JP3149295B2 - Two-liquid stirring method using a nozzle tip - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention
The present invention relates to an improvement of a liquid stirring method, particularly to a two-liquid stirring method when a diluting liquid is small in a dispenser.

[0002]

2. Description of the Related Art A dispensing apparatus is an apparatus for distributing a liquid sample to a plurality of containers. This liquid sample (hereinafter referred to as specimen)
In general, serum is used, but in order to perform a desired analysis, it is diluted with a diluent before the analysis step, and dispensed into a container for analysis. Examples of such dilution and analysis include a virus test, a drug test, and an antibody test using an immune reaction.

[0003] A sample is aspirated by a nozzle section 32 having a disposable (disposable) tip as shown in FIG. 4, for example.

FIG. 4 is a cross-sectional view of a main part of the nozzle portion 32. The nozzle portion 32 includes a nozzle base 35 and a disposable chip (hereinafter, referred to as a chip) 36 forming a nozzle chip. . Note that this chip 3
The distal end of the nozzle base 35 is press-inserted into the upper opening of the nozzle 6, and the distal end of the nozzle base 35 is fitted into the upper opening of the chip 36 in this manner. A small hole 36a is formed at the lower end of the tip 36, and serum or the like is sucked or discharged from the small hole 36a. The chip 36 is made of a transparent or translucent material, and is mainly made of a translucent hard plastic or the like. The nozzle base 35 is made of metal or the like.

[0005] As described above, when the sample needs to be diluted, the sample is dispensed into a dilution container by the chip 36, mixed with the diluent, stirred, and then analyzed.

Therefore, it is conceivable that after diluting a specimen into a dilution container with the above-mentioned chip 36 and dispensing a diluent with another chip 36, the flow rate of the diluent discharged from the chip 36 depends on the flow rate of the diluent inside the dilution container. Cannot be uniformly stirred with the specimen. In addition, contrary to this step, even if the sample is dispensed after dispensing the diluent, it cannot be stirred uniformly.

[0007] Therefore, as shown in FIG. 5, first, in step 200, the chip 36 discharges the sample 82 sucked into the dilution container 66. Then, in step 201, the chip 36 is raised, and in steps 202 and 203
Thus, a predetermined diluting liquid 84 is jetted from the diluter 80 into the diluting container 66 in a vigorous manner. By this diluent injection,
The sample 82 and the diluent 84 are stirred to obtain a uniformly stirred sample 88.

However, the range in which the above-mentioned method can be uniformly stirred is such that the volume ratio between the specimen 82 and the diluent 84 is about 1:20.
In the case of ~ 50 and the amount of the diluent 84 is small,
For example, when the volume ratio between the sample 82 and the diluent 84 is about 1: 1, uniform stirring cannot be performed by the above method.

The inventors of the present invention have proposed a method for diluting a high-viscosity liquid in which a diluent and a high-viscosity liquid are stirred by sucking and discharging a diluent and a high-viscosity liquid using a chip into which a high-viscosity liquid is dispensed. 260707. That is, in this dilution method, as shown in FIG. 6, in step 212, the chip 36 containing the sample 82 is located above the dilution container 66, and a predetermined amount of the diluent 84 is supplied from the diluent pipette 42 into the dilution container 66. Injected. Then, in step 213, the tip 36 descends from above, and its tip is
4 inside. In step 214, the diluent 84 is sucked into the chip 36 containing the sample 82. Step 2
At 15, the liquid mixture in the chip 36 is discharged into the dilution container 66. In step 216, the sample 82 and the diluent 84
, And Steps 215 and 216 are repeated about five times. Then, in step 217, the chip 36 is raised.

[0010]

However, in the case of the above-mentioned dilution method, the amount of the sample aspirated by the chip must be the required dispensing amount at one time, and the sample aspirated by the same chip is dispensed a plurality of times. Can not.

Further, if the sample aspirated by the same chip is to be dispensed a plurality of times, it is necessary to dispense the diluent into another chip and to perform agitation by discharge and suction. This method has a problem in that the chip consumption is large and the cost is slightly inferior.

The present invention has been made in view of the above-mentioned conventional problems, and has as its object to dispense a plurality of times with the same chip,
In addition, it is an object of the present invention to provide a two-liquid stirring method using a nozzle tip which performs stirring by discharge and suction using the tip.

[0013]

In order to achieve the above object, a two-liquid stirring method using a nozzle tip according to the present invention comprises:
It is as follows. (1) The nozzle tip and the air connected to the nozzle tip
Suction and discharge pons that perform suction and discharge functions via an hose
A dispensing device comprising:
By sucking the air inside the nozzle tip,
Wherein a sample suction step of sucking the first liquid into the nozzle tip, putting the tip of the nozzle tip the first liquid is retained in the inside of the second liquid in the stirring container Te, the required amount of the first liquid A first liquid discharging step of discharging the first liquid, and after the first liquid discharging step ,
While holding the first liquid, the nozzle tip is once raised from the liquid level in the stirring vessel , and the nozzle tip is further raised.
Under the tip from aspirated air, and the air layer forming step of forming an air layer on the tip of the nozzle tip, the residual first liquid
The nozzle tip in which the air layer is formed on the other side is again put into the mixed liquid of the first liquid and the second liquid in the stirring vessel, and first, suction is performed, and then, a discharge step and suction are repeatedly performed. And characterized in that: (2) In the two-liquid stirring method according to the above (1),
The amount of air sucked in the air layer forming step depends on the stirring.
Surplus volume to the stirring volume for the amount of the mixed liquid sucked in the process
Is the amount obtained by adding. (3) The two-liquid stirring method described in the above (1) or (2)
In the sample aspirating step, the nozzle tip
The amount of the first liquid to be sucked is determined by adding the surplus amount to the necessary amount.
And the excess amount is the stirring amount as the remaining first liquid.
In the process, it is held above the air layer
And (4) The two-liquid agitator according to any of (1) to (3) above
In the stirring method, further, the stirring is prepared at the end of the stirring step.
Aspirate the already prepared mixture, and then
Is dispensed.

[0014]

According to the above structure, once raised from the agitation vessel after discharge nozzle tip the required amount of the first liquid, further said nozzle
Since air is sucked from the tip of the nozzle tip and an air layer is formed at the tip of the nozzle tip, a portion of the sucked first liquid is held above the nozzle tip while the space at the tip of the nozzle tip is used to remove the air from the stirring vessel. Aspirates the liquid mixture of the second liquid and the first liquid
It can be discharged and stirred.

Further, the nozzle tip is again put into the mixed liquid of the first liquid and the second liquid in the stirring vessel, suction is first performed, and then discharge and suction are repeatedly performed. While a part of the first liquid is kept at the position where the air layer is formed, the liquid can be stirred at the tip of the nozzle tip. Further, in the air layer forming step, the nozzle chi is provided.
The mixed liquid sucked in the stirring step from the tip of the bottle
The amount of air that was added to the agitation volume for the amount and the excess volume was sucked
In the case, the first liquid left above the air layer in the nozzle tip
Part of the nozzle tip may come into contact with the stirring area at the tip of the nozzle tip.
This can be further suppressed. Further, the sample suction
In the process, the first liquid amount sucked by the nozzle tip is discharged.
By adding the surplus amount to the required discharge amount,
Even if a small amount of the first liquid remains in the nozzle tip,
It is possible to discharge the first liquid with high accuracy. Also before
At the end of the stirring process, pull the prepared mixture
Since dispensing is continued, the nozzle tip can be used effectively.

[0016]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below with reference to the drawings.

FIG. 1 shows an external view of an automatic dispensing apparatus 30 to which a two-liquid stirring method using a nozzle tip according to the present invention is applied, and FIG. 1 is a perspective view thereof.

A nozzle part 32 for aspirating a serum sample, which is illustrated substantially at the center of the figure, is held by an XYZ robot 34, and the nozzle part 32 is movable three-dimensionally. In this embodiment, the nozzle unit 32 shown in FIG. 4 is used.

In FIG. 1, the XYZ robot 34
Are the X drive unit 34x, the Y drive unit 34y, and the Z drive unit 3
An elevator unit 38 having a nozzle unit 32 is connected to the Z drive unit 34z so as to be able to move up and down.
The elevator unit 38 has a limit switch 40 that functions as a jamming sensor or the like. The limit switch 40 detects a certain upward external action force applied to the nozzle unit 32. One end of an air hose 44 is connected to the nozzle section 32, and the other end of the
It is connected to a cylinder 46 that acts as a discharge pump.

Between the cylinder 46 and the nozzle section 32,
Pressure sensor 5 for measuring the internal pressure in air hose 44
4 are connected. Note that a signal from the limit switch 40 is sent to the apparatus main body via the signal cable 56.

Test tube rack 60 placed on dispensing table 58
, A plurality of sample-containing test tubes 62 containing the serum sample after the centrifugation is performed are held upright. Also,
The horizontal table 64 provided on the dispensing table 58 has a dilution container 6
A dilution tray 68 having a plurality of 6 and a reaction container 70 such as a microplate are placed. Here, the reaction container 70 is formed with a plurality of wells that are containers for storing the dispensed and diluted serum.

A new chip is held upright in the chip stand 72, and the dispensed chip 36 is discarded on a chip discard tray 74.

Therefore, according to the above dispensing apparatus, the serum can be sucked by the tip 36 of the nozzle portion 32 and can be freely transferred to another container. Of course, it is also possible to use this dispensing device other than for dispensing serum samples,
Various applications are possible.

Next, an embodiment of a two-liquid stirring method using a nozzle tip used in the above dispensing apparatus will be described.
In the present embodiment, an amount of the sample 82 that can be dispensed a plurality of times is aspirated into the chip 36. And this chip 3
6 dispenses a required amount of the sample 82 into each well of the dilution container 66 into which the dilution solution 84 is injected.

FIGS. 2 and 3 specifically show a dilution and stirring process after the final dispensing.

First, in step 101 ("step" is abbreviated as "S" in the figure), the chip 36 from which the sample 82 has been aspirated is moved by the XYZ robot 34 to the position above the dilution container 66 in which the diluent 84 has been injected in advance. Transport to Here, in the tip 36, in addition to the dispensed amount V _S , the surplus amount V _E
Sample 82 is contained. The surplus amount _VE is a liquid amount in consideration of a small amount of liquid remaining in the chip during normal ejection. Further, the dispensing of the diluent 84 into the dilution container 66 may be performed simultaneously with the dispensing of the specimen 82.

In step 102, the chip 36 is lowered into the dilution container 66. In step 103, the chip 36
The sample 82 of the dispensed amount V _S is discharged into the inside.

[0028] At step 104, switch Tsu and leaving a sample 82 of the excess amount _{V E} in flop 36 raises the tip 36 above the liquid level in the dilution container 66.

In step 105, the air is sucked to form an air layer at the tip of the chip 36. At this time, in addition to the amount of agitation V _D min of air sucked in the next step, aspirating the excess volume V _alpha fraction of air. Contamination Here, by also sucking excess volume V _alpha fraction of air, the excess amount V _E of the specimen 82 remaining in the chip 36 is not in contact with the agitation area of the tip of the chip 36, surplus specimen during agitation during agitation Never do.

In step 106, the agitation amount V _D
+ Excess volume V _α ] and an air layer formed thereon
Is again lowered to the same dilution container 66.

[0031] At step 107, in the chip 36, to a mixture 90 stirred volume V _D min is first aspiration of a specimen 82 which is not yet equalized and the diluent 84. After air layer formation, perform suction earlier, while ensuring the air layer for agitation, the analyte 82 excess amount V _E remaining in the chip 36 is to keep is positioned above the chip 36.

[0032] At step 108, a mixture 90 of the chip 36 is discharged, in step 109, mixture 90 is sucked again stirred amount V _D min. By repeating step 108 and step 109 a plurality of times, the sample 8
2 and the diluent 84 are uniformly stirred to prepare a sample.

In step 110, the sample 88 prepared in step 108 and step 109 is aspirated by the same tip 36 in addition to the dispensed amount V _S 'and the surplus amount V _E '.

In step 111, the tip 36 from which the sample has been sucked is raised, and in step 112, the tip 36 is transported above the reaction vessel 70.
The dispensed amount V _S 'is discharged from 6.

In step 114, a surplus amount V _E 'remains in the chip 36 because a small amount of liquid remains during the ejection as described above.

Therefore, when dilution accuracy is required,
After the last dispensing, the above-described dilution and stirring step is applied to any one of the dilution containers 66, and the chip 36 is discarded. On the other hand, when the dilution accuracy is not so required, there is no need to consider the influence of the residual sample, so that the above-described dilution and stirring step can be performed every time dispensing.

The two-liquid stirring method according to the present invention described above is not limited to the case where a specimen is diluted with a diluent, but can be widely used as a method for stirring two types of liquids.

In this embodiment, a disposable chip is used. However, the present invention is not limited to this, and can be applied to a fixed chip and the like.

[0039]

As described above, according to the two-liquid stirring method using the nozzle tip according to the present invention, the air required for stirring in the next step and a small excess air are sucked into the nozzle tip. Since an air layer is formed at the tip of the nozzle, a part of the aspirated sample is held above the nozzle tip, and a mixture of the diluent and the sample is sucked and discharged from the dilution container in the space at the tip of the nozzle tip and agitated. can do.

Further, since the mixed liquid of the diluent and the sample is first sucked, and then the discharge and the suction are repeatedly performed, a part of the sucked sample held above the nozzle tip is kept at the position where the air layer is formed. Stirring can be performed at the tip of the tip.

Therefore, when dispensing a plurality of times with the same chip, the diluent and the dispensed sample can be agitated by the chip, and the sample held above the nozzle tip can be mixed with the liquid being stirred. There is no mixing.

In addition, even with a small amount of diluent, it is possible to sufficiently stir uniformly with the sample.

[Brief description of the drawings]

FIG. 1 is an external view showing an embodiment of an automatic dispensing apparatus to which a two-liquid stirring method using a nozzle tip according to the present invention is applied.

FIG. 2 is an explanatory diagram showing a process from ejection of a sample to retraction of an excess sample in a two-liquid stirring process according to the present invention.

FIG. 3 is an explanatory diagram showing a process from a stirring process to a sample dispensing process in a two-liquid stirring process.

FIG. 4 is a cross-sectional view illustrating a cross-sectional view of a main part of a nozzle unit 32.

FIG. 5 is an explanatory view showing a conventional stirring method.

FIG. 6 is an explanatory view showing a conventional dilution method using the same chip.

[Explanation of symbols]

36 Disposable Tip 66 Dilution Vessel 70 Reaction Vessel 82 Sample 84 Diluent 88 Sample 90 Mixture V _S Dispensing Volume V _E Surplus Volume V _D Stir Volume V _α Surplus Volume

──────────────────────────────────────────────────続 き Continued on front page (58) Field surveyed (Int.Cl. ⁷ , DB name) G01N 35/00-35/10

Claims (4)

(57) [Claims] And a nozzle tip which is in contact with said nozzle tip.
Suction that performs suction and discharge operations via an air hose
A discharge pump, the dispensing apparatus having the suction-discharge
The air inside the nozzle tip is sucked by a discharge pump.
Wherein a sample suction step of sucking the first liquid into the nozzle tip, putting the tip of the nozzle tip the first liquid is retained in the inside of the second fluid inside the stirring container, required of the first liquid by the A first liquid discharging step of discharging an amount, and after the first liquid discharging step , the nozzle tip is once raised from a liquid level in the stirring vessel while holding the remaining first liquid , and further, a tip of the nozzle tip It sucks air from the nozzle tip and the air layer forming step of forming an air layer on the tip of, the residual first liquid in the nozzle tip again the stirring vessel in which a air layer is formed under First liquid and second liquid
A two-liquid stirring method using a nozzle tip, comprising: a stirring step in which a liquid is mixed in a liquid, suction is first performed, and then discharge and suction are repeatedly performed. 2. A two-liquid stirring method according to claim 1.
The amount of air sucked in the air layer forming step is
Surplus in the stirring volume for the amount of the mixed liquid sucked in the stirring process
Nozzle tip characterized by adding volume
Two-liquid stirring method. 3. The two-fluid agitator according to claim 1 or 2.
In the stirring method, in the sample suction step, suction is performed on the nozzle tip.
The first liquid amount is the amount obtained by adding the surplus amount to the required amount.
The surplus amount is used as the residual first liquid in the stirring step.
Characterized by being held above the air layer.
A two-liquid stirring method using a nozzle tip. 4. The method according to claim 1, wherein :
In the two-liquid stirring method of the above , further, at the end of the stirring step, a prepared mixture having been prepared by stirring.
Aspirating the liquid and then dispensing the prepared mixture.
A two-liquid stirring method using a nozzle tip.