Automatic analysis device

Abstract

In order to provide an automatic analysis device that is capable of performing highly reliable analysis by detecting that a sample is suctioned in a state in which the tip of a probe is lowered to the vicinity of the bottom surface of a container without being in contact with the bottom surface, the present invention has the following configuration.　Provided is an automatic analysis device comprising: a container which stores a liquid; a probe which suctions the liquid; and a determination unit which, when the probe is lowered to the liquid so that the tip of the probe is immersed in the liquid, suction of a prescribed amount of the liquid by the probe is completed, and then the tip of the probe is further lowered by a prescribed distance, determines whether or not the tip has come into contact with the bottom of the container.

Description

automatic analyzer

[0001] The present invention relates to an automatic analyzer.

[0002] An automated analyzer is a device that reacts a sample, such as blood, with a target component in the sample and an analytical reagent, and analyzes this reaction using an optical method, automatically performing the entire process from detecting the target component to outputting the results. Such an automated analyzer has a step of aspirating the sample using a probe (also called a dispensing nozzle).

[0003] For example, Patent Document 1 discloses an invention in which, when aspirating a sample, the liquid level is detected, and then the tip of the sample dispensing mechanism is lowered below the liquid level and stopped, and then the tip of the sample dispensing mechanism is raised and stopped, and then further lowered while aspirating the sample, so that even a small amount of sample can be reliably aspirated.

[0004] International Publication No. 2022 / 176556

[0005] In general, automatic analyzers have a function of determining the height of the bottom of a sample container by storing the shape of the sample container containing the sample in advance or by detecting the shape of the sample container actually placed therein using various methods such as a laser or a camera, and controlling the probe tip so that it does not contact the bottom of the container. Even in the case of controlling the sample dispensing mechanism so that the sample is lowered while being aspirated, as described in Patent Document 1, the above function controls the probe tip so that it does not contact the bottom of the container.

[0006] However, the inventors discovered that when a sample is aspirated when the probe tip is not in contact with the bottom of the container but is lowered to the vicinity of the bottom, there is a possibility that the specified sample may not actually be aspirated due to reasons such as increased suction resistance.

[0007] The object of the present invention is to provide an automatic analyzer capable of highly reliable analysis by detecting when a sample has been aspirated while the probe tip is not in contact with the bottom of the container but is lowered to the vicinity of the bottom.

[0008] To achieve the above object, the present invention is configured as follows: An automatic analyzer comprising: a probe that aspirates a liquid from a container that contains the liquid; and a determination unit that lowers the probe into the liquid so that the tip of the probe is immersed in the liquid, and after the probe has finished aspirating a predetermined amount of the liquid, further lowers the tip of the probe a predetermined distance and determines whether the tip has struck the bottom of the container.

[0009] According to the present invention, an automatic analyzer capable of highly reliable analysis can be provided by detecting when a sample is aspirated while the probe tip is lowered near the bottom of the container but not in contact with the bottom.

[0010] 1 is a schematic diagram of an automatic analyzer; 2 is a schematic diagram showing a dispensing mechanism of an automatic analyzer; 3 is an explanatory diagram of the sample dispensing operation in an automatic analyzer; 4 is an explanatory diagram of a method for determining whether an abnormality has occurred during dispensing in Example 1; 5 is a diagram showing the flow of the determination in FIG. 4; 6 is a diagram explaining differences in pressure fluctuations after suction by a dispensing nozzle; and 7 is a diagram showing a method for determining whether an abnormality has occurred based on differences in pressure fluctuations.

[0011] Hereinafter, examples of the present invention will be described with reference to the drawings. It should be noted that the following are examples and the present invention is not limited to these examples.

[0012] FIG. 1 is a diagram showing an example of the configuration of an automatic analyzer.

[0013] Sample containers 103 can be placed in a ring shape on a sample disk 102 inside an automatic analyzer 101. When dispensing a sample, the disk rotates clockwise and counterclockwise, moving the sample containers 103 to an access position of a sample dispensing mechanism 104.

[0014] To simplify sample management, an identification barcode may be attached to the sample container 103. The barcode records information linked to the sample ID and information related to the sample type (e.g., serum, urine, etc.). The barcode attached to the sample container 103 is read by a barcode reader 120.

[0015] The sample dispensing mechanism 104 is composed of a rotation drive mechanism, a vertical drive mechanism, and a dispensing probe. The rotation drive mechanism and the vertical drive mechanism move the sample dispensing mechanism between a sample suction position and a sample dispensing position.

[0016] The reagent storage cabinet 105 has a reagent disk 106 and reagent container holders 107. Reagent storage cabinets generally have a cooling function to prevent reagents from deteriorating over time. The reagent container holders 107 are arranged in a double ring on the reagent disk 106 and are designed to hold multiple reagent bottles. The reagent disk 106 has a rotation drive mechanism, and by rotation, each reagent bottle is moved to a predetermined position on the circumference.

[0017] The reagent dispensing mechanism 108 is composed of a rotation drive mechanism, a vertical drive mechanism, and a dispensing probe. The reagent dispensing mechanism rotates and descends to the position of a predetermined type of reagent bottle on the reagent disk 106, and aspirates a predetermined amount of reagent. After aspirating the reagent, the dispensing mechanism ascends. Next, it rotates and descends to the reagent ejection destination (a predetermined reaction cell on the reaction disk 109), and ejects the reagent.

[0018] The flow of biochemical analysis will be explained in the order of processing (sample dispensing, reagent dispensing, reaction, and detection).

[0019] First, the specimen dispensing mechanism 104 dispenses a predetermined amount of specimen into a predetermined reaction cell on the reaction disk 109. Then, the reaction disk 109 rotates, and moves the reaction cell into which the specimen has been dispensed to an access position of the reagent dispensing mechanism 108.

[0020] The reagent dispensing mechanism 108 dispenses a predetermined amount of reagent into the reaction cell into which the sample has been discharged. Next, the reaction disk 109 rotates, and moves the reaction cell into which the sample and reagent have been discharged to a position where the mixing unit 110 is installed. The sample and reagent are then mixed by the mixing unit 110. The reaction disk 109 is kept at an appropriate temperature to promote the reaction between the sample and the reagent.

[0021] When the reaction process between the sample and the reagent on the reaction disk 109 is completed, the reaction disk 109 rotates and moves the reaction cell containing the reaction solution after the reaction to the installation position of the biochemical detection unit 111. Then, the reaction signal is measured by the detection unit in the biochemical detection unit 111. After the signal measurement, the reaction solution is discharged from the reaction cell by the reaction cell washing mechanism 112.

[0022] The above-described mechanism of the automatic analyzer is referred to as the “analysis operation unit.” In addition to the analysis operation unit, the automatic analyzer further includes a control unit 113 and an operation unit 114 that control the overall operation of the automatic analyzer.

[0023] The control unit 113 is composed of, for example, a hardware board and a computer, and is connected to a storage device 115 such as a hard disk. The operation unit 114 is composed of a display unit 117 which is a display equipped with a touch panel, and input devices such as a mouse 118 and a keyboard 119. The storage device 115 stores, for example, analysis items for samples registered by the user. The control unit 113 may be composed of hardware such as a dedicated circuit board, or may be composed of software executed on a computer.

[0024] When configured using hardware, it can be realized by integrating multiple arithmetic units that execute the processing on a wiring board, or in a semiconductor chip or package. When configured using software, it can be realized by installing a high-speed general-purpose CPU in a computer and running a program that executes the desired arithmetic processing. It is also possible to upgrade existing devices using a recording medium on which this program is recorded. Furthermore, these devices, circuits, and computers are connected via a wired or wireless network, and data is sent and received as appropriate.

[0025] The operation of the sample dispensing mechanism in the automatic analyzer is described below. The reagent dispensing mechanism also has a similar configuration, and liquid dispensing abnormality detection can be performed. To avoid duplication, a description of the reagent dispensing mechanism will be omitted.

[0026] 2 is a schematic diagram of the sample dispensing mechanism. A sample dispensing probe (hereinafter simply referred to as the “probe”) 201 is connected to a sample syringe (hereinafter simply referred to as the “syringe”) 203 via a flow channel 202, and the insides of these are filled with liquid.

[0027] The syringe 203 is composed of a cylinder 203a and a plunger 203b, and the plunger 203b is connected to a syringe driving means 204. The syringe driving means 204 drives the plunger 203b up and down relative to the cylinder 203a to aspirate and discharge the sample.

[0028] A motor is connected to the probe 201 as a probe driving means 205, which moves the probe up and down and in a rotational direction to a predetermined position. The syringe driving means 204 and the probe driving means 205 are controlled by a probe control unit 206 (denoted as "control unit" in FIG. 2).

[0029] When aspirating a specimen 208 in a container (also called a specimen container) 207, prior to the aspirating operation, a predetermined amount of air (called segmented air) is aspirated into the probe 201 to prevent the specimen 208 from mixing with the liquid filled in the probe 201.

[0030] Thereafter, the probe 201 is lowered by the probe driving means 205 until it reaches the specimen 208, and then a suction operation is performed.

[0031] The probe descent amount at this time is determined by monitoring the amount of change in capacitance caused by the probe 201 reaching the liquid surface of the specimen 208, and the probe control unit 206 controls the probe driving means 205 to determine the amount of probe descent.

[0032] In addition, although not shown, the probe 201 is equipped with a contact sensor (sometimes called a bottom sensor or crash sensor) that detects contact with the bottom surface of the container 207 when the probe 201 is lowered by the probe driving means 205 to reach the specimen 208.

[0033] The crash sensor detects that the probe 201 has hit the bottom by taking advantage of the fact that, for example, when the tip of the probe 201 has hit the bottom of the container 207 but the probe driving means 205 still tries to lower the probe, a light-shielding portion provided on the shaft of the probe 201 rises upward and a photointerrupter turns ON (or OFF).

[0034] When the sample aspirating operation is completed, the syringe 203 performs a backlash discharging operation to correct the sample discharging amount in the next discharging operation. Thereafter, the probe 201 moves to the sample discharging position, and the syringe 203 performs a discharging operation.

[0035] After the discharge, cleaning water 211 in a water supply tank 210 is sprayed at high pressure by a water supply pump 209, thereby cleaning the probe 201. The flow path to the water supply tank is opened and closed by an electromagnetic valve 212. The electromagnetic valve 212 is controlled by the probe control unit 206.

[0036] A pressure sensor 213 for measuring the pressure inside the flow path 202 is connected to a flow path system including the probe 201, the flow path 202, and the syringe 203 via a branch block 214. Here, the pressure sensor 213 is preferably installed as close to the probe 201 as possible in order to measure pressure fluctuations in the probe 201 with good sensitivity.

[0037] The output value of the pressure sensor 213 is amplified by a signal amplifier 215 and converted into a digital signal by an A / D converter 216. The digitally converted signal is sent to a calculation unit 218, which calculates a judgment index for judging whether the aspiration was successful (determining whether dry aspiration occurred or whether the probe is clogged with fibrin or the like) using the method described below. A judgment unit 219 compares the judgment index calculated by the calculation unit 218 with a threshold value to determine whether the sample was successfully aspirated. Furthermore, an aspiration volume calculation unit 220 calculates the volume of liquid aspirated by the probe based on information from the calculation unit 218. The calculation unit 218, judgment unit 219, and aspiration volume calculation unit 220 are collectively referred to as a probe control device 217.

[0038] In the above dispensing operation, the operation timing of each mechanism is defined within a predetermined time cycle, and continuous dispensing is performed by repeating this cycle.

[0039] The automated analyzer is not limited to a biochemical analyzer, but may be an analyzer capable of measuring different analysis items, such as an immunoanalyzer. Furthermore, the automated analyzer is not limited to a single analysis module configuration as shown in Fig. 1, but may be configured to connect two or more analysis modules capable of measuring various identical or different analysis items or pretreatment modules that perform pretreatment via a transport device.

[0040] Next, the sample dispensing operation will be described with reference to FIG. 3, with regard to the steps in which the probe 201 normally aspirates a sample from a sample container 207 holding a quantity of sample equivalent to a specified quantity.

[0041] First, as shown in FIG. 3A, the probe 201 is moved above the sample container 207 .

[0042] Next, as shown in FIG. 3b, after a liquid level detector (not shown) detects that the tip of the probe 201 has contacted the liquid surface, the probe 201 is further lowered until it has descended a predetermined amount.

[0043] Thereafter, as shown in FIG. 3c, the syringe 203 is operated to aspirate the sample while the probe 201 is lowered to prevent the probe 201 from being separated from the sample liquid surface.

[0044] Thereafter, as shown in FIG. 3d, after the suction is completed, the probe 201 is raised.

[0045] Meanwhile, as described above, the probe 201 is provided with a crash sensor that detects when the probe 201 hits the bottom of the sample container 207. However, since the crash sensor is a mechanical sensor in which a photointerrupter is turned on / off by moving the position of a light-shielding portion provided on the shaft of the probe 201, the sensor may not detect the probe 201 even if it only lightly touches the bottom of the sample container 207. On the other hand, the inventors have discovered that when a sample is aspirated with the tip of the probe 201 near the bottom of the container, an event occurs in which the desired sample cannot be aspirated due to factors such as increased aspiration resistance. A method of Example 1 for determining whether such an event has occurred will be described with reference to FIG. 4 . In normal sample dispensing, the probe 201 is lowered while aspirating liquid, as shown in c in FIG. 3 , and the descent of the probe 201 stops at the position where the liquid aspiration is completed.

[0046] In conventional technology, if the crash sensor is not ON when the descent of the probe 201 stops, it is determined that the tip of the probe 201 has not touched the bottom of the container. However, even if the tip of the probe 201 touches the bottom of the container, the crash sensor will not turn ON if it is within the range of the crash sensor's "play." In this embodiment, as shown in Figure 4d, the probe 201 is further lowered from the position where the liquid aspiration ended without aspirating any more liquid. If the crash sensor turns ON, it can be determined that the tip of the probe 201 may have been blocked while aspirating the sample. Since the dispensed sample may not be the required amount, it is not used for analysis and is discarded in a waste tank. On the other hand, if the crash sensor does not turn ON even after the probe 201 is further lowered, it is determined that the sample was aspirated normally, and the sample is discharged into a reaction container for analysis. The further distance the probe 201 is lowered varies depending on the size of the sample container and the amount of play in the crash sensor, but generally, approximately 1 to 2 mm is sufficient.

[0047] The flow of this series of dispensing operations will be described with reference to Figure 5. First, to aspirate the sample, the probe 201 is lowered toward the sample in the sample container 207 (S401). Next, the probe 201 begins to aspirate the sample, and the probe 201 is lowered accordingly as the liquid level drops (S402). When a predetermined amount of sample has been aspirated, the probe 201 stops lowering (S403). Before the probe 201 stops, it is checked whether abnormal descent has been detected (whether the crash sensor has turned ON). If abnormal descent is detected, it is determined that the probe 201 has bottomed out of the sample container 207, and the probe 201 is raised (S410). To discard the aspirated sample, the probe 201 is moved above a waste tank (S411), and the aspirated sample is discarded (S412).

[0048] On the other hand, if no abnormal descent is detected in S404, the probe 201 is further lowered a predetermined distance (several mm, as described above) to further detect the container bottom (S406). If the lowered probe 201 hits the bottom of the sample container 207 and abnormal descent is detected (the crash sensor is turned ON), the process proceeds to S410, and the aspirated sample is discarded in steps S411 and S412 described above. If no abnormal descent is detected in S406, the probe 201 is moved above the reaction container to dispense the aspirated sample into the reaction container (S408), and the aspirated sample is then dispensed into the reaction container (S409). Note that if the aspirated sample is discarded, it is preferable to notify the device operator of this. An example of a notification mechanism is to display a list of samples and their analysis results on the display unit 117, with a comment indicating that a dispensing error occurred for the sample. This notification method is also applicable to Example 2.

[0049] The method of Example 1 can determine whether the probe 201 has aspirated the sample in a semi-occluded state by detecting abnormal descent. However, there is a problem in that the probe 201 must be further lowered after sample aspiration is complete, which takes additional time.

[0050] When the amount of sample dispensed is large, the time required for sample aspirating may be long and there may not be sufficient cycle time, but it may be difficult to apply this method to such cases. Therefore, in Example 2, a method is provided that can determine whether or not the sample has been aspirated in a semi-occluded state without further lowering the probe 201.

[0051] As described above, the flow path 202 between the probe 201 and the syringe 203 is provided with a pressure sensor 213, which has the function of detecting whether the probe 201 is performing dry aspirating (a state in which aspirating is performed with the tip of the probe 201 above the liquid surface and the sample is not being aspirated normally) or whether the probe 201 is clogged due to the probe 201 aspirating fibrin generated in the sample, etc. The second embodiment determines whether the probe 201 has aspirated the sample in a semi-occluded state based on the output of this pressure sensor 213.

[0052] In Figure 6, the vertical axis represents the pressure value measured by pressure sensor 213, and the horizontal axis represents time. After aspirating a sample, probe 201 is raised. The solid line (upper curve in the graph) shows the pressure fluctuation when probe 201 is released without contacting the bottom of sample container 207, while the dotted line (lower curve in the graph) shows the pressure fluctuation when probe 201 is released after contacting the bottom. The pressure fluctuation in region 1 enclosed by the dashed rectangle differs in both graphs. That is, when a sample is aspirated while in contact with the bottom of the container, the amount of sample aspirated is insufficient to match the negative pressure applied to probe 201. Therefore, as soon as the blocked state of the tip of probe 201 is released, the residual pressure (negative pressure) in probe 201 causes further sample to be aspirated into probe 201. Therefore, the inventors discovered that the pressure fluctuation in the flow path tends to be larger than when a sample is aspirated while the flow path is not blocked. Furthermore, it was found that the pressure fluctuations in region 2 are a reaction to the large fluctuations in pressure in the flow path in region 1, and that the pressure fluctuations when the probe 201 is removed without contacting the bottom of the container tend to be larger than the pressure fluctuations when the probe is removed after contacting the bottom of the container.

[0053] That is, the present inventors have found that by focusing on the pressure fluctuations in both regions 1 and 2, it is possible to determine whether or not a sample has been aspirated in a blocked state.

[0054] One method for making this determination is shown in Figure 7. The maximum and minimum widths of pressure fluctuations in regions 1 and 2 are defined as shown in the figure. These maximum and minimum widths are used to determine whether suction has occurred in an occluded state.

[0055] As explained above, for region 1, when a sample is aspirated in a blocked state, the pressure fluctuates greatly, and the maximum and minimum pressure range is larger than when a sample is aspirated in an unblocked state. Therefore, a threshold is set for the maximum and minimum range, and if the maximum and minimum range exceeds the set threshold, it is estimated that abnormal aspiration has occurred, that is, the sample may have been aspirated in a blocked state.

[0056] Furthermore, for region 2, when a sample is aspirated in a blocked state, the maximum and minimum pressure range is smaller than when a sample is aspirated in an unblocked state. Therefore, if the maximum and minimum range is equal to or less than a set threshold, it is estimated that abnormal aspiration occurred, that is, the sample may have been aspirated in a blocked state. Combining these methods for determination makes the determination more accurate. Furthermore, the value used for determination may not be a simple threshold, but may be calculated using well-known techniques such as Mahalanobis distance or linear discriminant analysis. Furthermore, combining the method of Example 2 with the method of Example 1 enables more accurate determination.

[0057] <Others> The present invention is not limited to the above-described embodiments, and various modifications and applications are possible. The above-described embodiments have been described in detail to clearly explain the present invention, and the present invention is not necessarily limited to those having all of the described configurations.

[0058] 101: automatic analyzer, 102: specimen disk, 103: specimen container, 104: specimen dispensing mechanism, 105: reagent storage, 106: reagent disk, 107: reagent container holder, 108: reagent dispensing mechanism, 109: reaction disk, 110: stirring unit, 111: biochemical detection unit, 112: reaction cell cleaning mechanism, 113: control unit, 114: operation unit, 115: storage device, 116: control device, 117: display unit, 118: mouse, 119: keyboard, 120: barcode reader, 201: Probe, 202: flow path, 203: syringe, 203a: cylinder, 203b: plunger, 204: syringe drive means, 205: probe drive means, 206: probe control unit, 207: container, 208: specimen, 209: water supply pump, 210: water supply tank, 211: cleaning water, 212: solenoid valve, 213: pressure sensor, 214: branch block, 215: signal amplifier, 216: A / D converter, 217: probe control unit, 218: calculation unit, 219: judgment unit, 220: suction volume calculation unit.

Claims

1. An automatic analyzer comprising: a probe that aspirates a liquid from a container that contains the liquid; and a determination unit that lowers the probe into the liquid so that the tip of the probe is immersed in the liquid, and after the probe has finished aspirating a predetermined amount of the liquid, further lowers the tip of the probe a predetermined distance and determines whether the tip has hit the bottom of the container.

2. An automatic analyzer according to claim 1, further comprising: a control unit that controls the aspirated liquid to be discarded when the determination unit determines that the tip of the probe has collided with the bottom of the container.

3. An automatic analyzer according to claim 1, further comprising a detection mechanism for detecting that the axis of the probe has shifted upward from a predetermined position, and the determination unit determines whether the tip of the probe has collided with the bottom of the container based on the detection result of the detection mechanism.

4. An automatic analyzer comprising: a probe that aspirates a liquid from a container that stores the liquid; a pressure source that generates pressure in the probe for aspirating the liquid; a flow path that connects the probe to the pressure source; and a sensor that measures the pressure in the flow path; a determination unit that lowers the probe into the liquid to immerse the tip of the probe in the liquid, and after the probe has finished aspirating a predetermined amount of the liquid, measures the pressure when the tip of the probe is raised using the sensor, and determines whether the tip of the probe has hit the bottom of the container based on the measurement result; and a control unit that controls the aspirated liquid to be discarded if the determination unit determines that the tip of the probe has hit the bottom of the container.

5. An automatic analyzer according to claim 4, wherein the determination unit compares the result of measurement by the sensor with a predetermined reference value.

6. An automatic analyzer according to claim 5, wherein the results measured by the sensor are pressure measurement results for at least two cases, when the tip of the probe is in the liquid and when it is removed from the liquid surface, and the predetermined reference values ​​are different reference values ​​for each case.

7. An automatic analyzer according to claim 4, wherein the determination unit determines that the tip of the probe has collided with the bottom of the container by using Mahalanobis distance or linear discriminant analysis based on the results measured by the sensor.

8. An automatic analyzer according to claim 1, further comprising an alarm mechanism that, when the determination unit determines that the tip of the probe has collided with the bottom of the container, issues an alarm to that effect.

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