CN114226381A - Cleaning method - Google Patents

Abstract

The invention relates to a cleaning method, which comprises the following steps: injecting a cleaning solution into the reaction cup which is positioned at the liquid injection station and contains the magnetic particle combination through the liquid injection member, so that the cleaning solution flows downstream into the reaction cup along the inner wall surface of the reaction cup under the action of self gravity; enabling the reaction cup to generate eccentric oscillation so as to uniformly mix the magnetic particle combination and the cleaning solution; and moving the reaction cup undergoing eccentric oscillation to a liquid suction station, adsorbing the magnetic particle combination to the inner wall surface of the reaction cup through a magnetic member positioned outside the reaction cup, and extracting waste liquid from the reaction cup into which the cleaning liquid has been injected. The cleaning liquid falling from the liquid injection member is recorded as dynamic fluid, and the cleaning liquid already contained in the reaction cup is recorded as static fluid, so that the speed of the dynamic fluid reaching the static fluid is lower, bubbles generated by collision of the cleaning liquid can be greatly reduced, and the cleaning effect of the cleaning liquid on the magnetic particle combination is improved.

Description

Cleaning method

Technical Field

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

Background

The luminescence immunoassay is based on an immunological reaction of mutual combination of antigen and antibody, uses substances such as enzyme, luminescent agent and the like to mark the antigen and antibody, and relates a light signal with the concentration of an analyte and the like through a luminescence reaction, thereby finally determining the content of a target analyte in a sample to be detected. In the cleaning process, firstly, the target analyte in the sample to be detected in the reaction cup is captured by the magnetic particles serving as the solid phase carriers, so that the target analyte is combined with the magnetic particles, and a cleaning solution is injected to clean the magnetic particles. Then, the magnetic particles directly or indirectly combined with the target analyte are collected on the inner side wall of the reaction cup through a magnetic field, and waste liquid formed after the reaction cup is cleaned is extracted. After the reaction cup is injected with cleaning solution for multiple times and waste liquid is extracted, free markers and other interfering impurities which are not bonded on the magnetic particles can be removed, so that signal measurement is carried out on antigen-antibody conjugates (namely, magnetic particle conjugates) attached on the magnetic particles, and finally the content of a target analyte is determined according to the luminous value of the signal.

For the traditional cleaning method, the free markers and other interfering impurities on the magnetic particles cannot be effectively removed, so that the cleanliness of the magnetic particle combination cannot be improved, and finally the precision of the measurement result is influenced.

Disclosure of Invention

The invention solves a technical problem of how to improve the cleaning effect of the cleaning method on the magnetic particle combination.

A cleaning method can be applied to a cleaning mechanism to clean magnetic particle combinations in a reaction cup, wherein the cleaning mechanism comprises a liquid injection piece, and the cleaning method comprises the following steps:

injecting a cleaning solution into the reaction cup which is positioned at the liquid injection station and contains the magnetic particle combination through the liquid injection member, so that the cleaning solution flows downstream into the reaction cup along the inner wall surface of the reaction cup under the action of self gravity;

enabling the reaction cup to generate eccentric oscillation so as to uniformly mix the magnetic particle combination and the cleaning solution; and

and moving the reaction cup subjected to eccentric oscillation to a liquid suction station, adsorbing the magnetic particle combination to the inner wall surface of the reaction cup through a magnetic member positioned outside the reaction cup, and extracting waste liquid from the reaction cup into which the cleaning liquid has been injected.

In one embodiment, before the cleaning solution flows forward along the inner wall surface of the reaction cup into the reaction cup under the action of self gravity, the method further comprises: the liquid injection direction of the cleaning liquid flowing out of the liquid injection piece is intersected with the central axis of the reaction cup to form a set included angle.

In one embodiment, the liquid injection piece is positioned outside the reaction cup in the process of injecting the cleaning liquid.

In one embodiment, making the cleaning solution flow forward along the inner wall surface of the reaction cup into the reaction cup under the action of self gravity comprises: and recording the position where the cleaning liquid output from the liquid injection piece is firstly contacted with the reaction cup as a liquid dropping point, and enabling the liquid dropping point to be higher than the liquid level in the reaction cup.

In one embodiment, the generating eccentric oscillations in the reaction cup comprises: and enabling the reaction cup to generate eccentric oscillation at the liquid injection station.

In one embodiment, after the injection of the cleaning liquid is completed, the reaction cup is eccentrically oscillated; or, the reaction cup is eccentrically oscillated while the cleaning solution is injected.

In one embodiment, the method further comprises:

and moving the reaction cup after the waste liquid is extracted to the liquid injection station, and executing the cleaning method again, wherein the time duration and/or the oscillation intensity of the later eccentric oscillation are/is larger than that of the earlier eccentric oscillation.

In one embodiment, the cleaning mechanism further comprises a blending part and a rotating shaft which are connected with each other, the blending part is provided with a blending position, the blending position is arranged at intervals with the rotating shaft along the axial direction perpendicular to the rotating shaft, and the reaction cup is placed on the blending position of the blending part, so that the rotating shaft drives the reaction cup to generate eccentric oscillation through the blending part.

In one embodiment, the distance between the blending position and the rotating shaft along the axial direction perpendicular to the rotating shaft is recorded as an eccentric distance, so that the length of the eccentric distance and the speed of the rotating shaft can be adjusted.

In one embodiment, the method further comprises at least one of the following technical schemes:

making the cleaning liquid flow forward to the reaction cup along the inner wall surface of the reaction cup under the action of self gravity comprises: when the reaction cup moves to the liquid injection station at least once to inject the cleaning liquid, the liquid injection piece injects the cleaning liquid into the reaction cup in two parts; after the first part of cleaning solution is injected into the reaction cup, the reaction cup generates eccentric oscillation and lasts for a set time; then injecting a second part of cleaning solution into the reaction cup and enabling the reaction cup to generate eccentric oscillation;

leaving the reaction cups from the filling station and reaching the filling station comprises: and the reaction cup is made to do linear motion or circular motion between the liquid injection station and the liquid suction station.

One technical effect of one embodiment of the invention is that: the cleaning liquid falling from the liquid injection member is recorded as dynamic fluid, the cleaning liquid already contained in the reaction cup is recorded as static fluid, and in view of the fact that the dynamic fluid flows forward into the reaction cup along the inner wall surface of the reaction cup, energy loss is generated by the friction resistance between the dynamic fluid and the reaction cup, so that the speed of the dynamic fluid reaching the static fluid is low, and severe collision between the dynamic fluid and the static fluid is eliminated. Therefore, bubbles generated by collision of the cleaning liquid can be greatly reduced, the influence of the bubbles on uniform mixing between the cleaning liquid and the magnetic particle combination bodies in the reaction cup during eccentric oscillation is avoided, the turbulence formed by the cleaning liquid can be increased, all the magnetic particle combination bodies can be ensured to be uniformly suspended in the cleaning liquid, and the scouring force of the cleaning liquid on the magnetic particle combination bodies is improved so as to improve the cleaning effect.

Drawings

FIG. 1 is a schematic diagram of a cleaning mechanism according to one embodiment;

FIG. 2 is a schematic view of a structure in which a cleaning liquid in a liquid injection member flows down along the inner wall surface of a reaction cup;

FIG. 3 is a schematic view showing a structure in which a magnetic member adsorbs a magnetic particle conjugate to an inner wall surface of a reaction cup;

fig. 4 is a process 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.

Referring to fig. 1, 2, 3 and 4, a cleaning method according to an embodiment of the present invention is provided for cleaning magnetic particle conjugates 30 in a reaction cup 20, and the cleaning method can be implemented by a cleaning mechanism 10, where the cleaning mechanism 10 mainly includes a fixing plate 110, an imbibing member 120, an imbibing member 130, a carrier 140, a magnetic member 150, a rotating shaft 160 and a mixing member 170. By operating this cleaning mechanism 10, a cleaning method can be formed, which mainly comprises the steps of:

s210, injecting a cleaning solution into the reaction cup 20 which is positioned at the injection station 11 and contains the magnetic particle combination 30 through the injection member 120, so that the cleaning solution flows downstream into the reaction cup 20 along the inner wall surface 21 of the reaction cup 20 under the action of self gravity.

And S220, enabling the reaction cup 20 to generate eccentric oscillation so as to uniformly mix the magnetic particle combination 30 with the cleaning solution.

And

s230, the reaction cuvette 20 which has undergone eccentric oscillation is moved to the liquid suction station 12, the magnetic particle bonded material 30 is adsorbed to the inner wall surface 21 of the reaction cuvette 20 by the magnetic member located outside the reaction cuvette 20, and the waste liquid is extracted from the reaction cuvette 20 into which the cleaning liquid has been injected.

The specific details of the overall cleaning method are described below in conjunction with the specific structure and operation of the cleaning mechanism 10:

referring to fig. 1, 2 and 3, the reaction cups 20 are disposed on a carrier 140, and the carrier 140 can drive the reaction cups 20 to reciprocate between the pipetting station 12 and the priming station 11. For example, the carrying seat 140 can drive the reaction cup 20 to make reciprocating linear motion between the liquid suction station 12 and the liquid injection station 11; for example, the carrier 140 can also drive the reaction cup 20 to reciprocate between the pipetting station 12 and the filling station 11. When the reaction cup 20 is carried on the carrier block 140, the central axis of the reaction cup 20 is vertically disposed, i.e., the central axis is perpendicular to the horizontal plane.

The fixing plate 110 may be located above the carrier base 140, and both the liquid absorbing member 130 and the liquid injecting member 120 may be disposed on the fixing plate 110, and a distance of the fixing plate 110 in a vertical direction with respect to the carrier base 140 may be maintained constant. The liquid injection member 120 is located above the liquid injection station 11, and when the reaction cup 20 carrying the magnetic particle combination 30 moves to the liquid injection station 11, the liquid injection member 120 can inject a set amount of cleaning liquid into the reaction cup 20, so that the cleaning liquid can clean the magnetic particle combination 30. The injection member 120 may be a needle-shaped injection needle, and the injection direction of the cleaning solution flowing out of the injection member 120 intersects with the central axis of the reaction cup 20 to form a set included angle. For example, the central axis of the injection member 120 intersects with the central axis of the reaction cup 20 at a set angle, which may be understood as that the central axis of the injection member 120 is disposed non-parallel to the central axis of the reaction cup 20, so that the central axis of the injection member 120 is not perpendicular to the horizontal plane but inclined at a certain angle, such that the injection direction intersects with the central axis of the reaction cup 20 at the set angle. In view of the vertical arrangement of the central axis of the reaction cup 20, the reaction cup 20 can be understood as being vertically arranged; and the central axis of the injection member 120 is obliquely arranged, which can be understood as the oblique arrangement of the injection member 120.

In some embodiments, during the process of injecting the cleaning solution, the injection member 120 is located outside the reaction cup 20, i.e. the reaction cup 20 does not extend into the reaction cup 20. When the injection member 120 injects liquid, considering that the injection direction of the cleaning liquid flowing out of the injection member 120 intersects with the central axis of the reaction cup 20 at a set included angle, the cleaning liquid flowing out of the injection member 120 first contacts the inner wall surface 21 of the reaction cup 20, and then the cleaning liquid flows forward along the inner wall surface 21 of the reaction cup 20 into the reaction cup 20. The position where the cleaning liquid output from the injection unit 120 first contacts the reaction cup 20 is referred to as a liquid dropping point 22, and the liquid dropping point 22 is vertically spaced from the liquid surface 23 in the reaction cup 20 by a certain distance, so that the liquid dropping point 22 is higher than the liquid surface 23 in the reaction cup 20, and the cleaning liquid is ensured to flow down from the position above the liquid surface 23.

Since the cleaning liquid falling from the injection member 120 is dynamic liquid and the cleaning liquid already contained in the reaction cup 20 is static liquid, if the dynamic liquid is directly injected into the static liquid, the falling height of the dynamic liquid is the distance from the outlet of the injection member 120 to the liquid level 23 in the reaction cup 20, so the falling height of the dynamic liquid is relatively large, and in addition, the dynamic liquid has a certain velocity when flowing out of the injection member 120, so that the dynamic liquid has a large kinetic energy when contacting with the static liquid, and then a violent collision is generated between the dynamic liquid and the static liquid. On the one hand, the cleaning liquid is splashed due to collision, and then the magnetic particle combination 30 is splashed out of the reaction cup 20 along with the cleaning liquid, so that the magnetic particle combination 30 is lost and the accuracy of subsequent measurement is affected. On the other hand, the cleaning liquid is collided to generate a large amount of bubbles, which remain in the cuvette 20 for a long time.

Referring to fig. 2, the dropping point 22 in the above embodiment is higher than the liquid level 23 in the reaction cup 20, so that the cleaning liquid flows down along the inner wall surface 21 of the reaction cup 20 into the reaction cup 20, and the dropping point 22 is closer to the outlet of the liquid injection member 120 than the liquid level 23 of the reaction cup 20. The falling height of the dynamic fluid to the falling point 22 is relatively small, and the dynamic fluid will have small collision with the inner wall surface 21 of the reaction cup 20, so that the dynamic fluid will have energy loss during collision with the reaction cup 20. Then, in the process in which the dynamic fluid flows down along the inner wall surface 21 of the reaction cup 20, the frictional resistance between the dynamic fluid and the reaction cup 20 also causes energy loss. Therefore, in comparison with the dynamic fluid falling directly on the liquid surface 23 of the static fluid, in the process that the dynamic fluid of the above embodiment finally falls on the liquid surface 23 of the static fluid, the dynamic fluid collides with and rubs against the reaction cup 20 to generate two energy losses, so that the velocity of the dynamic fluid reaching the static fluid is smaller, thereby eliminating the generation of violent collision between the dynamic fluid and the static fluid. Therefore, on one hand, the cleaning liquid is prevented from sputtering due to collision, and then the magnetic particle combination 30 is prevented from sputtering to the outside of the reaction cup 20 along with the cleaning liquid, and the magnetic particle combination 30 is prevented from being lost. On the other hand, bubbles generated by collision of the cleaning liquid are greatly reduced.

Of course, the kinetic energy of the dynamic fluid reaching the dropping point 22 is relatively small, so that there will be a small collision between the dynamic fluid and the reaction cup 20, and although the small collision may also cause the cleaning solution to be splashed out of the reaction cup 20, the magnetic particle combination 30 is not mixed in the dynamic fluid, so the collision will not cause the loss of the magnetic particle combination 30.

In other embodiments, the filling end of the filling member 120 may extend into the reaction cup 20 and closely contact the inner wall surface 21 of the reaction cup 20, so that the cleaning solution flowing out of the filling member 120 may flow downstream along the inner wall surface 21 of the reaction cup 20 into the reaction cup 20, which may also reduce sputtering, thereby avoiding the loss of the magnetic particle combination 30 and reducing the generation of bubbles.

In some embodiments, the homogenizing member 170 has an upper surface and a lower surface spaced apart in the thickness direction, i.e., the upper surface and the lower surface are two outer surfaces facing opposite directions in the thickness direction of the homogenizing member 170. The upper surface is provided with a blending position 171, and a counter bore 172 can be arranged at the blending position 171, that is, the counter bore 172 is arranged at the blending position 171. The counterbore 172 is used to receive the reaction cup 20 such that the lower end of the reaction cup 20 is inserted into the counterbore 172. The rotating shaft 160 is fixedly connected to the lower surface of the mixing part 170, and the rotating shaft 160 extends in a vertical direction, i.e. the central axis of the rotating shaft 160 is vertically arranged, obviously, the central axis of the rotating shaft 160 is parallel to the central axis of the reaction cup 20. The rotation shaft 160 may be driven by a motor. The position of the blending position 171 can be abstracted as the position of the central axis of the counterbore 172, the axial direction of the rotating shaft 160 is the extending direction of the central axis of the rotating shaft 160, the axial direction perpendicular to the rotating shaft 160 is the horizontal direction, the central axis of the counterbore 172 and the central axis of the rotating shaft 160 are arranged at intervals along the horizontal direction, that is, the blending position 171 and the rotating shaft 160 are arranged at intervals along the horizontal direction by a set distance, which can be understood as an eccentric distance H. The rotation shaft 160 may be detachably coupled to the kneading member 170, and the rotation shaft 160 and the kneading member 170 have a plurality of installation positions, and when the installation position of the rotation shaft 160 is changed, the length of the eccentric distance H may be adjusted. Of course, the mixing positions 171 on the mixing member 170 may be respectively provided with the counter bores 172, and the rotating shaft 160 and different mixing positions 171 may have different eccentric distances H, that is, the eccentric distance H may also be adjusted.

When the reaction cup 20 is inserted into the counter bore 172, the motor can drive the rotating shaft 160 to rotate, and in view of the eccentric distance H between the blending position 171 and the rotating shaft 160, the cleaning solution in the reaction cup 20 will generate eccentric oscillation under the action of centrifugal force during the process that the reaction cup 20 rotates along with the blending member 170, so that the cleaning solution and the magnetic particle combination 30 are blended. In the process of uniform mixing, the turbulent flow generated by the vibration of the cleaning liquid can generate a cleaning effect on the magnetic particle combination 30; obviously, when the duration and intensity of the eccentric oscillation are relatively large, the more turbulent the cleaning liquid, the longer the duration and the stronger the scouring force will be applied to the magnetic particle combination 30, so as to provide better cleaning effect to the magnetic particle combination 30.

Specifically, the duration of the eccentric oscillation may be extended by extending the rotation time of the rotation shaft 160, and for increasing the intensity of the oscillation, it may be achieved by increasing the centrifugal force of the rotation of the reaction cup 20, and in order to increase the centrifugal force of the reaction cup 20, one may increase the rotation speed of the rotation shaft 160, and the other may increase the eccentric distance H. Therefore, the cleaning effect can be adjusted reasonably by changing the rotation time of the rotation shaft 160, the rotation speed of the rotation shaft 160, and the eccentric distance H.

In some embodiments, the blending member 170 may be located below the liquid injection station 11, and the blending member 170 may move up and down in the vertical direction to approach or depart from the liquid injection station 11 in addition to rotating along with the rotating shaft 160. When the reaction cup 20 is injected with the cleaning liquid at the injection station 11, the blending part 170 can be moved to the injection station 11, so that the reaction cup 20 is inserted into the counter bore 172 of the blending part 170; the mixing member 170 may also be vertically spaced from the reaction cup 20 such that the reaction cup 20 is located outside the counterbore 172. Obviously, when the reaction cup 20 needs to be eccentrically oscillated to achieve blending, the blending member 170 may be moved upward to the liquid injection station 11, so that the reaction cup 20 is inserted into the counter bore 172, and then the blending member 170 is moved by the rotating shaft 160 to form eccentric oscillation. When the eccentric oscillation is completed, the blending member 170 is moved downwards to be away from the liquid injection station 11, so that the reaction cup 20 is completely separated from the counter bore 172, and the blending member 170 is prevented from interfering with the movement of the reaction cup 20, so that the reaction cup 20 can be smoothly moved from the liquid injection station 11 to the liquid suction station 12 subsequently.

In the case that the reaction cup 20 located at the liquid injection station 11 is inserted into the counter bore 172 of the mixing member 170, for example, in the process of injecting the cleaning liquid into the reaction cup 20, the mixing member 170 may drive the reaction cup 20 to eccentrically oscillate to achieve mixing, that is, the two processes of injecting the cleaning liquid and eccentrically oscillating are performed simultaneously. For example, in the process of injecting the cleaning solution into the reaction cup 20, the mixing member 170 does not drive the reaction cup 20 to eccentrically oscillate, and after the injection of the cleaning solution is completed, the mixing member 170 is started to move to eccentrically oscillate the reaction cup 20, that is, the process of injecting the cleaning solution is performed first, and then the process of eccentrically oscillating is performed. For the situation that the reaction cup 20 located at the liquid injection station 11 is located outside the counter bore 172 of the mixing part 170, obviously, in the process of injecting the cleaning liquid into the reaction cup 20, the mixing part 170 cannot drive the reaction cup 20 to generate eccentric oscillation; only after the injection of the cleaning solution into the reaction cup 20 is completed, the mixing is moved upward to insert the reaction cup 20 into the counter bore 172, and then the mixing member 170 drives the reaction cup 20 to generate eccentric oscillation, that is, the process of injecting the cleaning solution is performed first, and then the process of eccentric oscillation is performed.

Therefore, in the case that the reaction cup 20 located at the liquid injection station 11 is inserted into the counter bore 172 of the mixing part 170, the two processes of injecting the cleaning liquid and eccentrically oscillating can be performed simultaneously, and the eccentrically oscillating process can be completed later than the cleaning liquid injection process. In the case that the reaction cup 20 located at the liquid injection station 11 is located outside the counter bore 172 of the mixing part 170, the eccentric oscillation process can be completed later than the liquid injection cleaning solution process.

The magnetic member 150 is disposed adjacent to the pipetting station 12 and the magnetic member 150 may be made of a permanent magnet material. The wicking member 130 can be moved in a vertical direction relative to the carrier block 140 to move toward or away from the wicking station 12. When the reaction cup 20 completes the eccentric oscillation, the bearing seat 140 can move the reaction cup 20 to the pipetting station 12. When the reaction cup 20 reaches the pipetting station 12, the magnetic particle combination 30 suspended in the liquid will be in the magnetic field generated by the magnetic member 150, and under the action of the magnetic field, the magnetic particle combination 30 in the suspended state will be adsorbed on the inner wall surface 21 of the reaction cup 20. When the magnetic particle assembly 30 is completely adsorbed, the liquid absorbing member 130 is moved downward close to the liquid absorbing station 12 and inserted into the liquid in the reaction cup 20, so that the waste liquid formed after the magnetic particle assembly 30 is washed is completely extracted by the washing liquid. When the waste liquid is completely extracted, the liquid absorbing member 130 moves upwards away from the liquid absorbing station 12 to completely leave the reaction cup 20, so that the liquid absorbing member 130 is prevented from continuing to extend into the reaction cup 20, and the liquid absorbing member 130 is prevented from interfering with the movement of the reaction cup 20, so that the reaction cup 20 can smoothly return to the liquid injecting station 11 or other stations (such as a measuring station).

For convenience of description, the injection cleaning solution is simply referred to as "injection", and the extraction waste solution is simply referred to as "suction", and for one complete cleaning process of the magnetic particle binder 30, the reaction cuvette 20 may undergo at least one injection, one eccentric oscillation, and one suction, each of which forms one sub-cleaning. For example, reaction cup 20 may be subjected to three priming shots, three eccentric oscillations, and three pipetting shots, such that a complete washing process includes three sub-washes. Also, for example, reaction cup 20 may be subjected to four priming cycles, four eccentric oscillations cycles, and four pipetting cycles, such that a complete washing process includes four sub-washes. The following describes a complete washing process of the magnetic particle conjugates 30 in the case where the reaction cup 20 undergoes three sub-washes:

in the first step, the bearing seat 140 drives the reaction cup 20 to move to the liquid injection station 11 for the first time, and liquid is injected into the reaction cup 20 through the liquid injection member 120, for example, while injecting liquid, the blending member 170 can drive the reaction cup 20 to generate eccentric oscillation, that is, the liquid injection and the eccentric oscillation processes are performed simultaneously. If the liquid injection is completed, the mixing member 170 drives the reaction cup 20 to eccentrically oscillate, that is, the liquid injection process is completed before the eccentric oscillation process is completed after the liquid injection process. So far, the reaction cup 20 completes the first injection and the first eccentric oscillation.

And in the second step, the bearing group drives the reaction cup 20 which has completed the first eccentric oscillation to leave the liquid injection station 11 and reach the liquid suction station 12 for the first time, and after the magnetic particle combination 30 is completely adsorbed on the inner wall surface 21 of the reaction cup 20 under the action of the magnetic member 150, the reaction cup 20 is sucked through the liquid suction member 130, so that all waste liquid in the reaction cup 20 is completely extracted. This is until the reaction cup 20 completes the first pipetting, and the first sub-washing is completed.

And thirdly, enabling the bearing group to drive the reaction cups 20 which have finished the first liquid suction to leave the liquid suction station 12 and reach the liquid injection station 11 for the second time, and repeating the related operations in the first step. So far, the reaction cup 20 completes the second injection and the second eccentric oscillation.

Fourthly, the reaction cup 20 which has finished the second eccentric oscillation is driven by the bearing group to leave the liquid injection station 11 and reach the liquid absorption station 12 for the second time, and the relevant operation in the second step is repeated. This time, the reaction cup 20 completes the second pipetting, and the second sub-washing is completed.

And fifthly, enabling the bearing group to drive the reaction cups 20 which finish the second liquid suction to leave the liquid suction station 12 and reach the liquid injection station 11 for the third time, and repeating the related operations in the first step. This completes the third injection and the third eccentric oscillation of the reaction cup 20.

And sixthly, enabling the bearing group to drive the reaction cup 20 which has completed the third eccentric oscillation to leave the liquid injection station 11 and reach the liquid suction station 12 for the third time, and repeating the related operations in the second step. This time, the reaction cup 20 completes the third pipette and the third sub-wash is completed.

At this time, after the reaction cup 20 undergoes the work flow from the first step to the sixth step, the reaction cup 20 undergoes three times of injection, three times of eccentric oscillation and three times of liquid suction, thereby completing three times of sub-washing, and finally completing one complete washing process for the magnetic particle combination 30. After the magnetic particle assembly 30 has completed a complete washing process, meaning that the magnetic particle assembly 30 is washed, the cuvette 20 may be transferred to a measurement station for measurement and analysis.

In view of the fact that during liquid injection, the inner wall surface 21 of the reaction cup 20 flows downstream into the reaction cup 20, air bubbles in the reaction cup 20 can be reduced, the influence of the air bubbles on uniform mixing between the cleaning liquid and the magnetic particle combination 30 in the reaction cup 20 during eccentric oscillation is avoided, turbulence formed by the cleaning liquid is increased, all the magnetic particle combinations 30 can be uniformly suspended in the cleaning liquid, and the washing force of the cleaning liquid on the magnetic particle combinations 30 is improved so as to improve the cleaning effect.

In some embodiments, when a complete washing process of magnetic particle conjugate 30 undergoes multiple eccentric oscillations, the eccentric oscillations that are relatively forward in time are designated as leading eccentric oscillations, and the eccentric oscillations that are relatively backward in time are designated as trailing eccentric oscillations. The duration and/or oscillation intensity of the following eccentric oscillation is relatively large compared to the preceding eccentric oscillation. For example, when a complete washing process of the magnetic particle binder 30 is subjected to three eccentric oscillations, the duration and/or oscillation intensity of the second eccentric oscillation is greater than that of the first eccentric oscillation, and the duration and/or oscillation intensity of the third eccentric oscillation is greater than that of the second eccentric oscillation, i.e., the duration and/or oscillation intensity of the next eccentric oscillation is greater than that of the previous eccentric oscillation. In other words, as the number of eccentric oscillations increases, the duration and/or intensity of the eccentric oscillations also increases.

Because the duration and/or the oscillation intensity of the next eccentric oscillation is larger than that of the previous eccentric oscillation, the cleaning effect of the next sub-cleaning is better than that of the previous sub-cleaning, so that the waste liquid remained on the magnetic particle combination 30 due to infiltration in the previous sub-cleaning process can be thoroughly cleaned, and the cleaning effect of the magnetic particle combination 30 in a complete cleaning process is finally improved. In other embodiments, the reaction cup 20 can also reciprocate once between the priming station 11 and the pipetting station 12, so that one complete washing process of the magnetic particle combination 30 experiences one eccentric oscillation.

In some embodiments, in the case that one complete cleaning process of the magnetic particle combination 30 includes multiple sub-cleaning, the reaction cup 20 will move to the filling station 11 multiple times to complete filling, so that the filling member 120 can inject the cleaning solution into the reaction cup 20 in two parts when the reaction cup 20 moves to the filling station 11 at least once to fill. In the operation mode of injecting the cleaning liquid into the cuvette 20 in two parts, the following steps may be formed: firstly, injecting a first part of cleaning solution into the reaction cup 20, and then enabling the reaction cup 20 to generate eccentric oscillation and continue for a set time; then, a second portion of the cleaning solution is injected into the reaction cup 20 and eccentrically oscillated. For example, a complete cleaning process of magnetic particle combination 30 includes three sub-cleans, and thus also includes three priming shots, and for at least one of the three priming shots, this may be accomplished by a two-shot mode of operation with cleaning fluid.

In fact, in the operation mode of injecting the cleaning solution into the reaction cup 20 in two parts, after the first part of the cleaning solution and the magnetic particle combination 30 are primarily mixed uniformly, after the second part of the cleaning solution is injected into the reaction cup 20 containing the first part of the cleaning solution, the reaction cup 20 is eccentrically oscillated to be mixed uniformly, so that the turbulence formed by the cleaning solution can be increased, the suspension effect of the magnetic particle combination 30 in the cleaning solution is improved, and finally, the cleaning effect of the two parts of the cleaning solution on the magnetic particle combination 30 is improved.

In some embodiments, the injection member 120 may be caused to suck up the cleaning solution and inject the cleaning solution into the reaction cup 20 by pushing the piston, and the amount of the cleaning solution injected into the reaction cup 20 at a time is set. Therefore, in order to improve the accuracy of the injection amount of the cleaning liquid, the movement stroke of the piston can be calibrated after the injection member 120 completes injection each time.

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 (10)

1. A cleaning method can be applied to a cleaning mechanism to clean magnetic particle combinations in a reaction cup, and is characterized in that the cleaning mechanism comprises a liquid injection piece, and the cleaning method comprises the following steps:

injecting a cleaning solution into the reaction cup which is positioned at the liquid injection station and contains the magnetic particle combination through the liquid injection member, so that the cleaning solution flows downstream into the reaction cup along the inner wall surface of the reaction cup under the action of self gravity;

enabling the reaction cup to generate eccentric oscillation so as to uniformly mix the magnetic particle combination and the cleaning solution; and

and moving the reaction cup subjected to eccentric oscillation to a liquid suction station, adsorbing the magnetic particle combination to the inner wall surface of the reaction cup through a magnetic member positioned outside the reaction cup, and extracting waste liquid from the reaction cup into which the cleaning liquid has been injected.

2. The cleaning method according to claim 1, wherein before allowing the cleaning liquid to flow forward along the inner wall surface of the reaction cup into the reaction cup by its own weight, the method further comprises: the liquid injection direction of the cleaning liquid flowing out of the liquid injection piece is intersected with the central axis of the reaction cup to form a set included angle.

3. The cleaning method according to claim 2, wherein the liquid injection member is located outside the reaction cup during the injection of the cleaning liquid.

4. The cleaning method according to claim 1, wherein causing the cleaning liquid to flow forward into the reaction cup along the inner wall surface of the reaction cup under its own weight comprises: and recording the position where the cleaning liquid output from the liquid injection piece is firstly contacted with the reaction cup as a liquid dropping point, and enabling the liquid dropping point to be higher than the liquid level in the reaction cup.

5. The cleaning method of claim 1, wherein generating eccentric oscillations in the reaction cup comprises: and enabling the reaction cup to generate eccentric oscillation at the liquid injection station.

6. The cleaning method according to claim 5, wherein after the injection of the cleaning liquid is completed, the eccentric oscillation of the reaction cup is further caused; or, the reaction cup is eccentrically oscillated while the cleaning solution is injected.

7. The cleaning method of claim 1, further comprising:

and moving the reaction cup after the waste liquid is extracted to the liquid injection station, and executing the cleaning method again, wherein the time duration and/or the oscillation intensity of the later eccentric oscillation are/is larger than that of the earlier eccentric oscillation.

8. The cleaning method according to claim 1, wherein the cleaning mechanism further comprises a blending part and a rotating shaft which are connected with each other, the blending part is provided with a blending position, the blending position is arranged at an interval with the rotating shaft along an axial direction perpendicular to the rotating shaft, and the reaction cup is placed on the blending position of the blending part, so that the rotating shaft drives the reaction cup to generate eccentric oscillation through the blending part.

9. The cleaning method according to claim 8, wherein the distance between the blending position and the rotating shaft along the axial direction perpendicular to the rotating shaft is recorded as an eccentric distance, so that the length of the eccentric distance and the speed of the rotating shaft can be adjusted.

10. The cleaning method according to claim 1, further comprising at least one of the following technical solutions:

making the cleaning liquid flow forward to the reaction cup along the inner wall surface of the reaction cup under the action of self gravity comprises: when the reaction cup moves to the liquid injection station at least once to inject the cleaning liquid, the liquid injection piece injects the cleaning liquid into the reaction cup in two parts; after the first part of cleaning solution is injected into the reaction cup, the reaction cup generates eccentric oscillation and lasts for a set time; then injecting a second part of cleaning solution into the reaction cup and enabling the reaction cup to generate eccentric oscillation;

leaving the reaction cups from the filling station and reaching the filling station comprises: and the reaction cup is made to do linear motion or circular motion between the liquid injection station and the liquid suction station.

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