JP3152710B2 - Liquid sample dispensing method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid sample dispensing method using an analyzer for measuring, for example, the amount of a substance contained in blood.

[0002]

2. Description of the Related Art For example, an automatic analyzer is used to measure the amount of a substance contained in blood. In this analyzer, a large number of liquids are dispensed using a nozzle. In this case, since the dispensing operation is performed using the same nozzle, it is necessary to prevent the liquid adhering to the nozzle surface from being mixed into another liquid during the dispensing operation. For this reason, an operation of cleaning the nozzle is required in the dispensing operation.

[0005] Further, the dispensing of liquids such as serum, urine, reagents and the like by nozzles and the washing of nozzles after dispensing will be specifically described. First, the nozzle holder which has been moved to the liquid suction position is lowered. Then, the nozzle and the liquid level detector held by the nozzle holder also descend, and the liquid level detector detects the liquid level in the liquid container. After detecting the liquid level,
The nozzle and the liquid level detection unit penetrate into the liquid in the liquid container and stop at a predetermined position. The amount of penetration in this case is
It is determined as follows. In other words, after the nozzle sucks the maximum amount of liquid determined by the device specifications, it is determined to be a constant amount that satisfies the condition that the tip of the nozzle is below the liquid level even if the liquid level drops.

Next, a predetermined amount of liquid is sucked by a nozzle,
The nozzle holder is moved to the liquid discharge position, and the liquid is discharged from the nozzle into the reaction vessel. Thereafter, the nozzle holder is moved to move the nozzle and the liquid level detection unit to the cleaning position. Therefore, after cleaning the nozzle and the liquid level detection unit, the nozzle and the like are moved to the original suction position. The dispensing operation is performed by repeating such a series of operations.

[0005] One of the conventional examples is disclosed in
No. 26473 is described.
This is to detect the height of the liquid level before the nozzle penetrates, so that the depth of penetration of the nozzle into the sample does not differ depending on the height of the liquid level due to the amount of the sample. Based on the detected value, the descending amount is controlled so that the amount of intrusion of the nozzle always has a constant depth from the liquid level regardless of the liquid level.

[0006]

However, in each of the above-mentioned prior arts, since the nozzle always penetrates to a constant depth from the liquid surface, the outer wall of the nozzle is moved every time the liquid is sucked regardless of the suction amount. Immersed in liquid over a wide area. Therefore, there is a problem that the liquid adhering to the nozzle outer wall is discharged together with the regular discharge liquid when discharging the discharge liquid from the nozzle inner wall. When a minute amount such as 3 μl is dispensed, the influence of the amount of adhesion on the outer wall of the nozzle becomes relatively large, and it becomes impossible to perform highly accurate dispensing. FIG. 9 shows a liquid container
This shows the nozzle 21 and the liquid level detector 22 that have penetrated into the liquid in 20, and since the position of the nozzle 21 is set below the water level 23 after suctioning the maximum value according to the device specifications, This shows a state in which the surplus intrusion amount E of the nozzle 21 has occurred between the water level 24 after the suction amount of the nozzle 21 has been sucked.

Further, even if the nozzle is washed after the liquid is ejected, the amount of adhesion on the outer wall of the nozzle is large, so that it is necessary to always wash the amount of adhesion corresponding to the maximum suction amount. In some cases, the nozzle may remain in the next suction liquid and the liquid remains attached to the next suction liquid. Therefore, when there is a large difference between components in the amount of a component to be measured, such as in an immunological test item, or when a reaction occurs between reagents, the pre-solution may adversely affect analytical data. . Further, in the method in which the tip of the nozzle penetrates into the liquid at the time of discharge, the smaller the amount of discharge, the greater the effect of the liquid attached to the outer wall, resulting in lower accuracy. In addition, the liquid adhering to the outside of the nozzle may be scattered to the periphery during the transfer of the nozzle, thereby contaminating the apparatus. Further, when the scattered liquid is serum, urine, or the like, there is a problem that the surroundings are contaminated by pathogenic bacteria, which causes an unexpected situation.

[0008] The present invention is proposed to solve the above-mentioned problems, and provides a liquid sample dispensing method capable of reducing the amount of liquid adhering to the outside of a nozzle and performing proper sample dispensing and automatic analysis. It is intended to do so.

[0009]

According to the present invention, in order to achieve the above object, a liquid dispensing nozzle is moved to a liquid suction position for suction, and after suction, the nozzle is moved to a discharge position for discharging. In the liquid sample dispensing method in which a series of operations for cleaning the nozzle by moving the nozzle to the cleaning position after the discharge is repeated, by controlling the nozzle movement amount at the liquid suction position according to the liquid suction amount, the liquid enters the liquid. In addition to restricting the amount of intrusion of the intruding nozzle, the amount of movement of the nozzle this time is stored, and the amount of movement of the nozzle for the next dispensing is moved so as to move by the difference from the amount of movement this time. This is a liquid sample dispensing method controlled.

[0010]

As described above, the nozzle does not intrude into the liquid to be sucked more than necessary, and the adhesion of the liquid to the outer wall of the nozzle can be minimized in accordance with the dispensed amount. Highly accurate analysis can be performed. In addition, the amount of movement of the nozzle this time is stored, and the amount of movement of the nozzle for the next dispensing can be controlled so as to move by the difference from the amount of movement this time. By the combination with the configuration that regulates the intrusion amount, due to the adhesion to the nozzle by the currently performed dispensing, the influence on the dispensing amount each time is small, so that the automatic dispensing every time according to the stored data, It is possible to be able to execute while obtaining appropriate analysis data.

[0011]

Embodiments of the present invention will be described below in detail with reference to the drawings. FIG. 1 is a schematic perspective view of the vicinity of a nozzle of an automatic analyzer for carrying out the first embodiment of the present invention. The nozzle 1 and the liquid level detector 2 are held by a nozzle holder 3. The nozzle holder 3 is movably connected to the nozzle transfer mechanism 5 via a connector 4 so that the nozzle holder 3 can be rotated horizontally and vertically. The liquid level detector 2 includes a pair of rod-shaped electrodes near the nozzle 1,
The liquid level can be detected by a change in electric resistance. The reaction container 6 is disposed at the moving position A of the nozzle holder 3, the cleaning tool 7 is provided at the moving position B of the nozzle holder 3, and the moving position C of the nozzle holder 3 is moved. Is provided with a liquid container 8.

The nozzle 1 of the automatic analyzer configured as described above performs a dispensing operation while being controlled by a control unit (not shown). By the operation of the nozzle transfer mechanism 5, the nozzle 1 moves to the liquid suction position C together with the liquid level detector 2 via the nozzle holder 4, and then the nozzle 1 and the liquid level detector 2 descend and enter the liquid container 8. I will do it. At this time, the liquid level detector 2 detects the liquid level in the liquid container 8. Based on the detected data, the nozzle 1 and the liquid level detector 2 enter the liquid in the liquid container 8 by a predetermined amount.

The amount of intrusion is obtained as follows.
Assuming that the amount of intrusion into the liquid is y and the constants determined by the size and shape of the liquid container 8 and the dimensions and shape of the automatic analyzer and the assembly accuracy are a and b, “y = a · liquid suction amount +
b ". The nozzle 1 is made to penetrate into the liquid in the liquid container 8 by the amount of penetration y thus obtained, and then stopped. Next, the liquid in the liquid container 8 is sucked by the nozzle 1. The sucked nozzle 1 is moved to the liquid discharge position A by the operation of the nozzle transfer mechanism 5, and discharges the liquid to the reaction container 6 arranged there. After the liquid is discharged, the nozzle 1 and the liquid level detector 2 are moved to the nozzle cleaning position B by the operation of the nozzle transfer mechanism 5, and are cleaned. After the cleaning, the nozzle 1 and the liquid level detector 2 are returned to the liquid suction position C again.

In this embodiment, when the nozzle 1 enters the liquid container 8 for sucking the liquid, the amount of the entry is controlled based on the above equation so as to be variable in accordance with the amount of liquid suction. . That is, when the liquid suction amount is small, the penetration amount is reduced. Therefore, the amount of liquid adhering to the outside of the nozzle 1 can be reduced by preventing the nozzle from entering the liquid more than necessary. FIG. 2 shows a state in which the nozzle 1 and the liquid level detector 2 have entered the liquid container 8. However, when the water level 10 is near the liquid level 9 after suction (FIG. 2A), When the water level 10 after suction is lower than the liquid level 9 as shown in FIG. 2B, the amount of intrusion is reduced so as to increase the amount of intrusion. There are various control methods for making the liquid suction amount variable, but in addition to a method of controlling according to a program, for example, the number of pulses corresponding to the suction amount is oscillated, and the stroke of the syringe is controlled by a pulse motor. Any method such as making the amount variable may be used.

Next, a second embodiment of the present invention will be described. The present embodiment is different from the first embodiment in the method of determining the amount of intrusion of the nozzle into the liquid by the control unit. In the first embodiment, the intrusion amount y
Is determined by “y = a · liquid suction amount + b”, but in the present embodiment, different liquid suction amounts are set for each of a plurality of stages, and the intrusion amount y is determined for each stage. That is, lμl ≦ liquid suction amount <mμl
When y = s (mm) mμl ≦ liquid suction volume <nμl When y =
t (mm) When nμl ≤ liquid suction volume <pμl, y =
u (mm) Here, l, m, n, and p are liquid set values determined by the conditions of the automatic analyzer and the liquid container, and s, y, and u represent the amount of intrusion.

After the nozzle has penetrated into the liquid in the liquid container by the amount of penetration y set in advance in this way, the nozzle is stopped. Next, the liquid in the liquid container is sucked by the nozzle. The sucked nozzle is moved to the liquid discharge position by the operation of the nozzle transfer mechanism, and discharges the liquid to the reaction container disposed there. After the liquid is ejected, the nozzle and the liquid level detector are moved to the nozzle cleaning position and cleaned by the operation of the nozzle transfer mechanism. After the cleaning, the nozzle and the liquid level detector are returned to the liquid suction position again.

In this embodiment, when the nozzle penetrates into the liquid container to suck the liquid, the amount of the penetrating is set in advance according to the liquid suction amount. That is, when the liquid suction amount is small, control is performed so that the intrusion amount is reduced. Therefore, the amount of liquid adhering to the outer wall of the nozzle can be reduced by preventing intrusion more than necessary.

Next, a third embodiment of the present invention will be described. The present embodiment is a method of dispensing a liquid sample using an apparatus that changes the relative positional relationship between a nozzle and a liquid level detection unit according to the amount of liquid suction. FIG. 3 is a perspective view showing the nozzle up / down movement mechanism used in the present embodiment. At the tip of the nozzle holder 3, a pulse motor 12 having a pinion 11 connected to an output shaft is provided. Pinion 11
Is connected to a slider 14 having a rack 13 so as to move up and down in the linear bearing 15.

The nozzle 1 is provided inside the slider 14 so as to be vertically movable, and can be moved relatively to the liquid level detector 2 provided on the nozzle holder 3. FIG. 4 is a cross-sectional view showing a state in which the nozzle 1 is provided in the slider 14, and the nozzle 1 is positioned by the stopper 16 such that the vertical position of the nozzle 1 substantially matches the liquid level detector 2 in the initial state. Stipulated.

In this embodiment, the control unit (not shown) oscillates a pulse corresponding to the liquid dispensing amount to rotate the pulse motor 12 in this embodiment. The nozzle 1 shown in FIG.
5B, the nozzle 1 projects from the liquid level detector 2 as shown in FIG. 5B. Pulse motor 12
Needless to say, when is rotated in the reverse direction, the nozzle 1 moves up to the initial state.

In order to perform liquid suction by the nozzle 1, the nozzle holder 3 is lowered at the suction position. Then
The nozzle 1 and the liquid level detector 2 provided on the nozzle holder 3 also descend, and the liquid level detector 2 detects the liquid level in the liquid container. After the liquid level is detected, the nozzle 1 and the liquid level detector 2 enter the liquid container 8. At the same time, as shown in FIG. 5B, the nozzle 1 intrudes into the liquid container 8 by an additional predetermined amount by the length L1 corresponding to the suction amount (dispensing amount) and stops. FIG.
Shows a state in which the nozzle 1 and the liquid level detector 2 are stopped in the liquid container 8 in this manner. However, the nozzle 1 penetrates into the liquid as described above, and the liquid level detector 2 is fixed. It has penetrated by the penetration amount L2.

In the state shown in FIG. 6, the nozzle 1 sucks the liquid by a predetermined suction amount. After suction, nozzle 1 is pulse motor 1
2A, the ascending movement is performed to the initial state of FIG. 5A. Thereafter, the nozzle holder 3 is moved to the liquid discharge position, and the liquid is discharged from the nozzle 1 into the reaction container. Then, the nozzle holder 3 is moved to the cleaning position, and the nozzle 1
Then, the liquid level detector 2 is cleaned, and after the cleaning, it is returned to the liquid suction position again.

In this embodiment, when the nozzle enters the liquid container in order to suck the liquid, the suction amount (dispensing) is determined by the liquid level detector which has also entered the liquid according to the liquid suction amount. The amount is controlled so as to penetrate deeply according to the amount. That is, when the liquid suction amount is small, the amount of intrusion is reduced. Therefore, the amount of liquid adhering to the outside of the nozzle can be reduced by preventing the liquid from entering more than necessary.

Next, a fourth embodiment of the present invention will be described. In this embodiment, an apparatus similar to that of the third embodiment is used. Nozzle 1
In order to perform the liquid suction by the above, first, the nozzle holder 3 is lowered at the suction position. Then, the nozzle 1 and the liquid level detector 2 provided on the nozzle holder 3 are also lowered, and the liquid level detector 2 detects the liquid level in the liquid container. After the liquid level is detected, the nozzle 1 and the liquid level detector 2 simultaneously enter the liquid in the liquid container 8, enter a predetermined amount, and stop. FIG. 7 shows a state in which the nozzle 1 and the liquid level detector 2 have thus entered the liquid in the liquid container 8 for a predetermined amount (L3) and stopped.

Thereafter, as shown in FIG. 8, the nozzle 1 intrudes into the liquid container 8 by a predetermined amount by a length L4 corresponding to the suction amount (dispensing amount) and stops. After sucking the liquid in this state, the nozzle 1 is rotated in the reverse direction by the pulse motor 12 as shown in FIG.
Then, the nozzle holder 3 is moved to the liquid discharge position, and the liquid is discharged from the nozzle 1 into the reaction container. Thereafter, the nozzle holder 3 is moved to the cleaning position, the nozzle 1 and the liquid level detector 2 are cleaned, and after the cleaning, the nozzle 1 is returned to the liquid suction position again.

In this embodiment, when the nozzle penetrates into the liquid container to suck the liquid, the nozzle and the liquid level detector are simultaneously penetrated into the liquid, and then the nozzle is moved in accordance with the liquid suction amount. The liquid level detector is controlled so as to penetrate deeply according to the suction amount (dispensing amount). That is, when the liquid suction amount is small, the amount of intrusion is reduced. Therefore, the amount of liquid adhering to the outside of the nozzle can be reduced by preventing the liquid from entering more than necessary. In the embodiment in which the liquid level detector is stopped at the liquid level detection position and only the nozzle is independently lowered for suction, contamination of the liquid level detector can be minimized.

The present invention is not limited to the above-described embodiment, and many modifications and variations are possible. For example, the vertical movement mechanism (FIG. 3) of the slider 14 used in the third and fourth embodiments can be configured using members such as gears, bearings, and ball screws. In addition, the liquid level detecting device 2 may employ various known devices such as optical detection other than the electrodes. The positioning of the nozzle 1 and the liquid level detector 2 in the initial state shown in FIG. 5A may be performed using an optical method such as a photo sensor. When setting the relative positional relationship between the nozzle and the liquid level detector, the liquid level detector may be configured to move up and down. Also, in each cycle of the dispensing operation, the current positional relationship between the nozzle and the liquid level detector is stored without returning the nozzle and the liquid level detector to the initial state, and the interval between the next nozzle and the liquid level detector is determined. The distance between the nozzle and the liquid level detector may be compared, and the nozzle may be moved by the difference between the two.

[0028]

As described above, according to the present invention, the amount of intrusion of the nozzle which enters the liquid container is controlled to the minimum necessary, so that the amount of liquid adhering to the outside of the nozzle is reduced. Can be. Therefore, it is possible to prevent dispensing of an excess liquid, and it is possible to improve dispensing accuracy. In addition, by reducing the influence of the remaining amount of the pre-solution, appropriate analysis data can be obtained. Further, in this case, the current movement amount of the nozzle can be stored, and the movement amount can be controlled so that the movement amount of the nozzle for the next dispensing is moved by the difference from the current movement amount. Therefore, by the combination of this configuration and the above-described configuration for controlling the amount of intrusion, there is little effect on the dispensed amount each time, which is caused by the adhesion of the currently dispensed nozzle to the nozzle. Dispensing can be performed each time while obtaining appropriate analysis data. Further, it is possible to prevent the periphery of the apparatus from being contaminated by the liquid adhering to the nozzle.

[Brief description of the drawings]

FIG. 1 is a perspective view schematically showing the vicinity of a nozzle of an automatic analyzer used in a first embodiment of the present invention.

FIG. 2 is an explanatory diagram showing a position state of a nozzle in a liquid container according to the first embodiment of the present invention.

FIG. 3 is a perspective view showing a nozzle vertical movement mechanism of an automatic analyzer used in a third embodiment of the present invention.

FIG. 4 is a cross-sectional view illustrating a joint state of a slider and a nozzle according to a third embodiment of the present invention.

FIG. 5 is an explanatory diagram illustrating a moving state of a nozzle according to a third embodiment of the present invention.

FIG. 6 is a sectional view showing a liquid suction start state according to a third embodiment of the present invention.

FIG. 7 is a cross-sectional view illustrating a state in which the liquid level detecting device according to a fourth embodiment of the present invention is stopped when the liquid level detector stops descending.

FIG. 8 is a sectional view showing a liquid suction start state according to a fourth embodiment of the present invention.

FIG. 9 is a cross-sectional view showing an intruded state of a nozzle according to a conventional method.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Nozzle 2 Liquid level detecting tool 3 Nozzle holding tool 4 Connecting tool 5 Nozzle transfer mechanism 6 Reaction vessel 7 Cleaning tool 8 Liquid vessel

Claims (1)

(57) [Claims] 1. A series of operations for moving a liquid dispensing nozzle to a liquid suction position for suction, moving the nozzle to a discharge position after suction and discharging after suction, and moving the nozzle to a cleaning position after discharge for cleaning. the liquid sample dispensing method for repeating, in accordance with the liquid suction amount, by controlling the nozzle moving amount in the liquid suction position, with so as to regulate the amount of intrusion nozzle entering into the liquid, the current nozzle Transfer
Memorize the amount of movement and calculate the amount of movement of the nozzle for the next dispensing.
Control the movement amount so that it moves by the difference from the current movement amount
A liquid sample dispensing method, characterized in that the liquid sample is dispensed.