Specimen analysis device and nozzle cleaning method

Abstract

In the present invention, a branch pipe is provided in a cleaning tank. The inside of the branch pipe serves as a flow path for injecting a nozzle cleaning liquid into the cleaning tank. In an advanced cleaning mode, a first nozzle cleaning process and a second nozzle cleaning process are sequentially performed. In the first nozzle cleaning process, a BF cleaning nozzle is cleaned using the nozzle cleaning liquid. In the second nozzle cleaning process, the BF cleaning nozzle is cleaned using a BF cleaning liquid. The nozzle cleaning liquid is an alkaline cleaning liquid. The BF cleaning liquid is a neutral cleaning liquid.

Description

Sample analyzer and nozzle cleaning method

[0001] The present invention relates to a sample analyzer and a nozzle cleaning method, and in particular to a technique for cleaning a BF cleaning nozzle.

[0002] A sample analyzer is a device that analyzes samples such as blood and urine collected from a subject. An immunoassay device is a well-known example of a sample analyzer. An immunoassay device measures a target substance in a sample by utilizing an immune reaction (antigen-antibody reaction). In an immunoassay device, washing for BF separation is performed after the immune reaction (although the term "B / F separation" is also accepted, the term "BF separation" is used in this application). Hereinafter, washing for BF separation will be referred to as "BF washing."

[0003] More specifically, BF separation is a process for separating substances bound to a solid phase (bound) from substances not bound to the solid phase (free) after an immune reaction. Generally, magnetic particles are used as the solid phase. An antibody (or antigen) is immobilized on the surface of each magnetic particle, and the antigen (or antibody) in the sample binds to the antibody (or antigen). This forms an immune complex. During BF washing, the magnetic particles (i.e., immune complexes) are captured in a reaction vessel by magnetic force. A BF washing solution is then injected into the reaction vessel, and the BF washing solution is then aspirated from the reaction vessel, thereby removing unreacted substances from the reaction vessel. In other words, only the unreacted substances are washed away.

[0004] In an immunoassay device, BF cleaning is performed using a BF cleaning facility equipped with a BF cleaning nozzle. A typical BF cleaning nozzle is a composite nozzle consisting of an integrated discharge nozzle and suction nozzle. The BF cleaning facility has a cleaning tank for cleaning the BF cleaning nozzle after use.

[0005] After use, the BF cleaning nozzle itself is cleaned using a cleaning tank. In this case, the BF cleaning nozzle is generally cleaned using a BF cleaning solution. Specifically, with the BF cleaning nozzle inserted into the cleaning tank, the BF cleaning solution is injected into the cleaning tank through a discharge nozzle of the BF cleaning nozzle. The BF cleaning solution in the cleaning tank is then sucked out by a suction nozzle of the BF cleaning nozzle. The discharge and suction of the BF cleaning solution are repeated as necessary. The BF cleaning solution is generally a neutral cleaning solution containing a buffer and a surfactant.

[0006] Patent Document 1 describes an analytical device having a detergent reservoir. When cleaning the dispensing nozzle, the dispensing nozzle is inserted into the detergent reservoir. A supply port is formed inside the detergent reservoir for supplying detergent for nozzle cleaning. The detergent reservoir also has a supply port formed inside the detergent reservoir for supplying a cleaning liquid for tank cleaning.

[0007] Patent Document 2 describes a nozzle cleaning unit for cleaning a dispensing nozzle. The nozzle cleaning unit has a cleaning tank. With the dispensing nozzle inserted in the cleaning tank, a cleaning liquid is sprayed onto the cleaning nozzle.

[0008] Patent Documents 1 and 2 do not describe a BF cleaning nozzle. In particular, these patent documents do not describe the combined use of a nozzle cleaning liquid and a BF cleaning liquid.

[0009] International Publication No. 2014 / 175018 Japanese Patent Application Laid-Open No. 2011-78881

[0010] If the BF cleaning nozzle is not cleaned properly, i.e., if previous reaction solutions (especially the previous specimen) continue to adhere to the surface of the BF cleaning nozzle, the previous reaction solution will be mixed into the subsequent reaction solution as a contaminant during the next BF cleaning. This phenomenon is called carryover. For highly accurate or sensitive measurements, it is necessary to minimize cross-contamination between containers (or reaction solutions) via the BF cleaning nozzle. To achieve this, it is necessary to improve the cleanliness of the BF cleaning nozzle itself. This is particularly important when the concentration of reagents or specimens in the reaction solution is high, or when special reagents that are not suitable for cleaning with BF cleaning solution are used.

[0011] An object of the present invention is to provide a sample analyzer that can improve the cleanliness of a BF cleaning nozzle, or to provide a nozzle cleaning method that can improve the cleanliness of a BF cleaning nozzle.

[0012] The sample analyzer of the present invention is characterized by including a BF cleaning nozzle having an ejection nozzle that ejects BF cleaning liquid into a reaction vessel during BF cleaning and an aspirating nozzle that aspirates liquid from the reaction vessel during the BF cleaning; a cleaning tank into which the BF cleaning nozzle is inserted when cleaning the BF cleaning nozzle; an injection mechanism that injects a nozzle cleaning liquid different from the BF cleaning liquid into the cleaning tank; and a control unit that controls the operation of the BF cleaning nozzle and the operation of the injection mechanism, and that controls a first nozzle wash that cleans the BF cleaning nozzle with the nozzle cleaning liquid and a second nozzle wash that cleans the BF cleaning nozzle with the BF cleaning liquid when cleaning the BF cleaning nozzle using the cleaning tank.

[0013] A cleaning method according to the present invention is a nozzle cleaning method for cleaning a BF cleaning nozzle. The BF cleaning nozzle includes a discharge nozzle that discharges a BF cleaning solution into a reaction vessel during BF cleaning, and a suction nozzle that sucks liquid from the reaction vessel during the BF cleaning. The nozzle cleaning method according to the present invention is characterized by including a first cleaning step in which a portion of the BF cleaning nozzle inserted into a cleaning tank is cleaned with a nozzle cleaning solution different from the BF cleaning solution, and a second cleaning step in which the portion inserted into the cleaning tank is cleaned with the BF cleaning solution.

[0014] According to the present invention, it is possible to provide a sample analyzer that can improve the cleanliness of a BF cleaning nozzle, or a nozzle cleaning method that can improve the cleanliness of a BF cleaning nozzle.

[0015] FIG. 1 is a diagram showing an example of the configuration of a sample analyzer according to an embodiment; FIG. 2 is a diagram showing alternate implementation of BF cleaning and nozzle cleaning; FIG. 3 is a diagram showing a BF cleaning facility according to an embodiment; FIG. 4 is a diagram showing the relationship between a first central axis and a second central axis; FIG. 5 is a diagram showing the horizontal offset of the second central axis; FIG. 6 is a diagram showing a first example of a nozzle cleaning operation; FIG. 7 is a diagram showing a second example of a nozzle cleaning operation; FIG. 8 is a flowchart showing an operation example of the BF cleaning facility; FIG. 9 is a diagram showing a first modified example of a cleaning tank; FIG. 10 is a diagram showing a second modified example of a cleaning tank; FIG. 11 is a diagram showing a third modified example of a cleaning tank; FIG. 12 is a diagram showing BF cleaning in a sample analyzer according to a cartridge system;

[0016] Hereinafter, an embodiment will be described with reference to the drawings.

[0017] (1) Overview of the embodiment The sample analyzer according to the embodiment includes a BF washing nozzle, a washing tank, an injection mechanism, and a controller. The BF washing nozzle includes a discharge nozzle that discharges BF washing solution into a reaction vessel during BF washing, and a suction nozzle that aspirates liquid from the reaction vessel during BF washing. The BF washing nozzle is inserted into the washing tank when washing the BF washing nozzle. The injection mechanism injects a nozzle washing solution different from the BF washing solution into the washing tank. The controller controls the operation of the BF washing nozzle and the operation of the injection mechanism. When washing the BF washing nozzle using the washing tank, the controller controls a first nozzle wash that washes the BF washing nozzle with nozzle washing solution, and a second nozzle wash that washes the BF washing nozzle with BF washing solution.

[0018] According to the above configuration, the first nozzle cleaning and the second nozzle cleaning are applied to the BF cleaning nozzle, which improves the cleanliness of the BF cleaning nozzle compared to when only the second nozzle cleaning is applied, thereby reducing cross-contamination that occurs via the BF cleaning nozzle.

[0019] In an embodiment, the BF cleaning nozzle is a composite nozzle consisting of an integrated discharge nozzle and suction nozzle. The discharge nozzle is provided at a height that prevents contamination. Therefore, the portion of the BF cleaning nozzle to be cleaned is a part of the suction nozzle, specifically, the portion that includes the area that comes into contact with the reaction solution. Multiple types of nozzle cleaning liquids may be used stepwise or simultaneously. Multiple nozzle cleaning liquids with different concentrations may be selectively used.

[0020] In this embodiment, in the first nozzle cleaning, the nozzle cleaning liquid is injected into the cleaning tank by the injection mechanism, and then the nozzle cleaning liquid in the cleaning tank is sucked by the suction nozzle. In the second nozzle cleaning, the BF cleaning liquid is ejected from the ejection nozzle into the cleaning tank, and then the BF cleaning liquid in the cleaning tank is sucked by the suction nozzle.

[0021] The above configuration eliminates the need for dedicated equipment for draining the liquid from the cleaning tank. Furthermore, because an injection mechanism is provided separate from the BF cleaning nozzle, the timing, amount, and speed of injection of the nozzle cleaning liquid can be freely determined. The suction of the nozzle cleaning liquid and the BF cleaning liquid by the suction nozzle also improves the cleanliness of the inside of the suction nozzle and the inside of the piping connected to the suction nozzle.

[0022] In this embodiment, the second nozzle cleaning is performed after the first nozzle cleaning. This configuration makes it possible to use a nozzle cleaning liquid that exerts a strong cleaning effect, assuming that the BF cleaning liquid is used as a rinse liquid.

[0023] In this embodiment, at the start of first nozzle cleaning, nozzle cleaning liquid is injected into the cleaning tank to form a reservoir of nozzle cleaning liquid, and then the BF cleaning nozzle is inserted into the cleaning tank (static cleaning method). Alternatively, at the start of first nozzle cleaning, nozzle cleaning liquid is injected into the cleaning tank during or after the BF cleaning nozzle is inserted into the cleaning tank (dynamic cleaning method). The static cleaning method makes it easier to increase the time the part to be cleaned is in contact with the nozzle cleaning liquid. In the dynamic cleaning method, cleaning liquid is directly poured or sprayed onto the BF cleaning nozzle during nozzle cleaning.

[0024] In one embodiment, the injection mechanism includes a flow path with an opening facing the interior space of the cleaning tank for injecting the cleaning liquid into the interior space of the cleaning tank. This configuration allows the nozzle cleaning liquid to be reliably and easily injected into the interior space of the cleaning tank. It also makes it easy to spray the cleaning liquid directly toward the highly contaminated area (usually the lower end) of the part to be cleaned.

[0025] In one embodiment, the cleaning tank has a first central axis that is a vertical axis. The flow path has a second central axis that is an inclined axis. The second central axis extends diagonally downward from the opening. The nozzle cleaning liquid is injected from the opening along the second central axis. This configuration can promote the generation of upstream / downstream or turbulent flow within the cleaning tank.

[0026] In the embodiment, the second central axis passes through a position horizontally shifted from the first central axis. This configuration facilitates rotational movement of the nozzle cleaning liquid in the cleaning tank. If the nozzle cleaning liquid is caused to move up and down or rotate in the cleaning tank while the BF cleaning nozzle is inserted in the cleaning tank, the cleanliness of the BF cleaning nozzle can be further improved.

[0027] In the embodiment, the internal space of the cleaning tank has a truncated cone shape that widens upward. This configuration increases the volume of the cleaning tank while reducing the amount of liquid remaining on the bottom surface of the cleaning tank after the nozzle cleaning liquid is sucked by the suction nozzle.

[0028] In a nozzle cleaning method according to an embodiment, the BF cleaning nozzle includes a discharge nozzle that discharges a BF cleaning solution into a reaction vessel during BF cleaning, and a suction nozzle that sucks the liquid from the reaction vessel during BF cleaning. The nozzle cleaning method according to an embodiment includes a first cleaning step and a second cleaning step. In the first cleaning step, a portion of the BF cleaning nozzle inserted into a cleaning tank is cleaned with a nozzle cleaning solution different from the BF cleaning solution. In the second cleaning step, a portion of the BF cleaning nozzle inserted into the cleaning tank is cleaned with the BF cleaning solution. According to this method, the combination of the first and second cleaning steps can improve the cleanliness of the BF cleaning nozzle.

[0029] The nozzle cleaning method according to the embodiment includes a selection step. In the selection step, either a first cleaning mode or a second cleaning mode is selected based on reference information including sample analysis items. When the first cleaning mode is selected, the second cleaning step is performed after the first cleaning step. When the second cleaning mode is selected, the second cleaning step is performed without performing the first cleaning step.

[0030] For example, the first cleaning mode is selected when the BF cleaning nozzle is highly contaminated, when a specific reagent that is difficult to clean is used, when a highly concentrated sample such as whole blood is used, or when high-precision measurement is required. The first cleaning mode increases the cleanliness of the BF cleaning nozzle compared to the second cleaning mode. On the other hand, the second cleaning mode is selected when the BF cleaning nozzle is less contaminated, when a general reagent is used, or when normal precision measurement is required. The second cleaning mode is economical because it reduces the consumption of nozzle cleaning liquid.

[0031] In an embodiment, the BF cleaning liquid is a neutral cleaning liquid. The nozzle cleaning liquid is an alkaline or acidic cleaning liquid. When the second cleaning process is performed after the first cleaning process, the BF cleaning liquid functions as a rinse liquid. The nozzle cleaning liquid used for nozzle cleaning may be switched depending on the reagent used in the sample analysis. The concentration of the nozzle cleaning liquid may be adjusted by the BF cleaning liquid. In this case, the nozzle cleaning liquid is injected and the BF cleaning liquid is discharged simultaneously or in stages, and then the cleaning liquid in the cleaning tank is aspirated by the suction nozzle.

[0032] (2) Details of the embodiment Figure 1 shows a sample analyzer 10 according to an embodiment. Figure 1 is a schematic diagram of the top surface of the sample analyzer 10. This sample analyzer 10 is an immunoassay device that analyzes samples using an immune reaction, that is, an antigen-antibody reaction, and more specifically, is an immunoassay device that performs a chemiluminescent enzyme immunoassay (CLEIA).

[0033] In Figure 1, the sample analyzer 10 has a sample supply unit 12, a reaction unit 14, a reagent supply unit 16, a light detection unit 18, a cuvette supply unit 20, a substrate refrigerator 22, cuvette transfer mechanisms 24, 26, a sample dispensing mechanism 28, and reagent dispensing mechanisms 30, 32, and further has multiple BF cleaning equipment 100.

[0034] The specimen supply unit 12 has a turntable 33 as a rotating table. A holding hole group 34 is formed on the turntable 33, and the holding hole group 34 is composed of a plurality of holding holes 34a. In the illustrated example, the holding hole group 34 is composed of an outer holding hole row consisting of a plurality of holding holes 34a arranged in a ring, and an inner holding hole row consisting of a plurality of holding holes 34a arranged in a ring. Each holding hole 34a is a portion that accommodates a specimen container as an original container. The specimen container contains a specimen.

[0035] In the embodiment, the specimen is blood, such as serum, plasma, or whole blood. Other liquids, such as saliva or urine collected from a living body, may also be used as specimens. For example, the specimen containers are blood collection tubes or other containers containing blood. Each specimen container is manually placed in each holding hole 34a by an examiner. Alternatively, each specimen container may be automatically placed by a specimen container rack or a mechanism for transporting specimen containers.

[0036] The sample supply unit 12 is provided with a barcode reader (BCR) (not shown). The BCR reads the contents of the barcode label affixed to each sample container held by the holding hole group 34. This reads sample information such as the sample ID for each sample. Based on the sample ID, subject information, analysis items, sample container type, etc. are identified. Analysis items are information that identifies the substance to be measured and the measurement method, and are also called test items. One or more reagents to be used are selected based on the analysis items.

[0037] The sample dispensing mechanism 28 includes a rail mechanism 46, a slide base 48, an arm 50, a nozzle 52, etc. The rail mechanism 46 has rails that extend in a direction inclined relative to the left-right direction and the depth direction of the device. The slide base 48 slides along the rails (see reference numeral 53). The base end of the arm 50 is rotatably held by the slide base 48, and the nozzle 52 is disposed at the tip of the arm 50.

[0038] The nozzle 52 is composed of a nozzle body and a nozzle tip. The nozzle tip is detachably attached to the nozzle body. The nozzle body is made of metal, and the nozzle tip is made of a transparent, semi-transparent, or opaque resin. The nozzle tip is replaced after dispensing the sample.

[0039] The movement area of ​​the nozzle 52 is expanded by a combination of the sliding movement of the slide base 48 and the pivoting movement of the arm 50. Under the control of a control unit (not shown in FIG. 1 ), during sample dispensing, the sample in a sample container (source container) at the aspiration position is aspirated by the nozzle 52, and the aspirated sample is discharged from the nozzle 52 into a specific cuvette on the reaction unit 14. The discharge destination position may be fixedly determined, or may be dynamically changed. The cuvette corresponds to the sample container and the reaction vessel.

[0040] The tip rack 54 is a member that holds a plurality of nozzle tips. When replacing a nozzle tip, the used nozzle tip is removed from the nozzle body and discarded. The tip of the nozzle body is then inserted into the upper opening of a nozzle tip selected from the tip rack 54. This attaches a new nozzle tip to the nozzle body. The tip rack is replaced by a tip rack replacement mechanism (not shown).

[0041] The reaction unit 14 has a turntable 39 serving as a rotating platform or movable table. A group of holding holes 40 is formed in the turntable 39, and the group of holding holes 40 is composed of a plurality of holding holes 40a. The group of holding holes 40 may be composed of an outer row of holding holes composed of a plurality of holding holes arranged in a ring, and an inner row of holding holes composed of a plurality of holding holes arranged in a ring. Each holding hole 40a is a portion for accommodating a cuvette. Reagents and specimens are injected into each cuvette in stages, thereby causing an immune reaction in each cuvette. The turntable 39 may be composed of a single ring-shaped member, or may be composed of a plurality of ring-shaped members arranged concentrically.

[0042] For example, a sample is measured based on a so-called two-step method. The two-step method includes a first immune reaction step using a first reagent containing a first antibody, a second immune reaction step using a second reagent containing a second antibody, an enzyme reaction step using a substrate (substrate solution), and a light detection step. The first immune reaction step, the second immune reaction step, and the enzyme reaction step are performed in the reaction unit 14. The reaction unit 14 also performs a BF washing step, a stirring step, and the like.

[0043] In the BF cleaning process, a BF cleaning facility 100 is used. In this embodiment, two BF cleaning facilities 100 operating in parallel are provided. More BF cleaning facilities 100 may be provided, or a single BF cleaning facility 100 may be provided. The two BF cleaning facilities 100 have the same configuration. The specific configuration of the BF cleaning facility 100 will be described in detail later.

[0044] The reagent supply unit 16 has a reagent tank 41 serving as a rotating refrigerator. The reagent tank 41 contains a reagent bottle row 42 and a reagent bottle row 44. The reagent bottle row 42 and the reagent bottle row 44 are each composed of a plurality of reagent bottles. Each reagent bottle contains a reagent. Each reagent used in the first immune reaction step contains a plurality of magnetic particles. Each magnetic particle functions as a solid phase. That is, an antibody layer (or antigen layer) is provided on the surface of each magnetic particle.

[0045] Reagent dispensing mechanisms 30 and 32 are provided adjacent to the reagent supply unit 16 and the reaction unit 14. The reagent dispensing mechanism 30 has a pivoting arm 60 and a nozzle 62 provided at the tip of the arm 60. The reagent dispensing mechanism 32 has a pivoting arm 64 and a nozzle 65 provided at the tip of the arm 64. The nozzles 62 and 65 are each non-replaceable nozzles, i.e., washable nozzles. The reagent dispensing mechanisms 30 and 32 aspirate a specific reagent and dispense the aspirated reagent into a specific cuvette.

[0046] The light detection unit 18 is a unit that detects luminescence generated in the cuvette after the enzyme reaction. The concentration of the analyte and other information are calculated based on the detected value. When the cuvette is transported, cuvette transport mechanisms 24 and 26 function.

[0047] 2 shows BF cleaning and nozzle cleaning that are performed alternately, with the BF cleaning being shown schematically on the left side of the figure, and the nozzle cleaning being shown schematically on the right side of the figure.

[0048] As shown on the left side of FIG. 2 , a cuvette 74 is held by a holding hole in the turntable 39. Multiple magnetic particles 78 in the cuvette 74 are captured by a magnetic force generated by a magnet 76. The BF cleaning nozzle 80 has an ejection nozzle 82 and an suction nozzle 84 that are integrated with each other. The ejection nozzle 82 and the suction nozzle 84 are each made of a metal such as stainless steel. The ejection nozzle 82 has an ejection port 82A, and the suction nozzle 84 has an suction port 84A. The ejection port 82A is located higher than the suction port 84A. In the configuration example shown in FIG. 2 , the ejection port 82A is located higher than the top surface of the cuvette 74, and the suction port 84A is in contact with the inner bottom surface of the cuvette 74. The suction nozzle 84 has multiple grooves or notches that are connected to the suction port 84A, but these are not shown in the figure.

[0049] After the capture state of the plurality of magnetic particles 78 is formed, the BF cleaning nozzle 80 moves downward. At this time, the reaction solution in the cuvette 74 is aspirated by the suction nozzle 84. In this case, the descent speed of the BF cleaning nozzle 80 is determined to match the descent speed of the liquid surface. The downward movement of the BF cleaning nozzle 80 ends when the lower end of the suction nozzle 84 contacts the inner bottom surface of the cuvette 74. After the entire reaction solution has been aspirated, the BF cleaning solution discharged from the discharge nozzle is poured into the cuvette 74. Thereafter, the BF cleaning solution in the cuvette 74 is aspirated by the suction nozzle 84. If necessary, a combination of discharging the BF cleaning solution and aspirating the BF cleaning solution is repeatedly performed. After BF cleaning, the BF cleaning nozzle 80 moves upward. Note that the reaction solution in the cuvette 74 may be aspirated by the suction nozzle 84 after the downward movement of the BF cleaning nozzle 80 is completed.

[0050] 2, a nozzle cleaning unit 102 is used for nozzle cleaning. Reference numeral 80A denotes a BF cleaning nozzle during nozzle cleaning. As already described, BF cleaning and nozzle cleaning are performed alternately.

[0051] 3 shows a BF cleaning equipment 100 according to an embodiment. This shows the state during nozzle cleaning. The BF cleaning equipment 100 includes a BF cleaning nozzle 80, a nozzle cleaning unit 102, an injection mechanism 110, a transport mechanism 130, a BF cleaning solution tank 132, a syringe pump 134, a pump 144, and the like.

[0052] The nozzle cleaning unit 102 is made of, for example, a transparent resin, and includes a cleaning tank 104, a frame 106, and a drain (drainage pipe) 108. In this embodiment, the cleaning tank 104, frame 106, and drain 108 are integrated. However, they may be configured as separate components. The frame 106 has a box-like shape with an opening facing upward. An upper portion 104A of the cleaning tank 104 is inserted into the frame 106. The cleaning tank 104 has an opening 104B. Cleaning liquid overflowing from the cleaning tank 104 is collected by the frame 106, and the cleaning liquid is discharged through the drain 108. The inner bottom surface of the frame 106 is inclined so as to guide the cleaning liquid to the drain 108. However, this is not shown in the drawing.

[0053] The internal space 114 of the cleaning tank 104 has a truncated conical shape that widens upward. Specifically, the size of the horizontal cross section of the internal space 114 gradually increases from bottom to top. The bottom surface of the internal space 114 is circular, and the opening 104B is also circular. The cleaning tank 104 itself also has a truncated conical shape. Figure 3 shows the BF cleaning nozzle 80 at the end of its downward movement. The lower end of the suction nozzle 84 is in contact with the inner bottom surface of the cleaning tank 104. In the illustrated configuration example, the discharge outlet of the discharge nozzle 82 is located lower than the height of the upper edge of the frame 106. The height of the upper edge of the frame 106 may also be lower.

[0054] The cleaning tank 104 is provided with a branch pipe 112. The cleaning tank 104 and the branch pipe 112 are integrated. A pipe 122 is connected to the branch pipe 112. In Fig. 3, a portion 122A of the pipe 122 is represented by a dashed line, and the remaining portion is represented schematically.

[0055] The injection mechanism 110 includes a nozzle cleaning liquid tank 116, a syringe pump 118, a three-way valve 120, and a flow path 128. The flow path 128 is inside the piping 122 and the branch pipe 112. The branch pipe 112 may be considered to be part of the injection mechanism 110.

[0056] The opening 128A is an outlet of the flow path 128. The opening 128A faces the internal space 114 of the cleaning tank 104 and is connected to the inner surface of the cleaning tank 104. As will be described later, a second central axis of the flow path 128 is inclined with respect to a first central axis of the cleaning tank 104.

[0057] A pipe 126 is provided between the nozzle cleaning liquid tank 116 and the three-way valve 120, a pipe 124 is provided between the syringe pump 118 and the three-way valve 120, and a pipe 122 is provided between the branch pipe 112 and the three-way valve. When cleaning the nozzles with the nozzle cleaning liquid, the nozzle cleaning liquid in the nozzle cleaning liquid tank 116 is first taken into the syringe pump 118. Next, the nozzle cleaning liquid is sent out from the syringe pump 118 toward the flow path 128. As a result, the cleaning liquid is injected from the opening 128A into the internal space 114 of the cleaning tank 104. The injection direction is obliquely downward.

[0058] A pipe 140 is provided between the BF cleaning liquid tank 132 and the three-way valve 136, a pipe 142 is provided between the syringe pump 134 and the three-way valve 136, and a pipe 138 is provided between the discharge nozzle 82 and the three-way valve 136. When the BF cleaning liquid is discharged, the BF cleaning liquid in the BF cleaning liquid tank 132 is first taken into the syringe pump 134. Then, the BF cleaning liquid is sent out from the syringe pump 134 toward the discharge nozzle 82. This causes the BF cleaning liquid to flow out from the discharge port.

[0059] The pump 144 is a pump for draining water. A pipe 146 is provided between the pump 144 and the suction nozzle 84. The cleaning liquid sucked by the suction nozzle 84 is discharged to the outside via the pipe 146 and the pump 144.

[0060] In an embodiment, the nozzle cleaning liquid is, for example, a strongly alkaline cleaning liquid that contains a surfactant or the like. A weakly alkaline cleaning liquid, or a strongly acidic cleaning liquid or a weakly acidic cleaning liquid may be used as the nozzle cleaning liquid. The BF cleaning liquid is a neutral liquid that contains a buffer and a surfactant or the like. It may have a certain range of neutrality. Note that any nozzle cleaning liquid may be used as long as it has a stronger cleaning action than the BF cleaning liquid, and the nozzle cleaning liquid may be switched depending on the reagent, specimen, or the like.

[0061] When an alkaline or acidic cleaning solution is used, for example, proteins on the surface of the container are likely to be decomposed or peeled off. When an acidic cleaning solution is used, corrosion of metal materials occurs. When corrosion of metal materials is a concern, it is desirable to use an alkaline cleaning solution.

[0062] The transport mechanism 130 transports the BF cleaning nozzle between the BF cleaning position and the nozzle cleaning position. The transport mechanism 130 has a vertical transport mechanism and a horizontal transport mechanism. A plurality of BF cleaning nozzles may be transported by a single transport mechanism 130.

[0063] The control unit 148 controls the operation of the sample analyzer. Specifically, the control unit 148 controls the operation of the syringe pumps 118, 134, the three-way valves 120, 136, the pump 144, and the transport mechanism 130. As will be described later, the control unit 148 has the function of selecting between the advanced cleaning mode and the normal cleaning mode based on reference information including the analysis items. The control unit 148 also has the function of controlling the first nozzle cleaning and the second nozzle cleaning performed in the advanced cleaning mode, and the function of controlling the nozzle cleaning (second nozzle cleaning) performed in the normal cleaning mode. The control unit 148 is configured, for example, by a CPU that executes a program.

[0064] FIG. 4 shows a vertical cross section of the cleaning tank 104. The x direction is the first horizontal direction, and the z direction is the vertical direction. The y direction, which is perpendicular to the x and z directions, is not shown in FIG. 4. The cleaning tank 104 has a first central axis 150. The first central axis 150 is parallel to the z direction. The flow path 128 has a second central axis 152. The second central axis 152 is also the central axis of the branch pipe 112. The second central axis 152 extends obliquely downward from the opening.

[0065] In the xz plane, the second central axis 152 is inclined with respect to the first central axis 150. The inclination angle is, for example, within a range of 20 to 80 degrees, and preferably within a range of 30 to 60 degrees. In the illustrated example, the inclination angle is 45 degrees. The inclination angle (angle with respect to the z direction) of the inner surface of the cleaning tank 104 is, for example, within a range of 2 to 20 degrees.

[0066] 5 shows an x'-y cross section of the cleaning tank 104 and the branch pipe 112. The x' direction is parallel to the second central axis 152. The second central axis 152 passes through a position shifted horizontally, specifically in the y direction, from the first central axis 150. Reference numeral 154 indicates the amount of shift (offset amount).

[0067] By tilting the second central axis 152 downward and shifting the second central axis 152 from the first central axis, it is possible to promote the formation of upstream, downstream, and rotational flows in the cleaning tank 104 when the nozzle cleaning liquid is poured into the cleaning tank 104. If such flows are generated when the BF cleaning nozzle is inserted in the cleaning tank 104, the nozzle cleaning efficiency can be improved.

[0068] Next, first and second examples of the nozzle cleaning operation in the advanced cleaning mode will be described with reference to FIGS.

[0069] 6 shows a first example of the nozzle cleaning operation. The horizontal axis is the time axis. Reference numeral 164 indicates a first nozzle cleaning process, and reference numeral 166 indicates a second nozzle cleaning process. In the first nozzle cleaning process 164, a nozzle cleaning liquid is used, and in the second nozzle cleaning process 166, a BF cleaning liquid is used.

[0070] Reference numeral 156 indicates the movement of the BF wash nozzle, reference numeral 158 indicates the operation of the suction nozzle, reference numeral 160 indicates the operation of the discharge nozzle, and reference numeral 162 indicates the operation of the injection mechanism.

[0071] 6 , before the first nozzle cleaning process 164 is started, the BF cleaning nozzle moves downward (see reference numeral 168) and the BF cleaning nozzle (specifically, the suction nozzle) is inserted into the cleaning tank. The downward movement of the BF cleaning nozzle stops when the lower end of the suction nozzle hits the inner bottom surface of the cleaning tank. Note that the step in which the downward movement is performed may be considered part of the first nozzle cleaning process 164.

[0072] The first nozzle cleaning process 164 consists of m steps, from step 1 to step m, where m is an integer equal to or greater than 1. When m is equal to or greater than 2, the steps are identical to one another. That is, in the first nozzle cleaning process 164, a combination of injection 170, waiting 172, and suction 174 is repeatedly performed.

[0073] The first step 165 will be described in detail. First, the nozzle cleaning liquid is poured into the cleaning tank by the injection mechanism (see symbol 170). The nozzle cleaning liquid is poured toward the highly contaminated area (lower end) of the suction nozzle. This type of operation can be called a dynamic cleaning method. Typically, the nozzle cleaning liquid is injected so as to overflow into the cleaning tank. In this case, the area to be cleaned is the entire portion of the suction nozzle inserted into the cleaning tank. However, a relatively small amount of nozzle cleaning liquid that does not cause overflow may also be injected. The injection volume and injection speed of the nozzle cleaning liquid may be determined arbitrarily. After the injection of the nozzle cleaning liquid, a standby state is entered (see symbol 172). The duration of the standby state may be set arbitrarily, or may be set to zero. After the standby state, the nozzle cleaning liquid in the cleaning tank is sucked by the suction nozzle (see symbol 174). Alternatively, to focus on cleaning the piping connected to the suction nozzle, the standby time may be set to zero and the suction nozzle may suck while the nozzle cleaning liquid is being injected.

[0074] After the first nozzle cleaning process 164 is performed, a second nozzle cleaning process 166 is performed. The second nozzle cleaning process 166 consists of n steps, from step 1 to step n, where n is an integer equal to or greater than 1. When n is equal to or greater than 2, the content of the multiple steps is the same. That is, the combination of the second nozzle cleaning process 166, discharge 176, and suction 178 is repeatedly performed.

[0075] To explain the details of the first step 167 in more detail, first, the BF cleaning liquid is poured into the cleaning tank from the discharge nozzle (see reference numeral 176). At this time, the BF cleaning liquid usually flows down into the cleaning tank along the outer surface of the suction nozzle. Usually, the BF cleaning liquid is poured so as to cause overflow in the cleaning tank. Exceptionally, a relatively small amount of BF cleaning liquid that does not cause overflow may be poured. The amount and speed of the BF cleaning liquid poured can be determined arbitrarily. A standby state may be established after the BF cleaning liquid is poured. In this case, the duration of the standby state can be set arbitrarily. After the BF cleaning liquid has been poured, the BF cleaning liquid in the cleaning tank is sucked up by the suction nozzle (see reference numeral 178).

[0076] After the second nozzle cleaning process 166 is completed, the BF cleaning nozzle moves upward (see reference numeral 180). In the second nozzle cleaning process 166, the BF cleaning liquid functions as a rinse liquid for washing away the nozzle cleaning liquid.

[0077] According to the first example, the cleanliness of the BF cleaning nozzle can be improved compared to when the BF cleaning nozzle is cleaned using only the BF cleaning solution. Therefore, cross-contamination between cuvettes, i.e., between reaction solutions, can be significantly reduced. Since the nozzle cleaning solution and the BF cleaning solution are both aspirated by the suction nozzle, the cleanliness of the inner surface of the suction nozzle as well as the outer surface is improved.

[0078] A second example of the nozzle cleaning operation is shown in Fig. 7. In Fig. 7, elements that are the same as those shown in Fig. 6 are given the same reference numerals, and their description will be omitted.

[0079] The first nozzle cleaning process 164 consists of m steps, from step 1 to step m, where m is an integer equal to or greater than 1. The content of the first step 165A is partially different from the content of each step from step 265B onwards. The content of each step from step 165B onwards is the same. The first step 165A consists of a combination of injection 230, lowering 232, waiting 234, and suction 236. Each step from step 165B onwards consists of a combination of injection 238, waiting 240, and suction 242.

[0080] To explain the first step 165A in more detail, first, the nozzle cleaning liquid is poured into the cleaning tank by the injection mechanism (see reference numeral 230). The nozzle cleaning liquid may be poured so as to cause overflow in the cleaning tank, or a quantity of nozzle cleaning liquid sufficient to prevent overflow may be poured into the cleaning tank. The injection amount and injection speed of the nozzle cleaning liquid may be determined arbitrarily. Next, the BF cleaning nozzle (specifically, the suction nozzle) is inserted into the cleaning tank by the downward movement of the BF cleaning nozzle (see reference numeral 232). The downward movement of the BF cleaning nozzle stops when the lower end of the suction nozzle hits the inner bottom surface of the cleaning tank. The BF cleaning nozzle is then placed in a standby state (see reference numeral 234). The standby state time may be set arbitrarily, or may even be set to zero. The above-described immersion method can be called a static cleaning method.

[0081] After the standby state, the nozzle cleaning liquid in the cleaning tank is sucked by the suction nozzle (see reference numeral 236). In the second step 165B, injection 238, standby 240, and suction 242 are performed in the same manner as in the first step 165A, except for the lowering 232. After the second nozzle cleaning process 166 is completed, the BF cleaning nozzle performs an upward movement (see reference numeral 180).

[0082] According to the second example, the cleanliness of the BF cleaning nozzle can be improved, as in the first example. Therefore, cross-contamination between cuvettes, i.e., between reaction solutions, can be significantly reduced. In addition to the outer surface of the aspiration nozzle, the cleanliness of its inner surface can also be improved. Either the first or second example may be selected depending on the type of sample, the reagent used, etc.

[0083] Figure 8 shows the operation of the BF cleaning equipment. The contents shown in Figure 8 also show the control of the control unit. In the example shown, in the initial state, the BF cleaning nozzle after cleaning is inserted into the cleaning tank. S10 to S14 correspond to the process of transporting the BF cleaning nozzle from the nozzle cleaning position to the BF cleaning position. Specifically, in S10, the BF cleaning nozzle moves upward, in S12, the BF cleaning nozzle moves horizontally, and in S14, the BF cleaning nozzle moves downward. This inserts the BF cleaning nozzle into the cuvette.

[0084] In S16, BF cleaning is performed. Steps S18 to S22 correspond to the process of transporting the BF cleaning nozzle from the BF cleaning position to the nozzle cleaning position. Specifically, in S18, the BF cleaning nozzle moves upward, in S20, the BF cleaning nozzle moves horizontally, and in S22, the BF cleaning nozzle moves downward. This inserts the BF cleaning nozzle into the cleaning tank.

[0085] In S24, either the advanced cleaning mode (first cleaning mode) or the normal cleaning mode (second cleaning mode) is selected based on the reference information. The reference information includes analysis items. The analysis items can also be said to be information that specifies the substance to be measured and the reagent set to be used. In S24, the advanced cleaning mode or the normal cleaning mode is selected depending on the reagent set to be used. S24 may also be executed earlier.

[0086] In S26, the advanced cleaning mode is performed. Specifically, as shown in Figures 6 and 7, a first nozzle cleaning process using the nozzle cleaning liquid and a second nozzle cleaning process using the BF cleaning liquid are performed. On the other hand, in S28, the normal cleaning mode is performed. Specifically, only the second nozzle cleaning process using the BF cleaning liquid is performed. If it is determined in S30 that the operation should be continued, the steps from S10 onwards are performed again.

[0087] In the above operational example, the advanced cleaning mode is selected, for example, when the BF cleaning nozzle is highly contaminated, when a specific reagent that is difficult to clean is used, or when high-precision measurement is required. The advanced cleaning mode increases the cleanliness of the BF cleaning nozzle compared to the normal cleaning mode. On the other hand, the normal cleaning mode is selected, for example, when the BF cleaning nozzle is only lightly contaminated, when a general reagent is used, or when measurement with normal precision is required. The normal cleaning mode is economical because it reduces the amount of nozzle cleaning liquid consumed.

[0088] Next, several modified examples of the cleaning tank will be described using Figures 9 to 11. Figure 9 shows a first modified example of the cleaning tank. A drain 186 is connected to the bottom of the cleaning tank 182, and a solenoid valve 188 is provided above the drain 186. The cleaning tank 182 is provided with a branch pipe 184 for injecting nozzle cleaning liquid. When discharging the cleaning liquid from the cleaning tank 182, the time required to discharge the cleaning liquid can be shortened by using the suction nozzle and drain 186 together. When collecting cleaning liquid in the cleaning tank 182, the solenoid valve 188 closes.

[0089] 10 shows a second modification of the cleaning tank. A branch pipe 192 is provided in the cleaning tank 190. The branch pipe 192 is horizontally oriented. That is, a second central axis 196 of the branch pipe 192 is perpendicular to a first central axis 194 of the cleaning tank 190. The branch pipe 192 may be provided in the cleaning tank 190 so that the second central axis 196 passes through a position horizontally offset from the first central axis 194. The branch pipe 192 may be provided at the top or bottom of the cleaning tank 190, rather than at the middle of the cleaning tank 190.

[0090] 11 shows a third modification of the cleaning tank. Three branch pipes 200, 202, and 204 are connected to the cleaning tank 198 at three vertical heights H1, H2, and H3. The central axes of the branch pipes 200, 202, and 204 are inclined. The angle of inclination with respect to the z-axis is, for example, 45 degrees.

[0091] 12 shows BF cleaning performed in a cartridge-based sample analyzer. Cartridge 208 has first tank 210, second tank 212, and third tank 214. For example, first tank 210 is previously filled with a first reagent. A sample is then injected into first tank 210, causing an immune reaction to occur in first tank 210. Second tank 212 and third tank 214 are previously filled with a second reagent, diluent, etc., as needed.

[0092] After the immune reaction, the reaction solution 216 in the first tank 210 is aspirated by the suction nozzle 84 of the BF cleaning nozzle 80, with the multiple magnetic particles 218 in the first reagent being captured by the magnetic force of the magnet 220. In this case, the descending speed of the BF cleaning nozzle 80 is determined according to the descending speed of the liquid surface 216A. The descending movement and suction operation of the BF cleaning nozzle 80 are controlled so that the insertion amount of the suction nozzle 84 into the reaction solution 216 is constant. After the reaction solution is aspirated, the BF cleaning solution discharged from the discharge nozzle 82 flows into the first tank 210. The discharge and suction of the BF cleaning solution are repeated.

[0093] After the BF cleaning, the BF cleaning nozzle 80 is transferred from the BF cleaning position to the nozzle cleaning position. Thereafter, the BF cleaning nozzle 80 is cleaned using the configuration shown in Fig. 3. At this time, the advanced nozzle cleaning mode or the normal nozzle cleaning mode is selected.

[0094] As described above, the BF cleaning equipment according to this embodiment can also be applied to a sample analyzer that uses a cartridge system.

[0095] 80 BF cleaning nozzle, 82 Discharge nozzle, 84 Suction nozzle, 100 BF cleaning equipment, 102 Nozzle cleaning unit, 104 Cleaning tank, 110 Injection mechanism, 112 Branch pipe, 128 Flow path, 128A Opening, 148 Control unit.

Claims

1. A BF cleaning nozzle including a discharge nozzle that discharges a BF cleaning liquid into a reaction vessel during BF cleaning, and a suction nozzle that sucks the liquid in the reaction vessel during the BF cleaning; a cleaning tank into which the BF cleaning nozzle is inserted during cleaning of the BF cleaning nozzle; an injection mechanism that injects a nozzle cleaning liquid different from the BF cleaning liquid into the cleaning tank; and a control unit that controls the operation of the BF cleaning nozzle and the operation of the injection mechanism, the control unit controlling a first nozzle cleaning for cleaning the BF cleaning nozzle with the nozzle cleaning liquid and a second nozzle cleaning for cleaning the BF cleaning nozzle with the BF cleaning liquid when cleaning the BF cleaning nozzle using the cleaning tank. A specimen analyzer characterized by including the above components.

2. In the specimen analyzer according to claim 1, in the first nozzle cleaning, the nozzle cleaning liquid is injected into the cleaning tank by the injection mechanism, and then the nozzle cleaning liquid in the cleaning tank is sucked by the suction nozzle; in the second nozzle cleaning, the BF cleaning liquid is discharged from the discharge nozzle into the cleaning tank, and then the BF cleaning liquid in the cleaning tank is sucked by the suction nozzle. A specimen analyzer characterized by the above.

3. In the specimen analyzer according to claim 1 or claim 2, the second nozzle cleaning is performed after the first nozzle cleaning. A specimen analyzer characterized by the above.

4. In the specimen analyzer according to any one of claims 1 to 3, at the start of the first nozzle cleaning, after the nozzle cleaning liquid is injected into the cleaning tank to form a storage state of the nozzle cleaning liquid, the BF cleaning nozzle is inserted into the cleaning tank. A specimen analyzer characterized by the above.

5. In the specimen analyzer according to any one of claims 1 to 3, at the start of the first nozzle cleaning, the nozzle cleaning liquid is injected into the cleaning tank during or after the insertion of the BF cleaning nozzle into the cleaning tank. A specimen analyzer characterized by the above.

6. In the specimen analyzer according to any one of claims 1 to 5, the injection mechanism is a flow path having an opening facing the internal space of the cleaning tank, and the flow path is for injecting the nozzle cleaning liquid into the internal space of the cleaning tank. A specimen analyzer characterized by the above.

7. In the specimen analysis apparatus according to claim 6, the cleaning tank has a first central axis which is a vertical axis, the flow path has a second central axis which is an inclined axis, the second central axis extends obliquely downward from the opening, and the nozzle cleaning liquid is injected from the opening along the second central axis. A specimen analysis apparatus characterized by this.

8. In the specimen analysis apparatus according to claim 7, the second central axis passes through a position horizontally displaced from the first central axis. A specimen analysis apparatus characterized by this.

9. In the specimen analysis apparatus according to claim 6, the internal space of the cleaning tank has a frustum of a cone shape that expands upward. A specimen analysis apparatus characterized by this.

10. In a nozzle cleaning method for cleaning a BF cleaning nozzle, the BF cleaning nozzle includes a discharge nozzle that discharges a BF cleaning liquid into a reaction vessel during BF cleaning and a suction nozzle that sucks the liquid in the reaction vessel during BF cleaning. The nozzle cleaning method includes a first cleaning step of cleaning a portion to be cleaned inserted into the cleaning tank in the BF cleaning nozzle with a nozzle cleaning liquid different from the BF cleaning liquid, and a second cleaning step of cleaning the portion to be cleaned inserted into the cleaning tank with the BF cleaning liquid. A nozzle cleaning method characterized by including this.

11. In the nozzle cleaning method according to claim 10, it includes a selection step of selecting either a first cleaning mode or a second cleaning mode based on reference information including specimen analysis items. When the first cleaning mode is selected, the second cleaning step is performed after the first cleaning step. When the second cleaning mode is selected, the second cleaning step is performed without performing the first cleaning step. A nozzle cleaning method characterized by this.

12. In the nozzle cleaning method according to claim 10, the BF cleaning liquid is a neutral cleaning liquid, and the nozzle cleaning liquid is an alkaline or acidic cleaning liquid. A nozzle cleaning method characterized by this.

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