(19)
(11) EP 4 005 692 A1

(12) EUROPEAN PATENT APPLICATION
published in accordance with Art. 153(4) EPC

(43) Date of publication:
01.06.2022 Bulletin 2022/22

(21) Application number: 19939286.1

(22) Date of filing: 26.07.2019
(51) International Patent Classification (IPC): 
B08B 9/32(2006.01)
B08B 9/44(2006.01)
(52) Cooperative Patent Classification (CPC):
B08B 9/32; B08B 9/44
(86) International application number:
PCT/CN2019/097850
(87) International publication number:
WO 2021/016733 (04.02.2021 Gazette 2021/05)
(84) Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
Designated Extension States:
BA ME
Designated Validation States:
KH MA MD TN

(71) Applicant: Shenzhen Increcare Biotech Co., Ltd
Shenzhen, Guangdong 518055 (CN)

(72) Inventors:
  • ZHANG, Zhen
    Shenzhen, Guangdong 518055 (CN)
  • HE, Taiyun
    Shenzhen, Guangdong 518055 (CN)
  • YU, Huaibo
    Shenzhen, Guangdong 518055 (CN)
  • YAO, Yanyi
    Shenzhen, Guangdong 518055 (CN)
  • LIU, Qilin
    Shenzhen, Guangdong 518055 (CN)

(74) Representative: Cabinet Laurent & Charras 
Le Contemporain 50 Chemin de la Bruyère
69574 Dardilly Cedex
69574 Dardilly Cedex (FR)

   


(54) CLEANING METHOD, CLEANING APPARATUS, AND IMMUNITY ANALYZER


(57) A cleaning method, comprising the following steps: transferring each reactor (30) between a liquid dispensation station and a collection station; dispensing a cleaning liquid into the reactor (30) at the liquid dispensation station; collecting a magnetic particle conjugate in the reactor (30) onto the inner side wall of the reactor (30) at the collection station, and at a liquid suction station, sucking a waste liquid from the reactor (30) to which the cleaning liquid is dispensed, wherein the number of liquid dispensation stations is less than that of liquid suction stations; and at the same liquid dispensation station, sequentially dispensing the cleaning liquid into at least two reactors (30), and separately and simultaneously sucking the waste liquid from multiple reactors (30) at all the liquid suction stations.




Description

TECHNICAL FIELD



[0001] The present disclosure relates to the technical field of in vitro diagnosis, and particularly to a cleaning method, a cleaning device, and an immunoassay analyzer including the cleaning device.

BACKGROUND



[0002] Based on immunological reactions for binding antigens and antibodies, luminescence immunoassay labels the antigens and the antibodies with enzymes, luminescence reagents and other substances, and associates optical signals with concentrations of analytes and the like by luminescence reactions to analyze the content of the analytes in samples.

[0003] In a cleaning separation (sometimes called cleaning herein for short) process, a target analyte in a sample is captured and bound at first by taking a magnetic particle (usually a main ingredient of a magnetic particle reagent component) as a solid-phase vector. Then, the magnetic particle directly or indirectly bound with the target analyte is collected onto an inner sidewall of a reaction cup under the action of a magnetic force. Finally, free markers and other interfering impurities not bound with any magnetic particle are finally removed by multiple cleaning liquid dispensations and waste liquid suctions, so as to perform signal measurement on an antigen-antibody conjugate (i.e., a magnetic particle conjugate) connected to the magnetic particle. Conventional cleaning methods have either low cleaning efficiency or poor cleaning effects, and thus devices executing such cleaning methods are complex in structure and large in size.

SUMMARY



[0004] According to various embodiments of the present application, a device capable of implementing a cleaning method based on a simplified structure and improving the cleaning efficiency is provided.

[0005] A cleaning method comprises the following steps:

transferring a reactor between a liquid dispensation station and a collection station;

dispensing cleaning liquid into the reactor at the liquid dispensation station; and

collecting magnetic microparticle conjugates suspended in the reactor onto an inner sidewall of the reactor at the collection station, and sucking waste liquid at a liquid suction station from the reactor to which the cleaning liquid is dispensed,

wherein a number of the liquid dispensation station is less than a number of the liquid suction station, the cleaning liquid is sequentially dispensed into at least two reactors at the same liquid dispensation station, and the waste liquid is simultaneously sucked from the reactors at all the liquid suction stations, respectively.



[0006] A cleaning device comprises:

a transferring assembly comprising a rotatable rotation plate configured to carry a reactor, the rotation plate being circumferentially provided with multiple spaced carrying positions configured to carry the reactor;

a liquid dispensation assembly comprising a liquid dispensation element configured to dispense cleaning liquid into the reactor;

a liquid suction assembly comprising a liquid suction element configured to suck waste liquid from the reactor to which the cleaning liquid is dispensed; and

a capturing assembly comprising a magnetic element configured to collect a magnetic particle conjugate in the reactor onto an inner sidewall of the reactor,

wherein a number of the liquid dispensation station is less than a number of the liquid suction station, and the rotation plate carrying the reactor rotates between positions of the liquid suction element and the liquid dispensation element.



[0007] An immunoassay analyzer is provided, which comprises the above-mentioned cleaning device.

[0008] Details of one or more embodiments of this application are provided in the accompanying drawings and descriptions below. Other features, objectives, and advantages of this application become apparent from the specification, the drawings, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS



[0009] To better describe and illustrate embodiments and/or examples of the present invention disclosed herein, reference may be made to one or more drawings. Additional details or examples used for describing the drawings are not to be considered as limiting the scope of any of the disclosure, currently described embodiments and/or examples, and the best modes of the present invention currently understood.

FIG. 1 is a schematic diagram of an overall assembled structure of a cleaning device according to an embodiment;

FIG. 2 is a schematic structural diagram of FIG. 1 at another view;

FIG. 3 is a schematic structural diagram after a bracket drives a liquid suction element to ascend in FIG. 1;

FIG. 4 is a partial schematic structural diagram after a liquid dispensation assembly and a signal element are removed in FIG. 1;

FIG. 5 is a partial schematic structural diagram after a liquid suction assembly is partially removed in FIG. 4;

FIG. 6 is a partial schematic structural diagram of a uniform mixing assembly in FIG. 1; and

FIG. 7 is a flowchart block diagram of a cleaning method according to an embodiment.


DETAILED DESCRIPTION OF THE EMBODIMENTS



[0010] For ease of understanding the present application, the present application is described more comprehensively below with reference to the accompanying drawings. The accompanying drawings illustrate preferred embodiments of this application. However, this application can be implemented in various different forms, and is not limited to the embodiments described in this specification. On the contrary, these embodiments provided are described for the purpose of providing a more thorough and comprehensive understanding of the content disclosed in this application.

[0011] It is to be noted that, when a component is referred to as "being fixed to" another component, the component may be directly on the other component, or an intervening component may be present. When a component is considered to be "connected to" another component, the component may be directly connected to the other component, or an intervening component may also be present. The terms "inner", "outside", "left", "right" and similar expressions used in this specification are merely used for the purpose of description but not indicate a unique implementation.

[0012] In the present application, a uniform mixture entering a reactor before cleaning separation is called a reactant for short. The reactant is usually a reaction mixture of a sample to be tested and a reagent, or a conjugate generated after a reaction of a sample and a reagent, or the like. A wash buffer dispensed into the reactor in a cleaning separation process is called cleaning liquid for short. The dispensation of the wash buffer into the reactor is called liquid dispensation for short. A mixture in the reactor to which the cleaning liquid is dispensed is called waste liquid for short. The waste liquid may consist of a mixture of the reactant and the cleaning liquid, a mixture of an immune complex generated after reaction and the cleaning liquid, an unbound ingredient that is not completely cleaned, and other substances. It can be understood by those skilled in the art that, in order to ensure more complete cleaning separation to maximally reduce remaining unbound ingredients in the reactant after the cleaning separation, cleaning separation usually includes multiple dispensations of the cleaning liquid and suctions of waste liquid in the reactor to which the cleaning liquid is dispensed. The first dispensation of the cleaning liquid, collection of a magnetic particle conjugate and suction of waste liquid after the dispensation of the cleaning liquid for cleaning are defined as a first-stage cleaning. The second dispensation of the cleaning liquid, collection of the magnetic particle conjugate and suction of the waste liquid are defined as a second-stage cleaning. By analogy, the Nth dispensation of the cleaning liquid, collection of the magnetic particle conjugate and suction of the waste liquid are defined as Nth-stage cleaning. Each cleaning separation usually includes 2-6 cleaning stages. In some immunoassay analyzers, for a reactant in a reactor that cleaning separation is about to be performed, there is also a procedure of pre-collecting a magnetic particle conjugate and pre-sucking the unbound reactant in the reactor before cleaning liquid is dispensed for the first time. In the present application, for the ease of description, the procedure of sucking the unbound reactant in the reactor before the dispensation of the cleaning liquid is defined as liquid pre-suction for cleaning. Liquid pre-suction is not included in the N-stage cleaning range of cleaning. In the present application, liquid suction or waste liquid suction refers in particular to the suction of the waste liquid in the reactor to which the cleaning liquid is dispensed, unless otherwise specified. In each test project, one to three cleaning separations may be performed correspondingly in the whole reaction process according to different reaction methods, such as a one-step method, a two-step method, and a three-step method. Each cleaning includes 2-6 cleaning stages.

[0013] Referring to FIG. 1 to FIG. 5, an immunoassay analyzer provided in an embodiment of the present disclosure includes a cleaning device 10, which is configured to clean a magnetic particle conjugate in a reactor 30. The cleaning device 10 includes a transferring assembly 100, a liquid dispensation assembly 200, a liquid suction assembly 300, a capturing assembly 400, a uniform mixing assembly 500, and a signal element 600. The liquid dispensation assembly 200 and the liquid suction assembly 300 may form a cleaning separation mechanism 20.

[0014] In some embodiments, the transferring assembly 100 includes a rotatable rotation plate 110 configured to carry the reactors 30. In addition, the transferring assembly 100 further includes a rotating shaft 120, a shaft sleeve 140, a bearing, and a second driver 130. The second driver 130 is fixed to a lower surface of a bottom plate 320 of the liquid suction assembly 300. The second driver 130 may be a stepping motor and the like. A lower end of the rotating shaft 120 is connected to an output shaft of the second driver 130. An upper end of the rotating shaft 120 extends through the bottom plate 320 and extends upwards relative to an upper surface of the bottom plate 320. The rotation plate 110 is of a disc-shaped structure, and is fixed to the upper end of the rotating shaft 120. The rotating shaft 120 drives the rotation plate 110 to rotate intermittently when the second driver 130 drives the rotating shaft 120 to rotate. The shaft sleeve 140 is fixed between the bottom plate 320 and the rotation plate 110. The shaft sleeve 140 is kept in a still state when the second driver 130 works. The bearing is sleeved on in the shaft sleeve 140. The rotating shaft 120 is matched with the bearing. With the arrangement of the bearing, a frictional force in a rotating process of the rotating shaft 120 may be reduced, and the rotating accuracy of the rotating shaft 120 and the rotation plate 110 may be improved.

[0015] The rotation plate 110 is circumferentially provided with a plurality of spaced carrying positions configured to carry the reactors 30. The carrying position may be any structure suitable for carrying the reactor 30, such as a hole, a slot, and a bracket. In an embodiment, the carrying position is a through hole 111 extending through an upper surface and a lower surface of the rotation plate 110. The plurality of through holes 111 are spaced in a circumferential direction of the rotation plate 110. The number of the through holes 111 is at least five. Specifically, the number may be 8, 10, 12 and the like. The through hole 111 may be a circular stepped hole. The stepped hole is composed of a large hole and a small hole which are coaxial. A diameter of the large hole is greater than that of the small hole. A bottom wall of the large hole forms a step surface of the whole stepped hole. The reactor 30 is substantially cylindrical. A convex ring 31 is arranged on a lateral circumferential surface of the reactor 30. The convex ring 31 extends for a set length relative to the lateral circumferential surface in a radial direction of the reactor 30. When the reactor 30 extends through the through hole 111, the convex ring 31 on the reactor 30 abuts against the step surface on the stepped hole, so as to prevent the reactor 30 from falling off from the through hole 111. Therefore, the through hole 111 plays a role of carrying the reactor 30. Each through hole 111 may form a carrying position 111a configured to carry the reactor 30 on the rotation plate 110. The reactor 30 in the through hole 111 rotates about the rotating shaft 120 along with the rotation plate 110 when the rotation plate 110 drives the rotation plate 110 to move.

[0016] In some embodiments, the liquid suction assembly 300 includes liquid suction elements 310, a bottom plate 320, a bracket 340, and a first driver 330. The liquid suction element 310 is mounted on the bracket 340. The first driver 330 is arranged on the bottom plate 320 and connected to the bracket 340. The first driver 330 is configured to drive the bracket 340 to move up and down, such that the liquid suction element 310 extends into or retracts from the reactor 30.

[0017] The liquid suction element 310 is configured to suck waste liquid from the reactor 30 to which cleaning liquid is dispensed. As described above, the liquid suction element 310 herein refers in particular to suck the waste liquid from the reactor 30 to which the cleaning liquid is dispensed, and does not include a liquid pre-suction element that pre-sucks a reactant in the reactor 30. The liquid suction element 310 may be an elongated liquid suction needle, a liquid suction pipe, or other structures suitable for liquid suction. The liquid suction element 310 corresponds to the carrying position 111a on the rotation plate 110. For example, an orthographic projection of the liquid suction element 310 on the rotation plate 110 may fall on the carrying position 111a. An absolute position of the liquid suction element 310 is a liquid suction station for sucking waste liquid from the reactor 30. Apparently, the liquid suction elements 310 and liquid suction stations are in one-to-one correspondence and have the same number. The bracket 340 includes an overlapping plate 341, a thrust plate 342, and a supporting plate 343. The supporting plate 343 is arranged horizontally and located above the rotation plate 110. The supporting plate 343 is spaced from the rotation plate 110 by a reasonable distance in an axial direction of the rotating shaft 120. The liquid suction element 310 may be fixed on the supporting plate 343. The number N (N=2, 3, 4, 5, 6, 7) of the liquid suction elements 310 is equal to the number N of cleaning stages of the reactor 30. For example, if the reactor 30 needs three cleaning stages for each cleaning, the number of the liquid suction elements 310 is 3, and the three liquid suction elements 310 are recorded as a first liquid suction element (or a first-stage liquid suction element), a second liquid suction element (or a second-stage liquid suction element), and a third liquid suction element (or a third-stage liquid suction element) respectively. If the reactor 30 needs four cleaning stages for each cleaning, the number of the liquid suction elements 310 is 4, and the four liquid suction elements 310 are recorded as a first liquid suction element (or a first-stage liquid suction element), a second liquid suction element (or a second-stage liquid suction element), a third liquid suction element (or a third-stage liquid suction element), and a fourth liquid suction element (or a fourth-stage liquid suction element) respectively. The numbers of the liquid suction elements 310 and the corresponding liquid suction stations may be two, more than four, or the like. The thrust plate 342 is arranged vertically. The overlapping plate 341 is arranged transversely close to the bottom plate 320. An upper end of the thrust plate 342 is connected to the supporting plate 343. A lower end of the thrust plate 342 is connected to the overlapping plate 341.

[0018] The first driver 330 includes a screw motor 331 and a first guide rod 332. The first guide rod 332 is arranged vertically with a lower end thereof fixed on the bottom plate 320. An upper end of the first guide rod 332 is a free end. The first guide rod 332 extends through the overlapping plate 341. Therefore, the overlapping plate 341 is slidably connected to the first guide rod 332. An avoiding slot 342a is provided in the thrust plate 342. The avoiding slot 342a extends in the axial direction of the rotating shaft 120. In brief, the avoiding slot 342a extends in a vertical direction. A screw shaft 331a of the screw motor 331 is rotatably connected to the overlapping plate 341. Meanwhile, the screw shaft 331a is located in the avoiding slot 342a, and is capable of moving relative to the avoiding slot 342a. Therefore, the avoiding slot 342a provides a good avoiding space for the movement of the screw shaft 331a. For example, when the screw shaft 331a of the screw motor 331 rotates clockwise, the rotational motion of the screw shaft 331a is converted into upward sliding of the overlapping plate 341 relative to the first guide rod 332. Meanwhile, the overlapping plate 341 drives the thrust plate 342 and the supporting plate 343 to move upwards. Then, the liquid suction element 310 moves upwards along with the supporting plate 343 to retract from the reactor 30. When the screw shaft 331a of the screw motor 331 rotates counterclockwise, the rotational motion of the screw shaft 331a is converted into downward sliding of the overlapping plate 341 relative to the first guide rod 332. Meanwhile, the overlapping plate 341 drives the thrust plate 342 and the supporting plate 343 to move downwards. Then, the liquid suction element 310 moves downwards along with the supporting plate 343 to extend into the reactor 30 to suck the waste liquid.

[0019] The liquid dispensation assembly is configured to dispense cleaning liquid into the reactor. In some embodiments, the liquid dispensation assembly 200 includes a liquid dispensation element 210 and a carrying plate 220. The carrying plate 220 is arranged horizontally and located above the rotation plate 110. The carrying plate 220 is spaced apart from the rotation plate 110 by a reasonable distance in the axial direction of the rotating shaft 120. A position of the carrying plate 220 relative to the rotation plate 110 may be fixed. Of course, the carrying plate 220 may also be connected to the bracket 340 of the liquid suction assembly 300. The bracket 340 moves up and down to drive the carrying plate 220 to move up and down. The liquid dispensation element 210 is fixed on the carrying plate 220, and may be an elongated liquid dispensation needle or a component capable of dispensing liquid such as a liquid dispensation pipe or a liquid dispensation orifice. The liquid dispensation element 210 corresponds to the carrying position 111a on the rotation plate 110. For example, an orthographic projection of a liquid dispensation part of the liquid dispensation element 210 on the rotation plate 110 may fall on the carrying position 111a. An absolute position of the liquid dispensation element 210 is a liquid dispensation station for dispensing cleaning liquid into the reactor 30. There may be one or two liquid dispensation elements 210. Of course, there may also be more than two liquid dispensation elements 210. It should to be noted particularly that the present application specifies that the number of the liquid dispensation element is one, corresponding to the same liquid dispensation station, no matter how many liquid dispensation outlets the liquid dispensation element corresponding to the liquid dispensation station has and no matter how many needles and pipes the liquid dispensation element includes. That is, each liquid dispensation station corresponds to one liquid dispensation element. Multiple liquid dispensation elements correspond to multiple stations. For example, two liquid dispensation stations correspond to two liquid dispensation elements. After the liquid dispensation element 210 dispenses the cleaning liquid into the reactor 30 at the liquid dispensation station, the cleaning liquid cleans the magnetic particle conjugate in the reactor 30 to remove free markers and other interfering impurities not bound with magnetic particles.

[0020] The capturing assembly 400 is configured to collect the magnetic particle conjugate in the reactor onto an inner sidewall of the reactor before each liquid suction stage. In some embodiments, the capturing assembly 400 includes magnetic elements 420 and a mounting frame 410. The mounting frame 410 may be substantially disc-shaped. The mounting frame 410 is fixed on the shaft sleeve 140 of the transferring assembly 100. The mounting frame 410 is provided with receiving holes 411. The receiving hole 411 is formed in a lateral circumferential surface of the mounting frame 410. An outer circumferential surface of the receiving hole 411 is partially recessed by a set depth in a radial direction of the mounting frame 410. There are a plurality of receiving holes 411. The plurality of receiving holes 411 may be uniformly spaced along an axis of the mounting frame 410. The magnetic element 420 may be a natural permanent magnet, an electromagnet, or the like. The magnetic element 420 has a shape matched with that of the receiving hole 411 and is accommodated in the receiving hole 411. An outer surface of the magnetic element 420 may be coplanar with the lateral circumferential surface of the mounting frame 410. A position of the receiving hole 411 and the magnetic element 420 is a collection station configured to collect the magnetic particle conjugate in the reactor 30 onto the inner sidewall of the reactor 30 before each liquid suction stage. When the rotation plate 110 drives the reactor 30 to be located at the collection station, the reactor 30 is located in a magnetic range of the magnetic element 420, and the magnetic particle conjugate in the reactor 30 is collected onto the inner sidewall of the reactor 30 under the action of a magnetic attraction force generated by the magnetic element 420.

[0021] The collection station includes the liquid suction station. In order to avoid the loss of magnetic particles, the magnetic particle conjugate in the reactor needs to be attracted magnetically when the liquid suction element in each stage sucks the waste liquid. Therefore, the magnetic element 420 needs to be mounted at the liquid suction station for each stage. Thus, the liquid suction station is also the collection station. That is, the collection station includes the liquid suction station. The number of collection station is no less than that of the liquid suction station. Specifically, the collection stations in each cleaning stage may correspond to the liquid suction stations one to one, or a plurality of collection stations may correspond to one liquid suction station. When the collection stations in each cleaning stage correspond to the liquid suction stations one to one, the collection of the magnetic particle conjugate in the reactor 30 and the suction of the waste liquid in the reactor are completed at the same station. When the plurality of collection stations in each cleaning stage correspond to one liquid suction station, the magnetic particle conjugate in the reactor 30 is collected gradually at the plurality of collection stations, and at the liquid suction station (also the last collection station in this cleaning stage), collection is continued and the waste liquid is sucked.

[0022] Recessed grooves 412 are further sunken into the lateral circumferential surface of the mounting frame 410. The recessed groove 412 extends in the vertical direction. An upper end of the recessed groove 412 extends through an upper surface of the mounting frame 410. A lower end of the recessed groove 412 extends through a lower surface of the mounting frame 410. The recessed groove 412 corresponds to the position of the liquid dispensation element 210 (i.e., the liquid dispensation station).

[0023] In some embodiments, the uniform mixing assembly 500 includes a connecting plate 510, a driving motor 520, a driving shaft 530, and a carrying cylinder 540. The connecting plate 510 is arranged transversely. A second guide rod 550 is further provided on the bottom plate 320 of the liquid suction assembly 300. The second guide rod 550 is arranged vertically, and one end thereof is fixed on the bottom plate 320 and extends through the connecting plate 510. The other end of the second guide rod 550 extends through the connecting plate 510 to form a free end. Therefore, the second guide rod 550 is slidably connected to the connecting plate 510, and the connecting plate 510 is capable of sliding up and down along the second guide rod 550. The driving motor 520 is placed on the bottom plate 320 and fixedly connected to the connecting plate 510. The driving motor 520 is not fixedly connected to the bottom plate 320. Therefore, the driving motor 520 may be carried on the bottom plate 320, or the driving motor 520 moves upwards away from the bottom plate 320. When the screw motor 331 drives the overlapping plate 341 to ascend along the first guide rod 332, the overlapping plate 341 abuts against the connecting plate 510. When the overlapping plate 341 continues ascending, the overlapping plate 341 carries the connecting plate 510 and the driving motor 520 to ascend together along the second guide rod 550. When the screw motor 331 drives the overlapping plate 341 to descend along the first guide rod 332, the overlapping plate 341 abuts against the connecting plate 510 to support the connecting plate 510. The connecting plate 510 and the driving motor 520 move downwards along the second guide rod 550 under the action of gravity. When the driving motor 520 is in contact with the bottom plate 320, the connecting plate 510 and the driving motor 520 are limited by the bottom plate 320 to stop moving downwards. In such a case, the screw motor 331 may further drive the overlapping plate 341 to continue descending along the first guide rod 332 until the overlapping plate 341 is in contact with the bottom plate 320. A surface of the overlapping plate 341 is partially recessed to form a first limiting surface 341a and a second limiting surface 341b which are in bending connection. For example, the first limiting surface 341a and the second limiting surface 341b may be perpendicular to each other. When the overlapping plate 341 carries the connecting plate 510, the connecting plate 510 abuts against the first limiting surface 341a and the second limiting surface 341b. The first limiting surface 341a and the second limiting surface 341b limit the connecting plate 510. Therefore, the whole uniform mixing assembly 500 is prevented from vibrating when moving up and down, and the running stability of the uniform mixing assembly 500 is improved.

[0024] A lower end of the driving shaft 530 is connected to an output shaft of the driving motor 520. The carrying cylinder 540 is fixed to an upper end of the driving shaft 530. The driving shaft 530 may be arranged coaxial with the carrying cylinder 540. The driving motor 520 is configured to drive the driving shaft 530 to rotate, such that the carrying cylinder 540 is further driven to rotate along with the driving shaft 530. Referring to FIG. 6, a uniform mixing hole 541 is provided in the carrying cylinder 540. The reactor 30 may be matched with the uniform mixing hole 541. A central axis of the uniform mixing hole 541 is parallel to that of the driving shaft 530. That is, there is a certain eccentricity due to a distance between the uniform mixing hole 541 and the driving shaft 530. After the reactor 30 is matched with the uniform mixing hole 541 and when the driving shaft 530 drives the carrying cylinder 540 to rotate, a suspension containing the magnetic particle conjugate in the reactor 30 is vibrated eccentrically under the action of the eccentric force, such that the whole suspension is uniformly mixed well.

[0025] When uniform mixing is needed, the overlapping plate 341 may be driven by the screw motor 331 to push the connecting plate 510 to ascend, such that the driving motor 520 and the carrying cylinder 540 are further driven to ascend. Meanwhile, the recessed groove 412 formed in the mounting frame 410 may provide an avoiding space for the movement of the carrying cylinder 540, so as to prevent interferences of the mounting frame 410 to the movement of the carrying cylinder 540. When the carrying cylinder 540 ascends to a certain height and is matched with the reactor 30, the screw motor 331 stops working. In such a case, the driving motor 520 drives the carrying cylinder 540 by the driving shaft 530 to vibrate eccentrically, such that the cleaning liquid in the reactor 30 forms a turbulent flow. The cleaning liquid cleans the magnetic particle conjugate effectively under the action of the turbulent flow, thereby maximally removing the free markers and other interfering impurities not bound with the magnetic particles. Moreover, the magnetic particle conjugate may be dispersed in the cleaning liquid uniformly. After the suspension in the reactor 30 is mixed uniformly, the screw motor 331 drives the overlapping plate 341 to move downwards to further drive the whole uniform mixing assembly 500 to move downwards and finally separates the bottom of the reactor 30 completely from the uniform mixing hole 541 in the carrying cylinder 540. That is, the reactor 30 retracts from the uniform mixing hole 541 completely. When the rotation plate 110 needs to drive the reactor 30 to be transferred from the liquid dispensation station to the liquid suction station, the carrying cylinder 540 separated from the reactor 30 may not interfere with the rotation of the reactor 30. Therefore, the reactor 30 is transferred from the liquid dispensation station to the liquid suction station smoothly.

[0026] The number of the liquid dispensation element 210 is less than that of the liquid suction element 310. For example, there are three liquid suction elements 310 and there is one liquid dispensation element 210; and correspondingly, there are three liquid suction stations and there is one liquid dispensation station. There are four liquid suction elements 310 and two liquid dispensation elements 210; and of course, there are four liquid suction stations and two liquid dispensation stations. Compared with a conventional design that the liquid suction element 310 and the liquid dispensation element 210 are equal in number, in the above-mentioned embodiments, the number of liquid dispensation element 210 is less than that of the liquid suction element 310, such that the total number of the liquid dispensation elements 210 is reduced relatively. Therefore, the number of fluid devices such as transmission pipes and electromagnetic valves connected to each liquid dispensation element 210 is reduced, which contributes to reducing the overall structures of the cleaning device 10 and the immunoassay analyzer as well as their sizes and manufacturing cost and miniaturizing the cleaning device 10 and the immunoassay analyzer. In addition, the reduction of the liquid dispensation elements 210 also correspondingly reduces the carrying positions 111a corresponding to the liquid dispensation elements 210 on the rotation plate 110 to further reduce the size of the rotation plate 110, which also contributes to miniaturizing the cleaning device 10 and the immunoassay analyzer. Moreover, the plurality of liquid suction elements 310 may suck the waste liquid from multiple reactors 30 simultaneously. Therefore, the total cleaning time of the magnetic particle conjugate is reduced, and the cleaning efficiency of the cleaning device 10 and the immunoassay analyzer is improved.

[0027] The signal element 600 is configured to dispense a signal reagent into the reactor 30 when the cleaning is completed. In some embodiments, the signal element 600 is provided on the carrying plate 220 of the liquid dispensation assembly 200. The signal element 600 may be an elongated needle-like structure. All of the signal element 600, the liquid dispensation element 210, and the liquid suction element 310 correspond to different carrying positions 111a on the rotation plate 110, respectively. An absolute position of the signal element 600 is a signal dispensation station. The signal element 600 dispenses the signal reagent into the reactor 30 where cleaning is completed at the signal dispensation station to subsequently perform optical signal measurement on the magnetic particle conjugate.

[0028] In order to transfer the reactor 30 needing cleaning in the transferring assembly 100 and transfer the reactor 30 where cleaning is completed out of the transferring assembly 100, a transfer position is further arranged on the transferring assembly 100. The transferring assembly 100 may transfer the reactor 30 between the transfer position, the liquid dispensation station, and the liquid suction station.

[0029] Since the dispensation of the cleaning liquid and the suction of the waste liquid in the reactor to which the cleaning liquid is dispensed are in one-to-one correspondence in the cleaning separation process, it is a general technical implementation mode in the art that the liquid suction element 310 and the liquid dispensation element 210 are equal in number. In the present disclosure, the situation that the number of the liquid dispensation element 210 is less than that of the liquid suction element 310 needs to be implemented by matching a special flowchart and method.

[0030] Referring to FIG. 1 and FIG. 7 simultaneously, the following cleaning method may be implemented by the above-mentioned cleaning device 10 and immunoassay analyzer. That is, the cleaning method may be implemented by the above-mentioned cleaning device 10 and immunoassay analyzer. Taking the completion of one cleaning stage of a reactor as an example, the cleaning method mainly includes the following steps.

[0031] In S710, a reactor 30 is transferred between a liquid dispensation station and a collection station.

[0032] In S720, cleaning liquid is dispensed into the reactor 30 at the liquid dispensation station.

[0033] In S730, a magnetic particle conjugate suspended in the reactor 30 is collected onto an inner sidewall of the reactor 30 at the collection station, and waste liquid is sucked at a liquid suction station from the reactor 30 to which the cleaning liquid is dispensed.

[0034] The number of the liquid dispensation stations is less than that of the liquid suction stations. The cleaning liquid is sequentially dispensed into at least two reactors 30 at the same liquid dispensation station. The waste liquid is simultaneously sucked from the multiple reactors 30 at all the liquid suction stations, respectively.

[0035] In some embodiments, the liquid dispensation stations and the liquid suction stations are circumferentially spaced along the same circumference of the rotation plate 110, such that the rotation plate 110 drives the reactor 30 to move circumferentially between the liquid dispensation station and the liquid suction station. The number of the liquid suction stations is equal to the number of cleaning stages for each cleaning of the reactor 30. There may be one liquid dispensation station and three liquid suction stations. The three liquid suction stations are recorded as a first liquid suction station, a second liquid suction station, and a third liquid suction station respectively. A first liquid suction element 310 is located at the first liquid suction station. A second liquid suction element 310 is located at the second liquid suction station. A third liquid suction element 310 is located at the third liquid suction station. There may be two liquid dispensation stations, which are recorded as a first liquid dispensation station and a second liquid dispensation station respectively. There may be four liquid suction stations, which are recorded as a first liquid suction station, a second liquid suction station, a third liquid suction station, and a fourth liquid suction station respectively. A first liquid suction element 310 is located at the first liquid suction station. A second liquid suction element 310 is located at the second liquid suction station. A third liquid suction element 310 is located at the third liquid suction station. A fourth liquid suction element 310 is located at the fourth liquid suction station.

[0036] For the same individual reactor 30, a complete cleaning process includes at least three cleaning stages, i.e., three cleaning liquid dispensations and waste liquid suctions, so as to ensure a good cleaning effect. The cleaning of an individual reactor 30 will be described below with the condition of three-stage cleaning as an example.

[0037] In step 1, the reactor 30 is transferred to the rotation plate 110. Pre-collection and liquid pre-suction may be performed to the reactor 30. That is, an unbound reactant in the reactor 30 is firstly sucked, such that only a magnetic particle conjugate and uncleaned residuals are left in the reactor 30. Then, the reactor 30 containing only the magnetic particle conjugate on the rotation plate 110 rotates to a liquid dispensation station. Of course, pre-collection and liquid pre-suction may also not be performed on the reactor 30, and instead, the reactor 30 containing the reactant is directly transferred to the liquid dispensation station. When the reactor 30 reaches the liquid dispensation station, the liquid dispensation element 210 dispenses cleaning liquid into the reactor 30 to clean the magnetic particle conjugate, so as to remove free markers and other interfering impurities not bound with any magnetic particle. When or after the first-stage liquid dispensation is performed on the reactor 30, a suspension containing the magnetic particle conjugate in the reactor 30 may or may not be mixed uniformly. During uniform mixing, the uniform mixing assembly 500 moves upwards, such that the reactor 30 is matched with the uniform mixing hole 541 in the carrying cylinder 540. The driving motor 520 drives the carrying cylinder 540 to rotate through the driving shaft 530. The suspension in the reactor 30 is vibrated eccentrically to be mixed uniformly, with the magnetic particle conjugate suspended uniformly in the cleaning liquid. The cleaning liquid has a good cleaning effect on the magnetic particle conjugate in an eccentric vibration process. After uniform mixing, the uniform mixing assembly 500 moves downwards. The reactor 30 is separated from the uniform mixing hole 541 in the carrying cylinder 540 completely, such that the rotation plate 110 drives the reactor 30 to leave the liquid dispensation station. After that, the first dispensation of the cleaning liquid into the reactor 30 is completed. That is, the first-stage dispensation of the cleaning liquid is completed.

[0038] In step 2, the rotation plate 110 transfers the reactor 30 dispensed with the cleaning liquid from the liquid dispensation station to a collection station or a first liquid suction station. When the reactor 30 is located at the collection station, the magnetic particle conjugate is gradually collected onto an inner sidewall of the reactor 30 by the magnetic element 420. When the magnetic particle conjugate in the reactor 30 is collected, the reactor 30 is located at the first liquid suction station. When the collection station equals to, namely overlaps with, the first liquid suction station, the rotation plate 110 does not rotate. When there are more collection stations than the liquid suction stations, the rotation plate rotates to transfer the reactor 30 to the first liquid suction station. The screw motor 331 drives the bracket 340 to drive the supporting plate 343 to move downwards, such that the liquid suction element 310 moves downwards along with the supporting plate 343 to extend into the reactor 30. The liquid suction element 310 sucks all waste liquid formed by cleaning the magnetic particle conjugate in the reactor 30, such that only the magnetic particle conjugate and uncleaned residuals are left in the reactor 30. After the waste liquid is sucked from the reactor 30, the screw motor 331 drives the bracket 340 to drive the supporting plate 343 to move upwards. The liquid suction element 310 moves upwards along with the supporting plate 343 to withdraw from the reactor 30, such that the rotation plate 110 drives the reactor 30 to leave the liquid suction station. After that, the first waste liquid suction of the reactor 30 is completed. That is, first-stage waste liquid suction is completed.

[0039] In step 3, the rotation plate 110 drives the reactor 30 and transfers it from the liquid suction station to the liquid dispensation station. When the reactor 30 reaches the liquid dispensation station, the related operations in step 1 are repeated. After that, the second dispensation of the cleaning liquid into the reactor 30 is completed. That is, the second-stage dispensation of the cleaning liquid is completed. Uniform mixing is usually performed during or after the second-stage dispensation of the cleaning liquid into the reactor 30.

[0040] In step 4, the rotation plate 110 drives the reactor 30 and transfers it from the liquid dispensation station to the collection station or a second liquid suction station. When the reactor 30 reaches the liquid suction station, the related operations in Step 2 are repeated. After that, the second waste liquid suction of the reactor 30 is completed. That is, second-stage waste liquid suction is completed.

[0041] In step 5, the rotation plate 110 drives the reactor 30 and transfers it from the liquid suction station to the liquid dispensation station. When the reactor 30 reaches the liquid dispensation station, the related operations in Step 1 are repeated. After that, the third dispensation of the cleaning liquid into the reactor 30 is completed. That is, the third-stage dispensation of the cleaning liquid is completed. Uniform mixing is usually performed during or after the third-stage dispensation of the cleaning liquid into the reactor 30.

[0042] In step 6, the rotation plate 110 drives the reactor 30 and transfers it from the liquid dispensation station to the collection station or a third liquid suction station. When the reactor 30 reaches the liquid suction station, the related operations in step 2 are repeated. After that, the third waste liquid suction of the reactor 30 is completed. That is, third-stage waste liquid suction is completed.

[0043] For the same individual reactor 30, after a complete cleaning process is completed, namely after cleaning liquid dispensation, magnetic particle conjugate collection, and waste liquid suction of all stages are completed for the same reactor 30, a signal reagent is added into the reactor 30 for subsequently optical signal measurement on the magnetic particle conjugate. In an embodiment, the rotation plate 110 drives the reactor 30 and transfers it from a liquid suction station to a signal dispensation station. When the reactor 30 reaches the signal dispensation station, the signal reagent is added into the reactor 30. Finally, the reactor 30 added with the signal reagent is transferred out of the rotation plate 110. Of course, the reactor 30 only containing the magnetic particle conjugate after cleaning may be directly transferred out of the rotation plate 110, and the signal reagent is dispensed outside the rotation plate 110.

[0044] When more than three cleaning stages are needed, cleaning of more than three stages may be performed on the same individual reactor 30 according to the above-mentioned operation mode.

[0045] For the same individual reactor 30, at least two cleaning liquid dispensations of the same reactor 30 are completed at the same liquid dispensation station. When there are two liquid dispensation stations, for example, under the condition that the cleaning liquid is dispensed for totally three times, the cleaning liquid dispensations of two stages are completed at one of the two liquid dispensation stations, while the cleaning liquid dispensation of the other stage is completed at the other liquid dispensation station. When there is only one liquid dispensation station, namely there is only one liquid dispensation element 210, the cleaning liquid dispensations of all stages for the same reactor 30 are completed at this liquid dispensation station. For example, under the condition that the cleaning liquid is dispensed for totally three times, the first-stage cleaning liquid dispensation, the second-stage cleaning liquid dispensation, and the third-stage cleaning liquid dispensation are all completed at the liquid dispensation station.

[0046] For the same individual reactor 30, liquid suctions of different stages are completed at different liquid suction stations, respectively. For example, when waste liquid is sucked for totally three times, there are totally three liquid suction stations. The first-stage waste liquid suction is completed at a first liquid suction station by a first liquid suction element. The second-stage waste liquid suction is completed at a second liquid suction station by a second liquid suction element. The third-stage waste liquid suction is completed at a third liquid suction station by a third liquid suction element.

[0047] In some embodiments, the plurality of reactors 30 on the rotation plate 110 may be cleaned simultaneously. Descriptions will be made below with the condition that there is only one liquid dispensation station and three-stage cleaning is performed on the plurality of reactors 30 as an example.

[0048] In step 1, the rotation plate 110 performs a first transferring to transfer a first reactor to the liquid dispensation station. The liquid dispensation element 210 dispenses cleaning liquid into the reactor.

[0049] In step 2, the rotation plate 110 performs a second transferring to transfer a second reactor to the liquid dispensation station. The liquid dispensation element 210 dispenses the cleaning liquid into the second reactor.

[0050] In step 3, the rotation plate 110 performs a third transferring to transfer a third reactor to the liquid dispensation station. The liquid dispensation element 210 dispenses the cleaning liquid into the third reactor.

[0051] In step 4, the rotation plate 110 performs a fourth transferring to transfer the first reactor, the second reactor, and the third reactor to different collection stations or liquid suction stations. Three liquid suction elements 310 simultaneously suck waste liquid from the three reactors 30 at different liquid suction stations, respectively. For example, a first liquid suction element sucks waste liquid from the first reactor. A second liquid suction element sucks waste liquid from the second reactor. A third liquid suction element sucks waste liquid from the third reactor. The first liquid suction element, the second liquid suction element and the third liquid suction element simultaneously suck the waste liquid.

[0052] In step 5, the reactor 30 is continuously transferred to the liquid dispensation station, the operations in step 1 to step 4 are repeated, and the reactors 30 where cleaning of all stages is completed are transferred out of the rotation plate 110 one after another.

[0053] In some embodiments, waste liquid suctions for the plurality of reactors 30 simultaneously performed at all the liquid suction stations are in different stages. For example, when there are three liquid suction stations, which are recorded as a first liquid suction station, a second liquid suction station, and a third liquid suction station, respectively, the reactor 30 at the first liquid suction station is right in a first waste liquid suction stage, the reactor 30 at the second liquid suction station is right in a second waste liquid suction stage, and the reactor 30 at the third liquid suction station is right in a third waste liquid suction stage. Since liquid suction elements 310 at the plurality of liquid suction stations may simultaneously suck the waste liquid, waiting time between each reactor 30 may be saved, and the cleaning efficiency may be improved.

[0054] In some embodiments, at least twice transferring are performed in each cleaning stage, i.e., at least two reactors 30 are sequentially transferred to the same liquid dispensation station to perform liquid dispensation in different stages. Cleaning liquid dispensations of different stages for at least two reactors 30 are sequentially completed at the same liquid dispensation station. For example, the first-stage cleaning liquid dispensation of a first reactor at the liquid dispensation station is followed by the second-stage cleaning liquid dispensation of a second reactor at the liquid dispensation station and then the third-stage cleaning liquid dispensation of a third reactor at the liquid dispensation station.

[0055] According to the cleaning method of the present disclosure, liquid suctions of different stages for N reactors needing N-stage cleaning are completed concurrently at N liquid suction stations. Cleaning liquid dispensations of different stages for at least two reactors are sequentially completed at the same liquid dispensation station. Not only is the liquid suction efficiency for cleaning improved, but also the structural size and cost for the implementation of liquid dispensation are also reduced effectively, and the number of liquid dispensation stations and liquid dispensation elements and the size of the rotation plate are reduced. On the other hand, differences between the accuracy of liquid dispensation volumes in different stages are also reduced, which contributes to the implementation of a cleaning device and an immunoassay analyzer that are compact in structure, high in test efficiency and good in performance.

[0056] The technical features in the foregoing embodiments may be randomly combined. For concise description, not all possible combinations of the technical features in the embodiments are described. However, provided that combinations of the technical features do not conflict with each other, the combinations of the technical features are considered as falling within the scope described in this specification.

[0057] The foregoing embodiments only describe several implementations of this application, which are described specifically and in detail, but cannot be construed as a limitation to the patent scope of this application. It should be noted that for a person of ordinary skill in the art, several transformations and improvements can be made without departing from the idea of this application. These transformations and improvements belong to the protection scope of this application. Therefore, the protection scope of the patent of this application shall be subject to the appended claims.


Claims

1. A cleaning method, comprising the following steps:

transferring a reactor between a liquid dispensation station and a collection station;

dispensing cleaning liquid into the reactor at the liquid dispensation station; and

collecting a magnetic particle conjugate in the reactor onto an inner sidewall of the reactor at the collection station, and sucking waste liquid at a liquid suction station from the reactor to which the cleaning liquid is dispensed;

wherein a number of the liquid dispensation station is less than a number of the liquid suction station, the cleaning liquid is sequentially dispensed into at least two reactors at the same liquid dispensation station, and the waste liquid is simultaneously sucked from the reactors at all of the liquid suction stations, respectively.


 
2. The cleaning method according to claim 1, wherein for the reactor, each cleaning comprises at least three cleaning stages.
 
3. The cleaning method according to claim 1 or 2, wherein at least two dispensations of the cleaning liquid for the same reactor are completed at the same liquid dispensation station.
 
4. The cleaning method according to claim 2, wherein liquid suctions of different stages for the same reactor are completed at different liquid suction stations, and a number of liquid suction stages is equal to a total number of the liquid suction stations.
 
5. The cleaning method according to claim 2, wherein liquid suctions for the plurality of reactors simultaneously performed at all the liquid suction stations are in different stages.
 
6. The cleaning method according to claim 2, wherein the cleaning liquid dispensations of different stages for at least two of the reactors are sequentially completed at the same liquid dispensation station.
 
7. The cleaning method according to claim 2, wherein transferring is performed at least twice in each cleaning stage to sequentially transfer at least two reactors to the same liquid dispensation station to dispense the cleaning liquid in different stages.
 
8. The cleaning method according to any one of claims 1 to 2 and 4 to 7, wherein one liquid dispensation station and three liquid suction stations are provided; or two liquid dispensation stations and four liquid suction stations are provided.
 
9. A cleaning device, comprising:

a transferring assembly comprising a rotatable rotation plate configured to carry a reactor,

the rotation plate being circumferentially provided with a plurality of spaced carrying positions configured to carry the reactors;

a liquid dispensation assembly comprising a liquid dispensation element configured to dispense cleaning liquid into the reactor;

a liquid suction assembly comprising a liquid suction element configured to suck waste liquid from the reactor to which the cleaning liquid is dispensed; and

a capturing assembly comprising a magnetic element configured to collect a magnetic particle conjugate in the reactor onto an inner sidewall of the reactor;

wherein a number of the liquid dispensation station is less than a number of the liquid suction station, and the rotation plate carrying the reactor rotates between positions of the liquid suction element and the liquid dispensation element.


 
10. The cleaning device according to claim 9, wherein three liquid suction elements and one liquid dispensation element are provided; or four liquid suction elements and two liquid dispensation elements are provided.
 
11. The cleaning device according to claim 9, wherein the capturing assembly further comprises a mounting frame spaced apart from the rotation plate, the mounting frame is provided with a receiving hole at a position thereof corresponding to the liquid suction element, and the magnetic element is accommodated in the receiving hole.
 
12. The cleaning device according to claim 9, further comprising a uniform mixing assembly, wherein the uniform mixing assembly comprises a driving shaft and a carrying cylinder connected to the driving shaft, the carrying cylinder is provided with a uniform mixing hole matched with the reactor, and a central axis of the uniform mixing hole is parallel to a central axis of the driving shaft.
 
13. The cleaning device according to claim 9, wherein the liquid suction assembly further comprises a bottom plate, a bracket, and a first driver; the liquid suction element is mounted on the bracket; the first driver is arranged on the bottom plate and connected to the bracket; and the first driver is configured to drive the bracket to move, such that the liquid suction element extends into or retracts from the reactor.
 
14. The cleaning device according to claim 13, further comprising a uniform mixing assembly having a connecting plate, wherein a guide rod is provided on the bottom plate; the uniform mixing assembly is slidably connected to the guide rod; the bracket is capable of pushing the connecting plate to drive the whole uniform mixing assembly to slide relative to the guide rod, such that the uniform mixing assembly is matched with the reactor.
 
15. The cleaning device according to claim 9, wherein the transferring assembly further comprises a rotating shaft, a shaft sleeve, a bearing, and a second driver; the bearing is arranged in the shaft sleeve; the rotating shaft is matched with the shaft sleeve and is connected to the rotation plate; the shaft sleeve is fixed between the liquid suction assembly and the rotation plate; and the second driver is fixed on the liquid suction assembly and configured to drive the rotating shaft to rotate.
 
16. An immunoassay analyzer, comprising the cleaning device according to any one of claims 9 to 15.
 




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