JPH0783939A - Method and apparatus for suction for microplate - Google Patents

Abstract

PURPOSE:To effectively remove an unreacted sample without having a bad influence on a reaction product formed at the inside of a well when the unreacted sample is sucked after a sample has been poured into the well in a microplate in which the inside of the well has been coated with a reagent. CONSTITUTION:Two suction nozzles 14 are arranged at the right and the left of a discharge nozzle 16, and the suction nozzles 14 are moved inside a well 12 to the front and the rear in a direction at right angles to their arrangement direction. When a sample is sucked during their horizontal movement, the sample which remains at corners is sucked and removed. Even after a cleaning liquid has been poured, it is sucked by the same movement.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a suction method and a suction device using a nozzle, and more particularly to a method and a device for sucking a sample in a well of a microplate.

[0002]

2. Description of the Related Art Microplates are used to test a sample (eg, blood or urine) by utilizing an antigen / antibody reaction or the like. For example, 12 × 8 circular well-shaped wells are formed in the microplate, and the wells have a diameter of about 7 mm and a depth of about 11.5 mm.

In the above-mentioned test utilizing the antigen-antibody reaction, in recent years, reagent-coated microplates in which the inner wall surface of each well has been coated with a reagent in advance have been put into practical use. The sample and the reagent can be easily reacted simply by pouring the mixture into the inside. After the reaction, suction is performed to remove the unreacted excess sample. Thereafter, in order to further enhance the effect of removing the sample, the inside of the well is usually washed with a washing liquid.

In the well after washing, an extremely thin solid-phase film as a reaction product after the reagent and the sample are bound is formed on the inner surface of the well, and the sample in the film is indexed by a coloring liquid or radioactive substance. Then, the antibody is determined and quantified. In addition,
Generally, the bottom surface of the well is formed flat, because it does not adversely affect the measurement light when performing an optical inspection.

As described above, after the reaction, the unreacted sample is removed by suction and washing, but if it is not completely removed, it becomes a factor of lowering the inspection accuracy. Therefore, it is necessary to remove the residual sample with high accuracy.
Shows a conventional suction device for microplates. A plurality of wells 12 are formed in the microplate 10. The microplate 10 is the above-mentioned reagent-coated microplate, and a sample 26 that causes a reaction with the reagent 25 is injected into the well 12 of the microplate 10.

As shown in FIG. 7, a suction nozzle 14 and a discharge nozzle 16 which move integrally with each other are movably arranged above the well 12, and both nozzles 14 and 1 are provided.
6 is a drive unit 18 including a motor and gears,
Driven. The movement of both nozzles 14 and 16 is performed by the drive unit 18
It is controlled by the control unit 20 via the.

A suction pump 22 is connected to the suction nozzle 14 via a tube to suck an unnecessary excess sample. A cleaning liquid supply device 24 is connected to the discharge nozzle 16 via a tube.

When the excess sample is sucked by the above apparatus, first, the suction nozzle 14 and the discharge nozzle 16 (hereinafter, both nozzles are integrated as a nozzle while suctioning from above the well 12 to be sucked). (Referred to as section 15), their tips are lowered to near the well bottom surface. And
After the suction, the nozzle portion 15 is pulled up from inside the well 12.

FIG. 8 shows the device shown in FIG.
The standard of the suction action when the sample in 2 is suctioned is shown. A shaded area 100 in the drawing schematically shows a range in which a certain suction action is exerted when suction is performed by the suction nozzle 14 at a predetermined suction pressure at the position where the suction nozzle 14 is most lowered. As shown in the figure, a certain suction action extends within a certain range around the tip of the suction nozzle, but the suction action weakens at a position far from the tip. This also applies to the washing process.

[0010]

As described above, in the conventional device, it was difficult to obtain a sufficient suction effect over the entire area of the well 12.

On the other hand, in order to enhance the suction effect of the sample,
It may be possible to increase the suction pressure by the suction pump 22, but if the suction pressure is increased, there is a problem that the important post-reaction membrane existing on the inner surface of the well is destroyed.
There is a limit to the suction pressure. Further, it is possible to increase the diameter of the nozzle to approach the well diameter, but positioning becomes difficult, and if suction is performed with a suction pressure corresponding to that, suction will be excessive and the above-mentioned problem will also occur.

The present invention has been made in view of the above conventional problems, and an object thereof is to provide a suction method for a microplate and a suction device capable of sufficiently sucking a sample without increasing suction pressure. To do.

[0013]

In order to achieve the above object, the invention according to claim 1 is a method for sucking a sample contained in a well of a microplate by a suction nozzle, wherein the suction is performed while the sample is being sucked. The descending step of vertically lowering the suction nozzle with respect to the microplate so that the tip of the suction nozzle enters the well, and the suction nozzle tip is moved along the bottom surface of the well in a predetermined path in the well while performing suction. Horizontal movement process to move,
After completion of sample suction, the nozzle is vertically lifted with respect to the microplate, and the lifting step of pulling out the suction nozzle tip from the well is included.

The invention according to claim 2 is characterized in that, after the sample is sucked, a cleaning liquid is injected into the well and the step of horizontally moving is executed again.

According to a third aspect of the present invention, in the horizontal moving step, the suction nozzle is moved along the vicinity of the side wall in the well.

According to a fourth aspect of the present invention, the plurality of suction nozzles are arranged side by side, and in the horizontal movement step, the plurality of nozzles are horizontally moved in a direction orthogonal to the suction nozzle arrangement direction. To do.

The invention according to claim 5 is a device for sucking a sample placed in a well of a microplate by a suction nozzle, and a plurality of suction nozzles arranged side by side to suck the sample, Nozzle drive unit for moving the plurality of suction nozzles, and means for controlling the movement of the plurality of suction nozzles via the nozzle drive unit, wherein each suction nozzle tip is placed in the well, And a movement control section that controls the horizontal movement of the tip of each suction nozzle along a bottom surface of the well along a predetermined path.

[0018]

According to the above construction, in the descending step, the suction nozzle descends while sucking, and the sample in the well is removed by suction. This is similar to the conventional method, but by itself, the sample is likely to remain on the bottom surface (particularly, the corner portion) in the well.

Therefore, in the present invention, in the horizontal movement step, the tip of the nozzle is horizontally moved along the bottom surface of the well along a predetermined path. As a result, it is possible to exert a suction action even on a corner region where suction is conventionally insufficient. At that time, ideally, it is desirable to move the tip of the suction nozzle along the vicinity of the side wall in the well. If there is a demand for simplification of the device, it is sufficient to move a plurality of nozzles horizontally in a direction orthogonal to the suction nozzle arrangement direction. That is, the suction effect is enhanced by the plurality of suction nozzles while simplifying the movement path.

When a sufficient removal effect cannot be obtained by a single suction, a washing solution is poured as in the conventional case, and the inside of the well is washed, taking care not to destroy the membrane after the reaction. In that case, the effect of removing the cleaning liquid can be enhanced by performing the horizontal movement process again.

The microplate suction device is a device for realizing the above method.

[0022]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT A preferred embodiment of the present invention will be described below with reference to the drawings.

FIG. 1 shows the principle of the suction method according to the present invention. In the suction method according to the present invention, after the suction nozzle 14 is inserted into the well 12, the tip of the nozzle is horizontally moved along the bottom surface of the well along a predetermined path. In the example shown in FIG. 1, the nozzle tip is circularly moved along the vicinity of the side wall of the well 12. By such movement accompanied by suction, the effect of removing the sample remaining in the corner can be extremely improved. If the bottom surface of the well 12 is a curved surface, the nozzle tip is moved up and down while following the curved surface to move horizontally.

In the example shown in FIG. 1, since the suction nozzle 14 is moved in a circular shape, the mechanism for moving the suction nozzle 14 becomes complicated. Therefore, in order to simplify the mechanism of the device,
The suction device shown in FIG. 2 may be adopted.

FIG. 2 shows the overall construction of the suction device according to the invention. The same components as those of the conventional device are designated by the same reference numerals, and the description thereof will be omitted.

In FIG. 2, the nozzle portion 15 is composed of a plurality of suction nozzles 14 and one discharge nozzle 16. In the present embodiment, the nozzle tips are aligned and parallel to each other, with the discharge nozzle 16 as the center. The two suction nozzles 14 are arranged side by side. These nozzles are integrally driven by the drive unit 18. Although at least two suction nozzles 14 need to be moved integrally, the discharge nozzles 16 may be moved independently. In this embodiment, the drive unit 18 is composed of a motor, a gear, etc., and can move the nozzle unit 15 freely in three dimensions.

The control unit 30 is composed of a computer or the like, and controls the movement of the nozzle unit 15 via the drive unit 18. A suction pump 22 is connected together to the two suction nozzles 14, and a cleaning liquid supply device 24 is connected to the discharge nozzle 16.

The drive unit 18 causes the nozzle unit 15 to
In addition to moving, the microplate 10 side may be moved by a movable table (not shown).

FIG. 3 shows the movement path of the nozzle portion 15 in the horizontal movement step performed after the descending step. In this embodiment, the nozzle portions 15 are moved back and forth in a direction orthogonal to the arrangement of the nozzle portions 15. That is, the nozzle portion 15 moves forward (upward in the drawing) from near the center to near the side wall of the well 12, then moves downward to near the opposite side wall, and then returns to the original central position.
The forward and backward movement is not limited to one round trip, and may be repeated a plurality of times.

In this embodiment, as shown by 104 in FIG. 3, the suction nozzles 14 are arranged at the center of the distance from the outside of the discharge nozzle 16 to the side wall of the well 12. Therefore, the two suction nozzles 14 move while suctioning in the vicinity of both side walls of the well 12, and the unnecessary excess sample can be efficiently sucked.

In FIG. 4, the shaded area 102 indicates the range of the suction action when suction is performed at a predetermined pressure using the suction nozzle 14 of this embodiment. As each of the suction nozzles 14 moves while sucking, as shown in the drawing, a uniform suction effect can be obtained over the entire area of the well 12. In particular, the sample is likely to remain in the lower corner portion of the side wall due to surface tension or the like, but that portion can be sucked in a focused manner.

FIG. 5 shows a modified example of the movement route shown in FIG. In this example, the movement path of the nozzle 14 is set in an arc shape. Compared to the movement path shown in FIG. 4, the suction effect at the corners can be improved, but a mechanism for moving in an arc shape is required. On the other hand, the device shown in FIG. 2 has a simple mechanism of simply sliding it back and forth, and a good suction effect can be obtained, which has been confirmed by the experiments of the present inventor.

In the apparatus of this embodiment, a plurality of units including the two suction nozzles 14 and one discharge nozzle 16 shown in FIG. 2 are arranged side by side, and the sample is sucked and washed in a plurality of wells. Are carried out simultaneously.

Next, the suction method according to the present invention will be described with reference to FIG. 1 and the flow chart shown in FIG.

In S1, the nozzle portion 1 is placed above the well 12.
5 is positioned, the suction pump 22 operates, and suction is started. Then, in S2, the nozzle portion 15 is moved downward, and at this time, the sample is sucked. In S3, the lowering of the nozzle portion 15 is stopped, for example, 0.2 mm before the bottom surface of the well 12. The process up to this point is the descending process, and then the horizontal moving process is executed.

That is, in S4, as shown in FIG. 3, the nozzle portion 15 is driven so as to slide in the direction orthogonal to the arrangement direction while maintaining the height of the nozzle tip. At that time, the suction of the sample is continued, and the sample remaining in the corner of the well 12 is effectively sucked. Then, in S5, the suction pump 22 is stopped, and as a result, suction is stopped.

If a sufficient suction effect is obtained in the above steps, the next washing step is unnecessary, but in order to realize the inspection with higher accuracy by completely removing the surplus sample, in this embodiment. The cleaning process is performed multiple times.

That is, in S6, since the outer periphery of the nozzle portion 15 is not unnecessarily contaminated by pouring the cleaning liquid, the nozzle portion 15 is once driven up, and in that state, it is set from the cleaning liquid supply device 24 in S7. A quantity of wash solution is supplied into the well 12. As above, S
In 8, the suction is started again, and in S9, the nozzle unit 1
5 is lowered and suction is performed. Then, after the descent is stopped in S10, in S11, the horizontal movement is executed simultaneously with the suction in the same manner as in S4. When the suction is completed in S12, the nozzle unit 15 is slightly lifted up again in preparation for another cleaning in S13.

Then, in S14, it is judged whether or not the cleaning has been performed the set number of times.
When the steps 7 to S13 are executed and completed, the nozzle portion 15 is finally driven upward, and suction to the next well 12 is performed.

The number of times of cleaning may be set as appropriate depending on the properties of the sample, required accuracy, and the like.

According to the above-mentioned suction method, unnecessary sample existing near the edge of the bottom surface of the well can be sucked efficiently. At that time, it is not necessary to unnecessarily increase the suction pressure, and it is possible to prevent the reaction product film formed on the inner surface of the well from being adversely affected.

In the above embodiment, two suction nozzles are used.
However, it may be three or more. When the three suction nozzles are arranged, they can be arranged in a triangular shape.

The present invention can be applied to microplates other than the reagent-coated microplate.

[0044]

As described above, according to the suction method of the present invention, unnecessary sample existing near the edge of the well bottom surface can be efficiently sucked, and the suction pressure needs to be increased unnecessarily. In addition, it is possible to prevent the reaction product film formed on the inner surface of the well from being adversely affected.

In the horizontal moving step, if the suction nozzle is moved along the vicinity of the side wall of the well, the suction effect can be further enhanced, and if a plurality of suction nozzles are moved horizontally,
Efficient suction removal can be performed with a simple structure.

[Brief description of drawings]

FIG. 1 is a principle explanatory view showing the principle of the present invention.

FIG. 2 is an explanatory diagram showing the overall configuration of a suction device according to the present invention.

FIG. 3 is an explanatory diagram showing a movement path of a nozzle unit 15.

FIG. 4 is a diagram for explaining a suction action by two suction nozzles.

FIG. 5 is a diagram showing a modified example of the moving path of the suction nozzle.

FIG. 6 is a flowchart showing a suction method according to the present invention.

FIG. 7 is an explanatory view showing a conventional suction device.

FIG. 8 is a diagram showing an operation of a conventional suction device.

[Explanation of symbols]

 10 Micro Plate 12 Well 14 Suction Nozzle 15 Nozzle Section 16 Discharge Nozzle 18 Drive Section 20 Control Section 22 Suction Pump 24 Cleaning Solution Supply Device

Claims (5)

[Claims] 1. A method of sucking a sample placed in a well of a microplate by a suction nozzle, wherein the suction nozzle is vertically lowered with respect to the microplate while performing suction, and a tip of the suction nozzle is in the well. And a horizontal movement step of moving the tip of the suction nozzle along the bottom surface of the well along a predetermined path in the well while performing suction; and An ascending step of vertically elevating the nozzle and pulling out the tip of the suction nozzle from inside the well. 2. The method for suctioning a microplate according to claim 1, wherein after the sample is sucked, a washing solution is injected into the well and the horizontal moving step is performed again. 3. The suction method for a microplate according to claim 1, wherein, in the horizontal movement step, the suction nozzle is moved along a vicinity of a side wall in a well. 4. The method according to claim 1, wherein a plurality of the suction nozzles are arranged side by side, and in the horizontal moving step, the plurality of nozzles are moved in a direction orthogonal to a suction nozzle arrangement direction. Suction method for microplates. 5. An apparatus for sucking a sample contained in a well of a microplate by a suction nozzle, wherein a plurality of suction nozzles are arranged side by side to suck the sample, and the plurality of suction nozzles are moved. A nozzle drive unit, and means for controlling the movement of the plurality of suction nozzles via the nozzle drive unit, wherein each suction nozzle tip is placed on the bottom surface of the well with each suction nozzle tip placed in the well. A microplate suction device comprising: a movement control section that controls movement along a predetermined path.