Method and system for mixing substances in magnetic control liquid drops

Abstract

The invention provides a method and a system for mixing substances in magnetic control liquid drops. The method for mixing the substances in the magnetic control liquid drops comprises the following steps: dropwise adding the liquid drops containing substances to be mixed into a hydrophobic solid base material filled with magnetic fluid, and enabling the magnetic fluid to quickly wrap the contacted liquid drops to form a magnetic response liquid shell; the magnetic response liquid shell is controlled to move to drive the liquid drops wrapped by the magnetic response liquid shell to move, and mixing of substances in the liquid drops is accelerated. The magnetic control liquid drop internal substance mixing system comprises a hydrophobic solid base material and magnetic fluid spread on the surface of the hydrophobic solid base material. The magnetofluid response shell wrapping the liquid drops rotates around the liquid drops, shear flow at a two-phase interface is generated, kinetics in the liquid drops is increased, and the process of mixing substances in the liquid drops is obviously accelerated.

Description

Technical Field

[0001] The invention relates to a method and a system for mixing substances inside a magnetically controlled droplet, belonging to the technical field of magnetically controlled droplets. Background Art

[0002] High-precision, digital manipulation of microdroplets, including precise droplet generation, transportation, and efficient droplet mixing control, is an important research foundation for many applications such as drug delivery, energy collection, and microfluidics. The key and core of microdroplet manipulation technology is the driving force and braking material of the droplets. At present, a variety of microdroplet manipulation technologies based on external stimuli such as electricity, light, heat, and sound have been successfully developed.

[0003] The micro-droplet control technology based on electrowetting is versatile and flexible, and constitutes the technical basis for building digital microfluidics. The current digital microfluidics technology, even the more mature electrowetting digital microfluidics technology (such as CN101679078B, CN103170384B, CN101679078B), requires complex circuit design, the setting of multiple dielectric layers, etc. Moreover, the electrowetting technology has high requirements on the size of the droplets and the dielectric properties of the surface materials, and the substrate is easily contaminated during the droplet transportation process.

[0004] Pipeline-based liquid pump microfluidic technology often requires complex pipeline design to assist liquid mixing (e.g., US20160264924A1, CN101718795B), which can easily cause pipeline blockage.

[0005] Other manipulation methods based on bionic structures, surface energy gradients and external stimuli accelerate the droplet mixing process by driving the droplets to displace, which makes the mixing efficiency largely dependent on the driving efficiency, resulting in slow mixing efficiency.

[0006] Various accelerated mixing modes based on sound waves, light, heat, or electric fields introduce external heat to the droplets, which cannot meet the continuous droplet mixing control. Therefore, droplet manipulation based on light, heat, acoustics, etc. is limited in response time and control flexibility, making these technologies difficult to be used in highly integrated biochemical applications.

[0007] Magnetron technology provides a new mode that is simpler and responds quickly. Currently, this control technology mostly relies on adding magnetic particles (such as magnetic beads) to droplets (such as CN113908897A, CN104345140B, CN105675900B), which easily interferes with the internal substances of the droplets and limits the volume of controllable droplets; or it is to prepare some complex magnetically responsive hydrophobic substrates (CN110523451A), and use the deformation of the substrate under the magnetic field to achieve mixing, but the surface of the substrate is also easily contaminated.

[0008] Therefore, the various droplet manipulation methods currently established still face challenges in controllable droplet mixing.

[0009] Recently, it has been reported that magnetic fluids have been used as control carriers to achieve rapid transport of tiny droplets. However, in existing systems, digital manipulation of tiny droplets, especially the regulation of droplet hybrid dynamics and the regulation of biochemical reactions based on this, is still difficult to achieve, which greatly limits the application of these manipulation systems in chemical microreactors and biochemical detection. Summary of the invention

[0010] In order to solve the above technical problems, the purpose of the present invention is to provide a method and system for magnetically controlling the mixing of substances inside droplets. The method and system of the present invention can control the dynamics of the mixing process of substances inside droplets.

[0011] In order to achieve the above object, the present invention provides a method for mixing substances inside a magnetically controlled droplet in a first aspect, which comprises the following steps:

[0012] (1) adding a liquid droplet containing a substance to be mixed onto a hydrophobic solid substrate infused with a magnetic fluid, so that the magnetic fluid quickly wraps the contacting liquid droplet to form a magnetically responsive liquid shell;

[0013] (2) controlling the movement of the magnetically responsive liquid shell to drive the enclosed droplets to move along a specific trajectory, thereby accelerating the mixing of substances inside the droplets;

[0014] The movement of the magnetically responsive liquid shell includes at least rotational movement, and the movement of the droplet (i.e., the movement trajectory of the droplet) includes at least rotational movement, linear movement, circular movement, oscillating movement, in-situ rotation, or a combination thereof.

[0015] It should be noted that, in the above-mentioned movement of the droplets, generally speaking, for a symmetrical system (such as a sphere), the meanings of "rotational movement" and "in-situ rotation" are the same. However, in the system of the present invention, the magnetically responsive liquid shell is asymmetric in most cases, and accordingly, the droplets will also rotate in different directions. Therefore, the movement of the droplets of the present invention can include both rotational movement and in-situ rotation.

[0016] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the rotation axis of the rotational motion is perpendicular to the surface of the hydrophobic solid substrate.

[0017] In the above-mentioned method for magnetically controlling the mixing of substances inside droplets, preferably, the magnetically responsive liquid shell includes a wetting ridge formed by the magnetic fluid between the droplet and the hydrophobic solid substrate, and a thin layer of magnetic fluid wrapped around the surface of the droplet.

[0018] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the movement of the droplets is affected by the movement mode of the magnetically responsive liquid shell and exhibits a periodic reciprocating characteristic. It should be noted that when the movement of the droplets includes linear movement and rotational movement, circular movement, oscillating movement, and / or in-situ rotation on the hydrophobic solid substrate, the rotational movement, circular movement, oscillating movement, and / or in-situ rotation can be performed before or after the linear movement.

[0019] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the magnetically responsive liquid shell moves under the action of an external magnetic field.

[0020] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the external magnetic field is arranged below the hydrophobic solid substrate.

[0021] According to a specific embodiment of the present invention, the present invention utilizes magnetic fluid to wrap droplets, and by applying a controllable magnetic field, the magnetic fluid outside the droplets is caused to rotate, resulting in viscous shearing of the droplets, thereby accurately controlling the dynamics of the mixing process of substances inside the droplets, thereby achieving dynamic control of the mixing process.

[0022] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the maximum magnetic field strength of the external magnetic field at the location of the droplet is 50 mT. More preferably, the external magnetic field can be generated by one or more of a permanent magnet, an electromagnet, and a magnet array composed of an iron needle array and an electromagnet. Among them, the iron needle array refers to an array composed of a single iron needle.

[0023] It should be noted that in the present invention, the magnetic field strength refers to the surface magnetic field strength. Due to the shielding effect of the hydrophobic solid substrate, the original magnetic field strength can be very large, and the present invention does not specifically limit it, but only limits the surface magnetic field strength, that is, the magnetic field strength at the location of the droplet.

[0024] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the external magnetic field is controlled by a rotary motor or an array thereof.

[0025] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the external magnetic field includes a rotating magnetic field, which is generated by a permanent magnet, or a coil-type electromagnet or its array. More preferably, the rotating magnetic field is generated by applying rotation to the center of the magnetic field generated by the permanent magnet, or the coil-type electromagnet or its array by a rotary motor to generate a rotating magnetic field.

[0026] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the rotation radius of the rotating magnetic field is 0.1 times to 3 times the radius of the droplet.

[0027] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the rotation axis of the rotating magnetic field is perpendicular to the surface of the hydrophobic solid substrate. The rotation axis of the rotating magnetic field may overlap or not overlap with the center of the droplet.

[0028] According to a specific embodiment of the present invention, when the rotating magnetic field is generated by a coil-type electromagnet array, it can be used to achieve individual or continuous manipulation of multiple droplets. By utilizing the spatial symmetry of the magnetic field, multiple droplets can simultaneously move toward the same magnetic field center and merge at the magnetic field center, thereby achieving sequential manipulation of a large-area droplet array.

[0029] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the movement of the droplets includes linear movement and rotational movement, circular movement, oscillating movement, and / or in-situ rotation, and the linear movement and rotational movement, circular movement, oscillating movement, and / or in-situ rotation of the droplets on the hydrophobic solid substrate are achieved by the following methods:

[0030] (a) energizing a single or multiple coil-type electromagnets away from the droplets to generate a magnetic field, driving the magnetically responsive liquid shell to drive the droplets wrapped therein to perform linear motion on the hydrophobic solid substrate toward the center of the magnetic field;

[0031] (b) applying rotation to the center of the magnetic field generated by the permanent magnet, or the coil-type electromagnet or its array by a rotary motor, thereby generating a rotating magnetic field to control the magnetically responsive liquid shell to perform rotational motion, thereby driving the enclosed droplets to perform rotational motion, circular motion, oscillating motion, and / or in-situ rotation.

[0032] The magnetically responsive liquid shell can guide the droplet to perform linear reciprocating motion on the hydrophobic solid substrate under the action of the magnetic field, thereby realizing the manipulation of the droplet. The present invention does not specifically limit the order of the above steps (a) and (b), and step (a) can be performed first, or step (b) can be performed first.

[0033] According to a specific embodiment of the present invention, the linear motion, rotational motion, circular motion, oscillating motion, and / or in-situ rotation of the droplets on the hydrophobic solid substrate can be used to achieve simultaneous mixing acceleration of multiple droplets.

[0034] Compared with the traditional magnetic bead-driven droplet movement, the method of the present invention does not require the addition of magnetic beads or other magnetically responsive substances inside the droplets, which can effectively avoid the possible contamination caused by the added substances and the interference with the mixing of substances and biochemical reactions in the droplets. At the same time, the method of the present invention does not require the (electric) magnet to move with the droplets, and the energized electromagnet coil does not need to cover the path of the droplet movement, which greatly simplifies the design of the system.

[0035] According to a specific embodiment of the present invention, preferably, the above method further comprises: the magnetically responsive liquid shell responds to different magnetic field strengths (0-50mT), and then opens or closes in situ on the surface of the droplet, which is used to regulate the exchange of droplets with external substances, and / or control the continuous merging and mixing of multiple droplets. More preferably, the magnetically responsive liquid shell is in a closed state under weak magnetic field strength, and the magnetically responsive liquid shell is opened due to strong interaction under strong magnetic field strength; wherein, the magnetic field strength is the magnetic field strength at the location of the droplet, the weak magnetic field strength is 0-1mT, and the strong magnetic field strength is>1mT.

[0036] In some specific embodiments of the present invention, when the magnetically responsive liquid shell is in a closed state ensured by continuous motion, it can seal the droplets, effectively slow down the evaporation of the droplets, and shield the droplets from material exchange with the external environment.

[0037] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, in step (2), the magnetically responsive liquid shell is rotated at a speed of 1 Hz-100 Hz under the guidance of an external magnetic field. It should be noted that, in the present invention, 1 Hz = 1 rps (revolutions per second, i.e., the number of rotations per second). In some specific embodiments of the present invention, a controllable rotational speed difference (speed difference of 0-100 Hz) can be generated between the magnetically responsive liquid shell and the droplet, thereby accelerating the fluid shear inside the droplet, and achieving rapid and efficient mixing of substances inside the tiny droplet.

[0038] In the above-mentioned method for mixing substances inside a magnetically controlled droplet, the rotation axis of the rotating magnetic field may not overlap with the center of the droplet, that is, the magnetically responsive liquid shell may rotate at an arbitrary radius, and the droplet will respond as it rotates. Preferably, in step (2), the rotation radius of the rotational motion of the magnetically responsive liquid shell is 0.1 times to 3 times the radius of the droplet.

[0039] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the water contact angle of the hydrophobic solid substrate is 90-180°, more preferably 150-180°.

[0040] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the surface roughness of the hydrophobic solid substrate is 0.1-1000 nm, more preferably 0.1-200 nm.

[0041] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the hydrophobic solid substrate comprises a porous aluminum plate having hydrophobic or super-hydrophobic properties.

[0042] In some specific embodiments of the present invention, the porous aluminum plate with hydrophobic properties or super-hydrophobic properties can be obtained by processing the following steps: the porous aluminum plate is put into 80-95 ° C hot water and soaked for 20-60 minutes to roughen its surface, and then hydrophobized using silane and / or siloxane to obtain the porous aluminum plate with hydrophobic properties or super-hydrophobic properties. The specific steps of hydrophobic modification of aluminum plate using silane and / or siloxane can be carried out according to the conventional steps in the art, such as soaking the surface roughened porous aluminum plate in silane and / or siloxane solution for a period of time. Afterwards, conventional drying and other steps can be carried out to obtain a porous aluminum plate with hydrophobic properties or super-hydrophobic properties. Wherein, the silane and / siloxane used can be conventional in the art, such as but not limited to dimethylsilane, perfluorodecyltriethoxysilane, hexadecyltrimethoxysilane, etc.

[0043] In some specific embodiments of the present invention, the porous aluminum plate can be prepared based on materials such as aluminum sheet, polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS) and glass. The specific preparation process can be carried out according to the conventional method in the art, and the present invention does not specifically limit it.

[0044] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the magnetic fluid comprises an oil-phase magnetic fluid loaded with magnetic nanoparticles. More preferably, the magnetic fluid comprises, but is not limited to, one or a combination of silicone oil-based magnetic fluid, kerosene-based magnetic fluid, engine oil-based magnetic fluid, polyphenylene ether-based magnetic fluid, and fluorine-based magnetic fluid.

[0045] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the oil phase in the oil phase magnetic fluid comprises dimethyl silicone oil and / or perfluoropolyether.

[0046] In some specific embodiments of the present invention, the magnetic nanoparticles include one or a combination of ferromagnetic nanoparticles, antiferromagnetic nanoparticles, ferrimagnetic nanoparticles, synthetic magnetic nanoparticles, paramagnetic nanoparticles and superparamagnetic nanoparticles, etc. Preferably, the magnetic nanoparticles include ferroferric oxide nanoparticles; more preferably, the particle size of the ferroferric oxide nanoparticles is 5-300 nm.

[0047] In some specific embodiments of the present invention, the magnetic nanoparticles are uniformly dispersed in the oil phase; taking the volume of the oil phase in the magnetic fluid as 100%, the mass / volume percentage of the magnetic nanoparticles is 1%-52%.

[0048] In some specific embodiments of the present invention, the magnetic fluid comprises a silicone oil-based magnetic fluid whose oil phase is dimethyl silicone oil and loaded with ferroferric oxide nanoparticles. Preferably, the silicone oil-based magnetic fluid can be prepared by the following steps: adding ferroferric oxide nanoparticles to dimethyl silicone oil, ultrasonic dispersion, and obtaining the silicone oil-based magnetic fluid. More preferably, the ferroferric oxide nanoparticles include siloxane-functionalized ferroferric oxide nanoparticles. Among them, siloxane-functionalized ferroferric oxide nanoparticles can be prepared by conventional methods in the art. For example, ferroferric oxide nanoparticles are mixed with functionalized monomers and reacted at a suitable temperature for a suitable time to prepare. Preferably, the siloxane-functionalized ferroferric oxide nanoparticles are prepared using monocarboxyl-terminated polysiloxane (PDMS-COOH) as a functionalized monomer.

[0049] In other specific embodiments of the present invention, the magnetic fluid includes a perfluoropolyether-based magnetic fluid whose oil phase is perfluoropolyether and loaded with ferroferric oxide nanoparticles. Preferably, the perfluoropolyether-based magnetic fluid can be prepared by the following steps: adding ferroferric oxide nanoparticles to perfluoropolyether, ultrasonically dispersing, and obtaining the perfluoropolyether-based magnetic fluid. More preferably, the ferroferric oxide nanoparticles include fluorine-functionalized ferroferric oxide nanoparticles. Among them, fluorine-functionalized ferroferric oxide nanoparticles can be prepared by conventional methods in the art. For example, ferroferric oxide nanoparticles are mixed with functionalized monomers and reacted at a suitable temperature for a suitable time to prepare. Preferably, the fluorine-functionalized ferroferric oxide nanoparticles are prepared using monocarboxyl-terminated perfluoropolyether as a functionalized monomer.

[0050] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, when the droplets are aqueous droplets, an oil-phase magnetic fluid loaded with magnetic nanoparticles whose oil phase is dimethyl silicone oil is selected as the magnetic fluid; when the droplets are oil-phase droplets, an oil-phase magnetic fluid loaded with magnetic nanoparticles whose oil phase is perfluoropolyether is selected as the magnetic fluid. According to a specific embodiment of the present invention, a suitable magnetic fluid can be selected according to the type of droplets, preferably a silicone oil-based magnetic fluid is used for aqueous droplets, and a perfluoropolyether-based magnetic fluid is used for oil-phase droplets.

[0051] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the viscosity of the magnetic fluid is 0.01-600 cst, and more preferably 0.1-100 cst.

[0052] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the contact angle of the magnetic fluid on the hydrophobic solid substrate is 0-50°, more preferably 0-30°.

[0053] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the hydrophobic solid substrate infused with magnetic fluid is obtained by the following steps: an appropriate amount of the magnetic fluid (preferably the above-mentioned silicone oil-based magnetic fluid or perfluoropolyether-based magnetic fluid) is dropped onto the surface of the hydrophobic solid substrate, and the magnetic fluid spreads spontaneously under the action of surface capillary force to obtain the hydrophobic solid substrate infused with magnetic fluid.

[0054] In the above-mentioned method for mixing substances inside magnetically controlled droplets, preferably, the droplets are selected from one or more of water, ethylene glycol, glycerol, silicone oil, dimethyl sulfoxide, petroleum ether, toluene, ethanol, ethyl acetate, plant essential oils, and ionic liquids, or are selected from one or more of nanoparticle solutions, cell culture fluids, bacterial culture fluids, protein solutions, and inorganic salt solutions.

[0055] According to a specific embodiment of the present invention, the substances to be mixed in the droplets containing substances to be mixed can include substances to be mixed or reacted in various fields such as substance drive, substance mixing, chemical reaction, biological detection, chemical process, etc., and the present invention does not specifically limit them. The present invention adds droplets containing substances to be mixed to a hydrophobic solid substrate infused with a magnetic fluid, so that the magnetic fluid quickly and perfectly wraps the contacted droplets to form a magnetically responsive liquid shell, controls the rotational motion of the magnetic field to control the magnetically responsive liquid shell to rotate, drives the droplets wrapped by it to rotate, and generates a controllable speed difference between the magnetically responsive liquid shell and the droplets, accelerates the fluid shear inside the droplets, and realizes rapid and efficient mixing of substances inside the tiny droplets, and can accurately control the dynamics of the mixing process of substances inside the droplets, and realize dynamic regulation of the mixing process.

[0056] The second aspect of the present invention provides a system for mixing substances inside magnetically controlled droplets, which is used to implement the above-mentioned method for mixing substances inside magnetically controlled droplets. The system includes: a hydrophobic solid substrate, and a magnetic fluid spread on the surface of the hydrophobic solid substrate; when in use, the magnetic fluid quickly wraps the contacted droplets to form a magnetically responsive liquid shell, and the movement of the magnetically responsive liquid shell drives the wrapped droplets to move along a specific trajectory, thereby accelerating the mixing of substances inside the droplets; wherein the movement of the magnetically responsive liquid shell includes at least rotational movement, and the movement of the droplets includes at least: rotational movement, linear movement, circular movement, oscillating movement, in-situ rotation, or a combination thereof.

[0057] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the rotation axis of the rotational motion is perpendicular to the surface of the hydrophobic solid substrate.

[0058] In the above-mentioned system for magnetically controlled material mixing inside droplets, preferably, the magnetically responsive liquid shell includes a wetting ridge formed by the magnetic fluid between the droplet and the hydrophobic solid substrate, and a thin layer of magnetic fluid wrapped around the surface of the droplet.

[0059] According to a specific embodiment of the present invention, preferably, the above system further comprises: a magnet or a magnet array. More preferably, the magnet or magnet array comprises a permanent magnet, an electromagnet, or a magnet array composed of an iron needle array and an electromagnet. Further preferably, the magnet or magnet array is a coil-type electromagnet or its array.

[0060] In the above-mentioned system for magnetically controlled mixing of substances inside droplets, preferably, the magnet or magnet array is disposed below the hydrophobic solid substrate.

[0061] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the magnet or magnet array generates a magnetic field, and the magnetically responsive liquid shell moves under the action of the magnetic field. More preferably, the magnetic field includes a rotating magnetic field, which is generated by a permanent magnet, or a coil-type electromagnet or its array. Further preferably, the rotating magnetic field is generated by applying rotation to the center of the magnetic field generated by the permanent magnet, or the coil-type electromagnet or its array by a rotating motor to generate a rotating magnetic field.

[0062] In the above-mentioned system for magnetically controlling the mixing of substances inside droplets, preferably, the maximum magnetic field strength of the magnetic field is 50 mT.

[0063] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the rotation axis of the rotating magnetic field is perpendicular to the surface of the hydrophobic solid substrate.

[0064] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the rotation radius of the rotating magnetic field is 0.1 times to 3 times the radius of the droplet.

[0065] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the magnetically responsive liquid shell rotates at a speed of 1 Hz-100 Hz.

[0066] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the water contact angle of the hydrophobic solid substrate is 90-180°, more preferably 150-180°.

[0067] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the surface roughness of the hydrophobic solid substrate is 0.1-1000 nm, more preferably 0.1-200 nm.

[0068] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the hydrophobic solid substrate comprises a porous aluminum plate having hydrophobic or super-hydrophobic properties.

[0069] In the above-mentioned system of material mixing inside magnetically controlled droplets, preferably, the magnetic fluid comprises an oil-phase magnetic fluid loaded with magnetic nanoparticles. More preferably, preferably, the magnetic fluid comprises, but is not limited to, one or a combination of silicone oil-based magnetic fluid, kerosene-based magnetic fluid, engine oil-based magnetic fluid, polyphenylene ether magnetic fluid, and fluorine-based magnetic fluid.

[0070] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the oil phase in the oil phase magnetic fluid is dimethyl silicone oil and / or perfluoropolyether.

[0071] In some specific embodiments of the present invention, the magnetic nanoparticles include one or a combination of ferromagnetic nanoparticles, antiferromagnetic nanoparticles, ferrimagnetic nanoparticles, synthetic magnetic nanoparticles, paramagnetic nanoparticles and superparamagnetic nanoparticles. More preferably, the magnetic nanoparticles include ferroferric oxide nanoparticles; further preferably, the particle size of the ferroferric oxide nanoparticles is 5-300 nm; particularly preferably, the magnetic nanoparticles include functionalized ferroferric oxide nanoparticles.

[0072] In the above-mentioned system of material mixing inside magnetically controlled droplets, preferably, the magnetic nanoparticles are uniformly dispersed in the oil phase; taking the volume of the oil phase in the magnetic fluid as 100%, the mass / volume percentage of the magnetic nanoparticles is 1%-52%.

[0073] In some specific embodiments of the present invention, the magnetic fluid comprises a silicone oil-based magnetic fluid whose oil phase is dimethyl silicone oil and loaded with ferroferric oxide nanoparticles. Preferably, the silicone oil-based magnetic fluid can be prepared by the following steps: adding ferroferric oxide nanoparticles to dimethyl silicone oil, ultrasonic dispersion, and obtaining the silicone oil-based magnetic fluid. More preferably, the ferroferric oxide nanoparticles include siloxane-functionalized ferroferric oxide nanoparticles. Among them, siloxane-functionalized ferroferric oxide nanoparticles can be prepared by conventional methods in the art. For example, ferroferric oxide nanoparticles are mixed with functionalized monomers and reacted at a suitable temperature for a suitable time to prepare. Preferably, the siloxane-functionalized ferroferric oxide nanoparticles are prepared using monocarboxyl-terminated polysiloxane (PDMS-COOH) as a functionalized monomer.

[0074] In other specific embodiments of the present invention, the magnetic fluid includes a perfluoropolyether-based magnetic fluid whose oil phase is perfluoropolyether and loaded with ferroferric oxide nanoparticles. Preferably, the perfluoropolyether-based magnetic fluid can be prepared by the following steps: adding ferroferric oxide nanoparticles to perfluoropolyether, ultrasonically dispersing, and obtaining the perfluoropolyether-based magnetic fluid. More preferably, the ferroferric oxide nanoparticles include fluorine-functionalized ferroferric oxide nanoparticles. Among them, fluorine-functionalized ferroferric oxide nanoparticles can be prepared by conventional methods in the art. For example, ferroferric oxide nanoparticles are mixed with functionalized monomers and reacted at a suitable temperature for a suitable time to prepare. Preferably, the fluorine-functionalized ferroferric oxide nanoparticles are prepared using monocarboxyl-terminated perfluoropolyether as a functionalized monomer.

[0075] In the above-mentioned system of mixing substances inside magnetically controlled droplets, preferably, when the droplets are water-phase droplets, an oil-phase magnetic fluid loaded with magnetic nanoparticles whose oil phase is dimethyl silicone oil is selected as the magnetic fluid; when the droplets are oil-phase droplets, an oil-phase magnetic fluid loaded with magnetic nanoparticles whose oil phase is perfluoropolyether is selected as the magnetic fluid. According to a specific embodiment of the present invention, a suitable magnetic fluid can be selected according to the type of droplets, preferably a silicone oil-based magnetic fluid is used for water-phase droplets, and a perfluoropolyether-based magnetic fluid is used for oil-phase droplets.

[0076] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the viscosity of the magnetic fluid is 0.01-600 cst, and more preferably 0.1-100 cst.

[0077] In the above-mentioned system for mixing substances inside magnetically controlled droplets, preferably, the contact angle of the magnetic fluid on the hydrophobic solid substrate is 0-50°, more preferably 0-30°.

[0078] In the above-mentioned system of material mixing inside magnetically controlled droplets, preferably, the magnetic fluid is spread on the surface of the hydrophobic solid substrate in the following manner: an appropriate amount of magnetic fluid (preferably the above-mentioned silicone oil-based magnetic fluid or perfluoropolyether-based magnetic fluid) is dropped onto the surface of the hydrophobic solid substrate, and the magnetic fluid spontaneously spreads on the surface of the hydrophobic solid substrate under the action of surface capillary forces.

[0079] In the above-mentioned system of material mixing inside magnetically controlled droplets, preferably, the droplets are selected from one or more of water, ethylene glycol, glycerol, silicone oil, dimethyl sulfoxide, petroleum ether, toluene, ethanol, ethyl acetate, plant essential oils, and ionic liquids, or are selected from one or more of nanoparticle solutions, cell culture fluids, bacterial culture fluids, protein solutions, and inorganic salt solutions.

[0080] The present invention provides a method and system for magnetically controlling the mixing of substances inside droplets. The method and system are a control method and system that does not require any additives and does not interfere with the droplets. The present invention uses magnetic fluid to pre-wet a hydrophobic solid substrate, so that the droplets do not directly contact the substrate during movement, thereby avoiding contamination and wear of the substrate. In addition, the present invention applies a rotating magnetic field so that the magnetic fluid response shell that wraps the droplets rotates around the droplets, generating a shear flow at the interface between the two phases, causing an increase in the dynamics inside the droplets, and significantly accelerating the process of mixing substances inside the droplets. Most importantly, the mixing process of the droplets can be controllably adjusted by changing the angular velocity of the rotating magnetic field.

[0081] Droplet mixing is of great significance in biochemical reactions and synthesis. Controllable droplet mixing expands the application range of droplets as separate microreactors. The technical solution of the present invention can realize chemical synthesis reactions in droplets of small volume and low cost in an open system, which is conducive to high-throughput screening of reaction conditions. The process of accelerating the internal dynamics of droplets is conducive to accelerating the probability of molecular collisions, which can be used to accelerate detection reactions in the field of molecular diagnosis.

[0082] Based on the control characteristics, the present invention provides a new magnetically controlled droplet method and system that is programmable, simple, resistant to substrate contamination, and fast in response. The present invention does not cause any interference to the droplets, nor does it introduce heat. Most importantly, the process of accelerating the mixing of substances in the droplets by the rotating magnetic field occurs in situ, which is conducive to the subsequent combination of various in situ detection technologies for the interpretation of the results of biochemical reactions.

[0083] From the perspective of application, the present invention is a low-cost, simple, sustainable and green new manipulation technology, which has a good application prospect in the development of new digital microfluidic technology. The manipulation of droplets is performed on an open surface, and does not require the design and preparation of pipelines. In addition, the current digital microfluidic technology, even the more mature electrowetting digital microfluidic technology, requires complex circuit design, the setting of multiple dielectric layers, etc. The magnetic responsive substrate of the present invention (i.e., a hydrophobic solid substrate infused with magnetic fluid) is simple to prepare, and thanks to its anti-pollution properties, it can achieve repetitive and reconfigurable droplet manipulation, greatly reducing the cost of use.

[0084] Specifically, the technical solution of the present invention can be designed into a microfluidic chip for detecting nitrate ions, which retains good detection stability compared with traditional detection technology. In addition, the novel droplet mixing method of the present invention can easily achieve rapid mixing of high-viscosity liquids, and can be used for protein crystallization and synthesis of functional materials. In addition, the technical solution of the present invention can be used for screening of material synthesis conditions. The droplet-based bioreactor has a huge advantage of small sample loss, and the in-situ reaction helps to directly combine the optical detection instrument to visualize the results. It has good commercial development potential as a product for production condition screening in pharmaceutical and chemical companies. In addition, in the present invention, the droplet technology controlled by the wetting ridge is expected to be combined with existing advanced diagnostic technologies, such as Raman enhanced spectroscopy detection technology, colorimetric detection reagents, etc., to achieve rapid on-site disease screening. Mature chips can also become spare biochemical analysis and detection equipment for every household, and have important market development potential in biomedicine.

[0085] In short, the technical solution of the present invention is green and simple, and is aimed at the major needs of various industries. It has broad application prospects in many fields such as biomedical research, drug synthesis screening, environmental monitoring and protection, health quarantine, forensic identification, detection and diagnosis of biological samples, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0086] Figure 1 Schematic diagram of the rotating magnetic field based on mechanical control in the system for mixing substances inside magnetically controlled droplets in Example 1.

[0087] Figure 2 It is a schematic diagram and a display diagram of the magnetically responsive liquid shell rotating under the condition of a surface magnetic field strength of <1 mT in Example 1 and driving the enclosed droplets to rotate in situ.

[0088] Figure 3 This is an optical image of the process in which the magnetically responsive liquid shell in Example 1 rotates and drives the enclosed droplet to rotate in situ.

[0089] Figure 4 This is a comparison diagram of the mixing of materials inside the droplet by controlling the rotation of the magnetically responsive liquid shell in Example 1 and the natural mixing of materials inside the droplet in the absence of a magnetic field.

[0090] Figure 5 This is an optical image of the process in which the magnetically responsive liquid shell in Example 1 performs a rotational motion and drives the enclosed liquid droplet to perform a circular motion.

[0091] Figure 6 This is a scanning electron microscope image of the surface of the porous aluminum plate in Example 1.

[0092] Figure 7This is an optical graph of the water drop contact angle on the surface of the porous aluminum plate with super-hydrophobic properties in Example 1.

[0093] Figure 8 This is an optical image of the spontaneous spreading of the silicone oil-based magnetic fluid of Example 1 on the surface of a porous aluminum plate with superhydrophobic properties.

[0094] Fig. 9 This is a state diagram of the magnetically responsive liquid shell in Example 2 under no magnetic field conditions, weak rotating magnetic field strength, and strong rotating magnetic field strength.

[0095] Fig.10 Schematic diagram and illustration of the magnetically responsive liquid shell guiding the droplet to perform linear motion under the action of the magnetic field in Example 3.

[0096] Fig.11 Optical images showing that different magnetic fluids in Example 4 guide water droplets and silicone oil droplets to move along paths of 'M' and 'N' in a programmable manner in a two-dimensional plane.

[0097] Fig.12 This is an optical image of manipulating multiple droplets using a coil-type electromagnet array in Example 5. DETAILED DESCRIPTION

[0098] In order to have a clearer understanding of the technical features, purposes and beneficial effects of the present invention, the technical solution of the present invention is now described in detail below, but it should not be construed as limiting the applicable scope of the present invention.

[0099] Example 1

[0100] The present embodiment provides a system for mixing substances inside magnetically controlled droplets, the system comprising: a hydrophobic solid substrate, a magnetic fluid spread on the surface of the hydrophobic solid substrate, and a coil-type electromagnet arranged below the hydrophobic solid substrate; when in use, the magnetic fluid quickly wraps the contacted droplets to form a magnetically responsive liquid shell, and the magnetically responsive liquid shell rotates to drive the wrapped droplets to rotate in situ, thereby accelerating the mixing of substances inside the droplets.

[0101] This embodiment also provides a method for mixing substances inside a magnetically controlled droplet, which comprises the following steps:

[0102] (1) adding a liquid droplet containing a substance to be mixed onto a hydrophobic solid substrate infused with a magnetic fluid, so that the magnetic fluid quickly wraps the contacting liquid droplet to form a magnetically responsive liquid shell;

[0103] (2) Controlling the magnetically responsive liquid shell to rotate under the action of a rotating magnetic field, driving the encapsulated droplets to rotate in situ, thereby accelerating the mixing of substances inside the droplets.

[0104] The magnetically responsive liquid shell includes a wetting ridge formed by the magnetic fluid between the droplet and the hydrophobic solid substrate, and a thin layer of magnetic fluid wrapped around the surface of the droplet.

[0105] In this embodiment, the liquid droplets are water droplets.

[0106] In this embodiment, a rotating magnetic field is generated by a coil-type electromagnet. The rotating magnetic field is generated by mechanically manipulating a single coil-type electromagnet to rotate, thereby applying a low offset rotation to the center of the magnetic field to generate a rotating magnetic field. Specifically, Figure 1 As shown, the rotating magnetic field is generated by rotating a coil type electromagnet fixed on a rotating motor, and the rotating motor is connected to a speed controller for controlling the angular velocity of the rotation. The rotating axis of the rotating magnetic field is perpendicular to the surface of the hydrophobic solid substrate. The maximum magnetic field strength of the rotating magnetic field at the position where the droplet is located is 50mT.

[0107] Figure 2 The figure is a schematic diagram and a demonstration diagram of the magnetic response liquid shell rotating and driving the enclosed droplet to rotate in situ under the condition of surface magnetic field strength <1mT (i.e., weak magnetic field). Figure 2 It can be seen that the asymmetric magnetically responsive liquid shell rotates around the droplet in response to the rotating magnetic field under a weak magnetic field. In this embodiment, by controlling the angular velocity of the coil-type electromagnet to rotate, the magnetically responsive liquid shell can be controlled to rotate at a speed of 0.1 Hz-100 Hz. Moreover, the rotation radius of the rotation motion is 1 times the radius of the droplet.

[0108] Figure 3 This is an optical image of the process in which a magnetically responsive liquid shell rotates and drives the liquid droplet it encloses to rotate in situ. Figure 3 It can be seen that in this embodiment, by adding a droplet containing a substance to be mixed onto a hydrophobic solid substrate infused with a magnetic fluid, the magnetic fluid quickly and perfectly wraps the contacted droplet to form a magnetically responsive liquid shell, and controls the rotational motion of the magnetic field to control the magnetically responsive liquid shell to rotate, thereby driving the wrapped droplet to rotate in situ, so that a controllable speed difference is generated between the magnetically responsive liquid shell and the droplet, thereby generating a viscous shear force on the droplet, which can accelerate the fluid shear inside the droplet, and further accurately control the dynamics of the mixing process of the substances inside the droplet, thereby realizing dynamic control of the mixing process.

[0109] Figure 4 This is a comparison of the mixing of the materials inside the droplet by controlling the rotation of the magnetically responsive liquid shell in this embodiment, and the natural mixing of the materials inside the droplet in the absence of a magnetic field. Figure 4 In the figure, the substances to be mixed in the droplet are Congo red and fruit green. Figure 4 In the experiment, the magnetically responsive liquid shell is controlled to rotate at a speed of 1 Hz, and the rotation radius of the rotation is 1 times the radius of the liquid droplet. Figure 4 It can be seen that this embodiment controls the rotation of the magnetically responsive liquid shell, driving the enclosed droplets to rotate in situ, and can generate viscous shear force on the droplets, which can accelerate the mixing of substances in the droplets and achieve rapid and efficient mixing of substances inside tiny droplets.

[0110] The method of this embodiment further includes the following steps: controlling the magnetically responsive liquid shell to rotate under the action of a rotating magnetic field, driving the enclosed droplets to perform circular motion, and accelerating the mixing of substances inside the droplets.

[0111] Figure 5 This is an optical image of the process in which a magnetically responsive liquid shell rotates and drives the enclosed liquid droplet to move in a circular motion. Figure 5 It can be seen that in this embodiment, the rotation radius of the magnetically responsive liquid shell is set to be twice the radius of the droplet, so as to drive the enclosed droplet to perform circular motion. The viscous friction between the magnetically responsive liquid shell and the droplet and between the droplet and the substrate accelerates the fluid shear inside the droplet, thereby accurately controlling the dynamics of the mixing process of the substances inside the droplet, thereby achieving dynamic control of the mixing process.

[0112] In the present embodiment, the hydrophobic solid substrate is a porous aluminum plate with super-hydrophobic properties, which is obtained by the following steps: the porous aluminum plate is put into 80-95 ° C hot water and soaked for 30 minutes to roughen its surface, and then perfluorodecyl triethoxysilane is used to hydrophobize it to obtain a porous aluminum plate with super-hydrophobic properties. The specific steps of hydrophobizing the porous aluminum plate using perfluorodecyl triethoxysilane can be carried out according to the conventional steps in the art, for example, the surface roughened porous aluminum plate is soaked in a perfluorodecyl triethoxysilane solution for a period of time. Afterwards, conventional drying and other steps can be performed to obtain a porous aluminum plate with super-hydrophobic properties.

[0113] The scanning electron microscope image of the surface of the porous aluminum plate used in this embodiment is as follows: Figure 6 As shown. Figure 6 It can be seen that the microstructure of the porous aluminum plate surface used in this embodiment. The optical graph of the water drop contact angle on the porous aluminum plate surface with super hydrophobic properties in this embodiment is as follows Figure 7 As shown. Figure 7 It can be seen that the surface contact angle of the porous aluminum plate modified with fluorosilane is about 161°, showing super hydrophobic properties. The surface roughness of the porous aluminum plate with super hydrophobic properties in this embodiment is 100 nm.

[0114] In the present embodiment, the magnetic fluid is a silicone oil-based magnetic fluid whose oil phase is dimethyl silicone oil and loaded with siloxane-functionalized ferroferric oxide nanoparticles. The silicone oil-based magnetic fluid is prepared by the following steps: adding siloxane-functionalized ferroferric oxide nanoparticles to dimethyl silicone oil, ultrasonic dispersion, and uniformly dispersing the siloxane-functionalized ferroferric oxide nanoparticles in dimethyl silicone oil to obtain a silicone oil-based magnetic fluid. Wherein, the particle size of the ferroferric oxide nanoparticles is 5-100nm. The siloxane-functionalized ferroferric oxide nanoparticles are prepared by the following steps: a monocarboxyl-terminated polysiloxane reacts with ferroferric oxide particles at 80°C for 12h. The mass / volume ratio of siloxane-functionalized ferroferric oxide nanoparticles and dimethyl silicone oil is 12%. The viscosity of the silicone oil-based magnetic fluid is 10cst.

[0115] In this embodiment, the magnetic fluid is spread on the surface of the hydrophobic solid substrate in the following manner: an appropriate amount of silicone oil-based magnetic fluid is dropped onto the surface of the hydrophobic solid substrate, and the silicone oil-based magnetic fluid spontaneously spreads on the surface of the hydrophobic solid substrate under the action of surface capillary force, thereby obtaining a hydrophobic solid substrate infused with magnetic fluid. Figure 8 This is an optical image of the spontaneous spreading of the silicone oil-based magnetic fluid on the surface of a porous aluminum plate with super-hydrophobic properties. Figure 8 It can be seen that the silicone oil-based magnetic fluid spreads rapidly on the surface of the porous aluminum plate with super-hydrophobic properties under the action of capillary force. In this embodiment, the contact angle of the magnetic fluid on the hydrophobic solid substrate is 3°.

[0116] Example 2

[0117] This embodiment provides a method for mixing substances inside a magnetically controlled droplet. The method uses the system for mixing substances inside a magnetically controlled droplet in Embodiment 1, and includes the following steps:

[0118] (1) adding a liquid droplet containing a substance to be mixed onto a hydrophobic solid substrate infused with a magnetic fluid, so that the magnetic fluid quickly wraps the contacting liquid droplet to form a magnetically responsive liquid shell;

[0119] (2) controlling the magnetically responsive liquid shell to rotate under the action of a rotating magnetic field, driving the enclosed droplets to rotate in situ, and accelerating the mixing of substances inside the droplets;

[0120] (3) The magnetically responsive liquid shell responds to different rotating magnetic field intensities and then opens or closes in situ on the droplet surface to regulate the exchange of droplets with external substances and / or control the continuous merging and mixing of multiple droplets.

[0121] Fig. 9 The state diagram of the magnetically responsive liquid shell under no magnetic field conditions, weak rotating magnetic field strength (0-1mT), and strong rotating magnetic field strength (>1mT). Fig. 9It can be seen that under the condition of no magnetic field, the droplet is wrapped by the magnetic fluid to form a magnetically responsive liquid shell; under weak rotating magnetic field strength, the magnetically responsive liquid shell is in a closed state; under strong rotating magnetic field strength, the magnetically responsive liquid shell is opened due to strong interaction.

[0122] Example 3

[0123] This embodiment provides a method for mixing substances inside a magnetically controlled droplet. The method uses the system for mixing substances inside a magnetically controlled droplet in Embodiment 1, and includes the following steps:

[0124] (1) adding a liquid droplet containing a substance to be mixed onto a hydrophobic solid substrate infused with a magnetic fluid, so that the magnetic fluid quickly wraps the contacting liquid droplet to form a magnetically responsive liquid shell;

[0125] (2) Controlling the movement of the magnetically responsive liquid shell to drive the movement of the droplets wrapped therein; the movement of the magnetically responsive liquid shell includes rotational movement, and the movement of the droplets includes in-situ rotation and linear movement on the hydrophobic solid substrate.

[0126] In this embodiment, the linear motion of the droplets on the hydrophobic solid substrate is achieved in the following manner: a single coil-type electromagnet far away from the droplets is energized to generate a magnetic field, driving the magnetically responsive liquid shell to drive the droplets wrapped therein to perform linear motion on the hydrophobic solid substrate toward the center of the magnetic field. Fig.10 Schematic diagram and illustration of a magnetically responsive liquid shell guiding a droplet to perform linear motion under the action of a magnetic field. Fig.10 It can be seen that in the presence of a strong magnetic field, the magnetically responsive liquid shell is magnetized, driving the droplet to move.

[0127] Example 4

[0128] This embodiment provides a system for mixing substances inside magnetically controlled droplets. The system is basically the same as the system for mixing substances inside magnetically controlled droplets in Example 1, except that the magnetic fluid is a perfluoropolyether-based magnetic fluid whose oil phase is perfluoropolyether and carries fluorine-functionalized ferrosoferric oxide nanoparticles.

[0129] The perfluoropolyether-based magnetic fluid is prepared by the following steps: adding fluorine-functionalized ferroferric oxide nanoparticles to perfluoropolyether, ultrasonically dispersing, and uniformly dispersing the fluorine-functionalized ferroferric oxide nanoparticles in the perfluoropolyether to obtain a perfluoropolyether-based magnetic fluid. The particle size of the ferroferric oxide nanoparticles is 5-100nm. The fluorine-functionalized ferroferric oxide nanoparticles are prepared by the following steps: reacting a monocarboxyl-terminated perfluoropolyether with ferroferric oxide particles at 90°C for 12 hours. The mass / volume ratio of the fluorine-functionalized ferroferric oxide nanoparticles and the perfluoropolyether is 12%. The viscosity of the perfluoropolyether-based magnetic fluid is 100cst.

[0130] In this embodiment, the contact angle of the perfluoropolyether-based magnetic fluid on the hydrophobic solid substrate is 3°.

[0131] When the droplets are water-phase droplets, the silicone oil-based magnetic fluid in Example 1 is selected; when the droplets are oil-phase droplets, the perfluoropolyether-based magnetic fluid in this example is selected.

[0132] In this embodiment, the silicone oil-based magnetic fluid in embodiment 1 is used to coat water droplets, and the perfluoropolyether-based magnetic fluid in this embodiment is used to coat silicone oil droplets. The magnetic responsive liquid shell is controlled to rotate under the action of the rotating magnetic field by the method in embodiment 3, driving the wrapped droplets to rotate in situ, accelerating the mixing of the substances inside the droplets, and allowing the magnetic responsive liquid shell to guide the droplets to perform linear motion under the action of the magnetic field. The results are shown in FIG. Fig.11 shown. Fig.11 Optical images of different magnetic fluids in this embodiment (the left picture shows a silicone oil-based magnetic fluid, and the right picture shows a perfluoropolyether-based magnetic fluid) guiding water droplets (left) and silicone oil droplets (right) to move in a programmable manner along the paths of 'M' and 'N' in a two-dimensional plane. Fig.11 It can be seen that the movement of various types of droplets can be achieved by replacing the magnetic fluid, and programmable droplet manipulation can be achieved in a two-dimensional plane.

[0133] Example 5

[0134] This embodiment provides a system for mixing substances inside magnetically controlled droplets, the system comprising: a hydrophobic solid substrate, a magnetic fluid spread on the surface of the hydrophobic solid substrate, and a coil-type electromagnet array arranged below the hydrophobic solid substrate; in use, the magnetic fluid quickly wraps the contacted droplets to form a magnetically responsive liquid shell, and the magnetically responsive liquid shell rotates to drive the wrapped droplets to rotate in situ, accelerating the mixing of substances inside the droplets. The magnetic fluid and the hydrophobic solid substrate are the same as those in Example 1, and the droplets are water droplets.

[0135] This embodiment also provides a method for mixing substances inside a magnetically controlled droplet, which comprises the following steps:

[0136] (1) adding a plurality of liquid droplets containing substances to be mixed onto a hydrophobic solid substrate infused with a magnetic fluid, so that the magnetic fluid quickly wraps the contacting liquid droplets to form a magnetically responsive liquid shell;

[0137] (2) Controlling the magnetically responsive liquid shell to rotate under the action of a rotating magnetic field, driving the encapsulated droplets to rotate in situ, and accelerating the mixing of substances inside the droplets.

[0138] The magnetically responsive liquid shell includes a wetting ridge formed between the magnetic fluid droplet and the hydrophobic solid substrate, and a thin layer of magnetic fluid wrapped around the surface of the droplet.

[0139] In this embodiment, the rotating magnetic field is generated by the following method: the center of the magnetic field generated by the coil-type electromagnet array is rotated by a rotary motor to generate a rotating magnetic field. The rotation axis of the rotating magnetic field is perpendicular to the surface of the hydrophobic solid substrate. The maximum magnetic field strength of the rotating magnetic field at the location of the droplet is 30mT. By controlling the rotary motor, the magnetic responsive liquid shell can be controlled to rotate at a speed of 1Hz-100Hz. In addition, the rotation radius of the rotation motion is 1 times the radius of the droplet.

[0140] In this embodiment, the rotating magnetic field is an array rotating magnetic field, and an offset rotation is applied to each magnetic field center simultaneously or individually, so that multiple droplets can be manipulated individually or continuously. By utilizing the spatial symmetry of the magnetic field, multiple droplets can move toward the same magnetic field center at the same time and merge at the magnetic field center, so that sequential manipulation of a large area droplet array can be achieved. Fig.12 In this embodiment, a coil-type electromagnet array is used to manipulate multiple droplets ( Fig.12 The method of this embodiment can be used to achieve mixing of multiple droplets. Fig.12 The white circle area in the figure is the water droplet covered by the magnetically responsive liquid shell. Fig.12 It can be seen that by building an electromagnet array, multiple droplets can be manipulated and mixed, which is expected to be used for high-throughput micro-droplet analysis in the future.

Claims

1. A method for mixing substances inside a magnetically controlled droplet, comprising the following steps: (1) adding a liquid droplet containing a substance to be mixed onto a hydrophobic solid substrate infused with a magnetic fluid, so that the magnetic fluid quickly wraps the contacting liquid droplet to form a magnetically responsive liquid shell; (2) controlling the movement of the magnetically responsive liquid shell to drive the enclosed droplets to move along a specific trajectory, thereby accelerating the mixing of substances inside the droplets; The movement of the magnetically responsive liquid shell at least includes rotational movement, and the movement of the droplet at least includes: rotational movement, linear movement, circular movement, oscillating movement, in-situ rotation, or a combination thereof.

2. The method for mixing substances inside magnetically controlled droplets according to claim 1, wherein: The magnetically responsive liquid shell includes a wetting ridge formed by the magnetic fluid between the liquid droplet and the hydrophobic solid substrate, and a thin layer of magnetic fluid wrapped around the surface of the liquid droplet.

3. The method for mixing substances inside magnetically controlled droplets according to claim 1, wherein: The magnetically responsive liquid shell moves under the action of an external magnetic field; Preferably, the external magnetic field is disposed below the hydrophobic solid substrate; Preferably, the maximum magnetic field strength of the external magnetic field at the location of the droplet is 50 mT; more preferably, the external magnetic field is generated by one or more of a permanent magnet, an electromagnet, and a magnet array consisting of an iron needle array and an electromagnet.

4. The method for mixing substances inside magnetically controlled droplets according to claim 3, wherein: The external magnetic field is controlled by a rotary motor or an array thereof; Preferably, the external magnetic field comprises a rotating magnetic field, which is generated by a permanent magnet, or a coiled electromagnet or an array thereof; More preferably, the rotating magnetic field is generated by: applying rotation to the center of the magnetic field generated by a permanent magnet, or a coil-type electromagnet or an array thereof by a rotating motor to generate a rotating magnetic field; More preferably, the rotation radius of the rotating magnetic field is 0.1 times to 3 times the radius of the droplet.

5. The method for mixing substances inside magnetically controlled droplets according to claim 1, wherein: The linear motion, rotational motion, circular motion, oscillatory motion, and / or in-situ rotation of the droplets on the hydrophobic solid substrate are achieved by: (a) energizing a single or multiple coil-type electromagnets away from the droplets to generate a magnetic field, driving the magnetically responsive liquid shell to drive the droplets wrapped therein to perform linear motion on the hydrophobic solid substrate toward the center of the magnetic field; (b) applying rotation to the center of the magnetic field generated by the permanent magnet, or the coil-type electromagnet or its array by a rotary motor, thereby generating a rotating magnetic field to control the magnetically responsive liquid shell to perform rotational motion, thereby driving the enclosed droplets to perform rotational motion, circular motion, oscillating motion, and / or in-situ rotation.

6. The method for mixing substances inside magnetically controlled droplets according to claim 1 or 3, wherein: The method further comprises: the magnetically responsive liquid shell responds to different magnetic field strengths, thereby opening or closing in situ on the surface of the droplet, for regulating the exchange of the droplet with external substances, and / or controlling the continuous merging and mixing of multiple droplets; More preferably, the magnetically responsive liquid shell is in a closed state under a weak magnetic field strength, and the magnetically responsive liquid shell is opened due to strong interaction under a strong magnetic field strength; wherein the magnetic field strength is the magnetic field strength at the position where the droplet is located, the weak magnetic field strength is 0 to 1 mT, and the strong magnetic field strength is >1 mT.

7. The method for mixing substances inside magnetically controlled droplets according to claim 1 or 3, wherein: In step (2), the magnetically responsive liquid shell is rotated at a speed of 0.1 Hz-100 Hz under the guidance of an external magnetic field.

8. The method for mixing substances inside magnetically controlled droplets according to claim 1, wherein: The water contact angle of the hydrophobic solid substrate is 90-180°, preferably 150-180°; Preferably, the surface roughness of the hydrophobic solid substrate is 0.1-1000 nm, more preferably 0.1-200 nm; Preferably, the hydrophobic solid substrate comprises a porous aluminum plate having hydrophobic or superhydrophobic properties.

9. The method for mixing substances inside magnetically controlled droplets according to claim 1, wherein: The magnetic fluid comprises an oil phase magnetic fluid loaded with magnetic nanoparticles; Preferably, the magnetic fluid comprises one or a combination of silicone oil-based magnetic fluid, kerosene-based magnetic fluid, engine oil-based magnetic fluid, polyphenylene ether magnetic fluid and fluorine-based magnetic fluid; Preferably, the oil phase in the oil phase magnetic fluid comprises dimethyl silicone oil and / or perfluoropolyether; Preferably, the magnetic nanoparticles include ferromagnetic nanoparticles, antiferromagnetic nanoparticles, ferrimagnetic nanoparticles, synthetic magnetic nanoparticles, paramagnetic nanoparticles and superparamagnetic nanoparticles, or a combination thereof; more preferably, the magnetic nanoparticles include ferroferric oxide nanoparticles; further preferably, the particle size of the ferroferric oxide nanoparticles is 5-300 nm; Preferably, the magnetic nanoparticles are uniformly dispersed in the oil phase; taking the volume of the oil phase in the magnetic fluid as 100%, the mass / volume percentage of the magnetic nanoparticles is 1%-52%; Preferably, the magnetic fluid comprises a silicone oil-based magnetic fluid whose oil phase is dimethyl silicone oil and loaded with ferroferric oxide nanoparticles, wherein the ferroferric oxide nanoparticles preferably include siloxane-functionalized ferroferric oxide nanoparticles; or, the magnetic fluid comprises a perfluoropolyether-based magnetic fluid whose oil phase is perfluoropolyether and loaded with ferroferric oxide nanoparticles, wherein the ferroferric oxide nanoparticles preferably include fluorine-functionalized ferroferric oxide nanoparticles; Preferably, when the droplets are aqueous droplets, an oil-phase magnetic fluid loaded with magnetic nanoparticles whose oil phase is dimethyl silicone oil is selected as the magnetic fluid; when the droplets are oil-phase droplets, an oil-phase magnetic fluid loaded with magnetic nanoparticles whose oil phase is perfluoropolyether is selected as the magnetic fluid; Preferably, the viscosity of the magnetic fluid is 0.01-600 cst, more preferably 0.1-100 cst; Preferably, the contact angle of the magnetic fluid on the hydrophobic solid substrate is 0-50°, more preferably 0-30°; Preferably, the droplets are selected from one or more of water, ethylene glycol, glycerol, silicone oil, dimethyl sulfoxide, petroleum ether, toluene, ethanol, ethyl acetate, plant essential oils, and ionic liquids, or are selected from one or more of nanoparticle solutions, cell culture fluids, bacterial culture fluids, protein solutions, and inorganic salt solutions.

10. A system for mixing substances inside a magnetically controlled droplet, which is used to implement the method for mixing substances inside a magnetically controlled droplet according to any one of claims 1 to 9, the system comprising: A hydrophobic solid substrate, and a magnetic fluid spread on the surface of the hydrophobic solid substrate; When in use, the magnetic fluid quickly wraps the contacted droplets to form a magnetically responsive liquid shell. The movement of the magnetically responsive liquid shell drives the wrapped droplets to move along a specific trajectory, accelerating the mixing of substances inside the droplets. The movement of the magnetically responsive liquid shell at least includes rotational movement, and the movement of the droplet at least includes: rotational movement, linear movement, circular movement, oscillating movement, in-situ rotation, or a combination thereof.

11. The system for mixing substances inside magnetically controlled droplets according to claim 10, wherein: The system further comprises: a magnet or a magnet array; Preferably, the magnet or magnet array comprises a permanent magnet, an electromagnet, or a magnet array composed of an iron needle array and an electromagnet; more preferably, the magnet or magnet array is a coil-type electromagnet or an array thereof; Preferably, the magnet or magnet array generates a magnetic field, and the magnetically responsive liquid shell moves under the action of the magnetic field; Preferably, the magnet or magnet array is disposed below the hydrophobic solid substrate; Preferably, the maximum magnetic field strength of the magnetic field is 50 mT; Preferably, the magnetic field comprises a rotating magnetic field; Preferably, the rotation radius of the rotating magnetic field is 0.1 times to 3 times the radius of the droplet; Preferably, the magnetically responsive liquid shell rotates at a speed of 1 Hz-100 Hz.

12. The system for mixing substances inside magnetically controlled droplets according to claim 10, wherein: The water contact angle of the hydrophobic solid substrate is 90-180°, preferably 150-180°; Preferably, the surface roughness of the hydrophobic solid substrate is 0.1-1000 nm, more preferably 0.1-200 nm; Preferably, the hydrophobic solid substrate comprises a porous aluminum plate having hydrophobic or superhydrophobic properties; Preferably, the magnetic fluid comprises an oil-phase magnetic fluid loaded with magnetic nanoparticles; Preferably, the magnetic fluid comprises one or a combination of silicone oil-based magnetic fluid, kerosene-based magnetic fluid, engine oil-based magnetic fluid, polyphenylene ether magnetic fluid and fluorine-based magnetic fluid; Preferably, the oil phase in the oil phase magnetic fluid is dimethyl silicone oil and / or perfluoropolyether; Preferably, the magnetic nanoparticles include ferromagnetic nanoparticles, antiferromagnetic nanoparticles, ferrimagnetic nanoparticles, synthetic magnetic nanoparticles, paramagnetic nanoparticles and superparamagnetic nanoparticles, or a combination thereof; more preferably, the magnetic nanoparticles include ferroferric oxide nanoparticles; further preferably, the ferroferric oxide nanoparticles have a particle size of 5-300 nm; particularly preferably, the magnetic nanoparticles include functionalized ferroferric oxide nanoparticles; Preferably, the magnetic nanoparticles are uniformly dispersed in the oil phase; taking the volume of the oil phase in the magnetic fluid as 100%, the mass / volume percentage of the magnetic nanoparticles is 1%-52%; Preferably, the magnetic fluid comprises a silicone oil-based magnetic fluid whose oil phase is dimethyl silicone oil and loaded with ferroferric oxide nanoparticles, wherein the ferroferric oxide nanoparticles preferably include siloxane-functionalized ferroferric oxide nanoparticles; or, the magnetic fluid comprises a perfluoropolyether-based magnetic fluid whose oil phase is perfluoropolyether and loaded with ferroferric oxide nanoparticles, wherein the ferroferric oxide nanoparticles preferably include fluorine-functionalized ferroferric oxide nanoparticles; Preferably, the viscosity of the magnetic fluid is 0.01-600 cSt, more preferably 0.1-100 cSt; Preferably, the contact angle of the magnetic fluid on the hydrophobic solid substrate is 0-50°, more preferably 0-30°.

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