Method for preparing magnetic nanoparticles based on microfluid focusing
By using microfluidic chips and sheath flow at both ends to prepare magnetic nanoparticles with a particle size of 5-20 nm, the problem of achieving small size and uniform distribution in existing technologies has been solved, and stable continuous production and industrial scale-up have been achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- ZHEJIANG UNIV
- Filing Date
- 2026-02-04
- Publication Date
- 2026-04-10
AI Technical Summary
Existing methods for preparing magnetite (Fe3O4) magnetic nanoparticles cannot simultaneously meet the requirements of small size, narrow size distribution, and continuous and stable production.
By employing a specially designed microfluidic chip and a sheath flow at both ends, the intermediate flow is focused and controlled. By increasing the flow rate at both ends, the intermediate liquid filament is squeezed to prepare magnetic nanoparticles of iron oxide (Fe3O4) with a particle size of 5-20 nm.
The preparation of magnetic nanoparticles with a particle size as low as 5 nm and uniform distribution was achieved, ensuring the uniformity of reaction conditions and the stability of the synthesis process, making it suitable for industrial-scale production.
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Figure CN121823664A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application relates to a method for preparing magnetic nanoparticles based on microfluidic focusing, and belongs to the technical field of nanomaterials. BACKGROUND
[0002] Iron oxide (Fe3O4) magnetic nanoparticles have become the core material for high-end biomedical applications such as targeted drug delivery, magnetic resonance imaging, magnetic hyperthermia, and magnetic separation due to their superparamagnetism, high saturation magnetization, low toxicity, and good biocompatibility. Over the past two decades, researchers have developed various batch preparation routes such as co-precipitation, sol-gel, microemulsion, and high-temperature thermal decomposition, and gradually achieved commercialization. Among them, the co-precipitation method has attracted much attention due to its simple operation, but the traditional co-precipitation method often leads to wide particle size distribution and poor uniformity due to the difficulty in controlling the reaction conditions; the sol-gel method is high in cost and difficult to mass industrialize; the microemulsion method requires a large amount of surfactant, has low yield, and the particles are easy to aggregate during the demulsification process, making it difficult to completely remove the surfactant, affecting the magnetic heat conversion efficiency, and making it impossible to achieve continuous production; the high-temperature thermal decomposition method has high temperature and expensive solvent, and requires inert protection throughout the process, significantly increasing equipment and operating costs, which is not suitable for industrial production. That is, conventional methods have problems such as poor controllability of particle size and morphology, difficulty in batch reproduction, complicated steps, and high cost.
[0003] The emergence of microfluidic technology provides a new way to solve the above problems. The use of tens to hundreds of micrometer channels in a laminar flow state enables millisecond-level uniform mixing of reactants, precise control of supersaturation, decoupling of nucleation and growth stages, and obtaining monodisperse nanocrystals; the closed continuous flow form avoids oxygen penetration and significantly inhibits oxidation; the reaction volume is reduced by three orders of magnitude, and the solvent consumption and waste liquid discharge are reduced synchronously, which is in line with the concept of green chemistry. However, existing microfluidic synthesis is mostly limited to microdroplets, "T" or "Y" simple mixing chips, which have low specific surface area and small flux, and iron salts are easy to deposit on the channel wall, causing blockage, making it difficult to achieve continuous and stable production of Fe3O4 smaller than 10 nm and more uniform.
[0004] Fe3O4 below 10 nm has superparamagnetism, ultra-high specific surface area, and abundant active sites, can adapt to biological microscale / micro-nano channels, has fast magnetic response and high relaxation rate; can realize in-situ diagnosis and treatment of biological microscale, ultra-high density magnetic storage, ultra-sensitive magnetic immunoassay, and precise driving of micro-nano robots, and has very wide application prospects. SUMMARY
[0005] [TECHNICAL PROBLEM] Existing methods for preparing iron oxide (Fe3O4) magnetic nanoparticles are difficult to simultaneously meet the requirements of small size, narrow size distribution, and continuous and stable production.
[0006] [TECHNICAL SCHEME] To solve the above problems, the application provides a method for preparing magnetic nanoparticles based on microfluidic focusing. Specifically, the application realizes the preparation of Fe3O4 magnetic nanoparticles with a particle size of 5-20 nm, especially the preparation of magnetic nanoparticles with a particle size as low as 5 nm and uniform distribution, by specially setting a microfluidic chip (adding sheath flow at both ends to control the focusing of the middle flow; and increasing the flow rate at both ends to realize the extrusion of the middle liquid filament to achieve a smaller diffusion distance).
[0007] The first object of the application provides a method for preparing magnetic nanoparticles based on microfluidic focusing, comprising the following steps: (1) Preparing a microfluidic chip: The cross section of the microfluidic chip is rectangular, having three inlet channels and one outlet channel. The inlet is divided into a middle flow inlet and two end sheath flow inlets, and the outlet is a product outlet. The two end sheath flow inlets are distributed on both sides of the middle flow inlet, and the included angle between the sheath flow inlet and the middle flow inlet is 30-60°. The middle flow inlet and the outlet channel are on the same straight line. (2) Preparing a precursor solution: Dissolve ferric salt and ferrous salt in water to obtain a precursor solution A; Dissolve the base in water to obtain a basic precipitant solution B; (3) Preparing Fe3O4 magnetic nanoparticles: Inject the precursor solution A into the microfluidic chip through the middle inlet of the microfluidic chip, and inject the basic precipitant solution B into the microfluidic chip from the two end sheath flow inlets. Moreover, heat the microfluidic chip to 60-80℃ for reaction. After the reaction is completed, collect the product through the outlet channel. After washing and drying the product, Fe3O4 magnetic nanoparticles are obtained.
[0008] In an embodiment of the application, the length of the microfluidic chip in step (1) is 300-450 μm, and the width is 100-150 μm.
[0009] In an embodiment of the application, the microfluidic chip in step (1) is formed by bonding an upper PDMS chip and a lower glass slide.
[0010] In an embodiment of the application, the microfluidic chip in step (1) is prepared by using soft lithography technology on a silicon substrate coated with SU8 photoresist, specifically as follows: Mix the PDMS matrix and the curing agent at a mass ratio of 10:1, then vacuum degas, and pour into the mold. Then, solidify at 80℃ on a hot plate for 3 hours. After solidification, separate the PDMS layer from the mold to obtain a PDMS chip with a thickness of 5 mm. The PDMS chip is punched by a puncher to form four holes (2mm in diameter) as three inlets and one outlet; then the three inlet channels and one mixing outlet channel are formed by plasma surface treatment, and the outlet is directly connected to a special hose; the product is introduced into a centrifuge tube for collection (the inlet width is 0.15mm, the inlet length is 4.82mm, and the mixing channel length is 21.11mm), and finally the microfluidic chip is formed by bonding with a glass slide (heated at 120℃ for 2h).
[0011] In an embodiment of the present application, the three inlet channels and one outlet channel of the microfluidic chip in step (1) can be inserted into a tube, which is preferably connected to a syringe containing the precursor solution.
[0012] In an embodiment of the present application, the ferric salt in step (2) is one or more of ferric chloride, ferric sulfate and ferric nitrate, and is further preferably ferric chloride.
[0013] In an embodiment of the present application, the ferrous salt in step (2) is one or more of ferrous chloride, ferrous sulfate and ferrous nitrate, and is further preferably ferrous sulfate.
[0014] In an embodiment of the present application, the molar ratio of the ferric ion in the ferric salt to the ferrous ion in the ferrous salt in step (2) is 1.5-2.5:1, and is further preferably 2:1; the concentration of the ferric salt in water is 95-105mM, and is further preferably 100mM.
[0015] In an embodiment of the present application, the base in step (3) is one of concentrated ammonia and sodium hydroxide.
[0016] In an embodiment of the present application, the concentration of the alkaline precipitant solution in step (3) is 1-3M.
[0017] In an embodiment of the present application, the injection speed ratio of the precursor solution A to the alkaline precipitant B in step (3) is 1:10-40.
[0018] In an embodiment of the present application, the washing in step (3) is washing with water, and the drying is oven drying at 35-55℃ for 10-30 mins.
[0019] In an embodiment of the present application, the particle size of the magnetite magnetic nanoparticles in step (3) is 5-20nm, and the nanoparticles have superparamagnetism.
[0020] [Advantages] (1) The present invention adopts a continuous flow microfluidic system, which ensures the uniformity of reaction conditions, the stability of the synthesis process and the batch-to-batch reproducibility of the product, and has higher mixing efficiency and controllable throughput compared with the traditional batch method. In addition, through chip parallelization design, it is easier to realize industrial-scale production.
[0021] (2) This invention achieves the preparation of magnetic nanoparticles ranging from 5 to 20 nm by precisely controlling a single flow rate ratio parameter R. In particular, it successfully prepared magnetic nanoparticles with a particle size as low as 5 nm and uniform distribution. Attached Figure Description
[0022] Figure 1 This is a schematic diagram of the microfluidic chip of the present invention.
[0023] Figure 2 The test results are for Example 1, where (a) 1:10; (b) 1:20; (c) 1:30; and (d) 1:40.
[0024] Figure 3 The test results are for Example 2, where (a) 1:10; (b) 1:20; (c) 1:30; and (d) 1:40.
[0025] Figure 4 The test results are for Example 3, where (a) 1:10; (b) 1:20; (c) 1:30; and (d) 1:40.
[0026] Figure 5 The test results are for Comparative Example 1, where the flow ratio is 1:3 (a) for Sample 1; (b) for Sample 2.
[0027] Figure 6 The test results are for Comparative Example 2, where the flow ratio is 1:5 (a) for Sample 1; (b) for Sample 2.
[0028] Figure 7 The results are for Comparative Example 3, where (a) is 2M and (b) is 3M. Detailed Implementation
[0029] The preferred embodiments of the present invention are described below. It should be understood that the embodiments are for better explanation of the present invention and are not intended to limit the present invention.
[0030] Test method: 1. Test for superparamagnetism: Disperse 10mg of magnetic nanoparticles in 1ml of deionized water, then apply a magnet to create a magnetic field and observe whether they settle completely.
[0031] 2. Particle size testing: Characterization using SEM images: The product was placed on an electron microscope stage and SEM images were taken (ZEISS Sigma 360).
[0032] Raw materials used in the examples: Concentrated ammonia solution: an aqueous solution of ammonia with a mass concentration of 25%-28%; FeCl3-6H2O and FeSO4-7H2O were obtained through commercial purchase. Water: Ultrapure water; Microfluidic chip: Fabricated using soft photolithography on a silicon substrate coated with SU8 photoresist, as detailed below: The PDMS matrix and curing agent were mixed at a mass ratio of 10:1, then degassed under vacuum and poured into a mold; then cured on a hot plate at 80°C for 3 hours; after curing, the PDMS layer was separated from the mold to obtain a PDMS chip with a thickness of 5mm. Four holes (2 mm in diameter) were drilled in the PDMS chip using a punch, serving as three inlets and one outlet. After drilling, the chip was cleaned with isopropanol and water, and then dried with nitrogen. Subsequently, plasma surface treatment was performed to form three inlet channels and one mixing outlet channel, with the outlet directly connected to a dedicated flexible tube. The product was then fed into a centrifuge tube for collection (inlet width 0.15 mm, inlet length 4.82 mm, mixing channel length 21.11 mm), and finally bonded to a glass slide (heated at 120°C for 2 hours) to form a microfluidic chip.
[0033] Example 1 A method for preparing magnetic nanoparticles based on microfluidic focusing includes the following steps: (1) Fabrication of microfluidic chips: The microfluidic chip has a rectangular cross-section (300μm × 100μm), with three inlet channels and one mixing outlet channel. The outlet is directly connected to a dedicated flexible tube to guide the product into a centrifuge tube for collection (inlet width is 0.15mm, inlet length is 4.82mm, and mixing channel length is 21.11mm). The inlet is divided into a middle flow inlet and two sheath flow inlets at both ends, and the outlet is the product outlet. The two sheath flow inlets are distributed on both sides of the middle flow inlet, with an angle of 45° between the sheath flow inlet and the middle flow inlet. The middle flow inlet and outlet channels are on the same straight line. (2) Preparation of precursor solution: 1352.5 mg FeCl3-6H2O and 695 mg FeSO4-7H2O were dissolved in 50 mL of water and stirred until homogeneous to obtain precursor solution A; wherein, Fe 3+ and Fe 2+ The concentrations were 100 mM and 50 mM, respectively, in a ratio of 2:1; Dilute 3.6 mL of concentrated ammonia to 50 mL and stir well to obtain alkaline precipitant solution B; wherein the concentration of ammonia is 1 M. (3) Preparation of magnetic nanoparticles of iron oxide: Precursor solution A and alkaline precipitant solution B were installed on the injection pump using a 5mL syringe and connected to the chip via a tubing; the injection rate at the middle inlet was 1mL / h, and the injection rates at both sheath inlets were 5, 10, 15, and 20mL / h, with flow ratios of 1:10, 1:20, 1:30, and 1:40. The microfluidic chip was heated to 70°C, and the injection pump was started. The precursor solution A was injected into the microfluidic chip through the middle inlet, and the alkaline precipitant solution B was injected into the microfluidic chip through the sheath inlets at both ends to carry out the reaction. After the reaction was completed, the product was collected through the outlet channel. The product was washed three times with ultrapure water and vacuum dried at 40°C for 10 mins to obtain magnetic nanoparticles of iron oxide.
[0034] The obtained magnetite nanoparticles were subjected to performance testing, and the results are as follows: The magnetic nanoparticles are black and superparamagnetic, and can completely settle under an applied magnetic field. Electron microscopy (SEM) characterization showed that when the injection rate ratio of precursor solution A to alkaline precipitant B was 1:10, the particle size was 10-30 nm; when the ratio was 1:20, the particle size was 10-30 nm; when the ratio was 1:30, the particle size was 5-15 nm; and when the ratio was 1:40, the particle size was 3-10 nm.
[0035] Example 2 A method for preparing magnetic nanoparticles based on microfluidic focusing includes the following steps: (1) Fabrication of microfluidic chips: The microfluidic chip has a rectangular cross-section (300μm × 150μm), with three inlet channels and one mixing outlet channel. The outlet is directly connected to a dedicated flexible tube to guide the product into a centrifuge tube for collection (inlet width is 0.15mm, inlet length is 4.82mm, and mixing channel length is 21.11mm). The inlet is divided into a middle flow inlet and two sheath flow inlets at both ends, and the outlet is the product outlet. The two sheath flow inlets are distributed on both sides of the middle flow inlet, with an angle of 45° between the sheath flow inlet and the middle flow inlet. The middle flow inlet and outlet channels are on the same straight line. (2) Preparation of precursor solution: 1352.5 mg FeCl3-6H2O and 695 mg FeSO4-7H2O were dissolved in 50 mL of water and stirred until homogeneous to obtain precursor solution A; wherein, Fe 3+ and Fe 2+ The concentrations were 100 mM and 50 mM, respectively, in a ratio of 2:1; Dilute 3.6 mL of concentrated ammonia to 50 mL and stir well to obtain alkaline precipitant solution B; wherein the concentration of ammonia is 1 M. (3) Preparation of magnetic nanoparticles of iron oxide: Precursor solution A and alkaline precipitant solution B were installed on the injection pump using a 5mL syringe and connected to the chip via a tubing; the injection rate at the middle inlet was 1mL / h, and the injection rates at both sheath inlets were 5, 10, 15, and 20mL / h, with flow ratios of 1:10, 1:20, 1:30, and 1:40. The microfluidic chip was heated to 70°C, and the injection pump was started. The precursor solution A was injected into the microfluidic chip through the middle inlet, and the alkaline precipitant solution B was injected into the microfluidic chip through the sheath inlets at both ends to carry out the reaction. After the reaction was completed, the product was collected through the outlet channel. The product was washed three times with ultrapure water and vacuum dried at 40°C for 10 mins to obtain magnetic nanoparticles of iron oxide.
[0036] The obtained magnetite nanoparticles were subjected to performance testing, and the results are as follows: The magnetic nanoparticles are black and superparamagnetic, and can completely settle under an applied magnetic field. Electron microscopy (SEM) characterization showed that when the injection rate ratio of precursor solution A to alkaline precipitant B was 1:10, the particle size was 10-30 nm; when the ratio was 1:20, the particle size was 10-25 nm; when the ratio was 1:30, the particle size was 10-25 nm; and when the ratio was 1:40, the particle size was 5-15 nm.
[0037] Example 3 A method for preparing magnetic nanoparticles based on microfluidic focusing includes the following steps: (1) Fabrication of microfluidic chips: The microfluidic chip has a rectangular cross-section (450μm × 150μm), with three inlet channels and one mixing outlet channel. The outlet is directly connected to a dedicated flexible tube to guide the product into a centrifuge tube for collection (inlet width is 0.15mm, inlet length is 4.82mm, and mixing channel length is 21.11mm). The inlet is divided into a middle flow inlet and two sheath flow inlets at both ends, and the outlet is the product outlet. The two sheath flow inlets are distributed on both sides of the middle flow inlet, with an angle of 45° between the sheath flow inlet and the middle flow inlet. The middle flow inlet and outlet channels are on the same straight line. (2) Preparation of precursor solution: 1352.5 mg FeCl3-6H2O and 695 mg FeSO4-7H2O were dissolved in 50 mL of water and stirred until homogeneous to obtain precursor solution A; wherein, Fe 3+ and Fe 2+ The concentrations were 100 mM and 50 mM, respectively, in a ratio of 2:1; Dilute 3.6 mL of concentrated ammonia to 50 mL and stir well to obtain alkaline precipitant solution B; wherein the concentration of ammonia is 1 M. (3) Preparation of magnetic nanoparticles of iron oxide: Precursor solution A and alkaline precipitant solution B were installed on the injection pump using a 5mL syringe and connected to the chip via a tubing; the injection rate at the middle inlet was 1mL / h, and the injection rates at both sheath inlets were 5, 10, 15, and 20mL / h, with flow ratios of 1:10, 1:20, 1:30, and 1:40. The microfluidic chip was heated to 70°C, and the injection pump was started. The precursor solution A was injected into the microfluidic chip through the middle inlet, and the alkaline precipitant solution B was injected into the microfluidic chip through the sheath inlets at both ends to carry out the reaction. After the reaction was completed, the product was collected through the outlet channel. The product was washed three times with ultrapure water and vacuum dried at 40°C for 10 mins to obtain magnetic nanoparticles of iron oxide.
[0038] The obtained magnetite nanoparticles were subjected to performance testing, and the results are as follows: The magnetic nanoparticles are black and superparamagnetic, and can completely settle under an applied magnetic field. Electron microscopy (SEM) characterization showed that when the injection rate ratio of precursor solution A to alkaline precipitant B was 1:10, the particle size was 10-45 nm; when the ratio was 1:20, the particle size was 10-30 nm; when the ratio was 1:30, the particle size was 10-20 nm; and when the ratio was 1:40, the particle size was 7-17 nm.
[0039] Comparative Example 1 In step (3) of Example 1, the injection rate of the intermediate inlet was adjusted to 1 mL / h, and the injection rates of the sheath inlets at both ends were 1.5 mL / h, with a flow ratio of 1:3. Specifically as follows: (1) Fabrication of microfluidic chips: The microfluidic chip has a rectangular cross-section (300μm × 100μm), with three inlet channels and one mixing outlet channel. The outlet is directly connected to a dedicated flexible tube to guide the product into a centrifuge tube for collection (inlet width is 0.15mm, inlet length is 4.82mm, and mixing channel length is 21.11mm). The inlet is divided into a middle flow inlet and two sheath flow inlets at both ends, and the outlet is the product outlet. The two sheath flow inlets are distributed on both sides of the middle flow inlet, with an angle of 45° between the sheath flow inlet and the middle flow inlet. The middle flow inlet and outlet channels are on the same straight line. (2) Preparation of precursor solution: 1352.5 mg FeCl3-6H2O and 695 mg FeSO4-7H2O were dissolved in 50 mL of water and stirred until homogeneous to obtain precursor solution A; wherein, Fe 3+ and Fe 2+ The concentrations were 100 mM and 50 mM, respectively, in a ratio of 2:1; Dilute 3.6 mL of concentrated ammonia to 50 mL and stir well to obtain alkaline precipitant solution B; wherein the concentration of ammonia is 1 M. (3) Preparation of magnetic nanoparticles of iron oxide: Precursor solution A and alkaline precipitant solution B were attached to the injection pump using a 5mL syringe and connected to the chip via a tubing; the injection rate at the middle inlet was 1mL / h, and the injection rates at both sheath inlets were 1.5mL / h, with a flow ratio of 1:3; The microfluidic chip was heated to 70°C, and the injection pump was started. The precursor solution A was injected into the microfluidic chip through the middle inlet, and the alkaline precipitant solution B was injected into the microfluidic chip through the sheath inlets at both ends to carry out the reaction. After the reaction was completed, the product was collected through the outlet channel. The product was washed three times with ultrapure water and vacuum dried at 40°C for 5 mins to obtain magnetite magnetic nanoparticles.
[0040] The obtained magnetite nanoparticles were subjected to performance testing, and the results are as follows: The magnetic nanoparticles are black and superparamagnetic, and can completely settle under an applied magnetic field. Characterization by electron microscopy (SEM) revealed sheet-like material and 1000 nm particles.
[0041] Comparative Example 2 In step (3) of Example 1, the injection rate of the intermediate inlet was adjusted to 1 mL / h, and the injection rates of the sheath inlets at both ends were 2.5 mL / h, with a flow ratio of 1:5. Specifically as follows: (1) Fabrication of microfluidic chips: The microfluidic chip has a rectangular cross-section (300μm × 100μm), with three inlet channels and one mixing outlet channel. The outlet is directly connected to a dedicated flexible tube to guide the product into a centrifuge tube for collection (inlet width is 0.15mm, inlet length is 4.82mm, and mixing channel length is 21.11mm). The inlet is divided into a middle flow inlet and two sheath flow inlets at both ends, and the outlet is the product outlet. The two sheath flow inlets are distributed on both sides of the middle flow inlet, with an angle of 45° between the sheath flow inlet and the middle flow inlet. The middle flow inlet and outlet channels are on the same straight line. (2) Preparation of precursor solution: 1352.5 mg FeCl3-6H2O and 695 mg FeSO4-7H2O were dissolved in 50 mL of water and stirred until homogeneous to obtain precursor solution A; wherein, Fe 3+ and Fe 2+ The concentrations were 100 mM and 50 mM, respectively, in a ratio of 2:1; Dilute 3.6 mL of concentrated ammonia to 50 mL and stir well to obtain alkaline precipitant solution B; wherein the concentration of ammonia is 1 M. (3) Preparation of magnetic nanoparticles of iron oxide: Precursor solution A and alkaline precipitant solution B were attached to the injection pump using a 5mL syringe and connected to the chip via a tubing; the injection rate at the middle inlet was 1mL / h, and the injection rates at both sheath inlets were 2.5mL / h, with a flow ratio of 1:5; The microfluidic chip was heated to 70°C, and the injection pump was started. The precursor solution A was injected into the microfluidic chip through the middle inlet, and the alkaline precipitant solution B was injected into the microfluidic chip through the sheath inlets at both ends to carry out the reaction. After the reaction was completed, the product was collected through the outlet channel. The product was washed three times with ultrapure water and vacuum dried at 40°C for 5 mins to obtain magnetite magnetic nanoparticles.
[0042] The obtained magnetite nanoparticles were subjected to performance testing, and the results are as follows: The magnetic nanoparticles are black and superparamagnetic, and can completely settle under an applied magnetic field. Electron microscopy (SEM) characterization revealed 1000 nm particles that are irregular in shape.
[0043] Comparative Example 3 In step (3) of Example 1, the injection rate of the intermediate inlet is adjusted to 1 mL / h, and the injection rates of the sheath inlets at both ends are 2.5 mL / h, with a flow ratio of 1:5; and the concentration of alkaline precipitant solution B in step (1) is adjusted to 2M and 3M. Specifically as follows: (1) Fabrication of microfluidic chips: The microfluidic chip has a rectangular cross-section (300μm × 100μm), with three inlet channels and one mixing outlet channel. The outlet is directly connected to a dedicated flexible tube to guide the product into a centrifuge tube for collection (inlet width is 0.15mm, inlet length is 4.82mm, and mixing channel length is 21.11mm). The inlet is divided into a middle flow inlet and two sheath flow inlets at both ends, and the outlet is the product outlet. The two sheath flow inlets are distributed on both sides of the middle flow inlet, with an angle of 45° between the sheath flow inlet and the middle flow inlet. The middle flow inlet and outlet channels are on the same straight line. (2) Preparation of precursor solution: 1352.5 mg FeCl3-6H2O and 695 mg FeSO4-7H2O were dissolved in 50 mL of water and stirred until homogeneous to obtain precursor solution A; wherein, Fe 3+ and Fe 2+ The concentrations were 100 mM and 50 mM, respectively, in a ratio of 2:1; Dilute 3.6 mL of concentrated ammonia to 50 mL and stir well to obtain alkaline precipitant solution B; wherein the concentration of ammonia is 3M. (3) Preparation of magnetic nanoparticles of iron oxide: Precursor solution A and alkaline precipitant solution B were attached to the injection pump using a 5mL syringe and connected to the chip via a tubing; the injection rate at the middle inlet was 1mL / h, and the injection rates at both sheath inlets were 2.5mL / h, with a flow ratio of 1:5; The microfluidic chip was heated to 70°C, and the injection pump was started. The precursor solution A was injected into the microfluidic chip through the middle inlet, and the alkaline precipitant solution B was injected into the microfluidic chip through the sheath inlets at both ends to carry out the reaction. After the reaction was completed, the product was collected through the outlet channel. The product was washed three times with ultrapure water and vacuum dried at 40°C for 5 mins to obtain magnetite magnetic nanoparticles.
[0044] The obtained magnetite nanoparticles were subjected to performance testing, and the results are as follows: The magnetic nanoparticles are black and superparamagnetic, and can completely settle under an external magnetic field. Electron microscopy (SEM) characterization showed that particles larger than 300 nm and irregular in shape appeared in alkaline precipitant solution B at concentrations of 2 M and 3 M.
[0045] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.
Claims
1. A method for preparing magnetic nanoparticles based on microfluidic focusing, characterized in that, Includes the following steps: (1) Fabrication of microfluidic chips: The microfluidic chip has a rectangular cross-section with three inlet channels and one outlet channel. The inlets are divided into a middle flow inlet and two sheath flow inlets at both ends, and the outlet is the product outlet. The two sheath flow inlets are distributed on both sides of the middle flow inlet, and the angle between the sheath flow inlet and the middle flow inlet is 30-60°. The middle flow inlet and the outlet channel are on the same straight line. (2) Preparation of precursor solution: Dissolve ferric salts and ferrous salts in water to obtain precursor solution A; Dissolve the alkali in water to obtain alkaline precipitant solution B; (3) Preparation of magnetic nanoparticles of iron oxide: Precursor solution A is injected into the microfluidic chip through the central inlet, and alkaline precipitant solution B is injected into the microfluidic chip through the sheath inlets at both ends; the microfluidic chip is heated to 60-80℃ to carry out the reaction; after the reaction is completed, the product is collected through the outlet channel. The product was washed and dried to obtain magnetic nanoparticles of iron oxide. In step (3), the injection rate ratio of precursor solution A to alkaline precipitant B is 1:10-40.
2. The method according to claim 1, characterized in that, In step (1), the length of the microfluidic chip is 300-450μm and the width is 100-150μm.
3. The method according to claim 1, characterized in that, In step (1), the microfluidic chip is formed by bonding an upper PDMS chip and a lower glass slide.
4. The method according to claim 1, characterized in that, In step (2), the molar ratio of ferric ions in ferric salt to ferrous ions in ferrous salt is 1.5-2.5:
1.
5. The method according to claim 1, characterized in that, The concentration of the alkaline precipitant solution in step (3) is 1-3M.
6. The method according to claim 1, characterized in that, In step (1), the microfluidic chip is fabricated using soft photolithography on a silicon substrate coated with SU8 photoresist, as detailed below: The PDMS matrix and curing agent were mixed at a mass ratio of 10:1, then degassed under vacuum and poured into a mold; then cured on a hot plate at 80°C for 3 hours; after curing, the PDMS layer was separated from the mold to obtain a PDMS chip with a thickness of 5mm. Four holes are drilled in the PDMS chip using a puncher, serving as three inlets and one outlet; then, plasma surface treatment is used to form three inlet channels and one mixed outlet channel, with the outlet directly connected to a dedicated flexible tube. The product is collected by passing it through a centrifuge tube and then bonded to a glass slide to form a microfluidic chip.
7. The method according to claim 1, characterized in that, In step (3), the alkali is either concentrated ammonia or sodium hydroxide.
8. The method according to claim 1, characterized in that, In step (2), the ferric salt is one or more of ferric chloride, ferric sulfate, and ferric nitrate.
9. The method according to claim 1, characterized in that, In step (2), the ferrous salt is one or more of ferrous chloride, ferrous sulfate, and ferrous nitrate.
10. The method according to claim 1, characterized in that, In step (3), the magnetic nanoparticles of iron oxide have a particle size of 5nm-20nm and exhibit superparamagnetism.