shown in FIG. While moving to the flow path forming plate 2 side as described above, the outer surface 23 of the sealing function portion 15 is pressed as shown in FIG. Thereby, the sealing function part 15 of the elastic sealing member 14 is elastically deformed as shown in FIG. In the illustrated example, the capillary 22 is moved to the flow path forming plate 2, that is, the flow path forming member 1 side. However, after the capillary is arranged at the position of FIG. The same function can be performed even if the is moved to the capillary side. 6 (a) and 6 (b) show an operation of inserting a capillary in a state where the capillary has not yet been inserted in the sealing function portion 15 of the elastic sealing member 14 as will be described later. Yes.

  In the example shown in FIG. 6, when the capillary 22 is further moved to the dispensing unit 12 side from the state shown in FIG. 6B, the sealing function part 15 of the elastic sealing member 14 is moved to the capillary 22 as shown in FIG. The tip is pierced by the tip, and the tip of the capillary 22 is inserted into the dispensing part 12. The position at which the elastic sealing member 14 is pierced in this way is obtained in advance by experiments, and the position where the capillary 22 moves somewhat earlier than that is set as the stop position of the capillary 22.

  When the capillary 22 is inserted into the dispensing unit 12 as shown in FIG. 6C, the liquid 24 in the dispensing unit 12 is sucked into the tube by capillary action of the capillary 22. Therefore, the dispensing amount can be determined by the inner diameter and length of the capillary 22. When the inner diameter of the capillary 22 is large or when the material is not sufficiently sucked by capillary action, the capillary 22 may be sucked by a pump or the like from another end. After a predetermined amount of liquid is sucked into the capillary 22 by such an action, the capillary 22 is extracted as shown in FIG.

  At this time, the sealing function part 15 of the elastic sealing member 14 pierced by the capillary 22 as described above is, for example, a partially enlarged view of FIG. 5A when the elastic sealing member 14 is made of PDMS. In FIG. 5B, a dispensing part 12 having a width L of 600 μm, the thinnest elastic sealing member 14 having a thickness T of 60 μm and a capillary diameter D of 200 μm is inserted. When the capillary 22 was inserted and pulled out as described above, it was confirmed that the portion of the elastic sealing member 14 through which the capillary broke due to self-elasticity and self-adhesiveness was automatically sealed. In FIG. 6 (d), this portion is indicated by a broken line as a self-sealing portion 25.

  Thereafter, another capillary was inserted into and pulled out of the self-sealing portion 25 in the same manner as described above, and as a result, sealing with sufficient self-adhesion was continued at least several times. From this, it was found that the operation of inserting and extracting the capillary many more times is possible. Therefore, the liquid present in the dispensing unit 12 can be dispensed into at least several capillaries 22. In order to further enhance the sealing effect, it is considered that the self-sealing portion 25 should be cut in advance.

  The dispensing apparatus of the present invention using the flow path forming member having the above-described configuration can perform dispensing work by using an apparatus as shown in FIG. 7, for example. In the apparatus shown in FIG. 6A, a first flow path forming member 32 having a disk shape like the CD is provided on the left side of the figure across a capillary gripping and conveying apparatus 31 provided at the center. The second flow path forming member 34 whose inner micro flow path is appropriately changed is disposed on the right side in the figure so as to be rotatable by the second motor 35. Yes.

  For example, the cross section of the first flow path forming member 32 is rotated by a first flow path forming member rotating / moving device 38 as shown in FIG. 7B, and the position is advanced and retracted toward the capillary gripping and conveying apparatus 31 side. It can be moved freely. In the example shown in the figure, a first flow path forming member 32 is placed on a table 36 that is rotationally driven by a first motor 33, and is sandwiched rotatably by a clamp 37. In this state, the first motor 33 is continuously provided. Therefore, the first flow path forming member 32 is rotated at an appropriate high speed and is rotated by a certain angle.

  Further, the first flow path forming member driving device 38 for driving the clamp 37 and placing the motor 33 is driven by the piston 40 of the first flow path forming member driving device moving member 39 fixed to the frame or the like as shown in FIG. It is possible to move left and right in the figure as shown in b). Thereby, the opening M of the dispensing part as described above of the first flow path forming member 32 is opposed to the tip of the capillary 22 held by the capillary holding / conveying device 31 as shown in FIG. When the first flow path forming member driving device 38 is moved to the capillary 22 side by the operation of the piston 40 of the first flow path forming member driving device moving member 39 in the state shown in FIGS. 6 (a) and 6 (b). As a result of the operation, the tip of the capillary 22 penetrates the elastic sealing member 14 and is inserted into the dispensing part 12, and the liquid in the dispensing part is extracted into the capillary 22 to its full length by capillary action as described above, and a predetermined amount Can be extracted. At this time, as shown in FIG. 7B, by providing the capillary holding guide 27 as shown in FIG. 5, the tip of the capillary 22 is surely aligned with the position of the opening M, and the capillary It is possible to prevent the capillary 22 from being bent by a force when the tip of the 22 breaks through the seal function part. In particular, by using the suppressor 30 as shown in FIG. 5 (b), the deflection of the flow path forming member can be suppressed, and the capillary 22 having a diameter of about several μm can be reliably inserted.

  On the other hand, the capillary gripping and conveying device 31 can be implemented by various devices. In the example shown in FIG. 7, a large number of capillaries 22 can be placed on the left and right rails 41 and 42. A capillary gripping device 44 is disposed in the gap 43 therebetween. In the capillary gripping device 44 shown in FIG. 7 (c), the clamp receiving member 45 located on one side of the capillary 22 is L-shaped, and its base portion 46 is fixed to the capillary transport device 47. In (c), for example, it is possible to move in one direction such as leftward.

  In the example of FIG. 7 (c), a gripping drive member 48 is fixed on the base 46 of the clamp receiving member 45, so that the clamp member 50 can be moved left and right in the figure by a piston 49 that moves left and right in the figure. Thus, the capillary 22 can be firmly gripped and released. By using the capillary gripping and conveying apparatus 31 as described above, in the example of FIG. 7A, a large number of rails 41 and 42 are placed at the capillary supply position 51 on one end side in the longitudinal direction. It is inclined downward appropriately from the supply position 51 side toward the other side.

  In addition, the first capillary 22 by a stopper that can be moved up and down (not shown) is always present at the position of the stopper, and the capillary gripping device 44 that is moved by a separate device as described above is raised at this portion. The capillary 22 is sandwiched from below and the capillary is firmly held by the movement of the clamp member 50. Thereafter, the stopper is lowered and moved to the dispensing position 52 with the capillary 22 held.

  At the dispensing position 52, one of the micro-channel structures arranged in a radial pattern as shown in FIG. 1 is selected in advance by driving the first motor 33, and the dispensing portion is placed at the dispensing position. When the first flow path forming member is moved to the capillary side by the operation of the first flow path forming member driving device moving member 39 when the capillary is transported to the dispensing position as described above, According to the embodiment shown in FIG. 6, the capillary 22 relatively penetrates the elastic sealing member and is inserted into the dispensing part, and is dispensed by the capillary phenomenon by the length of the capillary. This state is shown as the state of FIG. 8A in FIGS. 8 and 9 showing a series of operations of the dispensing device according to the present invention.

  After the elapse of a predetermined time required for such dispensing, the first flow path forming member 32 is moved away from the capillary by the operation of the first flow path forming member driving device moving member 39. As a result, the first flow path forming member 32 is pulled away from the capillary 22 as shown in FIG. Thereafter, in this embodiment, the capillary 22 is dispensed as described above into the second flow path forming member 34 symmetrically disposed on the opposite side of the first flow path forming member 32 with the rails 41 and 42 as the center. The liquid is injected.

  Therefore, in the state of FIG. 8B, the second flow path forming member 34 is moved to the capillary gripping and conveying apparatus 31 side by the same device as the first flow path forming member driving device moving member 39. Move to. At that time, an elastic sealing member similar to the elastic sealing member 14 of the first flow path forming member 32 is applied to a predetermined micro flow path formed in the second flow path forming member 34 as shown in FIG. The injection part 55 rotating to the dispensing position 52 is moved to the capillary 22 side by the movement of the second flow path forming member 34.

  As a result, as shown in FIG. 9A, the capillary 22 passes through the elastic sealing member of the second flow path forming member 34 and is inserted into the micro flow path formed inside the elastic sealing member. A vacuum pipe communicating with the suction hole of the pump is connected to an extraction hole 56 provided in the same configuration as the injection portion of the first flow path forming member, and the micro flow path is connected to the micro flow path via the micro flow path. The liquid in the capillary 22 is sucked. The suction is stopped by closing the valve of the vacuum pipe at the timing of sucking all the liquid in the capillary 22.

  Thereafter, the second flow path forming member 34 is moved to the side opposite to the capillary 22 to obtain the positional relationship shown in FIG. However, in the subsequent operation, the same capillary is used, or the empty capillary 22 is moved to the capillary accumulation position 53 side, and a new capillary is conveyed from the capillary supply position 51 to the dispensing position 52. Thereafter, the first flow path forming member 32 is moved with respect to the capillary 22 held at the dispensing position 52 as shown in FIG. 8A, and still remains in the empty capillary 22 by the same operation as described above. The liquid in the dispensing part is poured out. By repeating the operation as described above, the liquid existing in one dispensing part or the reaction part in the first flow path forming member 32 is sequentially dispensed into the micro flow path of the second flow path forming member 34. Can do.

  Then, after the dispensing in the dispensing part in one micro-channel constituting part of the first channel forming member 32 is completed, the first channel forming member 32 is moved as shown in FIGS. Rotate until the dispensing part of the next microchannel constituent part adjacent to the microchannel constituent part that has been dispensed is located. FIG. 9B shows an example in which the second flow path forming member 34 is also rotated, but this also causes the second flow path forming member 34 to rotate as well as the first flow path forming member 32. An example that can be shown.

  In the above example, when dispensing the liquid present in the dispensing part in one micro-channel constituting part of the first channel forming member 32, each of the capillaries 22 is removed from the first channel forming member. Although an example in which the liquid in the capillary 22 is dispensed into the capillary 22 by pouring and immediately after that the liquid in the capillary 22 is injected into the second flow path forming member 34 has been shown. For the liquid present in the dispensing part in one of the micro-channel constituent parts of 32, dispensing by inserting the capillary 22 is continuously performed, and the capillary into which the liquid has been injected is accumulated in the capillary collecting part, After all of the dispensing operations of the microchannel constituent parts are completed, these are sequentially conveyed to the dispensing position, the second channel forming member 34 is rotated by a predetermined angle, and the dispensed liquid in the capillary 22 is secondly Channel type It may be injected into the microchannel member. Further, with the end of the capillary inserted into the first flow path forming member 32, the other end of the capillary is simultaneously inserted into the second flow path forming member 34 and suctioned directly from the second flow path forming member side. Thus, a predetermined amount of liquid can be sequentially dispensed into the micro flow channel of the second flow channel forming member.

  It should be noted that when there is a large amount of dispensing of one microchannel constituent part of the first channel forming member 32, it is considered that only one microchannel of the second channel forming member 34 is insufficient. In this case, it is possible to easily cope with the problem by exchanging with another second flow path forming member 34 having a similar flow path configuration like a conventional disk changer for music CD. The same applies to the first flow path forming member 32. Prepare a plurality of the same flow path with the same micro flow path or those with other micro flow path configurations. Alternatively, the flow path forming members that perform dispensing can be sequentially replaced, and all dispensing operations can be performed continuously.

  After injecting the internal liquid into the second flow path forming member 34, the capillary 22 is transported to a dispensed capillary accumulation position 53, which is a position opposite to the supply side position 31 of the rails 41 and 42. When the capillaries held in the vicinity of the capillary accumulation position 53 are released, the rails are inclined as described above, so that they are sequentially accumulated on the stopper 54 provided at the end of the capillary accumulation position. After dispensing into the capillaries at the dispensing position, the capillaries 22 are released at this portion, and the dispensed capillaries are accumulated at the capillary accumulation position 53 by rolling on the rails of the capillaries. Is also possible. At the same time, the next capillary is moved to the dispensing position 52 in the same manner as described above by the capillary holding / conveying device 31 that has been holding and waiting in advance at the capillary supply position 51. This state is shown in FIG.

  In the embodiment, the first flow path forming member and the second flow path forming member are used, and a predetermined amount of liquid dispensed from the first flow path forming member to the capillary is sucked and supplied to the flow path of the second flow path forming member. Although an example has been shown, a flow path including a reaction chamber and an extraction portion similar to the first flow path forming member is formed in the first flow path forming member without using the second flow path forming member. In addition, the other part of the same member is provided with a channel and a sealing member for sucking the dispensed liquid similar to the second channel forming member, and only one channel forming member is used to separate the dispensing portion from the dispensing portion to the capillary. The suction and supply of the dispensed liquid after that may be performed.

  In addition, in the said Example, although the example which formed the flow-path formation member in the disk shape so that it could implement efficiently about this invention was shown, the rectangular flow-path formation member shown, for example in FIG. It can be carried out in various modes such as using a plurality of microchannels formed therein.

  Further, in the above embodiment, the present invention is applied to the flow path forming member in which the micro flow path is formed, but other rectangular or disk-shaped chips having a flow path of an appropriate size of 1 mm or more are used. The present invention can also be implemented by applying the elastic sealing member to the dispensing portion.

It is a figure which shows the Example of the flow-path formation member of this invention. It is an enlarged view of the dispensing part and elastic sealing member part of the Example. It is a figure which shows the other various Example of the flow-path formation member of this invention. It is a figure which shows other various Examples of the flow-path formation member of this invention. In the Example of the flow-path formation member of this invention, it is a figure which shows the various aspects when inserting a capillary. In the Example of the flow-path formation member of this invention, it is a figure explaining the effect | action of an elastic sealing member when penetrating and pulling out a capillary. It is a schematic diagram of the Example of the dispensing apparatus which dispenses using the flow-path formation member of this invention. It is a figure which shows the example when dispensing using the same dispensing apparatus, (a) is a 1st aspect, (b) is a figure which shows a 2nd aspect. It is a figure which shows the example when dispensing using the same dispensing apparatus, (a) is a 3rd aspect, (b) is a figure which shows a 4th aspect. It is a figure which shows the example of the dispensing device which dispenses using the microchip as a conventional flow-path formation member, and the microchip.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Flow path formation member 2 Flow path formation board 3 Flow path groove 4 Cover 5 Micro flow path 6 Substrate 7 Micro flow path component 8 Injection part 9 Buffer part 10 Reaction chamber 11 Discharge flow path 12 Outlet part 13 Outlet part 14 Elastic sealing member 15 Seal function part 17 Guide member M Opening

Claims (5)

  1. In a flat-plate-shaped flow path forming member formed with a liquid flow path provided with an injection part and an extraction part, at least one of the injection part and the extraction part communicating with the internal flow path is used as the flow path. A sealing member that seals the opening is provided at the injection opening of the injection portion or the extraction opening of the injection portion that opens to the side surface of the path forming member, and seals the opening from the opening. A flow path forming member provided with a guide member that guides a capillary for liquid suction in the flow path through the sealing member between the members,
    At least one of the flow path forming member and the capillary gripping device is arranged so that the opening of the flow path forming member faces the end of the capillary gripped by the capillary gripping device and the capillary axis is perpendicular to the surface of the sealing member. Set up to be movable,
    By relatively moving at least one of the flow path forming member and the capillary, the end of the capillary is guided by the guide member, inserted through the sealing member into the internal flow path, A dispensing mechanism is provided for dispensing the liquid in the flow path by repeating the operation of drawing the capillary in the flow path to the outside after the suction of the liquid in the flow path to a predetermined amount. Dispensing device.
  2. The capillary that sucks the predetermined amount of liquid passes through the wall of the sealing member in the other flow path provided with the same sealing member as the flow path forming member,
    The dispensing apparatus according to claim 1, wherein the predetermined amount of liquid is supplied and dispensed into a flow path inside the other flow path forming member.
  3. Fixing the capillary gripping device to a capillary moving device;
    The capillary moving device grips an unused capillary at a capillary supply position by a capillary gripping device and moves it to a dispensing position,
    2. The dispensing apparatus according to claim 1, wherein gripping of the capillary after the liquid is supplied and dispensed into the other flow path is released and the capillary is accumulated at a used capillary accumulation position.
  4.   The flow path forming member is formed in a disk shape, and a plurality of predetermined shape flow path constituting portions between the injection portion and the extraction portion are radially formed. The flow path forming member is continuously rotated at a predetermined angle. A motor that rotates each time is provided, and the operation of the motor moves the liquid in the flow path to the dispensing portion side by continuous rotation of the flow path forming member, and a plurality of rotations by a predetermined angle of the flow path forming member The dispensing device according to claim 1, wherein the opening of each of the extraction portions in the micro-channel constituting portion is rotated to the extraction position.
  5. A presser for pressing the flow path forming member is provided.
    The dispensing apparatus according to claim 1, wherein the pressing tool includes a guide for guiding the end of the capillary gripped by the gripping device to the opening of the flow path.
JP2007139787A 2007-05-25 2007-05-25 Dispensing device Active JP5055617B2 (en)

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JPS5977067U (en) * 1982-11-16 1984-05-24
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SG46491A1 (en) * 1991-03-19 1998-02-20 Hoffmann La Roche Closure for reagent container
JP3348949B2 (en) * 1993-12-28 2002-11-20 オリンパス光学工業株式会社 Suction and discharge apparatus
JPH10206748A (en) * 1997-01-17 1998-08-07 Daiichi Seimitsu Kk Capillary unit for stage installation of microscope, stage for microscope equipped with capillary unit, and microscope equipped with capillary unit
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JP3967331B2 (en) * 2004-03-23 2007-08-29 株式会社東芝 Liquid mixing method, liquid mixing apparatus and microchip
JP3927978B2 (en) * 2004-11-02 2007-06-13 キヤノン株式会社 Biochemical reaction cartridge and biochemical processing system
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