JPH0332025B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a dispensing method suitable for use in an automatic dispensing device of a biochemical analyzer, for example, and particularly to a dispensing method that improves dispensing accuracy. Figure 1 is an automatic dispensing device that aspirates a fixed amount of sample or reagent from the tip of a nozzle, and discharges the aspirated sample or reagent together with several times the amount of diluted liquid from the nozzle tip into a reaction container. and those shown in FIG. In Figure 1, tank 1
The diluent 2 is stored in the container. A pipe 4 is provided to guide this diluted liquid 2 to the nozzle 3 via valves A and B, and a cleaning syringe 5 is inserted between valve A and valve B of this pipe 4, and between valve B and nozzle 3. A syringe 6 for dispensing a sample or reagent is connected between and. The nozzle 3 is held via an arm 8 by a nozzle transfer device 7 as shown in FIG. It is adapted to be transferred onto a container 10, a sample or reagent container 11. The dispensing method of the automatic dispensing apparatus having such a configuration is shown in Table 1.

【table】

[Table] That is, in step 1, the cleaning syringe 5 is put into the suction state with valve A opened and valve B closed.
The diluent 2 inside is aspirated into the cleaning syringe 5. During this time, the nozzle 3 can be in any position.
The dispensing syringe 6 has stopped its operation. In step 2, the nozzle 3 is transferred into the cleaning container 10,
Valve A is closed, valve B is opened, cleaning syringe 5 is discharged, dispensing syringe 6 is suctioned, and diluted liquid 2 is discharged from nozzle 3 into cleaning container 10 to clean the inner wall of the nozzle. Further, the diluent 2 is sucked into the dispensing syringe 6 for later steps. In step 3, the nozzle 3 is transferred into the sample or reagent container 11, valves A and B are closed, the dispensing syringe 6 is placed in the suction state, and a predetermined amount of the sample or reagent is aspirated.
The cleaning syringe 5 has stopped its operation. Next, in step 4, the nozzle 3 is transferred onto a predetermined reaction container, the dispensing syringe 6 is discharged with valves A and B closed, and the sample or reagent aspirated in the previous step is transferred to the reaction container 17. Dispensing is performed by discharging a predetermined amount of the diluent. The above steps constitute one cycle, and a desired dispensing operation can be performed by repeating the necessary cycles depending on the type of sample, the number of reaction vessels, etc. In addition, some automatic dispensing apparatuses, such as the one shown in FIG. 2, are equipped with a separate tank for the diluent to be discharged into the reaction vessel. Piping 4 is provided to guide diluted liquid 2 from tank 1 to nozzle 3 via valves A and B, and a cleaning syringe 5 is connected between these valves A and B. Further, a diluent 12 to be discharged together with the sample or reagent into the reaction container 9 is stored in another tank 13, and this diluent 12 is connected to the pipe 4 via a pipe 14 via valves C and D. Further, a dispensing syringe 6 is connected between valves C and D. The dispensing method of the automatic dispensing apparatus having such a configuration is shown in Table 2.

[Table] That is, in step 1, valve A is opened and valve B is closed to put the cleaning syringe 5 into the suction state, and the diluent 2 is suctioned into the syringe 5. Further, the valve C is opened and the valve D is closed to put the dispensing syringe 6 into a suction state, and the diluted liquid 12 is also suctioned into the syringe 6. During this time, the nozzle 3 may be positioned anywhere. In step 2, the nozzle 3 is transferred into the cleaning container 10, valves A, D, and C are closed, valve B is opened, and the cleaning syringe 5 is
is in the discharge state, and the diluent 2 is discharged into the cleaning container 10 to clean the inner wall of the nozzle 3. The dispensing syringe 6 has stopped its operation. In step 3, the nozzle 3 is transferred into the sample or reagent container 11, valves A, B, and C are closed, valve D is opened, and the dispensing syringe 6 is put into the suction state to aspirate a predetermined amount of the sample or reagent. During this time, the cleaning syringe 5 has stopped its operation. Next, in step 4, the nozzle 3 is connected to the reaction vessel 9.
Then, valves A, B, and C are closed, and valve D is opened to put the syringe 6 into the discharge state and discharge a predetermined amount of the previously aspirated sample or reagent and diluent into the reaction container 9. Through the above steps, 1st dispensing operation is completed.
A cycle is constructed and can be repeated as needed. Further, as an example of the nozzle transfer device of this device, the one shown in FIG. 3 can be used. Figure 4 A, B, C and D are similar to Figures 1 and 2.
FIG. 2 is an enlarged vertical cross-sectional view of the tip of the dispensing nozzle shown in the figure. Figure 4A shows the state after cleaning the inner wall of the nozzle 3 with diluent 2, and Tables 1 and 2
This corresponds to the end of step 2 in . At the tip of the nozzle 3, there is an air layer 15 that naturally occurs when cleaning with the diluted liquid stops, and its volume is expressed as V ₁
shall be. FIG. 4B shows a state in which the sample or reagent 16 is sucked after cleaning the inner wall of the nozzle 3, which corresponds to the end of step 3 in Tables 1 and 2. The volume of this aspirated sample or reagent 16 is defined as _V2 . Next, FIG. 4C shows the state after a diluted solution several times the amount of the sample or reagent is discharged together with the sample or reagent sucked onto the reaction vessel 9, and is equivalent to the end of step 4 in Tables 1 and 2. At the tip of the nozzle 3, there is an air layer 17 that naturally occurs after the diluent is discharged, and its volume is defined as _V3 . The volumes of the air layers 15 and 17 generated when the diluent is discharged from the tips of these nozzles 3 vary depending on the state in which the discharge of the diluent is stopped. That is, if the discharge is suddenly stopped from a high discharge speed, an air layer with a large capacity is generated, and when the discharge is suddenly stopped from a small discharge speed, a small air layer is generated. Also, if the discharge speed before stopping discharge is too low,
As shown in FIG. 4D, no air layer is generated, and a droplet is left attached to the tip of the nozzle 3. However, as mentioned above, when dispensing using two syringes with different discharge speeds, the air layer volume V ₁ before aspirating the sample or reagent and the air layer volume after discharging the diluent along with the sample or reagent. V ₃ is generally different. Therefore, even if the diluent is accurately discharged with the dispensing syringe 6, an extra amount of diluent corresponding to V ₃ - _{V 1} will be dispensed and dispensed, which is not the same as the amount of sample or reagent. There was a drawback that the amount of diluent to be used was not accurate. In order to eliminate this drawback, in the automatic dispensing device shown in FIG. Later, the inner wall of the nozzle may be washed with the diluted liquid sucked into the dispensing syringe 6, but if the diluted liquid level in the tank 1 is below the nozzle, air may be sucked from the nozzle side. If the level of the diluted liquid in the tank 1 becomes equal to or higher than the position of the nozzle, the diluted liquid will flow out from the tip of the nozzle regardless of the operation of the syringe 6. I can't. Furthermore, it is conceivable to discharge the diluted liquid together with the sample or reagent using the cleaning syringe 5, but since the syringe 5 is generally large in size, it is not suitable for accurately discharging a minute flow rate. An object of the present invention is to eliminate the above-mentioned drawbacks and provide a dispensing method suitable for improving the dispensing accuracy of an automatic dispensing device that dispenses a predetermined amount of a sample or reagent together with a predetermined amount of diluent. It is in. The present invention involves sucking a sample or reagent into a nozzle using a sample or reagent dispensing syringe, then dispensing the sample or reagent together with a diluent into a predetermined reaction container, and then dispensing the sample or reagent. The cleaning dispensing syringe has a faster discharge speed than the nozzle tip of the cleaning syringe.
In a dispensing method in which the diluted liquid is discharged as a cleaning liquid through the nozzle to clean the inner wall of the nozzle, the diluted liquid is discharged as a cleaning liquid by a cleaning dispensing syringe, and Or, before aspirating the reagent, the diluent is aspirated into the nozzle by the sample or reagent dispensing syringe at the same discharge speed from the nozzle tip as when dispensing the sample or reagent into the reaction container. By discharging a portion of the sample or reagent, an air layer having the same volume as the air layer formed at the nozzle tip when dispensing the sample or reagent is completed is formed at the nozzle tip. The present invention will be described in detail below with reference to the drawings and operation tables. As the automatic dispensing apparatus used in the dispensing method of the present invention, for example, those shown in FIGS. 1 and 2 can be used, and since the configurations thereof are the same, only the operation will be described below. Table 3 is an operation table when the dispensing method according to the present invention is applied to the automatic dispensing apparatus shown in FIG.

[Table] That is, in step 1, valve A is opened, valve B is closed, the cleaning syringe 5 is in the suction state, and the tank 1 is
The diluent 2 inside is aspirated into the cleaning syringe 5. During this time, the nozzle 3 can be in any position.
The dispensing syringe 6 has stopped its operation. In step 2, the nozzle 3 is transferred into the cleaning container 10, valve A is closed, valve B is opened, the cleaning syringe 5 is in the discharge state, the dispensing syringe 6 is in the suction state, and the diluted liquid 2 is washed from the nozzle 3. The inner wall of the nozzle 3 is cleaned by discharging it into the container 10. At the same time, the dispensing syringe 6 is set to the suction state for the later process, and the washing syringe 5 is
Aspirate the diluted liquid 2 discharged by. The amount of diluent sucked here is in addition to the predetermined amount of diluent that will be later discharged into the reaction container 9 together with the sample or reagent, and the amount that will be further discharged into the cleaning liquid 10 after cleaning the inner wall of the nozzle 3 in the next step. (Hereinafter referred to as the amount discharged after cleaning.)
This is the amount including the diluted solution. Next, when or just before the discharge state of the cleaning syringe 5 ends, valves A and B are closed, the dispensing syringe 6 is brought into the discharge state, and a predetermined amount of the diluent in the syringe 6 is dispensed. The remainder is discharged from the nozzle 3 after cleaning. When this discharge is finished, the discharge by the cleaning syringe 5 must be completed and the diluted liquid is discharged from the nozzle 3 only by the dispensing syringe 6. Therefore, the volume V ₁ of the air layer formed at the tip of the nozzle 3 is determined only by the dispensing syringe 6, so it is an accurate value every time. Next, in step 3, the nozzle 3 is transferred into the sample or reagent container 11, valves A and B are closed, the dispensing syringe 6 is placed in the suction state, and a predetermined amount of the sample or reagent is aspirated.
The cleaning syringe 5 has stopped its operation. Next, in step 4, the nozzle 3 is transferred onto a predetermined reaction container 9, and the dispensing syringe 6 is moved with valves A and B closed.
is in a discharged state, and the sample or reagent aspirated in the previous step and a predetermined amount of diluent remaining in the dispensing syringe 6 are discharged into the reaction vessel 17 for dispensing. Therefore, the volume V ₃ of the air layer formed at the tip of the nozzle 3 at this time is also determined only by the dispensing syringe 6. The above steps constitute one cycle, and by repeating the cycle as many times as necessary depending on the type of sample, the number of reaction vessels, etc., a desired dispensing operation can be performed. Therefore, the air layer volume V ₁ before sample or reagent suction can be made equal to the air layer volume V ₃ after discharging the diluent into the reaction container. Moreover, according to such a dispensing method, there is no need to provide a separate valve or the like between the dispensing syringe 6 and the nozzle 3.
The configuration can be simplified and the dispensing accuracy can be improved. Table 4 is an operation table when the dispensing method according to the present invention is applied to the automatic dispensing apparatus shown in FIG.

[Table] That is, in step 1, valve A is opened and valve B is closed to put the cleaning syringe 5 in a suction state, and the diluent 2 is sucked into the syringe 5. Further, the valve C is opened and the valve D is closed to put the dispensing syringe 6 into a suction state, and the diluted liquid 12 is suctioned into the syringe 6. The amount of the diluted liquid sucked here is the predetermined amount of the diluted liquid that is later discharged into the reaction container 9 together with the sample or reagent, and the amount that is further discharged into the cleaning container 10 after cleaning the inner wall of the nozzle 3 in the next step (after cleaning is completed). This is the amount including the diluted liquid (discharged portion). During this time, the nozzle 3 may be positioned anywhere. In step 2, the nozzle 3 is transferred into the cleaning container 10, valves A, D, and C are closed, and valve B is opened.
With the cleaning syringe 5 in the discharge state, the diluent 2 is discharged into the cleaning container 10 to clean the inner wall of the nozzle 3. At this time, the dispensing syringe 6 closes the valve C and opens the valve D when the discharging state of the cleaning syringe 5, which has stopped its operation, ends or immediately before the discharging state ends. Syringe 6
A predetermined amount of the diluent in the diluent is left behind and the discharged amount after cleaning is discharged from the nozzle 3 through the pipes 14 and 4. When this discharge is finished, it is ensured that the discharge by the cleaning syringe 5 has been completed and the diluted liquid is being discharged from the nozzle only by the dispensing syringe 6. Therefore, the volume V ₁ of the air layer formed at the tip of the nozzle 3 is determined only by the dispensing syringe 6. In step 3, the nozzle 3 is transferred into the sample or reagent container 11, valves A, B, and C are closed, valve D is opened, and the dispensing syringe 6 is put into the suction state to aspirate a predetermined amount of the sample or reagent. During this time, the cleaning syringe 5 has stopped its operation. Next, in step 4, the nozzle 3 is transferred onto the reaction vessel 9, valves A, B, and C are closed, and while valve D is left open, the dispensing syringe 6 is set to the discharge state and the sample or reagent aspirated earlier is removed. A predetermined amount of the diluent remaining in the dispensing syringe 6 is discharged into the reaction container 9 for dispensing. Therefore, the volume V ₃ of the air layer formed at the tip of the nozzle 3 at this time is also determined only by the dispensing syringe 6. The above steps constitute one cycle of dispensing operation, and this cycle can be repeated as necessary. Therefore, the air volume V ₁ before sample or reagent suction can be made equal to the air layer volume V ₃ after discharging the diluent into the reaction container. FIG. 5 is a diagram showing the configuration of still another example of an automatic dispensing device to which the dispensing method according to the present invention is applied, and Table 5 is an operation table thereof. Components similar to those in FIG. 1 are denoted by the same reference numerals, and descriptions of similar structures and operations will be omitted, and descriptions similar to those in Table 3 will also be omitted. A valve E is provided in the pipe 4 between the dispensing syringe 6 and the nozzle 3. Table 5 shows the dispensing method according to the present invention using the automatic dispensing apparatus having such a configuration.

[Table] That is, in step 1-1, with valve A open and valve B and valve E closed, the cleaning syringe 5 is put into the suction state, and the diluted liquid 2 in the tank 1 is sucked into the cleaning syringe 5. In step 1-2, valve A and valve B are opened while valve E is closed to put the dispensing syringe 6 into a suction state, and the diluted liquid 2 is aspirated into the dispensing syringe 6.
The amount of the diluted liquid sucked here is determined by adding a predetermined amount of the diluted liquid to be discharged into the reaction container 9 together with the sample or reagent later, and a predetermined amount of the diluted liquid to be further discharged into the cleaning container 10 after cleaning the inner wall of the nozzle 3 in the next step. This is the amount plus the quantity. During this time, the dispensing syringe 5 has stopped its operation. The operations of Step 1-1 and Step 1-2 are independent, and their order may be changed, or they may be performed simultaneously with valve E closed.
Next, in step 2, the nozzle 3 is transferred into the cleaning container 10, valve A is closed, valve B and valve E are opened, and the cleaning syringe 5 is put into the discharge state, and the diluted liquid 2 is discharged from the nozzle 3 into the cleaning container 10. Clean the inner wall of the nozzle.
Next, when or just before the discharge state of the syringe 5 ends, valves A and B are closed, valve E is opened, and the dispensing syringe 6 is brought into the discharge state, and a predetermined amount of the diluted liquid from the diluted liquid in the syringe 6 is The amount left after cleaning is discharged from the nozzle 3. When this discharge is finished, the discharge by the cleaning syringe 5 must be completed and the diluted liquid is discharged from the nozzle 3 only by the dispensing syringe 6. Therefore, the volume V ₁ of the air layer formed at the tip of the nozzle 3 is determined only by the dispensing syringe 6. In the following steps 3 and 4, valve E remains open and is similar to steps 3 and 4 in Table 3 above, respectively. According to such a dispensing method, the diluent 2 in the tank 1 can be directly aspirated with the dispensing syringe 6 without suctioning air from the tip of the nozzle 3. As is clear from the above explanation, according to the dispensing method according to the present invention, after discharging a large amount of diluted liquid using a cleaning syringe and cleaning the inner wall of the nozzle,
Since the dispensing syringe discharges a small amount of diluted liquid to finish cleaning, the volume of the air layer created at the nozzle tip is equal to that before suctioning the sample or reagent and after discharging the sample or reagent and diluted liquid into the reaction container. It is possible to improve the dispensing accuracy of the diluted liquid. Note that the automatic dispensing device to which the dispensing method of the present invention is applied is not limited to the above-mentioned example;
Many variations or modifications are possible. For example, the air layer that naturally occurs in the nozzle is created by a dispensing syringe, and cleaning syringes do not need a function to naturally generate an air layer, so an inexpensive syringe drive mechanism (for example, a drive mechanism using an eccentric cam) is used. )
can be used. Furthermore, the discharge of the diluent for cleaning is not limited to a syringe, and an inexpensive pump (for example, a bellows pump, a diaphragm pump, etc.) may be used. There is also a dispensing device that uses a dispensing syringe to intentionally create an air layer after cleaning the inner wall of the nozzle, sucks in the sample, and separates the diluent from the sample; in this case, the diluent is discharged into the reaction container. The dispensing method according to the present invention can be applied as is, by simply discharging an amount corresponding to the capacity of the intentionally created air layer.

[Brief explanation of drawings]

FIG. 1 is a diagram showing the configuration of an example of an automatic dispensing device used in the conventional dispensing method and the present invention, and FIG. 2 is a diagram showing another automatic dispensing device used in the conventional dispensing method and the present dispensing method. Diagram showing example configuration, 3rd
The figure is a diagram showing the configuration of an example of the nozzle transfer device shown in Figs. 1 and 2, and Figs. 4A to 4D are longitudinal cross-sections showing enlarged nozzle tip portions shown in Figs. 1 and 2. 5 are diagrams showing the configuration of still another example of an automatic dispensing device using the dispensing method according to the present invention. 1... Tank, 2... Diluent, 3... Nozzle,
5... Dilution syringe, 6... Dispensing syringe,
9... Reaction container, 10... Washing container, 11... Sample or reagent container, 12... Diluent, A, B,
C, D, E... Valve, 13... Tank, 15, 17
...air layer.

Claims (1)

[Claims] 1. After aspirating the sample or reagent into the nozzle using the sample or reagent dispensing syringe, dispense the sample or reagent together with the diluent into a predetermined reaction container, and then use the sample or reagent dispensing syringe A dispensing method in which the diluted liquid is discharged as a cleaning liquid through the nozzle to clean the inner wall of the nozzle using a cleaning dispensing syringe having a discharge speed higher than the discharge speed from the nozzle tip, Dispensing the sample or reagent into the reaction container using the sample or reagent dispensing syringe after discharging the diluted liquid as a cleaning solution using the dispensing syringe and before aspirating the sample or reagent. By discharging a portion of the diluted liquid that has been sucked into the nozzle at the same discharge speed from the nozzle tip, the same air layer is formed at the nozzle tip at the end of sample or reagent dispensing. A dispensing method characterized by forming a volumetric air layer.