Magnetic bead mixing device

Abstract

The utility model discloses a magnetic bead blending device which comprises a driving mechanism, a fixing mechanism and a magnetic attraction mechanism, one end of the fixing mechanism is fixedly connected with the driving end of the driving mechanism, a containing groove is formed in the other end of the fixing mechanism, and the magnetic attraction mechanism is fixedly arranged in the containing groove; when the driving mechanism drives the magnetic attraction mechanism to rotate to drive the magnetic beads to move, the magnetic beads can be in full contact with a solution in the process of moving in the solution, so that the magnetic beads are uniformly mixed; the magnetic beads are in full contact with the cracked sample solution, so that more nucleic acid is adsorbed on the surfaces of the magnetic beads; the magnetic beads are in full contact with the cleaning liquid, so that impurities on the surfaces of the magnetic beads can be cleaned, the impurities are prevented from entering nucleic acid products eluted in the next step, and the purity of the nucleic acid products is improved; similarly, the magnetic beads rotate in the solution, so that the magnetic beads are in full contact with the cleaning solution and the eluent, the nucleic acid adsorbed on the magnetic beads is fully eluted by the eluent, and impurities are fully washed away, so that the nucleic acid purification efficiency is improved, and the accuracy and reliability of experimental results are ensured.

Description

TECHNICAL FIELD

[0001] The utility model relates to biochemical detection technical field especially, relate to a magnetic bead mixing device. BACKGROUND

[0002] The magnetic bead method extracts nucleic acid and is a commonly used nucleic acid extraction and purification method in the biochemical detection field, and experimental steps mainly include sample lysis, magnetic bead and nucleic acid adsorption combination, separation of the magnetic bead adsorbing nucleic acid from the remaining components in the solution by using a magnetic field, and finally elution of the nucleic acid adsorbed on the magnetic bead.

[0003] Using the microfluidic chip to drive the directional flow of liquid to realize the automation of the nucleic acid detection process is a kind of efficient detection means, which is conducive to realizing the "sample-in-result-out" integrated nucleic acid detection with sample processing. However, when adsorbing, the magnetic beads need to be gathered in the microfluidic chip by using a magnetic force frame, and the magnetic beads gathered together cannot fully contact the solution, so the amount of nucleic acid adsorbed on the magnetic beads is limited; when eluting, the eluent cannot fully contact the magnetic beads gathered together with the eluent, so the nucleic acid adsorbed on the magnetic beads cannot be fully and completely eluted, which will lead to low nucleic acid extraction efficiency and affect the final experimental results. Therefore, it is an urgent problem to design a magnetic bead mixing device. SUMMARY

[0004] The utility model discloses a magnetic bead mixing device, to solve the problem of prior art, namely provide a kind of for microfluidic chip's magnetic bead mixing device.

[0005] To achieve the above object, the utility model adopts the following technical scheme:

[0006] A kind of magnetic bead mixing device, including driving mechanism, fixed mechanism, magnetic attraction mechanism;The one end of the fixed mechanism is fixedly connected with the driving end of the driving mechanism, the other end of the fixed mechanism is equipped with containing groove, the magnetic attraction mechanism is fixedly arranged in the containing groove.

[0007] Preferably, it further includes position adjusting mechanism, one end of the position adjusting mechanism is fixedly connected with the driving end of the driving mechanism, the other end of the position adjusting mechanism is fixedly connected with the one end of the fixed mechanism away from containing groove.

[0008] Preferably, the position adjusting mechanism includes shaft coupling and shaft sleeve;The shaft coupling is arranged in the shaft sleeve, and the shaft coupling is fixed in the shaft sleeve by at least two limit blocks, one end of the shaft coupling is fixedly connected with the driving end of the driving mechanism, the other end of the shaft coupling is fixedly connected with the one end of the fixed mechanism away from containing groove.

[0009] Preferably, the magnetic attraction mechanism is permanent magnet.

[0010] Preferably, the end surface of the permanent magnet is not lower than the end surface of the accommodating groove.

[0011] Preferably, the permanent magnet is provided with at least two and arranged horizontally, and the magnetic poles of the end surfaces of the two adjacent permanent magnets are opposite.

[0012] Preferably, further comprising a microfluidic chip, the microfluidic chip is arranged directly below the magnetic attraction mechanism.

[0013] Compared with the prior art, the beneficial effects of the utility model are: when the driving mechanism drives the magnetic attraction mechanism to rotate, the magnetic field of the magnetic attraction mechanism rotates, drives the magnetic beads to make circular motion, the magnetic beads can be fully contacted with the solution in the process of making circular motion in the solution, so as to mix the magnetic beads; in the process of nucleic acid extraction and purification, when the magnetic beads and the sample solution after lysis are fully contacted, the surface of the magnetic beads can adsorb more nucleic acids; further, the magnetic beads and the cleaning liquid are fully contacted, so that the impurities on the surface of the magnetic beads can be cleaned, avoiding that the impurities enter the nucleic acid product of the next elution, and improving the purity of the nucleic acid product; similarly, the rotation of the magnetic beads in the solution makes the magnetic beads and the eluent fully contact, so that the nucleic acids adsorbed on the magnetic beads are fully eluted by the eluent, and the impurities are fully cleaned, thereby improving the efficiency of nucleic acid extraction and purification, and ensuring the accuracy and reliability of the experimental analysis results of the subsequent extracted and purified nucleic acids. BRIEF DESCRIPTION OF DRAWINGS

[0014] In order to more clearly illustrate the technical scheme in the embodiments of the utility model or the prior art, the drawings needed to be used in the embodiments will be briefly introduced below, and obviously, the drawings in the following description are only some embodiments of the utility model, and those skilled in the art can also obtain other drawings according to these drawings without creating creative labor.

[0015] Figure 1 The structure schematic view of the magnetic bead mixing device provided by the utility model cooperates with the microfluidic chip;

[0016] Figure 2 The structure schematic view of the magnetic bead mixing device provided by the utility model;

[0017] Figure 3 The structure schematic view of the cross slider coupling;

[0018] Figure 4 The structure explosion view of the cross slider coupling;

[0019] Figure 5 The structure schematic view of the microfluidic chip;

[0020] Figure 6Structure schematic view of magnetic bead mixing device for position adjusting mechanism and fixing mechanism not on the same straight line away from one end of containing groove;

[0021] Figure 7 Structure explosion view of magnetic bead mixing device;

[0022] Figure 8 Structure schematic view of magnetic bead mixing device provided for example three;

[0023] In the figure: 1 is a driving mechanism; 2 is a fixed mechanism; 3 is a magnetic attraction mechanism; 4 is a containing groove; 5 is a microfluidic chip; 501 is an annular flow channel; 502 is a first inlet; 503 is a second inlet; 504 is an outlet; 6 is a shaft sleeve; 7 is a cross slider coupling; 701 is a first movable connecting piece; 702 is a second movable connecting piece; 703 is a slider; 704 is a sliding groove; 8 is a limiting block. DETAILED DESCRIPTION

[0024] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0025] The purpose of the present application is to provide a magnetic bead mixing device to solve the problems existing in the prior art and to fully mix and contact the magnetic beads and the solution to improve the nucleic acid extraction and purification efficiency.

[0026] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the present application will be further described in detail below with reference to the drawings and specific embodiments. Embodiment one

[0027] The present embodiment provides a magnetic bead mixing device, please refer to Figure 1 and Figure 7 , including driving mechanism 1, fixed mechanism 2, magnetic attraction mechanism 3; one end of the fixed mechanism 2 is fixedly connected with the driving end of the driving mechanism 1, the other end of the fixed mechanism 2 is provided with a containing groove 4, and the magnetic attraction mechanism 3 is fixedly arranged in the containing groove 4.

[0028] In the present embodiment, the driving mechanism 1 can be one of motor, pneumatic motor and hydraulic motor, in order to simplify the structure of the device, the driving mechanism 1 of the present embodiment is preferably a motor.

[0029] Among them, please refer to Figure 1 and Figure 5The magnetic bead mixing device provided by the embodiment is in operation, the motor drives the fixed mechanism 2 to rotate and drives the magnetic attraction mechanism 3 to rotate. Therefore, the micro-fluidic chip 5 used in cooperation is provided with an annular flow channel 501 matched with the rotating track of the magnetic attraction mechanism 3. In order to smoothly drive the magnetic beads to move in the annular flow channel 501, the diameter of the annular flow channel 501 is not greater than the diameter of the magnetic attraction mechanism 3, so as to ensure the magnetic attraction of the magnetic field of the magnetic attraction mechanism 3 to the magnetic beads in the annular flow channel 501. In this way, the magnetic attraction mechanism 3 can smoothly drive the magnetic beads in the annular flow channel 501 to move in the annular flow channel 501 when the magnetic attraction mechanism 3 rotates. In addition, the micro-fluidic chip is further provided with a first inlet 502, a second inlet 503 and an outlet 504.

[0030] As shown in Figure 1 and Figure 5 , the annular flow channel 501 on the micro-fluidic chip 5 is oppositely arranged with the magnetic attraction mechanism 3. The distance between the magnetic attraction mechanism 3 and the micro-fluidic chip 5 is 5mm-10mm. In this way, the magnetic attraction mechanism 3 does not directly contact the micro-fluidic chip 5, which not only protects the magnetic attraction mechanism 3 from damaging the micro-fluidic chip 5 when rotating, but also drives the magnetic beads in the annular flow channel 501 to move.

[0031] Please refer to Figure 1 and Figure 5, when the magnetic beads are mixed by using the magnetic bead mixing device provided in the embodiment, the nucleic acid of the pathogenic microorganism in the sample is released in the solution after the magnetic beads are added into the sample solution after lysis, and the nucleic acid is adsorbed on the surface of the magnetic beads to form a magnetic bead lysis mixture. First, the magnetic bead mixture is pumped into the first inlet 502 of the microfluidic chip 5 by using a peristaltic pump, the motor is turned on, the motor drives the magnetic attraction mechanism 3 to rotate, the magnetic field of the magnetic attraction mechanism 3 also rotates, and the magnetic beads are driven to make circular motion in the annular flow channel 501. In the process of circular motion of the magnetic beads in the solution, the magnetic beads can be in full contact with the solution, so that the magnetic beads are thoroughly mixed. In this process, the magnetic beads and the sample solution after lysis are in full contact, so that more nucleic acid can be adsorbed on the surface of the magnetic beads. After completion, the excess solution is discharged from the outlet 504, and the magnetic beads adsorbed with the nucleic acid are retained in the annular flow channel 501 under the attraction of the magnetic field force of the magnetic attraction mechanism 3. Secondly, the cleaning solution is pumped into the first inlet 502 of the microfluidic chip 5 by using a peristaltic pump, the magnetic attraction mechanism 3 rotates to drive the magnetic beads to make circular motion in the annular flow channel 501, the magnetic beads are in full contact with the cleaning solution, so that the impurities on the surface of the magnetic beads can be thoroughly cleaned, avoiding the impurities entering the nucleic acid product in the next elution step, and improving the purity of the nucleic acid product. After completion, the cleaning solution is discharged from the outlet 504, and the magnetic beads adsorbed with the nucleic acid are retained in the annular flow channel 501 under the attraction of the magnetic field force of the magnetic attraction mechanism 3. Finally, the elution solution is pumped into the second inlet 503 of the microfluidic chip by using a peristaltic pump, the magnetic attraction mechanism 3 rotates to drive the magnetic beads to make circular motion in the annular flow channel 501, the magnetic beads are in full contact with the elution solution, so that the nucleic acid adsorbed on the magnetic beads is thoroughly and fully eluted by the elution solution, and the nucleic acid product is collected from the outlet 504. Thus, the efficiency of nucleic acid extraction and purification is improved, and the accuracy and reliability of the experimental results when the extracted nucleic acid is further analyzed are ensured.

[0032] As can be seen, the magnetic bead mixing device provided in the embodiment can mix the magnetic beads in the process of nucleic acid purification only by driving mechanism 1, fixing mechanism 2 and magnetic attraction mechanism 3, so as to improve the efficiency of nucleic acid extraction and purification, and ensure the accuracy and reliability of the experimental results when the extracted nucleic acid is further analyzed.

[0033] In some embodiments, please refer to Figure 6 and Figure 7 , in order to adjust the relative position of the driving end of the driving mechanism 1 and the end of the fixing mechanism 2 away from the containing groove 4, the relative position of the driving end and the fixing mechanism 2 is adjustable, and further comprising a position adjusting mechanism, one end of the position adjusting mechanism is fixedly connected with the driving end of the driving mechanism 1, and the other end of the position adjusting mechanism is fixedly connected with the end of the fixing mechanism 2 away from the containing groove 4; as shown in Figure 6 , when the position adjusting mechanism adjusts the driving end and the end of the fixing mechanism 2 away from the containing groove 4 not on the same straight line, the mixing effect of the magnetic beads in the annular flow channel 501 is the best.

[0034] In some embodiments, please refer to Figure 1、 Figure 2 、 Figure 3 、 Figure 4 、 Figure 5 and Figure 7 In order to simplify the structure of the position adjusting mechanism, the position adjusting mechanism comprises a shaft sleeve 6 and a coupling; the coupling is arranged inside the shaft sleeve 6 and is fixed in the shaft sleeve 6 by at least two limiting blocks 8, and in the embodiment, the limiting blocks 8 are preferably screws; one end of the coupling is fixedly connected with the driving end of the driving mechanism 1, and the other end of the coupling is fixedly connected with the fixing mechanism 2 away from one end of the accommodating groove 4.

[0035] In order to adjust the relative position between the driving end of the driving mechanism 1 and the end of the fixing mechanism 2 away from the accommodating groove 4, the coupling is preferably a cross slider coupling 7 in the embodiment, the cross slider coupling 7 comprises two first movable connecting pieces 701 and one second movable connecting piece 702, the two first movable connecting pieces 701 are provided with sliders 703, the second movable connecting piece 702 is provided with a sliding groove 704 matched with the sliders 703, the sliders 703 are slidingly arranged in the sliding groove 704, and in order to better drive the magnetic beads to move in the annular flow channel 501, the sliders 703 are partially arranged in the sliding groove 704, and by controlling the position of the sliders 703 in the sliding groove 704, the mixing effect of the magnetic beads in the annular flow channel 501 is best.

[0036] In some embodiments, please refer to Figure 2 In order to simplify the structure of the magnetic attraction mechanism 3, the magnetic attraction mechanism 3 is a permanent magnet.

[0037] In some embodiments, please refer to Figure 2 and Figure 7 In order to facilitate installation and control, the end surface of the permanent magnet is not lower than the end surface of the accommodating groove 4.

[0038] In some embodiments, please refer to Figure 2 and Figure 7 In order to ensure the magnetic field strength of the permanent magnet, the permanent magnet is provided with at least two and is arranged horizontally, and in order to simplify the structure, the number of the permanent magnets in the embodiment is two, the end surfaces of the two adjacent permanent magnets are opposite in magnetic pole, and in this way, the magnetic beads can be uniformly dispersed in the annular flow channel 501 under the action of the magnetic field of the permanent magnet in a shorter time, and the time for nucleic acid extraction and purification is saved.

[0039] In some embodiments, please refer to Figure 1 and Figure 5In order to apply the magnetic bead mixing device provided in the embodiment to nucleic acid extraction and purification experiments, a reagent bottle group required for nucleic acid extraction and purification is further included, and in order to simplify the steps of nucleic acid extraction and purification, the reagent bottle group is preferably a microfluidic chip 5, which is arranged directly below the magnetic attraction mechanism 3. In use, the microfluidic chip is fixed on the experiment table, and the magnetic bead mixing device and the microfluidic chip 5 provided in the embodiment jointly form a set of equipment for nucleic acid extraction and purification. Embodiment two

[0040] The use method of the magnetic bead mixing device provided in embodiment one is described in the embodiment, please refer to Figure 1 , Figure 2 , Figure 5 and Figure 7 In the embodiment, in order to better mix the magnetic beads, the cross slide coupling 7 is adjusted so that the driving end of the motor and the fixing mechanism 2 are not on the same straight line away from one end of the containing groove 4. Therefore, the use method of the magnetic bead mixing device provided in embodiment one is as follows:

[0041] Step one, adjust the distance between the microfluidic chip and the permanent magnet to 5mm;

[0042] Step two, uniform adsorption of magnetic beads to nucleic acid: turn on the peristaltic pump to pump the magnetic bead mixture (magnetic beads + sample solution after lysis, nucleic acid released in the lysis solution is adsorbed by the magnetic beads) from the first inlet 502 of the microfluidic chip, turn on the motor, and the motor drives the permanent magnet to rotate to drive the magnetic beads to make circular motion in the annular flow channel 501; change the rotation direction of the motor and repeat the above operation; finally, the peristaltic pump drives the excess solution to be discharged from the outlet 502, and the magnetic beads adsorbed with nucleic acid remain in the annular flow channel 501 under the action of the magnetic field force of the permanent magnet, and the peristaltic pump and the motor are turned off;

[0043] Step three, clean the magnetic beads: turn on the peristaltic pump to pump the cleaning solution from the first inlet 502 of the microfluidic chip, turn on the motor, and the motor drives the permanent magnet to rotate to drive the magnetic beads to make circular motion in the annular flow channel 501, change the rotation direction of the motor and repeat the above operation; finally, the peristaltic pump drives the cleaning solution to be discharged from the outlet 504, and the magnetic beads adsorbed with nucleic acid remain in the annular flow channel 501 under the action of the magnetic field force of the permanent magnet, and the peristaltic pump and the motor are turned off;

[0044] Step four, nucleic acid elution: turn on the peristaltic pump to pump the elution solution from the second inlet 503 of the microfluidic chip, turn on the motor, and the motor drives the permanent magnet to rotate to drive the magnetic beads to make circular motion in the annular flow channel 501, change the rotation direction of the motor and repeat the above operation; the magnetic beads remain in the annular flow channel 501 under the action of the magnetic field force of the permanent magnet, and the elution solution elutes the nucleic acid adsorbed on the magnetic beads, finally the peristaltic pump collects the purified nucleic acid product from the outlet 504, and the microfluidic chip is discarded. Embodiment three

[0045] The embodiment provides another magnetic bead mixing device, as shown in the figure. Figure 8

[0046] The embodiment has all advantages of the first embodiment, and details are not repeated here.

[0047] Please refer to Figure 8 Different from the first embodiment, the number of permanent magnets, in order to enhance the magnetic field strength, better drive the magnetic beads to move in the annular flow channel 501, the magnetic bead mixing device provided by the embodiment is provided with three permanent magnets, wherein the three permanent magnets are arranged in a straight line, and the magnetic poles of adjacent two permanent magnets are opposite.

[0048] The principle and implementation mode of the specific examples are described in the utility model, and the above embodiment is only used for helping to understand the method and core idea of the utility model; meanwhile, for the general technical personnel in the field, according to the idea of the utility model, the specific implementation mode and application range will be changed. In conclusion, the content of the specification should not be understood as the limitation of the utility model.​

Claims

1. A magnetic bead mixing device, characterized in that, It includes a driving mechanism, a fixing mechanism, and a magnetic attraction mechanism; one end of the fixing mechanism is fixedly connected to the driving end of the driving mechanism, and the other end of the fixing mechanism is provided with a receiving groove, and the magnetic attraction mechanism is fixedly disposed in the receiving groove.

2. The magnetic bead mixing device according to claim 1, characterized in that, It also includes a position adjustment mechanism, one end of which is fixedly connected to the drive end of the drive mechanism, and the other end of which is fixedly connected to the end of the fixing mechanism away from the receiving groove.

3. The magnetic bead mixing device according to claim 2, characterized in that, The position adjustment mechanism includes a coupling and a bushing; the coupling is disposed inside the bushing and is fixed inside the bushing by at least two limiting blocks; one end of the coupling is fixedly connected to the driving end of the driving mechanism, and the other end of the coupling is fixedly connected to the end of the fixing mechanism away from the receiving groove.

4. The magnetic bead mixing device according to claim 3, characterized in that, The magnetic attraction mechanism is a permanent magnet.

5. The magnetic bead mixing device according to claim 4, characterized in that, The end face of the permanent magnet is not lower than the end face of the receiving groove.

6. The magnetic bead mixing device according to claim 5, characterized in that, The permanent magnets are provided in at least two and arranged horizontally, with the magnetic poles of the end faces of two adjacent permanent magnets being opposite.

7. The magnetic bead mixing device according to claim 1, characterized in that, It also includes a microfluidic chip, which is positioned directly below the magnetic attraction mechanism.

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