WO2023204224A1

WO2023204224A1 - Cleaning device and nozzle cleaning method

Info

Publication number: WO2023204224A1
Application number: PCT/JP2023/015534
Authority: WO
Inventors: 恭央川上; 信太郎吉武; 武村中
Original assignee: 富士レビオ株式会社; 日本電子株式会社
Priority date: 2022-04-20
Filing date: 2023-04-19
Publication date: 2023-10-26

Abstract

A cleaning liquid (112-0) is stored in a cleaning tank (75) before cleaning of a cuvette (92). The cleaning liquid (112-0) in the cleaning tank (75) is retained while the cuvette (92) is being cleaned by a cleaning nozzle (72). At the start of nozzle cleaning after the cleaning of the cuvette (92), a suction nozzle (80) in the cleaning nozzle (72) is inserted into the cleaning liquid (112-0) in the cleaning tank (75). Then, the suction nozzle (80) is further cleaned through discharging and suctioning the cleaning liquid.

Description

Cleaning equipment and nozzle cleaning method

The present invention relates to a cleaning device and a nozzle cleaning method, and particularly to a technique for cleaning a cleaning nozzle for B/F separation.

A sample analyzer is a device that analyzes blood, urine, etc. collected from a subject. An immunoassay device is known as a sample analyzer. An immunoassay device is a device that measures a target substance in a specimen using an immune reaction (antigen-antibody reaction). In the immunoassay device, B/F separation (Bound/Free Separation) is applied to the solution after the immune reaction.

B/F separation is a process that separates a substance bound to a solid phase (Bound) and a substance not bound to a solid phase (Free) after an immune reaction. Specifically, when magnetic particles are used as a solid phase, antibodies (or antigens) are immobilized on the surface of the magnetic particles, and the antigens (or antibodies) in the sample are Join. This constitutes an immune complex. In that case, B/F separation leaves the immune complex in the reaction vessel and removes unreacted substances from the reaction vessel.

During B/F separation, the inside of the reaction container is cleaned while the magnetic particles inside the reaction container are captured by magnetic force. A cleaning device equipped with a cleaning nozzle does this. A typical cleaning nozzle consists of a discharge nozzle and a suction nozzle. The tip opening of the discharge nozzle is located at a higher position than the tip opening of the suction nozzle. Specifically, when cleaning the inside of the reaction container, the tip opening of the discharge nozzle is located at a higher position than the opening of the reaction container. The cleaning device has cleaning equipment for cleaning the cleaning nozzle after use. The cleaning equipment has a well-shaped cleaning tank. Note that a cleaning nozzle may be used in processes other than B/F separation.

Patent Document 1 and Patent Document 2 describe a method for cleaning the cleaning nozzle itself. In the cleaning method according to Patent Document 1, the cleaning nozzle is cleaned multiple times. In the cleaning method according to Patent Document 2, the tip of the suction nozzle (highly contaminated part) is first cleaned with a small amount of cleaning liquid, and then the entire suction nozzle (lowly contaminated part) is cleaned with a large amount of cleaning liquid. has been done.

Japanese Patent Application Publication No. 2005-283246 Japanese Patent Application Publication No. 2015-215277

In a cleaning device equipped with a cleaning nozzle, the cleaning nozzle is cleaned by cleaning equipment after use. If the cleaning nozzle is insufficiently cleaned, in other words, if the previous reaction solution (especially the previous sample) continues to adhere to the surface of the cleaning nozzle, the previous reaction solution will interfere with the subsequent reaction during the next reaction vessel cleaning. It gets mixed into the solution as a contaminant. This phenomenon is also called carryover. For highly accurate measurement or highly sensitive measurement, it is required to reduce contamination between containers (or between solutions) via the cleaning nozzle as much as possible.

An object of the present disclosure is to improve the degree of cleaning of a cleaning nozzle. Alternatively, an object of the present invention is to reduce carryover mediated by the cleaning nozzle.

A cleaning device according to the present disclosure includes a cleaning nozzle for cleaning a reaction vessel, and a nozzle cleaning equipment equipped with a cleaning tank for cleaning the cleaning nozzle after cleaning the reaction vessel, and includes a cleaning device for cleaning the reaction vessel. Before cleaning, the cleaning liquid is discharged from the cleaning nozzle into the cleaning tank, whereby the cleaning liquid is stored in the cleaning tank, and when the nozzle cleaning starts after cleaning the reaction vessel, the cleaning nozzle is discharged into the cleaning tank. The cleaning liquid is inserted into the cleaning liquid stored in the cleaning liquid.

In the nozzle cleaning method according to the present disclosure, before cleaning a reaction vessel, a cleaning liquid is discharged from a cleaning nozzle into a cleaning tank, whereby a stored cleaning liquid is accumulated in the cleaning tank, and the cleaning nozzle cleans the reaction vessel. The cleaning liquid stored in the cleaning tank is maintained during the cleaning process, and the cleaning nozzle is inserted into the cleaning liquid stored in the cleaning tank when nozzle cleaning is started after cleaning the reaction vessel. .

1 is a diagram illustrating a configuration example of a sample analyzer according to an embodiment. FIG. 1 is a diagram showing a cleaning device according to an embodiment. FIG. 7 is a schematic diagram showing an operation according to a comparative example. It is a schematic diagram which shows the operation|movement based on an Example. 7 is a timing chart showing an operation according to a comparative example and an operation according to an example. FIG. 6 is a diagram showing experimental results obtained using a method according to a comparative example and an experimental result obtained using a method according to an example. It is a figure showing a 1st modification. It is a figure showing a 2nd modification. It is a figure showing a 3rd modification. It is a figure which shows the 4th modification. It is a figure showing other examples of a cleaning nozzle.

Hereinafter, embodiments will be described based on the drawings.

(1) Overview of Embodiment A cleaning device according to an embodiment includes a cleaning nozzle and nozzle cleaning equipment. The cleaning nozzle is for cleaning the reaction vessel. The nozzle cleaning equipment includes a cleaning tank for cleaning the cleaning nozzle after cleaning the reaction vessel. Before cleaning the reaction vessel, the cleaning liquid is discharged from the cleaning nozzle into the cleaning tank, whereby the cleaning liquid (reserved cleaning liquid) is stored in the cleaning tank. At the start of nozzle cleaning after cleaning the reaction vessel, the cleaning nozzle is inserted into the cleaning liquid stored in the cleaning tank.

According to the above configuration, after cleaning the reaction vessel, the cleaning nozzle is inserted into the stored cleaning liquid, and the immersion state (post-immersion state) of the cleaning nozzle is formed. At that time, all or part of the substance adhering to the cleaning nozzle dissolves into the stored cleaning liquid, or peels off from the cleaning nozzle and is taken into the stored cleaning liquid. Thereafter, after the stored cleaning liquid is suctioned and removed, a new cleaning liquid is discharged and nozzle cleaning is performed by suctioning the new cleaning liquid. Through such a series of steps, the degree of cleaning of the cleaning nozzle is improved.

At the final stage of the nozzle cleaning process, the cleaning liquid is stored in the cleaning tank. At this time, if the cleaning nozzle is in a immersed state (pre-soaked state), the degree of cleaning of the cleaning nozzle can be further improved. If the cleaning device according to the embodiment is incorporated into a sample analyzer, the accuracy of analysis or the reliability of analysis results can be improved by reducing the amount of carryover.

Note that by injecting the cleaning liquid into the cleaning tank after cleaning the reaction vessel, it is also possible to form a post-immersion state in which the cleaning nozzle is immersed in the cleaning liquid. However, in that case, it takes a certain amount of time to complete the formation of the post-immersion state, making it difficult to bring a large amount of cleaning liquid into contact with each part of the cleaning nozzle within a finite time range. On the other hand, according to the above configuration, the post-immersion state can be quickly formed, and it becomes easy to bring a large amount of cleaning liquid into contact with each part of the cleaning nozzle within a finite time range.

In an embodiment, the cleaning nozzle includes a suction nozzle and a discharge nozzle. The suction port of the suction nozzle is located at a lower position than the discharge port of the discharge nozzle. Before cleaning the reaction vessel, the cleaning liquid is discharged from the discharge nozzle into the cleaning tank while the suction nozzle is inserted into the cleaning tank, thereby forming a pre-immersion state in which the suction nozzle is immersed in the stored cleaning liquid in the cleaning tank. Ru. At the start of nozzle cleaning, the suction nozzle is inserted into the cleaning liquid stored in the cleaning tank, thereby forming a post-immersion state in which the suction nozzle is immersed in the cleaning liquid stored in the cleaning tank.

In the above configuration, it is the suction nozzle that becomes contaminated during cleaning of the reaction container, and the suction nozzle is the cleaning target. By forming the pre-immersion state, the number of times or time that the suction nozzle is immersed in the cleaning liquid can be increased, so that the degree of cleaning of the suction nozzle can be improved. Furthermore, by forming the post-immersion state, the suction nozzle (particularly the highly contaminated portion of the suction nozzle) can be quickly subjected to primary cleaning.

In the embodiment, after completion of discharging the cleaning liquid for storing the stored cleaning liquid, the pre-immersion state is maintained for a certain period of time, and then the cleaning nozzle is transported to the reaction vessel. According to this configuration, the degree of cleaning of the suction nozzle can be further improved. We believe that if the surface of the suction nozzle can be kept moist after the suction nozzle is lifted from the stored cleaning liquid, it will be possible to reduce the amount of substances that adhere to the surface of the suction nozzle when the suction nozzle is inserted into the reaction vessel. It will be done.

In an embodiment, after the formation of the pre-soaked state, the cleaning nozzle is transported from the cleaning tank to the reaction vessel. The suction nozzle performs a suction operation during all or part of the process of transporting the cleaning nozzle from the cleaning tank to the reaction vessel. When transporting a cleaning nozzle in a pre-immersed state, the cleaning liquid is likely to drip from the cleaning nozzle. According to the above configuration, it is possible to prevent or reduce dripping of the cleaning liquid from the cleaning nozzle.

In an embodiment, the cleaning device is incorporated into an immunoassay device that uses immunoassay to analyze a sample removed from a living body. A control unit is provided that determines the amount of the stored cleaning liquid according to measurement items set for the specimen.

Measurement items are basic items that define the measurement method and measurement conditions depending on the type of target substance in the sample. Generally, the amount of specimen and reagent is determined according to the measurement item. Therefore, the above configuration determines the required amount of the stored cleaning liquid depending on the measurement item. By optimizing the amount of stored cleaning liquid, the degree of cleaning can be increased and at the same time, wastage of cleaning liquid can be suppressed.

In an embodiment, the immunoassay device operates on a cycle time basis. The nth container cleaning operation and the nth nozzle cleaning operation are performed within the nth cycle time. In the final stage of the nth nozzle cleaning operation, a pre-immersion state is formed in which the cleaning nozzle is immersed in the stored cleaning liquid in preparation for the n+1th nozzle cleaning operation. In this way, the n-th nozzle cleaning operation and the (n+1)-th nozzle cleaning operation cooperate. n=1, 2, 3, . . .

The nozzle cleaning method according to the embodiment includes a storage step, a cleaning step, and a dipping step. In the storage step, before cleaning the reaction vessel, the cleaning liquid is discharged from the cleaning nozzle into the cleaning tank, whereby the stored cleaning liquid is stored in the cleaning tank. In the cleaning step, the reaction container is cleaned by the cleaning nozzle. At this time, the cleaning liquid stored in the cleaning tank is maintained. In the immersion step, at the start of nozzle cleaning after cleaning the reaction vessel, the cleaning nozzle is inserted into the cleaning liquid stored in the cleaning tank.

(2) Details of Embodiment FIG. 1 shows a sample analyzer 10 according to an embodiment. FIG. 1 schematically shows the top surface of the sample analyzer 10. The sample analyzer 10 is an immunoassay device that analyzes a sample using an immune reaction, that is, an antigen-antibody reaction. Specifically, it is an immunoassay device that follows chemiluminescent enzyme immunoassay (CLEIA). be.

In FIG. 1, the sample analyzer 10 includes a sample supply section 12, a reaction section 14, a reagent supply section 16, a light detection section 18, a cuvette supply section 20, a substrate cooler 22,

cuvette transfer mechanisms

24 and 26, and a sample dispensing mechanism. 28 and

reagent dispensing mechanisms

30 and 32, and further includes cleaning mechanisms (cleaning devices) 70 and 71 according to the embodiment.

The sample supply unit 12 has a turntable 33 as a rotating table. A holding hole group 34 is formed in 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 includes an outer holding hole row consisting of a plurality of holding holes 34a arranged in an annular shape, and an inner holding hole row consisting of a plurality of holding holes 34a arranged in an annular shape. . Each holding hole 34a is a portion that accommodates a sample container as a source container. A specimen is contained within the specimen container.

In an embodiment, the specimen is blood such as serum or plasma. Other liquids such as saliva or urine collected from a living body may also be used as the specimen. The specimen container is a blood collection tube containing blood or other container containing blood. Each specimen container is inserted into each holding hole 34a manually by the examiner. In other words, each sample container is constructed. An arbitrary number of sample containers can be installed on the sample supply section 12. The examiner can also arbitrarily determine the timing for erecting each sample container. Sample containers may be automatically loaded using a mechanism for transporting sample container racks.

The sample supply unit 12 is provided with a barcode reader (BCR), which is not shown. The BCR reads the contents of the barcode labels affixed to each sample container held by the holding hole group 34. Thereby, sample information such as sample ID is read for each sample. Based on the sample ID, subject information, analysis items, sample container type, etc. are specified.

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

The nozzle 52 is composed of a nozzle body and a nozzle tip. A nozzle tip is removably attached to the nozzle body. The nozzle body is made of metal, and the nozzle tip is made of transparent, translucent, or non-transparent resin. After aspirating the sample, the nozzle tip is replaced.

The movement area of the nozzle 52 is expanded by the 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), during sample dispensing, the sample in the sample container (original container) at the suction position is aspirated by the nozzle 52, and the aspirated sample is transferred from the nozzle 52 to a specific location on the reaction section 14. is discharged into a cuvette. The discharge destination position may be fixedly determined, or the discharge destination position may be dynamically changed.

The chip rack 54 is a member that holds a plurality of nozzle chips. When replacing a nozzle tip, the used nozzle tip is removed from the nozzle body and discarded. Thereafter, the tip of the nozzle body is inserted into the upper opening of the nozzle tip selected from the tip rack 54. This attaches a new nozzle tip to the nozzle body. The tip rack is exchanged by a tip rack exchange mechanism (not shown).

The reaction section 14 has a turntable 39 as a rotating table. A holding hole group 40 is formed in the turntable 39, and the holding hole group 40 is composed of a plurality of holding holes 40a. The retaining hole group 40 may include an outer retaining hole row consisting of a plurality of retaining holes arranged in an annular shape, and an inner retaining hole row consisting of a plurality of retaining holes arranged annularly. Each holding hole 40a is a portion that accommodates a cuvette as a reaction container. Reagents and specimens are injected stepwise into each cuvette. This generates an immune reaction within each cuvette.

In the embodiment, the specimen is measured based on a so-called two-step method, for example. The two-step method included a first immunoreaction step using a first reagent containing a first antibody, a second immunoreaction step using a second reagent containing a second antibody, and a substrate (substrate solution). It includes an enzyme reaction step and a light detection step. In the reaction section 14, a first immune reaction step, a second immune reaction step, and an enzyme reaction step are performed. Further, in the reaction section 14, a B/F separation step, a stirring step, etc. are performed.

In the B/F separation step, cleaning

mechanisms

70 and 71 provided near the reaction section 14 operate. In the embodiment, two cleaning

mechanisms

70, 71 are provided, but more cleaning mechanisms may be provided. Each

cleaning mechanism

70, 71 basically has the same configuration. The cleaning

mechanisms

70 and 71 each have a cleaning nozzle 72, a transport mechanism 73, and a nozzle cleaning equipment 74.

The transport mechanism 73 includes a rotary table that rotates around a rotation axis, and the like. A cleaning nozzle 72 is fixed to the rotating table. The cleaning nozzle 72 rotates and moves up and down. The nozzle cleaning equipment 74 includes a cleaning container and a well-shaped cleaning tank 75 provided inside the cleaning container. The configuration and operation of the cleaning

mechanisms

70 and 71 will be detailed later.

The reagent supply unit 16 has a reagent tank 41 as a rotating cold storage. The reagent tank 41 accommodates a reagent bottle row 42 and a reagent bottle row 44 . The reagent bottle row 42 and the reagent bottle row 44 each include a plurality of reagent bottles. Each reagent bottle contains a reagent. Each reagent used in the first immunoreaction step includes 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.

Reagent dispensing mechanisms

30 and 32 are provided adjacent to the reagent supply section 16 and reaction section 14. The reagent dispensing mechanism 30 has a rotating arm 60 and a nozzle 62 provided at the tip of the arm 60. The reagent dispensing mechanism 32 has a rotating arm 64 and a nozzle 65 provided at the tip of the arm 64. The

nozzles

62 and 65 are each non-replaceable nozzles, that is, washable nozzles. The

reagent dispensing mechanisms

30 and 32 aspirate a specific reagent and discharge the aspirated reagent into a specific cuvette.

The light detection unit 18 is a unit that detects light emission generated within the cuvette after the enzyme reaction. The concentration of the substance to be analyzed is calculated based on the detected value. When transferring cuvettes,

cuvette transfer mechanisms

24 and 26 function.

Next, the configuration and operation of the cleaning mechanism will be explained using FIG. 2. The cleaning mechanism cleans the inside of the cuvette 92 using the cleaning nozzle 72 in the B/F separation step. The cleaning mechanism includes a cleaning nozzle 72, a transport mechanism 73, a nozzle cleaning equipment 74, pumps P1, P2, tanks T1, T2, a control section 86, and the like.

The cleaning nozzle 72 is composed of a discharge nozzle 78 and a suction nozzle 80 that are integrated with each other. The position of the discharge port 79 of the discharge nozzle 78 is higher than the position of the suction port 81 of the suction nozzle 80. When the cleaning liquid is discharged from the discharge port 79, the discharged cleaning liquid flows down the outer surface of the suction nozzle 80. A surface coating 82 is applied to the suction nozzle 80 over an area that may come into contact with the reaction solution.

The transport mechanism 73 is a mechanism that transports the cleaning nozzle 72. The transport mechanism 73 has a vertical transport mechanism and a horizontal transport mechanism. The vertical conveyance mechanism has a spring that absorbs the impact that occurs when the tip of the suction nozzle hits the cuvette or the bottom of the cleaning tank.

A discharge pump P1 is connected to the discharge nozzle 78 via a tube 83. Tank T1 connected to pump P1 is a cleaning liquid tank. The cleaning liquid is supplied to the discharge nozzle 78 by the action of the pump P1. A syringe pump may be used as the pump P1. In that case, the flow path may be switched by a three-way valve or the like. A pump P2 is connected to the suction nozzle 80 via a tube 84. Pump P2 is a suction pump. Tank T2 is a waste liquid tank. The waste liquid sucked by the suction nozzle 80 is sent to the tank T2. A diaphragm pump may be used as the pump P2.

The control unit 86 controls the operation of the transport mechanism 73 and pumps P1 and P2. In the embodiment, the control unit 86 has a function of controlling the container cleaning operation and the nozzle cleaning operation. When controlling the nozzle cleaning operation, the control unit 86 controls the discharge amount (including the storage amount described later), discharge speed, etc. of the cleaning liquid.

A cuvette 92 is arranged within the holding hole 40a of the turntable 39. Magnetic particles 96 in the reaction solution are captured by the magnet unit 94 . Reference numeral 72A indicates a cleaning nozzle inserted into the cuvette 92. The cleaning liquid discharged from the discharge nozzle 78A is injected into the cuvette 92. Thereafter, the cleaning liquid in the cuvette 92 is sucked by the suction nozzle 80A. Discharge and suction of the cleaning liquid are repeated as necessary. This performs B/F separation. Note that when the suction nozzle 80A is inserted, its suction port is brought into contact with the bottom surface of the cuvette 92. In this state, the cleaning liquid is sucked through the plurality of slits formed in the suction port.

The nozzle cleaning equipment 74 has a cleaning container 101 as a frame, and a well-shaped cleaning tank 75 is provided inside the cleaning container 101. The horizontal cross-sectional shape of the cleaning tank 75 is, for example, circular or rectangular. Reference numeral 104 indicates a drain for discharging waste liquid caused by overflow. The internal space 100 of the cleaning tank 75 has a capacity to store, for example, 420 μl of cleaning liquid. Reference numeral 72B indicates a cleaning nozzle during nozzle cleaning. The cleaning liquid is discharged from the discharge nozzle 78B and is injected into the cleaning tank 75. If necessary, an amount of cleaning liquid greater than the above-mentioned capacity is injected into the cleaning tank 75. In that case, an overflow occurs in the cleaning tank 75. The cleaning liquid in the cleaning tank 75 is sucked by the suction nozzle 80B.

Note that during nozzle cleaning, the suction port of the suction nozzle 80B is brought into contact with the bottom surface of the cleaning tank 75. In this state, the cleaning liquid is sucked through the plurality of slits formed in the suction port.

FIG. 3 shows a nozzle cleaning operation according to a comparative example. FIG. 4 shows a nozzle cleaning operation according to the embodiment. First, a comparative example will be explained, and then an example will be explained.

(a1) shows B/F separation. The suction nozzle 80 in the cleaning nozzle 72 is inserted into the cuvette 92 . In a state where the magnetic particles 96 in the cuvette 92 are captured by the magnet unit 94, the reaction solution in the cuvette 92 is sucked by the suction nozzle 80. Subsequently, the discharge nozzle discharges the cleaning liquid, and then the suction nozzle 80 suctions the cleaning liquid. They are repeated as many times as necessary. As a result, the inside of the cuvette 92 is cleaned, that is, B/F separation is performed. After performing B/F separation, the cleaning nozzle 72 is transported to the cleaning tank.

(b1) and (c1) indicate primary cleaning. As shown in (b1), the cleaning nozzle 72 is inserted into the cleaning tank 75, and in this state, the cleaning liquid is injected into the cleaning tank 75 from the discharge nozzle 78. The amount of cleaning liquid is determined to be enough to cover the highly contaminated area of the suction nozzle 80. For example, the volume is 100 μl. Reference numeral 106 indicates a small amount of cleaning liquid poured into the cleaning tank. Reference numeral 80A indicates a portion of the suction nozzle 80 that is immersed in the cleaning liquid 106. As already explained, the cleaning tank 75 has a capacity of, for example, 420 μl. After the cleaning liquid is discharged, the cleaning liquid 106 in the cleaning tank 75 is sucked by the suction nozzle 80, as shown in (c1).

(d1) and (e1) indicate secondary cleaning. As shown in (d1), a large amount of cleaning liquid is injected into the cleaning tank 98 from the discharge nozzle 78. The amount is, for example, 800 μl. In that case, 380 μl of cleaning liquid overflows from the cleaning tank 75 (see reference numeral 110). Reference numeral 80B indicates a portion of the suction nozzle 80 that comes into contact with the cleaning liquid. Thereafter, as shown in (e1), all of the cleaning liquid in the cleaning tank 75 is sucked by the suction nozzle 80. The state shown in (e1) is maintained until the cleaning nozzle starts to be transported.

Next, examples will be described. In FIG. 4, (f2') indicates the final stage of the previous nozzle cleaning process. The suction nozzle 80 of the cleaning nozzle 72 is inserted into the cleaning tank 75. A predetermined amount of cleaning liquid is injected into the cleaning tank 75 from the discharge nozzle 78 . Reference numeral 112-0 indicates the cleaning liquid (reserved cleaning liquid) accumulated in the cleaning tank 75. In the next B/F separation, the predetermined amount is determined so that the entire contaminated area (reaction solution contact area) generated in the suction nozzle 80 is immersed in the cleaning liquid 112-0. For example, the predetermined amount is 300 μl. However, more cleaning liquid may be stored or, conversely, less cleaning liquid may be stored so that only the highly contaminated area near the suction port is submerged.

By storing the cleaning liquid 112-0 in the cleaning tank 75, a pre-immersion state is formed in which the suction nozzle 80 is immersed in the cleaning liquid 112-0. Reference numeral 80C indicates a portion of the suction nozzle 80 that is immersed in the cleaning liquid 112-0. Thereafter, the cleaning nozzle 72 is transported from the cleaning tank 75 to the cuvette 92 prior to B/F separation. While B/F separation is being performed, the cleaning liquid 112-0 is maintained in a stored state. Note that the suction nozzle 80 performs a suction operation during all or part of the transport process of the cleaning nozzle 72. This prevents the cleaning liquid from dripping.

(a2) shows B/F separation. As already explained, the suction nozzle 80 of the washing nozzle 72 is inserted into the cuvette 92. Immediately before that, a pre-soaked state is formed, so the surface of the cleaning nozzle 72 is in a wet state. Therefore, it is expected that the amount or degree of adhesion of the reaction solution to the cleaning nozzle 72 will be reduced.

While the magnetic particles 96 in the cuvette 92 are captured by the magnet unit 94, the reaction solution in the cuvette 92 is sucked by the suction nozzle 80. Subsequently, the discharge nozzle 78 discharges the cleaning liquid and the suction nozzle 80 suctions the cleaning liquid. They are repeated as many times as necessary. As a result, the inside of the cuvette 92 is cleaned, that is, B/F separation is performed. After the B/F separation is performed, the cleaning nozzle 72 is transported to the cleaning tank 75. The suction nozzle 80 performs a suction operation during all or part of the conveyance process.

(b2) shows immersion of the cleaning nozzle 72. A cleaning liquid 112-0 is stored in advance in the cleaning tank 75, into which the suction nozzle 80 is inserted. This creates a post-soak condition. Reference numeral 80D indicates a portion of the suction nozzle 80 that is immersed in the cleaning liquid 112-0. The upper end level of the portion 80D is higher than the upper end level of the portion in contact with the reaction solution. Due to the formation of the post-immersion state, all or part of the contamination-causing substances adhering to the suction nozzle 80 are dissolved into the cleaning liquid 112-0, or all or part of the contamination-causing substances are peeled off from the suction nozzle 80. It is taken into the cleaning liquid 112-0. After the post-immersion state is formed, as shown in (c2), the cleaning liquid stored in the cleaning tank 75 is sucked by the suction nozzle 80.

Thereafter, as shown in (d2), a relatively large amount of cleaning liquid is injected into the cleaning tank 75 from the discharge nozzle 78. The amount is, for example, 600 μl. In that case, 180 μl of cleaning liquid overflows from the cleaning tank 75 (see reference numeral 110). Reference numeral 80B indicates a portion that comes into contact with the cleaning liquid. Thereafter, as shown in (e2), all of the cleaning liquid in the cleaning tank 75 is sucked by the suction nozzle 80.

Subsequently, as shown in (f2), the cleaning liquid is stored in the cleaning tank 75. Similar to the step shown in (f2'), in the step shown in (f2), a predetermined amount of cleaning liquid is injected into the cleaning tank 75 from the discharge nozzle 78. As a result, the cleaning liquid 112-1 accumulates in the cleaning tank 75, and a pre-immersion state is formed in which a portion 80C of the suction nozzle 80 is immersed in the cleaning liquid 112-1. After this state is maintained for a certain period of time, the cleaning nozzle 72 is transferred from the cleaning tank 75 to the cuvette to be cleaned. At that time, the suction nozzle 80 performs a suction operation during all or part of the conveyance process.

FIG. 5 shows the operation of the comparative example and the operation of the example as a timing chart. In FIG. 5, the horizontal axis is the time axis. The analyzer operates in cycle time units. The cycle time is, for example, 15 seconds. In FIG. 5, a plurality of gray boxes each indicate a discharge operation, and a plurality of white boxes each indicate a suction operation.

(A) shows a plurality of cycle times lined up on the time axis, and specifically shows the n-th cycle time and the n+1-th cycle time. n is the cycle time number. n is an integer of 1 or more. In the illustrated example, the cycle time starts at the time when the cleaning nozzle movement starts before performing B/F separation, but the cycle time may start at another time.

(B) shows multiple steps within the cycle time. In the illustrated example, one cycle time includes a movement process (outward movement process), a B/F separation process, a movement process (return movement process), and a nozzle cleaning process. In FIG. 5, from left to right, a B/F separation process 116n, a movement process 118n, a nozzle cleaning process 114n, a movement process 118n+1, and a B/F separation process 116n+1 are shown. Note that 120n indicates the timing of inserting the cleaning nozzle into the cleaning tank, and 121n+1 indicates the timing of lifting the cleaning nozzle from the cleaning tank.

(C) shows the operation of the comparative example. (a1) to (e1) in FIG. 5 indicate states (a1) to (e1) shown in FIG. First, a small amount of cleaning liquid is discharged into the cleaning tank (see numeral 122), and then the cleaning liquid in the cleaning tank is sucked (see numeral 124). Next, a large amount of cleaning liquid is discharged into the cleaning tank (see numeral 126), and then the cleaning liquid in the cleaning tank is sucked (see numeral 128).

(D) shows the operation of the embodiment. (a2) to (f2) in FIG. 5 indicate states (a2) to (f2) shown in FIG. 3.

Assuming that the cleaning liquid is stored in the cleaning tank at the final stage of the n-th cycle time, at the beginning of nozzle cleaning, a suction nozzle is inserted into the cleaning liquid (reserved cleaning liquid) in the cleaning tank (reference code 120n). ), a post-soaked state is formed. Reference numeral 132 indicates a period from when the suction nozzle comes into contact with the cleaning liquid during its descent until the suction nozzle completes its descent. In some embodiments, time period 132 may be a portion of nozzle cleaning step 114n'. In other words, the last part of the nozzle moving process 118n and the first part of the nozzle cleaning process 114n' overlap.

When the suction nozzle completes its descent, the cleaning liquid (reserved cleaning liquid) in the cleaning tank is sucked by the suction nozzle (see reference numeral 134). Thereafter, a relatively large amount of cleaning liquid is injected into the cleaning tank from the discharge nozzle (see reference numeral 136). Subsequently, the cleaning liquid in the cleaning tank is sucked by the suction nozzle (see reference numeral 138). After a certain period of time has elapsed, a predetermined amount of cleaning liquid is injected into the cleaning tank from the discharge nozzle (see reference numeral 142). This creates a pre-soaked condition. Reference numeral 143 indicates a certain period during which the pre-soaking state of the suction nozzle continues. A certain period of time is specified in advance. After the period 143 has elapsed, the cleaning nozzle is transferred from the cleaning tank to the cuvette to be cleaned. During B/F separation, the cleaning liquid remains in the cleaning tank. Note that the suction operation 138 may be made longer, or the suction operation may be performed after a certain period of time has elapsed after the suction operation 138.

According to the embodiment, after cleaning the cuvette, the suction nozzle can be immersed in a large amount of cleaning liquid immediately, so that the degree of initial cleaning of the contaminated area in the suction nozzle can be increased. In addition, since the suction nozzle can be immersed in a large amount of cleaning liquid at the final stage of the nozzle cleaning process, the contact time or number of times the cleaning liquid contacts the suction nozzle can be increased compared to the comparative example. Cleanliness can be improved. As described above, according to the embodiment, carryover can be effectively reduced without prolonging or complicating the cleaning process.

FIG. 6 shows the experimental results of the above comparative example and the experimental results of the above example. In the experiment, a highly concentrated antigen was used as a specimen (more specifically, a contaminant that causes carryover). Its concentration was 5 μg/ml, which corresponds to 5 times the concentration used in typical experiments. In FIG. 6, reference numeral 144 indicates the number of experiments, and three experiments were conducted. Reference numeral 146 indicates the experimental results of the comparative example. Reference numeral 148 indicates the experimental results of the example. The total amount of washing liquid used was 900 μl in the comparative example and 900 μl in the example. The amount of cleaning liquid discharged at each stage was as exemplified above.

As shown in FIG. 6, in each of the three experiments, the experimental results of the example were superior to the experimental results of the comparative example, and specifically, according to the example compared to the comparative example, A carryover reduction effect of about 5 times was confirmed.

Next, some modified examples will be explained using FIGS. 7 to 11. FIG. 7 shows a first modification. As shown in FIG. 7, when the cleaning liquid is stored in the cleaning tank 75 in advance, a larger amount of the cleaning liquid 150 may be stored. For example, the cleaning liquid 150 may be stored so that all or substantially all of the internal space of the cleaning tank 75 is filled. In that case, most part 80E of suction nozzle 80 is immersed in cleaning liquid 150.

A second modification example is shown in FIG. Specifically, FIG. 8 schematically shows control of the cleaning liquid storage amount 154. As illustrated, the storage amount 154 may be set based on the measurement item 152. When this configuration is adopted, the optimal storage amount 154 can be individually set for each sample. The measurement items 152 are basic items that define the measurement method and measurement conditions. The storage amount 154 may be determined based on information 156 other than the measurement items 152. For example, the storage amount may be determined based on conditions such as sample amount, reagent amount, cuvette size, washing tank size, and type of washing liquid. When forming the pre-immersion state, the descending speed of the cleaning nozzle and the residence time after stopping the descending may be changed depending on the measurement item.

A third modification and a fourth modification are shown in FIGS. 9 and 10. In FIGS. 9 and 10, elements similar to those shown in FIG. 5 are denoted by the same reference numerals, and their explanations will be omitted.

As shown in FIG. 9, at the final stage of the nozzle cleaning process, the cleaning nozzle may be immediately pulled up after the injection of the cleaning liquid without a certain waiting time (see reference numeral 121n+1). In that case, the period indicated by reference numeral 142A is the discharge period and the immersion period.

As shown in FIG. 10, after the suction indicated by reference numeral 138 is completed, the cleaning liquid is immediately discharged (see reference numeral 142B), and thereafter the cleaning nozzle is maintained in an immersed state for a relatively long period of time. (See reference numeral 143B). Thereafter, the cleaning nozzle is pulled up (see reference numeral 121n+1).

FIG. 11 shows another example of the configuration of the cleaning nozzle. The illustrated cleaning nozzle 160 is composed of one nozzle, which is a discharge/suction nozzle. By discharging the cleaning liquid from the cleaning nozzle 160, the stored cleaning liquid 162 is stored in the cleaning tank 75, and a portion 160A of the cleaning nozzle 160 is immersed in the stored cleaning liquid 162.

The cleaning mechanism (cleaning device) described above may be incorporated into a sample analyzer other than the immunoassay device. Similarly, the nozzle cleaning method described above may be performed in other processes than B/F separation.

Claims

a cleaning nozzle for cleaning the reaction vessel;
nozzle cleaning equipment including a cleaning tank for cleaning the cleaning nozzle after cleaning the reaction container;
including;
Before cleaning the reaction vessel, a cleaning liquid is discharged from the cleaning nozzle into the cleaning tank, whereby a stored cleaning liquid is stored in the cleaning tank,
When starting nozzle cleaning after cleaning the reaction vessel, the cleaning nozzle is inserted into the stored cleaning liquid in the cleaning tank.
A cleaning device characterized by:
The cleaning device according to claim 1,
The cleaning nozzle includes a suction nozzle and a discharge nozzle,
The suction port of the suction nozzle is located at a lower position than the discharge port of the discharge nozzle,
Before cleaning the reaction container, the suction nozzle is inserted into the cleaning tank, and the cleaning liquid is discharged from the discharge nozzle into the cleaning tank, so that the suction nozzle is connected to the stored cleaning liquid in the cleaning tank. A soaked pre-soaked state is formed;
When the nozzle cleaning starts, the suction nozzle is inserted into the stored cleaning liquid in the cleaning tank, thereby forming a post-immersion state in which the suction nozzle is immersed in the stored cleaning liquid in the cleaning tank.
A cleaning device characterized by:
The cleaning device according to claim 2,
After completion of discharging the cleaning liquid for storing the stored cleaning liquid, the pre-immersion state is maintained for a certain period of time, and then the cleaning nozzle is transported to the reaction vessel.
A cleaning device characterized by:
The cleaning device according to claim 2,
After forming the pre-soaked state, the cleaning nozzle is transported from the cleaning tank to the reaction vessel,
The suction nozzle performs a suction operation during all or part of the process of transporting the cleaning nozzle from the cleaning tank to the reaction vessel.
A cleaning device characterized by:
The cleaning device according to claim 1,
The cleaning device is incorporated into an immunoassay device that uses immunoassay to analyze samples taken from a living body.
a control unit that determines the amount of the stored cleaning liquid according to measurement items set for the specimen;
A cleaning device characterized by:
The cleaning device according to claim 1,
The cleaning device is incorporated into an immunoassay device that uses immunoassay to analyze samples taken from a living body.
The immunoassay device operates in cycle time units,
An n-th container cleaning operation and an n-th nozzle cleaning operation are performed within the n-th cycle time,
A pre-immersion state is formed in which the cleaning nozzle is immersed in the stored cleaning liquid in order to prepare for the n+1th nozzle cleaning operation in the final stage of the nth nozzle cleaning operation.
A cleaning device characterized by:
Before cleaning the reaction vessel, a cleaning liquid is discharged from a cleaning nozzle into a cleaning tank, whereby a stored cleaning liquid is stored in the cleaning tank,
While the reaction vessel is being cleaned by the cleaning nozzle, the cleaning liquid stored in the cleaning tank is maintained;
When starting nozzle cleaning after cleaning the reaction vessel, the cleaning nozzle is inserted into the stored cleaning liquid in the cleaning tank.
A nozzle cleaning method characterized by: