JP2007132855A - Liquid stirring method and liquid stirring device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid stirring method which enables the execution of efficient and proper stirring, and a liquid stirring device. <P>SOLUTION: The nozzle 11 connected to a pump 15 is inserted in a liquid container 100 to suck a liquid 101 into the nozzle 11 in the vicinity of the bottom part of the container and the liquid 101 is discharged in the vicinity of the surface of the liquid 101 by raising the nozzle 11. This process is repeated plurality of times to stirr the liquid 101 composed of a plurality of components. The inner pressure of the pump at the time of the suction of the liquid 101 is measured and the process is repeated until the inner pressure becomes predetermined pressure. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method and apparatus for stirring liquids in a container in which liquids having different components are dispensed from a plurality of suction sources.

  When dispensing liquids of different components from a plurality of aspiration sources into a single container in a dispensing device or analyzer, a liquid with a high specific gravity precipitates at the bottom of the container as it is, and a liquid with a low specific gravity (for example, distilled water or buffer) Etc.). Therefore, it is necessary to agitate the liquid in the container. As a general agitation method, a method is known in which a shaft with a blade at the tip is inserted into the container and the shaft is rotated. For example, in the apparatus described in Patent Document 1, a stirring blade is attached to the suction port.

  Further, as a method that does not use a shaft, there is a stirring method using a dispensing pump. For example, a liquid in a container is sucked into a nozzle (disposable tip) having a thin tip diameter, and the liquid is introduced into a large-diameter portion at the top. Then, by repeating the operation of discharging the liquid back to the original container through the nozzle, convection is generated in the liquid in the container, and stirring is performed. In the apparatus described in Patent Document 2, a main chamber and a sub chamber having an inner diameter larger than that of the nozzle are provided above the nozzle.

  Furthermore, as another method, liquid is discharged from the top of the container with the tip of the tip not touching the liquid surface (air discharge), or the nozzle is moved in the horizontal (XY axis) direction and sucked from the center of the container. There is a discharge direction at the edge of the container. For example, in the apparatus described in Patent Document 3, the nozzle (disposable chip) is shifted in the horizontal direction.

JP 2004-101271 A Japanese Patent No. 3239203 JP 2001-343310 A

However, in the conventional apparatus or method, in addition to the pump for dispensing, a mechanism for rotating the shaft and a mechanism for cleaning the shaft must be added.
Further, in the method using a dispensing pump, a tip or pump having a relatively large volume is required for a container in which liquid is dispensed, and the size of the mechanism is increased. In addition, when a large amount of liquid (for example, 1000 μl or more) is agitated with a chip having a small volume (for example, about 30 to 40 μl), this method cannot be used effectively.

  Further, in the air discharge, bubbles are generated at the time of discharge, which may cause inconvenience in the subsequent process. In the method of discharging at the edge of the container, the stirring efficiency may be lowered depending on the shape of the container bottom, and when the nozzle is moved, liquid splashing may occur in the horizontal direction, and contamination may occur in the adjacent container.

  In view of such circumstances, an object of the present invention is to provide a liquid stirring method and apparatus capable of efficiently and appropriately stirring while simplifying the configuration.

  In the liquid stirring method according to the present invention, a nozzle connected to a pump is inserted into a liquid container, the liquid is sucked into the nozzle near the bottom of the container, the nozzle is raised, and the liquid is discharged near the liquid surface. And the liquid which consists of a several component is stirred by repeating the above process in multiple times, It is characterized by the above-mentioned.

  In the liquid agitation method of the present invention, the pump internal pressure during the suction of the liquid is measured, and the above steps are repeated until the internal pressure reaches a predetermined pressure.

  Further, in the liquid stirring method of the present invention, when the nozzle is inserted into the liquid container, the liquid level of the liquid is detected by a change in the internal pressure of the pump above and below the liquid level at the tip of the nozzle, and the liquid level is near the liquid level. A liquid discharge position is set.

  In the liquid agitation method of the present invention, a position where the tip of the nozzle contacts the container bottom of the container is detected by a contact sensor, and a liquid suction position is set near the container bottom.

  The liquid agitating device according to the present invention includes a pump mechanism that sucks and discharges liquid by pressurizing and depressurizing the nozzle, and a nozzle vertical movement mechanism that moves the nozzle up and down, and the nozzle vertical movement mechanism moves the vicinity of the bottom of the container. The liquid is sucked into the moved nozzle by the pump mechanism, and the nozzle is raised to discharge the liquid near the liquid surface.

  Moreover, the liquid stirring apparatus of the present invention includes a pressure sensor for measuring a pump internal pressure of the pump mechanism.

  In the liquid stirring apparatus of the present invention, the liquid stirring device includes a contact type sensor that is attached to the nozzle vertical movement mechanism and detects a position where the tip of the nozzle contacts the container bottom of the container.

According to the present invention, since stirring is performed using a disposable tip, a cleaning mechanism such as a nozzle is unnecessary, and the configuration can be simplified. In addition, a large volume of liquid can be stirred with a small volume chip.
Since the apparatus is not driven in the X and Y directions, the operation is simplified and the processing speed is improved. Furthermore, there is no liquid splashing in the lateral direction, and contamination can be effectively prevented.

In addition, since the number of stirrings can be optimized, problems such as insufficient stirring and insufficient stirring, and excessive processing time is wasted.
By measuring the pressure waveform of the internal pressure of the pump, it is only necessary to set a large number of times of stirring even for components that are difficult to stir, so that even when the components of the liquid are different, it is possible to cope effectively.
Furthermore, the stirring efficiency is not affected by the container shape (V-shaped bottom, U-shaped bottom, etc.). Moreover, since it is not necessary to form a large convection, there is no concern that bubbles or the like are generated in the liquid.

Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings.
FIG. 1 is a block diagram showing a device configuration of the device of the present invention in this embodiment. In this embodiment, the dispensing device 10 has a function of stirring the liquid in a container in which liquids having different components are dispensed from a plurality of suction sources. In this example, the disposable tip 11 is used as a dispensing nozzle when dispensing. Is used. The disposable tip 11 is attached to the tip fitting 12 and is basically removed from the tip fitting 12 for each dispensing. For this reason, a chip remover (not shown) for removing the disposable chip 11 from the chip fitting 12 is arranged.

  As shown in FIG. 1, a disposable chip 11 is attached to the chip fitting 12, and the disposable chip 11 can be positioned at a desired position and conveyed via the chip fitting 12. Therefore, it has a transport mechanism for moving the tip fitting 12 freely on the work area. This transport mechanism is movable in, for example, an X, Y, and Z-axis coordinate system, and includes an XY axis drive mechanism that guides transport in the X and Y axis directions, and a Z axis that moves up and down in the Z axis direction (vertical direction). It has a drive mechanism (nozzle vertical movement mechanism) These drive mechanisms are driven and controlled via the X, Y, and Z axis control units 14 according to commands from the control unit 13 of the apparatus, and can cooperate to transport the chip fitting 12 and thus the disposable chip 11 appropriately and smoothly. Configured to be able to.

  Further, in FIG. 1, a pump 15 is connected to the chip fitting 12, and suction and discharge with respect to the disposable chip 11 are performed by this pump 15. The pump 15 is driven and controlled via a pump drive unit 16 according to a command from the control unit 13, and suction and discharge pressures as outputs thereof are detected by a pressure sensor 17. The pressure value detected by the pressure sensor 17 is amplified by the amplifier circuit 18. The comparator circuit 19 compares the pressure value with the data stored in the memory 20 converted by the DAC 21, and the comparison result of the comparator circuit 19 is determined by the determination unit 22.

  Further, in this example, the displacement type contact type jamming sensor 23 is provided, and the output thereof is sent to the jamming detection unit 25 through the amplifier circuit 24. In this case, a jamming spring (not shown) is attached to the chip fitting 12, and it is possible to determine whether or not the tip of the disposable chip 11 has contacted the object by measuring the amount of displacement of the jamming spring. it can. The displacement jamming sensor 23 can detect a displacement amount of about 0.1 to 0.2 mm.

  The apparatus according to the present invention also includes an input unit 26 for various data and a display unit 27 for various information, and further includes a memory 28 for storing data used for the operation of the device.

  Next, an example of operation of the apparatus of the present invention in the above configuration will be described with reference to the flowcharts of FIGS. First, in step S1, the disposable chip 11 is mounted on the chip fitting 12. Here, a container 100 in which liquids having different components are dispensed from a plurality of suction sources is set at a predetermined position of the dispensing apparatus 10, and the liquid 101 is dispensed into the container 100 ( Figure 2). Next, in step S2, the tip fitting 12 and thus the disposable tip 11 are moved to the upper side of the container 100 by the XY axis drive mechanism, and are positioned and held.

  Next, in step S3, the liquid level of the liquid 101 in the container 100 is detected. In this case, the disposable chip 11 is lowered by the Z-axis drive mechanism via the chip fitting 12. At this time, the pump 15 is operated to apply an appropriate minute pressure to the disposable chip 11. During this time, the pressure sensor 17 detects the internal pressure (discharge pressure) of the pump 15. When the tip (lower end) of the disposable chip 11 comes into contact with the liquid surface 101a of the liquid 101, the detected pressure value of the pressure sensor 17 increases, and it is determined that the tip of the disposable chip 11 has reached the liquid surface 101a.

  Here, in the present invention, as will be described later, the disposable chip 11 is inserted into the container 100, the liquid 101 is sucked into the disposable chip 11 near the bottom of the container 100, and the disposable chip 11 is raised to near the liquid surface 101 a. The liquid 101 is discharged. The liquid discharge position is set based on the liquid level 101a detected as described above. That is, as shown in FIG. 2A, the liquid discharge position A is preferably set in the vicinity of the liquid surface 101a so that the tip of the disposable chip 11 is not separated from the liquid surface 101a. Preferably, the distance from the liquid surface 101a is about A = 0.5 to 1.0 mm, and this numerical data is stored in the memory 28 (step S4).

  Next, in step S5, the disposable chip 11 is further lowered by the Z-axis drive mechanism, and it is detected by the jamming sensor 23 whether or not the disposable chip 11 has contacted the bottom of the container 100 (step S6). That is, when the tip of the disposable chip 11 comes into contact with the bottom of the container 100, the jamming sensor signal is turned on, and the Z-axis drive mechanism is stopped at the time when the tip is turned on (step S7). In step S8, the disposable tip 11 is slightly raised from this stop position, and the liquid suction position B is set. The distance from the bottom of the container 100 at the tip of the disposable chip 11 is about B = 0.5 to 1.0 mm as shown in FIG. 2 (b), and this numerical data is stored in the memory 28. Note that the distance between the liquid discharge position A and the liquid suction position B is h.

  In step S 9, the liquid 101 is sucked into the disposable chip 11 at the liquid suction position B. At this time, the pressure sensor 17 detects the suction pressure of the pump 15. Usually, a liquid having a high viscosity or a large specific gravity is accumulated at the bottom of the container 100, and when sucked at a high speed in this state, the internal pressure of the pump 15 rapidly decreases due to a viscous pressure loss. In this case, as shown in FIG. 5, the internal pressure decreases from the start of suction (the negative pressure increases), and a predetermined amount of the liquid 101 is sucked into the disposable chip 11 during this time.

When a liquid component such as a viscosity is present at the bottom of the container 100, the minimum value of the pump internal pressure during suction decreases (the maximum value as a negative pressure increases), and as the liquid component with high viscosity decreases The minimum value of the pump internal pressure gradually increases (decreases as negative pressure). Therefore, detecting the minimum value of the pressure inside the pump during the suction (step S10), and the smaller compared to the predetermined threshold value P _th (e.g. minimum pressure value P ₁ in FIG. 5) at step S11, Z-axis driving mechanism Thus, the disposable chip 11 is raised to the liquid ejection position A at a high speed (step S12).

In step S13, the liquid 101 in the disposable chip 11 is discharged at a high speed at the liquid discharge position A as shown in FIG. Since the liquid 101 having a high viscosity or a large specific gravity sucked at the liquid suction position B of the container 100 is ejected in the vicinity of the liquid surface 101a, the liquid collected near the liquid surface 101a in the upper part of the container 100 (low viscosity) Or a liquid such as distilled water or a buffer having a small specific gravity), and the viscosity of the liquid collected at the bottom of the container 100 is lowered by agitation of the liquid 101. Again, the disposable tip 11 is lowered by the Z-axis drive mechanism (step S14), and the minimum value of the pump internal pressure during suction is detected in the same manner as described above. This process is continued until the minimum value (peak pressure) of the pump internal pressure exceeds the threshold value P _th, and when it exceeds (for example, the minimum pressure value P _{2 in} FIG. 5), it is determined that the agitation is substantially completed (step). S11).

In order to perform stirring more reliably, the suction and discharge of the liquid 101 are repeated several times as shown by time T ₁ in FIG. 5 even after the minimum value of the pump internal pressure exceeds the threshold value P _th . Is the effect.

  Here, specific parameters in the above-described stirring operation are shown below. In this case, in order to shorten the processing time and increase the stirring efficiency, it is preferable to increase the operating speed of the Z-axis drive mechanism and the pump 15 as much as possible. On the other hand, it should be noted that the stirring efficiency is lowered when the operation speed of the pump 15 is increased so that the liquid 101 in the disposable chip 11 does not follow the suction and discharge operations of the pump 15.

Stirring operation parameters Suction / discharge speed (highest speed) ... 200μl / sec
Suction / discharge volume: approx. 30μl (Disposable chip maximum capacity)
Z-axis ascent / descent distance h = 45mm
Z-axis ascending / descending speed: approx. 160 mm / sec
Stirring liquid volume (maximum) ······· 1600μl (when 1.5ml container is used)
Number of stirrings: 60 times

For completion of stirring, in order not to leave a drop on the outside of the disposable tip 11, the slow rise in step S15 to the liquid discharge position A as shown at time T ₂ of the FIG. 5 (slow-up), at step S16, disposable The liquid 101 in the chip 11 is discharged. Thereafter, in step S17, a time lag (time T _{3 in} FIG. 5) is provided until the liquid 101 in the disposable chip 11 is partitioned, and the liquid 101 rises at a low speed and is separated from the liquid surface 101a (step S18). Ascend up fast. In step S20, the disposable tip 11 is moved to the tip remover by the XY axis drive mechanism, the disposable tip 11 is removed from the tip fitting 12 (step S21), and the stirring operation is finished.

  As described above, in the present invention, the liquid 101 stored in the lower part of the container 100 or having a high specific gravity is “moved” to the upper part of the container 100 so that the liquid 101 in the container 100 is uniformly stirred. The entire liquid 101 can be made uniform. Incidentally, in the technique described in Patent Document 1 or Patent Document 3 or the like, the liquid is stirred by causing convection in the container. In this case, in order to generate sufficient convection, a considerably high speed and a large amount of convection are required, and if the density difference between the upper and lower parts of the container is large or the container is elongated, the effect of convection must be limited. I don't get it. In contrast, the present invention can effectively compensate for the disadvantages associated with the convection stirring method.

As described above, whether or not sufficient agitation has been performed is determined by a pressure waveform. A method for further ensuring this will be described below. First, the peak pressure is measured for each suction, the difference from the peak pressure at the previous suction is calculated, and it can be determined that the agitation is completed when the value falls below a certain value.
Further, a suction / discharge operation of stirring may be added between step S4 and step S5 described above. In this case, the viscous pressure loss of a buffer or the like having a low viscosity before stirring or a low specific gravity at the liquid discharge position A is examined, and stored as a peak pressure based on this. During stirring, the peak of stirring suction at the liquid suction position B is measured, and stirring can be completed when this peak pressure approaches a reference peak pressure to some extent.

Further, a suction / discharge operation of stirring may be added between step S16 and step S17. In this case, it is determined whether or not sufficient agitation has been performed by comparing the peak pressure at the time of agitation and suction at the liquid discharge position A with a threshold value again (in this case, the threshold value becomes P _th −ρgh). If the peak pressure at the time of suction at the liquid discharge position A is smaller than the peak pressure at the time of suction at the liquid suction position B, the viscosity of the liquid is non-uniform and the stirring becomes insufficient. Become.

  Further, the stirring suction / discharge operation may be performed at any Z-axis direction position between the liquid discharge position A and the liquid suction position B during the stirring (steps S9 to S14). This makes it possible to check the viscous pressure loss at an arbitrary height during stirring, and to grasp the state of stirring in the height direction.

As mentioned above, although this invention was demonstrated with various embodiment, this invention is not limited only to these embodiment, A change etc. are possible within the scope of the present invention.
For example, the specific numerical values and the like described in the above embodiment are not limited to these, and can be appropriately changed as necessary.

It is a figure which shows schematic structure of the dispensing apparatus which concerns on embodiment of this invention. It is a figure which shows the relationship between the liquid discharge position and liquid suction position in embodiment of this invention. It is a flowchart which shows the operation example in embodiment of this invention. It is a flowchart which shows the operation example in embodiment of this invention. It is a figure which shows the effect | action in embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Dispensing apparatus 11 Disposable tip 12 Chip fitting 13 Control part 14 X, Y, Z-axis control part 15 Pump 17 Pressure sensor 20 Memory 23 Jamming sensor 25 Jamming detection part

Claims (7)

Insert a nozzle connected to the pump into the liquid container, suck the liquid into the nozzle near the bottom of the container, raise the nozzle to discharge the liquid near the liquid level,
A liquid stirring method, wherein the liquid composed of a plurality of components is stirred by repeating the above steps a plurality of times.   2. The liquid agitation method according to claim 1, wherein an internal pressure of the pump at the time of sucking the liquid is measured, and the step is repeated until the internal pressure reaches a predetermined pressure.   When inserting the nozzle into the liquid container, the liquid level of the liquid is detected by a change in the internal pressure of the pump above and below the liquid level at the tip of the nozzle, and a liquid discharge position is set near the liquid level. The liquid stirring method according to claim 1 or 2.   The position where the tip of the nozzle contacts the container bottom of the container is detected by a contact sensor, and the liquid suction position is set in the vicinity of the container bottom part. Liquid stirring method. A pump mechanism that sucks and discharges liquid by increasing and reducing the pressure of the nozzle, and a nozzle vertical movement mechanism that moves the nozzle up and down,
A liquid is sucked by the pump mechanism into the nozzle moved to the vicinity of the container bottom by the nozzle vertical movement mechanism, and the liquid is discharged near the liquid surface by raising the nozzle. Liquid stirring device.   The liquid stirring apparatus according to claim 5, further comprising a pressure sensor that measures a pump internal pressure of the pump mechanism.   The liquid stirring apparatus according to claim 5, further comprising a contact sensor attached to the nozzle vertical movement mechanism and configured to detect a position at which a tip of the nozzle contacts a container bottom of the container.

Images