Nanoparticle sorting device and sorting method

Abstract

The embodiment of the invention provides a nano-particle sorting device and method, the sorting device comprises a flow channel, the flow channel is used for flowing of a nano-particle and magnetic fluid mixture to be sorted, the first end of the flow channel is used for entering of the mixture, and the second end of the flow channel is connected with at least two sorting channels; the magnet is used for generating a magnetic field area at the flow channel, the magnetic field acts on the magnetic fluid, so that the distribution density of the magnetic fluid is in a gradient form, and the nano-particles with different sizes enter different separation channels under the action of the magnetic fluid with different gradients; and the micro-fluidic chip is used for analyzing the nano particles subjected to shunting. The magnetic control sorting technology is adopted to sort the nano-particles, under the action of a magnetic field, the nano-particles suspended in the magnetic fluid generate concentration difference in a magnetic field area, finally, the nano-particles of different sizes enter different sorting channels, unmarked and efficient nano-particle sorting can be achieved, the sorting resolution can reach 10 nm, and the sorting accuracy is high. And the separation purity is high.

Description

Technical Field

[0001] The present invention relates to the technical field of nanoparticle sorting, and in particular to a nanoparticle sorting device and a nanoparticle sorting method. Background Art

[0002] In the fields of nano-functional materials, nano-drug research and development, biomedical testing, virology, etc., it is often necessary to analyze and sort rice particles. Patent Network Publication No. CN215288770U discloses an ultracentrifugation extraction device for exosomes, including a centrifuge tube and a cap. The centrifuge tube includes an outer tube on the outside, and the upper end of the outer tube is integrally formed with a connector. A sealing groove is provided on the outer side of the outer tube opening in the middle of the connector. The inner tube is inserted into the sealing groove and the inner tube. A limit card is provided on the upper end of the inner tube. The limit card is connected to the sealing groove. The outer side of the upper end of the connector is fixedly connected to the cap by a thread. The above patent describes the separation and sorting technology of exosomes, a typical nano-biological particle, specifically using an ultracentrifugation method. This method can achieve the separation and sorting of nanoparticles such as exosomes within a large range. It is more difficult to sort nanoparticles with a large number of subsets and more complex nanoparticles. Summary of the invention

[0003] In view of this, the embodiments of this specification provide a nanoparticle sorting device and a sorting method, which use magnetic manipulation sorting technology to sort nanoparticles. Under the action of the magnetic field, the nanoparticles suspended in the magnetic fluid produce a concentration difference in the magnetic field area, and ultimately allow nanoparticles of different sizes to enter different sorting channels, thereby achieving label-free and efficient nanoparticle sorting.

[0004] The embodiments of this specification provide the following technical solutions: a nanoparticle sorting device, comprising:

[0005] A flow channel, wherein the flow channel is used for the flow of a mixture of nanoparticles and magnetic fluid to be sorted, wherein a first end of the flow channel is used for the mixture to enter, and a second end of the flow channel is connected to at least two sorting channels;

[0006] A magnet, wherein the magnet is used to generate a magnetic field region at the flow channel, and the magnetic field acts on the magnetic fluid, so that the distribution density of the magnetic fluid presents a gradient form, and nanoparticles of different sizes enter different sorting channels under the action of magnetic fluids with different gradients;

[0007] A microfluidic chip is used to analyze the nanoparticles after diversion.

[0008] Preferably, when the nanoparticles of different sizes pass through the magnetic field region, pressure is generated on the surface of the magnetic fluid, and the magnetic fluid is moved to the magnetic field region with a low gradient, forming negative magnetophoretic migration, so that the nanoparticles of different sizes enter different sorting channels.

[0009] Preferably, the magnetic fluid is a magnetic particle suspension or a magnetic particle solution.

[0010] Preferably, the magnetic fluid includes at least one of Fe3O4, FeCrMo and FeCr.

[0011] Preferably, when the magnetic fluid is a magnetic particle suspension, the size of the magnetic particles in the suspension is 1 nm to 15 nm.

[0012] Preferably, the flow channel is a square flow channel, the width of the flow channel is 50 μm to 100 μm, and the height of the flow channel is 100 μm to 1000 μm.

[0013] Preferably, the number of the sorting channels is 2 to 32.

[0014] Preferably, the magnet comprises a permanent magnet or an electromagnet, and the magnetic field area has a size range of 10 5 ~10 7 T / m.

[0015] Preferably, the microfluidic chip is made of one of quartz, glass, acrylic, and PWMS materials.

[0016] A sorting method, applied to the nanoparticle sorting device as described in any one of the above, comprising:

[0017] mixing the nanoparticles and the magnetic fluid to form a mixture;

[0018] The mixture enters the flow channel through the first end of the flow channel, and the mixture is focused near the side wall of the flow channel through the base liquid of the magnetic fluid. Under the action of the magnetic field area generated by the magnet, the nanoparticles suspended in the magnetic fluid produce a concentration difference in the magnetic field area. The higher the magnetic field gradient, the higher the concentration of magnetic particles.

[0019] The magnetic fluid forms negative magnetophoretic migration in the magnetic field area. The negative magnetic migration force on the nanoparticles is proportional to the particle size. Nanoparticles of different sizes will eventually enter different sorting channels.

[0020] Compared with the prior art, the at least one technical solution adopted in the embodiments of this specification can achieve the following beneficial effects:

[0021] Magnetic manipulation sorting technology is used to sort nanoparticles. Under the action of the magnetic field, the distribution density of the magnetic fluid presents a gradient form. Under the action of magnetic fluids with different gradients, the nanoparticles suspended in the magnetic fluid produce a concentration difference in the magnetic field area, and finally the nanoparticles of different sizes enter different sorting channels, which can realize label-free and high-efficiency nanoparticle sorting. Nanoparticles with a particle size distribution of 50nm to 500nm can be sorted, the sorting resolution can reach 10nm, and the sorting purity can reach more than 90%. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 is a schematic diagram of a nanoparticle sorting device provided in the present application;

[0024] Figure 2 yes Figure 1 Enlarged schematic diagram at point A in the middle.

[0025] In the figure, 1. magnetic fluid; 2. flow channel; 3. magnet; 4. sorting channel; 5. nanoparticles. DETAILED DESCRIPTION

[0026] The embodiments of the present application are described in detail below with reference to the accompanying drawings.

[0027] The following describes the implementation methods of the present application through specific examples, and those skilled in the art can easily understand other advantages and effects of the present application from the contents disclosed in this specification. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. The present application can also be implemented or applied through other different specific implementation methods, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present application. It should be noted that, in the absence of conflict, the following embodiments and the features in the embodiments can be combined with each other. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without making creative work belong to the scope of protection of the present application.

[0028] It should be noted that various aspects of the embodiments within the scope of the appended claims are described below. It should be apparent that the aspects described herein can be embodied in a wide variety of forms, and any specific structure and / or function described herein is merely illustrative. Based on the present application, it should be understood by those skilled in the art that an aspect described herein can be implemented independently of any other aspect, and two or more of these aspects can be combined in various ways. For example, any number and aspect described herein can be used to implement the device and / or practice the method. In addition, other structures and / or functionalities other than one or more of the aspects described herein can be used to implement this device and / or practice this method.

[0029] It should also be noted that the illustrations provided in the following embodiments are only schematic illustrations of the basic concept of the present application. The drawings only show components related to the present application rather than being drawn according to the number, shape and size of components in actual implementation. In actual implementation, the type, quantity and proportion of each component may be changed arbitrarily, and the component layout may also be more complicated.

[0030] Additionally, in the following description, specific details are provided to facilitate a thorough understanding of the examples. However, it will be understood by those skilled in the art that the aspects described may be practiced without these specific details.

[0031] In the fields of nano-functional materials, nano-drug research and development, biomedical testing, virology, etc., it is often necessary to analyze and sort rice particles. The current nanoparticle sorting mainly has the following problems:

[0032] 1. The existing nanoparticle sorting technology has low sorting purity;

[0033] 2. The existing nanoparticle sorting technology has a low recovery rate;

[0034] 3. Existing nanoparticle sorting technology requires labeling of nanoparticles, which is a cumbersome process and inefficient.

[0035] After extensive and in-depth experiments, the inventors designed a nanoparticle sorting device and a nanoparticle sorting method.

[0036] The technical solutions provided by various embodiments of the present application are described below in conjunction with the accompanying drawings.

[0037] like Figure 1-Figure 2 As shown, a nanoparticle sorting device comprises:

[0038] A flow channel 2, wherein the flow channel 2 is used for the mixture of the nanoparticles 5 to be sorted and the magnetic fluid 1 to flow, the first end of the flow channel 2 is used for the mixture to enter, and the second end of the flow channel 2 is connected to at least two sorting channels 4;

[0039] A magnet 3, wherein the magnet 3 is used to generate a magnetic field region at the flow channel 2, and the magnetic field acts on the magnetic fluid 1, so that the distribution density of the magnetic fluid 1 presents a gradient form, and nanoparticles 5 of different sizes enter different sorting channels 4 under the action of magnetic fluids 1 with different gradients;

[0040] A microfluidic chip is used to analyze the nanoparticles 5 after diversion.

[0041] The nanoparticles 5 and the magnetic fluid 1 are mixed to form a nanoparticle sorting system. The mixture enters the flow channel 2 through the first end of the flow channel 2. The magnetic field region is formed by setting the magnet 3. Due to the effect of the magnetic field force, the nanoparticles 5 suspended in the magnetic fluid 1 can produce a concentration difference in the magnetic field region. The higher the magnetic field gradient, the higher the concentration of magnetic particles. When nanoparticles 5 of different sizes pass through the magnetic field region, pressure is generated on the surface of the magnetic particles, and the latter are moved to the low-gradient magnetic field region to form negative magnetophoretic migration. The negative magnetic migration force on the nanoparticles 5 is proportional to the particle size. Therefore, nanoparticles 5 of different sizes will eventually enter different sorting channels 4 and be sorted out. It can achieve label-free and high-efficiency sorting of nanoparticles 5, and the sorting purity can reach more than 90%. The microfluidic chip analyzes the nanoparticles 5 after diversion.

[0042] It should be noted that an expansion portion may be provided between the flow channel 2 and the diversion channel, so as to facilitate the provision of a larger number of sorting channels 4 .

[0043] It should be further explained that the magnet 3 is used to construct a magnetic field, and the spatial positions of the N pole and the S pole of the magnet 3 can be interchanged according to installation requirements.

[0044] It should also be noted that the sorting device can sort nanoparticles with a particle size distribution of 50nm to 500nm, and the sorting resolution can reach 10nm.

[0045] like Figure 1-Figure 2 In some embodiments shown, the magnetic fluid 1 is a magnetic particle suspension or a magnetic particle solution. The magnetic fluid 1 can be a magnetic particle suspension or a magnetic particle solution as long as it can form the magnetic fluid 1. The selection can be made according to actual conditions.

[0046] In some embodiments, the magnetic fluid 1 includes at least one of Fe3O4, FeCrMo, and FeCr. The magnetic fluid 1 can be made of materials such as Fe3O4, FeCrMo, and FeCr.

[0047] It should be noted that, in other embodiments, other magnetic solid particles (such as Fe, Ni, Co, etc.) can also be selected as the material of the magnetic fluid 1.

[0048] In some embodiments, when the magnetic fluid 1 is a magnetic particle suspension, the size of the magnetic particles in the suspension is 1nm to 15nm. The magnetic fluid 1 with small particles has a higher coercive force and a lower specific magnetic susceptibility, while the magnetic fluid 1 with large particles has a higher capture rate and better fluidity. By setting the size of the magnetic particles to 1nm to 15nm, the sorting effect of the nanoparticles 5 can be guaranteed.

[0049] In some preferred embodiments, the magnetic particles are no larger than 10 nm in size.

[0050] like Figure 1 As shown, in some embodiments, the flow channel 2 is a square flow channel, the width of the flow channel 2 is 50μm to 100μm, and the height of the flow channel 2 is 100μm to 1000μm. By setting the square flow channel 2, the length and width of the square flow channel 2 are both 50μm to 100μm, ensuring that it can be in the magnetic field area, and the height of the flow channel 2 is 100μm to 1000μm, ensuring that magnetic particles of different sizes can be effectively separated during the flow process in the flow channel 2.

[0051] like Figure 1 As shown, in some embodiments, the number of the sorting channels 4 is 2 to 32, and the number of the sorting channels 4 can be determined according to the distribution range of the sorted nanoparticles and the sorting resolution requirements.

[0052] like Figure 1 As shown, in some embodiments, the magnet 3 includes a permanent magnet or an electromagnet, and the magnetic field area size range is 10 5 ~10 7 T / m, by using a permanent magnet or an electromagnet as the magnet 3, the magnetic field size range can be 10 5 ~10 7 T / m can ensure the sorting effect of nanoparticles 5.

[0053] It should be noted that, in the present embodiment, the magnet 3 is a U-shaped permanent magnet, and both ends of the U-shaped permanent magnet are located on a side close to the outer wall of the flow channel 2 .

[0054] In some embodiments, the microfluidic chip is made of one of quartz, glass, acrylic, and PWMS materials. The microfluidic chip can be made of quartz, glass, acrylic, PWMS, and other materials, which can be selected according to actual conditions.

[0055] See also Figure 1-Figure 2 Based on the same inventive concept, the present specification provides a sorting method, which is applied to the nanoparticle sorting device as described in any one of the above items. The sorting method sorts nanoparticles 5 of 50nm to 500nm, including:

[0056] Mixing non-magnetic nanoparticles 5 of different sizes with magnetic fluid 1 to form a mixture (i.e., a nanoparticle sorting system);

[0057] The mixture enters the flow channel 2 through the first end of the flow channel 2, and the mixture is focused near the side wall of the flow channel 2 by the base liquid (sheath liquid) of the magnetic fluid 1. Under the action of the magnetic field region generated by the magnet, the nanoparticles 5 suspended in the magnetic fluid 1 generate a concentration difference in the magnetic field region. The higher the magnetic field gradient, the higher the concentration of magnetic particles.

[0058] When nanoparticles 5 of different sizes pass through the magnetic field area, pressure is generated on the surface of the magnetic particles, and the latter are moved to the low gradient magnetic field area. The magnetic fluid 1 forms negative magnetophoretic migration in the magnetic field area. The negative magnetic migration force on the nanoparticles 5 is proportional to the particle size. Nanoparticles 5 of different sizes will eventually enter different sorting channels 4 and be sorted out.

[0059] In practice, the magnetic fluid 1 is composed of a suspension of magnetic particles with a certain concentration.

[0060] The same or similar parts between the various embodiments in this specification can be referred to each other, and each embodiment focuses on the differences from other embodiments. In particular, for the method embodiment described later, since it corresponds to the system, the description is relatively simple, and the relevant parts can be referred to the partial description of the system embodiment.

[0061] The above is only a specific implementation of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application shall be based on the protection scope of the claims.

Claims

1. A nanoparticle sorting device, characterized in that: include: A flow channel, wherein the flow channel is used for the flow of a mixture of nanoparticles to be sorted and magnetic fluid, wherein a first end of the flow channel is used for the mixture to enter, and a second end of the flow channel is connected to at least two sorting channels; A magnet, wherein the magnet is used to generate a magnetic field region at the flow channel, and the magnetic field acts on the magnetic fluid, so that the distribution density of the magnetic fluid presents a gradient form, and nanoparticles of different sizes enter different sorting channels under the action of magnetic fluids with different gradients; A microfluidic chip is used to analyze the nanoparticles after diversion.

2. The nanoparticle sorting device according to claim 1, characterized in that: When the nanoparticles of different sizes pass through the magnetic field region, pressure is generated on the surface of the magnetic fluid, and the magnetic fluid is moved to the magnetic field region with a low gradient, forming negative magnetophoretic migration, so that the nanoparticles of different sizes enter different sorting channels.

3. The nanoparticle sorting device according to claim 1, characterized in that: The magnetic fluid is a magnetic particle suspension or a magnetic particle solution.

4. The nanoparticle sorting device according to claim 3, characterized in that: The magnetic fluid includes at least one of Fe3O4, FeCrMo and FeCr.

5. The nanoparticle sorting device according to claim 3, characterized in that: When the magnetic fluid is a magnetic particle suspension, the size of the magnetic particles in the suspension is 1 nm to 15 nm.

6. The nanoparticle sorting device according to claim 1, characterized in that: The flow channel is a square flow channel, the width of the flow channel is 50 μm to 100 μm, and the height of the flow channel is 100 μm to 1000 μm.

7. The nanoparticle sorting device according to claim 1, characterized in that: The number of the sorting channels is 2 to 32.

8. The nanoparticle sorting device according to claim 1, characterized in that: The magnet includes a permanent magnet or an electromagnet, and the magnetic field area ranges from 10 5 ~10 7 T / m.

9. The nanoparticle sorting device according to claim 1, characterized in that: The microfluidic chip is made of one of quartz, glass, acrylic and PWMS materials.

10. A sorting method, characterized in that: The nanoparticle sorting device according to any one of claims 1 to 9 comprises: mixing the nanoparticles and the magnetic fluid to form a mixture; The mixture enters the flow channel through the first end of the flow channel, and the mixture is focused near the side wall of the flow channel through the base liquid of the magnetic fluid. Under the action of the magnetic field area generated by the magnet, the nanoparticles suspended in the magnetic fluid produce a concentration difference in the magnetic field area. The higher the magnetic field gradient, the higher the concentration of magnetic particles. The magnetic fluid forms negative magnetophoretic migration in the magnetic field area. The negative magnetic migration force on the nanoparticles is proportional to the particle size. Nanoparticles of different sizes will eventually enter different sorting channels.

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