Automated analysis device

Abstract

An automatic analysis device capable of performing analysis with high reliability by detecting a case where a sample is sucked in a state where a front end of a probe is not in contact with a bottom surface of a container but is lowered to a vicinity of the bottom surface, and configured to provide the automatic analysis device with the following structure. An automatic analysis device including: a container that accommodates a liquid; a probe that sucks the liquid; and a determination section that lowers the probe to the liquid to dip a front end of the probe in the liquid, further lowers the front end of the probe by a predetermined distance after a predetermined amount of sucking of the liquid by the probe ends, and determines whether the front end collides with a bottom of the container.

Description

Technical Field

[0001] This invention relates to an automated analysis device. Background Technology

[0002] An automated analytical apparatus refers to a device that reacts a sample, such as blood, with the target component in the sample and analytical reagents, and analyzes the reaction using optical methods, automatically producing results from the detection of the target component. Such an automated analytical apparatus includes a step of using a probe (also called a dispensing nozzle) to attract the sample.

[0003] For example, Patent Document 1 discloses an invention that controls a sample dispensing mechanism such that when aspirating a sample, after detecting the liquid surface, the front end of the sample dispensing mechanism is lowered below the liquid surface and stopped, then the front end of the sample dispensing mechanism is raised and stopped, and then the sample is aspirated while the front end is lowered further, so that even a small amount of sample can be reliably aspirated.

[0004] Existing technical documents

[0005] Patent documents

[0006] Patent Document 1: International Publication No. 2022 / 176556 Summary of the Invention

[0007] The problem that the invention aims to solve

[0008] Typical automated analysis devices include the following functions: pre-storing the shape of the sample container containing the sample in the automated analysis device, or detecting the shape of the actual sample container using various methods such as lasers or cameras; the automated analysis device controlling the height of the bottom surface of the sample container to prevent the probe tip from contacting the bottom surface of the container. Even in the case of the sample dispensing mechanism described in Patent Document 1, which controls the descent while simultaneously aspirating the sample, the above-mentioned function is used to control the probe tip to prevent contact with the bottom surface of the container.

[0009] However, the inventors of this invention have discovered that when a sample is attracted while the probe tip is not in contact with the bottom of the container but has descended to near the bottom, it is possible that the intended sample cannot be attracted due to increased suction resistance or other reasons.

[0010] The purpose of this invention is to provide an automated analysis device that can perform highly reliable analysis by detecting situations where a sample is attracted when the probe tip is not in contact with the bottom surface of the container but has descended to near the bottom surface.

[0011] Methods for solving problems

[0012] The structure of the present invention for achieving the above objectives is as follows.

[0013] An automatic analysis device includes: a probe that draws liquid from a container containing 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 drawing a predetermined amount of liquid, lowers the tip of the probe further by a predetermined distance and determines whether the tip collides with the bottom of the container.

[0014] Invention Effects

[0015] According to the present invention, an automated analysis device can be provided that can perform highly reliable analysis by detecting situations where a sample is attracted while the probe tip is not in contact with the bottom surface of the container but has descended to near the bottom surface. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the automatic analysis device.

[0017] Figure 2 This is a schematic diagram showing the dispensing mechanism of the automatic analysis device.

[0018] Figure 3 This is an explanatory diagram of the sample dispensing process in an automated analysis device.

[0019] Figure 4 This is an explanatory diagram of the method for determining whether an abnormality has occurred during dispensing in Example 1.

[0020] Figure 5 It means Figure 4 A flowchart illustrating the determination process.

[0021] Figure 6 This is a graph illustrating the difference in pressure changes after being aspirated by a dispensing nozzle.

[0022] Figure 7 This diagram illustrates a method for determining whether an anomaly has occurred based on differences in pressure variations. Detailed Implementation

[0023] The embodiments of the present invention are described below with reference to the accompanying drawings. Furthermore, the present invention is not limited to these embodiments.

[0024] Example 1

[0025] Figure 1 This is an example of a structural diagram of an automatic analysis device.

[0026] A sample container 103 can be arranged in a ring on a sample tray 102 within the automatic analysis device 101. During sample dispensing, the sample tray rotates clockwise / counterclockwise, causing the sample container 103 to move toward the access position of the sample dispensing mechanism 104.

[0027] To facilitate specimen management, a barcode for identification is sometimes affixed to the specimen container 103. The barcode records information related to the specimen ID, specimen type (serum, urine, etc.). The barcode assigned to the specimen container 103 is read by a barcode reader 120.

[0028] The sample dispensing mechanism 104 consists of a rotary drive mechanism, an up-and-down drive mechanism, and a dispensing probe. It moves between the sample aspiration position and the sample discharge position via the rotary drive mechanism and the up-and-down drive mechanism.

[0029] The reagent storage tank 105 includes a reagent tray 106 and a reagent container holding section 107. Typically, the reagent storage tank has a cooling function to suppress reagent deterioration caused by changes over time. The reagent container holding section 107 is arranged in a double ring on the reagent tray 106, holding multiple reagent bottles. The reagent tray 106 has a rotation drive mechanism that moves each reagent bottle to a predetermined position on the circumference via rotational motion.

[0030] The reagent dispensing mechanism 108 consists of a rotary drive mechanism, an up-and-down drive mechanism, and a dispensing probe. The reagent dispensing mechanism rotates and descends towards the predetermined reagent bottle position on the reagent tray 106, attracting a predetermined amount of reagent. After attracting the reagent, the dispensing mechanism rises. Then, it rotates and descends towards the reagent discharge destination (a predetermined reaction unit on the reaction tray 109) and discharges the reagent.

[0031] The biochemical analysis workflow is described in the order of processing (sample aliquoting, reagent aliquoting, reaction, and detection).

[0032] First, the sample dispensing mechanism 104 dispenses a predetermined amount of sample into a predetermined reaction unit on the reaction tray 109. Then, the reaction tray 109 rotates, causing the reaction unit from which the sample has been dispensed to move to the access position of the reagent dispensing mechanism 108.

[0033] The reagent dispensing mechanism 108 dispenses a predetermined amount of reagent into the reaction unit after the sample has been expelled. Next, the reaction dish 109 rotates, moving the reaction unit containing the expelled sample and reagent to the position set by the stirring unit 110. Then, the stirring unit 110 stirs the sample and reagent. Furthermore, the reaction dish 109 is heated to an appropriate temperature to promote the reaction between the sample and reagent.

[0034] When the reaction process between the sample and reagent on the reaction plate 109 is completed, the reaction plate 109 rotates, moving the reaction unit containing the completed reaction solution to the position set in the biochemical detection unit 111. Then, the reaction signal is measured by the detection section within the biochemical detection unit 111. After the signal is measured, the reaction solution is discharged from the reaction unit through the reaction unit cleaning mechanism 112.

[0035] Furthermore, the mechanism described above in the automatic analysis device is referred to as the analysis action unit. In addition to the analysis action unit, the automatic analysis device also includes a control unit 113 and an operation unit 114 that control the operation of the entire automatic analysis device.

[0036] The control unit 113 is, for example, composed of a hardware board and a computer, and connected to a storage device 115 such as a hard disk. The operation unit 114 is composed of an input device such as a display unit 117 with a touch panel, a mouse 118, and a keyboard 119. The storage device 115 stores, for example, the analysis items of the samples registered by the user. The control unit 113 can be constructed as hardware using a dedicated circuit board, or it can be constructed as software executed by a computer.

[0037] In the hardware configuration, this can be achieved by integrating multiple processing units onto a wiring substrate, or within a semiconductor chip or package. In the software configuration, it can be achieved by mounting a high-speed general-purpose CPU in a computer and executing a program to perform the desired processing. Existing devices can also be upgraded using a recording medium containing this program. Furthermore, these devices, circuits, and computers can appropriately transmit and receive data via wired or wireless network connections.

[0038] The following describes the operation of the sample dispensing mechanism in the automated analyzer. The same structure is also used in the reagent dispensing mechanism, enabling detection of abnormal liquid dispensing. Due to repetition, the description of the reagent dispensing mechanism is omitted.

[0039] Figure 2 This is a schematic diagram of the sample dispensing mechanism. The sample dispensing probe (hereinafter referred to as "probe") 201 is connected to the sample syringe (hereinafter referred to as "syringe") 203 via the flow path 202, and their interiors are filled with liquid.

[0040] The syringe 203 consists of a cylinder 203a and a plunger 203b, with the plunger 203b connected to the syringe drive unit 204. The syringe drive unit 204 drives the plunger 203b up and down relative to the cylinder 203a, thereby aspirating and discharging the sample.

[0041] A motor is connected to the probe 201 as a probe drive unit 205, thereby enabling the probe to move in the vertical and rotational directions to a predetermined position. Furthermore, the syringe drive unit 204 and the probe drive unit 205 are connected by the probe control unit 206 (in... Figure 2 The control is performed by the part marked "control unit".

[0042] When aspirating the specimen 208 in the aspirating container (also called the specimen container) 207, a predetermined amount of air (called segmented air) is aspirated into the probe before the aspiration action to prevent the liquid filling the probe 201 from mixing with the specimen 208.

[0043] Then, the probe 201 is lowered to the specimen 208 by the probe driving unit 205 and a suction action is performed.

[0044] As the probe descends, the probe control unit 206 monitors the change in electrostatic capacitance caused by the probe 201 reaching the liquid surface of the sample 208, and determines the amount of probe descent by controlling the probe drive unit 205.

[0045] Additionally, although not shown, it is equipped with a contact sensor (sometimes also called a bottom-touching sensor or collision sensor) that detects contact with the bottom surface of the container 207 when the probe 201 is lowered to the specimen 208 by the probe driving unit 205.

[0046] For example, when the probe driving unit 205 wants to lower the probe even though the tip of the probe 201 touches the bottom of the container 207, the collision sensor detects the bottoming of the probe 201 by lifting the light-shielding part provided on the axis of the probe 201 upwards, and the photoelectric circuit breaker is turned on (or off).

[0047] When the sample aspiration action ends, the syringe 203 performs a back gap discharge action to correct the sample discharge volume in the next discharge action. Afterwards, the probe 201 moves to the sample discharge position, and the syringe 203 performs the discharge action.

[0048] After discharge, the cleaning water 211 in the water supply tank 210 is sprayed out at high pressure by the water supply pump 209, thereby cleaning the probe 201. The flow path to the water supply tank is opened and closed by the solenoid valve 212. In addition, the solenoid valve 212 is controlled by the probe control unit 206.

[0049] Pressure sensor 213, used to measure pressure within flow path 202, is connected via branch block 214 to a flow path system including probe 201, flow path 202, and syringe 203. Here, to measure pressure changes in probe 201 with high sensitivity, pressure sensor 213 is preferably located as close as possible to probe 201.

[0050] The output value of pressure sensor 213 is amplified by signal amplifier 215 and converted into a digital signal by A / D converter 216. The digitally converted signal is sent to calculation unit 218, which calculates a judgment index for determining whether aspiration has been performed normally (determining whether there is empty aspiration or whether the probe is blocked by fibrin, etc.) using the method described below. In judgment unit 219, the relationship between the judgment index calculated by calculation unit 218 and a threshold is compared to determine whether the sample has been aspirated normally. In addition, aspiration volume calculation unit 220 calculates the aspiration volume of liquid aspirated by the probe based on the information from calculation unit 218. Calculation unit 218, judgment unit 219, and aspiration volume calculation unit 220 are collectively referred to as probe control device 217.

[0051] In the above betting action, the timing of each mechanism's action is defined within a predetermined time cycle, and continuous betting is performed by repeatedly implementing this cycle.

[0052] Furthermore, automated analytical devices are not limited to biochemical analytical devices; they can also be devices such as immunoassay devices capable of measuring different analytical items. Additionally, they are not limited to... Figure 1 The single analysis module structure shown can also be a structure that connects two or more modules, such as an analysis module capable of measuring various identical or different analytical items and a preprocessing module for preprocessing, via a conveyor device.

[0053] Next, use Figure 3 This describes the process in which the probe 201 normally draws the sample from the sample container 207, which holds a sample equivalent to a predetermined amount of liquid, during the sample dispensing operation.

[0054] First, such as Figure 3 As shown in a, probe 201 is moved onto the specimen container 207.

[0055] Next, as Figure 3 As shown in b, after the liquid level detection unit (not shown) detects that the tip of the probe 201 is in contact with the liquid surface, the probe 201 is lowered by a predetermined amount.

[0056] Then, as Figure 3 As shown in c, the syringe 203 is activated, and in order to prevent the probe 201 from detaching from the sample liquid surface while the sample is being aspirated, the probe 201 is lowered further.

[0057] After that, as Figure 3 As shown in d, probe 201 is raised after the attraction ends.

[0058] On the other hand, as described above, the probe 201 is equipped with a collision sensor for detecting when the probe 201 collides with the bottom of the sample container 207. However, this collision sensor is a mechanical sensor, which switches the photoelectric circuit breaker on / off by moving the position of the light-shielding part provided on the axis of the probe 201. Therefore, even if the probe 201 makes slight contact with the bottom of the sample container 207, the sensor may not be able to detect the contact. Furthermore, the inventors of this invention have discovered that when a sample is attracted while the tip of the probe 201 is near the bottom surface of the container, a phenomenon occurs where the intended sample cannot be attracted due to increased attraction resistance. Figure 4 This describes the method of Example 1 for determining whether such a phenomenon has occurred. In typical sample distribution, such as... Figure 3 As shown in c, while aspirating liquid, probe 201 is lowered further. When the liquid aspiration ends, the descent of probe 201 stops.

[0059] In previous technologies, if the collision sensor was not activated at the point when the descent of probe 201 had stopped, it was determined that the tip of probe 201 had not touched the bottom of the container.

[0060] However, even if the tip of probe 201 touches the bottom of the container, the collision sensor will not activate if it is within the "playback" range of the collision sensor. In this embodiment, as... Figure 4 As shown in d, from the position where liquid aspiration has ended, probe 201 is lowered further without aspirating liquid. Therefore, if the collision sensor is activated, it can be determined that the sample may have been aspirated while the tip of probe 201 is blocked, and the dispensed sample may be insufficient for analysis, thus it is discarded in the waste tank. On the other hand, if the collision sensor is not activated even when probe 201 is lowered further, it is determined that the sample has been aspirated normally, and the sample is discharged into the reaction vessel for analysis. The distance by which probe 201 is lowered further varies depending on the size of the sample container, the clearance of the collision sensor, etc., but generally about 1-2 mm is sufficient.

[0061] use Figure 5The dispensing process is explained below. First, to attract the sample, probe 201 is lowered toward the sample container 207 (S401). Next, probe 201 begins to attract the sample, and is lowered further in response to the decrease in liquid level (S402). At the point when the predetermined amount of sample attraction ends, the descent of probe 201 also stops (S403). It is checked whether any abnormal descent is detected before probe 201 stops (whether the collision sensor is activated). If an abnormal descent is detected, it is determined that probe 201 has contacted the bottom of sample container 207, and probe 201 is raised (S410). To discard the attracted sample, probe 201 is moved above the disposal tank (S411), and the attracted sample is discarded (S412).

[0062] On the other hand, if no abnormal descent is detected in S404, the probe 201 is lowered a predetermined distance (a few millimeters, as described above) in order to further detect the bottom of the container (S406). When the lowering probe 201 touches the bottom of the sample container 207, thereby detecting an abnormal descent (collision sensor activated), the process moves to S410, and the sample attracted through steps S411 to S412 is discarded. If no abnormal descent is detected in S406, the probe 201 is moved above the reaction container in order to discharge the attracted sample into the reaction container (S408), and the attracted sample is discharged into the reaction container (S409).

[0063] Furthermore, when the sampled specimen is discarded, it is preferable to notify the device operator to convey this information. For example, a notification mechanism could be a display that includes a note indicating the dispensing failure when the display unit 117 shows a list of specimens and analysis results related to those specimens. This notification method can also be applied to Embodiment 2.

[0064] Example 2

[0065] The method in Example 1 can determine whether the probe 201 has attracted the sample in a semi-blocked state based on whether an abnormal descent is detected. On the other hand, after the sample aspiration is completed, the probe 201 needs to be lowered further, which incurs additional time requirements.

[0066] When the sample volume is large, the time required for sample aspiration may be long and the circulation time may be insufficient, making it difficult to apply in such situations. Therefore, in Example 2, a method is provided to determine whether the sample has been aspirated in a semi-obstructed state without requiring the probe 201 to descend further.

[0067] As described above, a pressure sensor 213 is provided in the flow path 202 between probe 201 and syringe 203, and has the following functions: detecting whether the probe 201 is not properly aspirating (a state where the tip of probe 201 is above the liquid surface and aspiration is not performed), or whether the probe 201 is blocked due to fibrin or other substances generated in the sample aspirated by probe 201. Example 2 determines whether probe 201 aspirates the sample in a partially blocked state based on the output of the pressure sensor 213.

[0068] Figure 6 The vertical axis represents the pressure value measured by pressure sensor 213, and the horizontal axis represents time. When the probe 201 rises after attracting the sample, the solid line (the curve at the top of the graph) represents the pressure change when the probe 201 detaches from the bottom of the sample container 207 without contacting it, and the dashed line (the curve at the bottom of the graph) represents the pressure change when it detaches after contacting the bottom of the container. The pressure change in region 1 enclosed by the dashed quadrilateral differs in the two graphs. That is, when the sample is attracted while in contact with the bottom of the container, since it is impossible to attract a sample that matches the negative pressure applied to the probe 201, as soon as the blockage at the tip of the probe 201 is released after the probe 201 detaches from the bottom of the container, the residual pressure (negative pressure) in the probe 201 further attracts the sample into the probe 201. Therefore, the inventors of this invention have found that, compared to the case where the sample is attracted in a non-blocked state, there is a tendency for the pressure change within the flow path to be larger. In addition, it can be seen that the pressure change in region 2 is the reaction to the large pressure change in the flow path in region 1, and the pressure change when probe 201 is detached without contacting the bottom of the container tends to be larger than the pressure change when it is detached after contacting the bottom of the container.

[0069] That is, the inventors of this invention discovered that by focusing on the pressure changes in both region 1 and region 2, it is possible to determine whether the specimen was attracted under obstructed conditions.

[0070] exist Figure 7 This section describes a method used for identification. As shown in the figure, the maximum and minimum amplitudes of pressure variation in regions 1 and 2 are defined. These maximum and minimum amplitudes are used to determine whether suction exists under obstructed conditions.

[0071] As previously explained, regarding region 1, when the specimen was aspirated under obstructed conditions, the pressure fluctuated significantly, resulting in a larger maximum and minimum pressure amplitude compared to when the specimen was aspirated without obstruction. Therefore, a threshold was set for the maximum and minimum amplitude. If the maximum and minimum amplitudes exceeded the set threshold, it was presumed that abnormal aspiration may have occurred, i.e., specimen aspiration was performed under obstructed conditions.

[0072] Furthermore, regarding region 2, when the sample was aspirated under obstructed conditions, the maximum and minimum pressure amplitudes were smaller compared to when the sample was aspirated without obstruction. Therefore, when the maximum and minimum amplitudes are below the set threshold, it is presumed that abnormal aspiration may have occurred, i.e., sample aspiration was performed under obstructed conditions. By combining these factors for determination, the determination becomes more accurate. Additionally, the value used for determination may not be a simple threshold, but can be calculated using Mahalanobis distance or linear discriminant analysis, which are known techniques. Furthermore, by combining the method of Example 2 with the method of Example 1, determinations with even higher accuracy can be achieved.

[0073] <Other>

[0074] Furthermore, the present invention is not limited to the above embodiments and can be modified and applied in various ways. The above embodiments are examples provided for easy understanding and illustration of the present invention, and are not necessarily limited to having all the structures described.

[0075] Explanation of reference numerals in the attached figures

[0076] 101: Automatic analysis device; 102: Specimen tray; 103: Specimen container; 104: Specimen dispensing mechanism; 105: Reagent storage unit; 106: Reagent tray; 107: Reagent container holding unit; 108: Reagent dispensing mechanism; 109: Reaction tray; 110: Stirring unit; 111: Biochemical detection unit; 112: Reaction unit cleaning mechanism; 113: Control unit; 114: Operation unit; 115: Storage device; 116: Control device; 117: Display unit; 118: Mouse; 119: Keyboard; 120: Barcode reader; 201 202: Probe, 203: Flow path, 203: Syringe, 203a: Cylinder, 203b: Plunger, 204: Syringe drive unit, 205: Probe drive unit, 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 device, 218: Calculation unit, 219: Judgment unit, 220: Suction volume calculation unit.

Claims

1. An automatic analysis device, characterized in that, have: A probe that draws the liquid from a container holding the liquid; and The determination unit lowers the probe into the liquid to immerse the tip of the probe in the liquid. After the probe stops attracting a predetermined amount of the liquid, it lowers the tip of the probe further by a predetermined distance and determines whether the tip of the probe collides with the bottom of the container.

2. The automatic analysis device according to claim 1, characterized in that, The automatic analysis device includes a control unit. When the determination unit determines that the tip of the probe has collided with the bottom of the container, the control unit controls the disposal of the aspirated liquid.

3. The automatic analysis device according to claim 1, characterized in that, The automatic analysis device has a detection mechanism that detects whether the axis of the probe shifts upward from a predetermined position. The determination unit determines whether the tip of the probe has collided with the bottom of the container based on the detection results of the detection mechanism.

4. An automatic analysis device, characterized in that, have: A probe that draws the liquid from a container holding the liquid; A pressure source that generates pressure to draw the liquid into the probe; A flow path that connects the probe to the pressure source; and The sensor measures the pressure within the flow path. The automatic analysis device includes: The determination unit lowers the probe into the liquid so that the tip of the probe is immersed in the liquid. After the probe stops attracting a predetermined amount of the liquid, the sensor measures the pressure when the tip of the probe is raised. Based on the measured result, it determines whether the probe has collided with the bottom of the container. as well as The control unit, when the determination unit determines that the tip of the probe has collided with the bottom of the container, controls the disposal of the liquid that has been aspirated.

5. The automatic analysis device according to claim 4, characterized in that, The determination unit compares the result measured by the sensor with a predetermined reference value.

6. The automatic analysis device according to claim 5, characterized in that, The results measured by the sensor are pressure measurements for at least two scenarios: when the probe tip is in the liquid and when it is detached from the liquid surface, with the predetermined reference values ​​being different reference values ​​for each scenario.

7. The automatic analysis device according to claim 4, characterized in that, The determination unit uses Mahalanobis distance or linear discrimination method to determine the result measured by the sensor as the tip of the probe colliding with the bottom of the container.

8. The automatic analysis device according to claim 1, characterized in that, The automatic analysis device includes a notification mechanism that notifies the system when the determination unit determines that the tip of the probe has collided with the bottom of the container.

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