Dispensing device, cleaning method, and automatic analysis device

Abstract

This dispensing device (10) comprises a probe (22) for dispensing a specimen or a reagent, a tip (21) attached to the distal end of the probe (22), a probe drive mechanism (25) for moving the probe (22), a cleaning unit (1) provided with a cleaning nozzle (11) for discharging a cleaning liquid (8) to the side, and a control unit (4) for controlling the cleaning unit (1) and the probe drive mechanism (25). The probe (22) is controlled so as to be raised when the cleaning liquid (8) discharged from the cleaning nozzle (11) is in contact with the tip (21).

Description

Dispensing apparatus, cleaning method, and automatic analyzer

[0001] The present invention relates to a dispensing apparatus, a cleaning method, and an automatic analyzer.

[0002] Automatic analyzers such as biochemical analyzers and immunoanalyzers include, in addition to analyzers that detect and quantify components of specimens such as biological samples or reaction liquids of specimens and reagents, a dispensing apparatus that prepares a reaction liquid by introducing predetermined amounts of a specimen and a reagent into a reaction vessel, respectively.

[0003] The dispensing apparatus is configured of a probe that sucks and discharges liquids such as specimens and reagents from the tip, a syringe serving as a pressure source for sucking and discharging the liquid, a flow path connecting the probe and the syringe, a moving mechanism that moves the probe vertically and horizontally, and a reaction vessel. The dispensing apparatus dispenses a predetermined amount of liquid into the reaction vessel by: moving the probe over a container containing a specimen or a reagent, inserting the probe into the liquid in the container, driving the syringe to suck a predetermined amount of liquid, moving the probe over the reaction vessel, and driving the syringe to discharge the liquid in the probe.

[0004] When dispensing a plurality of types of liquids such as a specimen and a reagent, it is necessary to clean the outer surface near the tip of the probe before sucking the next liquid every time liquid is dispensed, to wash off the liquid adhered when the previous liquid was sucked, so as to prevent contamination of the container storing the reagent or the like to be sucked next. By ensuring a sufficient cleaning effect in the step of cleaning the outer surface of the probe, carry-over of components between liquids can be suppressed, and analysis accuracy can be maintained. Furthermore, by minimizing the residual cleaning liquid on the outer surface of the probe in the outer surface cleaning step, the reagent or the like to be dispensed next can maintain its concentration in the storage container, enabling highly reproducible analysis.

[0005] As a cleaning mechanism for cleaning the outer surface of a probe, for example, Patent Document 1 discloses a technique in which two nozzles each having a discharge port facing the probe are provided on both sides of the probe, while ejecting cleaning liquid obliquely downward from the two nozzles, the probe is lowered from above to bring the cleaning liquid into contact with the probe from the tip to the upper side, and then raised back to the original position, and the moving speed at that time and the ejection timing of the cleaning liquid relative to the position of the probe are controlled.

[0006] Patent No. 6748261

[0007] To shorten the time required for the analysis of numerous samples using automated analyzers, it is desirable to minimize the time required for dispensing. For this reason, depending on the analysis item, instead of dispensing reagents into the reaction vessel each time they are aspirated, all types of reagents and samples in the reaction solution may be aspirated continuously, and then these liquids held in the probe may be discharged all at once. However, even in this case, it is necessary to wash the outer surface of the probe each time various liquids are aspirated, and it is desirable to shorten the probe washing time. However, in the configuration described in Patent Document 1, as the probe descends through the washing solution sprayed from the nozzle, any attached reagents are spread over the probe by the washing solution that comes into contact with it, resulting in low efficiency in both washing time and washing solution volume. Furthermore, especially when the washing solution comes into contact with the small diameter portion near the tip of the probe, the washing solutions sprayed from the two opposing nozzles collide with each other, causing splashing onto the probe, and a large amount of washing solution tends to remain on the outer surface of the probe. In addition, since the tip of the probe is the first to come into contact with the sprayed washing solution, reagents attached to the tip tend to scatter over a wide area.

[0008] Furthermore, to more reliably prevent the carryover of components between samples, a disposable plastic tip is sometimes attached to the probe's tip to hold the aspirated liquid, and the tip is replaced each time the sample being analyzed is changed. Since the tip has a larger outer diameter than the probe's tip, and reagents and other substances that adhere to it are more difficult to remove by washing than with a metal probe, it requires more time and a larger amount of washing solution for cleaning the outer surface, thus demanding even greater efficiency.

[0009] The present invention has been made in view of the above, and provides an efficient cleaning technique that has a sufficient cleaning effect to suppress the carryover of components between liquids when a dispensing device dispenses multiple types of liquids such as samples and reagents, and also suppresses the amount of cleaning solution remaining on the outer surface of the probe.

[0010] To solve the above problems, the dispensing device according to the present invention comprises a probe for dispensing liquid, a liquid delivery mechanism for drawing in and discharging fluid from the tip of the probe, a flow path connecting the probe and the liquid delivery mechanism, a cleaning nozzle with its discharge port facing laterally, a cleaning liquid supply mechanism for discharging cleaning liquid from the discharge port of the cleaning nozzle, a drive mechanism for moving at least one of the probe and the discharge port of the cleaning nozzle up and down, and a control unit for controlling the cleaning liquid supply mechanism and the drive mechanism, wherein the control unit controls the drive mechanism and the cleaning liquid supply mechanism so that the probe moves relatively upward relative to the discharge port of the cleaning nozzle during the cleaning period when cleaning liquid is discharged from the cleaning nozzle toward the probe, thereby cleaning the outer surface of the probe with the cleaning liquid.

[0011] The automated analyzer according to the present invention includes the aforementioned dispensing device.

[0012] The present invention relates to a cleaning method for the outer surface of a probe in a dispensing apparatus, comprising: a probe for dispensing liquid; a liquid delivery mechanism for drawing in and discharging fluid from the tip of the probe; a flow path connecting the probe and the liquid delivery mechanism; a cleaning nozzle with its discharge port facing laterally; a cleaning liquid supply mechanism for discharging cleaning liquid from the discharge port of the cleaning nozzle; and a drive mechanism for moving at least one of the probe and the discharge port of the cleaning nozzle up and down. The cleaning method controls the probe to move relatively upward relative to the discharge port of the cleaning nozzle during the cleaning period in which cleaning liquid is discharged from the cleaning nozzle toward the probe.

[0013] Further features relating to the present invention will become apparent from the description herein and the accompanying drawings. Furthermore, aspects of the present invention are achieved and realized through elements and various combinations of elements, as well as in the manner of the detailed description and the accompanying claims. The description herein is merely illustrative and does not limit in any way the claims or applications of the present invention.

[0014] According to the present invention, it is possible to suppress the carryover of components between liquids during dispensing by a dispensing device, and to suppress the adhesion of cleaning solution to the outer surface of the probe or tip. Problems, configurations, and effects other than those described above will be clarified by the following description of embodiments.

[0015] This is a schematic diagram showing a dispensing device according to the first embodiment. This is a schematic diagram illustrating the shape of the discharge port of the cleaning nozzle of the dispensing device shown in Figure 1. This is a flowchart showing the procedure of the dispensing method according to the first embodiment. This is a flowchart showing the procedure of the tip outer wall cleaning step in the dispensing method according to the first embodiment. This is a schematic diagram illustrating the probe internal cleaning step in the dispensing method according to the first embodiment. This is a schematic diagram illustrating the probe internal cleaning step in the dispensing method according to the first embodiment. This is a schematic diagram illustrating the probe internal cleaning step in the dispensing method according to the first embodiment. This is a schematic diagram illustrating the sorting step in the dispensing method according to the first embodiment. This is a schematic diagram illustrating the sorting step in the dispensing method according to the first embodiment. This is a schematic diagram illustrating the sorting step in the dispensing method according to the first embodiment. This is a schematic diagram illustrating the tip outer wall cleaning step in the dispensing method according to the first embodiment. This is a schematic diagram illustrating the tip outer wall cleaning step in the dispensing method according to the first embodiment, and corresponds to an enlarged view of the main part of Figure 11. This is a schematic diagram illustrating the tip outer wall cleaning process in the dispensing method according to the first embodiment, and corresponds to an enlarged view of the main part of Figure 11. This is a schematic diagram illustrating the tip outer wall cleaning process in the dispensing method according to the first embodiment, and corresponds to an enlarged view of the main part of Figure 11. This is a schematic diagram illustrating the tip outer wall cleaning process in the dispensing method according to the first embodiment, and corresponds to an enlarged view of the main part of Figure 11. This is a schematic diagram illustrating the dispensing process in the dispensing method according to the first embodiment. This is a schematic diagram illustrating the discharge process in the dispensing method according to the first embodiment. This is a timing chart of probe movement and cleaning solution supply in the tip outer wall cleaning process shown in Figures 11 to 15. This is a timing chart of probe movement and cleaning solution supply in the probe internal cleaning process shown in Figures 4 to 6. This is a schematic configuration diagram showing the dispensing device according to the second embodiment. This is a flowchart illustrating the procedure of the dispensing method according to the second embodiment. This is a flowchart illustrating the procedure of the probe outer wall cleaning process in the dispensing method according to the second embodiment. This is a schematic diagram illustrating the probe outer wall cleaning process in the dispensing method according to the second embodiment, and corresponds to an enlarged view of the main part of Figure 20.This is a schematic diagram illustrating the probe outer wall cleaning process in the dispensing method according to the second embodiment, and corresponds to an enlarged view of the main part of Figure 20. This is a schematic diagram illustrating the probe outer wall cleaning process in the dispensing method according to the second embodiment, and corresponds to an enlarged view of the main part of Figure 20. This is a schematic diagram illustrating the probe outer wall cleaning process in the dispensing method according to the second embodiment, and corresponds to an enlarged view of the main part of Figure 20. This is a schematic diagram illustrating the probe outer wall cleaning process in the configuration of the dispensing device and the dispensing method according to a modified example of the second embodiment, and corresponds to an enlarged view of the main part of Figure 20. This is a schematic diagram illustrating the probe outer wall cleaning process in the configuration of the dispensing device and the dispensing method according to a modified example of the second embodiment, and corresponds to an enlarged view of the main part of Figure 20. This is a top view showing the schematic configuration of an automatic analyzer equipped with the dispensing device shown in Figure 1.

[0016] Examples of the dispensing apparatus and the cleaning method for the dispensing apparatus according to the present invention will be described below. It should be noted that the embodiments of the present invention are not limited to the examples described later, and various modifications are possible within the scope of the technical concept. In the drawings used herein, the same or corresponding components are denoted by the same or similar reference numerals, and repeated descriptions of these components may be omitted.

[0017] In the dispensing device according to the embodiment of the present invention, there are several possible methods for raising and lowering the probe relative to the discharge port of the cleaning nozzle. First, in Figures 14 and 15 below, the drive mechanism drives the probe up and down. Next, in Figures 24 and 25 below, the drive mechanism drives the cleaning nozzle up and down. Finally, in Figures 26 and 27 below, the probe and cleaning nozzle are not driven up and down, but the drive mechanism tilts the cleaning nozzle up and down so that the probe rises relative to the discharge port of the cleaning nozzle.

[0018] [First Embodiment] (Dispensing Device) The dispensing device according to the first embodiment adopts a configuration in which a detachable tip is attached to the tip of the probe.

[0019] Figure 1 is a schematic diagram showing the general configuration of a dispensing device 10 according to the first embodiment. As shown in Figure 1, the dispensing device 10 comprises a washing unit 1, a tip 21, a probe 22, a flow path 23, an arm 24 supporting the probe 22, a probe driving mechanism 25, a syringe 3, a syringe driving mechanism 33, and a control unit 4. The dispensing device 10 is installed in an automated analyzer 100 and dispenses the sample 91 in the sample container 61 and the reagents 92 and 93 in the reagent containers 62 and 63 into the reaction vessel 5. The automated analyzer 100 according to the present invention is a biochemical analyzer, an immunoassay analyzer, etc.

[0020] Figure 28 is a top view showing a schematic configuration of an automated analyzer 100 equipped with a dispensing device 10. The automated analyzer 100 according to the present invention comprises a dispensing device 10 and a detection unit (not shown) for detecting and quantifying the components of a sample in a reaction vessel 5. Furthermore, as shown in Figure 28, for example, it comprises a sample disk 71 for holding a sample container 61, a reagent disk 72 for holding reagent containers 62 and 63, a reaction disk 73 for holding a reaction vessel 5, a gripper 74 for transporting the tip 21 and the reaction vessel 5, a reaction vessel rack 75, a tip rack 76, a tip buffer 77, a tip disposal port 78, and a reaction vessel disposal port 79. In Figure 28, only the washing unit 1 and the arm 24 of the dispensing device 10 are shown. The elements constituting the dispensing device 10 will be described below.

[0021] The cleaning unit 1 cleans the outer wall of the tip 21 and the inner wall of the probe 22. The cleaning unit 1 includes a cleaning nozzle 11, flow paths 13 and 14, a liquid supply pump 15, solenoid valves 16 and 17, a cleaning liquid tank 18 containing cleaning liquid 8, and a cleaning tank 19.

[0022] The cleaning nozzle 11 is positioned near the inner side wall of the cleaning tank 19, with its discharge port (opening) 11a facing inward (towards the center in plan view). The base of the cleaning nozzle 11 is connected to the flow path 14, and the cleaning liquid tank 18 is connected via the flow paths 14 and 13. In Figure 1, the cleaning nozzle 11 is fixed to the side wall of the cleaning tank 19, and the flow path 14 penetrates the side wall of the cleaning tank 19, but the structure is not particularly defined. In this embodiment, the flow path of the cleaning nozzle 11 up to the discharge port 11a is horizontal (elevation angle 0°), and the opening surface is a vertical plane, but it may be installed at an inclination upward or downward.

[0023] The flow path 13 is positioned so that its opening is immersed in the cleaning fluid 8 in the cleaning fluid tank 18, and branches to the flow path 14 and the cylinder 31 of the syringe 3. The liquid supply pump 15 is installed in the flow path 13 and draws the cleaning fluid 8 from the cleaning fluid tank 18 up from the flow path 13 and sends it to the flow path 14 and the cylinder 31. The solenoid valve 16 is installed between the flow paths 13 and 14 and opens when supplying cleaning fluid 8 to the cleaning nozzle 11, and is closed at other times. The solenoid valve 17 is installed between the flow path 13 and the cylinder 31 and opens when supplying cleaning fluid 8 to the cylinder 31, and is closed at other times. The liquid supply pump 15 and the solenoid valve 16 constitute a cleaning fluid supply mechanism that supplies cleaning fluid 8 to the cleaning nozzle 11, and the liquid supply pump 15 and the solenoid valve 17 constitute a means for supplying cleaning fluid 8 from the cylinder 31 to the probe 22 via the flow path 23.

[0024] The cleaning solution tank 18 is the source of the cleaning solution 8 and contains the cleaning solution 8. The cleaning tank 19 is a receptacle for the cleaning solution 8 discharged from the cleaning nozzle 11 and probe 22, and for the sample 91 and reagents 92, 93 washed off from the outer wall of the tip 21. The cleaning tank 19 has an internal horizontal cross-sectional shape that can accommodate the cleaning nozzle 11 and the vicinity of the tips of the tip 21 and probe 22 with a gap between them, and has a depth that prevents the cleaning solution 8 discharged from the cleaning nozzle 11 and probe 22 from splashing out when cleaning the outer wall of the tip 21 and the inner wall of the probe 22. The cleaning tank 19 also has a through hole formed in its bottom surface and is connected to a waste liquid tank (not shown) via a drainage channel.

[0025] In this configuration, the cleaning unit 1 discharges cleaning liquid 8 laterally from the discharge port 11a of the cleaning nozzle 11 to clean the outer wall of the chip 21 that has entered the cleaning tank 19. To this end, the arrangement of the cleaning nozzle 11 and the shape of the discharge port 11a are designed so that the water flux 8f of the cleaning liquid 8 discharged from the cleaning nozzle 11 intersects with the trajectory of the chip 21 in the cleaning tank 19.

[0026] Here, the shape of the discharge port 11a of the cleaning nozzle 11 will be explained with reference to Figure 2. Figure 2 is a schematic diagram illustrating the shape of the discharge port 11a of the cleaning nozzle 11, and is a front view (side view) of the discharge port 11a of the cleaning nozzle 11 in the cleaning tank 19, with the tip 21 positioned towards the front. As shown in Figure 2, the discharge port 11a of the cleaning nozzle 11 is an elongated oval (rounded rectangle) that is long horizontally, and its horizontal length (maximum length in the horizontal direction) W1 is longer than the maximum diameter W2 of the area 21a to be cleaned on the outer wall of the tip 21. With this opening shape, the water flow 8f of the cleaning liquid 8 discharged from one cleaning nozzle 11 is wider than the outer diameter of the tip 21, and the cleaning liquid 8 that lands on the side of the tip 21 facing the discharge port 11a can easily flow around to the opposite side, making contact with the entire circumference of the outer wall of the tip 21, making it difficult for any areas to be left uncleaned. However, if the horizontal length of the discharge port 11a is excessively long, the opening area will be large, requiring a larger flow rate of the cleaning liquid 8 supplied from the cleaning liquid tank 18 to give the discharged cleaning liquid 8 sufficient force to reach the tip 21. This would necessitate a larger supply pump 15 and increase the consumption of cleaning liquid 8. For this reason, it is preferable that the discharge port 11a has an opening shape in which the vertical length is shorter than the horizontal length W1, so as to reduce the opening area, and the force of the discharged cleaning liquid 8 can be increased relative to the flow rate of the cleaning liquid 8 supplied from the cleaning liquid tank 18. It is even more preferable that the shape of the discharge port 11a has an aspect ratio of 1 / 3 or less (vertical length is 1 / 3 or less of horizontal length W1). Note that the discharge port 11a is not limited to the shape shown in Figure 2, and any flat shape that is long horizontally is acceptable, such as an ellipse or rectangle.

[0027] The tip 21 serves as a dispensing nozzle for the dispensing device 10 and is detachable and can be attached to the tip of the probe 22 as needed. The tip 21 is a single-use component for each sample 91. Before use, it is stored in the tip rack 76 and transported to the tip buffer 77 by the gripper 74 before being attached to the probe 22. The tip 21 can then be attached to the tip of the probe 22 by lowering the probe 22 from above the tip buffer 77. Alternatively, the tip 21 may be directly attached to the probe 22 via the tip rack 76. After use, the tip 21 is removed from the probe 22 and discarded in the tip disposal port 78.

[0028] Here, the area 21a of the tip 21 to be cleaned (see Figure 2) is at least the portion that was immersed in each liquid when the sample 91 and reagents 92 and 93 were aspirated. Therefore, it is preferable to set it to match the area that was most widely immersed among the sample 91 and reagents 92 and 93 (or liquid 9, if not distinguished). For example, as the maximum area that may have been immersed in liquid 9, if the containers 61, 62, and 63 (or container 6, if not distinguished) contain liquid 9 up to their upper limit, the area that is below the liquid surface when the probe 22 is lowered and the tip 21 is inserted is set as the area to be cleaned 21a.

[0029] The probe 22, together with the tip 21, is the dispensing nozzle of the dispensing device 10. It aspirates the sample 91 from the sample container 61 and the reagents 92 and 93 from the reagent containers 62 and 63 from its tip (via the tip 21) and temporarily holds them inside. Note that if the tip 21 is attached, the aspirated sample etc. may be held inside the tip 21 and may not reach the probe 22. The flow path 23 is provided in the arm 24 and connects the base of the probe 22 to the cylinder 31 of the syringe 3. The arm 24 supports the probe 22 and is structured to allow the probe 22 to move horizontally (rotate around the vertical support column of the arm 24 as the axis of rotation) and vertically. The horizontal movement path of the probe 22 is shown by a dashed line in Figure 28. The probe drive mechanism 25 is a motor or actuator, etc., and moves the probe 22 horizontally and vertically via the arm 24. The probe drive mechanism 25 can also change the movement speed of the probe 22 during vertical movement.

[0030] Syringe 3 is a fluid delivery mechanism that draws in and discharges fluid (liquid, air) from the tip of the tip 21 or probe 22. It consists of a cylinder 31 connected to the probe 22 via a flow path 23 and a plunger 32 fitted inside the cylinder 31. The plunger 32 moves linearly in the direction of pushing (pressurizing) and pulling out (depressurizing) the cylinder 31 (up and down in Figure 1) by the syringe drive mechanism 33. The syringe drive mechanism 33 is a linear motion mechanism and is connected to the plunger 32. This allows for the draw in and discharge of fluid (liquid and gas) from the tip of the tip 21 attached to the probe 22. Furthermore, as described above, the cylinder 31 is connected to the cleaning fluid tank 18 via the flow path 13 of the cleaning unit 1. As will be described later, cleaning fluid 8 can be supplied from the cleaning fluid tank 18 into the cylinder 31 and clean the inside of the probe 22 and tip 21 via the flow path 23.

[0031] The control unit 4 controls the probe drive mechanism 25, the syringe drive mechanism 33, and the liquid supply pump 15 and solenoid valves 16 and 17 of the washing unit 1. The control unit 4 may be configured to control not only these components of the dispensing device 10, but also the operation of the entire automated analyzer.

[0032] (Automated analyzer) The elements of the automated analyzer 100 other than the dispensing device 10 will now be described. The sample disk 71, reagent disk 72, and reaction disk 73 are each driven to rotate, moving the container 6 and reaction vessel 5 to be held along the movement path of the probe 22 of the dispensing device 10 (the dashed line in Figure 28). Furthermore, the reaction disk 73 has a temperature control function, and the sample and reaction solution (sample) are prepared in the reaction vessel 5 that it holds.

[0033] The gripper 74 transports the tip 21 and the reaction vessel 5. The reaction vessel 5, like the tip 21, is a single-use component for each sample 91. For this reason, the reaction vessel rack 75 stores the reaction vessel 5 before use. The tip rack 76 and tip buffer 77 each contain and temporarily hold the tip 21 before use, as described above. The tip disposal port 78 and the reaction vessel disposal port 79 are disposal ports for the used tip 21 and reaction vessel 5, respectively. Therefore, in the automated analyzer 100, the reaction vessel 5, like the tip 21, is stored in the reaction vessel rack 75 before use and transported to the reaction disk 73 by the gripper 74. The dispensing device 10 then dispenses the sample 91 and reagents 92 and 93 into the reaction vessel 5 held on the reaction disk 73. After the sample in the reaction vessel 5 is analyzed by the detection unit, the reaction vessel 5 is transported to the reaction vessel disposal port 79 by the gripper 74.

[0034] (Dispensing Method) Figure 3A is a flowchart showing the procedure of the dispensing method according to the first embodiment. In the dispensing method according to this embodiment, the dispensing device 10 sequentially aspirates one or more types of reagents and samples into the tip 21 and simultaneously discharges them into the reaction vessel 5. To this end, the dispensing method according to this embodiment first performs the probe cleaning step S1 and the tip mounting step S2, and repeats the sorting step S3 and the tip outer wall cleaning step S4 until all the samples 91 and reagents 92, 93 required for the sample (reaction solution) are performed (step S5: YES), and then performs the discharge step S6 and the tip removal step S7. In practice, the dispensing method according to this embodiment is carried out by the control unit 4 controlling the operation of each component of the dispensing device 10 (probe driving mechanism 25, syringe driving mechanism 33, liquid supply pump 15 and solenoid valves 16, 17 of the cleaning unit 1), but in the following, each component of the dispensing device 10 may be described as the main operator of the operation.

[0035] The probe cleaning process S1 is performed. In step S11, the probe drive mechanism 25 moves the probe 22 onto the cleaning tank 19 as shown in Figure 4, and then in step S12, as shown in Figure 5, it lowers the probe 22 so that the tip of the probe 22 is inserted into the cleaning tank 19. In step S13, as shown in Figure 6, the solenoid valve 17 is opened and the liquid supply pump 15 is driven to supply the cleaning liquid 8 from the cleaning liquid tank 18 into the probe 22 via the flow path 13, cylinder 31, and flow path 23, and discharge it from the tip. Once a predetermined amount of cleaning liquid 8 has been supplied, the liquid supply pump 15 is stopped and the solenoid valve 17 is closed. This cleans the inner wall of the probe 22. Then, in step S14, the probe drive mechanism 25 raises the probe 22 back to its position on the cleaning tank 19 before lowering in step S12 (see Figure 4). Also, the syringe drive mechanism 33 depressurizes the syringe 3 to draw air from the tip of the probe 22. The detailed operation of the probe cleaning process S1 will be described later.

[0036] In the chip mounting process S2, the probe drive mechanism 25 moves the probe 22 onto the unused chip 21 held in the chip buffer 77 (see Figure 28), then lowers it so that its tip is inserted into the chip 21 and mounted.

[0037] The dispensing process S3 is executed. In step S31, the probe driving mechanism 25 moves the probe 22 onto the reagent container 62 as shown in Figure 7, and then in step S32, it lowers it as shown in Figure 8 so that the tip of the tip 21 is below the liquid level of the reagent 92 in the reagent container 62. Specifically, even when the aspiration of a predetermined amount of reagent 92 is completed in the subsequent step S33, the liquid level of the reagent 92 is kept above the tip of the tip 21. In step S33, the syringe driving mechanism 33 depressurizes the syringe 3 and aspirates a predetermined amount of reagent 92 into the tip 21 as shown in Figure 9.

[0038] In step S34, the probe driving mechanism 25 raises the probe 22 and returns it to the position it was in before being lowered in step S32. Then, in step S35, as shown in Figure 10, the syringe driving mechanism 33 depressurizes the syringe 3, draws a predetermined amount of air from the tip of the tip 21, and delivers the reagent 92 contained in the tip of the tip 21 to the probe 22.

[0039] The chip outer wall cleaning process S4 is performed. Figure 3B is a flowchart showing the procedure for the chip outer wall cleaning process in the dispensing method shown in Figure 3A.

[0040] In step S41, as shown in Figure 11, the probe driving mechanism 25 moves the probe 22 onto the cleaning tank 19, and in step S42, as shown in Figure 12, the probe 22 is lowered at a speed v3 to insert the tip 21 into the cleaning tank 19 to a predetermined depth.

[0041] In step S43, as shown in Figure 13, the solenoid valve 16 is opened and the liquid supply pump 15 is started to supply the cleaning liquid 8 in the cleaning liquid tank 18 to the cleaning nozzle 11 via the flow paths 13 and 14, and discharge it from the discharge port 11a. The cleaning liquid 8 discharged from the cleaning nozzle 11 then lands on the side of the outer wall of the tip 21 facing the discharge port 11a (the right side in the figure; hereafter referred to as the front), some of which flows around to the opposite side, and another part falls down the outer wall (not shown). The position where the water flux 8f of the cleaning liquid 8 discharged from the cleaning nozzle 11 collides with the tip 21 is called the landing spot SP.

[0042] Then, in step S44, as shown in FIG. 14, the probe driving mechanism 25 starts raising (relative movement) of the probe 22 at a first speed v4. Accordingly, the tip 21 vertically cuts through the water stream 8f of the cleaning liquid 8 discharged from the cleaning nozzle 11 from bottom to top, and the water landing spot SP of the cleaning liquid 8 moves on the front surface of the outer wall of the tip 21 from top to bottom.

[0043] As shown in FIG. 15, when the tip 21 passes through the water stream 8f of the cleaning liquid 8 and rises to a position where it does not contact the cleaning liquid 8, in step S45, the liquid supply pump 15 is stopped and the electromagnetic valve 16 is closed. In addition, in step S46, the probe driving mechanism 25 accelerates the raising speed of the probe 22 to a second speed higher than v4, and returns the probe 22 to the position before lowering in step S42, as shown in FIG. 11. Although FIG. 3B shows that step S46 is executed in this order after step S45, as will be described in detail later, the order of starting step S46 (acceleration of the raising speed of the probe 22) and executing step S45 (stopping the supply of the cleaning liquid 8) may be reversed or they may be performed simultaneously. Through steps S43 to S45, the cleaning liquid 8 contacts the entire cleaning target region 21a on the outer wall of the tip 21, and the reagent 92 adhered in the fractionation step S3 (step S33) is washed away.

[0044] In step S47, the syringe driving mechanism 33 reduces the pressure of the syringe 3, sucks a predetermined amount of air from the tip of the tip 21, and feeds the reagent 92 accommodated in the tip 21 to the probe 22 side. Detailed operations in the tip outer wall cleaning step S4 will be described later.

[0045] The fractionation step S3 is performed again. In the second fractionation step S3, the reagent 93 is aspirated. To this end, in step S31, the probe driving mechanism 25 moves the probe 22 onto the reagent container 63. Steps S32 to S35 can be performed in the same manner as in the first fractionation step. Since air has been aspirated in step S35 of the first fractionation step S3 and step S47 of the chip outer wall cleaning step S4, as shown in FIG. 16, the space between the reagent 92 and the reagent 93 in the chip 21 is segmented by air. Then, the second chip outer wall cleaning step S4 is performed, and the third fractionation step S3 is performed to aspirate the specimen 91. The third chip outer wall cleaning step S4 is performed, and since aspiration of the specimen 91 and the reagents 92 and 93 has been completed (step S5: YES), the discharge step S6 is performed.

[0046] In step S61, the probe driving mechanism 25 moves the probe 22 onto the reaction container 5, and further lowers the probe 22 such that the tip end of the chip 21 is lower than the upper end of the reaction container 5, as shown in FIG. 17. Then, in step S62, the syringe driving mechanism 33 pressurizes the syringe 3 to discharge all of the specimen 91 and the reagents 93 and 92 held in the chip 21. Furthermore, the probe driving mechanism 25 may lower the probe 22 to move the tip end of the chip 21 to the vicinity of the bottom surface of the reaction container 5, and the syringe driving mechanism 33 depressurizes the syringe 3 to aspirate the liquid in the reaction container 5 and discharge it again. Through this operation, the dispensed specimen 91 and reagents 92 and 93 are stirred, and the reaction efficiency between the specimen 91 and the reagents 92 and 93 can be increased.

[0047] In the chip removing step S7, the probe driving mechanism 25 moves the probe 22 to the chip disposal port 78 (see FIG. 28), and removes the chip 21 from the tip end of the probe 22.

[0048] When another specimen is dispensed to prepare a new sample, the process is performed again starting from the probe inner cleaning step S1. The order of aspirating the reagents 92, 93 and the specimen 91 is not particularly limited, but it is preferable to aspirate the specimen 91 last. Furthermore, when only one type of reagent or three or more types of reagents are dispensed, steps S3, S4, and S5 may be repeatedly performed in this order according to the number of types of the liquid 9.

[0049] The chip outer wall cleaning process S4 (steps S41 to S46) will be described in detail. As shown in Figures 13 to 15, the cleaning liquid 8 discharged laterally from the cleaning nozzle 11 falls, so if the discharge force is weak, the cleaning liquid 8 will fall without reaching the side of the chip 21 opposite the discharge port 11a, resulting in uncleaned areas. On the other hand, if the force of the cleaning liquid 8 is excessively strong, the cleaning liquid 8 will strongly collide with the chip 21, scattering over a wide area along with the reagent 92 attached to the chip 21, or strongly colliding with the inner wall of the cleaning tank 19, causing water to splash onto the chip 21. Therefore, the pressure of the liquid supply pump 15 is set so that the cleaning liquid 8 is discharged with appropriate force.

[0050] Furthermore, the position of the probe 22 after lowering in step S42 is such that, at the start of the subsequent step S43, the cleaning fluid 8 discharged from the cleaning nozzle 11 contacts the upper end or above the area 21a of the tip 21 to be cleaned. Depending on the distance from the discharge port 11a of the cleaning nozzle 11 to the tip 21 (horizontal length), the elevation angle of the cleaning nozzle 11, the flow rate of the cleaning fluid 8, etc., when the cleaning nozzle 11 is horizontal (elevation angle 0°), in the height direction, as shown in Figures 2 and 12, the distance L from the center z0 of the discharge port 11a of the cleaning fluid 8 to the tip of the tip 21 (lowering depth) max However, the height of the cleaning target area 21a of the tip 21 (length from the tip of the tip 21 to the upper end of the cleaning target area 21a) is La or greater (L max (L) ≥ La, preferably longer than La. max >La). That is, the area 21a of the tip 21 to be cleaned is positioned below the height center z0 of the discharge port 11a of the cleaning solution 8. On the other hand, if the probe 22 is lowered too deeply, the cleaning time will be longer and the consumption of cleaning solution 8 will also increase. Therefore, for example, the descent depth L of the tip 21 max is less than or equal to three times the height La of the area to be cleaned 21a (L max It is preferable to set it to ≤ 3La.

[0051] Furthermore, the position of the probe 22 after it has been raised in step S44, in other words, the position at the start of step S45 (when the supply of cleaning solution 8 is stopped), is preferably a position where the cleaning solution 8 discharged from the cleaning nozzle 11 contacts the tip of the tip 21, or a position higher than that where it does not contact the tip 21. When the cleaning nozzle 11 is horizontal (elevation angle 0°), in the height direction, it is preferable that the tip of the tip 21 coincides with the center of the discharge port 11a of the cleaning nozzle 11, and more preferably higher, as shown in Figure 15. On the other hand, if the probe 22 is raised excessively in step S44, and the supply of cleaning solution 8 is continued until the probe 22 is raised excessively high, the consumption of cleaning solution 8 will increase, and the cleaning time will also be longer.

[0052] Figure 18 is a timing chart of probe movement and cleaning fluid supply during the chip outer wall cleaning process S4. Time t40 to t41 corresponds to Figure 11, time t42 to t44 to Figure 12, time t44 to t45 to Figure 13, time t45 to t46 to Figure 14, time t46 to t47 to Figure 15, and time t49 onwards to Figure 11.

[0053] Here, the cleaning period can be broadly defined as the period during which the chip outer wall cleaning process S4 is performed. However, in this specification, the cleaning period refers to the period during which the cleaning liquid 8 is discharged from the cleaning nozzle 11. This period is approximated as the period in steps S43 to S45 when the solenoid valve 16 is open and the liquid supply pump 15 is running (times t44 to t47). Furthermore, the cleaning period can be more narrowly defined as the period during which the water flux 8f of the cleaning liquid 8 discharged from the cleaning nozzle 11 collides with the chip 21, creating a water spot SP.

[0054] Time t40 indicates the state at the completion of step S41 and before step S42. Step S42 is started at time t41 to lower the probe 22 at speed v3, and is completed at time t42 when the tip of the tip 21 reaches a predetermined position in the cleaning tank 19. Step S43 is started at time t43, after time t42 when the descent of the probe 22 stops, to open the solenoid valve 16, and the liquid supply pump 15 is started to drive at time t44, after time t43. Step S44 is executed at time t45, after time t44, to start the rise of the probe 22 at speed (first speed) v4. At time t47, after a predetermined time has elapsed from time t45, the liquid supply pump 15 is stopped, and the solenoid valve 16 is closed at time t48, after time t47. At time t47, step S46 is initiated to accelerate the probe 22 to a speed (second speed) v5, return it to its position before time t41, and is completed at time t49.

[0055] Here, as the probe 22 rises from time t45 in step S44, at time t46 the tip of the tip 21 passes the center z0 of the discharge port 11a of the cleaning fluid 8. In Figure 18, the area that comes into contact with the cleaning fluid 8 is shown by hatching at the tip position. This area is just below z0, which is represented by a dashed line in the figure. Therefore, after time t46, the cleaning fluid 8 does not come into contact with the tip 21 (see Figure 15). From this, it can be said that after time t46, either the start of step S46 or step S45 can come first, or they can be performed simultaneously as shown in Figure 18. Also, if step S45 is performed before step S46, the probe 22 can be stopped during execution, but it is preferable to continue raising it.

[0056] Note that the opening and closing times of the solenoid valve 16 and the start and stop times of the liquid supply pump 15 shown in Figure 18 are actual times, and the electrical signals transmitted by the control unit 4 occur before these times. For example, solenoid valves 16 and 17 generally require a response time of about 10 to 20 ms after receiving an electrical signal. Therefore, it is preferable that the control unit 4 be configured to transmit electrical signals for operation taking into account the response time of each component.

[0057] The downward (step S42) speed v3 of the probe 22 in the chip outer wall cleaning step S4 can be set in accordance with the downward (step S32) speed in the preparative step S3. On the other hand, the upward (step S44) speed v4 of the probe 22 when cleaning the outer wall of the chip 21 is preferably slower than speed v3 so that each part of the outer wall is exposed to the cleaning solution 8 for a certain period of time or longer in order to wash off the dirt (liquid 9) adhering to the outer wall. Furthermore, if the upward speed v4 is slow, less cleaning solution 8 adheres to the outer wall of the chip 21, and mixing of the cleaning solution 8 into the container 6 containing the liquid 9 to be aspirated in the next preparative step S3 is suppressed. In addition, the upward (step S46) speed v5 of the probe 22 after the supply of cleaning solution 8 is stopped (step S45) can be set in accordance with the upward (step S34) speed in the preparative step S3.

[0058] The rising speed v4 when supplying the cleaning solution 8 is preferably set according to the surface properties of the outer wall of the tip 21 and the wettability of the liquid 9. Therefore, it is possible to configure the system so that different rising speeds v4 are set after aspirating reagents 92, 93 and sample 91, respectively. Furthermore, for liquid 9 that is particularly difficult to remove from the outer wall of the tip 21, the rising speed v4 of the probe 22 is gradually reduced at times t45 to t46 so that the area near the tip of the tip 21, where a relatively large amount of cleaning solution 8 adheres, is in contact with the cleaning solution 8 for a longer period of time, and the probe 22 may be brought to a standstill before step S45.

[0059] In Figure 18, the descent and ascent of the probe 22 (steps S42, S44, S46) are represented by constant velocities v3, v4, and v5, but these can vary. For example, the velocity can gradually increase from 0 at the start of movement (ascent, descent), and then gradually decrease to decelerate and stop a little before completion. This also applies to the vertical movement of the probe in the sorting step S3 and the probe cleaning step S1 (see Figure 19) described later. Furthermore, during the ascent of the probe 22 from step S44 to just before the start of step S46, it is possible to decelerate and accelerate or pause midway, within an effective range. Also, at the start of step S46, the ascent velocity can gradually increase from the ascent velocity in step S44. Here, velocities v3, v4, and v5 are compared as average velocities during the movement period, and it is preferable that velocities v3 and v5 are faster than the ascent velocity v4 in step S44.

[0060] In Figures 3B and 18, step S44 is performed after step S43, meaning that immediately after the start of supplying the cleaning fluid 8, the cleaning fluid 8 discharged from the cleaning nozzle 11 comes into contact with the stationary tip 21. However, steps S43 and S44 may be performed simultaneously, or step S43 may be performed after step S44. However, if the tip 21 is rising when the cleaning fluid 8 discharged from the cleaning nozzle 11 begins to come into contact with the tip 21, the timing of steps S43 and S44 and the lowering position of the probe 22 in step S42 are adjusted so that at the time of contact, the cleaning fluid 8 comes into contact with the upper end or above the cleaning target area 21a of the tip 21.

[0061] The probe cleaning process S1 (steps S11 to S14) will be described in detail. When the cleaning liquid 8 is discharged, the position of the probe 22 is preferably such that the probe 22 does not come into contact with the inner surface of the cleaning tank 19 or the cleaning nozzle 11, as shown in Figure 5, and the cleaning liquid 8 discharged from the tip of the probe 22 does not splash outside the cleaning tank 19. For example, the tip of the probe 22 should be below the upper end of the cleaning tank 19. However, if the tip of the probe 22 is too close to the bottom of the cleaning tank 19, the cleaning liquid 8 may collide with the bottom of the cleaning tank 19, causing splashing onto the probe 22. Also, if the force of the cleaning liquid 8 discharged from the probe 22 is excessively strong, it may splash outside the cleaning tank 19, so the pressure of the liquid supply pump 15 should be set in conjunction with the position of the probe 22.

[0062] Figure 19 is a timing chart of probe movement and cleaning fluid supply during the probe cleaning process S1. Times t10 to t11 correspond to Figure 4, times t12 to t13 to Figure 5, and times t14 to t15 to Figure 6.

[0063] Time t10 indicates the state at the completion of step S11 and before step S12. Step S12 is started at time t11 to lower the probe 22 at speed v1, and is completed at time t12 when the tip of the probe 22 reaches a predetermined position in the cleaning tank 19. Step S13 is started at time t13, after time t12 when the descent of the probe 22 stops, to open the solenoid valve 17, and at time t14, after time t13, the liquid supply pump 15 is started to discharge the cleaning liquid 8 from the tip of the probe 22. At time t15, after a predetermined time has elapsed from time t14, the liquid supply pump 15 is stopped, and at time t16, after time t15, the solenoid valve 17 is closed. After time t15, when the cleaning liquid 8 is no longer discharged from the tip of the probe 22, step S14 is started at time t17 to raise the probe 22 at speed v2, returning it to the position before time t11, and is completed at time t18.

[0064] In the probe internal cleaning step S1, the tip 21 is not attached to the tip of the probe 22, and when the probe 22 descends (step S12), the tip of the probe 22 enters the cleaning tank 19, so the travel distance h1 tends to be longer than the descent distance h2 (see Figure 18) in the tip outer wall cleaning step S4 (step S42). Also, the speeds v1 and v2 of the descent and ascent (steps S12, S14) of the probe 22 in the probe internal cleaning step S1 can be set in accordance with the descent and ascent (steps S32, S34) speeds in the dispensing step S3. However, in this step S1, the probe 22 does not hold the liquid 9 to be dispensed, so there is no risk of leakage of the liquid 9 due to the impact of the movement of the probe 22, and because the travel distance is long, in order to shorten the time, the speeds can be set faster than the descent and ascent (steps S42, S46) speeds v3 and v5 in the tip outer wall cleaning step S4, within a range that does not cause problems.

[0065] In the dispensing method according to this embodiment, the tip outer wall cleaning step S4 is performed between the first and second dispensing steps S3, that is, after aspirating reagent 92 into the tip 21 and before aspirating reagent 93. This washes off the reagent 92 adhering to the outer wall of the tip 21, preventing contamination of the reagent 92 when the tip 21 is inserted into the reagent 93 in the reagent container 63 during the second dispensing step S3. Similarly, the tip outer wall cleaning step S4 is performed between the second and third dispensing steps S3, preventing contamination of the reagent 93 into the sample 91 in the sample container 61. Furthermore, the tip outer wall cleaning step S4 is performed after the final dispensing step S3, that is, after aspirating the sample 91 and before the discharge step S6. This prevents the sample 91 adhering to the outer wall of the tip 21 from falling into the reaction container 5 after the tip 21 is moved onto the reaction vessel 5 together with the probe 22 in the discharge step S6 (step S61), thereby increasing the accuracy of the amount of sample 91 dispensed into the reaction vessel 5.

[0066] Furthermore, after aspirating the liquid 9 in the preparative step S3 (step S33), air is aspirated from the tip of the tip 21 before the next tip outer wall cleaning step S4 (step S35), causing the aspirated liquid 9 to move towards the probe 22 side, leaving the area near the tip empty. As a result, the cleaning solution 8 that enters from the tip of the tip 21 in the tip outer wall cleaning step S4 does not come into contact with the liquid 9 inside the tip 21, preventing the liquid 9 from being diluted. Also, after stopping the supply of the cleaning solution 8 in the tip outer wall cleaning step S4 (step S45), air is aspirated from the tip of the tip 21 before the next preparative step S3 (step S47), causing the cleaning solution 8 adhering to the tip of the tip 21 and its vicinity to be drawn into the tip 21. As a result, after the probe 22 is moved from the washing tank 19 to the outside (on the container 6 or reaction vessel 5), dripping and splashing of the washing solution 8 is suppressed, and contamination of the container 6 containing the liquid 9 to be aspirated in the next preparation step S3 with the washing solution 8 is suppressed. In addition, since the sample and one or more reagents are contained within the tip 21 separated from each other by air, it is possible to prevent them from reacting before being discharged into the reaction vessel 5.

[0067] Furthermore, the probe cleaning step S1 allows the probe 22 to be cleaned by circulating the cleaning solution 8 inside it before aspirating the first liquid 9 (reagent 92). This ensures that even if liquid 9, particularly the first reagent 92 aspirated, is delivered to and adheres to the probe 22 during the previous sample preparation dispensing, the analysis can be performed without any impact. Additionally, by aspirating air from the tip of the probe 22 after circulating the cleaning solution 8 inside the probe 22, any remaining cleaning solution 8 at the tip of the probe 22 is sent to the flow path 23. As a result, dripping of liquid during the subsequent tip mounting step S2 is prevented.

[0068] According to the cleaning unit 1 of the dispensing device 10 in this embodiment, the cleaning liquid 8 can be brought into contact with the entire circumference of the outer wall of the tip 21 using only one cleaning nozzle 11, and without the need for a drive mechanism such as the revolution of the cleaning nozzle 11 or the rotation of the probe 22. Therefore, the number of parts can be reduced and the structure can be simplified. In addition, there is no risk of the cleaning liquids discharged from multiple cleaning nozzles colliding and scattering. Furthermore, with the cleaning unit 1, the water landing spot SP on the tip 21 is shifted from top to bottom during cleaning, so the contact area with the cleaning liquid 8 shifts from top to bottom, where the amount of liquid 9 adhering to the outer wall of the tip 21 is relatively small. As a result, the dirt does not spread to areas above the area to be cleaned 21a that do not have dirt (adhesion of liquid 9), suppressing the carryover of components between dispensed liquids, and improving the efficiency of both the consumption of cleaning liquid 8 and the cleaning time.

[0069] (Modification) In the chip outer wall cleaning step S4, the following may be performed to enhance the effect, such as washing off liquid 9 which is particularly difficult to remove from the outer wall of the chip 21. In the rise of the probe 22 from step S44 to before the start of step S46 (times t45 to t47 in Figure 18), as described above, it may be decelerated or stopped midway, or the direction of movement may be reversed to descend, then reversed again to rise, or it may be raised while repeatedly rising and falling in small increments.

[0070] Furthermore, in order to further increase the contact time of the cleaning solution 8 with the tip 21 while suppressing an increase in cleaning time, the cleaning solution 8 may be supplied to the cleaning nozzle 11 and discharged when the probe 22 is descending (times t41 to t42 in Figure 18). In this case, it is preferable to start supplying the cleaning solution 8 after the probe 22 has descended to a certain extent, so that the tip of the tip 21 does not enter the water flux 8f of the discharged cleaning solution 8 from above. This suppresses the scattering of the liquid 9 attached to the tip of the tip 21 over a wide area. It is also preferable to stop supplying the cleaning solution 8 before the descent of the probe 22 (step S42) is completed (time t42 in Figure 18), so that the dirt does not spread over the area 21a of the tip 21 that is to be cleaned and not washed off. Furthermore, it is preferable that the descent speed of the probe 22 is slow (for example, speed v4) at least while the cleaning solution 8 is being supplied. After the descent of the probe 22 (step S42) is completed, steps S43 and S44 are performed in the same manner as in the above embodiment.

[0071] In the dispensing method according to this embodiment, reagents 92, 93, and sample 91 may be discharged into the reaction vessel 5 each time they are aspirated; that is, steps S3, S4, S6, and S5 can be repeatedly performed in this order.

[0072] In the dispensing method according to this embodiment, for example, if reagent 92 and reagent 93 have similar components and a small amount of reagent 92 is mixed into reagent 93 in the reagent container 63 without affecting the analysis, then the tip outer wall cleaning step S4 does not need to be performed between the first and second dispensing steps S3 in which reagents 92 and 93 are aspirated.

[0073] In the dispensing method according to this embodiment, for example, if the wettability of the sample 91 to the outer wall of the tip 21 is low and the amount of adhesion is sufficiently small, or if the amount of sample 91 adhering to the outer wall of the tip 21 satisfies the accuracy of the amount of sample 91 dispensed in the sample, the dispensing step S6 may be performed after the final sorting step S3 in which the sample 91 is aspirated, without performing the tip outer wall cleaning step S4. Also, if either reagent 92 or 93 is aspirated last, the subsequent tip outer wall cleaning step S4 may not be performed.

[0074] In the dispensing method according to this embodiment, if the total amount of liquid 9 (sample 91, reagents 92, 93) to be dispensed for sample preparation is sufficiently less than the volume of the tip 21, and even including the air aspirated in between, the liquid will not be delivered into the probe 22, then the probe cleaning step S1 may not be performed before the tip mounting step S2.

[0075] By omitting the tip outer wall cleaning step S4 and the probe internal cleaning step S1 as described above, the time required for dispensing can be reduced, and the amount of cleaning solution 8 consumed can be decreased.

[0076] The dispensing device 10 according to this embodiment may include a probe 22A (see Figure 20 below) that does not have a tip 21 attached to its tip. Generally, the maximum diameter near the tip of the probe 22A, which is the area to be cleaned, is smaller than that of the tip 21 (W2 in Figure 2). Accordingly, it is preferable for the cleaning unit 1 to be equipped with a cleaning nozzle 11 with a short horizontal length of the opening (discharge port 11a) in order to reduce the consumption of cleaning solution 8. Also, in the flowchart shown in Figure 3A, the tip attachment step S2 and tip removal step S7 are not performed, and the dispensing step S3 is performed after the probe internal cleaning step S1 (see Figure 21A below). In the dispensing step S3, reagents 92, 92 and sample 91 are aspirated from the tip of the probe 22, and in the tip external wall cleaning step S4, the cleaning solution 8 is brought into contact with the external wall of the probe 22 for cleaning.

[0077] [Second Embodiment] The dispensing device according to the first embodiment is equipped with a probe that moves up and down, and a cleaning unit discharges cleaning liquid while raising the probe in order to clean the outer wall of the probe or tip. In contrast, even if the probe is fixed and the cleaning unit discharges cleaning liquid downward, the probe or tip rises relative to the discharged cleaning liquid, so a similar effect can be obtained.

[0078] (Dispensing device) The dispensing device according to the second embodiment employs a configuration in which the sample or reagent is directly aspirated and dispensed from the tip of the probe.

[0079] Figure 20 is a schematic diagram showing the general configuration of a dispensing device 10A according to the second embodiment. As shown in Figure 20, the dispensing device 10A includes a washing unit 1A, a probe 22A, a flow path 23, an arm 24 supporting the probe 22, a probe driving mechanism 25, a syringe 3, a syringe driving mechanism 33, and a control unit 4A.

[0080] The cleaning unit 1A cleans the outer and inner walls of the probe 22A. The cleaning unit 1A includes a cleaning nozzle 11A, a cleaning nozzle drive mechanism 12, flow paths 13 and 14A, a liquid supply pump 15, solenoid valves 16 and 17, a cleaning liquid tank 18, and a cleaning tank 19A.

[0081] The cleaning nozzle 11A is fixed inside the cleaning tank 19A, similar to the cleaning nozzle 11 of the first embodiment. The opening (discharge port) 11a (see Figure 22) of the cleaning nozzle 11A is a flattened shape such as an elongated oval, similar to the cleaning nozzle 11, and its horizontal length is longer than the maximum diameter of the area to be cleaned on the outer wall of the probe 22A. The flow path 14A is configured to follow the vertical movement of the cleaning nozzle 11A and is, for example, a flexible tube. The cleaning tank 19A has a structure that allows it to move vertically together with the cleaning nozzle 11A fixed inside. The other configurations of the cleaning nozzle 11A, the flow path 14A, and the cleaning tank 19A can be the same as those of the cleaning nozzle 11, the flow path 14, and the cleaning tank 19 of the first embodiment, respectively.

[0082] The cleaning nozzle drive mechanism 12 is a linear motion mechanism that moves the cleaning nozzle 11A up and down together with the cleaning tank 19A. The range of motion of the cleaning nozzle 11A should be h3 or greater as shown in Figure 18.

[0083] The control unit 4A has the same configuration as the control unit 4 of the first embodiment, except that it further controls the cleaning nozzle drive mechanism 12. The other components of the dispensing device 10A can be the same as those of the dispensing device 10 according to the first embodiment.

[0084] (Dispensing Method) Figure 21A is a flowchart showing the procedure of the dispensing method according to the second embodiment. In this embodiment, the dispensing device 10A sequentially aspirates one or more reagents and samples into the probe 22A and simultaneously discharges them into the reaction vessel 5. To this end, the dispensing method according to this embodiment first performs the probe internal cleaning step S1, then repeats the sorting step S3 and the probe outer wall cleaning step S4A until all the samples 91 and reagents 92, 93 required for the sample (reaction solution) are performed (step S5: YES), and finally performs the discharge step S6. That is, similar to the dispensing method according to the modified version of the first embodiment in which the tip 21 is not attached, the tip attachment step S2 and tip removal step S7 are not performed in the flowchart shown in Figure 3A. In this embodiment, the probe outer wall cleaning step S4A is performed in the procedure shown in Figure 21B instead of the tip outer wall cleaning step S4. Figure 21B is a flowchart showing the procedure of the probe outer wall cleaning step in the dispensing method according to this embodiment. Steps S1, S3, and S6 are the same as in the first embodiment shown in Figure 3A, except that the liquid 9 is drawn in and discharged from the tip of the probe 22A.

[0085] In this embodiment, at the start of the probe outer wall cleaning process S4A, the cleaning nozzle 11A is positioned above the movable range. Step S41 is the same as the tip outer wall cleaning process S4. Then, in step S42, similar to the tip outer wall cleaning process S4, the probe 22A is lowered and inserted into the cleaning tank 19A to a predetermined depth, as shown in Figure 22. In this embodiment, the probe 22A is lowered to a position where the upper end of the area to be cleaned of the probe 22A is below the height center of the discharge port 11a of the cleaning nozzle 11A positioned above the movable range.

[0086] Step S43 is the same as in the first embodiment, and as shown in Figure 23, the solenoid valve 16 is opened and the liquid supply pump 15 is started to supply the cleaning liquid 8 in the cleaning liquid tank 18 to the cleaning nozzle 11A and discharge it from its outlet. In step S44A, as shown in Figure 24, the probe 22A is not moved, and the cleaning nozzle drive mechanism 12 lowers the cleaning nozzle 11A to a predetermined position. That is, the probe 22A is raised (relatively moved) relative to the cleaning nozzle 11A. As a result, with the cleaning nozzle 11A as the reference, the probe 22A traverses the water flux 8f of the cleaning liquid 8 discharged from the cleaning nozzle 11A from bottom to top, and the landing spot SP of the cleaning liquid 8 moves from top to bottom on the side (front) of the outer wall of the probe 22A facing the outlet 11a. The position of the cleaning nozzle 11A after lowering in step S44A is preferably such that the cleaning liquid 8 discharged from the cleaning nozzle 11A contacts the tip of the probe 22A, or is lower and does not contact the probe 22A, as shown in Figure 25. When the cleaning nozzle 11A is horizontal (elevation angle 0°), in the height direction, it is preferable that the center of the discharge opening of the cleaning nozzle 11A coincides with the tip of the probe 22A, and more preferably is lower than that.

[0087] After step S44A, step S45 is performed in the same manner as in the first embodiment. Then, in step S46A, the probe drive mechanism 25 raises the probe 22A back to its position before lowering in step S42. The distance traveled by the probe 22A in step S46A is the same as that in step S42.

[0088] Step S47 is the same as in the first embodiment. In the probe outer wall cleaning step S4A, in step S48, the cleaning nozzle driving mechanism 12 raises the cleaning nozzle 11A and returns it to the position it was in before being lowered in step S44A.

[0089] The speeds v3 and v5 of the descent and ascent of the probe 22A in the probe outer wall cleaning process S4A (steps S42 and S46A) can be set in the same way as the speeds v3 and v5 in steps S42 and S46 of the tip outer wall cleaning process S4 in the first embodiment. Also, the descent speed v4 of the cleaning nozzle 11A in step S44A can be set in the same way as the ascent speed v4 of the probe 22 in step S44 of the tip outer wall cleaning process S4. When the cleaning nozzle 11A descends, it may be decelerated or stopped midway, similar to the ascent of the probe 22 in step S44 of the first embodiment, or the direction of movement may be reversed to ascend, and then reversed again to descend, or it may be descended while repeatedly making small descents and ascents.

[0090] In Figure 21B, step S44A is executed after step S43, but as in the first embodiment, step S44A and step S43 can be started simultaneously, or step S43 can be executed after step S44A has been started.

[0091] Furthermore, in Figure 21B, step S46A is performed after step S45, but as in the first embodiment, step S46A and step S45 can be started simultaneously, or step S45 can be performed after step S46A has been started. Also, step S48 can be started after step S45 and only needs to be completed by the start of step S43 of the next probe outer wall cleaning process S4A, and may be performed before or in parallel with steps S46A and S47. Alternatively, the following sorting process S3 may be performed before step S48.

[0092] The cleaning unit 1A of the dispensing device 10A according to this embodiment provides the same effects as the cleaning unit 1 of the first embodiment. Furthermore, with the dispensing device 10A, in the probe outer wall cleaning step S4A, it is possible to combine the high-speed (v3, v5) long-distance (h2) movement of the probe 22A with the low-speed (v4) short-distance (h3) movement of the cleaning nozzle 11A by the cleaning unit 1A.

[0093] (Modification) In the dispensing method according to this embodiment, similar to the modification of the first embodiment, one of the reagents 92, 93 and the sample 91 may be discharged into the reaction vessel 5 each time it is aspirated, that is, steps S3, S4A, S6, and S5 may be repeatedly performed in this order. Also, depending on the components of the reagents 92, 93 and the sample 91, it may be necessary to omit some of the probe outer wall cleaning steps S4A.

[0094] In this embodiment, the cleaning unit 1A of the dispensing device 10A may be configured such that the cleaning nozzle 11A is not fixed to the cleaning tank 19, and the cleaning nozzle 11A moves independently up and down. Alternatively, the dispensing device 10A in this embodiment may be configured such that the range of motion of the cleaning nozzle 11A and the cleaning tank 19A is extended to h2 or more as shown in Figure 18. With such a configuration, the probe 22A can be moved in the vertical direction without moving the probe 22A in the probe outer wall cleaning process S4A or the probe internal cleaning process S1, and the cleaning nozzle 11A can be moved together with the cleaning tank 19A.

[0095] In this embodiment, the cleaning unit 1A of the dispensing device 10A is configured to lower the discharged cleaning liquid 8 by the linear movement of the cleaning nozzle 11A. However, since a short distance (h3) of movement is sufficient, the cleaning nozzle 11A may rotate to change its elevation angle, thereby changing the discharge angle of the cleaning liquid 8.

[0096] Figures 26 and 27 are schematic diagrams showing the configuration of the cleaning unit 1B of the dispensing device according to a modified example of the second embodiment. As shown in Figures 26 and 27, the cleaning unit 1B includes a cleaning nozzle 11B, flow paths 13 and 14, a solenoid valve 16, and a cleaning tank 19, and further includes the cleaning nozzle drive mechanism 12, liquid supply pump 15, solenoid valve 17, and cleaning liquid tank 18 of the cleaning unit 1A shown in Figure 20. This modified example has a cleaning nozzle 11B that rotates so that the discharge port 11a moves up and down, and a cleaning nozzle drive mechanism 12 that rotates the cleaning nozzle 11B.

[0097] The cleaning nozzle 11B is located inside the cleaning tank 19, but is not fixed to the cleaning tank 19 and is independently movable. Specifically, the cleaning nozzle 11B has a rotatable structure such that the discharge port 11a moves up and down around the base 11b as the axis of rotation, in other words, it tilts up and down. The other configurations of the cleaning nozzle 11B can be the same as those of the cleaning nozzle 11A in the second embodiment.

[0098] In this modified example, the cleaning nozzle drive mechanism 12 is a drive mechanism that moves the discharge port 11a of the cleaning nozzle 11B up and down. More specifically, it rotates the cleaning nozzle 11B so that its discharge port 11a moves up and down (the cleaning nozzle 11B oscillates up and down). The range of motion of the cleaning nozzle 11B is such that the water flux 8f of the cleaning liquid 8 discharged from the cleaning nozzle 11B changes to h3 or more as shown in Figure 18 along the trajectory of the probe 22A. The cleaning nozzle 11B may also rotate from horizontal (elevation angle 0°) so that the discharge port 11a is upward (+), downward (-), or vertically on either side of the horizontal, as shown in Figures 26 and 27. Other components of the cleaning unit 1B can be the same as those of the cleaning unit 1A in the second embodiment.

[0099] The dispensing method using the dispensing device 10A equipped with a cleaning nozzle 11B is the same as the dispensing method shown in Figures 21A and 21B. In this modified example, at the start of the probe outer wall cleaning step S4A, the cleaning nozzle 11B is positioned upward in its range of motion. Then, in step S43, as shown in Figure 26, the cleaning liquid 8 discharged from the cleaning nozzle 11B collides with the front surface of the outer wall of the probe 22A. In this modified example, in step S44A, the cleaning nozzle 11B is rotated so that the discharge port 11a descends. That is, the probe 22A is raised (relatively moved) relative to the discharge port 11a of the cleaning nozzle 11B. As a result, the water landing spot SP moves from top to bottom on the front surface of the outer wall of the probe 22A. Then, as shown in Figure 27, when the cleaning nozzle 11B is tilted downward in its range of motion, the water flux 8f of the cleaning liquid 8 passes through the probe 22A and becomes non-contact, and step S44A is completed.

[0100] The dispensing device 10A according to this embodiment and its modified form may also be configured to include a probe 22 with a tip 21 attached to its tip, similar to the dispensing device 10.

[0101] The present invention is not limited to the embodiments described above, but includes various modifications. For example, the embodiments described above are described in detail for the purpose of clearly illustrating the present disclosure, and it is not necessary to have all the configurations described. Furthermore, parts of one embodiment can be replaced with the configurations of another embodiment. Furthermore, configurations of other embodiments can be added to the configuration of one embodiment. Furthermore, parts of the configurations of each embodiment can be added, deleted, or replaced with parts of the configurations of other embodiments.

[0102] The dispensing methods of each embodiment described above can be implemented not only in automated analyzers but also in other devices having a fluid dispensing mechanism. For example, the methods of each embodiment can be applied to pharmaceutical manufacturing equipment and the like.

[0103] 100 Automatic analyzer 10, 10A Dispenser 1, 1A, 1B Washing unit 11, 11A, 11B Washing nozzle 11a Discharge port 12 Washing nozzle drive mechanism 13 Flow path 14, 14A Flow path 15 Supply pump 16, 17 Solenoid valve 18 Washing solution tank 19, 19A Washing tank 21 Tip 22, 22A Probe 23 Flow path 24 Arm 25 Probe drive mechanism 3 Syringe 31 Cylinder 32 Plunger 33 Syringe drive mechanism 4, 4A Control unit 5 Reaction vessel 61 Sample container 62, 63 Reagent container 8 Washing solution 91 Sample 92, 93 Reagent

Claims

1. A dispensing device comprising: a probe for dispensing liquid; a liquid delivery mechanism for drawing in and discharging fluid from the tip of the probe; a flow path connecting the probe and the liquid delivery mechanism; a cleaning nozzle with its discharge port facing laterally; a cleaning liquid supply mechanism for discharging cleaning liquid from the discharge port of the cleaning nozzle; a drive mechanism for moving at least one of the probe and the discharge port of the cleaning nozzle up and down; and a control unit for controlling the cleaning liquid supply mechanism and the drive mechanism, wherein the control unit controls the drive mechanism and the cleaning liquid supply mechanism so that, during the cleaning period in which cleaning liquid is discharged from the cleaning nozzle toward the probe, the probe moves relatively upward relative to the discharge port of the cleaning nozzle, thereby cleaning the outer surface of the probe with the cleaning liquid.

2. The dispensing device according to claim 1, wherein, in the relative movement, when the cleaning liquid discharged from the cleaning nozzle is in contact with the probe, the probe or the discharge port of the cleaning nozzle moves at a first velocity, and after the cleaning liquid is no longer in contact with the probe, the probe or the discharge port of the cleaning nozzle moves to a predetermined position at a second velocity faster than the first velocity.

3. The dispensing device according to claim 2, wherein, before the start of the washing period, the probe or the discharge port of the washing nozzle is moved at a speed faster than the first speed such that the probe descends relative to the discharge port of the washing nozzle from a position where the tip of the probe is above the water flow of the washing solution discharged from the washing nozzle to a position where it is below the water flow.

4. The dispensing apparatus according to any one of claims 1 to 3, wherein the cleaning period is started when the probe and the cleaning nozzle are stationary before the start of the relative movement.

5. The dispensing device according to any one of claims 1 to 3, wherein at the start of the washing period, the tip of the probe is below the water flow of the washing solution discharged from the washing nozzle.

6. The dispensing device according to any one of claims 1 to 3, wherein the device sequentially aspirates multiple types of liquids from the tip of the probe and does not discharge until all of the multiple types of liquids have been aspirated, and after aspirating one of the multiple types of liquids and before aspirating the next type, the device provides the cleaning period to clean the outer surface of the probe.

7. The dispensing device according to claim 6, wherein air is drawn from the tip of the probe before and after the washing period, after aspirating one of the plurality of liquids and before aspirating the next liquid.

8. The dispensing device according to any one of claims 1 to 3, wherein the horizontal length of the discharge port of the cleaning nozzle is longer than the horizontal length of the region of the probe that comes into contact with the cleaning liquid discharged from the cleaning nozzle.

9. The dispensing device according to any one of claims 1 to 3, wherein the probe has a tip attached to its tip, holds the liquid aspirated from the tip within the tip until it is discharged, and cleans the outer surface of the tip during the cleaning period.

10. The dispensing device according to any one of claims 1 to 3, further comprising means for supplying a cleaning solution into the probe via the flow path, wherein the liquid delivery mechanism cleans the inner wall of the probe by discharging the cleaning solution supplied into the probe from its tip.

11. The dispensing device according to claim 10, wherein, during the relative movement, when the cleaning liquid discharged from the cleaning nozzle is in contact with the probe, the probe or the discharge port of the cleaning nozzle moves at a first velocity, and after the cleaning liquid is no longer in contact with the probe, the probe or the discharge port of the cleaning nozzle moves at a second velocity faster than the first velocity, and after cleaning the inner wall of the probe, the probe is raised at a velocity faster than the second velocity.

12. An automated analyzer comprising a dispensing device according to any one of claims 1 to 3.

13. A method for cleaning the outer surface of a probe in a dispensing apparatus, comprising: a probe for dispensing liquid; a liquid delivery mechanism for drawing in and discharging fluid from the tip of the probe; a flow path connecting the probe and the liquid delivery mechanism; a cleaning nozzle with its discharge port facing laterally; a cleaning liquid supply mechanism for discharging cleaning liquid from the discharge port of the cleaning nozzle; and a drive mechanism for moving at least one of the probe and the discharge port of the cleaning nozzle up and down, wherein the cleaning method controls the probe to move relatively upward relative to the discharge port of the cleaning nozzle during the cleaning period in which cleaning liquid is discharged from the cleaning nozzle toward the probe.

14. The cleaning method according to claim 13, wherein, during the relative movement, when the cleaning liquid discharged from the cleaning nozzle is in contact with the probe, the probe or the discharge port of the cleaning nozzle is moved at a first speed, and after the cleaning liquid is no longer in contact with the probe, the probe or the discharge port of the cleaning nozzle is moved to a predetermined position at a second speed faster than the first speed.

15. The cleaning method according to claim 14, wherein, before the start of the cleaning period, the probe or the discharge port of the cleaning nozzle is moved at a speed faster than the first speed such that the probe descends relative to the discharge port of the cleaning nozzle from a position where the tip of the probe is above the water flow of cleaning liquid discharged from the cleaning nozzle to a position below the water flow.

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