Non-intrusive on-chip droplet segmentation magnetic control chip

Abstract

The invention provides a non-invasive on-chip droplet segmentation magnetic control chip, and relates to the field of micro-fluidic chips. The non-intrusive on-chip droplet segmentation magnetic control chip provided by the invention comprises an upper-layer chip, a permanent magnet layer and a lower-layer chip which are packaged in sequence, a pincerlike liquid separation opening is arranged at the top of the upper-layer chip; the pincerlike liquid separation open groove comprises a main runner and a plurality of pincerlike runners; the pincerlike runners are located on the same side of the main runner and are sequentially arranged in the extending direction of the main runner; the pincerlike flow channel comprises a flat flow channel and an inclined flow channel which are communicated in sequence; the extension direction of the flat runner is consistent with that of the main runner, and the extension direction of the inclined runner outwards deviates from that of the main runner. Magnetic additives do not need to be added, the oil-based ferrofluid is used for transporting the sample liquid drops, liquid separation is carried out through the pincer-shaped flow channel, the process of preparatory work can be simplified, the sample does not need to be endowed with magnetism, and the sample liquid drops are prevented from being polluted.

Description

Technical Field

[0001] The invention relates to the field of microfluidic chips, in particular to a non-invasive on-chip droplet segmentation magnetic control chip. Background Art

[0002] Microfluidic chip is an integrated chip platform used to operate, analyze and process tiny fluid samples. Its biggest advantage is that it can accurately control the flow of liquid at the micrometer scale and perform small-volume mixing, reaction, separation and other operations. It has been widely used in fields such as drug toxicity analysis, water quality testing and food safety monitoring. It has the advantages of small reaction volume, small amount of reagents required, automation and fast reaction speed. Driving droplets by magnetic field force is a very common droplet driving method. Usually, nanomagnetic particles are added to the sample droplets to respond to the permanent magnet or electromagnet under the chip structure to achieve the movement, segmentation and fusion of droplets, which is of great significance for biological experiments and drug research.

[0003] However, the traditional "invasive" magnetic control chip requires the addition of magnetic particles inside the sample droplets, which will contaminate the sample droplets to a certain extent, and there is a risk of changing the properties of certain droplets or reagents, reducing the reliability of experimental results. In addition, due to the necessary operation process of adding additional substances inside the "invasive" magnetic drive, the types of samples that can be driven are subject to certain restrictions.

[0004] As a new type of magnetically driven microfluidic chip, the "non-invasive" magnetic control chip does not require the addition of additional magnetic particles inside the droplet sample, thus avoiding contamination of the sample droplets and simplifying the experimental steps.

[0005] The existing "non-invasive" magnetic drive methods include ferrofluid wrapping, charge response, and deformable magnet grippers. For charge response, the sample needs to have a certain amount of charge and dielectric constant to respond to the controllable electrode above. The production of the electrode is a difficult point, and solid samples cannot be controlled; for deformable magnet grippers, magnetic drive is very complicated, and samples of different sizes require grippers of different structures.

[0006] Therefore, the present invention adopts the method of ferrofluid packaging. Compared with the other two methods, ferrofluid is simple to make and recyclable, has good reusability, and can be adapted to various types of samples. In addition, the present invention proposes a liquid separation structure, which uses ferrofluid and permanent magnets to perform droplet segmentation, and builds a non-invasive on-chip droplet segmentation magnetic control chip. Summary of the invention

[0007] In order to solve the above problems, the present invention provides a non-invasive on-chip droplet segmentation magnetic control chip. The present invention does not need to add magnetic additives. It uses oil-based ferromagnetic fluid to transport sample droplets and separates them through a clamp-shaped flow channel. It can not only simplify the preparation process, but also eliminate the need to give magnetism to the samples, thereby preventing the sample droplets from being contaminated.

[0008] The present invention provides a non-invasive on-chip droplet splitting magnetron chip, which comprises an upper chip, a permanent magnet layer and a lower chip which are packaged in sequence; the permanent magnet layer is a permanent magnet, the lower chip is a permanent magnet driver, and the permanent magnet is connected to the driving shaft of the permanent magnet driver; a clamp-shaped liquid separation groove is provided on the top of the upper chip, and the clamp-shaped liquid separation groove is used to load oil-based ferromagnetic fluid and sample droplets; the clamp-shaped liquid separation groove comprises a main channel and a plurality of clamp-shaped flow channels; each of the clamp-shaped flow channels is located on the same side of the main channel and is arranged in sequence along the extension direction of the main channel, and each of the clamp-shaped flow channels is connected to the main channel; the clamp-shaped flow channel comprises a flat flow channel and an oblique flow channel which are connected in sequence; the extension direction of the flat flow channel is consistent with the extension direction of the main channel, and the extension direction of the oblique flow channel deviates outward from the extension direction of the main channel.

[0009] In some feasible embodiments of the present invention, the depth of the clamp-shaped liquid separation groove is 0.3 to 2 mm; and / or the straight-line distance between the bottom of the upper chip and the bottom of the clamp-shaped liquid separation groove is 0.3 to 1.5 mm; and / or the length of the inclined flow channel is 2 to 8 mm; and / or the width of the inclined flow channel is 0.9 to 3 mm; and / or the volume of the oil-based ferromagnetic fluid is 5 to 15 μL; and / or the magnetic field size of the permanent magnet is 1800GS to 2200GS.

[0010] In a feasible implementation manner of the present invention, the number of the clamp-shaped flow channels is 3 to 5.

[0011] In a feasible embodiment of the present invention, the material of the upper layer of the chip is polymethyl methacrylate.

[0012] In a feasible implementation manner of the present invention, the oil-based ferromagnetic fluid is obtained by a method for preparing an oil-based ferromagnetic fluid, and the method for preparing the oil-based ferromagnetic fluid comprises the following steps:

[0013] Step 1): adding mineral oil and oil-based ferrofluid;

[0014] Step 2): Mix the mineral oil and the oil-based ferromagnetic fluid to obtain a mixed oil-based ferromagnetic fluid.

[0015] In a feasible embodiment of the present invention, step 1) of the method for preparing the oil-based ferromagnetic fluid further includes:

[0016] Step 1-1) Use a pipette to draw mineral oil and add it dropwise into a centrifuge tube:

[0017] Step 1-2) Replace the pipette tip to suck up the EMG oil-based ferromagnetic fluid and drop it into the centrifuge tube.

[0018] In a feasible embodiment of the present invention, step 2) of the method for preparing the oil-based ferromagnetic fluid further includes:

[0019] Step 2-1) mixing mineral oil and oil-based ferrofluid in a centrifuge tube;

[0020] Step 2-2) placing the centrifuge tube on an adjustable mixer for oscillation and mixing to obtain a mixed oil-based ferrofluid.

[0021] In a feasible implementation manner of the present invention, the preparation method of the oil-based ferromagnetic fluid comprises the following steps:

[0022] Step 1) adding n μL of mineral oil and m μL of oil-based ferromagnetic fluid; the volume of the oil-based ferromagnetic fluid after mixing is n+m μL, and the concentration of the oil-based ferromagnetic fluid after mixing is n / (m+n)*100%, 4≤n+m≤12;

[0023] Step 2) mixing the mineral oil and the oil-based ferromagnetic fluid for x minutes to obtain a mixed oil-based ferromagnetic fluid; 0.5mins≤x≤10mins;

[0024] In addition, the components of the mixed oil-based ferromagnetic fluid include the following by volume:

[0025] Mineral oil: 30% to 96%;

[0026] Oil-based ferrofluid: 4% to 70%.

[0027] In a feasible implementation manner of the present invention, it further includes a host computer, which is connected to the permanent magnet driver via an optical fiber; the host computer includes a driving module, and the driving module is used to drive the movement of the permanent magnet driver.

[0028] The present invention also provides a method for using a non-invasive on-chip droplet segmentation magnetic control chip, comprising the following steps:

[0029] Step S1): pouring oil-based ferromagnetic fluid and sample droplets into the forceps-shaped separation groove;

[0030] Step S2): the permanent magnet driving member drives the permanent magnet to move from one end of the main flow channel to the other end and generates a magnetic potential well, and the sample droplets wrapped by the oil-based ferromagnetic fluid are driven by the magnetic potential well and move along the clamp-shaped flow channel;

[0031] Step S3): After the sample droplet moves to the end of the flat channel, it forcibly crosses the end of the flat channel and enters the main channel. When crossing the end of the flat channel, the sample droplet is divided into sub-droplets, and the sub-droplets move to the oblique channel.

[0032] The non-invasive on-chip droplet segmentation magnetic control chip provided by the present invention has the following beneficial effects:

[0033] 1) The present invention does not require the addition of magnetic additives. Using oil-based ferromagnetic fluid to transport sample droplets and performing liquid separation through a clamp-shaped flow channel can not only simplify the preparation process, but also eliminate the need to impart magnetism to the sample, thereby preventing the sample droplets from being contaminated.

[0034] 2) The present invention has a high degree of automation. The driving module is used to control the permanent magnet displacement stage and drive the permanent magnet. The oil-based ferromagnetic fluid drives the sample droplets by responding to the magnetic field force generated by the permanent magnet, and the liquid separation operation is completed fully automatically.

[0035] 3) The present invention has strong plasticity, and the liquid separation structure and subsequent reaction system can be integrated on the chip to realize functions such as drug sensitivity detection and drug screening.

[0036] 4) The present invention has the potential to drive solid samples, because there is no need to add magnetic additives, and instead it is driven by oil-based ferrofluid wrapping. This "non-invasive" driving method has more potential possibilities for driving sample types, and may even drive solid samples.

[0037] 5) The "non-invasive" magnetically controlled droplet segmentation chip adopted by the present invention can realize the fully automatic movement and segmentation of the target solution, with high dilution accuracy and no potential cross-contamination in the reaction process. It can be applied to drug screening, cell analysis and other scenarios, and has a wide range of application scenarios. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 It is a schematic diagram of the overall structure of the present invention.

[0039] Figure 2 It is a side view of the overall structure of the present invention.

[0040] Figure 3 It is a schematic diagram of the structure of the clamp-shaped liquid separation slot in the present invention.

[0041] Figure 4 It is a front view of the clamp-shaped liquid separation slot in the present invention.

[0042] Figure 5 The present invention provides a preparation process for the oil-based ferromagnetic fluid.

[0043] Figure 6 It is a schematic diagram of the oil-based ferromagnetic fluid driving the sample droplet to move and be separated by the clamp-shaped flow channel in the present invention.

[0044] Reference numerals

[0045] Upper chip 1

[0046] Permanent magnet layer 2

[0047] Lower chip 3

[0048] Clamp-type liquid separation slot 4

[0049] Main channel 41

[0050] Clamp-type flow channel 42

[0051] Horizontal channel 42.1

[0052] Inclined channel 42.2 DETAILED DESCRIPTION

[0053] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without creative work belong to the scope of protection of the present invention. In the description of the present invention, it should be noted that the orientation or position relationship indicated by the terms "left side", "right side", "upper side", "lower side", "above", "below" and the like is based on the orientation or position relationship shown in the drawings, which is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention. In addition, the terms "first" and "second" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance.

[0054] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0055] Furthermore, in the description of the present invention, unless otherwise specified, “plurality” means two or more.

[0056] Before describing the embodiments of the present invention in detail, the oil-based ferrofluid is described first: the oil-based ferrofluid is a stable colloidal dispersion system, which is composed of magnetic nanoparticles (usually ferroferric oxide) dispersed in an oily carrier fluid (such as silicone oil, kerosene, etc.). When an external magnetic field is applied, the nanoparticles in the ferrofluid will be arranged along the direction of the magnetic field, so that the fluid exhibits macroscopic magnetism. The use of oil-based ferrofluid to drive water phase droplets is mainly based on the following principles:

[0057] Magnetic field gradient force: In a non-uniform magnetic field, ferrofluids are affected by magnetic field gradient force, which points in the direction of increasing magnetic field strength. The magnitude of this force is related to factors such as magnetic field strength, magnetic field gradient, and magnetic susceptibility of the ferrofluid. By designing a specific magnetic field distribution, precise control of the ferrofluid can be achieved, thereby driving the aqueous phase droplets in contact with it.

[0058] Interfacial tension and Marangoni effect: There is interfacial tension between the aqueous phase droplets and the oil-based ferrofluid. When a magnetic field acts on the ferrofluid, it may cause a change in the surface tension gradient inside the ferrofluid or at the interface, thereby inducing the Marangoni effect. The Marangoni effect refers to the fluid flow phenomenon caused by the surface tension gradient. This flow can effectively drive the movement of aqueous phase droplets. For example, a magnetic field may cause the local temperature of the ferrofluid to increase, thereby reducing its surface tension and generating a Marangoni flow that drives the droplets.

[0059] The embodiment of the present invention provides a non-invasive on-chip droplet segmentation magnetic control chip, referring to Figure 1 and Figure 2 , the magnetron chip includes an upper chip 1, a permanent magnet layer 2 and a lower chip 3 which are packaged in sequence; the permanent magnet layer 2 is a permanent magnet, the lower chip 3 is a permanent magnet driver, the permanent magnet is connected to the driving shaft of the permanent magnet driver, generally speaking, the permanent magnet is tightly attached to the bottom of the upper chip 1, the permanent magnet driver can be a two-axis translation stage, the two-axis translation stage can move the permanent magnet along the length and width direction of the upper chip 1, the model of the permanent magnet driver can be the DXH4-50L-XY high-precision electric two-axis translation stage produced by Dediweiye, as a supplementary explanation, the material of the upper layer of the chip is PMMA (polymethyl methacrylate). Continue reading Figure 3 The top of the upper chip 1 is provided with a clamp-shaped liquid separation slot 4, which is used to load oil-based ferromagnetic fluid and sample droplets; the clamp-shaped liquid separation slot 4 includes a main channel 41 and a plurality of clamp-shaped flow channels 42, the main channel 41 is generally rectangular in shape, with a length of 0.9 to 1.8 mm and a width of 2 to 4 mm, each of the clamp-shaped flow channels 42 is located on the same side of the main channel 41 and is arranged in sequence along the extension direction of the main channel 41, and each of the clamp-shaped flow channels 42 is connected to the main channel 41. Continue reading Figure 3The clamp-shaped flow channel 42 includes a flat flow channel 42.1 and an oblique flow channel 42.2 which are connected in sequence. The extension direction of the flat flow channel 42.1 is consistent with the extension direction of the main flow channel 41, and the extension direction of the oblique flow channel 42.2 deviates outward from the extension direction of the main flow channel 41. In a specific embodiment, the number of the clamp-shaped flow channels 42 is 3 to 5, preferably 3.

[0060] In the non-invasive on-chip droplet splitting magnetic control chip provided by an embodiment of the present invention, the depth of the clamp-shaped liquid separation groove 4 is 0.3 to 2 mm; and / or the straight-line distance between the bottom of the upper chip 1 and the bottom of the clamp-shaped liquid separation groove 4 is 0.3 to 1.5 mm; and / or the length of the inclined flow channel 42.2 is 2 to 8 mm; and / or the width of the inclined flow channel 42.2 is 0.9 to 3 mm; and / or the volume of the oil-based ferromagnetic fluid is 5 to 15 μL; and / or the magnetic field size of the permanent magnet is 1800 GS to 2200 GS.

[0061] The non-invasive on-chip droplet segmentation magnetic control chip provided by the embodiment of the present invention also includes a host computer, which is connected to the permanent magnet driver through an optical fiber; the host computer includes a drive module, which is used to drive the movement of the permanent magnet driver. As an illustration, the drive module can be programmed using a Raspberry Pi, and the specific control program belongs to the conventional means in this field, so it is not repeated here.

[0062] The embodiment of the present invention further provides a method for using a non-invasive on-chip droplet segmentation magnetic control chip, comprising the following steps:

[0063] Step S1): filling the clamp-shaped liquid separation slot 4 with oil-based ferromagnetic fluid and sample droplets; for illustration, the sample droplets are usually water-phase sample droplets;

[0064] Step S2): The permanent magnet driving member drives the permanent magnet to move from one end of the main flow channel 41 to the other end and generates a magnetic potential well. The sample droplets wrapped by the oil-based ferromagnetic fluid are driven by the magnetic potential well and move along the clamp-shaped flow channel 42. The movement trajectory of the sample droplets can be seen in Figure 1 The key point is that the sample droplet should always move close to the side wall of the clamp-shaped liquid separation slot 4;

[0065] Step S3): After the sample droplet moves to the end of the flat channel 42.1, it forcibly passes over the end of the flat channel 42.1 and enters the main channel 41. When passing over the end of the flat channel 42.1, the sample droplet is divided into sub-droplets, and the sub-droplets move to the oblique channel 42.2; as an illustration, the volume of the divided sub-droplets is related to the size of the clamp-shaped channel 42, and the details can be seen in Example 3.

[0066] Embodiment 1

[0067] In the non-invasive on-chip droplet segmentation magnetic control chip provided by the embodiment of the present invention, the oil-based ferromagnetic fluid is obtained by the preparation method of the oil-based ferromagnetic fluid, see Figure 5 The preparation method of the oil-based ferromagnetic fluid comprises the following steps:

[0068] Step 1): adding mineral oil and oil-based ferrofluid;

[0069] Optionally, step 1) may also include:

[0070] Step 1-1) Use a pipette to draw mineral oil and add it dropwise into a centrifuge tube:

[0071] Step 1-2) Replace the pipette tip to suck up the EMG oil-based ferromagnetic fluid and drop it into the centrifuge tube.

[0072] Step 2): Mix the mineral oil and the oil-based ferromagnetic fluid to obtain a mixed oil-based ferromagnetic fluid.

[0073] Optionally, step 2) may also include:

[0074] Step 2-1) mixing mineral oil and oil-based ferrofluid in a centrifuge tube;

[0075] Step 2-2) placing the centrifuge tube on an adjustable mixer for oscillation and mixing to obtain a mixed oil-based ferrofluid.

[0076] In the preparation method of the oil-based ferromagnetic fluid provided in the embodiment of the present invention, step 1) can be: adding n μL of mineral oil and m μL of oil-based ferromagnetic fluid; and the volume of the oil-based ferromagnetic fluid after mixing is n+m μL, and the concentration of the oil-based ferromagnetic fluid after mixing is n / (m+n)*100%, 4≤n+m≤12

[0077] In addition, the components of the mixed oil-based ferromagnetic fluid include the following by volume:

[0078] Mineral oil: 30% to 96%;

[0079] Oil-based ferrofluid: 4% to 70%.

[0080] Embodiment 3

[0081] In this embodiment, the sample droplets are phosphate buffer solutions, and the number of the clamp-shaped flow channels 42 is 3. By inputting instructions to the two-axis translation stage, it manipulates the permanent magnet to form a magnetic potential well on the surface of the oil-based ferromagnetic fluid, and drives the sample droplets through three clamp-shaped flow channels 42 of exactly the same size to achieve continuous liquid separation. The initial volume of the droplet sample is 20 μL, and the volume of the oil-based ferromagnetic fluid in the clamp-shaped separation groove 4 is 80 μL.

[0082] The parameters of the various features of the clamp-shaped flow channel 42 can be found in Tables 1 and Figure 4 The parameters of various characteristics in the oil-based ferrofluid can be seen in Table 2.

[0083] Table 1

[0084]

[0085] Table 2

[0086]

[0087]

[0088] The process of dividing the sample droplet into sub-droplets is as follows. Figure 6 As shown:

[0089] 1) In the initial state, the sample droplet to be split is placed at the leftmost end of the forceps-shaped liquid separation groove 4.

[0090] 2) The biaxial translation stage controls the lateral movement of the permanent magnet to generate a magnetic potential well. The sample droplet wrapped by the oil-based ferromagnetic fluid is driven by the magnetic potential well and moves toward the right end of the clamp-shaped liquid separation slot 4, and the first sub-droplet is separated when passing through the first clamp-shaped flow channel 42.

[0091] 3) The dual-axis translation stage controls the permanent magnet to continue to move laterally, generating a magnetic potential well. The sample droplet wrapped by the oil-based ferromagnetic fluid is driven by the magnetic potential well and moves toward the right end of the clamp-shaped liquid separation slot 4, and the second sub-droplet is separated when passing through the second clamp-shaped flow channel 42.

[0092] 4) The dual-axis translation stage controls the permanent magnet to continue to move laterally, generating a magnetic potential well. The sample droplet wrapped by the oil-based ferromagnetic fluid is driven by the magnetic potential well and moves toward the right end of the clamp-shaped liquid separation slot 4. When passing through the third clamp-shaped flow channel 42, the third sub-droplet is separated, thus realizing three consecutive liquid separation operations.

[0093] Embodiment 4

[0094] In this embodiment, the sample droplets are phosphate buffer solutions, and the number of the clamp-shaped flow channels 42 is 3. By inputting instructions to the two-axis translation stage, it manipulates the permanent magnet to form a magnetic potential well on the surface of the oil-based ferromagnetic fluid, and drives the sample droplets through three clamp-shaped flow channels 42 of exactly the same size to achieve continuous liquid separation. The initial volume of the droplet sample is 30 μL, and the volume of the oil-based ferromagnetic fluid in the clamp-shaped separation groove 4 is 10 μL.

[0095] The parameters of the various features of the clamp-shaped flow channel 42 can be found in Tables 3 and Figure 4 The parameters of various characteristics in the oil-based ferrofluid can be seen in Table 4.

[0096] Table 3

[0097]

[0098] Table 4

[0099]

[0100] The process of dividing the sample droplet into sub-droplets is as follows. Figure 6 As shown:

[0101] 1) In the initial state, the sample droplet to be split is placed at the leftmost end of the forceps-shaped liquid separation groove 4.

[0102] 2) The biaxial translation stage controls the lateral movement of the permanent magnet to generate a magnetic potential well. The sample droplet wrapped by the oil-based ferromagnetic fluid is driven by the magnetic potential well and moves toward the right end of the clamp-shaped liquid separation slot 4, and the first sub-droplet is separated when passing through the first clamp-shaped flow channel 42.

[0103] 3) The dual-axis translation stage controls the permanent magnet to continue to move laterally, generating a magnetic potential well. The sample droplet wrapped by the oil-based ferromagnetic fluid is driven by the magnetic potential well and moves toward the right end of the clamp-shaped liquid separation slot 4, and the second sub-droplet is separated when passing through the second clamp-shaped flow channel 42.

[0104] 4) The dual-axis translation stage controls the permanent magnet to continue to move laterally, generating a magnetic potential well. The sample droplet wrapped by the oil-based ferromagnetic fluid is driven by the magnetic potential well and moves toward the right end of the clamp-shaped liquid separation slot 4. When passing through the third clamp-shaped flow channel 42, the third sub-droplet is separated, thus realizing three consecutive liquid separation operations.

[0105] Embodiment 5

[0106] In this embodiment, the sample droplets are phosphate buffer solutions, and the number of the clamp-shaped flow channels 42 is 3. By inputting instructions to the two-axis translation stage, it manipulates the permanent magnet to form a magnetic potential well on the surface of the oil-based ferromagnetic fluid, and drives the sample droplets through three clamp-shaped flow channels 42 of exactly the same size to achieve continuous liquid separation. The initial volume of the droplet sample is 20 μL, and the volume of the oil-based ferromagnetic fluid in the clamp-shaped separation groove 4 is 8 μL.

[0107] The parameters of the various features of the clamp-shaped flow channel 42 can be found in Tables 5 and Figure 4 The parameters of various characteristics in the oil-based ferrofluid can be seen in Table 6.

[0108] Table 5

[0109]

[0110]

[0111] Table 6

[0112]

[0113] The process of dividing the sample droplet into sub-droplets is as follows. Figure 6 As shown:

[0114] 1) In the initial state, the sample droplet to be split is placed at the leftmost end of the forceps-shaped liquid separation groove 4.

[0115] 2) The biaxial translation stage controls the lateral movement of the permanent magnet to generate a magnetic potential well. The sample droplet wrapped by the oil-based ferromagnetic fluid is driven by the magnetic potential well and moves toward the right end of the clamp-shaped liquid separation slot 4, and the first sub-droplet is separated when passing through the first clamp-shaped flow channel 42.

[0116] 3) The dual-axis translation stage controls the permanent magnet to continue to move laterally, generating a magnetic potential well. The sample droplet wrapped by the oil-based ferromagnetic fluid is driven by the magnetic potential well and moves toward the right end of the clamp-shaped liquid separation slot 4, and the second sub-droplet is separated when passing through the second clamp-shaped flow channel 42.

[0117] 4) The dual-axis translation stage controls the permanent magnet to continue to move laterally, generating a magnetic potential well. The sample droplet wrapped by the oil-based ferromagnetic fluid is driven by the magnetic potential well and moves toward the right end of the clamp-shaped liquid separation slot 4. When passing through the third clamp-shaped flow channel 42, the third sub-droplet is separated, thus realizing three consecutive liquid separation operations.

[0118] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and substitutions can be made without departing from the technical principles of the present invention. These improvements and substitutions should also be regarded as the scope of protection of the present invention.

Claims

1. A non-invasive on-chip droplet segmentation magnetic control chip, characterized in that: The magnetron chip comprises an upper chip (1), a permanent magnet layer (2) and a lower chip (3) which are packaged in sequence; the permanent magnet layer (2) is a permanent magnet, the lower chip (3) is a permanent magnet driving component, and the permanent magnet is connected to a driving shaft of the permanent magnet driving component; A clamp-shaped liquid separation groove (4) is provided on the top of the upper chip (1), and the clamp-shaped liquid separation groove (4) is used to load oil-based ferromagnetic fluid and sample droplets; the clamp-shaped liquid separation groove (4) includes a main channel (41) and a plurality of clamp-shaped flow channels (42); each of the clamp-shaped flow channels (42) is located on the same side of the main channel (41) and is arranged in sequence along the extension direction of the main channel (41), and each of the clamp-shaped flow channels (42) is connected to the main channel (41); The clamp-shaped flow channel (42) comprises a flat flow channel (42.1) and an oblique flow channel (42.2) which are connected in sequence; the extension direction of the flat flow channel (42.1) is consistent with the extension direction of the main flow channel (41), and the extension direction of the oblique flow channel (42.2) deviates outward from the extension direction of the main flow channel (41).

2. The non-invasive on-chip droplet segmentation magnetic control chip according to claim 1, characterized in that: The depth of the clamp-shaped liquid separation groove (4) is 0.3 to 2 mm; and / or the straight-line distance between the bottom of the upper chip (1) and the bottom of the clamp-shaped liquid separation groove (4) is 0.3 to 1.5 mm; and / or the length of the inclined flow channel (42.2) is 2 to 8 mm; and / or the width of the inclined flow channel (42.2) is 0.9 to 3 mm; and / or the volume of the oil-based ferromagnetic fluid is 5 to 15 μL; and / or the magnetic field size of the permanent magnet is 1800 GS to 2200 GS.

3. The non-invasive on-chip droplet segmentation magnetic control chip according to claim 1, characterized in that: The number of the clamp-shaped flow channels (42) is 3 to 5.

4. The non-invasive on-chip droplet segmentation magnetic control chip according to claim 1, characterized in that: The material of the upper chip (1) is polymethyl methacrylate.

5. The non-invasive on-chip droplet segmentation magnetic control chip according to claim 1, characterized in that: The oil-based ferromagnetic fluid is obtained by a preparation method of an oil-based ferromagnetic fluid, and the preparation method of the oil-based ferromagnetic fluid comprises the following steps: Step 1): adding mineral oil and oil-based ferrofluid; Step 2): Mix the mineral oil and the oil-based ferromagnetic fluid to obtain a mixed oil-based ferromagnetic fluid.

6. The non-invasive on-chip droplet segmentation magnetic control chip according to claim 5, characterized in that: Step 1) also includes: Step 1-1) Use a pipette to draw mineral oil and add it dropwise into a centrifuge tube: Step 1-2) Replace the pipette tip to suck up the EMG oil-based ferromagnetic fluid and drop it into the centrifuge tube.

7. The non-invasive on-chip droplet segmentation magnetic control chip according to claim 5, characterized in that: Step 2) also includes: Step 2-1) mixing mineral oil and oil-based ferrofluid in a centrifuge tube; Step 2-2) placing the centrifuge tube on an adjustable mixer for oscillation and mixing to obtain a mixed oil-based ferrofluid.

8. The non-invasive on-chip droplet segmentation magnetic control chip according to any one of claims 5 to 7, characterized in that: The preparation method of the oil-based ferromagnetic fluid comprises the following steps: Step 1) adding n μL of mineral oil and m μL of oil-based ferromagnetic fluid; the volume of the oil-based ferromagnetic fluid after mixing is n+m μL, and the concentration of the oil-based ferromagnetic fluid after mixing is n / (m+n)*100%, 4≤n+m≤12; Step 2) mixing the mineral oil and the oil-based ferromagnetic fluid for x minutes to obtain a mixed oil-based ferromagnetic fluid; 0.5mins≤x≤10mins; In addition, the components of the mixed oil-based ferromagnetic fluid include the following by volume: Mineral oil: 30% to 96%; Oil-based ferrofluid: 4% to 70%.

9. The non-invasive on-chip droplet segmentation magnetic control chip according to claim 1, characterized in that: It also includes a host computer, which is connected to the permanent magnet driver through an optical fiber; the host computer includes a driving module, and the driving module is used to drive the movement of the permanent magnet driver.

10. The method for using the non-invasive on-chip droplet segmentation magnetic control chip according to any one of claims 1 to 9, characterized in that: The steps include: Step S1): pouring oil-based ferromagnetic fluid and sample droplets into the clamp-shaped liquid separation slot (4); Step S2): the permanent magnet driving member drives the permanent magnet to move from one end of the main flow channel (41) to the other end and generates a magnetic potential well, and the sample droplets wrapped by the oil-based ferromagnetic fluid are driven by the magnetic potential well and move along the clamp-shaped flow channel (42); Step S3): After the sample droplet moves to the end of the flat channel (42.1), it forcibly passes over the end of the flat channel (42.1) and enters the main channel (41). When passing over the end of the flat channel (42.1), the sample droplet is divided into sub-droplets, and the sub-droplets move to the oblique channel (42.2).

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