CN112296048A

CN112296048A - Cleaning method

Info

Publication number: CN112296048A
Application number: CN202010680698.1A
Authority: CN
Inventors: 张震; 何太云; 于怀博; 姚言义; 刘奇林
Original assignee: Shenzhen Increcare Biotech Co Ltd
Current assignee: Shenzhen Increcare Biotech Co Ltd
Priority date: 2019-07-26
Filing date: 2019-07-26
Publication date: 2021-02-02
Also published as: CN112296049A; CN110404910A; CN112296049B; CN110404910B

Abstract

A method of cleaning comprising the steps of: the reactor is transferred among the liquid injection station, the collection station and the signal injection station. And injecting a cleaning solution into the reactor at the liquid injection station. Collecting the magnetic particle combination in the reactor to the inner side wall of the reactor at the collecting station, and extracting waste liquid from the reactor injected with the cleaning liquid at the liquid absorbing station. And the number of the liquid injection stations is smaller than that of the liquid suction stations, and a signal reagent for measuring an optical signal is injected into the reactor which extracts the waste liquid at the signal injection station. The number of the liquid injection stations is smaller than that of the liquid suction stations, so that the number of parts corresponding to the liquid suction stations and used for injecting the cleaning liquid is reduced, the structure and the parts of the device for implementing the cleaning method are simplified and optimized, the size of the device for implementing the cleaning method is small, and the manufacturing cost is reduced.

Description

Cleaning method

Technical Field

The invention relates to the technical field of in-vitro diagnosis, in particular to a cleaning method.

Background

Luminescence immunoassay is based on immunological reaction of antigen-antibody combination, uses enzyme, luminescent agent and other substances to mark antigen-antibody, and analyzes the content of analyte in sample by linking light signal with analyte concentration through luminescence reaction.

In the washing separation (sometimes referred to as washing) process, firstly, magnetic particles (usually, the main component of a magnetic particle reagent component) are used as a solid phase carrier to capture and bind a target analyte in a sample, then the magnetic particles directly or indirectly bound with the target analyte are collected on the inner side wall of a reaction cup through magnetic force, and after a washing solution is injected and waste liquid is extracted for multiple times, free markers and other interfering impurities which are not bound on the magnetic particles are finally removed, so that signal measurement is carried out on antigen-antibody conjugates (i.e. magnetic particle conjugates) which are connected on the magnetic particles. For the traditional cleaning method, the cleaning efficiency is low or the cleaning effect is poor, and meanwhile, the structure of a device for executing the cleaning method is complex and large.

Disclosure of Invention

The invention solves a technical problem of how to simplify the structure of the device for implementing the cleaning method and improve the cleaning efficiency.

A method of cleaning comprising the steps of:

transferring the reactor among a liquid injection station, a collection station and a signal injection station;

injecting a cleaning solution into the reactor at the liquid injection station;

collecting the magnetic particle combination in the reactor to the inner side wall of the reactor at the collecting station, and extracting waste liquid from the reactor injected with the cleaning liquid at the liquid absorbing station;

and the number of the liquid injection stations is smaller than that of the liquid suction stations, and a signal reagent for measuring an optical signal is injected into the reactor which extracts the waste liquid at the signal injection station.

In one embodiment, the reactor is driven by the same turntable to be transferred among the liquid injection station, the collection station and the signal injection station.

In one embodiment, a cleaning solution is injected into the reactor by using the liquid injection part, a signal reagent is injected into the reactor by using the signal part, and the liquid injection part and the signal part are fixed on the same bearing plate.

In one embodiment, a liquid absorbing part is adopted to extract waste liquid from the reactor, so that the signal part, the liquid absorbing part and the liquid injecting part respectively correspond to different bearing positions on the turntable.

In one embodiment, the signal elements are formed as elongated needle-like structures.

In one embodiment, the signaling agent is added to the reactor after a complete wash procedure is completed.

In one embodiment, the reactor injected with the cleaning liquid is used for uniformly mixing the suspension in the reactor at the liquid injection station.

In one embodiment, the suspension is mixed by eccentric oscillation.

In one embodiment, cleaning liquid is sequentially injected into at least two reactors in the same liquid injection station, and waste liquid is simultaneously extracted from a plurality of reactors in all liquid absorption stations.

In one embodiment, at least two times of injecting the cleaning liquid into the same reactor are completed in the same injection station.

The number of the liquid injection stations is smaller than that of the liquid suction stations, so that the number of parts corresponding to the liquid suction stations and used for injecting cleaning liquid is reduced, the structure and the parts of the device for implementing the cleaning method are simplified and optimized, the volume of the device for implementing the cleaning method is small, and the manufacturing cost is reduced; and cleaning liquid is sequentially injected into at least two reactors at the same liquid injection station, so that the liquid injection accuracy and repeatability can be ensured, and the cleaning effect is improved.

Drawings

FIG. 1 is a schematic view of an overall assembly structure of a cleaning apparatus according to an embodiment;

FIG. 2 is a schematic view of the structure of FIG. 1 from another perspective;

FIG. 3 is a schematic view of the liquid absorbing member of FIG. 1 after the liquid absorbing member is lifted by the stand;

FIG. 4 is a schematic view of the injection assembly and the signal member of FIG. 1 with portions removed;

FIG. 5 is a schematic view of a portion of the wicking assembly of FIG. 4 with portions removed;

FIG. 6 is a schematic view of a portion of the homogenizing assembly of FIG. 1;

fig. 7 is a block flow diagram of a cleaning method according to an embodiment.

Detailed Description

To facilitate an understanding of the invention, the invention will now be described more fully with reference to the accompanying drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

It will be understood that when an element is referred to as being "secured to" another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present. The terms "inner", "outer", "left", "right" and the like as used herein are for illustrative purposes only and do not represent the only embodiments.

The invention refers to the even mixture in the reactor before cleaning and separating as reactant, the reactant is usually the mixed reactant of the sample and the reagent to be measured or the combination of the sample and the reagent after reaction; a cleaning buffer solution (Wash buffer) injected into the reactor in the cleaning and separating process is called cleaning solution for short, and the injection of the cleaning buffer solution into the reactor is called injection solution for short; the mixture in the reactor after the washing solution is injected is referred to as a waste solution, and the waste solution may be composed of a mixture of the reactant and the washing solution, a mixture of the immune complex after the reaction and the washing solution, and an uncleaned, unbound component, and the like. As can be appreciated by those skilled in the art, in order to achieve more thorough cleaning and separation and minimize the residual of unbound components in the reactants after cleaning and separation, cleaning and separation usually comprises injecting cleaning solution many times and extracting waste liquid in the reactor after injecting the cleaning solution, defining the waste liquid after cleaning by injecting the cleaning solution, collecting magnetic particle conjugates and extracting the injected cleaning solution for the first time as first-order cleaning, defining the waste liquid after cleaning by injecting the cleaning solution, collecting magnetic particle conjugates and extracting the injected cleaning solution for the second time as second-order cleaning … and defining the cleaning solution injected the nth time, collecting magnetic particle conjugates and absorbing the waste liquid as nth-order cleaning. Each wash separation typically comprises 2-6 wash stages. In some immunoassays, there is a step of collecting magnetic particle combination in advance and extracting non-combined reactant in the reactor in advance before injecting the cleaning liquid for the first time for the reactant in the reactor to be cleaned and separated, for convenience of description, the step of extracting non-combined reactant in the reactor without injecting the cleaning liquid for the second time is defined as pre-imbibition of cleaning, the pre-imbibition is not calculated in the range of N-step cleaning of cleaning, and the imbibition or waste liquid absorption of the invention refers to the absorption of waste liquid in the reactor after injecting the cleaning liquid unless otherwise specified. According to different reaction methods, such as a one-step method, a two-step method and a three-step method, each test item can be correspondingly cleaned and separated for 1-3 times in the whole reaction process, and each cleaning comprises 2-6 steps of cleaning.

Referring to fig. 1 to 5, an immunoassay analyzer according to an embodiment of the present invention includes a cleaning apparatus 10, the cleaning apparatus 10 is used for cleaning magnetic particle combinations inside a reactor 30, the cleaning apparatus 10 includes a transport assembly 100, a priming assembly 200, a wicking assembly 300, a capture assembly 400, a mixing assembly 500, and a signal assembly 600, wherein both the priming assembly 200 and the wicking assembly 300 may form a cleaning and separating mechanism 20.

In some embodiments, the transfer assembly 100 includes a rotatable carousel 110 for carrying the reactors 30. In addition, the transferring assembly 100 further includes a rotating shaft 120, a shaft sleeve 140, a bearing, and a second actuator 130, the second actuator 130 is fixed on the lower surface of the bottom plate 320 of the wicking assembly 300, and the second actuator 130 may be a stepping motor or the like. The lower end of the rotation shaft 120 is connected to the output shaft of the second driver 130, and the upper end of the rotation shaft 120 passes through the bottom plate 320 and extends upward relative to the upper surface of the bottom plate 320. The turntable 110 is a disc-shaped structure and is fixed at the upper end of the rotating shaft 120, and when the second driver 130 drives the rotating shaft 120 to rotate, the rotating shaft 120 drives the turntable 110 to rotate intermittently. The sleeve 140 is fixed between the base plate 320 and the turntable 110, and the sleeve 140 remains stationary when the second driver 130 is operated. The bearing is sleeved in the shaft sleeve 140, the rotating shaft 120 is matched with the bearing, and the friction force in the rotating process of the rotating shaft 120 can be reduced by arranging the bearing, and the rotating precision of the rotating shaft 120 and the rotating disc 110 is improved.

The rotary table 110 is provided with a plurality of carrying positions at intervals along its circumference for carrying the reactors 30. The support sites may be any structure suitable for supporting the reactor 30, such as holes, slots, brackets, and the like. In one embodiment, the bearing position is a through hole 111, and the through hole 111 penetrates through the upper surface and the lower surface of the turntable 110. The plurality of through holes 111 are arranged at intervals in the circumferential direction of the turntable 110, and the number of the through holes 111 is at least 5. Specifically, it may be 8, 10, 12, etc. The through hole 111 may be a circular stepped hole, the stepped hole is formed by a large hole and a small hole which are coaxially arranged, the diameter of the large hole is larger than that of the small hole, and the bottom wall of the large hole forms a stepped surface of the whole stepped hole. The reactor 30 is substantially cylindrical, the side peripheral surface of the reactor 30 is provided with a protruding ring 31, the protruding ring 31 extends for a set length along the radial direction opposite to the side peripheral surface of the reactor 30, when the reactor 30 is inserted into the through hole 111, the protruding ring 31 on the reactor 30 will contact with the step surface on the step hole to prevent the reactor 30 from falling out of the through hole 111, so the through hole 111 plays a role of bearing the reactor 30, and each through hole 111 can form a bearing position 111a for bearing the reactor 30 on the rotating disc 110. When the turntable 110 drives the turntable 110 to move, the reactor 30 in the through hole 111 will follow the turntable 110 to rotate around the rotating shaft 120.

In some embodiments, the wicking assembly 300 includes a wicking member 310, a base plate 320, a bracket 340, and a first actuator 330. The wicking member 310 is mounted on the support frame 340, and the first actuator 330 is provided on the base plate 320 and connected to the support frame 340, and the first actuator 330 is used to drive the support frame 340 up and down to extend or withdraw the wicking member 310 out of or from the reactor 30.

The liquid absorbing member 310 is used to extract waste liquid to the reactor 30 into which the cleaning liquid has been injected. As mentioned above, the liquid absorbing member 310 is specifically used to extract waste liquid from the reactor 30 into which the cleaning liquid has been injected, and does not include a pre-absorbing member for pre-absorbing the reactant in the reactor 30. The liquid absorbing member 310 may be an elongated liquid absorbing needle, a pipette or other structure suitable for sucking liquid. The liquid absorbing member 310 corresponds to the carrying position 111a on the rotating disc 110, for example, the orthographic projection of the liquid absorbing member 310 on the rotating disc 110 can fall on the carrying position 111a, and the absolute position of the liquid absorbing member 310 is the liquid absorbing station for extracting the waste liquid from the reactor 30. It should be apparent that the pipetting members 310 are in one-to-one correspondence with the pipetting stations, which are the same in number. The support 340 includes a bridging plate 341, a pushing plate 342, and a supporting plate 343, the supporting plate 343 is horizontally disposed above the turntable 110, and the supporting plate 343 is spaced from the turntable 110 by a reasonable distance in the axial direction of the rotating shaft 120. The wicking member 310 may be secured to the support plate 343. The number N of the liquid absorbing members 310 (N is 2,3,4,5,6,7) is equal to the number N of the cleaning steps of the reactor 30. For example, if 3-stage cleaning is required for each cleaning of the reactor 30, the number of the liquid absorbing members 310 is 3, and the three liquid absorbing members 310 are respectively referred to as a first liquid absorbing member (or a first-stage liquid absorbing member), a second liquid absorbing member (or a second-stage liquid absorbing member), and a third liquid absorbing member (or a third-stage liquid absorbing member); if 4-stage cleaning is required for each cleaning of the reactor 30, the number of the liquid absorbing members 310 is 4, and the four liquid absorbing members 310 are respectively marked as a first liquid absorbing member (or a first-stage liquid absorbing member), a second liquid absorbing member (or a second-stage liquid absorbing member), a third liquid absorbing member (or a third-stage liquid absorbing member), and a fourth liquid absorbing member (or a fourth-stage liquid absorbing member). The number of wicking members 310 and their corresponding wicking sites can be two or more than four, etc. The top pushing plate 342 is vertically arranged, the lapping plate 341 is transversely arranged close to the bottom plate 320, the upper end of the top pushing plate 342 is connected with the supporting plate 343, and the lower end of the top pushing plate 342 is connected with the lapping plate 341.

The first driver 330 includes a screw motor 331 and a first guide rod 332, the first guide rod 332 is vertically disposed and the lower end of the first guide rod 332 is fixed on the bottom plate 320, the upper end of the first guide rod 332 is a free end, and the first guide rod 332 is inserted into the bridging plate 341, so as to achieve the sliding connection between the bridging plate 341 and the first guide rod 332. The pushing plate 342 is provided with a space-avoiding groove 342a, the space-avoiding groove 342a extends along the axial direction of the rotating shaft 120, in short, the space-avoiding groove 342a extends along the vertical direction, the screw shaft 331a of the screw motor 331 is rotatably connected with the bridging plate 341, and meanwhile, the screw shaft 331a is located in the space-avoiding groove 342a and can move relative to the space-avoiding groove 342a, so the space-avoiding groove 342a provides a good space for the movement of the screw shaft 331 a. For example, when the screw shaft 331a of the screw motor 331 rotates clockwise, the rotation of the screw shaft 331a is converted into the upward sliding of the bridging plate 341 relative to the first guide rod 332, and at the same time, the bridging plate 341 brings the pushing plate 342 and the supporting plate 343 to move upward, so that the pipette 310 follows the supporting plate 343 to move upward to exit the reactor 30. When the screw shaft 331a of the screw motor 331 rotates counterclockwise, the rotation of the screw shaft 331a is converted into the downward sliding of the bridging plate 341 relative to the first guide rod 332, and at the same time, the bridging plate 341 drives the pushing plate 342 and the supporting plate 343 to move downward, so that the liquid absorbing member 310 moves downward along with the supporting plate 343 to extend into the reactor 30 to extract the waste liquid.

And the liquid injection assembly is used for injecting cleaning liquid into the reactor. In some embodiments, the injection assembly 200 comprises an injection member 210 and a bearing plate 220, wherein the bearing plate 220 is horizontally disposed above the rotating disc 110, and the bearing plate 220 and the rotating disc 110 are spaced apart from each other at a reasonable distance in the axial direction of the rotating shaft 120. The position of the carrier plate 220 relative to the turntable 110 can be fixed, and of course, the carrier plate 220 can also be connected to the bracket 340 of the liquid suction assembly 300, and the carrier plate 220 can be driven to move up and down by the up-and-down movement of the bracket 340. The injection member 210 is fixed on the carrier plate 220, and may be an elongated injection needle, or may be replaced by a member capable of injecting liquid, such as an injection tube or an injection nozzle. The filling member 210 corresponds to the bearing position 111a on the turntable 110, for example, an orthographic projection of a filling portion of the filling member 210 on the turntable 110 may fall on the bearing position 111a, and an absolute position of the filling member 210 is a filling station for filling the cleaning solution into the reactor 30. The number of the injection members 210 may be one, two, and of course, the number of the injection members 210 may be more than two. It should be noted that, corresponding to the same liquid injection station, no matter how many liquid injection outlets are provided on the liquid injection member corresponding to the liquid injection station, and no matter how many needles, tubes, etc. are included in the liquid injection member, the present invention provides that the number of the liquid injection members is one, that is, each liquid injection station corresponds to one liquid injection member. The plurality of liquid injection parts correspond to the plurality of stations, for example, two liquid injection stations correspond to two liquid injection parts. After the injection member 210 injects the cleaning solution into the reactor 30 at the injection station, the cleaning solution cleans the magnetic particle combination in the reactor 30 to remove the free label and other interfering impurities that are not bound to the magnetic particles.

A catching assembly 400 for collecting the magnetic particle conjugates in the reactor onto the inner sidewall of the reactor before each step of pipetting. In some embodiments, the catching assembly 400 includes a magnetic member 420 and a mounting frame 410, the mounting frame 410 may have a substantially disk shape, the mounting frame 410 is fixed on the shaft sleeve 140 of the transferring assembly 100, a receiving hole 411 is formed in the mounting frame 410, the receiving hole 411 is opened in a side circumferential surface of the mounting frame 410, and a portion of an outer circumferential surface of the receiving hole 411 is recessed along a radial direction of the mounting frame 410 by a set depth. The number of the receiving holes 411 is plural, and the plural receiving holes 411 may be arranged at regular intervals along the axis of the mounting bracket 410. The magnetic member 420 may be a natural permanent magnet, an electromagnet, or the like, the magnetic member 420 is adapted to the shape of the receiving hole 411 and is received in the receiving hole 411, and the outer surface of the magnetic member 420 may be flush with the side circumferential surface of the mounting frame 410. The receiving hole 411 and the magnetic member 420 are located at a collecting station for collecting the magnetic particle combination in the reactor 30 onto the inner sidewall of the reactor 30 before each step of pipetting. When the rotating disc 110 drives the reactor 30 to be located at the collecting station, the reactor 30 will be located within the magnetic force range of the magnetic member 420, and the magnetic particle conjugates in the reactor 30 are collected onto the inner sidewall of the reactor 30 under the action of the magnetic attraction force generated by the magnetic member 420.

The collection station includes a pipetting station. In order to avoid the loss of magnetic particles, the magnetic particle combination in the reactor needs to be carried out under magnetic adsorption when each step of the liquid absorbing component extracts waste liquid, so that each step of the liquid absorbing station needs to be provided with the magnetic component 420, and therefore the liquid absorbing station is also a collecting station at the same time, namely the collecting station comprises the liquid absorbing station. The number of collecting stations is not less than the number of imbibing stations. Specifically, the collection station of each cleaning step can correspond to the liquid suction station one by one, and a plurality of collection stations can also correspond to one liquid suction station. When the collecting station of each cleaning step corresponds to the liquid suction station one by one, the collection of the magnetic particle bonding substances in the reactor 30 and the extraction of the waste liquid in the reactor are completed at the same station; when a plurality of collecting stations of each cleaning stage correspond to one liquid suction station, the magnetic particle combination in the reactor 30 is gradually collected in the plurality of collecting stations, and the collection is continued at the liquid suction station (which is also the last collecting station of the cleaning stage) to finish the extraction of the waste liquid.

The side circumference of the mounting frame 410 is further concavely formed with a sinking groove 412, the sinking groove 412 extends in the vertical direction, the upper end of the sinking groove 412 penetrates through the upper surface of the mounting frame 410, the lower end of the sinking groove 412 penetrates through the lower surface of the mounting frame 410, and the sinking groove 412 corresponds to the position (i.e., the liquid injection station) where the liquid injection member 210 is located.

In some embodiments, the blending assembly 500 includes an attachment plate 510, a drive motor 520, a drive shaft 530, and a load-bearing cartridge 540. The connecting plate 510 is disposed transversely, the bottom plate 320 of the wicking assembly 300 is further provided with a second guide rod 550, the second guide rod 550 is disposed vertically, one end of the second guide rod 550 is fixed on the bottom plate 320 and penetrates through the connecting plate 510, the other end of the second guide rod 550 penetrates through the connecting plate 510 to form a free end, so that the second guide rod 550 is slidably connected with the connecting plate 510, and the connecting plate 510 can slide up and down along the second guide rod 550. The driving motor 520 is disposed on the bottom plate 320 and fixedly connected to the connecting plate 510, and the driving motor 520 and the bottom plate 320 are not fixedly connected, so that the driving motor 520 can be carried on the bottom plate 320 or the driving motor 520 can move upward away from the bottom plate 320. During the process that the lead screw motor 331 drives the bridging plate 341 to ascend along the first guide rod 332, the bridging plate 341 will abut against the connecting plate 510, and when the bridging plate 341 continues to ascend, the bridging plate 341 will carry the connecting plate 510 and the driving motor 520 to ascend along the second guide rod 550. In the process that the lead screw motor 331 drives the lapping plate 341 to descend along the first guide rod 332, the lapping 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 stop moving downwards under the limiting action of the bottom plate 320, and at the moment, the lead screw motor 331 can also drive the lapping plate 341 to continue to descend along the first guide rod 332 until the lapping plate 341 is in contact with the bottom plate 320. A part of the surface of the lapping plate 341 is recessed to form a first limit surface 341a and a second limit surface 341b which are connected in a bending manner, for example, the first limit surface 341a and the second limit surface 341b can be perpendicular to each other, when the lapping plate 341 bears the connecting plate 510, the connecting plate 510 is abutted against the first limit surface 341a and the second limit surface 341b, and the first limit surface 341a and the second limit surface 341b play a limiting role on the connecting plate 510, so that the whole blending assembly 500 is prevented from vibrating in the up-and-down movement process, and the running stability of the blending assembly 500 is improved.

The lower end of the driving shaft 530 is connected with an output shaft of the driving motor 520, the bearing cylinder 540 is fixed at the upper end of the driving shaft 530, the driving shaft 530 and the bearing cylinder 540 can be coaxially arranged, and the driving motor 520 is used for driving the driving shaft 530 to rotate, so that the bearing cylinder 540 rotates along with the driving shaft 530. Referring to fig. 6, a blending hole 541 is formed in the bearing cylinder 540, the reactor 30 can be matched with the blending hole 541, a central axis of the blending hole 541 is parallel to a central axis of the driving shaft 530, that is, a certain eccentricity exists between the blending hole 541 and the driving shaft 530, after the reactor 30 is matched with the blending hole 541, when the driving shaft 530 drives the bearing cylinder 540 to rotate, a suspension containing a magnetic particle compound in the reactor 30 eccentrically vibrates under the action of the eccentricity force, so that the whole suspension is in a good blending state.

When needing the mixing, under the effect of lead screw motor 331, can drive lapping plate 341 top and push away the connecting plate 510 and rise, and then make driving motor 520 and bearing cylinder 540 rise, simultaneously, the heavy groove 412 of seting up on mounting bracket 410 can provide for the motion of bearing cylinder 540 and keep away a space, prevents that mounting bracket 410 from constituting the interference to the motion of bearing cylinder 540, when bearing cylinder 540 rises to a take the altitude and cooperates with reactor 30, lead screw motor 331 stops work. At this time, the driving motor 520 drives the carrying cylinder 540 to generate eccentric oscillation through the driving shaft 530, so that the cleaning liquid in the reactor 30 forms turbulent flow, and under the action of the turbulent flow, the cleaning liquid can effectively clean the magnetic particle combination, thereby removing the free markers and other interference impurities which are not combined on the magnetic particles as much as possible; furthermore, the magnetic particle combinations can be uniformly dispersed in the cleaning solution. After the suspension in the reactor 30 is completely mixed, the lead screw motor 331 drives the lap-joint plate 341 to move downwards, so that the whole mixing assembly 500 moves downwards, and finally the bottom of the reactor 30 is completely separated from the mixing hole 541 on the bearing cylinder 540, i.e. the reactor 30 completely exits from the mixing hole 541; when the turntable 110 needs to drive the reactor 30 to transfer from the liquid injection station to the liquid suction station, the carrying cylinder 540 which is separated from the reactor 30 will not interfere with the rotation of the reactor 30, so that the reactor 30 can be smoothly transferred from the liquid injection station to the liquid suction station.

The number of priming members 210 is less than the number of wicking members 310. For example, the number of the liquid absorbing members 310 is three, the number of the liquid injecting members 210 is one, and correspondingly, the number of the liquid absorbing stations is three, and the number of the liquid injecting stations is one; the number of the liquid suction members 310 is four, and the number of the liquid injection members 210 is two, however, the number of the liquid suction stations is four, and the number of the liquid injection stations is two. Compared with the design that the number of the traditional liquid injection pieces 310 is equal to that of the liquid injection pieces 210, the number of the liquid injection pieces 210 in the above embodiment is less than that of the liquid injection pieces 310, so that the total number of the liquid injection pieces 210 is relatively reduced, the number of fluid devices such as a transmission pipe and an electromagnetic valve connected with each liquid injection piece 210 is reduced, the overall structures of the cleaning device 10 and the immunoassay analyzer are favorably reduced, the volumes and the manufacturing costs of the cleaning device 10 and the immunoassay analyzer are reduced, and the miniaturization design of the cleaning device 10 and the immunoassay analyzer is favorably realized; in addition, the reduction of the injection member 210 also reduces the number of the bearing positions 111a on the turntable 110 corresponding to the injection member 210, and further reduces the volume of the turntable 110, which is also beneficial to the miniaturization design of the cleaning device 10 and the immunoassay analyzer. Meanwhile, the plurality of liquid suction members 310 can simultaneously extract waste liquid from the plurality of reactors 30, which reduces the total washing time of the magnetic particle conjugates, thereby improving the washing efficiency of the washing apparatus 10 and the immunoassay analyzer.

A signal member 600 for injecting a signal agent into the reactor 30 where the cleaning is completed. In some embodiments, the signal element 600 is disposed on the carrier plate 220 of the priming assembly 200, and the signal element 600 may be an elongated needle-like structure. The signal member 600, the liquid injection member 210 and the liquid absorption member 310 all correspond to different carrying positions 111a on the turntable 110 respectively, the absolute position of the signal member 600 is a signal injection position, and the signal member 600 injects a signal reagent into the cleaned reactor 30 at the signal injection position so as to measure an optical signal of the magnetic particle combination in the following process.

In order to move the reactor 30 to be cleaned into and the reactor 30 after cleaning out of the transfer module 100, a transfer position is further provided on the transfer module 100, and the transfer module 100 can transfer the reactor 30 among the transfer position, the liquid injection position and the liquid suction position.

Because of the one-to-one correspondence between the injection of the cleaning solution and the extraction of the waste liquid in the reactor after the injection of the cleaning solution during the cleaning and separation process, it is a common technical implementation manner in the art that the number of the liquid absorbing members 310 is equal to that of the liquid injecting members 210. The number of priming members 210 of the present invention is less than the number of priming members 310 and requires a particular process and method set-up to accomplish this.

Referring to fig. 1 and 7 together, a washing method may be formed by the washing apparatus 10 and the immunoassay analyzer, and the washing method may be performed by the washing apparatus 10 and the immunoassay analyzer. Taking the example that the reactor completes the first-order cleaning, the cleaning method mainly comprises the following steps:

s710, transferring the reactor 30 between the liquid injection station and the collection station;

s720, injecting cleaning fluid into the reactor 30 at a liquid injection station;

s730, collecting the suspended magnetic particle combination in the reactor 30 to the inner side wall of the reactor 30 at a collecting station, and extracting waste liquid from the reactor 30 injected with the cleaning liquid at a liquid suction station;

the number of the liquid injection stations is smaller than that of the liquid suction stations, the cleaning liquid is sequentially injected into the at least two reactors 30 at the same liquid injection station, and the waste liquid is extracted from the reactors 30 simultaneously at all the liquid suction stations.

In some embodiments, the injection and pipetting stations are spaced circumferentially around the same circumference of the carousel 110 such that the carousel 110 moves the reactor 30 in a circular motion between the injection and pipetting stations. The number of the liquid suction stations is equal to the cleaning order of one cleaning of the reactor 30. The number of the liquid injection stations can be one, the number of the liquid suction stations is three, the three liquid suction stations are respectively marked as a first liquid suction station, a second liquid suction station and a third liquid suction station, the first liquid suction piece 310 is positioned at the first liquid suction station, the second liquid suction piece 310 is positioned at the second liquid suction station, and the third liquid suction piece 310 is positioned at the third liquid suction station; the quantity of annotating the liquid station can be two, annotate the liquid station and mark respectively as first notes liquid station, the second annotates the liquid station, the quantity of imbibition station is four, four imbibition stations are marked respectively as first imbibition station, second imbibition station, third imbibition station and fourth imbibition station, first imbibition piece 310 is located first imbibition station, second imbibition piece 310 is located the second imbibition station, third imbibition piece 310 is located the third imbibition station, fourth imbibition piece 310 is located the fourth imbibition station.

To ensure good cleaning performance for a single and the same reactor 30, a complete cleaning process includes at least three-stage cleaning, i.e. three times of injecting cleaning liquid and extracting waste liquid, the following describes the cleaning of a single reactor 30 in the case of three-stage cleaning:

in the first step, the reactor 30 is moved to the rotating disc 110, and the reactor 30 can be pre-collected and pre-absorbed, that is, the unbound reactant in the reactor 30 is first pumped, so that only the magnetic particle binder and the residue that is not cleaned are left in the reactor 30, and then the rotating disc 110 rotates the reactor 30 with only the magnetic particle binder to the liquid injection station. Of course, it is also possible to transport the reactor 30 containing the reactants directly to the injection station without pre-collecting and pre-pipetting the reactor 30. When the reactor 30 reaches the injection station, a cleaning solution is injected into the reactor 30 through the injection member 210 to clean the magnetic particle binder to remove the free label and other interfering impurities not bound to the magnetic particles. The suspension containing the magnetic particle conjugate in the reactor 30 may be mixed with or without the first-stage injection or after the first-stage injection into the reactor 30. During mixing, the mixing component 500 moves upwards to match the reactor 30 with the mixing holes 541 on the bearing cylinder 540, the driving motor 520 drives the bearing cylinder 540 to rotate through the driving shaft 530, the suspension in the reactor 30 generates eccentric oscillation to mix uniformly, the magnetic particle combination is uniformly suspended in the cleaning solution, and the cleaning solution forms a good cleaning effect on the magnetic particle combination in the process of eccentric oscillation. After the blending is completed, the blending assembly 500 moves downwards, and the reactor 30 is completely separated from the blending hole 541 on the bearing cylinder 540, so that the rotating disc 110 drives the reactor 30 to leave the liquid injection station. At this point, the reactor 30 has completed the first injection of cleaning fluid, i.e., the first injection of cleaning fluid.

In the second step, the turntable 110 transfers the reactor 30 filled with the cleaning solution from the filling station to the collecting station or the first liquid suction station, and the magnetic particle combination is gradually collected onto the inner sidewall of the reactor 30 by the magnetic member 420 while the reactor 30 is located at the collecting station. When the collection of the magnetic particle combination in the reactor 30 is completed, the reactor 30 is located at the first liquid suction station. When the collection station is equal to the first imbibition station, i.e., coincides with the first imbibition station, the turntable 110 does not rotate, and when the collection station is more than the imbibition station, the turntable rotates to transfer the reactor 30 to the first imbibition station. The lead screw motor 331 drives the bracket 340 to drive the supporting plate 343 to move downwards, so that the liquid absorbing member 310 moves downwards along with the supporting plate 343 to extend into the reactor 30, and the liquid absorbing member 310 extracts all waste liquid formed by cleaning the magnetic particle combination in the reactor 30, so that only the magnetic particle combination and residue which is not cleaned are left in the reactor 30. After the reactor 30 finishes extracting the waste liquid, the screw motor 331 drives the bracket 340 to drive the supporting plate 343 to move upwards, and the liquid absorbing member 310 moves upwards along with the supporting plate 343 to withdraw from the reactor 30, so that the turntable 110 drives the reactor 30 to leave the liquid absorbing station. At this point, the reactor 30 has completed the first extraction of waste, i.e., the first stage of waste extraction.

Thirdly, the turntable 110 drives the reactor 30 to transfer from the liquid-absorbing station to the liquid-injecting station, and when the reactor 30 arrives at the liquid-injecting station, the related operations in the first step are repeated. At this point, the reactor 30 has completed injecting the cleaning solution for the second time, i.e., the second stage of injecting the cleaning solution is completed. The reactor 30 is typically homogenized during or after the second stage of injecting the cleaning fluid.

Fourthly, the turntable 110 drives the reactor 30 to transfer from the liquid injection station to the collection station or the second liquid suction station, and when the reactor 30 reaches the liquid suction station, the related operations in the second step are repeated. At this point, the reactor 30 has completed the second extraction of waste liquid, i.e., the second extraction of waste liquid.

Fifthly, the turntable 110 drives the reactor 30 to transfer from the liquid suction station to the liquid injection station, and when the reactor 30 reaches the liquid injection station, the related operations in the first step are repeated. At this point, the reactor 30 has completed the third injection of the cleaning solution, i.e., the third injection of the cleaning solution is completed. The third stage of injecting the cleaning solution into the reactor 30 is usually followed by mixing.

Sixthly, the turntable 110 drives the reactor 30 to transfer from the liquid injection station to the collection station or the third liquid suction station, and when the reactor 30 reaches the liquid suction station, the related operations in the second step are repeated. At this point, the reactor 30 has completed a third extraction of waste liquid, i.e., a third stage of waste liquid extraction.

For a single same reactor 30, after a complete cleaning process is completed, that is, after the same reactor 30 completes all the steps of injecting cleaning solution, collecting magnetic particle conjugates and extracting waste liquid, a signal reagent is added into the reactor 30, so as to measure the optical signal of the magnetic particle conjugates subsequently. In one embodiment, the turntable 110 moves the reactor 30 from the pipetting station to the signal injection station, and the signal agent is added to the reactor 30 when the reactor 30 arrives at the signal injection station. Finally, the signal reagent-added reactor 30 is removed from the rotating disk 110. Of course, the reactor 30 with only the magnetic particle conjugates can be cleaned directly out of the rotating disk 110, and the signal reagent can be filled outside the rotating disk 110.

When more than three-stage cleaning is required, it is still possible to perform more than three-stage cleaning of a single and the same reactor 30 in the above-described manner of operation.

For a single same reactor 30, at least two injections of cleaning fluid into the same reactor 30 are performed at the same injection station. When the number of the liquid injection stations is two, for example, in the case that the total number of times of injecting the cleaning liquid is three, the injection of the cleaning liquid in two stages is completed in one of the liquid injection stations, and the injection of the cleaning liquid in the other stage is completed in the other liquid injection station. When the number of the liquid injection stations is only one, that is, the number of the liquid injection members 210 is only one, all the injection cleaning liquids of all the orders in the same reactor 30 are completed in the liquid injection station, for example, in the case that the total number of the injection cleaning liquids is three, the injection cleaning liquid of the first order, the injection cleaning liquid of the second order, and the injection cleaning liquid of the third order are completed in the liquid injection station.

Different orders of pipetting are performed at different pipetting stations for a single, same reactor 30. For example, when the total number of times of extraction waste liquid is the cubic, the total number of imbibition station is the same three, accomplishes first order extraction waste liquid through first imbibition piece at first imbibition station, accomplishes second order extraction waste liquid through second imbibition piece at second imbibition station, accomplishes third order extraction waste liquid through third imbibition piece at third imbibition station.

In some embodiments, the reactors 30 on the carousel 110 may be cleaned simultaneously, and the following description is provided for a case where a plurality of reactors 30 are cleaned in three stages at one filling station:

in the first step, the turntable 110 transports the first reactor to the filling station, and the filling member 210 fills the first reactor with the cleaning solution.

And secondly, the turntable 110 is transported for the second time, the second reactor is transported to the liquid injection station, and the liquid injection piece 210 injects the cleaning liquid into the second reactor.

And thirdly, transferring the rotating disc 110 for the third time, transferring a third reactor to a liquid injection station, and injecting a cleaning liquid into the third reactor by the liquid injection piece 210.

And fourthly, transferring the first reactor, the second reactor and the third reactor to different collecting stations or liquid absorption stations by the fourth transfer of the turntable 110, and simultaneously extracting waste liquid from the three reactors 30 by the three liquid absorption members 310 at different liquid absorption stations. For example, the first liquid-absorbing member extracts waste liquid for a first reactor, the second liquid-absorbing member extracts waste liquid for a second reactor, the third liquid-absorbing member extracts waste liquid for a third reactor, and the first liquid-absorbing member, the second liquid-absorbing member, and the third liquid-absorbing member simultaneously extract waste liquid.

And fifthly, continuously transferring the reactor 30 to a liquid injection station, repeating the operations from the first step to the fourth step, and sequentially moving the reactor 30 which is completely cleaned in the first step out of the rotating disc 110.

In some embodiments, multiple reactors 30 are simultaneously operated at all pipetting stations to draw differing orders of effluent. For example, when the liquid suction stations are three, the liquid suction stations are respectively marked as a first liquid suction station, a second liquid suction station and a third liquid suction station, the reactor 30 located at the first liquid suction station is just in the first-order extraction of waste liquid, the reactor 30 located at the second liquid suction station is just in the second-order extraction of waste liquid, and the reactor 30 located at the third liquid suction station is just in the third-order extraction of waste liquid. Since the liquid absorbing members 310 at the plurality of liquid absorbing stations can simultaneously extract the waste liquid, the waiting time between the reactors 30 can be saved, thereby improving the cleaning efficiency.

In some embodiments, at least two transfers are performed for each cleaning step, and at least two reactors 30 are transferred to the same filling station sequentially for filling of different stages. At least two reactors 30 are sequentially filled with cleaning liquid of different orders at the same filling station. For example, after the first reactor completes the first-order injection of the cleaning solution at the injection station, the second reactor completes the second-order injection of the cleaning solution at the injection station, and the third reactor completes the third-order injection of the cleaning solution at the injection station.

According to the cleaning method, N reactors needing N-order cleaning complete liquid suction of different orders in parallel at N liquid suction stations, wherein at least two reactors complete injection of cleaning liquid of different orders sequentially at the same liquid injection station, so that the cleaning liquid suction efficiency is improved, the structural volume and the cost of liquid injection realization are effectively reduced, the number of liquid injection stations and liquid injection pieces is reduced, the size of a transfer disc is reduced, and the difference of accuracy of liquid injection amount of different orders is reduced, so that the cleaning device and the immunoassay analyzer which are compact in structure, high in testing efficiency and good in performance are favorably realized.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims

1. A cleaning method, comprising the steps of:

injecting a cleaning solution into the reactor at the liquid injection station; and

2. The cleaning method according to claim 1, wherein the reactor is moved between the liquid injection station, the liquid suction station and the signal injection station by the same turntable.

3. The cleaning method according to claim 2, wherein the cleaning solution is injected into the reactor by using an injection member, the signal agent is injected into the reactor by using a signal member, and the injection member and the signal member are fixed on the same carrier plate.

4. The cleaning method according to claim 3, wherein a liquid absorbing member is used to extract waste liquid from the reactor, and the signal member, the liquid absorbing member and the liquid injecting member are respectively corresponding to different carrying positions on the turntable.

5. The cleaning method of claim 3, wherein the signal element is an elongated needle-like structure.

6. The method of claim 2, wherein the signal reagent is added to the reactor after a complete cleaning process is completed.

7. The cleaning method according to claim 1, wherein the reactor into which the cleaning liquid is injected is subjected to the liquid injection station to uniformly mix the suspension in the reactor.

8. The cleaning method according to claim 7, wherein the suspension is mixed by eccentric oscillation.

9. The cleaning method according to claim 1, wherein a cleaning liquid is sequentially injected into at least two of the reactors at a same liquid injection station, and waste liquid is simultaneously extracted from a plurality of the reactors at all the liquid suction stations, respectively.

10. The cleaning method according to claim 1, wherein at least two times of injecting the cleaning solution into the same reactor are performed in the same injection station.