JP4045211B2 - Automatic analyzer - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an automatic analyzer that automatically performs qualitative and quantitative analysis of biological samples such as blood and urine, and more particularly, an automatic analyzer having a function of dispensing a liquid from one container to another using a dispensing probe. About.
[0002]
[Prior art]
The automatic analyzer dispenses a sample consisting of a biological sample such as blood or urine from the sample container to the reaction container on the reaction line, and further dispenses the reagent from the reagent container to the reaction container on the reaction line. Qualitative or quantitative analysis is performed by measuring the mixture of the reagent and the reagent by a measuring means such as a photometer.
[0003]
During the dispensing operation for both the sample and the reagent, the tip of the dispensing probe is immersed in the liquid to be dispensed. The greater the immersion depth, the greater the amount of liquid attached to the outer wall of the probe and the greater the contamination. Therefore, in order to reduce the immersion depth of the dispensing probe as much as possible, the liquid level of the liquid in the container is detected, and the descending operation of the probe is stopped at the position where the tip of the probe reaches slightly below the liquid level. A general technique is to control the operation so that a predetermined amount of liquid is sucked into the probe. As a means for detecting the liquid level of the sample, a method of measuring the capacitance between the sample probe and the sample is used. In this method, the liquid level is detected by utilizing the fact that the capacitance greatly changes when the sample probe comes into contact with the sample.
[0004]
When a sample is sucked using such a sample probe, there may be a case where a film or a bubble is generated above the liquid surface of the specimen or the reagent due to a problem during the dispensing operation of the operator. In this case, the capacitance changes greatly when the tip of the dispensing probe comes into contact with the film or bubbles on the liquid level, so the film or bubbles are detected as the liquid level and set slightly below the existing liquid level. There is a possibility that the liquid level cannot be reached at the probe immersion height. That is, in a subsequent suction operation, a liquid less than a fixed amount or air is sucked instead of a liquid, and an analysis result different from an expected value may be output. In order to solve this problem, in Patent Document 1, a pressure sensor is provided in the suction flow path, the pressure in the suction flow path after the suction operation is stopped is detected, the rate of change is calculated from the detected pressure, and the calculated rate of change is predetermined. And a method for detecting clogging of the suction flow path or insufficient suction amount.
[0005]
[Patent Document 1]
Japanese Patent Laid-Open No. 2000-46846
[Problems to be solved by the invention]
In the method described in Patent Document 1, the rate of change in pressure is compared with a threshold value to detect an insufficient suction amount.
[0007]
However, when the suction flow path is clogged, the amount of change in pressure is large and detection is relatively easy, whereas the amount of change in pressure is very small when the suction amount is insufficient, that is, when air is also sucked in during suction, and the rate of change is low. It may be difficult to determine whether the amount of suction is insufficient compared to a predetermined threshold.
[0008]
Further, the pressure sensor often uses a semiconductor, but such a semiconductor pressure sensor cannot avoid an output drift due to temperature or the like. In this case, there is a possibility that the output drift is larger than the pressure change due to the insufficient suction amount, and therefore there is a possibility of erroneous detection. In particular, when determining whether or not the suction amount is insufficient with a fixed threshold value, the influence of this drift is large.
[0009]
In view of such a problem, the present invention has a function in an automatic analyzer that can accurately detect even when a predetermined amount of liquid is not sucked due to the presence of a film or a bubble on the liquid surface. It is to provide an automatic analyzer equipped.
[0010]
[Means for Solving the Problems]
The configuration of the present invention for achieving the above object is as follows.
[0011]
A dispensing device that dispenses a sample from a sample container to a reaction container using a dispensing probe, and a pressure that measures the pressure in the dispensing probe when the sample is aspirated from the sample container using the dispensing probe. Measuring means; and analyzing means for analyzing the contents of the reaction vessel;
In an automatic analyzer equipped with
Storage means for sucking different amounts of air with the dispensing probe before the sample suction operation and storing pressure values at the time of suction of the different amounts of air measured by the pressure measuring means;
The calculation means for calculating the threshold value during air suction based on the pressure value during suction of different amounts of air stored in the storage means, and the sample is normal during the suction operation by comparing the pressure during sample suction with the threshold value. And an automatic analyzer having a detecting means for detecting whether or not the liquid has been aspirated quantitatively.
[0012]
The present invention is applicable not only to sample dispensing probes but also to reagent dispensing probes. The probe means a mechanism that immerses a part in a liquid to be dispensed and sucks the liquid. The sample container and the reaction container are not necessarily in the shape of a container, and any container that can hold a liquid may be used. The pressure measuring means generally includes a sensor that outputs a pressure value as a change in voltage, such as a semiconductor pressure sensor, and an amplifier that amplifies the output from the sensor as necessary. is not. The analyzing means may be any means as long as it can analyze the contents in addition to detecting the color change of the liquid in the reaction vessel with a photometer.
[0013]
DETAILED DESCRIPTION OF THE INVENTION
Embodiments of the present invention will be described below in order from FIG.
[0014]
FIG. 1 is a schematic view of the periphery of a dispensing mechanism of a general automatic analyzer. Since the function of each part is well-known, detailed description is omitted. The sampling arm 2 of the sampling mechanism 1 moves up and down and rotates. Using the probe 105 attached to the sampling arm 2, the sample 7 in the sample container 101 arranged on the sample disk 102 rotating left and right is sucked and reacted. It is comprised so that it may discharge to the container 106. FIG. As can be seen from this figure, the sample container (sample container) 101 can be placed on the sample disk 102 directly on the sample disk 102 or the sample container 101 can be placed on a test tube (not shown). A structure that can accommodate a universal arrangement is generally used.
[0015]
The configuration of the automatic analyzer in FIG. 1 will be further described. On the rotatable reagent disk 125, reagent bottles 112 corresponding to a plurality of analysis items to be analyzed are arranged. The reagent dispensing probe 110 attached to the movable arm dispenses a predetermined amount of reagent from the reagent bottle 112 to the reaction container 106.
[0016]
The sample dispensing probe 105 performs a sample suction operation and a discharge operation in accordance with the operation of the sample syringe pump 107. The reagent dispensing probe 110 executes a reagent suction operation and a discharge operation in accordance with the operation of the reagent syringe pump 111. The analysis items to be analyzed for each sample are input from an input device such as a keyboard 121 or a CRT 118 screen. The operation of each unit in this automatic analyzer is controlled by the computer 103.
[0017]
As the sample disk 102 rotates intermittently, the sample container 101 is transferred to the sample suction position, and the sample dispensing probe 105 is lowered into the stopped sample container. When the tip of the dispensing probe 105 comes into contact with the liquid level of the sample along with the lowering operation, a detection signal is output from the liquid level detection circuit 151, and the computer 103 lowers the driving unit of the sampling arm (movable arm) 2 based on the detection signal. Control to stop operation. Next, after a predetermined amount of sample is sucked into the dispensing probe 105, the dispensing probe 105 rises to the top dead center. While the dispensing probe 105 is sucking a predetermined amount of sample, the pressure detection circuit uses the signal from the pressure sensor 152 to detect the pressure fluctuation in the flow channel during the suction operation between the dispensing probe 105 and the sample pump 107 flow channel. When monitoring is performed at 153 and an abnormality is found in the pressure fluctuation during suction, an alarm is added to the analysis data because there is a high possibility that a predetermined amount has not been sucked.
[0018]
Next, the sampling arm 2 rotates in the horizontal direction, the sample dispensing probe 105 is lowered at the position of the reaction vessel 106 on the reaction disk 109, and the sample held in the reaction vessel 106 is discharged. When the reaction container 106 containing the sample is moved to the reagent addition position, a reagent corresponding to the corresponding analysis item is added from the reagent dispensing probe 110. As the sample and reagent are dispensed, the liquid level of the sample in the sample container 101 and the reagent in the reagent bottle 112 is detected. The sample and the mixture in the reaction vessel to which the reagent has been added are stirred by the stirrer 113. During the transfer of the reaction container row, a plurality of reaction containers cross the light beam from the light source 114, and the absorbance or luminescence value of each mixture is measured by a photometer 115 as a measuring means. The absorbance signal enters the computer 103 via the interface 104 via the A / D converter 116, and the concentration of the analysis item is calculated. The analysis result is printed out to the printer 117 via the interface 104 or output to the CRT 118 and stored in the hard disk 122 as a memory. After completion of photometry, the reaction vessel 106 is cleaned at the position of the cleaning mechanism 119. The cleaning pump 120 supplies cleaning water to the reaction container and discharges waste from the reaction container. In the example of FIG. 1, three rows of container holders are formed so that three rows of sample vessels 101 can be set concentrically on the sample disk 102, and the sample suction position by the sample dispensing probe 105 is in each row. One by one is set.
[0019]
Next, the adverse effects of the film or bubbles generated on the liquid surface of the sample container or the liquid in the reagent container will be described below.
[0020]
When dispensing serum into a specimen container after centrifuging human blood, especially when performed manually, the probability of the formation of a film or air bubbles on the liquid surface is very high depending on the operation of the pipetting pipette. Therefore, even if the presence / absence of bubbles is visually inspected after dispensing, the possibility that the presence of bubbles cannot be detected due to a human error or the like may be sufficiently considered. In addition, some reagents contain surfactants and have a composition that easily foams, and the number of liquid levels may vary depending on the shaking of the liquid in the container when the device is mounted or the wave of the internal liquid depending on the container capacity. It is possible that a film is formed on mm.
[0021]
However, the immersion depth of the tip of the dispensing probe into the liquid at the time of detecting the liquid level is slightly below the liquid level to prevent contamination as much as possible, specifically, the probe descends at a position immersed in a reagent of about 2 to 4 mm. Control is performed so that the operation is stopped, and then a predetermined amount of liquid is sucked into the probe.
[0022]
For this reason, if there is a difference of several mm or more, specifically about 5 mm or more, between the height at which the liquid level is recognized by the film or bubbles and stopped, and the true liquid level height, more specifically, about 5 mm or more, If the immersion depth with the reagent does not reach the true liquid level, the liquid reagent is not aspirated from the true liquid level, and bubbles or films formed on the true liquid level are formed The air was dispensed, and finally the analysis results had a risk of being different from the expected value.
[0023]
Next, an embodiment of the present invention will be described below with reference to FIGS.
[0024]
FIG. 2 shows the pressure waveform applied to the probe and the pressure waveform applied to the probe when air is sucked in place of the liquid by detecting the film when the fixed amount is normally sucked. As can be seen from FIG. 2, these waveforms are similar. (1) No clear difference can be confirmed in the pressure value before suction. However, a difference of about 20% is recognized between the waveforms in (2) pressure value during suction and (3) pressure value after suction. That is, the gist of the present invention is to calculate (2) pressure value during suction-(1) pressure value before suction, or (3) pressure value after suction-(1) difference in pressure value before suction, Compared to the threshold value derived from the expected value of the pressure for each suction operation, these differences are in a function of recognizing an abnormal state when a difference greater than a specific value, that is, the threshold value is recognized.
[0025]
As specific means for calculating the difference, (2) the average value of the pressure during suction for a specific period-(1) the average value of the pressure before suction for a specific period, or (2) the pressure increase value for the specific period of pressure during suction- (1) A pressure increase value in a specific period of the pre-suction pressure can be considered. Similarly, (3) the average value of the post-suction pressure for a specific period-(1) the average value of the pre-suction pressure for a specific period, or (3) the pressure increase value of the post-suction pressure for a specific period-(1) the pre-suction pressure A method of comparing the pressure increase values for a specific period can be easily considered. Further, the value of the specific period may be several tens of ms, specifically about 50 ms to 1100 ms, but it is not intended to specify this value in the present embodiment.
[0026]
Next, an example of means for calculating a threshold for determining non-quantitative suction will be described below. In normal analyzers, preparation operations such as removal of bubbles in the flow path and confirmation of the number of remaining tests for the analysis reagent are performed immediately after the start of the analysis operation, which generally takes several minutes, and then the analyte is aspirated. Is called. In the present invention, a predetermined amount of air is sucked in advance by a dispensing probe during this preparation operation, and a threshold for non-quantitative suction determination is calculated each time. In other words, the present invention can be realized by calculating the threshold value in the preparatory operation immediately after the start of analysis without affecting the processing capability of the analysis item that is subsequently performed.
[0027]
Furthermore, by calculating the threshold value every time analysis is started, unstable factors such as daily fluctuations in the flow path system can be removed, and a stable and highly reliable threshold value can be set. When clogging occurs in the dispensing probe, the change in the pressure in the probe is large, so that it is relatively easy to detect the presence or absence of clogging even if the threshold value is fixed. In particular, if no clogging occurs after sample suction, the pressure inside the probe should return to atmospheric pressure after a while, but if clogging occurs, the pressure inside the probe remains negative. For this reason, it is possible to detect clogging with high accuracy by comparing the pressure after a while after suction with a threshold value. However, when the suction amount is insufficient, the pressure fluctuation amount is small compared to the case of normal suction, and the pressure inside the probe returns to atmospheric pressure for a while after suction. It is necessary to determine using Therefore, determination by comparison with a fixed threshold value is extremely difficult in practice. Therefore, the present invention is characterized in that different amounts of air are sucked before the start of dispensing, and the threshold value is set based on the pressure value at that time. Thereby, an error due to a drift of the semiconductor pressure sensor can be eliminated.
[0028]
Next, a specific example of the threshold value calculation method will be described. For example, means for calculating two air suction pressure values of the maximum suction amount and the minimum suction amount that can be dispensed as a device, and calculating a threshold value of the total suction amount from an approximate expression connecting the pressure values between these two points. Conceivable. Naturally, the pressure value at the time of air suction of three points of the maximum suction amount, the intermediate threshold suction amount, and the minimum suction amount may be calculated, and the threshold value may be calculated from the approximate expression as described above. Alternatively, various calculation methods such as a means of preparing a threshold value table in advance and selecting an optimum threshold value from a specific amount of air suction operation without newly calculating the threshold value for each routine operation can be considered. The method is not specified in the examples.
[0029]
Next, an example of a technique for improving the detection accuracy of this embodiment will be described. Since pressure sensors are semiconductor gauges, they are susceptible to temperature effects. For this reason, it is common practice to guarantee the ambient temperature, but there is a slight change in pressure detection sensitivity due to fluctuations in the temperature of the wash water in the flow path. In rare cases, it can be assumed. Even in such a case, (1) the pressure value before suction during the preparatory operation and (1) the difference between the pressure values before suction, that is, the pre-suction pressure value, that is, the minute fluctuation is corrected to the threshold value for each detection operation, A technique for improving the accuracy of the threshold is also considered as an example.
[0030]
FIG. 3 shows an example of the threshold value and the detected pressure proposed in the present invention. Specifically, the above-mentioned (2) average value of the pressure during suction for a specific period− (1) the average pressure value of the pressure before suction for the specific period. The threshold values from which the pressure values at the time of air suction at the two points of the maximum suction amount and the minimum suction amount are calculated by the difference and the preparation operation, respectively, are shown. As can be seen from this figure, there is a clear difference between the pressure at the time of quantitative suction and the pressure value at the time of non-quantitative suction. It turns out that it can be recognized reliably.
[0031]
As an example of an application using this recognition result, an alarm is automatically added to analysis data that may output data outside the expected value when it is recognized as non-quantitative aspiration, which may differ from the expected value Accompany information and output analysis results. Alternatively, it is conceivable that the analysis data is masked and the result is not output, and it is possible to easily configure a system that prevents the reporting of data outside the expected value.
[0032]
In other words, as described above, by applying the present invention, it is possible to automate the work that has been relied on the human part so far and contribute to a significant improvement in the reliability of the dispensing operation.
[0033]
【The invention's effect】
As described above, according to the present invention, when a film or a bubble is present on the sample liquid surface in the sample container or on the reagent liquid surface in the reagent container, the film or the bubble is not a true liquid surface. In other words, the tip of the probe does not reach the liquid level and is dispensed.In other words, a liquid that is less than the expected value is dispensed instead of the expected amount of liquid. Although there was a risk of output, by carrying out the present invention, even if a bubble layer exists on the sample liquid surface in the sample container or the reagent liquid surface in the reagent container, It is possible to provide an automatic analyzer that can reach the liquid level, perform quantitative suction of the expected amount, perform a reliable suction operation, and obtain a stable analysis result.
[Brief description of the drawings]
FIG. 1 is a schematic diagram showing the overall configuration of an automatic analyzer to which the present invention is applied.
FIG. 2 is a pressure detection waveform during quantitative suction and non-quantitative suction.
FIG. 3 shows an example of a pressure difference between quantitative suction and non-quantitative suction to which the present invention is applied.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 ... Sampling mechanism, 2 ... Sampling arm, 7 ... Sample, 101 ... Sample container, 102 ... Sample disc, 103 ... Computer, 104 ... Interface, 105 ... Probe, 106 ... Reaction container, 107 ... Sample syringe pump, 109 ... Reaction disk, 110 ... reagent dispensing probe, 111 ... reagent syringe pump, 112 ... reagent bottle, 113 ... stirrer, 114 ... light source, 115 ... photometer, 116 ... A / D converter, 117 ... printer, 118 ... CRT, 119 ... Cleaning mechanism, 120 ... Cleaning pump, 121 ... Keyboard, 122 ... Hard disk, 125 ... Reagent disk, 151 ... Liquid level detection circuit, 152 ... Pressure sensor,
153: Pressure detection circuit.

Claims (8)

A dispensing device for dispensing a sample from a sample container to a reaction container using a dispensing probe;
Pressure measuring means for measuring the pressure in the dispensing probe when a sample is aspirated from the sample container using the dispensing probe;
Analyzing means for analyzing the contents of the reaction vessel;
In an automatic analyzer equipped with
Before the sample aspirating operation, different amounts of air are aspirated with the dispensing probe,
Storage means for storing pressure values during suction of different amounts of air measured by the pressure measuring means;
Calculating means for calculating a threshold value during air suction based on pressure values during suction of different amounts of air stored in the storage means;
An automatic analyzer comprising: detecting means for detecting whether or not a sample is normally aspirated quantitatively during an aspiration operation by comparing a pressure at the time of sample aspiration and the threshold value. The automatic analyzer according to claim 1, wherein
An automatic analyzer characterized by using an average value of pressure during a specific period or a pressure increase value during a specific period as the pressure value during suction of different air and the pressure value during sample suction. The automatic analyzer according to claim 1, wherein
2. The automatic analyzer according to claim 1, wherein the pressure value at the time of sucking different air and the pressure value at the time of sucking the sample use an average value of pressure during a specific period after completion of suction or a pressure increase value during a specific period after completion of suction. The automatic analyzer according to claim 2 or 3,
The automatic analyzer is characterized in that the length of the specific period is 50 to 100 ms. In the automatic analyzer in any one of Claims 1-4,
The automatic analyzer according to claim 1, wherein the suction of the different air is performed during a preparatory operation including bubble removal in the flow channel immediately after the start of the analysis operation. In the automatic analyzer in any one of Claims 1-4,
As the different air amounts, two types of maximum and minimum values that can be sucked by the dispensing probe are used, and the threshold values for the air suction amounts in all ranges are calculated from an approximate expression that connects these two pressure values. An automatic analyzer characterized by having a function. In the automatic analyzer in any one of Claims 1-6,
An automatic analysis system comprising a function of adding an alarm to analysis data of a sample detected that the sample is not normally quantitatively aspirated by the detection means. In the automatic analyzer in any one of Claims 1-6,
An automatic analysis system comprising a function of masking analysis data of a sample detected that the sample is not normally quantitatively sucked by the detection means and not outputting a result.

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