JP2010236967A - Automatic analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an automatic analyzer for carrying out a qualitative-quantitative analysis of a biological sample such as blood or urine which includes a liquid dispensing mechanism for executing a dispensing operation accurately, regardless of kinds of liquids when spitting a sample to an empty reaction vessel, and for executing the dispensing operation without bringing the head of a sample probe into contact with the bottom of the reaction vessel. <P>SOLUTION: In the automatic analyzer, a gap between the reaction vessel bottom and the sample probe head is kept constant when executing the dispensing operation to the reaction vessel, and the sample probe 3 is moved up while executing the dispensing operation, thereby preventing any sample from adhering to the side face of the sample probe and enabling a dispensing accuracy to be improved. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an automatic analyzer that performs qualitative / quantitative analysis of biological samples such as blood and urine, and more particularly to an automatic analyzer that includes a probe that discharges liquid into a reaction container.

  Among automated analyzers that perform qualitative / quantitative analysis of biological samples such as blood and urine, for analysis with a relatively large amount of components to be measured in the sample, the reaction reagent is mixed and reacted with the sample in the reaction vessel. Colorimetric analysis is used to measure the color change of the reaction solution. In this colorimetric analysis, a sample and a reagent are added to a reaction container whose upper side is open, and a change in the color of the reaction solution is measured as a change in absorbance at a plurality of wavelengths.

  In the case of a blood sample, since a large amount of sample cannot be obtained, it is desirable that many items can be analyzed with as little sample as possible. In recent years, there has been a demand for cost reduction of analysis, and it is required to reduce the amount of reagent used per analysis. Correspondingly, as a method of discharging a predetermined amount of sample into one reaction vessel, it is required to use a smaller amount of sample per analysis, and the current sample amount per analysis is one digit microliter. It is as follows. Various inventions have been made to discharge a very small amount of such a sample into a reaction container. For example, in Patent Document 1, when the discharge amount to the reaction container is 5 microliters or less, the surface tension of the sample is discharged by pressing the tip of the sample dispensing nozzle against the bottom of the reaction container and then discharging the sample. In order to prevent the sample from the nozzle from moving smoothly into the reaction vessel and to prevent the outer periphery of the nozzle tip from becoming contaminated with the discharged sample when the discharge volume is greater than 5 microliters. A technique is disclosed in which the sample is discharged after the tip is positioned several millimeters above the bottom of the reaction vessel.

JP-A-6-242126

  In order to improve the analysis throughput, a general automatic analyzer is equipped with hundreds of reaction vessels, and the bottom surface of each reaction vessel is a small one of 10 mm square or less. Although the reaction vessel is made of glass or plastic, the molding accuracy cannot be improved so much due to the manufacturing cost, and there is also an installation error when setting the reaction vessel on the automatic analyzer. The height is slightly different for each reaction vessel.

  When there is a large amount of sample, the variation in the bottom height of the reaction vessel does not affect the dispensing error so much, but the smaller the sample amount, the more accurately the bottom height of the reaction vessel is desirable. . The technique described in Patent Document 1 describes that when the amount of sample is larger than 5 microliters, the dispensing nozzle is stopped several millimeters above the bottom of the reaction vessel. This seems to determine the position of the bottom by the design value of the apparatus, but in fact the bottom height seems to be different for each reaction vessel, and the distance between the bottom of the reaction vessel and the nozzle is different for each reaction vessel. Seems to be different. In addition, when dispensing by pressing the sample probe against the bottom of the reaction vessel, either detect that the nozzle has contacted the bottom of the reaction vessel by some means, or decide uniformly on the design value of the apparatus. It is necessary to adopt. In the former method, it is necessary to make the nozzle collide with the bottom of the reaction container every time it is dispensed, so there is a concern that the life of the nozzle and the reaction container may be shortened. In the latter method, the distance between the nozzle and the bottom of the reaction container varies from reaction container to reaction container, and there is a concern that an adverse effect may occur particularly when a small amount of sample is accurately dispensed.

  An object of the present invention is to provide an automatic analyzer equipped with a dispensing mechanism capable of dispensing accurately even when a dispensing amount is very small when dispensing a liquid into a reaction vessel.

  The configuration of the present invention for achieving the above object is as follows.

  An automatic analyzer comprising a reaction container for mixing a sample and a reagent, a probe for discharging a liquid to the reaction container, and a liquid level detection mechanism for detecting the liquid level of the liquid contained in the reaction container , The liquid level height of the liquid discharged from the probe to the reaction container is detected by the liquid level detection mechanism, information on the detected liquid level height, and the amount of liquid discharged from the probe to the reaction container And a bottom surface height calculating mechanism for calculating the height of the bottom surface of the reaction vessel based on the information of the above.

  When dispensing a liquid into a reaction vessel, it is possible to provide an automatic analyzer equipped with a dispensing mechanism capable of accurately dispensing even if the dispensing amount is very small.

Schematic diagram of a general automatic analyzer. A reaction vessel in the form of a divided block. Height measurement method using liquid level detection. Height measurement method using liquid level detection. The size of the liquid ball that can be made on the sample probe.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 1 shows an outline of a general automatic analyzer in which the present invention is implemented.

  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 sample probe 3 attached to the sampling arm 2, the sample in the sample container 101 arranged on the sample disk 102 rotating left and right is sucked and reacted. It is configured to dispense into the container 5. As can be seen from this figure, the sample container 101 is placed on the sample disk 102 in a universal arrangement in which the sample container 101 can be placed directly on the sample disk 102 or on the test tube (not shown). In general, a structure that can cope with the above is applicable.

  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 5.

  The sample probe 3 performs a sample suction operation and a dispensing operation in accordance with the operation of the sample syringe pump 107. The reagent dispensing probe 110 performs a reagent aspirating operation and a dispensing operation with the operation of the reagent pump 111. An analysis item to be analyzed for each sample is 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.

  As the sample disk 102 rotates intermittently, the sample container 101 is transferred to the sample suction position, and the sample probe 3 is lowered into the stopped sample container. When the tip of the sample probe 3 comes into contact with the liquid level of the sample in accordance with the lowering operation, a detection signal is output from the liquid level detection circuit 151, and based on this, the computer 103 stops the lowering operation of the driving unit of the sampling arm 2. Control. Next, after a predetermined amount of sample is sucked into the sample probe 3, the sample probe 3 rises to the top dead center. While the sample probe 3 is sucking the sample by a predetermined amount, the pressure detection circuit 153 uses the signal from the pressure sensor 152 to detect the pressure fluctuation in the channel during the suction operation between the sample probe 3 and the sample pump 107 channel. If an abnormality is detected in the pressure fluctuation during the suction, there is a high possibility that the predetermined amount is not sucked, so an alarm is added to the analysis data.

  Next, the sampling arm 2 rotates in the horizontal direction, the sample probe 3 is lowered at the position of the reaction vessel 5 on the reaction disk 4, and the sample held in the reaction vessel 5 is dispensed. When the reaction container 5 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 mixture in the reaction vessel to which the sample and the reagent are added is stirred by the stirrer 113. The reaction container containing the mixture is transferred to the photometer 115, and the luminescence value or absorbance of each mixture is measured by a photomultiplier tube or photometer as a measuring means. The light emission signal or the light reception 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 memory 122. After completion of photometry, the reaction vessel 5 is washed at the position of the reaction vessel washing mechanism 119. The cleaning pump 120 supplies cleaning water to the reaction container and discharges waste liquid 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 disc 102, and one sample suction position by the sample probe 3 is provided in each row. It is set one by one.

  The above is the general operation of the automatic analyzer.

  FIG. 3 shows an example of the embodiment.

  In order to improve the dispensing accuracy, when the sample probe 3 is pressed against the bottom surface 201 of the reaction container and the sample is discharged, the sample probe 3 may be scattered on the side surface of the discharged reaction container 5 when it rises after discharge. .

  In addition, the sample probe 3 is pressed against the reaction vessel bottom surface 201 and discharged, and when the sample probe 3 rises with the sample attached to the side surface of the sample probe 3, the sample discharged even though the specified amount of sample has been discharged. As a result, the adhering amount on the side surface of the sample probe 3 is brought back, leading to deterioration of the dispensing accuracy and affecting the analysis result.

  In order to improve the dispensing accuracy, the sample probe 3 can be raised while being discharged by providing a certain gap between the reaction vessel bottom surface 201 and the sample probe 3 without bringing the sample probe 3 into contact with the reaction vessel bottom surface 201. It is important that a dispensing method that does not adhere to the side surface of the sample probe 3 by being raised while being discharged into the reaction vessel 5 is effective in improving the dispensing accuracy. This effect becomes greater as the sample discharge becomes smaller.

  Further, the liquid ball height 209 that can be formed at the tip of the sample probe 3 varies depending on the outer dimensions, the tip shape, and the type of the sample probe.

  If a large liquid ball is to be produced, it is advantageous that the outer diameter of the sample probe 3 is larger. However, the effect of running out of liquid when the discharged sample and the sample probe 3 are separated is less affected by the thinner outer diameter of the sample probe 3. .

  As shown in FIG. 5, when the tip of the sample probe 3 is flat, the sample can be pushed out from the tip about three times as compared with the case of oblique cutting of the tip, and can be held at the liquid ball height 209. Further, when the tip is flat, the liquid ball height 209 is a size that can be held with a liquid ball about twice as much as when the sample is water and serum.

  From the results of Tables 1 and 2, it can be seen that when the sample is discharged, it is necessary to control the gap provided between the bottom surface 201 of the reaction vessel and the sample probe 3 with an accuracy of 0.1 mm or less.

  Thus, when correcting the dispersion of the reaction vessel 5 and dispensing the sample, the liquid ball height 209 that can be produced differs depending on the type of sample to be discharged, so the gap between the sample probe 3 and the reaction vessel bottom surface 201 is accurately changed. This is effective, and accurate control of the gap becomes essential as a minute amount is dispensed.

  In order to perform accurate stop position control of the sample probe 3 tip and the reaction vessel bottom surface 201 when discharging the sample, it is essential to accurately control the sample probe descending distance 211 of the sample probe 3, There is variation in the distance from the tip of the sample probe 3 at the sample probe HOME position to the bottom surface 201 of each reaction vessel. The reaction vessel 5 is made of a resin molded product as a cause of dimensional variation, and a slight warp occurs due to heat shrinkage deformation at the time of molding, and the reaction vessel shape is integrated with the entire reaction disk. Since it is very difficult to mold the resin, a reaction vessel having a divided block shape as shown in FIG. 2 is used. Deformation of the reaction vessel 5 by forming one round with a plurality of blocks and firmly fixing the reaction vessel block 17 to the reaction disk 4 with screws using the screw holes 11 also causes variations in the gap of the reaction vessel 5. .

  Hereinafter, a method for accurately calculating the sample probe descending distance 211 by correcting the variation in the depth dimension of each reaction vessel 5 will be described.

  As shown in FIG. 3, a certain amount of water, for example, is discharged into the reaction vessel 5 via the reagent probe 110 and the reagent pump 111. The sample probe 3 is lowered from the HOME position by a pulse motor driving the vertical movement of the sampling mechanism 1, and the tip of the sample probe 3 reacts by using the liquid level detection of the function provided in the sampling mechanism 1 conventionally. The sample probe 3 is lowered until the liquid level is detected with the water discharged into the container 5.

  With this operation, the descending amount of the sample probe is calculated and stored from the number of pulses used until the liquid level is detected from the HOME position.

  Alternatively, after the reaction vessel 5 is cleaned by the reaction vessel cleaning mechanism 119, the bottom surface of the reaction vessel is wet with the remaining water 212 of the aqueous solution that has been slightly washed as shown in FIG. Even when the remaining water 212 remains or is wet with the remaining water 212, the sample probe 3 is lowered and the position where the sample probe 3 is stopped by the liquid level detection is measured. .

  Next, the liquid level 210 discharged into the reaction vessel 5 can be calculated from the volume of water discharged into the reaction vessel 5 and the area of the reaction vessel bottom surface 201.

  Here, the reaction vessel 5 is manufactured by a resin mold. Since the dimensional accuracy of the reaction vessel 5 can be managed by managing the dimensional accuracy of the mold to be molded, this is not a difficult technique.

  Accordingly, the height of the water discharged first from the reaction vessel bottom surface 201 is the same in each reaction vessel 5.

  From the above results, the dimension from the tip of the sample probe 3 to the reaction container bottom 201 is the dimension obtained by converting the number of pulses used until the liquid level is detected from the HOME position into the movement distance, and the height of the water in the reaction container 5. By adding the dimensions, the dimensions of the reaction vessel bottom surface 201 can be accurately calculated from the tip of the sample probe 3.

  If the tip shape of the sample probe is flat, the tip of the sample probe 3 can be brought into contact with the water in the reaction vessel 5 at the surface, so that the accuracy is improved, but the liquid level detection is possible even with a sample probe whose tip is cut obliquely. Since the liquid level can be accurately detected by increasing the sensitivity of the drive motor or by increasing the resolution per pulse of the drive motor, the shape of the tip of the sample probe is not affected.

  By performing the above operation on all reaction vessels 5, it becomes possible to measure the variation in the dimensions of all reaction vessels 5, and it is possible to accurately grasp and control the necessary dimensions for lowering the sample probe 3 for each reaction vessel 5. It becomes.

  By accurately controlling the descending amount of the sample probe 3, the kind of sample, for example, urine, serum, control specimen, and the size of the liquid ball height 209 that can be formed at the tip of the sample probe 3 change when the sample is discharged. Therefore, the lowering amount can be controlled, and the discharge operation can be performed at an optimum distance according to the sample. Since the sample probe 3 is lifted while discharging without bringing the sample probe 3 into contact with the bottom surface 201 of the reaction vessel, the set dispensing amount can be discharged without attaching the specimen to the side surface of the sample probe 3. It is possible to improve the system.

  In addition, since the sample probe 3 can be discharged without contacting the bottom surface 201 of the reaction container, there is no fear of scratching the bottom surface 201 of the reaction container. The contamination of the reaction vessel 5 can be reduced.

  Here, the dimension measurement from the sample probe 3 to the reaction vessel bottom surface 201 may be performed after the reaction vessel 5 is exchanged, synchronized with the cell blank operation, after the sample probe 3 is exchanged, or during the cleaning of the reaction vessel 5. desirable. Specifically, it is automatically performed periodically at the time of maintenance operation, cell blank operation, and initial operation after device startup. After exchanging the sample probe 3, measurement is performed by providing a sample probe 3 exchange button on the operation screen and pressing the button, or by performing automatic measurement by pressing a sample probe 3 exchange button (not shown) installed in the apparatus. I will carry out.

  Further, as shown in FIG. 3, the liquid level 210 when water is discharged into the reaction vessel 5 in advance does not vary from the bottom of the reaction vessel 5 to the reaction vessel 5, and therefore from the reaction vessel bottom 201. Is set as a threshold value. Here, by storing the liquid level height 210 discharged to the reaction vessel 5 last time, when the calculated liquid level 210 is compared with the previous measurement value and exceeds the threshold value, the reagent sampling mechanism It is possible to determine that the flow path is abnormal (not shown), and to improve reliability.

  In the present embodiment, only the case where the reaction vessel 5 is dispensed using dispensing of a reagent sample has been described. However, even if the same operation is performed by the sampling mechanism 1, the same effect can be exhibited.

  Moreover, although the liquid discharged to the reaction container 5 was demonstrated about water, the detergent which exhibits the washing | cleaning effect of the reaction container 5 is also possible, and the use range is restricted for the liquid type of the object dispensed to the reaction container 5. It is not something.

DESCRIPTION OF SYMBOLS 1 Sampling mechanism 2 Sampling arm 3 Sample probe 4 Reaction disk 5 Reaction container 11 Screw hole 17 Reaction container block 101 Sample container 102 Sample disk 103 Computer 104 Interface 107 Sample pump 110 Reagent dispensing probe 111 Reagent pump 112 Reagent bottle 113 Agitation Mechanism 114 Light source lamp 115 Photometer 116 A / D converter 117 Printer 118 CRT
119 Reaction vessel cleaning mechanism 120 Cleaning pump 121 Keyboard 122 Memory 125 Reagent disk 151 Liquid level detection circuit 152 Pressure sensor 153 Pressure detection circuit 201 Reaction vessel bottom surface 209 Liquid ball height 210 Liquid level height 211 Sample probe descending distance 212 Remaining water

Claims (5)

A reaction vessel for mixing the sample and the reagent;
A probe for discharging liquid into the reaction vessel;
A liquid level detection mechanism for detecting the liquid level height of the liquid contained in the reaction vessel;
In an automatic analyzer equipped with
The liquid level height of the liquid discharged from the probe to the reaction vessel is detected by the liquid level detection mechanism,
A bottom surface height calculation mechanism for calculating the height of the bottom surface of the reaction container based on the detected liquid surface height information and the information on the amount of liquid discharged from the probe to the reaction container;
An automatic analyzer characterized by comprising: The automatic analyzer according to claim 1, wherein
A probe vertical movement mechanism for moving the probe up and down,
Based on the bottom height information calculated by the bottom height calculation mechanism,
An automatic analyzer comprising a control mechanism for controlling the probe vertical movement mechanism. The automatic analyzer according to claim 1, wherein
A plurality of the reaction vessels,
An automatic analyzer comprising a storage mechanism for storing the bottom surface height calculated by the bottom surface height calculation mechanism for each reaction container. The automatic analyzer according to claim 1, wherein
Whether a predetermined amount of liquid is discharged from the probe to the reaction container based on the information on the bottom surface height calculated by the bottom surface height calculating mechanism and the information on the liquid surface height detected by the liquid level detection mechanism. An automatic analyzer comprising a determination mechanism for determining whether or not. The automatic analyzer according to claim 1, wherein
An automatic analyzer characterized in that the liquid is a sample.

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