JP2886894B2 - Automatic analyzer - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an automatic analyzer, and more particularly to an automatic analyzer for dispensing a liquid sample or the like with a dispensing nozzle.

[Conventional technology]

At present, in an automatic analyzer, a liquid sample set in the device in a sample container is transferred and dispensed into a reaction container installed in another place by a dispensing device, and further reacted in the reaction container. Many systems employ a method in which a reagent is dispensed, reacted for a certain period of time, and then optically measure the concentration of the item to be measured. FIG. 1 shows an example of the configuration of the analysis unit of the automatic analyzer.

In FIG. 1, a dispensing nozzle 2 is provided at a tip end of a dispensing arm 1, and the dispensing arm 1 is fixed to a main shaft 3, and vertically and pivotally around the main shaft 3. Perform the operation. In addition, a reaction table 4, a sample table 6, and a reagent table 8, which individually perform a rotating operation, are provided in proximity to the dispensing arm 1. A plurality of reaction vessels 5 are set in the reaction table 4, and during a dispensing operation, a predetermined reaction vessel is transferred to a predetermined dispensing position on a swirl locus of the dispensing nozzle 2 by a rotating operation. The samples to be analyzed are dispersed in the sample container 7 and set on the sample table 6. A reagent container 9 containing reagents necessary for the analysis of each item is set on a reagent table 8. Similarly to the reaction container 5, the sample container 7 and the reagent container 9 are transferred to predetermined dispensing positions by rotating the respective installation tables. Further, the dispensing nozzle 2 is washed by the washing unit 10 in order to prevent carryover between each sample and the reagent. By the operation of each unit described above, a predetermined sample and a predetermined reagent are sequentially dispensed into a predetermined reaction container.
Each reaction vessel 5 is maintained at a constant temperature by a constant temperature device (not shown), and after a reaction is performed for a predetermined time, the concentration of an item to be measured is measured by a photometer (not shown).

However, in the automatic analyzer having the above configuration, the dispensing nozzle 2 is immersed in a fixed amount in a liquid sample or a liquid reagent to dispense each sample and reagent. Carryover (contamination) due to the adhesion occurs, and the sample and reagent attached to the dispensing nozzle 2
It is scattered when transferred to the reaction vessel 5. Cleaning unit
In 10, cleaning is performed in a cleaning liquid such as water, so that after cleaning, the cleaning liquid attached to the dispensing nozzle is carried into the sample container 7 and the reagent container 9 to dilute the sample and the reagent. As described above, at the time of dispensing, the adhesion and scattering of the liquid to the dispensing nozzle 2 are factors that significantly lower the analytical performance and safety of the apparatus.

[Problems to be solved by the invention]

Conventionally, as a countermeasure, the dispensing of a sample with a relatively small dispensing amount and the dispensing of the reagent are performed by separate devices, thereby preventing carryover between the sample and the reagent, and a dispensing nozzle for the sample. The diameter is made as small as possible to reduce the amount of liquid adhering. However, the sample / reagent separation of the dispensing device becomes large and complicated as it is, and it is difficult to apply it to a small device. In recent years, the analysis items have been diversified. In particular, in order to measure highly dilute substances such as viruses and hormones using the immune reaction with high sensitivity, the amount of sample used in many cases is larger than that of conventional biochemical measurement. It is in a situation where an expansion of the volume range is required and it is difficult to make the dispensing nozzle thin in order to maintain the processing capacity. Also, as described in Japanese Patent Application Laid-Open No. 62-182665, dispensing nozzles are made disposable tips to prevent carryover between items and to eliminate the cleaning step. Supply and disposal mechanism and chip attachment / detachment mechanism are required,
The equipment becomes larger and costs increase. In addition, the running cost is increased, and the chip diameter is larger than that of a metal nozzle.Therefore, a large opening is required in the sample container. In an apparatus using an immunoreaction that requires a long time, there is an increasing demand that the opening be made as narrow as possible in order to minimize the spontaneous evaporation of the sample / reagent, and it is difficult to cope with the disposable tip.

An object of the present invention is to provide an automatic analyzer that can prevent scattering of a sample or a reagent at the time of dispensing without substantially reducing the amount of analysis processing.

[Means for solving the problem]

In order to prevent the liquid from adhering to the dispensing nozzle or scattering the liquid adhering to the dispensing nozzle, a series of dispensing operations may be performed slowly. In other words, the dispensing nozzle immersed in the sample for a certain length is lifted at a high speed to suck the sample, and when the nozzle is pulled out of the liquid surface, the sample in the area near the dispensing nozzle rises due to the viscosity of the sample. At the speed given, the sample liquid comes off the surface of the sample liquid together with the dispensing nozzle and adheres to the dispensing nozzle or moves to the tip of the nozzle as a droplet. However, if the dispensing nozzle is slowly lifted up here, the sample will hardly adhere unless the dispensing nozzle is very dirty, because the ascending speed of the sample is low and the bonding force between the samples is large. In addition, scattering of the adhered liquid can be prevented by reducing the rotation speed of the dispensing nozzle and reducing the change in acceleration during start / stop. However, the above dispensing speed is directly linked to the processing capacity of the automatic analyzer (the number of analysis items per unit time), and it is necessary to increase the dispensing speed and shorten the time required for dispensing. This is an indispensable element, and the dispensing operation cannot simply be slowed down.

In the present invention, the dispensing nozzle is moved from the position of the reaction container to the position of the washing device, rather than the swirling speed of the dispensing arm when moving the dispensing nozzle from the position of the liquid container containing the liquid to be dispensed to the position of the reaction container. The dispensing arm is configured so that the swirling speed of the dispensing arm when moving is high, and is lower than the speed when the dispensing nozzle descends into the reaction vessel and when the dispensing nozzle rises from inside the reaction vessel. The dispensing nozzle lowers into the liquid container and the dispensing nozzle rises from the liquid container at a lower speed.

[Action]

The sample adheres to the dispensing nozzle and scatters due to the liquid sample dispensing occurs as follows.

1) When the dispensing nozzle is pulled out of the sample after aspirating the sample, the sample adheres to the dispensing nozzle and the attached sample is scattered during transfer to the reaction vessel.

2) When the dispensing nozzle is removed from the washing liquid after washing the dispensing nozzle, the washing liquid adheres to the dispensing nozzle and further aspirates the sample.
When transferring to the sample container position, the washing liquid scatters,
In addition, during the next sample suction process without being scattered, the sample is inserted into the sample together with the dispensing nozzle, which causes the sample to be thinned.

For this reason, the operation pattern of the drive motor is such that when the dispensing nozzle is pulled out of the sample and the washing liquid in the series of dispensing operations, and that only the transfer operation to the reaction vessel is performed at a low speed after dispensing the sample. By switching between them, it is possible to prevent the liquid attached to the dispensing nozzle from scattering.

〔Example〕

Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings.

FIG. 2 shows a typical dispensing method in the automatic analyzer having the configuration shown in FIG. In FIG. 1, the sample table 6 and the reagent table 8 are arranged concentrically, and the dispensing of the sample and the reagent is shared by a single dispensing device. In other words, the dispensing of the sample and the reagent is performed by the same dispensing device, thereby miniaturizing and simplifying the device.

A series of dispensing operations will be described with reference to FIG. In this drawing, the dispensing arm 1 is connected to a pipetting mechanism (not shown) via a tube, a switching valve, and the like, and aspirates and discharges a predetermined amount of a sample / reagent by the pipetting mechanism.

Before starting the dispensing operation, the dispensing arm 1 is previously positioned at a predetermined position (for example, on the cleaning device) by a reset operation of the device or the like. Then, when the dispensing operation is started, first, in order to dispense a predetermined sample (reagent) 11, the sample is rotationally transferred onto the sample container (reagent container) 7 positioned at the dispensing position (). Is positioned. Next, in order to perform sample suction, the dispensing nozzle 2 descends, and the sample 11
It is immersed in a predetermined amount. (). At this time, the immersion amount of the dispensing nozzle can be controlled by a liquid level detecting function added to the dispensing device. When the dispensing nozzle 2 is immersed in the sample liquid, a predetermined amount of the sample 11 is sucked into the dispensing nozzle 2 by the pipettor mechanism described above. Rises, detaches the sample 11, and stops at the top dead center (). Next, in order to dispense the sucked sample 11 into the reaction container 5, the sample 11 is transferred by rotation to the reaction container 5 positioned at the dispensing position (). The dispensing nozzle 2 positioned on the predetermined reaction vessel 5 descends to discharge the sucked sample 11 into the reaction vessel 5, descends to a predetermined position in the reaction vessel, and stops (). When a predetermined amount of the dispensing nozzle 2 is inserted into the reaction container, the pipette mechanism discharges a predetermined amount of the sucked sample into the reaction container. When this discharge operation is completed, the dispensing nozzle 2 rises again to the top dead center position (). The dispensing nozzle 2 transferred to the top dead center is transferred onto the cleaning device by a rotating operation to clean the dispensing nozzle 2 (). The dispensing nozzle 2 positioned on the cleaning device 10 descends and is inserted into the cleaning device 10 by a predetermined amount (). In this state, the cleaning liquid 13 is discharged from the nipple 12 installed in the cleaning apparatus 10, and the cleaning liquid 13 is discharged from the dispensing nozzle 2 at the same time as cleaning the outside of the dispensing nozzle 2. Wash. After performing the washing for a predetermined time, the dispensing nozzle 2 rises to the top dead center position (), and again (a) to (d).
The sample and the reagent are sequentially dispensed by repeating the dispensing operation (e).

FIG. 3 shows a configuration diagram of an embodiment of a dispensing device for realizing the above-described dispensing operation.

The dispensing nozzle 2 is installed at the tip of the dispensing arm 1, and the dispensing arm 1 is fixed to a main shaft 3 that can rotate vertically and rotate. The spindle 3 has a spline shape,
The linear guide 16 is configured to be held without play. The main shaft 3 is attached to the base 14 by a linear guide 16 and a metal bearing 15.
Is held by a ball bearing 17 and is capable of rotating. That is, the main shaft 3 is connected to the linear guide 16.
Up and down movement is performed by mating with the linear guide 16
And rotate together. The main shaft 3 is connected to a slider 18, and a linear bearing (not shown) is incorporated in the slider 18, so that a guide shaft 19 attached to the base 14 in parallel with the main shaft 3 is provided. Up and down movement is possible along. That is, the slider 18 is held by the guide shaft 19 and can move in parallel with the main shaft 3.
Further, a rack 20 is attached to the slider 18, and can be vertically moved by a vertical drive pulse motor 21 via a pinion 22. By the vertical drive pulse motor 21,
The slider 18 is moved up and down, and the spindle 18 and the dispensing arm 1 are moved up and down by interlocking the slider 18 and the spindle 3. A pulley 26 is attached to the linear guide 16 via a housing 25, and is connected to a pulse motor 23 for rotational driving by a timing belt 24. That is, by driving the rotation drive pulse motor 23, the linear guide 16 is given a rotational movement via the timing belt 24, and the linear guide 16 and the main shaft 3 are integrally moved in the rotational direction. Rotational motion can be given. As described above, in the dispensing mechanism shown in FIG. 3, by controlling two pulse motors for up and down and rotation, rotation and up and down operations can be individually given to the dispensing arm 1.

4 and 5 show the driving pulse rate of the pulse motor. FIG. 4 shows the pulse rate of the up / down driving pulse motor 21, and FIG.
Shows the pulse rate. In this figure, the left side of each pulse rate shows a slow-up state at the time of startup, and the right side shows a slow-down state at the time of stoppage. For example, when the vertical movement is performed at a high speed, the pulse rate is as shown in FIG. 4 (a), the starting is performed at a starting pulse number of 300 pps (pulses / s), and the acceleration up to 1700 pps is performed by two times.
Perform with 5 pulses. The time for acceleration at this time is 25 ms
It is. In the case of vertical operation, dispensing nozzle 2 immersed in liquid
It is important how to relax and pull out quietly,
As shown in (b), in addition to decreasing the ascending speed from 1700 pps to 700 pps, the number of slow-up pulses is increased from 25 pulses to 5 pulses to reduce the acceleration at the time of ascending.
If the ascent speed is reduced to 700pps or less,
The vibration generated from 21 increases rapidly, and this vibration is transmitted to the dispensing nozzle 2, thereby increasing the adhesion and scattering of the liquid. Therefore, the lower limit of the low speed value is a value specific to the dispensing device used. .

In order to cause the dispensing nozzle 2 to perform the two kinds of operations, the high-speed operation and the low-speed operation, the driving pulse rates of the upper, lower, and rotating pulse motors are set according to the operation contents in the routine operation using program software. This is realized by rewriting as appropriate. That is, a plurality of operation patterns can be realized by rewriting the pulse rates of the single drive pulse motors for the up and down and rotation. Thus, an optimal operation pattern for each operation can be selected by a single dispensing device.

FIG. 6 and FIG. 7 show time charts for up / down and rotation operations of the dispensing apparatus. Here, FIG. 6 shows a time chart at the time of sample dispensing, and FIG. 7 shows a time chart at the time of reagent dispensing. The indications such as high-speed rise and low-speed rotation in the figure indicate which of the pulse rates shown in FIGS. 4 and 5 is operated at the high-speed or low-speed pulse rate. The dispensing operation is 18 seconds per cycle for both sample and reagent dispensing. In addition, in the analysis, in many cases, a plurality of reaction reagents are dispensed to a biological sample such as serum.
Reagent dispensing is set to be performed twice. Further, compared to the reagent, the sample such as serum has much higher viscosity, and the clogging is easily generated in the dispensing nozzle 2 and the piping system, and the risk of infection is large. It takes a lot of time to clean the dispensing nozzle 2. For this reason, the dispensing operation of the sample and the reagent is often quite different, and the dispensing devices for the sample and the reagent are separately equipped with different time charts as shown in FIGS. In most cases, a note operation is performed. In contrast, in this embodiment, two types of time charts, one for the sample and one for the reagent, are prepared in advance, and these two time charts continue at the start point and the end point of one cycle operation without any contradiction. By setting as possible and selecting and operating the time chart itself according to the object to be dispensed, both a sample and a reagent are dispensed by one dispensing device. Next, the sample dispensing operation will be described with reference to FIG. The contents of the operation are the same as those described in FIG. 2, but the operation starts from the washing step of the dispensing nozzle 2 at the beginning of the cycle. First, at time 0.1 (S), high-speed rotational movement from the initial position to the cleaning position is performed, and after the rotation operation is completed, at time 0.5, it descends into the cleaning device at high speed, and the inner and outer circumferences of the dispensing nozzle 2 are cleaned with the cleaning liquid. . After the cleaning is completed, if the liquid is raised at a high speed as it is, it causes water droplets as described above. Therefore, the rising pulse rate is switched to a low speed, and the speed is raised at a low speed at time 8.7. However, at this time, the dispensing nozzle 2 needs to be raised at a low speed while being immersed in the cleaning liquid. For this reason, as shown in FIG.
The diameter of the waste liquid hole in the lower part is reduced, and the liquid with a high sample concentration discharged from the dispensing nozzle 2 is directly discharged, but the cleaning liquid discharged from the nipple accumulates in the cleaning device during the cleaning operation. . In addition, rewriting of the pulse rate requires rewriting time, and in this embodiment, at the time of rewriting, the stop time of the target pulse motor is set to 0.5S or more.
The cleaning device is rotated to the sample suction position in order to suck the sample after ascending at a low speed to the top dead center. However, the rotation operation is performed at a low speed to prevent the washing liquid from scattering. The rotation and the rising pulse rate from the cleaning device are both changed to a low speed during the cleaning time. At time 10.0, it descends into the sample container 7, and after sucking a predetermined amount of sample, it rises again at time 13.0 at a low speed.
Here, a delay occurs in the actual suction into the dispensing nozzle 2 as compared with the suction operation due to the viscosity of the sample or the like. Therefore, a stabilization time is provided between the end of the suction operation and the ascent operation. After ascending the dispensing nozzle 2, the dispensing nozzle 2 is transferred at a low speed to the position of the reaction vessel 5. Here, the amount of descent at the position of the reaction container is larger than that of the sample container, and the lowering operation at the position of the reaction container needs to be performed at a high speed due to the limitation of the stop time of the reaction table 4. In the meantime, the pulse rate for up and down is changed to that for high speed, descends at high speed at time 14.8, rises at high speed after discharging the sample, rotates at high speed to the washing position, and thereafter repeats the same operation. When moving from sample aspiration to reagent aspiration,
From time 18.0 in FIG. 6, it is linked to time 0 in FIG.
Here, since the rotation operation immediately after the transition to the reagent dispensing time chart is for high-speed operation, the rotation pulse rate must be changed to high-speed operation during the sample discharging operation. In the reagent dispensing time chart shown in FIG. 7, it is necessary to dispens the reagent twice per cycle, there is no time margin as compared with the dispensing of the sample, the reagent viscosity is small, and this embodiment In the reagent container 9 used in the above, silicone rubber is stuck on the container opening to prevent spontaneous evaporation of the reagent, and is sealed. When the reagent is sucked, the dispensing nozzle 2 penetrates the silicone rubber. When the nozzle 2 rises, the reagent adhering to the dispensing nozzle 2 is wiped off by the silicone rubber, so that all the reagent suction operation is performed at high speed unlike the sample suction. However, only the ascent operation after cleaning is performed at a low speed. At this time, the pulse rate is changed during the washing operation, and the lowering operation for the next suction of the reagent is performed at a high speed. Making changes.

〔The invention's effect〕

ADVANTAGE OF THE INVENTION According to this invention, the turning operation of the dispensing nozzle which can prevent the liquid from being scattered from the dispensing nozzle without lowering the processing capacity of the entire dispensing process including suction, discharge, and cleaning is realized. It is possible to reduce the amount of the adhering liquid that causes scattering from the dispensing nozzle.

[Brief description of the drawings]

FIG. 1 is a configuration diagram of an automatic analyzer, FIG. 2 is a diagram showing a typical dispensing method, FIG. 3 is a structural diagram of the dispensing device, and FIG. 4 is a diagram showing a pulse rate for a vertical operation of the dispensing device. FIG. 5 shows a pulse rate for the rotation operation of the dispenser, FIG. 6 shows a time chart for sample dispensing, and FIG. 7 shows a time chart for reagent dispensing. 1 ... dispensing arm, 2 ... dispensing nozzle, 4 ... reaction table,
5 ... reaction container, 6 ... sample table, 7 ... sample container, 8 ...
Reagent table, 9 ... Reagent container.

──────────────────────────────────────────────────続 き Continued on front page (58) Field surveyed (Int.Cl. ⁶ , DB name) G01N 35/00-35/10 G01N 1/00 101

Claims (1)

(57) [Claims] A dispenser for sucking a liquid to be dispensed from a liquid container into a dispensing nozzle held by a pivotable dispensing arm and discharging the liquid to be dispensed sucked into the dispensing nozzle to a reaction container. When,
In the automatic analyzer equipped with a washing device for washing the dispensing nozzle after discharging the liquid to be dispensed, turning of the dispensing arm when moving the dispensing nozzle from the position of the liquid container to the position of the reaction container. The dispensing arm is configured so that the turning speed of the dispensing arm when moving the dispensing nozzle from the position of the reaction container to the position of the cleaning device is higher than the speed, and the dispensing arm is moved into the reaction container. The lowering speed of the dispensing nozzle into the liquid container and the rising of the dispensing nozzle from within the liquid container are lower than the speeds when the dispensing nozzle is lowered and when the dispensing nozzle is raised from within the reaction container. An automatic analyzer characterized in that the speed at the time is reduced.