CN217466939U

CN217466939U - Incubation magnetic separation equipment applied to chemiluminescence determination

Info

Publication number: CN217466939U
Application number: CN202220393425.3U
Authority: CN
Inventors: 杨文涛; 刘长生; 陈卫民; 宋国理
Original assignee: Nanjing Norman Biotechnology Co ltd
Current assignee: Nanjing Norman Biotechnology Co ltd
Priority date: 2022-02-25
Filing date: 2022-02-25
Publication date: 2022-09-20
Anticipated expiration: 2032-02-25

Abstract

The utility model discloses an incubation magnetic separation equipment applied to chemiluminescence measurement, which belongs to the technical field of medical appliances. The method comprises the following steps: the incubation device is arranged inside the cavity; a magnetic separation device, comprising: the device comprises a lifting mechanism arranged outside the cavity, a cleaning mechanism in transmission connection with the lifting mechanism, and an adsorption mechanism arranged between the incubation device and the cavity; the transfer clamping jaw is arranged above the incubation device and the adsorption mechanism; the photon detection device is arranged on the outer wall of the rack and communicated with the magnetic separation device; the cleaning mechanism is positioned between the lifting mechanism and the photon detection device. The utility model discloses integrated the incubation of reagent and sample, wash and measurement function, reduced device area more than 60%.

Description

Incubation magnetic separation equipment applied to chemiluminescence determination

Technical Field

The utility model belongs to the technical field of medical instrument, especially relate to an incubation magnetic separation equipment who is applied to chemiluminescence survey.

Background

In the field of medical detection, the chemiluminescence immunoassay technology is recognized as a clinical test by a detection technology integrating sensitive chemiluminescence analysis and specific antigen-antibody immunoassay. Among them, direct chemiluminescence is favored by many research institutes and medical device manufacturers because it does not require a catalyst, emits light only by changing conditions such as the pH of the solution, has a rapid reaction, a low background, a high signal to noise ratio, and a linear relationship between the amount of luminescence and the AE concentration

With the increasing maturity of direct chemiluminescence technology and the increasing demand of the market for miniaturization and clinics, customers have placed increasing demands on the size of the instrument. The chemiluminescence detection device and the incubation magnetic separation used in the current market are separated, so that the occupied area is large, the time of a detection period is increased due to mutual transfer, and the efficiency is low.

SUMMERY OF THE UTILITY MODEL

The utility model provides an incubation magnetic separation equipment applied to chemiluminescence determination for solving the technical problems existing in the prior art.

The utility model adopts the following technical scheme: an incubated magnetic separation device for use in a chemiluminescent assay comprising: the top of the frame is provided with a cavity with a hollow structure inside; further comprising:

the incubation device is arranged inside the cavity;

a magnetic separation device, comprising: the device comprises a lifting mechanism arranged outside the cavity, a cleaning mechanism in transmission connection with the lifting mechanism, and an adsorption mechanism arranged between the incubation device and the cavity;

the transfer clamping jaw is arranged above the incubation device and the adsorption mechanism;

the photon detection device is arranged on the outer wall of the rack and communicated with the magnetic separation device; the cleaning mechanism is positioned between the lifting mechanism and the photon detection device;

after the blood to be measured is incubated in a predetermined environment for a predetermined time in a heat preservation manner in an incubation device, the blood to be measured is transferred into an adsorption mechanism from the incubation device through a transfer clamping jaw, the multistage magnetic separation and cleaning of the blood to be measured are realized by combining a liquid pumping structure, and finally, photon detection is carried out on the cleaned blood through a photon detection device.

In a further embodiment, the transfer jaw has one degree of freedom of movement in the X-axis direction and the Z-axis direction, respectively.

In a further embodiment, the incubation device comprises:

the incubation disc is rotatably arranged in the cavity; the top of the incubation tray is sunken to a preset depth from top to bottom to form a plurality of incubation grooves; the incubation tank is configured to hold a reaction cup;

the first rotating source is arranged at the bottom of the frame and is in transmission connection with the incubation disc; the first rotation source drives the incubation disc to rotate;

and the heating element is arranged on the lower surface of the incubation disc.

In a further embodiment, the cleaning mechanism comprises:

the mounting piece is in transmission connection with the lifting mechanism;

at least two sets of needle assemblies mounted at predetermined intervals at the edge of the mounting member;

wherein the needle assembly comprises: the inner part of the liquid injection needle is of a hollow structure; the top of the liquid injection needle is provided with a liquid injection part communicated with the liquid injection needle;

the liquid suction needle penetrates through the interior of the liquid injection needle along the axial direction; the top and the bottom of the imbibition needle are exposed to the pipetting needle; and the top end of the liquid injection needle is hermetically connected with the outer wall of the liquid suction needle.

In a further embodiment, the cleaning mechanism further comprises:

the first liquid injection needle is arranged between the lifting mechanism and the needle assembly; the first liquid injection needle is used for injecting part of cleaning liquid into the reaction cup in advance;

the second liquid injection needle is arranged between the needle assembly and the photon acquisition device; the second liquid injection needle is used for injecting the enhancement liquid A into the reaction cup;

the third liquid injection needle is arranged between the second liquid injection needle and the photon acquisition device; and the third liquid injection needle is used for injecting the reinforcing liquid B into the reaction cup.

In a further embodiment, the cleaning mechanism further comprises:

the waste liquid needle is arranged at the edge of the mounting piece and is positioned on the opposite surface of the needle assembly; the waste liquid needle is used for sucking the detected waste liquid.

In a further embodiment, the adsorption mechanism comprises:

the adsorption rotor is provided with a certain thickness along the radial direction to form a bearing surface; the bearing surface is downwards recessed from top to bottom by a preset depth to form a plurality of adsorption grooves; the adjacent adsorption tanks are arranged according to a preset interval;

the adsorption pieces are distributed in the cavity at the preset intervals; the adsorption piece has certain magnetism;

the second rotating source is arranged at the bottom of the rack and is in transmission connection with the adsorption rotor; and the second rotating source drives the adsorption rotor to complete intermittent autorotation according to a preset time interval, and the adsorption rotor is rotated to the position of the photon detection device from the position of the lifting mechanism through the cleaning mechanism.

In a further embodiment, the adsorption mechanism further comprises:

and the heater is arranged at the bottom of the cavity and is positioned below the adsorption rotor.

In a further embodiment, the outer side surface of the bottom of the adsorption groove is in a hollow structure.

The utility model has the advantages that: the utility model discloses integrated the incubation of reagent and sample, wash and measurement function, reduced device area more than 60%.

The incubation area of the device is arranged in the middle of the magnetic separation area, so that the space of the original solid area in the middle is fully utilized on the premise of not changing the size of the magnetic separation area.

The magnetic separation cleaning and the enhancement liquid are injected into the outer area, and the light-emitting value is measured into a whole, so that all actions and functions are completed in one circle, the number of motors and optical couplers is greatly reduced, the linkage transportation among the functions is also reduced, and the compiling difficulty of a control algorithm is reduced.

The liquid injection needle, the liquid suction needle and the solid-liquid separation needle are integrated in the lifting of the needle cleaning area, the injection and the drawing of the cleaning liquid and the solid-liquid separation of the waste liquid after the reaction are completed under one action, the use of a motor and an optical coupler is also reduced, the synchronism of the action is increased, and the control is more favorably realized.

Drawings

FIG. 1 is a first schematic structural diagram of an incubation magnetic separation device for chemiluminescence assay according to the present invention.

FIG. 2 is a cross-sectional view of the whole of an incubated magnetic separation apparatus for chemiluminescence assay according to the present invention.

FIG. 3 is a partial cross-sectional view of a magnetic separation device for incubation for chemiluminescence assay according to the present invention.

FIG. 4 is a schematic structural diagram of a magnetic separation device for incubation for chemiluminescence assay according to the present invention.

Each of fig. 1 to 4 is labeled as: the device comprises a frame 1, a cavity 2, an incubation device 3, a magnetic separation device 4, a photon detection device 5, an incubation tray 301, an incubation groove 302, a first rotation source 303, a heating member 304, a lifting mechanism 401, a cleaning mechanism 402, an adsorption mechanism 403, a mounting member 4021, a needle assembly 4022, a liquid injection needle 4023, a liquid injection part 4024, a liquid injection needle 4025, a first liquid injection needle 4026, a second liquid injection needle 4027, a third liquid injection needle 4028, a waste liquid needle 4029, an adsorption rotor 4031, an adsorption groove 4032, a second rotation source 4033, a heater 4034, a hollowed-out structure 4035, a first motor 501, a first belt pulley 502, a second belt pulley 503, a first rotating shaft 504, a second motor 505 and a second rotating shaft 506.

Detailed Description

The invention is further described with reference to the drawings and examples.

Example 1

In order to solve the technical problems in the background art, the present embodiment provides an incubation magnetic separation apparatus for chemiluminescence assay, as shown in fig. 1, comprising: the top of frame 1, frame 1 is provided with a cavity 2. The cavity 2 is hollow for placing the incubation device 3. The incubation device 3 is used for incubation of human antigens, antibodies and defined reagents at a predetermined temperature. Also include the magnetic separation device 4 that is used for also carrying out the washing to the cultivation, specifically include: an elevating mechanism 401, a cleaning mechanism 402, and a suction mechanism 403. The lifting mechanism 401 is arranged on the outer wall of the cavity 2, the cleaning mechanism 402 is connected to the lifting mechanism 401 in a transmission manner, the cleaning mechanism 402 is driven by the lifting mechanism 401 to realize positioning at a preset height, and when liquid pumping or liquid suction is required, the lifting mechanism 401 controls the cleaning mechanism 402 to be at the lowest position; on the contrary, when the liquid pumping or liquid sucking is not needed, the lifting mechanism 401 controls the cleaning mechanism 402 to be at the highest position to empty in the cavity 2. The adsorption mechanism 403 is arranged between the incubation device 3 and the cavity 2, and realizes solid-liquid separation through magnetic adsorption.

Further comprising: a transfer jaw, which is arranged above the incubation device 3 and the adsorption mechanism 403, and is used for completing the scheduling of the reaction cups between the incubation device 3 and the adsorption mechanism 403.

The photon detection device 5 is arranged on the outer wall of the rack 1 and communicated with the magnetic separation device 4; the cleaning mechanism 402 is positioned between the lifting mechanism 401 and the photon detection device 5;

after the blood to be measured is incubated in the incubation device 3 in a preset environment for a preset time, the blood to be measured is transferred into the adsorption mechanism 403 from the incubation device 3 through the transfer clamping jaws, the multistage magnetic separation cleaning is realized on the blood to be measured by combining the liquid pumping structure, and finally, the photon detection is carried out on the cleaned blood through the photon detection device 5.

In this embodiment, since the whole device integrates at least three functions (incubation, cleaning and detection) and needs to meet the reduced floor space of the market, the apparatus is compact and has the following limitations for the transfer jaws: the transfer jaw has one degree of freedom of movement in the X-axis direction and the Z-axis direction, respectively. In other words, in this embodiment, the top of the cavity 2 is fixed with a cover body, and the cover body is arranged to create a sealed environment, so as to avoid the influence of external illumination on the measurement of the later-period light emission value. Therefore, an opening is formed at one edge of the cover body, and the opening provides enough clamping space for the transfer clamping jaw: operation in the longitudinal direction of the opening (movement of the cuvette in the longitudinal direction is effected inside the opening and includes picking up the cuvette from the incubation device 3 and moving it upward, moving it downward from above and placing it into the washing mechanism 402). While satisfying the requirement that the transfer jaws are in the specified lateral direction (movement of the cuvette in the lateral direction outside the chamber 2, i.e. transfer of the cuvette from above the incubation unit 3 to above the washing means 402, within the limits allowed by the opening).

Due to the lack of movement in at least one dimension, the transfer jaw described above has a dead angle in terms of scheduling, i.e. a cuvette which is not in the transverse direction specified by the transfer jaw cannot be gripped. Therefore, in order to solve this technical problem, the present embodiment makes the following improvements to the incubation device 3:

as shown in fig. 2, the incubation device 3 comprises: an incubation tray 301 having a top portion recessed by a predetermined depth from top to bottom to form a plurality of incubation grooves 302; the incubation well 302 is configured to hold reaction cups.

Further comprising: a first rotation source 303, which is arranged at the bottom of the frame 1 and is in transmission connection with the incubation tray 301; the first rotation source 303 drives the incubation disc 301 to rotate; that is, the reaction cups in the self-rotating incubation tray 301 are rotated to the horizontal direction designated by the transfer jaw, and then the gripping of the reaction cups at each angle on the incubation tray 301 is completed by the combination of the transfer jaw. In this embodiment, the first rotation source 303 includes: the first motor 501 is disposed at the bottom of the rack 1. The bottom of the output shaft of the first motor 501 is connected with a first belt pulley 502 in a transmission manner. Further comprising: the first shaft 504 is rotatably mounted to the frame 1 at its bottom and is fixedly connected to the bottom surface of the incubation plate 301 at its top. A second belt pulley 503 is fixed on the first rotating shaft 504, and the second belt pulley 503 is in transmission connection with the first belt pulley 502 through a transmission belt. It is driven by a first motor 501 and spins the incubation on a first pulley 502, a second pulley 503, a first drive belt and a first spindle 504.

Meanwhile, in order to create a predetermined environment temperature, which is better than a 37 ℃ heat preservation environment, the present embodiment is implemented by the heating element 304 disposed on the lower surface of the incubation plate 301, in the present embodiment, the heating element 304 is a heating sheet in the prior art to implement heating, the temperature is monitored, fed back and controlled by the temperature sensor, and the over-temperature protection is implemented by the over-temperature protection switch (SEKI-ST-22), so that the details are not described herein.

In a further embodiment, the cleaning mechanism 402 comprises: the mounting member 4021 is drivingly connected to the lifting mechanism 401, in this embodiment, the lifting mechanism 401 is driven by a motor in the prior art, and is combined with the guide rail to achieve lifting in a fixed direction, so that details are not described herein. And mounting members 4021 are preferably mounting plates having an outer edge with a curvature.

Further comprising: at least two sets of needle assemblies 4022, in this embodiment, four sets are exemplified. The four sets of needle assemblies 4022 are mounted at the edges of the mounting members 4021 at predetermined intervals, in other words, the distance between the needle assemblies 4022 of two adjacent sets is equal, defined as L. Four-stage magnetic separation cleaning is realized through four groups of needle assemblies 4022 which are arranged in series. As shown in fig. 3, each set of needle assemblies 4022 has the same structure, and specifically includes: the interior is the liquid beating needle 4023 of hollow structure, and the top of liquid beating needle 4023 has the liquid beating portion 4024 that is linked together with it, and wherein liquid beating portion 4024 is through pipeline and cleaning solution case, is provided with the electric pump on the pipeline, through the electric pump with the washing liquid by the cleaning solution case suction to the liquid beating needle 4023 in to throw the washing liquid into the reaction cup that is located adsorption apparatus 403 by liquid beating needle 4023. Further comprising: a pipette needle 4025 axially penetrating the inside of the pipette needle 4023, and the top and bottom of the pipette needle 4025 are exposed to the pipette needle 4023, and thus the purpose of the design is: since the liquid can flow from a high position to a low position by gravity during pipetting, but the liquid at the low position needs to be sucked as much as possible during pipetting, the bottom end of the pipetting needle 4025 is lower than the bottom end of the pipetting needle 4023. At the same time, the distal end of the pipette needle 4023 is sealingly connected to the outer wall of the pipette needle 4025 in order to allow the liquid to smoothly flow back into the waste liquid tank during liquid suction. And the top of the liquid pumping box passes through the waste liquid box through a pipeline, and an electric pump is arranged on the pipeline.

To increase the intensity of the cleaning, in another embodiment, the cleaning mechanism 402 further comprises: a first injection needle 4026 provided between the lifting mechanism 401 and the needle assembly 4022; the first liquid injection needle 4026 is used for injecting part of cleaning liquid into the reaction cup in advance; the second liquid injection needle 4027 is arranged between the needle assembly 4022 and the photon collection device and is used for prolonging the cleaning time as a pre-cleaning; the second liquid injection needle 4027 is used for injecting the reinforcing liquid A into the reaction cup; in this embodiment, the enhancing solution A provides a reagent environment for detection of the analyte.

The third injection needle 4028 is arranged between the second injection needle 4027 and the photon acquisition device; the third injection needle 4028 is used to inject the reinforcing liquid B into the reaction cup. In this embodiment, the enhancing liquid B is used to promote luminescence for detection.

In a further embodiment, the washing mechanism 402 further comprises: a waste needle 4029 disposed at an edge of the mounting member 4021 and on an opposite side of the needle assembly 4022; the waste liquid needle 4029 is used for sucking the detected waste liquid.

Based on the above description, the adsorption mechanism 403 includes: an adsorption rotor 4031 having a certain thickness in a radial direction to form a bearing surface; the bearing surface is downwards recessed from top to bottom by a preset depth to form a plurality of adsorption grooves 4032; the adjacent adsorption grooves 4032 are arranged at predetermined intervals. Note that the distance between adjacent suction grooves 4032 is equal to the distance between the needle assemblies 4022 in the adjacent two groups, and is L. That is, the installation groove is matched with the needle assembly 4022, so that high-precision liquid pumping and liquid suction are realized.

The number and position of the adsorption pieces corresponding to the needle assembly 4022 are also included, in other words, the distance between each adjacent group of adsorption pieces is L. In this embodiment, the adsorbing member is a magnet for adsorbing magnetic beads in the sample.

In order to realize the four-step magnetic separation of the cuvettes in the same adsorption vessel 4032, a transfer process is required. Thus, the method further comprises the following steps: a second power source in transmission connection with the adsorption rotor 4031, wherein the second rotation source 4033 drives the adsorption rotor 4031 to complete intermittent rotation according to a preset time interval, the adsorption rotor 4031 is rotated to the position of the photon detection device 5 from the position of the lifting mechanism 401 through the cleaning mechanism 402 (namely, the previous work of detection is completed according to the sequence of first-order separation, second-order separation, …, fourth-order separation, addition of the enhancement liquid A and addition of the enhancement liquid B.)

In a further embodiment, the second rotational source 4033 includes: a second motor 505 fixed to the frame 1; a third belt wheel is mounted on an output shaft of the second motor 505 in a transmission manner. And a second rotating shaft 506, wherein the second rotating shaft 506 is sleeved outside the first rotating shaft 504 and is not in contact with the first rotating shaft 504. The second rotating shaft 506 has a top end fixedly connected to the adsorbing rotor 4031 and a bottom end rotatably mounted on the frame 1. A fourth belt wheel is fixed on the outer side wall of the second rotating shaft 506, and the fourth belt wheel and the third belt wheel are driven by a transmission belt, so that the adsorption rotor 4031 rotates. And performs equidistant intermittent rotations according to distance and time interval by inputting a predetermined algorithm to the second motor 505.

In a further embodiment, the object to be detected needs to be kept in the incubation unit 3 until detection, i.e. the environment must not have too high a temperature difference, in order not to affect the detection result. Therefore, a heater 4034 for heating the adsorption rotor 4031 is disposed below the adsorption rotor 4031, in this embodiment, the heater 4034 is also heated by a heating sheet in the prior art, temperature is monitored, fed back and controlled by a temperature sensor, and over-temperature protection is achieved by an over-temperature protection switch (SEKI-ST-22), which is not described herein again.

In a further embodiment, the photon detection device 5 may adopt the prior art, but it should be noted that the photon detection device 5 scans the object to be detected inside the reaction cup, so that the external side surface of the bottom of the adsorption groove 4032 is a hollow structure 4035 so as not to affect the normal operation of the photon detection device 5, that is, the photon detection device 5 detects the object to be detected inside the reaction cup through the hollow structure 4035.

The working principle of the embodiment is as follows:

placing human antigens, antibodies and specified reagents into a reaction cup, placing the reaction cup into an incubation groove in an incubation tray, and incubating for a preset time at a specified temperature; the reaction cup in the incubation tray and the substances in the reaction cup are subjected to heat preservation treatment by the heating element arranged below the incubation tray. The temperature can be controlled to be 37 ℃.

Step two, the first rotation source drives the incubation disc to rotate, the incubated reaction cup is transferred into an adsorption groove of the adsorption rotor by matching with the movable clamping jaw, and the current reaction cup and the corresponding adsorption groove are controlled to be positioned at the first liquid injection needle;

thirdly, a first liquid injection needle injects part of cleaning liquid into the reaction cup; at the moment, the magnet matched with the first liquid injection needle begins to adsorb magnetic beads in the reaction cup, and solid-liquid separation of substances in the reaction cup begins to be realized.

Step four, the second rotation source drives the adsorption rotor to rotate for a preset distance, so that the current reaction cup sequentially stops N needle assemblies, and each group of needle assemblies sequentially performs liquid pumping and liquid suction on the current reaction cup when each reaction cup stops; taking the first stay as an example, when the current reaction cup is transferred to the position of the second group of needle assemblies, the cleaning liquid in the cleaning liquid tank is pumped into the reaction cup through the liquid pumping needle of the needle assemblies, and after the preset time, the liquid in the reaction cup is taken out to the waste liquid tank through the liquid suction needle of the needle assemblies. In the process, the cleaning liquid has certain fluidity in the reaction cup, and the adsorption piece adsorbs the magnetic beads all the time, so that the two combinations increase the mixing strength and realize more thorough solid-liquid separation.

Step five, the second rotation source continues to drive the adsorption rotor to rotate for a preset distance, and the reinforcement liquid A and the reinforcement liquid B are respectively injected into the current reaction cup through a second liquid injection needle and a third liquid injection needle; the second liquid injection needle and the third liquid injection needle are respectively communicated with the containers of the enhancement liquid A and the enhancement liquid B through pipelines, and are respectively provided with an electric pump for providing certain external force.

Step six, the photon detection device finishes detection through the hollow structure of the adsorption tank;

and step seven, the second rotating source continues to drive the adsorption rotor to rotate for a preset distance, and the waste liquid needle sucks the detected waste liquid in the reaction cup.

The liquid injection needle, the liquid suction needle and the solid-liquid separation needle are integrated in the lifting of the needle cleaning area, the injection and the suction of cleaning liquid and the solid-liquid separation of waste liquid after the reaction are completed under one action, the use of a motor and an optical coupler is also reduced, the synchronism of the action is increased, and the control is more favorably realized.

Claims

1. An incubated magnetic separation device for use in a chemiluminescent assay comprising: the top of the frame is provided with a cavity with a hollow structure inside; it is characterized by also comprising:

the incubation device is arranged inside the cavity;

2. An incubated magnetic separation apparatus for chemiluminescent assay according to claim 1 wherein the transfer jaw has one degree of freedom of movement in each of the X and Z axes.

3. An incubated magnetic separation device for use in chemiluminescent assays according to claim 2 wherein said incubation means comprises:

4. The device for incubated magnetic separation for chemiluminescent assay of claim 1 wherein the washing mechanism comprises:

the mounting piece is in transmission connection with the lifting mechanism;

5. The device for incubated magnetic separation for chemiluminescent assay according to claim 4 wherein the washing mechanism further comprises:

6. The device for incubated magnetic separation for chemiluminescent assay according to claim 4 wherein the washing mechanism further comprises:

7. The device for incubated magnetic separation for chemiluminescent assay of claim 1 wherein the adsorption mechanism comprises:

8. The apparatus of claim 7, wherein the adsorption mechanism further comprises:

9. The device for incubated magnetic separation for chemiluminescence assay according to claim 7, wherein the outer side of the bottom of the adsorption tank is hollow.