JPH0640100B2 - Automatic analyzer sample dispensing method - Google Patents

Description

The present invention relates to a sample dispensing method for an automatic analyzer, and particularly to a sample dispensing suitable for accurately dispensing a very small amount of sample such as serum. It is about the method.

[Conventional technology]

As described in JP-A-62-137565, a sample dispensing device in a conventional automatic analyzer is a sample nozzle, a liquid level sensor, a microsyringe connected to the sample nozzle, and a sampling device for driving the sample nozzle. It is composed of a mechanism, a washing tank for the sample nozzle, etc., and the supplement dispensing operation is performed as follows. The supple nozzle is moved into the sample in the sample container, a predetermined amount of sample is sucked into the sample nozzle by the microsyringe, and then the sample nozzle is moved onto the reaction container by the sampling mechanism, and the reaction container is discharged by the microsyringe. Dispense the sample in the sample nozzle inside. After that, the sample nozzle is moved to the cleaning tank, and the inner and outer circumferences of the nozzle are cleaned to wait for the suction of the next sample.

This series of operations is performed in a single machine cycle that is fixed by the device, for example, with a single line and a processing capacity of 60.
In the 0T / h device, the machine cycle is 6 seconds, and the machine cycle is controlled to be completed within this time.

[Problems to be solved by the invention]

In the conventional automatic analyzer, an analysis method is designed such that the sample amount per analysis is, for example, 3 to 20 μ, regardless of the processing capacity of the device, the cycle time, etc., and analysis is performed based on that. The lower limit of this sample amount is 3μ
Is determined as a limit value with which the device can secure the sampling accuracy when the cycle time is 6 seconds, for example, which cannot be measured by the conventional analysis method described above.

1. Analysis using samples of immunological items and urine with high sample concentrations.

2. Even for colorimetric measurement items, the result of analysis under the above-mentioned analysis conditions shows a value that exceeds the measurement range of the device, and the same sample is analyzed again within the measurement range of the device. It is desirable to measure within the measurement range of the device by converting the concentration of the sample to a lower concentration by diluting or reducing the sample amount due to expansion of the application range of the device and higher functionality, and to convert the result into concentration. ing. Of the above two proposals, the former requires a device for diluting the sample in the device, which complicates the device. The latter is 1/3 to 1/5 of the lower limit of the conventional sample amount.
It requires a technical solution to accurately and accurately sample the amount of.

Fig. 5 shows the accuracy and precision of sample dispensing with the conventional device. As can be seen from the figure, both the accuracy and precision are drastically impaired when the sample dispensing amount is below a certain lower limit value. Therefore, in the conventional device, the sample dispensing limit was set with a lower limit at which both of them are stable.

An object of the present invention is to provide a sample of an automatic analyzer capable of realizing highly accurate dispensing for a sample with an extremely small amount even though the number of sample dispensing processes per unit time can be maintained at a high capacity. To provide a dispensing method.

[Means for solving problems]

The present invention, in the sample dispensing method of the automatic analyzer for sucking the sample from the sample container into the sample nozzle at the sample suction position and discharging the sample in the sample nozzle to the reaction container at the sample discharge position, When the injection amount is larger than a predetermined amount, the inner and outer circumferences of the sample nozzle are washed with a washing liquid while the sample nozzle is discharged into the reaction container and the sample nozzle returns from the sample discharge position to the sample suction position. However, when the sample dispensing amount is less than the predetermined amount, the time for sucking the sample into the sample nozzle and the time for discharging from the sample nozzle to the reaction container are set to be smaller than the predetermined amount. Shorter than many,
Moreover, the outer periphery of the sample nozzle before ejecting the aspirated sample is washed with a cleaning liquid, and after the ejection of the sample, the inner periphery and outer periphery of the sample nozzle are also washed so that the sample dispensing amount is larger than a predetermined amount. It is characterized in that the cycle time of the sample dispensing operation is the same when it is large and when it is small. Factors that affect the accuracy and precision of extremely minute sample dispensing include: a. The sample attached to the outer circumference of the sample nozzle during sample suction is pulled and dispensed together when a predetermined amount of sample is dispensed from the nozzle into the reaction vessel. The accuracy is not obtained because the amount is unstable.

B. Scattering of the sample in the nozzle due to the centrifugal force and inertial force of the liquid in the pipe that connects the nozzle and the microsyringe when the sample nozzle moves at high speed and during acceleration / deceleration.

In particular, the influence of the sump attached to the outer circumference of the nozzle in (a) is large. Therefore, in order to ensure the accuracy of sample dispensing, first remove the sample from the outer periphery of the nozzle or remove the adhered sample by some method before dispensing the sample in the nozzle to the reaction vessel. However, sample adhesion at the tip of the nozzle is unavoidable due to the wettability between the sample and the nozzle. On the other hand, with a cycle time of 6 seconds, sample suction, discharge, nozzle cleaning and sample container, reaction container, nozzle cleaning tank There is only time to move the nozzle in between, so it is difficult to shake off the excess sample adhering to the tip of the nozzle during the movement of the nozzle from the sample container to the reaction container. For example, if the moving speed of the nozzle is increased for the sake of caution, the effect of sample scattering will occur. Therefore, providing the time to blow off the sample adhering to the nozzle tip while maintaining the movement speed of the nozzle in a state where it does not affect the sample dispensing accuracy is not accurate in the current sample dispensing method. I can't get it. For example, the operation of the part excluding the sample dispensing microsyringe, the sampling mechanism, the sample nozzle washing tank, etc. relating to the sample dispensing only for the sample dispensing of less than 3 μ is kept as the original time chart operation. The control time chart of each unit described above can be changed by the following method, for example.

a. The time chart is normally designed with the maximum capacity of the device. Therefore, the time chart for sample dispensing also has the maximum dispensing capacity, 20 μm in the above example.
It is made for. Therefore, if the sample dispensed amount is limited to, for example, less than 3 μm, the suction and discharge times can be shortened, whereby the cleaning time of the tip of the sample nozzle can be secured.

b. In the case of (a), if sufficient time for cleaning the nozzle tip is not secured, 2 cycles are used only for dispensing less than 3μ.

[Action]

As described above, the extra time for aspirating and discharging the sample is shortened within the conditions only for the dispensing of a very small amount of the sample beyond the range of the usual analytical method. As a result, high processing capacity can be maintained, and the sample adhering to the outer circumference of the nozzle can be washed out by washing the outer circumference of the nozzle in the nozzle washing tank before the discharge without changing the conditions such as the moving speed and range of the nozzle, the suction and discharge speed of the sample. The dropping time can be secured, and the sample dispensing accuracy can be secured.

〔Example〕

An embodiment of the method of the present invention will be described in detail below with reference to FIGS.

FIG. 1 is a block diagram for explaining an embodiment of the sample dispensing method of the automatic analyzer of the present invention. In FIG. 1, reference numeral 1 is a sample nozzle in which a metal pipe made of stainless steel is squeezed at its tip, and a liquid level sensor 2 is insulated and integrated by a coating tube 3. Reference numeral 4 denotes a sampling arm to which the sample nozzle 1 is attached. Although not shown in the drawing, the sampling arm 4 is configured to be rotatable and vertically movable. Reference numeral 5 denotes a microsyringe, which is configured such that a plunger 5b sealed by a sealing member 5a can be moved up and down. One end of the plunger 5b is made of a flexible material and is connected to the sample nozzle 1 by the pipe nozzle 5c. First solenoid valve 6, water pump 7
Is connected to the water supply tank 8 containing the wash water 8a. Reference numeral 9 denotes a sample disk on which a sample container 10 having a sample injected therein is mounted, and a support mechanism (illustration is possible) for transporting and positioning each sample container 10 at a predetermined position on the rotation of the sample nozzle 1 described above. (Omitted). Reference numeral 11 is a reaction disk, which also has a plurality of rectangular parallelepiped elongated reaction cells 1 on the outer periphery thereof.
A plurality of reaction vessels 12 formed by integrally molding 2a are fixed by a plurality of screws 13. Although not shown in the figure, the reaction disk 11 also sequentially conveys the reaction cells 12a to a predetermined position on the turning trajectory of the sample nozzle 1 by a rotation support mechanism.
It is supported so that it can be positioned. Reference numeral 14 denotes a cleaning tank for the sample nozzle 1, which has a cylindrical shape, of which a portion corresponding to the swirling locus of the sample nozzle 1 is cut open in a V shape or a U shape so as not to hinder its movement.
A nozzle 15 for cleaning the outer periphery of the sample nozzle 1 is fixed so as to face the sample nozzle 1 in the radial direction of the swirl from diagonally above. The cleaning nozzle 15 is piped to the water supply pump 7 via the second electromagnetic valve 16. Reference numeral 17 is a detection circuit for detecting the liquid level of the sample in the sample container 10 by using the liquid level sensor 2 as a positive electrode and the sample nozzle 1 as a negative electrode, and 18 is a micro computer system for controlling the operation of these components described above. Is.

The operation of the sample dispensing device configured as described above will be described with reference to the time chart shown in FIG. FIG. 2 shows the operation of the reaction disk 11 as a reference. The reaction disk 11 is fed one by one in each cycle of the reaction cell 12a such as one rotation + 1 reaction cell or half rotation + 1 reaction cell. Then, a predetermined amount of the sample is dispensed by the sample dispenser having the above configuration into the reaction cell 12a which has been washed and reusable within the stop time, and in the next cycle,
Although not shown, a predetermined amount of reagent is dispensed by the reagent dispensing mechanism on the sample, and the sample is dispensed in a new reaction cell. The sample to which the reagent is added exhibits a color reaction depending on the concentration, and the absorbance is the reaction disk 11
Is measured for each rotation of. In this way, the reaction disk 1
Discontinue analysis by repeating sample dispensing, reagent dispensing, stirring, if necessary, dispensing of the second reagent at a predetermined position, stirring, washing of the reaction cell after the predetermined measurement, etc. . Here, the normal operation of each component in one cycle shown in a to a'of FIG. 2 will be described. Sample nozzle 1 attached to sampling arm 4 at time a
Are located above the sample container 10. From there, the sampling arm 4 starts descending, the liquid level sensor 2 detects the liquid level of the sample, and stops at the position where the tip of the sample nozzle 1 is thrust into the sample by a predetermined amount. Then a
_When the time goes to 1, the sample obtained by adding a certain amount of margin to the predetermined amount of the sample nozzle 1 is sucked by the microsyringe 5. Therefore, the suction time of this sample is set in accordance with the maximum sample dispensing amount in the device specifications as described above. a In ₂ time, is performed Batsukuratsushiyu correction of the feed mechanism of the plunger 5b, reaches the a ₃ point, start the sampling arm 4 is raised, stops at its top dead center. The above operations are performed during rotation of the reaction disk 11, the a ₄ when the rotation is stopped reaction disk 11, the sampling arm 4 starts to move over the sample container 10 on the reaction cell 12a. With its movement is terminated by a ₅ point sampling arm 4 begins to descend into the reaction cell 12a, discharging a sample of predetermined amount thereof microsyringe 5 from a ₆ point of falling halfway operating into a reaction cell 12a Meanwhile, the sample attached to the outer circumference of the sample nozzle 1 is also placed. The discharge time of this sample is also set in accordance with the maximum dispensing amount of the device specifications, like the suction time of the sample described above. After one end of the discharge of the sample, the sample nozzle 1 from a ₇ point increase, starts to move from the reaction cell 12a at a ₈ into the cleaning tank 14. When the sample nozzle 1 comes into the cleaning tank 14, a small amount of the sample remaining in the sample nozzle 1 at the time of a ₉ is discharged and the first solenoid valve 6
The second solenoid valve 16 is opened and the outer circumference of the sample nozzle 1 does not interfere with the next sample. Cleaning is performed by spraying cleaning water on the tip of the sample nozzle 1. At time a ₁₀ when the cleaning is completed, the sample nozzle 1 moves to the sample container 10 and, in order to prevent the thinning of the sample due to the contact between the cleaning water and the sample in the sample nozzle 1, a small amount of air is introduced into the sample nozzle 1. The sample nozzle 1 of a'is again sucked by the microsyringe 5 into the sample container 10
Positioned above to start the next cycle operation. The above description shows the case where the sample dispensing amount is relatively large and the securing and maintaining of the dispensing accuracy is easy. Even in this case, the sample adhered to the outer periphery of the sample nozzle 1 at the time of sucking the sample is the same amount. Although it does not affect the accuracy and precision of injection, for example, as described above, in the device with the cycle time of 6 seconds, the sample suction and discharge speeds, the moving speed of the sample nozzle 1 and the sample nozzle 1 Of
The cleaning time of the outer circumference is close to the limit to maintain its performance and accuracy, and it is impossible to find the time to remove the sample adhering to the tip of the sample nozzle 1 between the suction and the discharge of the sample. Since its ratio to the injection amount is minute, its influence can be ignored, and the sample nozzle 1 described above can be used.
The operation of removing the adhered sample at the tip of was not required.

Next, a device for removing the adhered sample at the tip of the sample nozzle 1 for accurately and accurately performing a smaller amount than the above sample dispensing amount due to the function and performance requirements of the device. The operation will be described with reference to FIG. FIG. 3 shows the operation time for removing the adhered sample by limiting the sample dispensing amount to an extremely small amount. For example, the limiting amount is less than 3 μ, and the maximum amount in the case of FIG. Two
When it is set to 0 μ, the time required for suction and discharge can be shortened to 1/3 to 1/6. Here, a time chart is shown in which the time is reduced by half. Even in this case, the performance as a sample dispensing apparatus, the above-described sample suction and discharge speeds, which affect the securing of accuracy, the moving speed of the sample nozzle 1, the cleaning time of the inside and the outside of the sample nozzle 1, etc. Even if the same as the above, as shown in FIG. 3, while the sampling arm 4 moves from the sample container 10 onto the reaction cell 12a, the sampling arm 4 is stopped on the nozzle cleaning tank 14 and the second solenoid valve 16 is opened. Then, it is possible to provide a time for discharging the cleaning water toward the tip of the sample nozzle 1 by the two cleaning nozzles 15 by the water supply pump 7 and removing the adhered sample.

As is clear from the above description, according to the embodiment of the method of the present invention, in order to secure and maintain the performance and accuracy of a single device, for example, a sample dispensing device, over a wide range of specifications. , A plurality of operating conditions are used according to the amount of the sample dispensed, so that even if the sample dispensed is less than 3 μm, more operation is performed. It is possible to ensure the same accuracy and precision as in the case of the quantity, and the operation control of the apparatus by the dispensed quantity is selected and executed by the micro computer system, so that it can be performed very easily.

FIG. 4 shows a time chart of an example in which the change of the above-mentioned operation control is carried out by designating 2 cycles only for dispensing less than 3 μ. In this case, only the portion related to the sample dispensing operation for 2 cycles is performed. One cycle operation is performed using time, and the reaction disk 11 and the like do not require cycle time change as in the conventional case. 2 for each sample dispense
By specifying the cycle, the processing capacity of the apparatus is reduced only in the limited cycle, but the control of the sample dispensing apparatus is facilitated and the accuracy thereof is facilitated.

〔The invention's effect〕

According to the present invention described above, stable accuracy and precision can be secured and maintained for a wide range of sample dispensing of 1 to 20 μ without deteriorating the processing capacity as an automatic analyzer. A high-concentration sample can be analyzed without providing a sample dilution function, and it can be used in an automatic analyzer to improve its performance and have an economical effect.

[Brief description of drawings]

FIG. 1 is a block diagram for explaining an embodiment of the sample dispensing method of the automatic analyzer of the present invention, and FIG. 2 is a time chart showing the operation control of the constituent elements in the embodiment of FIG.
FIG. 3 is a time chart showing a modified example of the operation control in the section aa ′ in FIG. 2, and FIG. 4 is a bb ″ in FIG.
FIG. 5 is a characteristic chart of sample dispensing by a conventional device, which is a time chart showing a modified example of the operation control in the section. 1 ... Sample nozzle, 2 ... Liquid level sensor, 4 ... Sampling arm, 5 ... Micro syringe, 6, 16 ...
… Solenoid valve, 7… Water pump, 8… Water tank, 9…
… Sample disc, 10 …… Sample container, 11 ……
Reaction disk, 12 ... Reaction container, 12a ... Reaction sensor, 14 ... Nozzle cleaning tank, 15 ... Cleaning nozzle, 18
...... Microcomputer system.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-62-228954 (JP, A) JP-A-58-85168 (JP, A) Actually-opened Sho-58-62267 (JP, U) JP-B-61- 56784 (JP, B2) Actual public Sho 53-12224 (JP, Y2)

Claims (1)

[Claims] 1. A sample dispensing method for an automatic analyzer, which sucks a sample from a sample container into a sample nozzle at a sample suction position and discharges the sample from the sample nozzle into a reaction container at a sample discharge position. When the amount to be dispensed is larger than the predetermined amount,
While the sample is discharged to the reaction container and the sample nozzle returns from the sample discharge position to the sample suction position, the inner and outer circumferences of the sample nozzle are cleaned with a cleaning liquid, and the sample dispensing amount is less than the predetermined amount. Occasionally, the time for sucking the sample into the sample nozzle and the time for discharging the sample from the sample nozzle to the reaction container are shorter than when the sample dispensing amount is larger than the predetermined amount, and the sample is sucked. When the outer circumference of the sample nozzle before discharging the sample is cleaned with a cleaning liquid, and the inner circumference and outer circumference of the sample nozzle are also cleaned after the sample has been discharged, and the sample dispensing amount is larger than the above specified amount. The sample dispensing method of the automatic analyzer is characterized in that the cycle time of the sample dispensing operation when the number is small is the same.