JP2007078470A - Automatic dispensing device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an automatic dispensing device capable of dispensing liquid accurately by performing discharge operation under certain specified conditions, regardless of the properties of the liquid dispensed. <P>SOLUTION: The automatic dispensing device 1 is equipped with a dispensing head 6 for suction and discharging of the liquid, a robot (transport means) 5 for moving the head 6, a group of vessels (suction vessels) 10 to store the liquid sucked by a dispensing tip 8 mounted on the head 6, and a filter-fitted vessel (discharge vessel) 11 through which the liquid is discharged, wherein the distance between the bottom of a liquid drop produced at the tip of the dispensing tip 8 and the liquid surface in the filter-fitted vessel 11 is set fixed (for example, 10 mm or smaller), when the liquid is to be discharged to the filter-fitted vessel 11. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an automatic dispensing apparatus used for dispensing specimens, reagents, enzymes and the like in drug metabolism tests and the like.

  In addition to drug metabolism tests, the work of dispensing samples and reagents is frequently performed, and the work tends to be enormous, and there is a desire to eliminate human errors due to manual labor. Shifting from work to automation.

  In order to automate the dispensing operation, a suction container containing the necessary liquid is placed in the device in advance, and the robot is moved to a position where the dispensing tip attached to the dispensing head can suck the liquid. In general, control is performed such that a predetermined amount of liquid is sucked into the chip and discharged into a predetermined discharge container.

  Here, when discharging the reagent liquid, it is necessary to move the robot so that the discharge port at the lower tip of the dispensing tip is above the liquid level in the dispensing container. The position in the vertical direction is not a problem as long as it is above the liquid level, and it is desirable to move it as close as possible to the liquid level. The reason is that, when discharged from a position away from the liquid surface, the dispensing accuracy decreases due to the splashing of the liquid and the rebounding of the liquid.

  Also, when a highly volatile liquid such as alcohol is discharged from the sky, the liquid evaporates before reaching the liquid surface, and the amount dispensed is reduced. Further, bubbles are easily formed because the liquid is dropped from the sky. In the case of a test that causes a chemical reaction by mixing liquids together like a drug metabolism test, the measurement results are adversely affected by bubbles.

  In addition, the work of once discharging the liquid into the discharge container and then sucking the liquid from the discharge container and transferring the liquid to another container is generally performed. Can not be sucked.

Therefore, a method has been proposed in which the discharge height is kept constant from the relationship between the dispensing amount and the liquid level in the discharge container (see Patent Document 1). According to this method, the liquid level is calculated from the shape of the discharge container and the amount of liquid in the discharge container, and from the relationship between the amount dispensed and the liquid level, the discharge port at the lower tip of the dispensing tip and the discharge The distance from the liquid level of the container can always be controlled to a constant distance.
Japanese Patent Laid-Open No. 11-287811

  However, in the above method, when the liquid is discharged, the liquid does not continuously flow out from the discharge port at the lower end of the dispensing tip, but intermittently discharged as droplets having different sizes depending on the type of the liquid. Fall into the container. Therefore, even if the distance between the discharge port at the lower tip of the dispensing tip and the liquid level of the discharge container is controlled to a predetermined distance, the liquid is large in the case of a liquid having a large surface tension. The distance between and becomes smaller. In some cases, there is a possibility of causing so-called contamination in which the droplet touches the liquid surface.

  On the other hand, in the case of a liquid with a small surface tension, the droplet is small and the distance between the droplet and the liquid surface is large. Become. That is, conditions differ depending on the type of liquid to be dispensed.

  The present invention has been made in view of the above problems, and the target process is that high-precision dispensing can be performed by performing a discharge operation under certain conditions regardless of the properties of the liquid to be dispensed. It is to provide an automatic dispensing device.

  In order to achieve the above-mentioned object, the invention according to claim 1 is equipped with a dispensing head capable of sucking and discharging a liquid, a transfer means for moving the dispensing head, and the dispensing head. In an automatic dispensing apparatus having a suction container for storing a liquid sucked by a dispensing tip and a discharge container for ejecting a liquid, when the liquid is discharged to the discharge container, the tip of the dispensing tip is The distance between the lowermost end of the generated droplet and the liquid level of the discharge container is made constant.

  The invention described in claim 2 is characterized in that, in the invention described in claim 1, the distance between the lowest end of the droplet formed at the tip of the dispensing tip and the liquid level of the discharge container is 10 mm or less.

  According to a third aspect of the present invention, in the first aspect of the present invention, the size of the droplet can be input to a control device.

  According to a fourth aspect of the present invention, in the first aspect of the present invention, the size of the droplet is calculated.

  According to the first aspect of the present invention, when the liquid is discharged into the discharge container, the discharge operation is performed with a constant distance between the lowest end of the droplet formed at the tip of the dispensing tip and the liquid level of the discharge container. Therefore, the discharge operation can be performed under certain conditions regardless of the properties of the liquid to be dispensed, and high-precision dispensing is possible.

  According to the second aspect of the present invention, by setting the distance between the lowermost end of the droplet formed at the tip of the dispensing tip and the liquid level of the discharge container to a minute distance of 10 mm or less, the liquid splatters, Problems caused by rebound, evaporation, foaming, etc. can be minimized.

  According to the third and fourth aspects of the invention, the distance between the lowermost end of the droplet formed at the tip of the dispensing tip and the liquid level of the discharge container can be made constant regardless of the experimental conditions.

  Embodiments of the present invention will be described below with reference to the accompanying drawings.

  In the present embodiment, an automatic dispensing apparatus (hereinafter referred to as “automatic solid phase extraction apparatus”) that realizes a solid phase extraction process performed as a pretreatment when analyzing organic chemical components contained in pharmaceuticals, agricultural chemicals, water, and the like. Will be described.

  FIG. 1 is a perspective view of an automatic solid-phase extraction apparatus 1 according to the present invention. The automatic solid-phase extraction apparatus 1 includes an automatic solid-phase extraction apparatus main body 2, a vacuum controller 15 with a built-in vacuum pump, and these. It is comprised by the control apparatus 3 which controls. The control device 3 is composed of, for example, a general-purpose personal computer, and is connected to the automatic solid-phase extraction device main body 2 and the vacuum controller 15 via a communication cable 4 such as a LAN (Local Area Network).

  The automatic solid-phase extraction device main body 2 is input to a robot 5 which is a transfer means capable of moving and positioning in a three-dimensional space, a dispensing head 6 provided at the tip of the robot 5, and a control device 3. A circuit unit (not shown) for driving the automatic solid-phase extraction apparatus main body 2 based on the above conditions is provided. Here, the robot 5 has an X axis, a Y axis, and a Z axis that are orthogonal to each other, and is configured to be driven and positioned by a stepping motor (not shown). A servo motor or the like may be used as a drive motor for driving the robot 5.

  FIG. 2 is a perspective view showing the internal structure of the automatic solid-phase extraction apparatus main body 2.

  A plurality of dispensing tips 8 arranged in a line can be attached to and detached from the dispensing head 6, and by attaching the dispensing tips 8, liquid can be sucked and discharged. For example, the dispensing head 6 is configured such that 12 series of syringes (not shown) are driven by one stepping motor, and the intervals between the syringes are arranged at the same 9 mm pitch as the intervals of the wells of the container 11 with the filter. The liquid suction and discharge operations are executed by mounting the dispensing tip 8 and driving the syringe.

  Below the movable range of the dispensing head 6 attached to the robot 5, a dispensing tip container in which the dispensing tips 8 attached to the dispensing head 6 can be arranged at the same 9 mm pitch as the spacing of the wells of the filter-equipped container 11. 9 is arranged. Also, reagent containers 10a and 10b containing reagents, a standard solution container 10c containing a solution called a standard solution, and a sample container 10d used for preparing a sample in advance as a pretreatment for performing solid phase extraction. Four plate container groups 10 are arranged.

  The filter-equipped container 11 is placed in a carrier 12 disposed on the upper part of the vacuum container 13. And the convex parts 12a and 12b of the carrier 12 are attached to the upper left and right of the carrier 12 upward. Further, hooks 6a and 6b that can come into contact with the convex portions 12a and 12b of the carrier 12 are attached to the left and right of the dispensing head 6, and the robot 5 is moved so that the hooks 6a and 6b of the dispensing head 6 are moved. The carrier 12 can be moved to the front side 13 a and the back side 13 b of the vacuum vessel 13 by hooking 6 b on the convex portions 12 a and 12 b of the carrier 12.

  Here, the carrier 12 is moved in the front-rear direction, but in the solid-phase extraction, there are cases where a liquid vacuumed from the filter-equipped container 11 is necessary and unnecessary. Therefore, in the present embodiment, the front side 13a of the vacuum vessel 13 is a side for receiving unnecessary liquid (hereinafter referred to as “Load side”), and the back side 13b is a side for receiving necessary liquid (hereinafter referred to as “Collect side”). Called). Further, by moving the robot 5 and pressing the protrusions 12 a and 12 b of the carrier 12 with the hooks 6 a and 6 b of the dispensing head 6, the lower surface of the filter-equipped container 11 placed in the carrier 12 and the vacuum container 13 are pressed. The space formed by the load side 13a or the collect side 13b is sealed, and the vacuum controller 15 is controlled to make the inside of the space into a vacuum state, so that the liquid in the filter-equipped container 11 is sucked into the vacuum container 13 by vacuum. .

  In addition, a waste container 14 for disposing of the dispensing tip 8 that is no longer needed for reagent dispensing is disposed inside the automatic solid phase extraction apparatus main body 2.

  By the way, the container 11 with a filter is provided with a plurality of wells of vertical n × horizontal m. For example, 96 wells of 12 vertical × 8 horizontal are arranged in a grid.

  Further, the automatic solid-phase extraction apparatus 1 is covered with a safety cover 16 so that hands or the like cannot be put inside the automatic solid-phase extraction apparatus body 2 during operation. A structure is adopted in which the power supply to the robot 5 is automatically shut off when the safety cover 16 is opened.

  FIG. 3 is a diagram showing a specific operation process example 30 using the automatic solid-phase extraction apparatus 1 according to the present invention. An experimenter using the automatic solid-phase extraction apparatus 1 determines an operation process in advance using the control device 3 shown in FIG. 1 before starting the operation. Step 1 shown in the operation process example 30 means that 50 μl of MeOH solvent previously placed in the standard solution container 10c is sucked and discharged to the first and second rows of the sample container 10d.

  A specific operation of the automatic solid-phase extraction apparatus 1 will be described with reference to FIG.

  First, the robot 5 is moved so that the nozzle portion 6 c at the lower end of the dispensing head 6 is press-fitted into the upper opening of the dispensing tip 8 placed in the dispensing tip container 9. Insert the tip 8 Thereafter, the dispensing head 6 is moved to the sky to complete the mounting of the dispensing tip 8.

  Next, the dispensing head 6 is moved to the row of the standard solution containers 10c in which the MeOH solvent is placed, and the dispensing head 6 is lowered to a position where the tip of the dispensing tip 8 is immersed in the MeOH solvent. Then, a syringe (not shown) is controlled in the suction direction, 50 μl of MeOH solvent is sucked into the dispensing tip 8 attached to the dispensing head 6, and the dispensing head 6 is moved upward to suck the MeOH solvent. Complete.

  Next, the dispensing head 6 is moved to the first row of the sample container 10d, and the syringe is controlled in the discharge direction to discharge the MeOH solvent in the dispensing tip 8 to the sample container 10d.

  MeOH (methanol) solvent is sucked in the same manner as described above, and a discharge operation is performed on the second row of the sample container 10d. After this operation is completed, the dispensing head 6 is moved above the disposal container 14 and the dispensing tip 8 that is no longer necessary is removed from the dispensing head 6 using a dispensing tip removal mechanism (not shown). To complete the step 1.

  The steps from Step 2 to Step 6 are different in the position to be sucked due to different reagents, the amount to be dispensed, the position to be ejected, and the number of columns are different, but from the mounting of the dispensing tip 8 to the suction of the reagent, The flow up to the discharge and disposal of the dispensing tip 8 is the same as in Step 1 described above.

  Next, the operation of the automatic solid-phase extraction apparatus 1 of Step 7 “Reagent → Dispensing into Load → Vacuum suction” will be described.

  First, the carrier 12 must be moved to the load side 13 a of the vacuum vessel 13. When the carrier 12 is not on the load side 13a, the hooks 6a and 6b of the dispensing head 6 are hooked on the convex portions 12a and 12b of the carrier 12 and moved to the load side 13a. Here, in a state where the dispensing tip 8 is mounted, the dispensing tip 8 collides with the filter-equipped container 11 before the hooks 6a, 6b of the dispensing head 6 contact the convex portions 12a, 12b of the carrier 12. Therefore, the carrier 12 is moved before mounting the dispensing tip 8.

  Next, as in Step 1, the robot 5 is moved so that the nozzle portion 6c at the lower end of the dispensing head 6 is press-fitted into the upper opening of the dispensing tip 8 placed in the dispensing tip container 9. The dispensing tip 8 is attached to the dispensing head 6. Thereafter, the dispensing head 6 is moved to the sky to complete the mounting of the dispensing tip 8.

  Next, the dispensing head 6 is moved to the row of reagent containers 10a or 10b in which the reagent MeOH to be dispensed is placed, and the dispensing head 6 is lowered to a position where the tip of the dispensing tip 8 is immersed in MeOH. Then, a syringe (not shown) is controlled in the suction direction, 500 μl of MeOH is sucked into the dispensing tip 8 attached to the dispensing head 6, and the dispensing head 6 is moved to the sky to complete the suction of MeOH. .

  Next, the dispensing head 6 is moved to the first row of the filter-equipped container 11 placed on the carrier 12 that has been moved to the load side 13a of the vacuum container 13, and the syringe is controlled in the discharge direction to dispense the tip. The MeOH in 8 is discharged into the container 11 with a filter.

  MeOH is sucked in the same manner as described above, and the discharge operation is performed in the second row of the container 11 with the filter. Similarly, MeOH is dispensed from the third row to the twelfth row of the filter-equipped container 11, and after completion, the dispensing head 6 is moved over the waste container 14 and a dispensing tip removal mechanism (not shown) is used. Then, the dispensing tip 8 that has become unnecessary is removed from the dispensing tip 6.

  Next, by moving the robot 5 and pressing the convex portions 12a and 12b of the carrier 12 with the hooks 6a and 6b of the dispensing head 6, the container 11 with a filter placed in the carrier 12 on the load side 13a The space formed by the lower surface and the load side 13a of the vacuum vessel is sealed. From this state, the vacuum pump in the vacuum controller 15 is driven, and the space is evacuated to suck the liquid in the filter-equipped container 11 into the load side 13 a of the vacuum container 13. After holding this state for 1 minute, the vacuum controller 15 stops the operation of the vacuum pump, moves the dispensing head 6 to the sky, and ends the step 7.

  The steps from Step 8 to Step 12 are different in the position for sucking the reagent to be dispensed (reagent drug container 10a or 10b, sample container 10d), the dispensing amount is different, and the position of the filter-equipped container 11 (that is, the carrier 12). Although the position is different, the carrier 12 is moved, the dispensing tip 8 is attached, the reagent is aspirated, the reagent is discharged, the dispensing tip 8 is discarded, the convex portions 12 a and 12 b of the carrier 12 are pressed, and the vacuum controller 15 is controlled. The flow up to this point is the same as in Step 7 described above.

  Finally, the carrier 12 on which the filter-equipped container 11 is mounted is moved to the collect side 13b of the vacuum container 13 in Step 12, and vacuum suction is performed on the collect side 13b of the vacuum container 13, and the sucked liquid is subjected to solid phase extraction. And collected in a collection container 13c, and this liquid is applied to a detector (for example, a differential refraction detector, an ultraviolet absorption detector, an ultraviolet spectrophotometer, a fluorometer, etc.) to analyze the components.

  The above is a series of operations of the automatic solid-phase extraction apparatus 1.

  FIG. 4 is a model diagram showing how liquid is discharged from the dispensing tip 8.

  The liquid does not flow out of the dispensing tip 8 continuously, but drops intermittently as droplets of a certain size. The length H in the height direction of the droplet is uniquely determined by the diameter of the discharge port at the lower end of the dispensing tip 8, the discharge speed, the properties of the liquid to be discharged (viscosity, surface tension, etc.), and the ambient temperature. Is determined.

  In this embodiment, the length H of the droplets measured by experiment is about 4 mm for water, about 2 mm for methanol, and about 2 mm for plasma at a certain discharge speed and ambient temperature. It was 5 mm. When setting the operation process example 30 shown in FIG. 3, in addition to setting and selecting the type of liquid to be dispensed by the experimenter and the area to be dispensed, etc. The droplet length H can be set and used for calculating the movement amount of the dispensing head 6 in the height direction during the discharge operation.

  Of course, in the case of a liquid to be used for the first time, the length H of the droplet is unknown, but by classifying the properties of the liquid as water-based, alcohol-based, or sample-based, the droplet length H can be easily obtained. Can be entered. It is also possible to correct the droplet length H by performing a trial run and observing the state during discharge.

  Further, as described above, the experimenter does not directly set the droplet length H with respect to the control device 3, but the coefficient determined from the diameter of the dispensing tip 8, the discharge speed, and the ambient temperature is set to a fixed value in advance. A method may be employed in which the droplet length H is automatically calculated simply by inputting the type of liquid by the experimenter by storing the information in the control device 3. In this case, the method may be a method in which the experimenter inputs the ambient temperature to the control device 3 or a method in which the automatic dispensing device 1 has a function of measuring the ambient temperature.

  FIG. 5 is a diagram showing a state in which liquid is discharged from the dispensing tip 8 to one well 50 of the sample container 10d that is a discharge container.

  FIG. 5 shows, as an example, a case where a liquid with a small drop (for example, methanol) is discharged (for example, methanol) 51 (the length of the liquid is H1), and a liquid with a large drop (for example, methanol) , (Plasma sample) is discharged 52 (droplet length is H2).

  Thus, in any case, the dispensing head 6 is arranged so that the distance L between the lowest end of the droplet just before dropping formed at the tip of the dispensing tip 8 and the liquid level in the well 50 is constant. Control the amount of movement in the height direction. By setting the distance L to a very small distance of 10 mm or less, it is possible to minimize problems caused by liquid splashing, liquid splashing, evaporation, foaming, and the like.

  Here, the height of the liquid level in the well 50 always fluctuates with the change in the liquid amount, but the liquid level height is calculated from the relationship between the shape of the well 50 and the liquid amount in the well 50. A method for correcting the amount of movement of the dispensing head 6 in the height direction according to the dispensing amount and the liquid level is known as described in Patent Document 1.

It is a perspective view of the automatic solid phase extraction apparatus as one form of the automatic dispensing apparatus which concerns on this invention. It is a perspective view which shows the structure inside the main body of the automatic solid-phase extraction apparatus which concerns on this invention. It is a figure which shows the example of a solid-phase extraction driving | operation. It is a model figure which showed a mode that the liquid was discharged from the dispensing tip. It is a figure which shows the positional relationship of a dispensing tip, a droplet, and a liquid level.

Explanation of symbols

1 Automatic solid phase extraction device (automatic dispensing device)
2 Automatic solid phase extraction device body 3 Control device 4 Communication cable 5 Robot (transfer means)
6 Dispensing head 6a, 6b Hook 6c Nozzle part 8 Dispensing tip 9 Dispensing tip container 10 Container group (suction container)
10a, 10b Reagent container 10c Standard solution container 11 Container with filter (discharge container)
12 Carrier 12a, 12b Protruding part 13 Vacuum container 13a Load side 13b Collect side 14 Waste container 15 Vacuum controller 16 Safety cover 30 Solid phase extraction operation example 50 well

Claims (4)

A dispensing head capable of sucking and discharging liquid, a transfer means for moving the dispensing head, a suction container for storing liquid sucked by a dispensing tip mounted on the dispensing head, and a liquid In an automatic dispensing device provided with a discharge container for discharging
An automatic dispensing apparatus characterized in that, when discharging a liquid into the discharge container, the distance between the lowest end of a droplet formed at the tip of the dispensing tip and the liquid surface of the discharge container is made constant.   The automatic dispensing apparatus according to claim 1, wherein a distance between a lowermost end of a droplet formed at a tip of the dispensing tip and a liquid level of the discharge container is 10 mm or less.   2. The automatic dispensing device according to claim 1, wherein the size of the droplet can be input to a control device.   2. The automatic dispensing apparatus according to claim 1, wherein the size of the droplet is calculated.

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