JPS6345069B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a dispensing method suitable for use in sample dispensing devices and reagent dispensing devices used in automatic analyzers that quantitatively analyze predetermined components in samples such as blood and urine. It is related to.

Automated analyzers with various configurations have been proposed in the past, but in general, samples such as blood are sequentially transported by a sampler, and are intermittently transported along a predetermined path by a sample dispensing device. At the same time, the sample and reagent are reacted by dispensing a fixed amount of reagent according to the measurement item into the reaction tube using a reagent dispensing device, and the absorbance of the reaction solution is measured. A discrete method is used to measure and quantitatively analyze the measured items. Such automatic analyzers are generally constructed so that multiple analysis items can be analyzed, and accordingly, reagents used for each analysis item can be set at the same time. In this case, it is possible to provide a separate dispensing device for each reagent, but this makes the device expensive, large and complex, so in recent years, reagent dispensing devices have been used in the same way as sample dispensing devices. In addition, a single dispensing device is configured to discretely dispense a plurality of different reagents. In this way, when dispensing multiple types of samples or reagents discretely using one dispensing device, in order to prevent contamination, the tip of the probe is generally filled with diluent, and then the air is removed first. After aspirating, a predetermined amount of the required liquid (for example, a sample) is aspirated, and the sample adhering to the inner wall of the probe is peeled off at the interface between the air layer and the diluent, while the aspirated sample is discharged together with a predetermined amount of the diluent. There is. However, in this case, the ratio of the amount of sample discharged to the amount of sample aspirated changes depending on the discharge flow rate, as shown in Figure 1, and when the discharge flow rate is increased, the diluted liquid flows inside the probe 1 as shown in Figure 2A. The air layer 4 formed between the probe 2 and the sample 3 is collapsed, and the sample 3 attached to the inner wall of the probe 1 is not sufficiently peeled off.
The sample 3 remains attached to the inner wall of the probe 1 and is discharged from the tip of the probe 1 together with the diluent 2. As a result, as shown in FIG. 2B, the sample 3 remains on the inner wall of the probe 1 and the discharge rate decreases. This tendency becomes more pronounced as the viscosity of the sample increases. In this way, if the aspirated sample 3 remains on the inner wall of the probe 1, it will not be possible to dispense the desired amount, and it will cause contamination with the next aspirated sample, which will have a negative impact on the accuracy of analysis. Become. In order to solve this drawback, it may be possible to slow down the discharge flow rate, but this would result in a long discharge time, which would slow down the analysis processing speed, as well as make it difficult for water to drain at the tip of the probe, resulting in poor reproducibility. , the dispensing accuracy will be reduced. The characteristic curve shown in FIG. 1 was measured under conditions of a diluent (discharge amount) of 400 μ, an air layer of 5 μ, and a sample suction amount (sample viscosity of 24.8 centistokes) of 100 μ.

As a dispensing method that eliminates the various drawbacks mentioned above, after discharging the aspirated sample into the probe through an air layer, for example, the piston of a syringe pump is reciprocated, and the interface between the diluent and air is removed within the probe. It is conceivable to clean the inner wall of the probe by reciprocating the probe a plurality of times and then discharge a predetermined amount of the diluent. In this way, the sample remaining on the inner wall of the probe after the sample is discharged can be effectively peeled off by the reciprocating movement of the interface between the diluent and the air. However, in this case, it is difficult to control the diluent to move back and forth multiple times within the probe, and the dispensing operation takes a long time, resulting in a reduction in the analysis processing speed. In addition, when the diluent is reciprocated, the sample peeled off from the inner wall of the probe may enter the upstream side of the diluent inside the probe, and air bubbles may be generated within the diluent, causing contamination. In addition, there is a risk that the dispensing accuracy of the diluent may be adversely affected.

The object of the present invention is to eliminate the various drawbacks mentioned above,
To provide a dispensing method capable of dispensing a liquid to be aspirated and discharged with high precision and speed, even if the liquid is highly viscous, without causing contamination.

The dispensing method of the present invention involves sucking a predetermined amount of the second liquid into the probe, which has previously contained the first liquid with an air layer left at the tip, through the air layer. When discharging the liquid together with a predetermined amount of the first liquid, the flow rate until substantially all of the second liquid sucked through the air layer is discharged is lower than the discharge flow rate of the first liquid to be discharged thereafter. It is characterized by:

The present invention will be described in detail below with reference to the drawings.

FIG. 3 shows the configuration of an example of a dispensing device for carrying out the dispensing method of the present invention. This dispensing device is configured as a sample dispensing device for an automatic analyzer, and is used to collect the sample liquid (second liquid) 1 in the sample container 11.
2 into the diluent (first
dilute with liquid) 14 at a predetermined ratio and add to reaction tube 15.
It is to be dispensed within. An on-off valve 17, a syringe pump 18, and a probe 16 that can be raised and lowered at a sample liquid 12 suction position and moved to a position where a predetermined amount of the sample liquid 12 that has been sucked is discharged into a reaction tube 15 together with a predetermined amount of diluent 14. It is connected to the diluent container 13 via an on-off valve 19. In this example, the piston 20 of the syringe pump 18 is connected to a reversible motor 21 via a power transmission mechanism such as a pinion-rack mechanism (not shown), and the piston 20 is reciprocated by the rotation of this motor, and the sample liquid 12 and diluent During the discharge process of 14, sample liquid 1
The rotational speed of the motor 21, that is, the pushing speed of the piston 20, is controlled by the control circuit 22 via the motor drive circuit 23 so that the flow rate until almost all of the diluent 2 is discharged is slower than the discharge flow rate of the diluent 14 that is subsequently discharged. Configure to control.

An example of the operation of the dispensing apparatus of this embodiment will be described below with reference to the time chart shown in FIG.
In this example, the dispensing period is 7 seconds, and the flow path from the diluent container 13 to the tip of the probe 16 is filled with the diluent 14. First, the on-off valve 17 is closed, the on-off valve 19 is opened, the motor 21 is driven for a predetermined time, its output shaft is rotated in a predetermined direction, the piston 20 is lowered, and a predetermined amount of diluent 14 is pumped into the syringe pump 18. suction inside. Next, with the tip of the probe 16 positioned in the air, open/close valve 1
7 is opened, the on-off valve 19 is closed, and the motor 21 is slightly driven so that its output shaft rotates in the same direction as described above to suck air from the probe 16 and form an air layer at its tip. Thereafter, with the tip of the probe 16 immersed in the sample liquid 12 in the sample container 11, the motor 21 is driven for a predetermined period of time, and its output shaft is rotated in the same direction as described above to place the sample liquid 12. Aspirate a fixed amount. Next, after placing the tip of the probe 16 facing the opening of the reaction tube 15, the motor 21 is driven, its output shaft is rotated in the opposite direction to the above, and the piston 20 is raised to raise the predetermined amount of the aspirated amount. The diluent 14, the air layer, and the sample liquid 12 are discharged into the reaction tube 15, but in this discharge process, almost all of the sample liquid 12, in this example, the sample liquid 12, the air layer, and a part of the diluent 14 are exposed to the probe. 16, the control circuit 22 controls the rotation speed of the motor 21 via the motor drive circuit 23 so that the pushing speed of the piston 20, that is, the discharge flow velocity is relatively slow, and thereafter the discharge flow velocity is relatively slow. The remaining diluent 14 is discharged into the reaction tube 15 by controlling the rotation speed of the motor 21 so as to increase the rotation speed. In order to switch the discharge flow rate during the discharge process as described above, the position at which the piston 20 discharges the sample liquid, the air layer, and a part of the diluted liquid can be detected and the switching timing can be determined, or the motor 21 can be used as a pulse generator. When using a motor, count the number of pulses,
When the count value reaches a predetermined value, that is, a value corresponding to a portion of the diluted liquid being ejected, various methods can be adopted, such as increasing the frequency of the drive pulse.

Thereafter, by repeating the above-described sequential operations, successive sample solutions are diluted and dispensed into successive reaction tubes.

According to the embodiment described above, the diluent 14 and the sample liquid 1 are mixed in the probe 16 as shown in FIG. 5A.
Since the air layer 24 formed between the diluent 14 and the diluent 14 has a slow discharge flow rate until a part of the diluent 14 is discharged, the air layer 24 is discharged without collapsing as shown in FIGS. 5B and 5C. Therefore, even if the sample liquid 12 is highly viscous, the sample liquid 12 adhering to the inner wall of the probe 16 is effectively peeled off at the interface between the diluting liquid 14 and the air layer 24. Can be dispensed with high precision. Furthermore, since the diluent 14 is discharged at a relatively high flow rate after the sample liquid 12 is discharged, the water from the diluent 14 drains well at the tip of the probe 16, and the inner wall of the probe 16 is effectively cleaned, thereby preventing contamination. nation can also be effectively prevented. Furthermore, after discharging the sample liquid 12, diluted liquid 1
4 is not reciprocated within the probe 16, air bubbles do not enter the diluent within the probe 16, and therefore the diluent 14 can be dispensed with high precision and is easily controlled. Moreover, since the dispensing time is short, the analysis processing speed can be accelerated.

If it is difficult to change the flow rate instantaneously during the dispensing process, as shown in the time chart in Figure 6, after discharging almost all of the sample liquid, the piston is temporarily stopped and the dispensing flow rate is changed. After performing the switching operation, the remaining discharge steps may be performed.

The present invention is not limited to the above-mentioned examples, but can be modified or modified in many ways. For example, as a means for switching the discharge flow rate, the motor 21
It is also possible to interpose a gear between the motor 21 and the piston, and change the gear ratio at a predetermined timing to change the discharge flow rate.If a DC motor is used as the motor 21, the drive voltage can be changed to change the discharge flow rate. Flow rate can be changed. Also, piston 20
When the reciprocating motion is performed using pneumatic pressure or hydraulic pressure, the discharge flow rate can be controlled by controlling the driving pressure. Furthermore, in the embodiments described above,
The dispensing method of the present invention was adopted in a dispensing device configured with one syringe pump 18, but the syringe pump for aspirating and discharging the diluted liquid, and the syringe pump for aspirating and discharging the sample liquid and air layer are used. The present invention can also be effectively applied to a dispensing device configured using the following. Furthermore, the discharge flow rate can be changed to increase the discharge flow rate before a part of the diluent is discharged, that is, from the time when a part of the sample liquid remains or when an air layer is discharged. Effects similar to those described above can be obtained.
Furthermore, in the example described above, the present invention was applied to a sample dispensing device used in an automatic analyzer, but the present invention can also be effectively applied to a reagent dispensing device and various other dispensing devices used other than automatic analyzers. can do.

As explained in detail above, according to the present invention,
Since the discharge flow rate of the liquid sucked through the air layer is made slower than the discharge flow rate of other liquids that are subsequently discharged, it is possible to effectively utilize the peeling effect of the liquid due to the boundary surface of the air layer. Even if the liquid to be sucked is highly viscous, it can be dispensed with high precision and quickly without causing contamination, and the object of the present invention can be effectively achieved.

[Brief explanation of drawings]

Fig. 1 is a diagram showing the discharge ratio of liquid with respect to the discharge flow rate, Fig. 2 A and B are diagrams for explaining the drawbacks of the conventional dispensing method, and Fig. 3 is a diagram showing the dispensing method of the present invention. FIG. 4 is a diagram showing the configuration of an example of the dispensing device; FIG. 4 is a diagram showing a time chart for explaining an example of the operation of the dispensing device shown in FIG. 3; FIG.
Figures A, B, and C are cross-sectional views showing the state of the liquid in the probe in the dispensing device shown in FIG. 3, and FIG. 6 is a cross-sectional view for explaining another example of the operation of the dispensing device shown in FIG. It is a diagram showing a time chart. 11... Sample container, 12... Sample liquid (second liquid), 13... Diluent liquid container, 14... Diluent (first liquid), 15... Reaction tube, 16... Probe,
17, 19...Opening/closing valve, 18...Syringe pump, 20...Piston, 21...Motor, 22...
...Control circuit, 23...Motor drive circuit, 24...
air layer.

Claims (1)

[Claims] 1. A predetermined amount of the second liquid is sucked through the air layer into a probe that has previously contained the first liquid, leaving an air layer at the tip, and this second liquid is mixed into a predetermined amount of the first liquid. When discharging the second liquid together with the liquid, the flow rate until almost all of the second liquid sucked through the air layer is discharged is made slower than the discharge flow rate of the first liquid to be subsequently discharged. Method.