WO2020041923A1

WO2020041923A1 - Cleaning method and sample analysis method

Info

Publication number: WO2020041923A1
Application number: PCT/CN2018/102453
Authority: WO
Inventors: 张震; 何太云
Original assignee: 深圳迎凯生物科技有限公司
Priority date: 2018-08-27
Filing date: 2018-08-27
Publication date: 2020-03-05

Abstract

A cleaning method comprises the following steps: injecting a cleaning fluid into a reactor (20) at a first station (401) (S810); adhering, onto the reactor (20), a magnetic particle combined substance (21) in the reactor (20) at a second station (402), and using a liquid suction member (441) to perform waste liquid suction on the reactor (20) (S820); using a bearing assembly (410) to drive the reactor (20) to reciprocally move between the first station (401) and the second station (402), such that cleaning liquid injection and waste liquid suction are alternately performed on the reactor (20), wherein the same liquid suction member (441) performs waste liquid suction on the same reactor (20) (S830); and and moving the reactor (20) out of a cleaning position of the bearing assembly (410) once cleaning liquid injection and waste liquid suction have been performed on the reactor (20) a preset number of times, and continuing to move, along with the bearing assembly (410), a reactor (20) on which cleaning liquid injection and waste liquid suction have not been performed the preset number of times, and moving, to the cleaning position (412) of the bearing assembly (410), a new reactor (20) on which cleaning liquid injection and waste liquid suction have not yet been performed (S840).

Description

Cleaning method and sample analysis method

Technical field

The invention relates to the technical field of in vitro diagnostics, in particular to a cleaning method and a sample analysis method including the cleaning method.

Background technique

Fully automated immunoassay uses the immunological reaction based on the combination of antigen and antibody to label the antigen antibody with enzyme label, lanthanide label or chemiluminescent agent, and then amplifies the light signal or electrical signal with the analyte through a series of cascade amplification reactions Concentration, etc., to analyze the antigen or antibody to be tested in human samples.

In the measurement and analysis, Bound-free (hereinafter referred to as cleaning) is involved in the measurement, that is, the magnetic force is used to capture the bound magnetic particle, the complex of the antigen and the labeled antibody (that is, the test object), and finally the Bound free labels and other interfering impurities.

Generally, the conventional cleaning method and sample analysis method may affect the cleaning effect and analysis performance due to the formation of contamination to the next reaction container during the pumping of waste liquid, or due to the adsorption of the test object.

Summary of the Invention

According to various embodiments of the present application, a sample analysis method capable of improving cleaning effect and analysis performance is provided.

A cleaning method includes the following steps:

Inject the cleaning solution into the reactor at the first station;

Adsorbing the magnetic particle conjugate in the reactor at the second station on the inner side wall of the reactor, and sucking the waste liquid to the reactor through the liquid absorbing member;

The carrier component drives the reactor to circulate back and forth between the first and second stations, so that the reactor alternately performs treatment of injecting cleaning liquid and sucking waste liquid, and the same reactor sucks waste liquid through the same suction member ;and

Move the reactor that has reached the set round to inject the cleaning liquid and suck the waste liquid and remove it from the cleaning position of the carrier component, and the reactor that has not reached the set round to inject the cleaning liquid and suck the waste liquid to treat it, continue to follow the carrier component , And move the new reactor, which has not been injected with cleaning liquid and pumping waste liquid, into the cleaning position of the bearing component.

A sample analysis method includes the steps in any one of the cleaning methods described above.

Details of one or more embodiments of the invention are set forth in the accompanying drawings and description below. Other features, objects, and advantages of the invention will be apparent from the description, the drawings, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to better describe and illustrate embodiments and / or examples of those inventions disclosed herein, reference may be made to one or more drawings. The additional details or examples used to describe the drawings should not be considered as limiting the scope of any of the disclosed inventions, the presently described embodiments and / or examples, and the best mode of these inventions as currently understood.

FIG. 1 is a schematic plan view of an immune analyzer according to an embodiment; FIG.

Figure 2 is a schematic diagram of a magnetic particle conjugate suspended in a reactor;

Figure 3 is a schematic diagram of magnetic particle conjugate adsorption on the reactor;

4 is a schematic top view of the bearing block in FIG. 1;

5 is a perspective view of a first example cleaning device in FIG. 1;

6 is a perspective view of a second example cleaning device in FIG. 1;

7 is a flowchart of a cleaning method according to an embodiment;

FIG. 8 is a flowchart of a sample analysis method according to an embodiment.

detailed description

In order to facilitate understanding of the present invention, the present invention will be described more fully with reference to the accompanying drawings. The drawings show a preferred embodiment of the invention. However, the invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough understanding of the present disclosure.

It should be noted that when an element is referred to as being “fixed to” another element, it may be directly on the other element or there may be a centered element. When an element is considered to be "connected" to another element, it can be directly connected to the other element or intervening elements may also be present. The terms "inside", "outside", "left", "right" and similar expressions used herein are for illustrative purposes only and are not meant to be the only implementations.

1 to 4, an immune analyzer 10 according to an embodiment of the present invention includes a supply device 100, a storage device 200, an incubation device 300, a cleaning device 400, a measurement device 500, a sampling device 600, a mixing device 700, and a transfer device. . The supply device 100 sorts and arranges the empty and clean reactors 20 for transfer and grabbing. The storage device 200 stores the sample and the target reagent, the sampling device 600 adds the sample and the target reagent to the reactor 20, the mixing device 700 mixes the sample and the target reagent in the reactor 20, and the incubation device 300 holds the sample The reactor 20 is heated and incubated with the target reagent, the cleaning device 400 cleans the reactor 20 heated by the incubation device 300, and the measurement device 500 tests the reactor 20 containing the signal reagent and the washed magnetic particle conjugate 21 . The transfer device transfers the reactor 20 between the supply device 100, the incubation device 300, the cleaning device 400, and the measurement device 500. For example, the transfer device can transfer the reactor 20 on the supply device 100 to the incubation device 300, or the incubation device The reactor 20 on 300 is transferred to the cleaning device 400, or the reactor 20 on the cleaning device 400 is mounted on the measurement device 500.

In some embodiments, the supply device 100 includes a feed sorting mechanism 100, a supply slide 120, and a supply tray 130. The feed sorting mechanism 100 can be located above the storage device 200, so that the space of the whole machine can be fully utilized, and the mechanism of the whole machine is more compact; the supply slide 120 is connected between the feed sorting mechanism 100 and the supply tray 130. The feed sorting mechanism 100 includes a silo and a sorting unit. The silo is used to store unused clean reactors 20. The sorting unit arranges the scattered reactors 20 from the silo in an orderly manner. The supply chute 120 transports the reactors 20 arranged in order to the supply tray 130. The supply tray 130 is used to buffer the sorted reactors 20. The reactors 20 may be distributed along the circumferential interval of the supply tray 130. The supply tray 130 may Rotate so that the transfer device transfers the reactor 20 on the supply tray 130 into the incubation device 300 at a designated appropriate position.

In some embodiments, the storage device 200 includes a rotating disk 210 on which a sample position and a reagent position are set, for placing a sample container and a reagent container and transferring a sample and a target reagent to the sampling position 211. The sample container is used to hold the sample to be tested, and the sample contains the target detection substance such as the target antibody and antigen to be tested. Reagent containers are used to hold target reagents. A test item usually includes reagent components such as magnetic particle reagents, enzyme-labeled reagents, and diluents. Target reagents with different components can be packed in different reagent containers. The sampling position 211 is provided on the storage device 200 and is used by the sampling device to suck a sample from a sample container and a target reagent from a reagent container through the storage device 200. The storage device 200 may further include a barcode scanner. The barcode scanner is used to identify the barcode information on the sample container and the reagent container so that the sampling device can accurately sample it. In order to make the overall structure compact and reduce costs, the barcode scanner adopts a fixed design. The storage device 200 may further include a refrigerator. In order to store the target reagent online for a long time, the refrigerator may refrigerate the reagent in the reagent container.

In some embodiments, the sampling device 600 includes a sampling member, which is used to suck a sample and a target reagent, and the sampling member includes a sampling steel needle. Of course, the sampling member may also include a disposable suction nozzle and the like. The sampling piece can have three degrees of freedom of linear movement in the three-dimensional space, that is, up, down, left and right, and forward and backward, of course, there can also be degrees of freedom of rotation. In order to improve the compactness of the whole machine and reduce the cost, the sampling steel needle can be used to suck both the sample and the target reagent, that is, the sampling steel needle can be used to suck both the sample and the target reagent. The sampling device 600 may further include a cleaning station 610, which is located beside the rotating disk 210 on the storage device 200, the cleaning station 610 is located on the movement track of the sampling piece, and the cleaning station 610 is used to clean the sampling piece. For example, when sampling After the steel needle sucks the sample from the sample container, the sampling steel needle after the sample can be washed in the cleaning station 610, and then the cleaned sampling steel needle can suck the target reagent from the reagent container. The cleaning station 610 can effectively prevent Contamination during sample and target reagent aspiration.

In some embodiments, the incubation device 300 includes a temperature control unit and an incubation block 310, and the incubation block 310 is fixedly disposed, so that a driving mechanism for driving the movement of the incubation block 310 can be omitted, and the space required for the movement of the incubation block 310 is also saved. It can also improve the compactness of the whole machine and reduce costs. The incubation block 310 may be an aluminum block or a copper block having excellent thermal conductivity. The temperature control unit is used to provide a constant temperature environment and reduce heat loss. The temperature control unit may include a heat insulator, a heater, a temperature sensor, a temperature control circuit, and the like. The incubation block 310 has an incubation position 311, and the incubation position 311 is used for accommodating the reactor 20. According to the actual test speed, the number of incubation positions 311 can be 5 to 100, and all incubation positions 311 can be arranged in a matrix, that is, an arrangement of multiple rows and multiple columns.

In some embodiments, for the sampling positions 211 set on the storage device 200, the sampling positions 211 may be distributed on a straight line 30 where a certain diameter on the storage device 200 is located, and a part of the incubation positions 311 on the incubation block 310 is located at On the straight line 30, the straight line 30 coincides with the movement trajectory of the sampling element; that is, the movement trajectory of the sampling element covers the sampling position 211 and a part of the incubation position 311 on the incubation block 310. After the sampler sucks the sample or the target reagent, so that the sampler moves in the shortest path and the shortest time to directly above the reactor 20 on the incubation block 310, thereby increasing the sample of the reactor 20 on the incubation block 310 and Filling efficiency of target reagent.

In some embodiments, the mixing device 700 is located within the movement range of the transfer unit or can be moved to the movement range of the transfer unit by horizontal movement. The mixing device 700 receives and carries the reactor 20 transferred from the transfer unit, and at least one reactor position is set thereon for placing the reactor 20 to be mixed, and the reactants in the reactor 20 are mixed. The mixing device 700 performs ultrasonic mixing, partial rotation or shaking mixing on the reactor 20 after each time the sample and the target reagent are filled. When an independent filling station is provided, the mixing device 700 and the filling station can be integrated together to form a filling mixing device, which has a simpler and more compact structure.

In some embodiments, the reactor on the mixing device 700 is located under the motion trajectory of the sampling member, and the sampling member can fill the sample and target reagent on the reactor position on the mixing device 700.

In addition to the above functions and functions, the mixing device 700 of the present embodiment can also receive the reactor 20 that needs to be mixed after the signal reagent is added. The transfer unit transfers the reactor 20 after the cleaning and separation and the signal reagent is added to the mixing device 700, and the mixing device 700 completes the mixing of the reactor 20 after the signal reagent is added, so that the cleaning device can be omitted. The mixing unit is set on the 400, which further simplifies the structure and components, reduces the volume and the cost, and also improves the reliability of the whole machine.

The reactor 20 containing the sample and the target reagent can be incubated in the incubation device 300 for about 5-60 minutes. After the incubation is completed, the magnetic particles, the substance to be measured, and the labeling reagent in the reactor 20 react with each other and combine to form a magnetic particle binding. The substance 21, the labeling reagent that did not participate in the reaction, did not bind to the magnetic particles and was free in the suspension of the reactor 20. The cleaning device 400 cleans the magnetic particle conjugate 21 to remove free labeling reagents and other unreacted non-bound components.

1 to FIG. 6 at the same time. In some embodiments, the cleaning device 400 has an initial station 403, a first station 401, and a second station 402. The cleaning device 400 includes a bracket 450, a bearing assembly 410, and a magnetic assembly 420. A liquid injection component 430 and a liquid suction component 440. All four of the bearing component 410, the magnetic suction component 420, the liquid injection component 430, and the liquid suction component 440 are disposed on the bracket 450. The carrier assembly 410 is used to drive the reactor 20 between the initial station 403, the first station 401, and the second station 402, and the magnetic attraction assembly 420 is used to adsorb the reactor 20 at the second station 402. The magnetic particle combination 21 and the liquid injection assembly 430 include a liquid injection member 431, which is used to inject a cleaning solution into the reactor 20 at the first station 401. The liquid suction assembly 440 includes a liquid suction member 441 capable of one-to-one correspondence with the cleaning positions 412. The liquid suction member 441 is configured to suck waste liquid from the reactor 20 at the second station 402. The liquid injection member 431 may be a liquid injection needle, a liquid injection tube, or a liquid injection nozzle, which is suitable for injecting liquids. Similarly, the liquid suction member 441 may also be a liquid injection needle, a liquid suction tube, or a liquid injection nozzle suitable for aspiration of liquid. component. The setting of the first station 401 and the second station 402 in this embodiment can avoid the injection of the cleaning liquid and the absorption of the waste liquid during the cleaning process at the same station, which is not only conducive to the resuspension of the magnetic particle combination 21 after the liquid injection. , Can also reduce cleaning residues, thereby improving the cleaning effect and final analysis performance.

5 and FIG. 6 at the same time, the bearing assembly 410 is slidably disposed on the bracket 450 and can slide between the initial station 403, the first station 401, and the second station 402. At least one cleaning station is provided on the carrier assembly 410 412, the cleaning position 412 is used to place the reactor 20. In some embodiments, the bearing assembly 410 includes a bearing block 411, the bearing block 411 is integrally formed, and the cleaning position 412 is an accommodation hole on the bearing block 411. Of course, the number of the bearing blocks 411 may be multiple, and the cleaning position 412 may also be Other clamping structures are used as long as the reactor 20 can be moved with the bearing block 411. The bracket 450 may be provided with a slide rail 451. The slide rail 451 is a linear slide rail 451, and the load-bearing block 411 slides and cooperates with the slide rail 451. Therefore, the load-bearing assembly 410 is at the initial station 403, the first station 401, and the second station. The movement trajectory between the stations 402 is a straight line.

The bearing assembly 410 further includes a belt transmission unit, which is mounted on the bracket 450. The belt transmission unit is used to drive the bearing block 411 to move along the slide rail 451. In some embodiments, the belt transmission unit includes a stepper motor 414, a driving wheel 415, a driven wheel 416, and a timing belt 417. The stepping motor 414 is fixed on the bracket 450, the driving wheel 415 is disposed on the output shaft of the stepping motor 414, the driven wheel 416 is rotatably disposed on the bracket 450, and the timing belt 417 is set between the driving wheel 415 and the driven wheel 416. The bearing block 411 is fixedly connected to the timing belt 417. When the stepping motor 414 rotates, the timing belt 417 pulls the bearing block 411 to move along the slide rail 451 to realize the movement of the bearing block 411 between the initial station 403, the first station 401, and the second station 402. Therefore, The movement trajectory of the bearing assembly 410 between the initial station 403, the first station 401, and the second station 402 is a straight line. In other embodiments, the belt transmission unit may also be replaced with a rack and pinion mechanism, and the movement trajectory of the carrier assembly between the initial station 403, the first station 401, and the second station 402 may be circular or Triangles, etc.

In some embodiments, the loading block 411 of the bearing assembly 410 is further provided with a filling position 413. The filling position 413 has the same structure as the cleaning position 412, and the filling position 413 is located beside the cleaning position 412. 413 is used for the reactor 20 where the magnetic particle conjugate 21 needs to be added with a signal reagent after the cleaning is completed. The liquid injection assembly 430 further includes an injection member 432. When the carrier assembly 410 is at the first station 401, the injection member 432 can inject the signal reagent into the reactor 20 located at the filling station 413. Therefore, in addition to the cleaning function, the cleaning device 400 may also have a function of adding a signal reagent to the reactor 20 to achieve the "one-machine-dual-use" effect, and reduce the manufacturing cost on the basis of improving the compactness of the entire machine.

Referring to FIG. 5, in some embodiments, the accommodating holes (washing positions 412) on the bearing block 411 are arranged in a straight line (denoted as a first straight line), and the extending direction of the straight line is perpendicular to the sliding direction of the bearing block 411. Similarly, the liquid injection members 431 are arranged in a straight line (denoted as a second straight line), and the liquid injection members 431 correspond to the accommodation holes on the bearing block 411 one by one. The liquid absorbing members 441 are arranged in a straight line (referred to as a third straight line), and the liquid absorbing members 441 correspond to the receiving holes on the supporting block 411 one by one. The first straight line, the second straight line, and the third straight line are spatially parallel to each other, that is, the straight lines in which the accommodation hole, the liquid injection member 431, and the liquid suction member 441 are arranged are parallel to each other.

Referring to FIG. 5, in some embodiments, the magnetic attraction assembly 420 includes a mounting frame 421 and at least one permanent magnet unit 422. The mounting frame 421 is provided with a receiving cavity 421 a, and the permanent magnet unit 422 is received in the receiving cavity 421 a. The mounting frame 421 supports and protects the permanent magnet unit 422. When the bearing assembly 410 is at the second station 402, all the permanent magnet units 422 have an orthographic projection on the bearing block 411 of the bearing assembly 410, and are in a direction (Y-axis direction) perpendicular to the sliding direction (X-axis direction) of the bearing block 411. Above, that is, in the arrangement direction of the cleaning positions 412, the orthographic projections of all the permanent magnet units 422 cover all the cleaning positions 412. When the number of the permanent magnet units 422 is only one, the orthographic projection of the one permanent magnet unit 422 on the bearing assembly 410 can cover all the cleaning positions 412; when the number of the permanent magnet units 422 is greater than one, there is at least one permanent magnet The orthographic projection of the unit 422 on the carrier assembly 410 may cover at least two cleaning positions 412. For example, in a direction perpendicular to the sliding direction of the bearing block 411, when the permanent magnet unit 422 and the bearing block 411 are symmetrically disposed with respect to the slide rail 451, the length of the permanent magnet unit 422 is greater than or equal to the length of all the cleaning positions 412, so that Ensure that the orthographic projection covers all the cleaning positions 412, and further ensure that the magnetic field lines of the permanent magnet unit 422 can cover the reactors 20 located in different cleaning positions 412, so that the magnetic particle combination 21 in all the reactors 20 can form an effective adsorption. At the same time, the magnetic field lines of the permanent magnet unit 422 can be evenly distributed on each cleaning position 412, avoiding placing multiple magnets in multiple cleaning positions 412, and preventing the uneven magnetic distribution of different cleaning positions 412 and the influence of adjacent cleaning positions 412 on each other. Problem, further avoiding the difference in cleaning effect of multiple cleaning positions 412, and improving the cleaning effect and analysis performance.

In some embodiments, the reactor 20 can be treated at the same station for injecting cleaning liquid and sucking waste liquid, that is, the reactor 20 does not need to reciprocate between the first station 401 and the second station 402; meanwhile, The same reactor sucks the waste liquid through the same liquid suction member 441. On this basis, the magnet unit 422 disposed near the station has an orthographic projection on the supporting block 411 of the supporting component 410, and in the arrangement direction of the cleaning position 412 (in the Y-axis direction), the orthographic projection covers all the cleaning positions. 412. The magnetic field lines of the permanent magnet unit 422 can be evenly distributed on each cleaning position 412, which can also prevent the problem of uneven magnetic distribution of different cleaning positions 412 and the mutual influence of adjacent cleaning positions 412, and further avoid the cleaning effect of multiple cleaning positions 412. Differences to improve cleaning and analytical performance.

Referring to FIG. 6, the permanent magnet unit 422 may include a permanent magnet 422 a. In order to provide a stronger and more stable magnetic field environment, the permanent magnet 422 a may be a neodymium iron boron magnet or an aluminum-nickel-cobalt alloy magnet. One of the poles of the permanent magnet 422a is disposed toward the bearing block 411 on the bearing assembly 410, for example, the N pole of the permanent magnet 422a is disposed toward the bearing block 411, or the S pole of the permanent magnet 422a is disposed toward the bearing block 411, and the permanent magnet 422a is N The length of the pole or S pole in the Y-axis direction is not less than the total length occupied by each cleaning bit 412 in the Y-axis direction. In order to further enhance the magnetic field strength of the permanent magnet unit 422, the time for the magnetic particle combination 21 in the reactor 20 to adsorb and accumulate on the inner wall surface of the reactor 20 is reduced, and the magnetic particle combination 21 is prevented from being sucked away during the process of sucking the waste liquid To improve the cleaning efficiency and cleaning effect of the cleaning device 400, referring to FIG. 5, the permanent magnet unit 422 may include two permanent magnets 422a. Two permanent magnets 422a are stacked next to each other. The polarity of the magnetic poles of the two permanent magnets 422a facing the bearing block 411 is just opposite. For example, the N pole of one permanent magnet 422a is arranged toward the bearing block 411, and the other permanent magnet 422a is opposite. The S pole is disposed toward the bearing block 411. The magnetic force near the position where the two permanent magnets 422 a are superimposed is the largest. Therefore, the magnetic particle combination 21 in the reactor 20 is adsorbed on the inner side wall of the reactor 20, and the magnetic particle combination 21 is on the inner side wall of the reactor 20. The adsorption position on the reactor is kept at a certain distance from the bottom wall of the reactor 20.

The liquid suction assembly 440 further includes a slide plate 442, a first beam 443, and a belt transmission unit 444. The slide plate 442 is vertically arranged. The slide plate 442 and the bracket 450 slide to cooperate with each other. The belt transmission unit 444 can drive the slide plate 442 to slide up and down relative to the bracket 450. The first cross beam 443 is connected to the sliding plate 442, and the first cross beam 443 is disposed laterally. Similarly, the belt transmission unit 444 includes a stepping motor 444b, a driving wheel 444c, a driven wheel 444d, and a timing belt 444a. The stepping motor 444b is fixed on the bracket 450, the driving wheel 444c is disposed on the output shaft of the stepping motor 444b, the driven wheel 444d is rotationally disposed on the bracket 450, and the timing belt 444a is sleeved between the driving wheel 444c and the driven wheel 444d. The slider 442 is fixedly connected to the timing belt 444a. When the stepping motor 444b rotates, the timing belt 444a pulls the sliding plate 442 up and down along the bracket 450.

Referring to FIG. 5, in some embodiments, the liquid injection member 431 and the liquid absorption member 441 are both disposed on the first beam 443, that is, the first beam 443 can drive the liquid injection member 431 and the liquid absorption member 441 to move up and down. When the loading block 411 drives the reactor 20 to move to the first station 401, the liquid injection member 431 is located directly above the reactor 20. At this time, the sliding plate 442 drives the first beam 443 to move downward, and the liquid injection member 431 extends into The cleaning liquid is injected into the reactor 20. After the cleaning liquid is injected, the sliding plate 442 drives the first beam 443 to move upward to move the liquid injection member 431 out of the reactor 20. When the loading block 411 drives the reactor 20 to move to the second station 402, the liquid-absorbing member 441 is located directly above the reactor 20. At this time, the sliding plate 442 drives the first beam 443 to move downward to extend the liquid-absorbing member 441. The waste liquid is sucked into the reactor 20, and after the waste liquid is sucked, the sliding plate 442 drives the first beam 443 to move upward to make the liquid-absorbing member 441 extend and away from the reactor 20.

Referring to FIG. 6, in some embodiments, only the liquid absorbing member 441 is disposed on the first beam 443, and at the same time, the liquid injection assembly 430 further includes a second beam 433, the second beam 433 is fixed on the bracket 450, and the liquid injecting member 431 It is arranged on the second beam 433. That is, the first beam 443 can only drive the liquid-absorbing member 441 up and down. Therefore, when the loading block 411 drives the reactor 20 to the first station 401, the liquid-injecting member 431 is located directly above the reactor 20. At this time, The liquid injection member 431 does not move up and down relative to the reactor 20, and the liquid injection member 431 directly injects the cleaning liquid into the reactor 20. When the loading block 411 drives the reactor 20 to move to the second station 402, the liquid-absorbing member 441 is located directly above the reactor 20. At this time, the first beam 443 can move up and down to drive the liquid-absorbing member 441 into or out. Out of the reactor 20.

The cleaning device 400 may further include a mixer, which is used to cause the reaction mixture in the reactor 20 to oscillate. For example, the mixer may be installed on the bracket 450 and corresponding to the first station 401. When the bearing block 411 drives After the reactor 20 moves to the first station 401 and the liquid injection member 431 injects the cleaning liquid into the reactor 20, the mixer oscillates the reactor 20 through the bearing block 411. Under the action of the vibration vortex, the magnetic particles are made The conjugate 21 is uniformly dispersed and suspended in the reaction mixture, thereby improving the cleaning effect of the magnetic particle conjugate 21. For another example, the mixer is installed on the bearing component 410, that is, the mixer is directly integrated on the bearing block 411, so that the mixer can directly oscillate the reactor 20.

Referring to FIGS. 4 to 6, when the cleaning device 400 is operating, a description is given by taking only three cleaning positions 412 arranged in a straight line and without placing the reactor 20 on the supporting block 411 as an example, and recorded as the first cleaning position 412 a, The second cleaning bit 412b and the third cleaning bit 412c. When the bearing block 411 is at the initial station 403, the transfer device adds the reactor 20 to the first cleaning station 412a only. Next, the bearing block 411 moves from the initial station 403 to the first station 401 along the slide rail 451 and stops. At this time, the liquid injection member 431 injects the cleaning solution into the reactor 20 in the first cleaning station 412a, and injects the cleaning solution. In the process of the liquid, the cleaning liquid has a certain impact force and flow rate, so that the cleaning liquid can well rinse the magnetic particle combination 21 suspended in the reactor 20. Then, the bearing block 411 moves from the first station 401 to the second station 402 along the slide rail 451 and stops. At this time, before sucking the waste liquid, the magnetic assembly 420 adsorbs the magnetic particle combination 21 to the reactor 20 On the inner side wall, the magnetic particle conjugate 21 in a suspended state is adsorbed onto the reactor 20 during swimming, and the magnetic particle conjugate 21 is also washed by the cleaning solution. After all the magnetic particle conjugates 21 are adsorbed on the reactor 20, the liquid absorbing member 441 moves downward to extend into the reactor 20, and the liquid absorbing member 441 sucks the waste liquid, which will be the reactor on the first cleaning position 412a. The liquid absorbing member 441 that sucks the waste liquid is referred to as a first liquid absorbing member 441a. Since the magnetic particle conjugate 21 has been adsorbed, the liquid absorbing member 441 cannot suck the magnetic particle conjugate 21 away. It is defined that the reactor 20 completes the first injection of the cleaning liquid and the first suction of the waste liquid as the first round of cleaning, completes the second injection of the cleaning liquid and the second suction of the waste liquid as the second round of cleaning, and so on. Therefore, when the reactor 20 moves from the first station 401 to the second station 402, the reactor 20 will complete one round of cleaning.

After the reactor 20 in the first cleaning position 412a completes a round of cleaning, it continues to directly return the load block 411 from the second station 402 to the initial station 403. At this time, the reactor 20 on the first cleaning position 412a remains. Meanwhile, the transfer device only adds the reactor 20 to the second cleaning position 412b, so the reactor 20 is placed on the first cleaning position 412a and the second cleaning position 412b on the load block 411. Next, the bearing block 411 drives the two reactors 20 to move from the initial station 403 to the first station 401 and stops. At this time, the two liquid injection parts 431 respectively inject the cleaning liquid into the two reactors 20, and the cleaning liquid The cleaning of the magnetic particle conjugate 21 is as described above and will not be repeated. Then, the bearing block 411 moves from the first station 401 to the second station 402 along the slide rail 451 and stops. At this time, the magnetic attraction module 420 adsorbs the magnetic particle combination 21 in the two reactors 20, and the adsorption is completed. The last two liquid-absorbent members 441 respectively suck the waste liquid. It is particularly emphasized that, for the reactor 20 in the first cleaning position 412a, the liquid absorbing member 441 is still the first liquid absorbing member 441a used in the first cleaning, that is, the same is used for the reactor 20 in the same cleaning position 412. The liquid absorbing member 441 sucks up waste liquid. For the reactor 20 in the second cleaning position 412b, the liquid absorbing member 441 for sucking the waste liquid is referred to as the second liquid absorbing member 441b. So far, the reactor 20 in the first cleaning position 412a has completed the second round of cleaning, and the reactor 20 in the second cleaning position 412b has completed the first round of cleaning.

Continue to directly return the carrier block 411 from the second station 402 to the initial station 403. At this time, the reactor 20 in the first cleaning station 412a and the second cleaning station 412b is still retained, and at the same time, the transfer device moves to the third cleaning station. The reactor 20 is added to 412c, so the reactor 20 is placed on the first cleaning position 412a, the second cleaning position 412b, and the third cleaning position 412c on the bearing block 411. Next, the bearing block 411 drives the three reactors 20 to move from the initial station 403 to the first station 401 and stops. At this time, the three liquid injection parts 431 respectively inject the cleaning solution into the three reactors 20. Then, the bearing block 411 moves from the first station 401 to the second station 402 along the slide rail 451 and stops. At this time, the first liquid suction member 441a is still used to suck the waste liquid from the reactor 20 on the first cleaning position 412. At the same time, the second liquid suction member 441b is used to suck the waste liquid from the reactor 20 on the second cleaning position 412, and for the reactor 20 in the third washing position 412c, the liquid suction member 441 for the waste liquid is recorded as the first Three liquid absorbing pieces 441c. It is ensured that the reactors 20 on the same cleaning position 412 use the same liquid suction member 441 to suck the waste liquid. At this point, the reactor 20 in the first cleaning station 412a has completed the third cleaning cycle, the reactor 20 in the second cleaning station 412b has completed the second cleaning cycle, and the reactor 20 in the third cleaning station 412c has just completed the first cleaning. Wheel cleaning.

Continue to directly return the bearing block 411 from the second station 402 to the initial station 403. Assuming that the reactor 20 has completed the third round of cleaning (that is, three rounds of cleaning have been completed), the cleaning has been completed. At this time, the transfer device will The cleaned reactor 20 at the cleaning position 412a is removed from the first cleaning position 412a. If a filling position 413 is provided on the bearing block 411, the transfer device transfers the reactor 20 from the first cleaning position 412a to the filling position. Note the position 413, and at the same time, the transfer device will add a new reactor 20 to be cleaned at the vacant first cleaning position 412a. Then, the loading block 411 moves to the first station 401, the injection member 432 will inject the signal reagent into the reactor 20 in the filling position 413, and at the same time, the three liquid injection members 431 inject the cleaning liquid into the three reactors 20. Then, when the carrier block 411 is moved to the second station 402 for suctioning waste liquid, it returns to the initial station 403 directly. At this time, the reactor 20 on the first cleaning station 412a has just completed the first cleaning and the second cleaning. The reactor 20 in position 412b has completed the third round of cleaning, and the reactor 20 in the third cleaning position 412c has completed the second round of cleaning. Therefore, first, the transfer device transfers the reactor 20 which has been injected with the signal reagent on the filling position 413 to the measurement device 500 for signal measurement or incubation device 300 for signal incubation. Second, the transfer device completes the second cleaning position 412b. The reactor 20 cleaned for three rounds is transferred to the filling position 413 that has just been vacated. Finally, the transfer device will place a new reactor 20 to be cleaned into the second cleaning position 412b that is just vacant.

Therefore, according to the above-mentioned laws of movement and cleaning, the loading block 411 drives the reactor 20 to slide back and forth between the initial station 403, the first station 401, and the second station 402, and the set round injection is reached. The reactor 20 after cleaning liquid and suction waste liquid treatment (that is, reaching the set round of cleaning) is removed from the cleaning position 412 of the bearing block 411 at the initial station 403, hereinafter referred to as "set round injection of cleaning liquid and suction of waste liquid" The "treatment" is "set cleaning cycle", and the reactor 20 that has not reached the set cleaning cycle will continue to follow the carrier assembly 410, and at the same time, the new belt cleaning reactor 20 will be moved to the cleaning position 412 of the bearing block 411 According to the requirements of the actual analysis performance, the cleaning cycle can be flexibly determined, and the setting cycle can be three, four, five, six or even more, so that the best cleaning effect and the maximum cleaning efficiency can be balanced. . .

For different rounds of cleaning of the same reactor 20, the same liquid-absorbent piece 441 is always used to suck the waste liquid. When the liquid-absorbed piece 441 finishes the liquid-absorbed waste liquid in the previous round (the Nth round) of cleaning, due to the liquid-absorption The piece 441 is immersed in the suspension of the reactor 20, and after the liquid absorbing member 441 leaves the reactor 20, the liquid absorbing member 441 carries a relatively high concentration of residual waste liquid. (Wheel) After the waste liquid is removed during cleaning, since the magnetic particle combination 21 has been cleaned in the Nth round, the concentration of the waste liquid in the reactor 20 is relatively low, and the liquid absorbent 441 will carry a relatively low concentration of residual waste. Liquid, after the liquid absorbent 441 finishes processing the liquid waste in the next round (N + 2) cleaning, the liquid absorbent 441 carries a relatively low concentration of residual liquid waste. Therefore, as the number of cleaning cycles increases, the concentration of the residual waste liquid carried on the liquid-absorbent member 441 can be ignored, so that no carry-over pollution will be caused in the next liquid waste suction, thereby improving the cleaning effect and analysis performance. For the traditional mode in which multiple different reactors 20 suck waste liquid through the same liquid suction member 441, the high concentration waste liquid carried by the liquid suction member 441 in the previous reactor 20 will enter the next reactor 20, thereby affecting Cleaning effect of the next reactor 20.

The cleaning bits 412 on the bearing block 411 can be set to not only three, but also four, five or more. The reactors 20 on the two adjacent cleaning positions 412 differ by one round of cleaning, that is, when the reactor 20 on the Nth cleaning position 412 completes the Mth cleaning, the The reactor 20 completes the M-1 cleaning cycle. In other words, the reactor 20 placed in the cleaning position 412 first is washed one more round than the next reactor 20 placed in the cleaning position 412, and the bearing block 411 is in the first station 401 and the second station 402. After the number of times of movement greater than the set number of rounds, when the load block 411 directly reaches the initial position 403 from the second station 402, a reactor 20 must be removed from the cleaning position 412 because it has reached the set number of rounds of cleaning At the same time, a new reactor 20 to be cleaned will be moved into the cleaning position 412. Therefore, the cleaned reactor 20 will be continuously moved from the initial position 403 to the cleaning position 412, and the new reactor 20 to be cleaned will be moved from the initial position 403. It is continuously moved into the cleaning position 412, so as to achieve the "metabolism" between the reactor 20 after cleaning and the new reactor 20 to be cleaned, and finally the continuous circulation cleaning of the reactor 20 by the cleaning device 400 is finally achieved.

In some embodiments, the initial station 403 of the cleaning device 400 may be omitted, that is, the cleaning device 400 is provided with only the first station 401 and the second station 402. After the reactor 20 is cleaned, the reactor 20 may be directly removed from The first station 401 or the second station 402 moves out of the cleaning station 412 on the bearing block 411.

In some embodiments, the measurement device 500 includes a measurement room 510 and a light detector 520. The measurement room 510 is a dark room for measurement that is protected from light. The light detector 520 is installed on the measurement room 510. A measurement position 511 is provided in the measurement room 510. The reactor 20 that has been cleaned and added with the signal reagent is placed on the measurement position 511. When the signal reagent reacts with the magnetic particle conjugate 21 and emits light, the light detector 520 will detect the light signal in the reactor 20, and according to the light signal In order to perform measurement analysis on the magnetic particle conjugate 21.

When the immune analyzer 10 is turned on, one of the working modes is described below as an example. First, the supply device 100 sorts and buffers the empty and clean reactors 20. Then, the transfer device transfers the reactor 20 on the supply device 100 to the incubation position 311 of the incubation device 300, and the sampling device adds the sample and the target reagent on the storage device 200 to the reactor 20 on the incubation position 311 and incubates The device 300 heats and incubates the reactor 20 having the sample and the target reagent for a set time. Next, the transfer device transfers the reactor 20 after the incubation to the cleaning device 400. After the cleaning device 400 finishes cleaning the reactor 20, the signal reagent can be continuously injected into the cleaned reactor 20. Finally, the transfer device transfers the reactor 20 that has been cleaned and filled with the signal reagent to the measurement chamber 510 for measurement and analysis.

Referring to FIG. 7, the present invention also provides a cleaning method. The cleaning method can clean the magnetic particle combination 21 in the reactor 20 through the cleaning device 400. The cleaning method mainly includes the following steps:

S810: Inject the cleaning solution into the reactor 20 at the first station 401.

S820: The magnetic particle conjugate 21 in the reactor 20 at the second station 402 is adsorbed on the inner wall of the reactor 20, and the waste liquid is sucked into the reactor 20 through the liquid absorbing member 441.

S830. The carrier assembly 410 is used to drive the reactor 20 to reciprocate between the first and

second stations

401 and 402, so that the reactor 20 is alternately processed by injecting cleaning liquid and sucking waste liquid, and the same reactor 20 The waste liquid is sucked by the same liquid-absorbing member 441.

S840, removing the reactor 20 that has reached the set number of rounds for injecting cleaning liquid and sucking waste liquid for processing out of the cleaning position 412 of the carrier assembly 410, and bringing the reactor that has not reached the set number of rounds for injecting cleaning liquid and sucking waste liquid for processing 20 continues to follow the carrier assembly 410, and moves the new reactor 20, which has not been treated with the cleaning liquid injection and waste liquid pumping, into the cleaning position 412 of the carrier assembly 410.

When the reactor 20 is at the first station 401, a cleaning liquid may be injected into the reactor 20 through the liquid injection member 431, so that the magnetic particle combination 21 is washed by the cleaning liquid. When the reactor 20 is at the second station 402, the magnetic particle conjugate 21 is adsorbed on the inner wall of the reactor 20 before the waste liquid is sucked by the liquid absorbing member 441, so that the magnetic particle conjugate 21 is not drawn when the waste liquid is sucked. Loss and affect analysis performance. After the reactor 20 has been reciprocated between the first station 401 and the second station 402 multiple times, the reactor 20 will alternately perform the treatment of injecting the cleaning liquid and sucking the waste liquid, thereby forming multiple rounds of cleaning. In each round, During the cleaning process, the same reactor 20 sucks waste liquid through the same suction member 441. As the number of cleaning cycles of the reactor 20 increases, the concentration of the residual waste liquid carried on the suction member 441 gradually decreases to prevent suction. The liquid piece 441 causes carryover pollution to the reactor 20.

In some embodiments, the carrier assembly 410 drives the reactor 20 to cycle back and forth between the initial station 403, the first station 401, and the second station 402 in sequence, that is, the initial station 403 serves as a buffer station. When the component 410 is moved to the initial station 403, the reactor 20 that has been cleaned in a round may be moved out of the cleaning position 412, and the new reactor 20 to be cleaned may be moved into the cleaning position 412. In order to improve the cleaning efficiency, the carrier assembly 410 is moved on the same linear trajectory between the initial station 403, the first station 401 and the second station 402, that is, the carrier assembly 410 is on the initial station 403, the first station A linear motion is performed between 401 and the second station 402. After the same reactor 20 is filled with cleaning liquid for three or four rounds and the waste liquid is sucked out, the carrier assembly 410 is removed, that is, the reactor 20 after three or four rounds of cleaning has been cleaned.

In some embodiments, a permanent magnet unit 422 is used to adsorb the magnetic particle combination 21 in the reactor 20, so that the magnetic field lines of the permanent magnet unit 422 uniformly cover a plurality of cleaning positions 412 on the load-bearing component 410 at the second station 402. In order that the permanent magnet unit 422 can adsorb the magnetic particle combination 21 in each reactor 20. When the load-bearing component 410 is at the second station 402, the distance between the permanent magnet unit 422 and the load-bearing component 410 is changed to adjust the adsorption range or shape of the magnetic particle conjugate 21 on the reactor 20. According to the actual situation, It can be considered in a balanced manner from the risk of loss of magnetic particle combination 21 and the cleaning effect, and finally a reasonable distance between the permanent magnet unit 422 and the bearing component 410 is formed.

In some embodiments, after the reactor 20 has reached the set number of rounds for injecting cleaning liquid and sucking waste liquid, the reactor 20 is transferred from the cleaning position 412 of the carrier assembly 410 to the filling position 413 of the carrier assembly 410 At the first station 401, a signal reagent is injected into the reactor 20 located in the filling station 413. This increases the use function of the cleaning device 400 and makes the structure of the cleaning device 400 more compact.

Referring to FIG. 8, the present invention further provides a sample analysis method. The sample analysis method includes the following steps:

S910: Supply: The empty reactor 20 is sorted and sorted by the supply device 100.

S920. Sampling: The sample and the target reagent are added to the empty reactor 20 through the sampling device 600.

S940, incubation: the reactor 20 containing the sample and the target reagent is heated by the incubation device 300 for a set time.

S950, cleaning: the magnetic particle conjugate 21 in the reactor 20 is cleaned by the cleaning device 400.

S980. Measurement: The measuring device 500 measures the luminescence amount of the reactor 20 that has been processed by the cleaning method and added a signal reagent.

In some embodiments, before the incubation step, the reactor 20 containing the sample and the target reagent after sampling is subjected to a mixing process step (S930), that is, the sample and the target reagent are mixed by the mixing device 700 before being incubated, To improve the incubation effect. Prior to the measurement step, the reactor is processed by adding a signal reagent (S960), and the reactor 20 containing the signal reagent is heated for a set time, that is, the reactor 20 containing the signal reagent and the magnetic particle conjugate 21 is signaled. In the incubation process step (S970), during the signal incubation process, the incubation device 300 will heat process the reactor 20 to improve the analysis performance. In the sampling step, the structure of the cleaning device 400 can be simplified and the cost can be reduced by simultaneously sucking the sample and the target reagent with the sampling steel needle.

In the incubation step, the incubation time is about 5-60 minutes. In some embodiments, the incubation step may further include the following sub-steps:

In the first incubation, the reactor 20 containing the sample and the first kind of target reagent is heated for a set time.

In the second incubation, a second kind of target reagent is added to the reactor 20 after the first incubation, and the heating is performed for a set time.

When the incubation step includes the first and second incubation sub-steps, that is, after the supplying step and the sampling step, and before the washing step, the two target reagents are added to the reactor 20 in two portions, each of which adds one target. After the reagent, the reactor 20 is heated by the incubation device 300 for incubation.

In some embodiments, the sample analysis method further includes the following steps:

The reactor 20 after the first incubation is subjected to the steps in the first cleaning method.

The reactor 20 after the treatment in the first cleaning method is subjected to a second incubation.

The reactor 20 after the second incubation is subjected to the steps in the cleaning method again.

Specifically, after the reactor 20 has passed through the supplying step and the sampling step, the reactor 20 is firstly incubated by the incubation device 300, and then the reactor 20 after the first incubation is cleaned for the first time by the cleaning device 400, and the first cleaning is performed. Then add the second kind of target reagent, and then transfer the reactor 20 after the first cleaning and add the second kind of target reagent to the incubation device 300 for the second incubation, and then pass the second incubation reactor 20 through the cleaning device 400 After performing the cleaning again, finally, the reactor 20 after the cleaning is added to the signal reagent and then sent to the measurement device 500 for measurement.

The technical features of the embodiments described above can be arbitrarily combined. In order to simplify the description, all possible combinations of the technical features in the above embodiments have not been described. However, as long as there is no contradiction in the combination of these technical features, It should be considered as the scope described in this specification.

The above-mentioned embodiments only express several implementation manners of the present invention, and their descriptions are more specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be noted that, for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can be made, which all belong to the protection scope of the present invention. Therefore, the protection scope of the invention patent shall be subject to the appended claims.

Claims

A cleaning method includes the following steps:

Inject the cleaning solution into the reactor at the first station;

Adsorbing the magnetic particle conjugate in the reactor at the second station on the inner side wall of the reactor, and sucking the waste liquid to the reactor through the liquid absorbing member;

The carrier component drives the reactor to circulate back and forth between the first and second stations, so that the reactor alternately performs treatment of injecting cleaning liquid and sucking waste liquid, and the same reactor sucks waste liquid through the same suction member ;and

Move the reactor that has reached the set round to inject the cleaning liquid and suck the waste liquid and remove it from the cleaning position of the carrier component, and the reactor that has not reached the set round to inject the cleaning liquid and suck the waste liquid to treat it, continue to follow the carrier component , And move the new reactor, which has not been injected with cleaning liquid and pumping waste liquid, into the cleaning position of the bearing component.
The cleaning method according to claim 1, characterized in that the reactor is driven by the load-bearing component to cycle back and forth between the initial station, the first station and the second station in sequence, and when the load-bearing assembly is located at the initial station, The reactor is moved into or out of the carrier assembly.
The cleaning method according to claim 2, wherein the load-bearing component is moved on the same linear trajectory between the initial station, the first station and the second station.
The cleaning method according to claim 1, characterized in that the same reactor is treated by injecting cleaning liquid and sucking waste liquid after three or four rounds to remove it from the bearing assembly.
The cleaning method according to claim 1, wherein at least one permanent magnet unit adsorbs the magnetic particle combination in the reaction cup, so that the magnetic lines of force of all the permanent magnet units are uniformly covered on the load-bearing component at the second station Full cleaning bit.
The cleaning method according to claim 5, wherein the magnetic field lines of at least one permanent magnet unit uniformly cover at least two cleaning positions.
The cleaning method according to claim 5, characterized in that the permanent magnet unit is formed by two stacked permanent magnets, and the magnetic poles of the two permanent magnets which are disposed toward the bearing component are arranged oppositely.
The cleaning method according to claim 5, characterized in that, when the carrier assembly is at the second station, the distance between the permanent magnet unit and the carrier assembly is changed to adjust the magnetic particle combination on the reactor. Adsorption range or shape.
The cleaning method according to claim 1, characterized in that when the reactor has reached a set number of rounds for injecting cleaning liquid and sucking waste liquid for treatment, the reactor is transferred from the cleaning position of the bearing component to the filling of the bearing component. The signal reagent is injected into the reactor at the first station and at the first station.
A sample analysis method comprising the steps in the cleaning method according to any one of claims 1 to 8.
The sample analysis method according to claim 10, further comprising the following steps:

Supply: supply empty reactors;

Sampling: Add samples and target reagents to the empty reactor;

Incubation: Incubate the reactor containing the sample and target reagent for a set time; and

Measurement: The reactor that has been processed by the cleaning method and added with a signal reagent is measured for luminescence.
The sample analysis method according to claim 11, wherein before the incubating step, the reactor containing the sample and the target reagent is mixed and processed.
The sample analysis method according to claim 11, wherein before the measuring step, the reactor containing the signal reagent is incubated for a set time.
The sample analysis method according to claim 11, wherein in the sampling step, the sample and the target reagent are aspirated simultaneously by a sampling steel needle.
The sample analysis method according to claim 11, wherein in the incubation step, the incubation time is 5-60 minutes.
The sample analysis method according to claim 11, wherein the incubation step comprises:

First incubation, incubating the reactor containing the sample and the first type of target reagent for a set time; and

In the second incubation, a second type of target reagent is added to the reactor after the first incubation, and the incubation is performed for a set time.
The sample analysis method according to claim 16, further comprising the following steps:

Performing the steps in the first cleaning method for the reactor after the first incubation;

Performing a second incubation of the reactor treated by the steps in the cleaning method described for the first time; and

The reactor subjected to the second incubation is subjected to the steps in the cleaning method again.