JPH01141357A - Sample partial injection method for automatic analyzing device - Google Patents

Abstract

PURPOSE:To raise the partial injection accuracy at the time of partial injection of a small quantity of samples by controlling the cleaning operation of a sample nozzle after having sucked the sample in accordance with the sample partial injection quantity. CONSTITUTION:First of all, a sample nozzle 1 attached to a sampling arm 4 is moved onto a sample container 10, and thereafter, allowed to descend, and by a microsyringe 5, the prescribed quantity of sample is sucked into the sample nozzle 1. Subsequently, the sample nozzle 1 is moved onto a reaction cell 12a, and the sample is discharged into the reaction cell 12a. Thereafter, the sample nozzle is moved to a cleaning tank 14, and the inside and the outside of the sample nozzle 1 are cleaned by discharging the cleaning water from the sample nozzle 1 and a cleaning nozzle 15. In such a sample partial injection, when the partial injection quantity is small, the time for cleaning the outside surface of the sample nozzle 1 in the cleaning tank 14 between the sample suction and the sample discharge is secured by shortening the time required for sucking and discharging the sample. In such a way, the partial injection accuracy is improved.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a sample dispensing method for an automatic analyzer, and particularly to a sample dispensing method suitable for accurately dispensing extremely small amounts of samples such as serum. It is about the method.

[Conventional technology]

A sample dispensing device in a conventional automatic analyzer includes a sample nozzle, a liquid level sensor, a microsyringe connected to the sample nozzle, and a sampling device that drives the sample nozzle, as described in Japanese Patent Laid-Open No. 137565/1983. It consists of a mechanism, a cleaning tank for the sample nozzle, etc., and the sample dispensing operation is performed as follows. Move the sample nozzle into the sample in the sample container, aspirate a predetermined amount of sample into the sample nozzle using the microsyringe, then move the sample nozzle onto the reaction container using the sampling mechanism, and react with the discharge operation of the microsyringe. Dispense the sample in the sample nozzle into the container. Thereafter, the sample nozzle is transferred to a cleaning tank, the inside and outside of the nozzle are cleaned, and the next sample is sucked.

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

[Problem that the invention seeks to solve]

In conventional automatic analyzers, an analysis method is designed with the amount of sample per one analysis light set to, for example, 3 to 2 μQ, regardless of the processing capacity, cycle time, etc. of the device, and analysis is performed based on this. The lower limit of the sample amount, 3 μQ, was determined as the limit value at which the device can ensure sampling accuracy when the cycle time is, for example, 6 seconds, whereas the conventional analysis method described above cannot measure it. It was possible.

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

2. Even if it is a colorimetric measurement item, the result of analysis under the above 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.

For example, it is desirable to expand the scope of application of the device and improve its functionality, making it possible to lower the concentration of the sample by diluting it or reducing the amount of sample to perform measurements within the measurement range of the device and convert the results into concentration. ing.

Of the above two proposals, the former requires a sample dilution device within the apparatus, making the apparatus complicated. Furthermore, the latter requires a technical solution to accurately and accurately sample an amount that is 1/3 to 115 times smaller than the lower limit of the conventional sample amount.

Figure 5 shows the accuracy of sample dispensing using the conventional device.

Show accuracy. As is not clear from the figure, when the amount of sample dispensed is below a certain lower limit value, both accuracy and precision are rapidly and significantly impaired. Therefore, in the conventional apparatus, the lower limit at which both of these are stable is defined as the sample dispensing limit.

The purpose of the present invention is to add a sample dilution device to a high-throughput device with a cycle time of 6 seconds by accurately and precisely dispensing extremely small amounts of samples with unstable accuracy and precision. An object of the present invention is to provide a sample dispensing method for an automatic analyzer, which allows a highly accurate sample to be analyzed within the measurement range of the device.

[Means for solving problems]

The above purpose is to provide a sample nozzle, a sample nozzle moving mechanism that holds this sample nozzle, moves and positions the sample container, reaction vessel, nozzle cleaning tank, etc. of this sample nozzle, and supplies cleaning water to the sample nozzle. Using a sample dispensing device that is equipped with a microsyringe connected to a pump and configured with the sample nozzle cleaning tank, etc., the operation of the device can be controlled depending on the amount of sample dispensed, regardless of whether it is in operation or not. I made it possible to achieve it by making it possible to choose.

What are the factors that affect the accuracy and precision of dispensing extremely small amounts of samples?

B. When a predetermined amount of sample is dispensed from the nozzle into the reaction vessel, the sample that adheres to the outer periphery of the sample nozzle during sample suction is pulled and dispensed together, and this effect becomes larger as the amount of sample dispensed decreases. , the accuracy is lost, and since the quantity is unstable, precision cannot be obtained.

When the moving speed of the sample nozzle is high or when the sample nozzle is accelerated or decelerated, the sample inside the nozzle scatters due to the centrifugal force and inertial force of the liquid in the piping connecting the nozzle and microsyringe.

Among these, the influence of the sample attached to the outer periphery of the nozzle (a) is particularly large. Therefore, in order to ensure sample dispensing accuracy, it is first necessary to eliminate sample adhesion to the nozzle periphery or remove the adhering sample by some method before dispensing the sample inside the nozzle into the reaction vessel. However, it is difficult to avoid sample adhesion at the nozzle tip due to the wettability between the sample and the nozzle.On the other hand, at a cycle time of 6 seconds, sample adhesion, sample suction, discharge, nozzle cleaning, and separation between the sample container, reaction container, and nozzle cleaning tank are difficult to avoid due to the wettability between the sample and the nozzle. Therefore, it is difficult to shake off excess sample that has adhered to the nozzle tip while the nozzle is moving from the sample container to the reaction container, and it is difficult to remove the excess sample that adheres to the nozzle tip while the nozzle is moving from the sample container to the reaction container. Therefore, for example, if the moving speed of the nozzle is increased, the sample may be thrown away. Therefore, the current sample dispensing method cannot achieve this accuracy by maintaining the nozzle moving speed at a state that does not affect the sample dispensing accuracy and providing time to shake off the sample adhering to the nozzle tip. do not have.

For example, only for sample dispensing of less than 3 μQ, the operation of the parts other than the sample dispensing microsyringe, sampling mechanism, sample nozzle cleaning tank, etc., can be maintained at the original time chart operation. , can be achieved by changing the control time chart of each unit described above, for example, in the following manner.

a. The time chart is usually designed at the maximum capacity of the device, and therefore the time chart for sample dispensing is also designed at the maximum dispensing capacity.

The above example is made for 20μQ.

Therefore, by limiting the amount of sample dispensed to, for example, less than 3 μQ, the suction and ejection time can be shortened, thereby ensuring the time for cleaning the tip of the sample nozzle.

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

[Effect]

As described above, the extra time for sample suction and ejection is shortened within the conditions only when dispensing a very small amount of sample that exceeds the range of normal analysis methods. Alternatively, by using two cycles for sample dispensing, the sample adhering to the nozzle periphery can be removed from the nozzle in a nozzle cleaning tank before being discharged without changing conditions such as nozzle movement speed, range, sample suction, and discharge speed. By washing the outer periphery, it is possible to secure time for brushing off, and it is possible to ensure sample dispensing accuracy.

〔Example〕

An embodiment of the method of the present invention will be described in detail below with reference to FIGS. 1 to 4.

FIG. 1 is a block diagram for explaining one embodiment of the sample dispensing method of the automatic analyzer of the present invention.

In FIG. 1, reference numeral 1 denotes a sample nozzle made of a metal pipe made of stainless steel with a narrowed end, and a liquid level sensor 2 is insulated and integrated with a covering tube 3. Reference numeral 4 denotes a sampling arm to which the sample nozzle 1 is attached, and although not shown, it is configured to be able to freely rotate and move up and down. Reference numeral 5 designates a microsyringe, in which a plunger 5b sealed with a sealing member 5a is configured to be able to move up and down, one end of which is connected to the sample nozzle 1 through a flexible pipe 5C, and the other end is connected to the sample nozzle 1 for cleaning the inner periphery of the sample nozzle 1. First solenoid valve6.
It is connected via a water pump 7 to a water tank 8 containing cleaning water 8a. Reference numeral 9 denotes a sample disk on which a sample container 10 into which a sample is injected is mounted, and a support mechanism (not shown) is used to transport and position each sample container 10 at a predetermined position on the rotation of the sample nozzle 1. (omitted). Reference numeral 11 denotes a reaction disk, on the outer periphery of which a plurality of reaction vessels 12 each having a plurality of rectangular parallelepiped long-hole reaction cells 12a integrally molded therein are fixed with screws 13. This reaction disk 1
1, each reaction cell 12a is also placed at a predetermined position on the rotation trajectory of the sample nozzle 1 by a rotation support mechanism (not shown).
are supported so that they can be sequentially transported and positioned. 14 is a cleaning tank for the sample nozzle 1, which has a cylindrical shape;
The part corresponding to the turning trajectory of the sample nozzle 1 is cut out in a 7-shape or a U-shape so as not to impede its movement, and the part corresponding to the turning trajectory of the sample nozzle 1 is cut out in a 7-shape or a U-shape so as not to interfere with its movement. A nozzle 15 for cleaning the outer periphery is fixed. The cleaning nozzle 15 is connected to the water pump 7 via a second electromagnetic valve 16 .

17 is a detection circuit for detecting the liquid level of the sample in the sample container 10 with the liquid level sensor 2 as the positive electrode and the sample nozzle 1 as the negative electrode, and 18 is a microcomputer system that controls the operation of these components described above. It is.

The operation of the sample dispensing device configured as described above will be explained with reference to the time chart shown in FIG.

FIG. 2 shows the operation of the reaction disk 11 as a reference, and the reaction disk 11 rotates once per cycle.
The reaction cell 12a, such as a +1 rotation reaction cell or a half rotation +1 reaction cell, is fed step by step, and a predetermined amount of sample is transferred to the reaction cell 12a, which has been cleaned and can be re-filled, during the stoppage time of the sample having the above configuration. The sample is dispensed by a dispensing device, and in the next cycle, a predetermined amount of reagent is dispensed onto the sample by a reagent dispensing mechanism (not shown), and the sample is dispensed into a new reaction cell. The sample to which the reagent is added exhibits a color reaction depending on the concentration, and its absorbance is measured each time the reaction disk 11 rotates.

In this way, each time the reaction disk 11 is stopped, sample dispensing, reagent dispensing, stirring, and secondary
Analysis is continued by repeating the dispensing of reagents, stirring, and washing of the reaction cell after a predetermined measurement. Here, the normal operation of each component within one cycle, indicated by a'' in FIG. 2, will be explained.

At time a, the sample nozzle 1 attached to the sampling arm 4 is located above the sample container 10. From there, the sampling arm 4 begins to descend, 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 has plunged into the sample by a predetermined amount. Next, when time advances to al, a predetermined amount of sample from the sample nozzle 1 plus a slight margin is aspirated by the microsyringe 5. Therefore, the sample suction time is set in accordance with the maximum sample dispensing amount in the device specifications, as described above. At time 82, backlash correction of the sending mechanism of the plunger 5b is performed, and when reaching time 83, the sampling arm 4 begins to rise and stops at the top dead center. The above operations are performed while the reaction disk 11 is rotating, and at time 84 when the reaction disk 11 stops rotating, the sampling arm 4 starts moving from above the sample container 10 to above the reaction cell 12a. The movement ends at point as, and the sampling arm 4 begins to descend into the reaction cell 12a, and during its descent, a
From time s, the microsyringe 5 operates and the reaction cell 12
While discharging a predetermined amount of sample into the sample nozzle 1, the sample attached to the outer periphery of the sample nozzle 1 is also placed. The sample ejection time is also set in accordance with the maximum dispensing amount of the device specifications, similar to the sample suction time described above.

After the sample has been discharged, the sample nozzle 1 rises from time 87, and starts moving from above the reaction cell 12a into the cleaning tank 14 at time 86.

When the sample nozzle 1 enters the cleaning tank 14, the sample remaining in the sample nozzle 1 at time 89 is discharged, and the first solenoid valve 6 and the second solenoid valve 16 are opened. Before the inner and outer periphery of the sample nozzle 1 interferes with the next sample, the water pump 7 discharges cleaning water from the sample nozzle 1 and sprays a cleaning bottle from the cleaning nozzle 15 onto the tip of the sample nozzle 1. and then washed. At the ato point when cleaning is completed, the sample nozzle 1 moves to the sample container 10, and a small amount of air is introduced into the sample nozzle 1 to prevent the sample from diluting due to contact between the cleaning water and the sample inside the sample nozzle 1. Aspirated by the microsyringe 5, a'
The sample nozzle 1 is again positioned on the sample container 10 to start the next cycle operation. The above explanation shows a case where the amount of sample dispensed is relatively large and it is easy to ensure and maintain the dispensing accuracy. Even in this case, the amount of sample attached to the outer periphery of the sample nozzle 1 during sample suction is Note: Although it does affect precision and accuracy, for example,
As mentioned above, in a device with a cycle time of 6 seconds, the performance and accuracy of the sample suction and discharge speeds, the moving speed of the sample nozzle 1, the cleaning time of the inner and outer periphery of the sample nozzle 1, etc. are maintained. However, it is almost impossible to find the time to remove the sample adhering to the tip of sample nozzle 1 between suction and discharge of the sample, and the ratio of the sample to the dispensed amount is small, so the influence of This was negligible, and the operation to remove the sample adhered to the tip of the sample nozzle 1 described above was also unnecessary.

Next, in order to accurately and precisely dispense a smaller amount of sample than the above-mentioned sample dispensing amount due to the function and performance requirements of the device, we will introduce a device for removing the sample adhered to the tip of the sample nozzle 1. The operation will be explained with reference to FIG. In Figure 3, the amount of sample dispensed is limited to an extremely small amount to provide operating time for removing the adhered sample.1For example, the limited amount is set to less than 3 μQ, and the maximum amount in the case of Figure 2 is 2
When it is set to 0 μQ, the time required for suction and discharge can both be shortened to ⅓ to 176 times. Here, a time chart is shown in which the time is shortened to 172. Even in this case, the above-mentioned sample suction and discharge speeds, sample nozzle 1 movement speed, cleaning time for the inside and outer periphery of the sample nozzle 1, etc., which affect the performance and accuracy of the sample dispensing device, are conventional. However, as shown in FIG. 3, while the sampling arm 4 moves from the sample container 1o to the reaction cell 12a, it stops above the nozzle cleaning tank 14 and closes the second solenoid valve 16. When the sample nozzle 1 is opened, the water pump 7 discharges washing water from the two washing nozzles 15 toward the tip of the sample nozzle 1, allowing time to remove the adhered sample.

As is clear from the above description, according to the embodiment of the method of the present invention, in order to ensure and maintain the performance and accuracy of one device, for example, a sample dispensing device, over a wide range of specifications, Multiple operating conditions are used depending on the amount of sample dispensed, so that, for example, when dispensing a sample of less than 3 μQ, it can be used for dispensing a sample of less than 3 μQ. It is possible to ensure similar accuracy and precision, and since the selection and execution of the operation control of the apparatus based on the dispensed amount is performed by a microcomputer system, it can be performed very easily.

Figure 4 is a time chart of an example in which the above-mentioned change in operation control is performed using two cycles only for dispensing less than 3 μQ. The system uses time to perform one cycle operation, and the reaction disk 11 and the like are the same as before, and there is no need to change the cycle time. 2 for one sample dispensing
By using cycles, the throughput of the device is reduced only for the limited cycles, but it becomes easier to control the sample dispensing device and ensure its accuracy.

〔Effect of the invention〕

According to the present invention described above, a wide t! Ensuring stable accuracy and precision for large sample dispensing,
Furthermore, it is possible to analyze high-concentration samples without providing a sample dilution function, and it can be used in automatic analyzers to improve their performance and have economical effects.

[Brief explanation of the drawing]

FIG. 1 is a block diagram for explaining one embodiment of the sample dispensing method of the automatic analyzer of the present invention, and FIGS.
FIG. 5 is a time chart showing the operation control of the components shown in the figure, and FIG. 5 is a characteristic diagram of sample dispensing of the conventional apparatus. 1...Sample nozzle, 2...Liquid level sensor, 4...
・Sampling arm, 5...Microsyringe, 6
゜16...Solenoid valve, 7...Water pump, 8...Water tank, 9...Sample disk, 10...Sample container, 11...Reaction disk, 12...Reaction container, 12a... Reaction sensor, 14... Nozzle cleaning tank, 15... Cleaning nozzle, 18... Microcomputer system. Agent: Patent attorney Shinobu Ogawa (,. 5th method of writing amendments to patent attorney procedures) Showa FL-Mon. 11

Claims (1)

[Claims] 1. A sample nozzle, a sample nozzle moving mechanism that holds the sample nozzle, moves and positions the sample nozzle to a sample container, reaction container, nozzle cleaning tank, etc., and a pump that supplies cleaning water to the sampling nozzle. The sample dispensing device is equipped with a microsyringe connected to the nozzle cleaning tank, etc., and the operation of the device is controlled whether the device is in operation or not, depending on the amount of sample dispensed. A sample dispensing method for an automatic analyzer, characterized in that the sample dispensing method is selectable.