Device and method for uniformly mixing fluid in micro-fluidic chip

Abstract

The invention discloses a device and a method for uniformly mixing fluid in a micro-fluidic chip, the device comprises a magnetic field loading unit and a magnetic unit, the magnetic unit is packaged in a mixing chamber of the micro-fluidic chip, the magnetic field loading unit is arranged outside the micro-fluidic chip, and the magnetic field loading unit is arranged in the mixing chamber of the micro-fluidic chip. The magnetic field loading unit is used for applying a magnetic field to the magnetic unit and driving the magnetic unit to move in the micro-fluidic chip under the action of the magnetic field, so that turbulent flow is generated in the micro-fluidic chip, and fluid in the micro-fluidic chip is uniformly mixed. A magnetic field is applied through the magnetic field loading unit, and the magnetic unit moves in the mixing chamber in a non-contact manner under the action of the magnetic field, so that turbulent flow is generated in the mixing chamber, uniform mixing of to-be-mixed fluid in the mixing chamber is ensured, the requirements on the structure and the driving precision of the micro-fluidic chip are reduced, and the working efficiency is improved. Meanwhile, the device has the effects of simple structure, high mixing efficiency, low cost and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biochemical equipment, in particular to a microfluidic chip internal mixing device and method. BACKGROUND

[0002] Microfluidic chip is a fast analysis platform that can integrate sample preparation, reaction, separation, detection and other basic operations involved in biological, chemical and medical analysis processes. The latest development of microfluidic technology makes it possible to apply to chip laboratories or micro total analysis systems. It allows controlling a small amount of liquid in micro-machined channels, and in some cases, it also allows effective automatic execution of analysis steps on microchips, including sample pretreatment, reaction, separation and detection, etc. Based on its small size, low reagent consumption and high integration, it has great application potential in the fields of biology, chemistry, medicine, etc., and has gradually developed into a highly cross-integrated research field of biochemistry, fluid mechanics, microelectronics, materials, machinery, etc. Among them, in the field of medical diagnosis, microfluidic chip is an important implementation platform for POCT (point-of-care testing) diagnostic equipment. It has been proven to have great potential in a variety of biological applications, including cell sorting, enzyme analysis, immunohybridization reaction, nucleic acid analysis, nucleic acid sequencing, etc.

[0003] Since general biochemical reaction processes (such as cell sorting, nucleic acid analysis or other sample processing reactions) involve fluid mixing, distribution, separation and other steps, they all need to be realized simultaneously on a microfluidic chip through the structural design of microchannels. Since the fluid in the microfluidic chip is in a laminar flow state, the mixing process in the chip is a difficulty.

[0004] The existing mixing methods of fluid in the microfluidic chip are generally divided into active and passive types. Passive mixing is achieved by setting special structures in the chip, such as the peach heart-shaped fixed wall and split baffle structure of Chinese patent CN222219516U, and the diamond obstacle array structure in the microfluidic chip channel disclosed by CN112934283A. Although passive mixing can achieve the mixing of two liquids in the microfluidic chip, this scheme requires the setting of specific mixing structures in the extremely small space in the microfluidic chip, which has high requirements for structural precision, can handle a small amount of liquid and has high requirements for liquid flow rate control. Active mixing uses surface acoustic waves to introduce vibration into the chamber to accelerate liquid mixing. A dynamic mechanism (pneumatic membrane) periodically generates positive / negative air pressure to drive the liquid to flow back and forth between the solution cavity and the buffer cavity, achieving closed and leak-free mixing. Although the above-mentioned active mixing scheme has high mixing efficiency, it needs to introduce an external energy field, which is relatively complex to implement and has high cost. SUMMARY

[0005] To address the problems existing in the prior art, the purpose of this invention is to provide a fluid mixing device and method for microfluidic chips that can achieve rapid mixing of fluids within the microfluidic chip, and which is simple in structure and low in cost.

[0006] To achieve the above objectives, the microfluidic chip fluid mixing device of the present invention includes a magnetic field loading unit and a magnetic unit. The magnetic unit is encapsulated in the mixing chamber of the microfluidic chip, and the magnetic field loading unit is disposed outside the microfluidic chip. The magnetic field loading unit is used to apply a magnetic field to the magnetic unit and drive the magnetic unit to move in the microfluidic chip under the action of the magnetic field, thereby generating turbulence in the microfluidic chip to mix the fluid in the microfluidic chip.

[0007] Furthermore, a protective layer is formed on the surface of the magnetic unit, and the protective layer material is silicon dioxide or polytetrafluoroethylene.

[0008] Furthermore, the magnetic unit is a cylindrical magnet, the cross-sectional diameter of which is 0.6-0.95 times the minimum cross-sectional dimension of the mixing chamber, and the height of which is 0.3-1 times the cross-sectional radius of the magnet.

[0009] Furthermore, the magnetic field loading unit is a permanent magnet or an electromagnet, and the magnetic pole surface of the magnetic field loading unit is parallel to the bottom surface of the mixing chamber.

[0010] Furthermore, the fluid in the mixing chamber is a mixture of multiple liquids or a solid-liquid mixture.

[0011] Furthermore, the mixing chamber can encapsulate multiple of the magnetic units.

[0012] Furthermore, it also includes a magnetic pole control unit, which is used to change the magnetic pole direction of the magnetic field loading unit in order to change the direction of the applied magnetic field.

[0013] Furthermore, when the magnetic field loading unit is a permanent magnet, the magnetic field loading unit changes the magnetic pole direction by driving the permanent magnet to flip; when the magnetic field loading unit is an electromagnet, the magnetic field loading unit changes the magnetic pole direction by changing the direction of the electromagnet current.

[0014] The mixing method of the fluid mixing apparatus of the present invention includes the following steps:

[0015] Encapsulating magnetic units within the hybrid chamber of a microfluidic chip;

[0016] The magnetic unit is positioned in the mixing chamber by applying a magnetic field through the magnetic field loading unit;

[0017] The fluid to be mixed is introduced into the mixing chamber;

[0018] The direction of the magnetic field applied by the magnetic field loading unit to the magnetic unit is changed, driving the magnetic unit to move in the mixing chamber, causing turbulence in the fluid to be mixed in the mixing chamber, so as to mix the fluid to be mixed in the microfluidic chip.

[0019] Furthermore, it also includes:

[0020] The magnetic field loading unit is placed at the bottom of the mixing chamber of the microfluidic chip, such that the magnetic pole surface of the magnetic field loading unit is parallel to the bottom surface of the mixing chamber.

[0021] This invention applies a magnetic field through a magnetic field loading unit. The magnetic unit moves in the mixing chamber without contact under the action of the magnetic field, thereby generating turbulence in the mixing chamber. This ensures that the fluid to be mixed in the mixing chamber is mixed uniformly, reduces the requirements for the structure and driving accuracy of the microfluidic chip, and has the advantages of simple structure, high mixing efficiency and low cost. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0023] Figure 1 This is a schematic diagram of the structure of a microfluidic chip fluid mixing device according to an embodiment of the present invention;

[0024] Figure 2 This is a schematic diagram of the working condition of a microfluidic chip fluid mixing device according to an embodiment of the present invention.

[0025] Figure 3 This is a flowchart of a mixing method for a microfluidic chip fluid mixing device according to an embodiment of the present invention. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0027] like Figure 1 and 2The fluid mixing device within the microfluidic chip of the present invention includes a magnetic field loading unit 1 and a magnetic unit 2. The magnetic unit 2 is encapsulated within a mixing chamber 3 of the microfluidic chip, while the magnetic field loading unit 1 is disposed outside the microfluidic chip. The magnetic field loading unit 1 applies a magnetic field to the magnetic unit 2, driving the magnetic unit 2 to move within the microfluidic chip under the influence of the magnetic field, thereby generating turbulence within the microfluidic chip to mix the fluid. Since the magnetic unit 2 moves without contact within the mixing chamber 3 under the influence of the magnetic field, compared to the existing vibration mixing chamber method, this improves mixing efficiency and ensures that the internal structure of the microfluidic chip is not damaged by external forces. The fluid in the mixing chamber 3 is a mixture of multiple liquids or a solid-liquid mixture. The present invention is applicable to the mixing needs of multiple liquids or solids required for biochemical reactions in microfluidic chips.

[0028] In one embodiment of the present invention, a protective layer is formed on the surface of the magnetic unit 2, and the protective layer material is silicon dioxide or polytetrafluoroethylene. Since the magnetic unit 2 is in direct contact with the liquid in the mixing chamber 3, its surface is generally treated to avoid interfering with the biochemical reaction. The protective layer of the magnetic unit 2 can be formed on the surface of the magnetic unit by means of spraying or other methods.

[0029] In one embodiment of the present invention, the magnetic unit 2 is a cylindrical magnet, the cross-sectional diameter of which is 0.6-0.95 times the minimum cross-sectional dimension of the mixing chamber 3, and the height of which is 0.3-1 times the cross-sectional radius of the magnet. To further improve the mixing efficiency and mixing effect, the dimensions of the magnetic unit and the mixing chamber can be controlled. The magnetic unit can be rotated in the mixing chamber, allowing the fluids in the upper and lower layers of the mixing chamber to be fully mixed.

[0030] In one embodiment of the present invention, the magnetic field loading unit 1 is a permanent magnet or an electromagnet, and the magnetic pole surface of the magnetic field loading unit 1 is parallel to the bottom surface of the mixing chamber 3.

[0031] In one embodiment of the present invention, the mixing chamber 3 can encapsulate multiple magnetic units 2. Controlling the movement of these multiple magnetic units via a magnetic field loading unit can further improve mixing efficiency.

[0032] In one embodiment of the present invention, the mixing device further includes a magnetic pole control unit, which is used to change the magnetic pole direction of the magnetic field loading unit 1 to change the direction of the applied magnetic field.

[0033] In one embodiment of the present invention, when the magnetic field loading unit 1 is a permanent magnet, the magnetic field loading unit 1 changes the magnetic pole direction by driving the permanent magnet to flip; when the magnetic field loading unit 1 is an electromagnet, the magnetic field loading unit 1 changes the magnetic pole direction by changing the direction of the electromagnet current.

[0034] In one embodiment of the present invention, the magnetic pole surface area of ​​the magnetic field loading unit 1 is larger than that of the magnetic pole surface area of ​​the magnetic unit 2, so that the magnetic field of the magnetic field loading unit 1 covers all positions in the mixing chamber of the microfluidic chip, which not only ensures the mixing efficiency, but also allows the magnetic unit to be moved in the mixing chamber according to the needs of biochemical reaction.

[0035] like Figure 2 and 3 As shown, the mixing method of the fluid mixing device of the present invention includes the following steps:

[0036] Step S310: Encapsulate the magnetic unit in the hybrid chamber of the microfluidic chip;

[0037] Step S320: Position the magnetic unit in the mixing chamber by applying a magnetic field through the magnetic field loading unit;

[0038] Step S330: Introduce the fluid to be mixed into the mixing chamber; positioning the magnetic unit before introducing the fluid can prevent the magnetic unit from being carried out of the mixing chamber of the microfluidic chip by the introduced fluid.

[0039] Step S340: Change the direction of the magnetic field applied by the magnetic field loading unit to the magnetic unit, drive the magnetic unit to move in the mixing chamber, and generate turbulence in the mixing chamber to mix the fluid to be mixed in the microfluidic chip.

[0040] Specifically, during the assembly of microfluidic chips, magnetic units are placed inside the mixing chamber and encapsulated. During the encapsulation process, it is necessary to confirm that the N-S orientation of the magnetic units is consistent.

[0041] According to actual needs, such as Figure 2 If it is necessary to ensure that the magnetic unit remains at the top of the mixing chamber, then the polarity of the upper surface of the magnetic field loading unit must be the same as the polarity of the lower surface of the magnetic unit. If it is necessary to ensure that the magnetic unit remains at the bottom of the mixing chamber, then the magnetic field loading unit can be de-energized or the polarity of the upper surface of the magnetic field loading unit can be opposite to the polarity of the lower surface of the magnetic unit.

[0042] During the mixing process, the magnetic poles of the magnetic field loading unit are reversed by a reversing current (if the magnetic field loading unit is a permanent magnet, the reversal is performed physically by an external mechanical mechanism). At this time, since the polarity of the upper surface of the magnetic field loading unit is the same as that of the lower surface of the magnetic unit, the magnetic unit rotates upward under the repulsive force and eventually falls back to the bottom. At this point, the polarity of the upper surface of the magnetic field loading unit is opposite to that of the lower surface of the magnetic unit.

[0043] The magnetic pole reversal process of the magnetic loading unit is repeated. During the movement of the magnetic unit, external disturbances are generated in the cavity to achieve a mixing effect.

[0044] In summary, this invention applies a magnetic field through a magnetic field loading unit, and the magnetic unit moves in the mixing chamber without contact under the action of the magnetic field, thereby generating turbulence in the mixing chamber, ensuring uniform mixing of the fluid to be mixed in the mixing chamber, reducing the requirements for microfluidic chip structure and driving accuracy, and has the advantages of simple structure, high mixing efficiency and low cost.

[0045] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A fluid mixing device within a microfluidic chip, characterized in that, The device includes a magnetic field loading unit and a magnetic unit. The magnetic unit is encapsulated in the mixing chamber of the microfluidic chip, and the magnetic field loading unit is disposed outside the microfluidic chip. The magnetic field loading unit is used to apply a magnetic field to the magnetic unit and drive the magnetic unit to move in the microfluidic chip under the action of the magnetic field, thereby generating turbulence in the microfluidic chip to mix the fluid in the microfluidic chip.

2. The fluid mixing device as described in claim 1, characterized in that, A protective layer is formed on the surface of the magnetic unit, and the material of the protective layer is silicon dioxide or polytetrafluoroethylene.

3. The fluid mixing device as described in claim 1, characterized in that, The magnetic unit is a cylindrical magnet, the diameter of the magnet's cross-section is 0.6-0.95 times the minimum cross-sectional dimension of the mixing chamber, and the height of the magnet is 0.3-1 times the radius of the magnet's cross-section.

4. The fluid mixing device as described in claim 1, characterized in that, The magnetic field loading unit is a permanent magnet or an electromagnet, and the magnetic pole surface of the magnetic field loading unit is parallel to the bottom surface of the mixing chamber.

5. The fluid mixing device as described in claim 1, characterized in that, The fluid in the mixing chamber is a mixture of multiple liquids or a solid-liquid mixture.

6. The fluid mixing apparatus as described in claim 1, characterized in that, The mixing chamber can encapsulate multiple magnetic units.

7. The fluid mixing apparatus as described in claim 4, characterized in that, It also includes a magnetic pole control unit, which is used to change the magnetic pole direction of the magnetic field loading unit in order to change the direction of the applied magnetic field.

8. The fluid mixing apparatus as described in claim 7, characterized in that, When the magnetic field loading unit is a permanent magnet, the magnetic field loading unit changes the magnetic pole direction by driving the permanent magnet to flip; when the magnetic field loading unit is an electromagnet, the magnetic field loading unit changes the magnetic pole direction by changing the direction of the electromagnet current.

9. A mixing method using the fluid mixing apparatus as described in any one of claims 1-8, characterized in that, Includes the following steps: Encapsulating magnetic units within the hybrid chamber of a microfluidic chip; The magnetic unit is positioned in the mixing chamber by applying a magnetic field through the magnetic field loading unit; The fluid to be mixed is introduced into the mixing chamber; The direction of the magnetic field applied by the magnetic field loading unit to the magnetic unit is changed, driving the magnetic unit to move in the mixing chamber, causing turbulence in the fluid to be mixed in the mixing chamber, so as to mix the fluid to be mixed in the microfluidic chip.

10. The mixing method as described in claim 9, characterized in that, Also includes: The magnetic field loading unit is placed at the bottom of the mixing chamber of the microfluidic chip, such that the magnetic pole surface of the magnetic field loading unit is parallel to the bottom surface of the mixing chamber.

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