JP4189913B2 - Protein dispenser - Google Patents

Description

The present invention relates to a protein dispensing apparatus for discharging a liquid supplied into a nozzle tube by air.

Conventionally, a nozzle tube (dispensing tube) connected to a liquid pump for dispensing is provided in a dispensing unit that is transported forward, backward, left, and right by a transport robot so that it can be moved up and down. Samples such as proteins and samples such as reagents A dispensing apparatus that discharges and dispenses liquid into a dispensing container (test container) such as a microplate (tray) by a nozzle tube is known as disclosed in Patent Document 1.
The nozzle tube shown in Patent Document 1 sucks the sample liquid in the collection container for dispensing through a liquid pump, and controls the opening time of the three-way valve valve to determine the dispensing amount. By discharging, the sample liquid is continuously dispensed into the dispensing container.

JP-A-7-218977

  The dispensing apparatus shown in Patent Document 1 controls the opening and closing time of the three-way valve valve to determine the dispensing amount and feeds it out from the pipette-like nozzle tube. When dispensing work is repeated continuously, the three-way valve valve opens and discharges due to deterioration due to long-term use, etc., and a subtle deviation occurs in the stoppage stop time. Since there are variations in the discharge amount and liquid balls are generated at the tip of the nozzle tube, there are drawbacks in that it is difficult to accurately perform a small amount of dispensing and continuously perform a dispensing operation that maintains a constant amount.

  On the other hand, in order to eliminate the above-mentioned drawbacks and perform a small amount dispensing using a pipette-like nozzle tube, it is also attempted to provide a control valve that opens and closes electrically or mechanically directly in the nozzle tube, In this case, since a minute amount dispensing is performed with high accuracy, the structure of the control valve is complicated and the cost is increased, and the weight of the nozzle tube moved up and down is increased.

The present invention for solving the above problems is the downward nozzle tube 2 for discharging from the opening to extrude the liquid supplied to the nozzle pipe portion 26 connected liquid to the liquid pump 3 2 supplies to the downstream side, The nozzle tube portion 26 is provided with a surface tension stop conduit 34 formed with a nozzle hole 25 having an inner diameter for stopping the movement of the liquid downstream by surface tension, and air is supplied to the middle portion of the surface tension stop conduit 34. An air supply port 30 connected to the air supply pipe 22 to be fed into the nozzle hole 25 from the side is formed, and a liquid reservoir 29 having a diameter larger than the surface tension stop pipe 34 is formed on the upstream side of the surface tension stop pipe 34. Is connected to the connecting pipe 20 on the liquid pump 32 side for supplying the liquid via the liquid reservoir 29, and a predetermined amount of liquid held in the nozzle hole 25 on the downstream side of the air supply port 30, Supply from air supply port 30 In the air supply stop state after the liquid pushed out to the downstream side of the air supply port 30 is discharged, the downstream side movement of the liquid on the upstream side of the air supply port 30 is stopped by the surface tension. It is characterized by that.

  According to the present invention configured as described above, a predetermined amount of liquid pushed and moved in the nozzle hole to the downstream side of the air supply port is discharged by the air supplied from the air supply port, thereby It is possible to provide a nozzle tube that smoothly discharges liquid with a simple and inexpensive configuration without complicating the structure by providing a mechanical control valve mechanism in the nozzle tube portion like the above.

  In addition, the liquid that has been extruded and stopped to the downstream side of the air supply port is discharged by air, and when the air supply is stopped, the liquid in the nozzle hole upstream of the air supply port is moved downstream by surface tension or capillary action. By stopping the operation, it is possible to dispense a small amount of liquid in a small amount while suppressing variations even with respect to changes in the type and viscosity of the liquid. In other words, since the force (adhesive force) acting between the inner wall surface of the nozzle hole and the liquid molecule is larger than the cohesive force between the liquid molecules, the liquid does not fall by its own weight, and the inside of the nozzle hole It uses the phenomenon that remains in

  Therefore, the nozzle tube with this liquid discharge structure can be easily provided on the elevating and lowering side of the dispensing unit that is transported and moved, and can be optimized as a nozzle tube for a dispensing device, and a small amount of dispensing work can be performed. Since the liquid in the nozzle hole is pushed out and discharged by air when performing the process, smooth discharge with good liquid breakage can be accurately performed.

  DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring to the drawings, an embodiment of the present invention will be described. In the drawings, reference numeral 1 designates a dispensing device in which a nozzle tube 2 related to a liquid discharge structure of the present invention is configured as a dispensing unit 3 that can move in the front-rear, left-right, and up-down directions. Show. A dispensing apparatus 1 shown as a utilization device of the nozzle tube 2 includes a sample container T that can store various proteins and the like, and a reagent container S that stores various reagent liquids on a plate base 5 formed on the body frame 4. A dispensing container M into which these sample liquids are dispensed is detachably provided.

  Further, the machine frame 4 is provided with a transport unit (transport robot) 6 that supports the dispensing unit 3 so as to be able to perform dispensing work above the plate base 5. The transport unit 6 can position and move a dispensing unit 3 having a plurality of nozzle tubes 2 and 2 and another type of nozzle tube 2a in the X (horizontal) direction, the Y (vertical) direction, and the Z (vertical) direction. Composed. Also, on one side of the body frame 4, a pump unit 7 that switches and controls the suction action and the discharge action of the nozzle tubes 2, 2 a, a cleaning unit 8 that cleans the nozzle tubes 2, 2, 2 a, a transport unit 6, and a pump A control unit 9 and the like for controlling the driving operation of the working unit such as the unit 7 so that it can be automatically controlled and manually operated are provided.

  The various containers used in the dispensing apparatus 1 are plastic dish-shaped microplates having about 72 sample holes that are generally used as the dispensing container M, and the reagent container S is a solution. A suspension plate capable of accommodating various reagents (sample solutions) is shown, and the sample container T is an assembly in which about 10 sample tubes capable of accommodating various protein samples and chemical solutions (sample solutions) are assembled. It is supported by a cooling and holding device (not shown).

  Next, the configuration of each working unit will be described in detail. First, as shown in FIGS. 1 to 2, the transport unit 6 includes a Y-axis operating unit 11 that moves up and down each lifting rod 10 that includes the nozzle tubes 2 and 2 a of the dispensing unit 3, and the Y-axis operating unit 11 back and forth. The Z-axis operating unit 12 is movably supported in the (vertical) direction, and the X-axis operating unit 13 is supported so as to be movable in the horizontal direction.

  The X-axis operating unit 13 and the Z-axis operating unit 12 in the illustrated example are both constituted by a linear guide mechanism, and the X-axis operating unit 13 supports the base of the Z-axis operating unit 12 so that the X-axis (lateral) movement is possible. And the Z-axis action | operation part 12 attaches and supports the base part 15 of the Y-axis action | operation part 11 to the free end side so that Z-axis movement is possible.

  The Y-axis actuating portion 11 is composed of the base portion 15, a plurality of (three in the illustrated example) lifting rods 10 supported so as to be movable up and down with respect to the base portion 15, and the lifting rod 10 attached and fixed to the base portion 15. And an up-and-down operation unit 16 composed of an air cylinder, a linear cylinder, or the like that moves the Y axis separately.

  The Y-axis actuating portion 11 has three rows of vertical guide holes formed in the base portion 15 in parallel in the front-rear direction, and three lifting rods 10 are slidably inserted into the vertical guide holes, The upper end of the lifting rod 10 and the middle part below are attached to and supported by the piston rod 17 of the lifting operation unit 16. As a result, when the lifting / lowering operation unit 16 operates and the piston rod 17 moves up and down, the paired lifting rods 10 are moved up and down together.

Next, the dispensing unit 3 will be described with reference to FIGS. The three elevating rods 10 included in the dispensing unit 3 have the nozzle tubes 2 and 2 according to the present invention attached and fixed to the two elevating rods 10 downward, and the other elevating rods 10 have conventional nozzles. The tube 2a is attached and fixed.
Each lifting rod 10 is integrally provided at the lower end of the round pipe rod with a joint portion 19 for detachably mounting and fixing the nozzle tubes 2, 2, 2 a via a mounting screw portion 18. A connecting pipe 20 connected to the pump unit 7 is attached and supported in the bag 10.

  The lifting rod 10 for mounting and supporting the nozzle tube 2 inserts and supports an air tube 23 that connects an air supply tube 22 and an air supply unit 45 of the nozzle tube 2 described later. The lifting rod 10 of the illustrated example has a pipe hole 21 formed above the joint portion 19, an air tube 23 inserted and supported in the lifting rod 10 is pulled out from the pipe hole 21, and a nozzle tube is formed at the lower end of the air tube 23. The two air supply pipes 22 can be detachably mounted and supported. The air tube 23 is made of a plastic material having flexibility.

  As shown in FIG. 4, the nozzle tube 2 is integrated with a nozzle tube portion 26 provided with a nozzle hole 25 for discharging the sample liquid supplied from the connecting tube 20 so as to be dispensed, and a base side of the nozzle tube portion 26. The mounting portion 27 is formed with a screw portion that is detachably fastened to the mounting screw portion 17 of the joint portion 19, and air is supplied into the nozzle hole 25 provided in the middle portion of the nozzle tube portion 26. An air supply pipe 22 is used.

  The nozzle pipe portion 26 in the illustrated example has an outer diameter of about 1.23 mm, a nozzle hole 25 having an inner diameter of about 0.3 mm at the center, and an inner diameter of about 0.9 mm at the upper part (upstream side) of the nozzle hole 25. The liquid storage passage 29 is formed to have a predetermined length (about 6 mm). An air supply port 30 having an inner diameter of about 0.2 mm is formed in the middle of the nozzle tube portion 26 in a direction substantially orthogonal to the nozzle hole 25, and a tube hole 31 of the air supply tube 22 is formed in the air supply port 30. Are connected and integrated.

In this configuration, a surface tension stop pipe (liquid stop path) is provided between the air supply port 30 of the nozzle hole 25 and the liquid reservoir 29 to stop the downstream movement of the liquid by the surface tension in the pipe as will be described later. ) 34 is provided with a length of about 4 mm.
The air supply pipe 22 formed in a substantially L shape in a side view sends air into the nozzle hole 25 from the air pipe 23 connected to the end via the air supply port 30 in a substantially orthogonal shape. It can be discharged into the atmosphere from the opening formed at the lower end of 25.

As shown in FIG. 7, the nozzle tube 2 configured as described above is configured such that the liquid supplied from the upstream side of the nozzle hole 25 is pushed out by the discharge distance L from the air supply port 30 to the downstream side. Is supplied from the air supply pipe 22 into the nozzle hole 25 through the air supply port 30, as shown in FIG. 8, the liquid amount corresponding to the discharge distance L is set upstream of the air supply port 30 at the initial stage of air supply. It can be separated via liquid and air.
Next, the liquid component separated below the air supply port 30 is pushed and moved downstream in the nozzle hole 25 by the subsequently supplied air, and discharged and discharged from the opening (FIG. 9).

  At this time, in the nozzle hole 25 where the supply of the liquid is stopped and the pipe line is closed, the liquid located above the air supply port 30 is in the surface tension stop pipe line 34 formed above the nozzle hole 25. Then, the liquid level is slightly pressed upward by the supply air pressure, but when the supply air supply is stopped, the liquid level is directly above the air supply port 30 by its own surface tension as shown in FIG. It stops in a state where it is positioned against the dead weight of the liquid.

According to the nozzle tube 2 of this embodiment, when the discharge distance L in the nozzle hole 25 is set to about 1.4 mm, the amount of liquid to be discharged, that is, the dispensing amount is, for example, 0. This makes it possible to smoothly discharge a small amount of about 1 microliter. Further, when the supply amount of the liquid is increased or decreased and the length of the discharge distance L is changed, the dispensing amount can be adjusted very easily.
And since the nozzle pipe part 26 which forms the discharge distance L imparts directivity to a very small amount of discharged liquid and prevents the generation of liquid balls, the liquid level of the liquid already dispensed in the dispensing container M or the like. There is a feature such as enabling dispensing work from a position where the liquid is well separated without being close to the liquid.

  Further, since a liquid reservoir 29 having a larger diameter than this is formed on the upstream side of the surface tension stop conduit 34, the connecting tube 20 of the pump device 7 can be fitted and easily connected, and the liquid reservoir 29 is also connected. The liquid in the small-diameter surface tension stop conduit 34 can be reliably pushed out toward the downstream side by the liquid fed into the inside.

  In such a very small amount dispensing operation, the discharged liquid in the nozzle hole 25 is pushed out and discharged by air, so that the liquid is smoothly drained at the opening and does not cause dripping or generation of liquid balls. It can be performed. Further, the liquid level in the nozzle hole 25 is always positioned at a fixed position, so that the downstream side movement can be easily stopped, and the liquid discharged to the next order can be discharged with high accuracy. There are advantages such as.

  Next, the pump unit 7 will be described with reference to FIGS. This pump unit 7 supplies cleaning liquid to the liquid pumps 32, 33, and 35 connected to the nozzle tubes 2 and 2 and the nozzle tube 2a via connecting pipes 20, 20, and 20, respectively, and a cleaning unit 8 to be described later. It consists of a liquid pump 36 and the like. The suction pipes 37 and 37 of the liquid pumps 32 and 33 connected to the nozzle pipes 2 and 2 are both connected to an auxiliary liquid tank 39 that stores auxiliary liquid. The auxiliary liquid uses pure water to clean the nozzle holes 25 and prevent contamination.

The nozzle tube 2 a is connected to a dispensing auxiliary liquid tank 41 that contains a dispensing auxiliary liquid such as paraffin oil through a suction pipe 40 of the liquid pump 35.
On the other hand, an air adjusting valve 42 and an air switching valve 43 are arranged in the middle of the air pipes 23 and 23 connected to the air supply pipes 22 and 22 of the nozzle pipes 2 and 2, respectively, and the most upstream side of the air pipe 23 Is connected to an air supply unit 45 comprising an air compressor or the like installed inside or outside the machine.

  In this embodiment, each of the liquid pumps employs a syringe pump similar to the conventional one, and the adjustment of the suction amount and the discharge amount (supply amount) of each liquid is performed by changing the pump stroke or the rotation speed. Is done by doing. The nozzle tube 2a uses a disposable type dispensing tube having the same configuration as the conventional one, and the description thereof is omitted.

  Next, the cleaning unit 8 will be described with reference to FIG. The supply pipe 51 of the liquid pump 36 connected to the cleaning unit 8 via the switching valve 50 has a suction side connected to a cleaning liquid tank 52 that stores the cleaning liquid. The cleaning unit 8 blows air onto the cleaning nozzle unit 55 formed on the supply pipe 51 and the object to be cleaned into the cleaning container 53 formed so that the nozzle tubes 2 and 2 and the nozzle tube 2a can be inserted from above. An air nozzle 56 is provided for drying.

  The air nozzle 56 is formed by an air supply pipe 58 connected to the air supply unit 45 via a switching valve 57. Reference numeral 59 denotes a collection box for collecting the cleaning water and air after use. With this configuration, air can be blown and dried from the air nozzle 56 onto the nozzle tubes 2, 2, 2 a cleaned with the cleaning liquid ejected from the cleaning nozzle portion 55 in the cleaning container 53. In addition, nozzle tube cleaning can be automatically performed as needed during dispensing operations, and dispensing with different nozzles for switching between different materials and preventing contamination of all sample holes in the dispensing container M. Enable.

  The dispensing apparatus 1 configured as described above has an X-axis operation unit 13, a Y-axis operation unit 11, and a Z-axis operation unit 12 of the transport unit 6 by a dispensing operation program set by the control unit 9 or a manual operation. For example, the dispensing unit 3 is moved back and forth, right and left, and up and down to perform dispensing work. In this case, one nozzle tube 2 is exclusively used for dispensing various samples (protein A, protein B...) In the sample container T, and the other nozzle tube 2 is used for various solutions (reagent No. 1, reagent in the reagent container S). No. 2) is dispensed, and an appropriate amount of sample liquid is dispensed and mixed into the dispensing container M at a predetermined ratio. The nozzle tube 2a dispenses and supplies liquid (oil) to the dispensing container M in the same manner as the conventional one.

  In such a dispensing operation, the nozzle tube 2, 2 and the nozzle tube 2 a are retracted and moved into the cleaning container 53 from above by the dispensing unit 3 retreating toward the cleaning unit 8 every time each dispensing is finished. Then, the sample solution is washed off, washed and dried to prepare for the re-dispensing operation. As a result, the nozzle tube is automatically cleaned to prevent mixing of foreign materials, contamination, and the like, and the dispensing operation for all the sample holes of the dispensing container M is efficiently performed.

  In addition, the nozzle tube 2 provided with an air supply port 30 in the middle of the nozzle tube portion 26 and provided with an air supply tube 22 for pumping air into the nozzle hole 25 performs the dispensing operation as shown in FIGS. Since it can be performed by the process as shown in F), it is possible to accurately perform a minute amount dispensing with contamination.

  That is, in the initial stage of the dispensing operation, when the liquid (sample liquid) is not supplied into the nozzle hole 25 and the connecting pipe 20 of the nozzle pipe 2, the auxiliary liquid tank 39 is obtained by the auxiliary liquid filling step of FIG. The auxiliary liquid is supplied to the nozzle hole 25 by the liquid pump 32 (33), and the liquid pump 32 (33) is stopped in a state where a part thereof is discharged. As a result, fine dusts adhering to or floating in the pipe line can be discharged together with the auxiliary liquid to be discharged, and the auxiliary liquid can be filled in the nozzle hole 25.

  Next, when the auxiliary liquid is sucked into the nozzle pipe 2 due to the reverse rotation of the liquid pump 32 by the air gap forming step in FIG. 5B, air is introduced into the nozzle hole 25 from the tip of the nozzle pipe 2 to a predetermined position. The liquid pump 32 is stopped.

  Next, the nozzle tube 2 is moved and stopped at a predetermined position of the sample container T or the reagent container S by the sample liquid suction process of FIG. After inserting into T and operating the liquid pump 32 to suck the sample liquid, the nozzle tube 2 is raised and stopped at a predetermined position outside the sample container T.

  At this time, mixing of the auxiliary liquid and the sample liquid is prevented by a minute air reservoir (air gap portion) 60 formed between the auxiliary liquid and the sample liquid in the nozzle hole 25. The air gap portion 60 is positioned in a predetermined position above the air supply port 30 in the nozzle hole 25.

Next, in the sample liquid positioning step shown in FIG. 4D, air is supplied from the air supply pipe 22 into the nozzle hole 25, and the sample liquid existing below the air supply port 30 is pushed out and discharged, and discarded in the atmosphere. Or automatically collected in the collection containers (S), (M).
As a result, the sample liquid in the nozzle hole 25 can be positioned and held above (upstream) the air supply port 30 as a reference.

  Next, when the liquid pump 32 is operated by a predetermined dispensing amount in the sample liquid discharge preparation step shown in FIG. 5E, the sample liquid held in the nozzle hole 25 passes through the auxiliary liquid and the air gap portion 60, and the air The discharge distance L is pushed out toward the lower side of the supply port 30.

  Next, in the state in which the nozzle tube 2 is stopped at the predetermined hole position of the dispensing container M by the transport unit 6 through the sample liquid discharge process shown in FIG. Air is supplied into the nozzle hole 25. Accordingly, the sample liquid corresponding to the discharge distance L existing below the air supply port 30 is discharged by the discharge action described in FIGS. 7 to 9, and the sample liquid is dispensed and supplied into the dispensing container M. Can do.

When a series of dispensing operations is completed as described above, the re-dispensing operation by the nozzle tube 2 is performed by repeating the above steps again.
The nozzle tube 2 used in the dispensing apparatus 1 that performs such a dispensing operation includes a surface tension stop conduit 34 that stops the downstream movement of the liquid by surface tension in the nozzle tube portion 26, and a surface tension on the upstream side thereof. Since the liquid reservoir 29 having a diameter larger than that of the stop conduit 34 is formed, the liquid reservoir 32 can be easily connected to the connecting pipe 20 on the liquid pump 32 side.

If the length of the surface tension stop conduit 34 is set to be a multiple of the discharge distance L, in this case, the sample liquid sucked and held in the surface tension stop conduit 34 is divided into multiples thereof. The liquid can be discharged sequentially and accurately, and the dispensing operation can be performed efficiently.
Further, when the sample liquid is accommodated in the liquid reservoir 29 provided on the upstream side of the surface tension stop conduit 34, the amount of the sample liquid retained can be greatly increased, thereby suppressing the waste and deterioration of the sample liquid. Continuous dispensing work can be performed efficiently. The reagent solution can also be continuously supplied from the liquid pumps 32 and 33 side as in the conventional case.

  The nozzle tube 2 is detachably attached to and supported by the lifting / lowering rod 10 of the dispensing unit 3, and the connecting tube 20 and the air tube 23 are inserted and supported in the hollow lifting / lowering rod 10. Since the nozzle pipe portion 26 and the air supply pipe 22 are detachably provided on the air pipe 23, the connecting pipe 20 and the air pipe 23 are not exposed to the outside, so that dust or the like does not accumulate, and the nozzle pipe 2 moves up and down. Can be done smoothly. In addition, the lifting / lowering rod 10 can be easily subjected to maintenance work such as replacement of the nozzle tube according to the present invention having a different size and shape, and cleaning of the nozzle tube.

  The nozzle tube 2 in the illustrated example is attached downward with respect to the lifting / lowering rod 10 and discharges the sample liquid to the downstream side of the air supply port 30 by air and stops the nozzle hole on the upstream side of the air supply port 30. 25, the downstream movement is stopped by surface tension, and continuous dispensing work is performed, so that it is possible to prevent the occurrence of contamination due to the installation of a three-way valve, etc., and a high-pressure pump for discharging the liquid is required. Although there is an advantage such as not, it is not limited to the use of this embodiment.

That is, the liquid discharge structure, the diameter and length of the nozzle hole 25 of the Roh nozzle tube 2 has to be set according to the cohesive force between molecules with the liquid to be applied (determined).

  The liquid discharge structure of the nozzle tube of the present invention can be used as a nozzle tube of a dispensing device that dispenses a small amount of sample liquid as an example of use, and the nozzle of a liquid discharge device that discharges liquid intermittently or substantially continuously It can also be a tube or the like.

It is a front view of the dispensing apparatus provided with the nozzle tube concerning this invention. It is a side view which shows the structure of the principal part of FIG. It is a top view of FIG. It is a sectional side view which shows the structure of the dispensing part and nozzle tube of FIG. It is a circuit diagram which shows the structure of a pump part. It is a circuit diagram which shows the structure of a washing | cleaning part. It is side sectional drawing which shows the effect | action of a nozzle pipe | tube. It is side sectional drawing which shows the effect | action of a nozzle pipe | tube. It is side sectional drawing which shows the effect | action of a nozzle pipe | tube. It is an operation | movement sectional drawing which shows the process of the dispensing operation | work concerning this invention, (A) shows the auxiliary liquid filling process by a nozzle tube. (B) shows the air gap formation process by a nozzle pipe. (C) shows the sample liquid suction step by the nozzle tube. (D) shows the sample liquid positioning process by a nozzle tube. (E) shows the sample liquid discharge preparation process by a nozzle tube. (F) shows the sample liquid discharge process by a nozzle tube.

Explanation of symbols

1 Dispensing device (use device)
2 Nozzle pipe 3 Dispensing part 6 Conveying part 10 Lifting rod 20 Connecting pipe 22 Air supply pipe 23 Air pipe 25 Nozzle hole 26 Nozzle pipe part 29 Liquid reservoir 30 Air supply port 32, 33, 35 Liquid pump 34 Surface tension stop pipe Route 45 Air supply section

Claims (1)

In the downward nozzle pipe (2) that pushes the liquid supplied into the nozzle pipe section (26) connected to the liquid pump (32 ) for supplying the liquid to the downstream side and discharges it from the opening section, the nozzle pipe section (26 ) Is provided with a surface tension stop pipe (34) having a nozzle hole (25) having an inner diameter for stopping the movement of the liquid downstream by surface tension, and air is provided in the middle of the surface tension stop pipe (34). An air supply port (30) connected to an air supply pipe (22) for pressure-feeding into the nozzle hole (25) from the side is formed, and the surface tension stop pipe is located upstream of the surface tension stop pipe (34). A liquid reservoir passage (29) having a diameter larger than that of the passage (34) is formed and connected to the connecting pipe (20) on the liquid pump (32) side through which the liquid is supplied through the liquid reservoir passage (29). (25) In the place held on the downstream side of the air supply port (30) A fixed amount of liquid is discharged by the air supplied from the air supply port (30), and in the air supply stop state after the liquid pushed out downstream of the air supply port (30) is discharged, the air supply port (30 The protein dispensing apparatus which stops the downstream movement of the liquid which exists upstream) by surface tension.

Images