JP2000171470A - Automatic analyzer - Google Patents

Abstract

(57) [Problem] To provide an automatic analyzer suitable for reducing the possibility of erroneous liquid level detection due to extraneous noise and further reducing contamination. Prior to dispensing a sample in a sample container to a reaction container through a dispensing probe,
The liquid level of the sample in the sample container is detected by the liquid level detection device 151. In detecting the liquid level, the dispensing probe 105 is first lowered at a high speed to a predetermined position. The dispensing probe 105 is then switched to a low speed, and descends at that low speed to enter the sample and stop. The type of the sample container 101 is detected by the type detection device 150, and the switching timing of the dispensing probe 105 from high speed to low speed is changed according to the type.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an automatic analyzer and, more particularly, to an automatic analyzer having a liquid level detecting means suitable for detecting a liquid level such as a sample or a reagent before dispensing the liquid.

[0002]

2. Description of the Related Art When analyzing a biological sample such as blood or urine by an automatic analyzer, a sample in a sample container is dispensed into a reaction container through a dispensing probe. When dispensing the reagent in the reagent container to the reaction container, the dispensing is performed through the dispensing probe. The dispensing is performed by lowering the dispensing probe, entering the liquid to be dispensed, stopping the liquid, and aspirating the liquid in that state. The sample and the reagent dispensed into the reaction vessel are mixed by stirring, and the mixed solution is measured by the measuring means.

When the dispensing probe is immersed in a liquid, the larger the amount of the immersion probe, the greater the amount of the liquid attached to the outer wall, which results in an increase in contamination. For this reason, the automatic analyzer detects the liquid level of the liquid to be dispensed, and controls the descending amount of the dispensing probe based on the result, thereby minimizing the amount of the dispensing probe entering the liquid. Limit. As a means for detecting the liquid level, a method of detecting changes in the capacitance value or resistance value of the sample, a method using refraction or reflection by light or ultrasonic waves, detecting a pressure change of the liquid in the dispensing probe There are known methods. Among these known techniques, an example of detecting a change in capacitance value is disclosed in, for example, Japanese Patent Application Laid-Open No. 62-28976.
No. 9 and Japanese Patent Publication No. 6-7112.

[0004] On the other hand, high analytical processing capability is one of the important factors in automatic analysis. To improve this processing capacity, it is necessary to increase the dispensing efficiency. Therefore, the speed at which the dispensing probe is lowered during liquid level detection is usually set to a constant value as high as possible.

[0005]

However, in the method in which the lowering speed of the dispensing probe is set to a constant value as high as possible, the liquid level detection is easily affected by extraneous noise, so that an incorrect liquid level detection may be performed. There is a problem that the nature is large. The external noise includes noise that is suddenly generated from equipment used around the automatic analyzer. Also, in the case of a capacitance level detection type liquid level detection device using a dispensing probe as an electrode for liquid level detection, since the container containing the liquid to be dispensed is non-conductive, Discharge of electric charges generated by charging the inside also becomes external noise.

An object of the present invention is to provide an automatic analyzer suitable for reducing the possibility of erroneous liquid level detection due to extraneous noise.

[0007] Another object of the present invention is to provide an automatic analyzer suitable for further reducing contamination.

[0008]

An automatic analyzer according to the present invention comprises: means for lowering the dispensing probe so that the dispensing probe enters the liquid in the first container;
Means for dispensing the liquid in the first container to the second container through the dispensing probe, means for measuring the contents in the second container, and the liquid level of the liquid in the first container. Means for detecting the pipetting probe to a predetermined position.
Lower at the speed of 1, then switch to a second speed slower than the first speed and lower the dispensing probe lowering speed so as to enter and stop the liquid in the first container while lowering. Control means.

According to another aspect of the present invention, there is further provided a means for detecting a type of the first container, and the control means controls the second type of the dispensing probe according to the detected type of the first container. 1
The timing for switching from the second speed to the second speed is changed.

[0010]

FIG. 1 shows an embodiment of an automatic analyzer according to the present invention. In FIG. 1, since the function of each unit is known, detailed description of each unit is omitted.

The dispensing mechanism 1 has a dispensing arm 2 and drives the dispensing probe 105 attached to the tip of the dispensing arm 2 to move the dispensing probe 105 up and down and to position it at the sampling position and the dispensing position. The sample disk 102 holds a number of sample containers 101 containing samples, and is intermittently rotated at predetermined intervals. When the dispensing probe 105 moves to the sampling position, the dispensing probe 105 first descends toward the sample container 101 moved to the sampling position, and the liquid level of the sample contained therein is detected by the liquid level detecting device 151. As described later, when various types are used as the sample container 101, the type is detected by the container type detection device 150 prior to the liquid level detection, and the type detection signal is output to the computer 103. . The lowering speed of the dispensing probe 105 is controlled by the computer 103 based on the detected type detection signal. That is, the computer 103 determines the descending speed of the dispensing probe 105 based on the type detection signal.
05 is lowered at a constant high speed from the top dead center position A to a predetermined position (for example, a position several mm before the opening end of the container 101) from the viewpoint of improving the dispensing efficiency, and thereafter is lowered to a constant low speed. Dispense probe 105 so that it switches and slowly descends to enter and stop the sample in container 101.
Control the speed of the car. In the case of an automatic analyzer configured to use only one type of sample container 101, the distance from the top dead center position A to a predetermined position (for example, a position several mm before the container 101) is Since it is a value that can be known in advance as a constant and can be stored in the computer 103 in advance, there is no need to use the container type detection device 150.

The liquid level detecting device 151 detects a change in capacitance or resistance value of a sample, a method using refraction or reflection by light or ultrasonic waves, and detects a change in pressure of liquid in a dispensing probe. The method is well known. In the present invention, any of them can be used. However, in the embodiments of the present invention, it is assumed that a capacitance change detection type is used for convenience, and a detailed description of itself is omitted because it is publicly known. In addition, since the container type detection device 150 itself is a known device, detailed description thereof will be omitted.

A reaction disk 109 holding a large number of reaction vessels 106 is arranged on a constant temperature water bath and is rotated intermittently at predetermined intervals. In a state where the dispensing probe 105 descends and enters the sample in the sample container 101 at the sample dispensing position and stops, the sample is sucked through the dispensing probe 105 by the sample pump 107. Thereafter, the dispensing probe 105 moves upward and moves to the sample dispensing position, where the aspirated sample is dispensed into the reaction vessel 106 by the sample pump 107.

When the liquid level detecting device 151 is of the capacitance change detecting type, the dispensing probe 105 is used for detecting the liquid level.
It is common to stop the sample by infiltrating into the sample while lowering it, and then inhale the sample for dispensing to the dispensing probe 105 in that state. In the case of a system using refraction or reflection, liquid level detection and dispensing are usually performed separately.

After dispensing the sample, the dispensed reaction vessel 106 is moved to a reagent dispensing position. A reagent disk 125 holding a number of reagent containers 112 containing reagents is intermittently rotated, whereby each reagent container can be moved to a reagent sampling position. The reagent in the reagent container at the reagent sampling position is sucked through the dispensing probe 110 by the reagent pump 111. The dispensing probe 110 is moved to the reagent dispensing position, where the inhaled reagent is dispensed by the reagent pump 111 to the reaction vessel 106 where the sample has been dispensed.

A reaction container 10 into which a sample and a reagent are dispensed.
6 is moved to the position of the stirrer 113 and is stirred by the stirrer 113. The mixed liquid mixed by stirring is subjected to light absorption measurement when the reaction vessel 106 containing the mixed liquid crosses the axis of the light emitted from the light source 114 of the photometer 115. The measured light absorption signal is A / D converted by the A / D converter 116, introduced into the computer 103 via the interface 104, and converted into an absorbance. The analysis result is printed out by the printer 117 via the interface 104 and displayed on the screen of the CRT 118. The analysis result is further stored on a hard disk 122 as a memory.

The reaction vessel 106 containing the mixed solution after the measurement is moved to the washing position and washed by the washing mechanism 119. That is, the reaction vessel 106 moved to the cleaning position
Is cleaned by the cleaning liquid supplied by the cleaning pump 120.

The analysis items to be analyzed are input to the computer 1 by operating an input device 121 such as a keyboard.
Entered in 03. The operation of each unit and the cooperative operation between the units are controlled by the computer 103.

Although the detection of the reagent liquid level at the time of dispensing the reagent was not described, the same apparatus as the liquid level detecting apparatus 151 and the container type detecting apparatus 150 was used in the same manner as in the case of dispensing the sample. Alternatively, the liquid level may be detected.

In the case of liquid level detection, it is desirable to prevent erroneous liquid level detection due to external noise. The external noise includes noise suddenly generated from a peripheral device in which the automatic analyzer is arranged. In addition, when the liquid level detection device 151 is of the capacitance change detection type, there is noise generated in the container that stores the liquid. That is, since a container for containing a liquid such as a sample or a reagent is non-conductive, the inner surface thereof is easily charged. on the other hand,
When the liquid level detecting device is a capacitance change detection type, the dispensing probe is conductive because it is used as an electrode for liquid level detection. For this reason, when the dispensing probe is introduced into the container at the time of liquid level detection, the electric charge charged inside the container is discharged through the dispensing probe, and this becomes liquid level detection noise, giving erroneous liquid level detection.

FIG. 2 shows a process in which the dispensing probe descends and is introduced into the container for accommodating the liquid until the liquid level is detected. In FIG. 2, as an example, the dispensing probe is shown as a dispensing probe 105 for dispensing a sample in FIG. 1, and the container is a sample container 101 for containing a sample.

A and D indicate the positions of the top dead center and the bottom dead center of the dispensing probe, B indicates the position near the upper end of the sample container 101, and C indicates the liquid level position. The probe 105 starts descending from the top dead center position A, passes through a position B near the upper end of the container 101, and penetrates the liquid 7 which is a sample in the container 101. The liquid level detection circuit 151 detects the liquid level of the liquid through the dispensing probe 105, and the dispensing probe 105 stops slightly below the liquid level position C.

The dispensing probe 105 has both a function as a dispensing probe for dispensing the liquid 7 which is a sample contained in the container 101 and a function as an electric liquid level detecting sensor. Therefore, conductivity is required as a material of the dispensing probe 105, and a metal such as stainless steel or a conductive plastic material is generally used. However, since the sample container 101 is non-conductive, its inner surface is charged. This charging is particularly likely to occur when the humidity in the atmosphere is low. The charging position is often B near the upper part of the sample container 101 (position near the opening). However,
When the charging voltage is high, discharge may occur in a portion several cm below the opening of the container 101. When the charging occurs, the dispensing probe 105 descends, and when reaching the charged portion, the charged electric charge is discharged through the dispensing probe 105, which gives a noise signal of the liquid level detecting device.

FIG. 3 shows an example of a general liquid level detection signal when the dispensing probe descending speed is constant and no countermeasures against external noise are taken. In the figure, the horizontal axis represents time, and the vertical axis represents a voltage signal level. A, B and C on the time axis are shown in Fig. 2.
Indicates the time position corresponding to each of them. Since no external noise countermeasures have been taken, as can be seen from FIG.
In addition to the normal liquid level detection voltage signal, a discharge voltage signal generated in the container 101 exists as an external noise signal. This noise signal width depends on the discharge voltage. The noise width is generally on the order of several milliseconds, but may reach ten and several milliseconds depending on the discharge voltage. An external noise signal due to such a discharge hinders normal detection of the liquid level. That is, incorrect liquid level detection information is given.

FIG. 4 shows a normal automatic operation in which the dispensing mechanism 1 includes a pulse motor as a power source for moving the dispensing probe 105 up and down (moving in the vertical direction), and the pulse motor lowers the dispensing probe at a constant high speed. FIG. 5 shows an example of a liquid level detection signal in the analyzer. The dispensing mechanism 1 includes a pulse motor as a power source for moving the dispensing probe 105 up and down (moving in the vertical direction). 5 shows an example of a liquid level detection signal according to an embodiment of the present invention, in which the sample is lowered at a constant high speed to a predetermined position, and is then switched to a constant low speed to enter and stop the sample while descending. In both figures, the horizontal axis represents time, and the vertical axis represents the descending speed of the dispensing probe 105 (number of pulses per second = pps). The meanings of A, B, C and D are the same as those in FIG.

First, paying attention to FIG. 4, the total descending movement amount of the dispensing probe 105, that is, the movement amount from the top dead center position A to the bottom dead center position D is set as one control value. In order to lower and stop the dispensing probe 105 from a mechanical point of view such as the moment of inertia, a slow-up (S
U) When stopped, slow down (SD) control is used. That is, the dispensing probe 105 immediately rises from 0 pps to about 300 pps and starts to descend, and then slowly increases to about 3000 pps,
After that it descends at that speed. When stopped, the dispensing probe 105 slowly decreases its descending speed from 3000 pps to 300 pps, and immediately returns to 0 pps from that speed.
In this case, the computer 103 sets an allowable operation time for each descent operation, monitors whether the operation is completed within the allowable time, and generates an error if the processing is not completed. is there. Further, it is desirable that each operation is completed in as short a time as possible. This is because shortening each operation substantially contributes to shortening of a machine cycle and, as a result, improvement of processing capacity. This is why the descending speed is set to a high speed of about 3000 pps.

When the dispensing probe 105 has a high descent speed, the allowable noise value for the liquid level detection signal is 20 mse.
When it is set to about c to 30 msec, it depends on the resolution of the dispensing probe 105 by the dispensing mechanism 1 up and down.
The amount of immersion (the amount of infiltration) of Sample 05 into Sample 7 is about 10 mm in total of the allowable noise value and the amount of slowdown, increasing cross contamination and causing a problem in analytical performance.
For this reason, the amount of slowdown is set to the smallest possible value, the allowable noise value is set to about 5 msec, and the amount of
A control value as small as possible from 3 mm to 3 mm is used. However, as described above, the noise width generated by the charge discharge from the sample container 101 is about several milliseconds, and may reach + several milliseconds depending on the discharge voltage. Therefore, in a normal automatic analyzer, when the above-mentioned wide noise of + several msec occurs near the position B, the erroneous detection position B ′ which does not reach the liquid level position C as shown in FIG.
Is determined to be the liquid surface position C, and the sample probe is
105 stops. That is, an incorrect liquid level detection result is given.

Next, focusing on FIG. 5, in the present invention, as described above, the container type detecting device 150 is incorporated in the apparatus as a part of the automatic analyzer, and the type of the sample container 101 is set before the liquid level detecting operation. The detection result, that is, the type of the sample container is output to the computer 103. Thereby, the computer 103 can automatically recognize the range of the liquid level position C from the container type detected by the container type detection device 150 before the dispensing probe 105 descends from the top dead center A. .

Therefore, in the control method according to the embodiment of the present invention, the dispensing probe 105 is slowed down a few mm before the opening end of the container 101 using the detection result of the container type detecting device 150, To set the operation control value so that the liquid level detection signal is input at the time of low speed lowering. With this control value, the liquid level detection signal is always input in a low speed state, that is, in a state where the amount of descent per unit time is small. For this reason,
The following merits can be expected.

(1) When the amount of penetration of the dispensing probe 105 into the liquid is the same as that in the normal case, the allowable noise value is several tens to several hundreds of msec, which is several tens of milliseconds compared to the normal example.
As shown in FIG. 5, even when a wide noise is generated at the position B near the opening end, the dispensing probe 105 exceeds the noise allowable value and the dispensing probe 105 is moved to the liquid level position C as shown in FIG.
Without stopping at a position that does not reach
To detect the liquid level.

(2) Since the dispensing probe 105 is stopped from a low speed, it is not subject to mechanical restrictions and can be stopped immediately, which is normally impossible. Therefore, by setting the infiltration amount of the probe 105 after detecting the liquid level to the minimum necessary value in accordance with the suction amount of the liquid 7, cross contamination is further reduced, and a more stable analysis result is obtained. It is possible to obtain.

(3) When the sample container 101 is a large-diameter container such as a test tube, the inner diameter is about 16 to 17 mm, and the cross-sectional area increases accordingly. In other words, when the liquid 7 is stored, the area of the liquid surface becomes large, so that even if the amount of penetration of the dispensing probe 105 is about 3 mm, the dead volume is as large as about 500 μl. However, according to the embodiment of the present invention, the dead volume of the container 101, which is normally impossible, can be significantly reduced by setting the infiltration amount of the dispensing probe 105 to the necessary minimum as described above. . That is, specifically, 100 μl or 50 μl depending on the control set value.
Even when a test tube is used as the container 105, it is possible to realize a dead volume value as small as approximately μl as in the case where a container other than a test tube is used.

FIGS. 6 and 7 show the dispensing probe 1 of the dispensing mechanism 2.
When a DC motor with an encoding function is used instead of the pulse motor as the drive source for the vertical movement of 05,
4 and 5 show an example of a normal automatic analyzer corresponding to FIG. 4 and an example of liquid level detection in an embodiment of the present invention, respectively. The vertical axis is 1
Instead of the number of pulses per second, the number of revolutions per second (r
pm). 1000rpm as high speed setting
However, 100 rpm is used as the low speed setting value.
6 and 7 that the same results as those obtained from FIGS. 4 and 5 can be obtained.

FIG. 8 shows the relationship between each container and the dispensing probe when detecting the liquid level when three types of containers are used as sample containers. In the drawing, (A) shows an example using a test tube, (B) shows an example using a cup-shaped container, and (C) shows an example using a cup-shaped container as a sample container. An example of holding on a unit is shown. As shown in FIG. 8, the distance (total descending amount) between the top dead center position and the bottom dead center position is X _A ,
Different X _b and _{X C} respectively.

FIG. 9 shows an example of a descent speed control by a normal example of the dispensing probe, which is performed corresponding to the examples of FIGS. 8A, 8B and 8C, respectively. (A),
7A and 7B show examples of lowering speed control of the dispensing probe according to the embodiment of the present invention, which are performed corresponding to the examples of FIGS. 9 and 10, the vertical axis indicates the descending speed of the dispensing probe, and the horizontal axis indicates the descending time.

As shown in FIG. 9, in the normal control, a value that requires the maximum descending amount, that is, the descending speed of the X-axis, and the horizontal axis represents the descending time.

_A is set for all sample container examples, and the penetration amount is also D _A for all sample container examples.
Is set to On the other hand, as shown in FIG. 10, in the embodiment of the present invention, the total descending amount is X
_A, is set to X _B and X _C respectively different values, entering amount D _B, and D _C and D _D, is set to the optimum value corresponding to the individual suction amount. Therefore, the timing of switching the speed from the high speed to the low speed differs depending on the container type. Note that D _B = D _C depending on individual conditions.
= May of course also serving as _{D D.}

By controlling the lowering speed of the dispensing probe shown in FIG. 10, even if the type of the sample container is different, the aforementioned (1)
The advantages of (3) are not impaired.

Next, as described above, a pulse motor or a DC motor having an encoding function is used as a drive source of the dispensing probe 105 of the dispensing mechanism 1. Thereby, the lowered position of the dispensing probe can be detected. Thereby, the computer 103 can verify at what position from the top dead center to the bottom dead center the dispensing probe has stopped. Therefore also computer 103
Is to compare the liquid level position information that can be estimated from the container type (type) information obtained from the container type detection device with the position where the dispensing probe actually stopped, that is, the dispensing probe position during the liquid level detection operation. Thus, it can be determined whether the liquid level detection has been performed normally. If the detection is not normal, the cause of the failure, specifically, whether the dispensing probe 105 did not drop due to step-out or any failure, or stopped due to external noise such as static electricity, etc. Can be determined from the dispensing probe position information.

Also, from the liquid level position information that can be estimated from the type detection result of the container type detecting device 150, it is possible to estimate at which position the liquid level detection signal is input. Therefore, based on the estimated liquid level position information, the liquid level is not detected outside the estimated liquid level range, for example, in the upper part outside the range,
By performing liquid level detection only within the range of the estimated liquid level position, the possibility of malfunction due to external noise can be further reduced.

[0041]

According to the present invention, an automatic analyzer suitable for reducing the possibility of erroneous liquid level detection due to extraneous noise is provided. According to the present invention, there is also provided an automatic analyzer suitable for further reducing contamination.

[Brief description of the drawings]

FIG. 1 is an overall configuration diagram showing an embodiment of an automatic analyzer according to the present invention.

FIG. 2 is a diagram showing a process according to the present invention from when a dispensing probe is lowered into a container for containing a liquid until liquid level detection is performed.

FIG. 3 is a diagram showing an example of a general liquid level detection signal when the descending speed of the dispensing probe is constant and no external noise countermeasures are taken.

FIG. 4 shows a liquid in a normal automatic analyzer in which a dispensing mechanism includes a pulse motor as a power source for vertically moving (vertically moving) the dispensing probe, and the pulse motor lowers the dispensing probe at a constant high speed. FIG. 6 is a diagram illustrating an example of a surface detection signal.

FIG. 5 shows a dispensing mechanism including a pulse motor as a power source for moving the dispensing probe up and down (moving in the vertical direction). The pulse motor lowers the dispensing probe at a predetermined high speed to a predetermined position. FIG. 7 is a diagram showing an example of a liquid level detection signal in the embodiment of the present invention, in which the sample is switched to a constant low speed and then descends to enter the sample and stop.

FIG. 6 shows a liquid in a normal automatic analyzer corresponding to FIG. 4 when a DC motor with an encoding function is used in place of a pulse motor as a drive source for up and down movement of a dispensing probe of a dispensing mechanism. The figure which shows the example of surface detection.

FIG. 7 shows a liquid according to an embodiment of the present invention corresponding to FIG. 5 in the case where a DC motor with an encoding function is used instead of a pulse motor as a driving source for the vertical movement of a dispensing probe of a dispensing mechanism. The figure which shows the example of surface detection.

FIG. 8 is a diagram showing a relationship between each container and a dispensing probe when detecting a liquid level when three types of containers are used as sample containers.

9 is a diagram showing an example of a descent speed control by a normal example of a dispensing probe, which is performed corresponding to the examples of FIGS. 8A, 8B, and 8C, respectively.

FIG. 10 is a diagram showing an example of a descent speed control according to the embodiment of the present invention of the dispensing probe, which is performed corresponding to the examples of FIGS. 8A, 8B, and 8C, respectively.

Claims (6)

[Claims] 1. A means for lowering the dispensing probe so that the dispensing probe enters the liquid in the first container, and the liquid in the first container is transferred to the second container through the dispensing probe. Means for dispensing, means for measuring the contents in the second container, means for detecting the liquid level of the liquid in the first container, and dispensing probe up to a predetermined position. The dispensing probe is lowered at a first speed, and then switched to a second speed slower than the first speed while being lowered and penetrated into the liquid in the first container to stop. And an automatic analyzer. 2. The apparatus according to claim 1, further comprising: means for detecting a type of the first container, wherein the control means is configured to detect the type of the first container.
An automatic analyzer, wherein the timing of switching the dispensing probe from the first speed to the second speed is changed in accordance with the type of one container. 3. The automatic analyzer according to claim 1, wherein the dispensing probe also serves as an electrode for detecting the liquid level by the liquid level detecting means. 4. An automatic analyzer according to claim 3, wherein said liquid level detecting means is of a capacitance change detection type. 5. The automatic analyzer according to claim 1, wherein a stop position of the dispensing probe when the dispensing probe descends and stops is detected. 6. A liquid level detection range according to claim 2, wherein a liquid level detection range is estimated from a type of said first container detected by said type detection means. An automatic analyzer, wherein liquid level detection by means is not performed.