Method for stabilizing residual magnetism of injectable magnetic fluid

Abstract

The invention relates to the field of magnetic fluids, and discloses a method for stabilizing residual magnetism of an injectable magnetic fluid, the magnetic fluid is injectable magnetic hydrogel with a three-dimensional network structure, and the method comprises the following steps: after magnetic moment uniformity in the magnetic hydrogel is disrupted, the magnetic hydrogel is prepared into a magnetic hydrogel; and applying a low-intensity magnetic field to the magnetic hydrogel or an object containing the magnetic hydrogel so as to perform in-situ reorientation of the low-intensity magnetic field on the magnetic hydrogel, so that the magnetic moments of magnetic particles in the magnetic hydrogel are uniform, and the fluid magnetism with stable residual magnetism is presented. The remanence stability of the magnetic hydrogel is maintained within five days by adopting 150mT, the magnetization time does not exceed 1min, the harm to organisms is low, the magnetic moment reduction degree is small, and the method is easy to popularize and use.

Description

Technical Field

[0001] The invention relates to the field of magnetic fluids, and in particular to a method for stabilizing the residual magnetism of injectable magnetic fluids. Background Art

[0002] Magnetic liquids are usually composed of nano-magnetic particles and base liquid. When magnetic materials are in a flowing form (magnetic fluids, injectable magnetic hydrogels, etc.), under the influence of the Brownian motion of magnetic particles and the gravity sedimentation effect, the magnetic particles in the fluid cannot maintain magnetization stability. That is, the magnetic particles in the fluid cannot form a uniform magnetism, they will rotate randomly, the magnetism will weaken or even disappear, the net magnetic moment will become zero, and the typical hysteresis phenomenon cannot be presented, which has caused certain limitations on the biological application of liquid electronics of magnetic materials.

[0003] Especially in the application field of marking and tracking lesions / lymph nodes, since traditional magnetic fluid materials are paramagnetic / superparamagnetic materials, they are easily demagnetized and can only show a stable outward macroscopic net magnetic moment and sense magnetic signals under the maintenance of an external magnetic field. Especially in the application field of biological bodies, when magnetic particles are injected into the body, the injection process will cause the magnetic particles inside the fluid to be randomly oriented, the magnetic domains to be scattered, and the macroscopic magnetism to disappear. An external magnetic field is also needed to intervene in the magnetic particles. At the same time, after the external magnetic field is withdrawn, the magnetism of the magnetic particles will be weakened again or even disappear, which has caused certain restrictions on the biological application of liquid electronics of magnetic materials. Summary of the invention

[0004] The object of the present invention is to provide a method for stabilizing the residual magnetism of an injectable magnetic fluid, so as to solve the technical problem in the prior art that it is difficult to maintain the residual magnetism of the magnetic fluid after magnetization.

[0005] In order to solve the above technical problems, the present invention specifically provides the following technical solutions:

[0006] The present invention provides a method for stabilizing the residual magnetism of an injectable magnetic fluid, wherein the magnetic fluid is an injectable magnetic hydrogel having a three-dimensional network structure, and the method comprises the following steps:

[0007] After the uniformity of the magnetic moment inside the magnetic hydrogel is disrupted, a weak magnetic field is applied to the magnetic hydrogel or an object containing the magnetic hydrogel to perform in-situ reorientation of the magnetic hydrogel with a weak magnetic field, so that the magnetic moment of the magnetic particles inside the magnetic hydrogel is unified, presenting fluid magnetism with stable remanent magnetism.

[0008] As a preferred solution of the present invention, in the weak magnetic field in-situ reorientation, the strength of the weak magnetic field is 100-500 mT, and the magnetization time is 0.1 min to 1 min.

[0009] As a preferred embodiment of the present invention, after the in-situ reorientation in the weak magnetic field, the magnetic hydrogel maintains stable magnetism for at least 5 days.

[0010] As a preferred embodiment of the present invention, the magnetic hydrogel is prepared by cross-linking NdFeB@SiO2 magnetic nanoparticles with a sodium alginate precursor solution and a polyvinyl alcohol precursor.

[0011] As a preferred embodiment of the present invention, the method for preparing the magnetic hydrogel comprises the following steps:

[0012] The NdFeB@SiO2 magnetic nanoparticles are mixed with the sodium alginate precursor solution and the polyvinyl alcohol precursor solution, and stirred at high speed to obtain a mixed reactant B;

[0013] The mixed reactant B is subjected to vacuum degassing treatment to improve the cross-linking tightness of the three-dimensional network in the hydrogel to obtain a hydrogel precursor;

[0014] The hydrogel precursor is magnetized under a magnetic field of 2 to 3 T, and then subjected to repeated freeze-thaw treatment to promote the close cross-linking of sodium alginate chains and polyvinyl alcohol chains to form a polymer aggregation area, and promote the formation of hydrogen bonds and crystals to provide a three-dimensional network for the directional linking of magnetic particles, so as to obtain the magnetic colloidal fluid.

[0015] As a preferred embodiment of the present invention, the repeated freeze-thaw treatment comprises the following steps:

[0016] The magnetized hydrogel precursor was frozen at -20°C for 12-48 hours, and thawed at 25°C for 2-4 hours, and the cycle was repeated 3-5 times.

[0017] As a preferred embodiment of the present invention, the high-speed stirring time is 15-30 minutes;

[0018] The vacuum degassing time is 15-30min.

[0019] As a preferred embodiment of the present invention, the preparation steps of the NdFeB@SiO2 magnetic nanoparticles are as follows:

[0020] The NdFeB particles are mixed with an ethanol aqueous solution and stirred for 15-30 minutes to obtain a NdFeB dispersion;

[0021] Adding ammonia water and tetraethyl orthosilicate to the NdFeB dispersion successively to obtain a mixed reactant A;

[0022] The mixed reactant A is repeatedly washed with ethanol and then water to obtain a precipitate;

[0023] The precipitate is dried to obtain the NdFeB@SiO2 magnetic nanoparticles.

[0024] As a preferred embodiment of the present invention, the amount of ethanol aqueous solution is 100-200 ml per 1 g of NdFeB;

[0025] In the NdFeB dispersion, for every 1g of NdFeB, the amount of ammonia water is 4-8ml, and the amount of ethyl orthosilicate is 2-4ml;

[0026] The drying temperature is 50-60°C;

[0027] The concentration of the sodium alginate precursor solution is 0.5-2%;

[0028] The concentration of the polyvinyl alcohol precursor solution is 5-10%.

[0029] As a preferred embodiment of the present invention, the magnetic hydrogel is used for biological tissue labeling and in vivo tracing.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] The present invention in situ reorients the magnetic hydrogel with a densely cross-linked three-dimensional network inside, and stabilizes the magnetic orientation links disrupted by injection and other operations with a weak magnetic field, so that the hydrogel can show an outward macroscopic net magnetic moment again, and achieves a stable residual magnetization intensity of the magnetic fluid after the external magnetic field disappears. The hydrogel can be used as a tracer and has applications in continuous tissue labeling in vivo, biological signal measurement, etc.

[0032] The in-situ reorientation magnetic field disclosed by the present invention is weak, and at 150 mT, the magnetic hydrogel can exhibit stable hysteresis within five days, and the magnetization time does not exceed 1 minute. When the magnetic hydrogel with a three-dimensional network structure is injected into a living body, the residual magnetism of the magnetic hydrogel can be restored by in-situ reorientation using a weak magnetic field. The magnetic field strength requirement is low, the damage to objects is low, the safety is good, and the residual magnetism is stable, so it is easy to promote and use as a tracer in a living body. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the implementation methods of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for the implementation methods or the description of the prior art. Obviously, the drawings in the following description are only exemplary, and for ordinary technicians in this field, other implementation drawings can be derived from the provided drawings without creative work.

[0034] Figure 1 The present invention provides a method for stabilizing the residual magnetism of an injectable magnetic fluid;

[0035] Figure 2 The invention provides a preparation process of magnetic hydrogel;

[0036] Figure 3 The invention provides a preparation process of NdFeB@SiO2 magnetic nanoparticles;

[0037] Figure 4 The present invention provides an electron microscope image of the magnetic hydrogel with stable remanent magnetism as shown in Example 1;

[0038] Figure 5 Provided for the present invention are statistical graphs of the magnetic moment changes of the magnetic hydrogels after in-situ reorientation in Examples 1 to 6. DETAILED DESCRIPTION

[0039] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0040] like Figure 1 As shown, the present invention provides a method for stabilizing the residual magnetism of an injectable magnetic fluid, wherein the magnetic fluid is an injectable magnetic hydrogel having a three-dimensional network structure, and the method comprises the following steps:

[0041] After the uniformity of the magnetic moment inside the magnetic hydrogel is disrupted, a weak magnetic field is applied to the magnetic hydrogel or an object containing the magnetic hydrogel to perform in-situ reorientation of the magnetic hydrogel with a weak magnetic field, so that the magnetic moment of the magnetic particles inside the magnetic hydrogel is unified, presenting fluid magnetism with stable remanent magnetism.

[0042] Generally speaking, after a magnetic liquid is injected into an object, the particles move irregularly due to the push, the magnetic domains become scattered, the magnetic moment weakens, and eventually the fluid's magnetism disappears. If the fluid is to be given magnetism again, a stronger magnetic field needs to be applied to the object. However, a stronger magnetic field requires a large coil device, which has low practicality. In addition, there is a risk of accidental injury to personnel when a strong magnetic field is used in a medical environment. Therefore, it is difficult for magnetic fluids to maintain residual magnetism in existing applications.

[0043] In order to maintain the residual magnetism in an object after the magnetic fluid is injected into the object (the macroscopic magnetic moment disappears), the present invention proposes a magnetic fluid and an application method. In particular, after being injected into a living body, only a weak magnetic field is applied. The magnetic fluid in the living body can achieve magnetic moment unification in a weak magnetic field environment due to its stable structure, and can maintain the residual magnetism, thereby completing in vivo tracing, biological measurement and other tasks without the intervention of an external magnetic field.

[0044] Specifically, the magnetic fluid is an injectable magnetic hydrogel with a three-dimensional network structure. Optionally, the magnetic hydrogel is prepared by cross-linking NdFeB@SiO2 magnetic nanoparticles with a sodium alginate precursor solution and a polyvinyl alcohol precursor.

[0045] In addition, similar hydrogels include SmCo, AlNiCo, FeCrCo magnetic hydrogels, etc. The common characteristics of these hydrogels are that they have a three-dimensional network structure, which can maintain the stability of the magnetic particles and at the same time maintain injectability. After preparation, they have residual magnetism, that is, after being magnetized in a strong magnetic field, they can retain magnetism for a certain period of time without the intervention of an external magnetic field.

[0046] However, after such hydrogel is injected into an object, the injection process is equivalent to disrupting all fluid particles, resulting in the disruption of the uniformity of the internal magnetic moment, the disappearance of magnetism, and the difficulty in maintaining the stability of residual magnetism. In order to solve this problem, the present invention applies a weak magnetic field to the magnetic hydrogel with disrupted uniformity of the internal magnetic moment, or applies a weak magnetic field to an object containing the injectable magnetic hydrogel with disrupted uniformity of the internal magnetic moment, so that the magnetic moment of the magnetic particles inside the magnetic hydrogel is unified, and the outward macroscopic net magnetic moment is presented again, and the residual magnetism is exhibited within a week.

[0047] The above steps are called weak magnetic field in-situ reorientation. The present invention uses an external magnetic field to intervene in the magnetic fluid. The technical means are used in conjunction with a magnetic fluid with a three-dimensional network structure to restore the magnetism in the magnetic fluid. Weak magnetic field in-situ reorientation is a technical means of adding a weak magnetic field. The energy applied is small, but it can help the magnetic fluid regain its magnetism. When the magnetism disappears, the magnetism in the magnetic fluid still remains, and its magnetism can remain for a period of time without an external magnetic field.

[0048] Generally speaking, if you want to apply magnetism to liquid magnetic particles, you need a strong magnetic field to magnetize them. However, the present invention uses a magnetic fluid with a three-dimensional network structure with magnetic directional links. The network structure can maintain the stability of the magnetic particles. Its own characteristic is that it has residual magnetism, that is, after the intervention of an external magnetic field, this magnetic fluid can obtain magnetism, but when the external magnetism disappears, the magnetism of the magnetic fluid will not disappear immediately, and it can still be maintained for a period of time.

[0049] In actual use, taking the magnetic hydrogel made by cross-linking NdFeB@SiO2 magnetic nanoparticles with sodium alginate precursor solution and polyvinyl alcohol precursor as an example, the intensity of the weak magnetic field is 100-500mT, the magnetization time is 0.1min~1min, and the retention time of the fluid magnetism is one week (the fluid magnetism will slowly decay over time).

[0050] In the present invention, a preferred embodiment of the magnetic fluid is a magnetic hydrogel prepared by cross-linking NdFeB@SiO2 magnetic nanoparticles with a sodium alginate precursor solution and a polyvinyl alcohol precursor.

[0051] like Figure 2 As shown, the present invention provides a preparation process of a magnetic colloid fluid, comprising the following steps:

[0052] (1) NdFeB@SiO2 magnetic nanoparticles are mixed with a sodium alginate precursor solution and a polyvinyl alcohol precursor solution, and the mixture is stirred at high speed for 15-30 minutes to obtain a mixed reactant B, wherein the concentration of the sodium alginate precursor solution is 0.5-2%, and the concentration of the polyvinyl alcohol precursor solution is 5-10%.

[0053] (2) The mixed reactant B is subjected to vacuum degassing treatment for 15-30 minutes to obtain a hydrogel precursor. The vacuum degassing treatment can improve the cross-linking tightness of the three-dimensional network in the hydrogel and improve the stability of the directional linking of the magnetic particles.

[0054] (3) The hydrogel precursor is magnetized under a magnetic field of 2 to 3 T to achieve magnetization of the magnetic particles. The hydrogel precursor is then subjected to repeated freeze-thaw treatments to promote the tight cross-linking of the sodium alginate chains and the polyvinyl alcohol chains to form polymer aggregation areas and promote the formation of hydrogen bonds and crystals, thereby providing a three-dimensional network for the directional linking of the magnetic particles to obtain a magnetic hydrogel.

[0055] Magnetic hydrogels have high remanence, coercivity and fluidity.

[0056] The present invention mixes sodium alginate, polyvinyl alcohol precursor solution and neodymium iron boron particles by high-speed stirring, and then performs vacuum degassing treatment. Vacuum degassing can improve the cross-linking tightness of the hydrogel three-dimensional network and improve the stability of the directional linking of the magnetic particles.

[0057] The present invention adopts a physical cross-linking method of freeze-thaw cycles to realize the preparation of the permanent magnetic fluid, and the physical cross-linking can form a biosafe hydrogel structure with a stable modulus.

[0058] The present invention constructs a three-dimensional network through a hydrogel cross-linked network, uses micron-sized permanent magnetic particles to reduce the influence of Brownian motion, and exhibits hysteresis. After the hydrogel precursor is magnetized by a magnetic field, the magnetic particles in the matrix present a directional link in the three-dimensional network structure and still maintain a fluid state, so that the material has high remanence, coercive force and fluidity.

[0059] The sodium alginate precursor solution and the polyvinyl alcohol precursor form a three-dimensional network. The micron-sized magnetic particles are structurally fixed by the three-dimensional network in the matrix in the hydrogel cross-linked network. After being structurally fixed, the micron-sized magnetic particles are difficult to disperse, so they can maintain magnetism for a long time, are not easily affected by external forces, and exhibit a certain degree of permanent magnetism.

[0060] It is worth noting that the permanent magnetism described in the present invention means that the magnetic particles can maintain magnetism for a long time after being structurally fixed in the hydrogel matrix. The magnetic fluid prepared by the above method weakens the free movement of magnetic particles in the fluid through structural design, maintains the retention of magnetism, but is still an injectable fluid. After in-situ reorientation magnetization, it can maintain magnetism for a long time without the need for an additional external magnetic field. In this way, when lesion tracing and positioning, injection into the tissue surface for physiological function testing, etc., the versatility and ease of use will be higher.

[0061] In particular, the permanent magnetic fluid disclosed in the present invention can be used for continuous marking of tissues in vivo, measurement of biological signals, etc. based on high remanence, coercive force and fluidity.

[0062] The principle is that the above preparation process ensures that the internal network structure of the magnetic fluid material is not completely destroyed after being injected (such as the polymer monomer link is broken), so a weak magnetic field can be used to promote the unification of the magnetic moment of the internal magnetic particles.

[0063] After the injection, the internal structure of the magnetic hydrogel with ordinary structure is completely disordered. If it is magnetized again, it needs to be magnetized with a higher magnetic field (2T to 3T, which is much larger than the safe magnetic field) than the first magnetization during the preparation process. The difference brought by this magnetic field strength is that 2T to 3T requires a large coil to generate, the current is very high, and the magnetic attraction is very large, which limits the use scenarios and safety.

[0064] The network structure of the magnetic colloid prepared by the present invention has certain functions and has residual magnetism itself. After the injection action, the residual magnetism is gone. This is because the uniformity of the internal magnetic moment is disrupted when it is sucked into the syringe and then injected through the needle.

[0065] However, since the hydrogel disclosed in the present invention has a stable three-dimensional network structure, even after the injection action, under the support of a weak magnetic field for a short time (no more than 1 minute), its magnetic directional link can be quickly restored and the residual magnetism can be re-exhibited.

[0066] The safety of the magnetic colloid fluid disclosed in the present invention has been verified by biological safety, including pathological results of tissue sections.

[0067] Furthermore, in order to further ensure the structural stability of the magnetic fluid and facilitate its rapid recovery to a uniform magnetic moment state after reorientation, the repeated freeze-thaw treatment includes the following steps:

[0068] The magnetized hydrogel precursor was frozen at -20°C for 12-48h and thawed at 25°C for 2-4h, and the cycle was repeated 3-5 times.

[0069] Repeated freeze-thaw treatments can help the hydrogel structure become tighter and reduce the impact of actions such as injection.

[0070] See also Figure 3 , the preparation steps of NdFeB@SiO2 magnetic nanoparticles are as follows:

[0071] (1) Mix 1-20 μm NdFeB particles with ethanol aqueous solution and stir for 15-30 min to prepare NdFeB dispersion. The amount of ethanol aqueous solution is 100-200 ml for every 1 g of NdFeB.

[0072] (2) Ammonia water and tetraethyl orthosilicate are successively added dropwise to a NdFeB dispersion to prepare a mixed reactant A. In the NdFeB dispersion, for every 1 g of NdFeB contained, the amount of ammonia water is 4-8 ml, and the amount of tetraethyl orthosilicate is 2-4 ml;

[0073] (3) repeatedly washing the mixed reactant A with ethanol and then with water to obtain a precipitate;

[0074] (4) Drying the precipitate at a temperature of 50-60° C. to obtain NdFeB@SiO2 magnetic nanoparticles.

[0075] In the present invention, the permanent magnetic particles are 1-20um NdFeB particles, which are coated with silicon by the Stober method to improve the dispersibility of the magnetic particles in the hydrogel matrix and the stability in the liquid environment.

[0076] The magnetic particles provided by the present invention are directionally linked in a three-dimensional network structure, and the internal structure is tightly cross-linked and has residual magnetism. After injection or other operations that may cause the fluid magnetism to disappear, the stable fluid structure can be restored by applying a weak magnetic field (greater than 150 mT), and the residual magnetism can be stable for at least five days, which is convenient for application in the field of in vivo tracing and biometry, thus broadening its application range.

[0077] The present invention constructs a three-dimensional network structure by cross-linking sodium alginate and polyvinyl alcohol. After the sodium alginate, polyvinyl alcohol precursor solution and neodymium iron boron particles are mixed by high-speed stirring, a physical cross-linking method of freeze-thaw cycle is adopted to realize the preparation of permanent magnetic fluid, promote the close cross-linking of sodium alginate chains and polyvinyl alcohol chains to form a polymer aggregation area, promote the formation of hydrogen bonds and crystals, and provide a three-dimensional network for the directional linking of magnetic particles, further forming a biosafe and stable modulus hydrogel structure.

[0078] The use of the tracer is the preferred application mode of the present invention for stabilizing the residual magnetism. Specifically, before orientation, there must be an operation to disrupt the uniformity of the magnetic moment inside the magnetic fluid. That is to say, the magnetic fluid just prepared has residual magnetism because its preparation process has a magnetization process. However, since it is a fluid that needs to be injected before use, its wide application also leads to the loss of residual magnetism after injection. This is because it is sucked into the syringe and then injected through the needle, and the uniformity of the internal magnetic moment is disrupted.

[0079] Therefore, since it needs to be applied in vivo, when the magnetic fluid is injected, the magnetic domains will be scattered and the magnetic moment will be weakened. In order to regain the magnetism in the organism, the present invention reorients the organism in situ during the application process so that the magnetic fluid regains the residual magnetism stability.

[0080] In the present invention, the reorientation magnetic field is relatively low, 100 mT or more, and the applied magnetic field is weak, with little effect on organisms, thus ensuring safety and wide application.

[0081] The following examples are provided for further explanation:

[0082] Embodiment 1:

[0083] 1. Preparation of magnetic hydrogel:

[0084] Take 2g of 5um NdFeB particles and mix them with 300ml of ethanol water solution, stir for 15-30min to obtain NdFeB dispersion;

[0085] 12 ml of ammonia water and 6 ml of ethyl orthosilicate were successively added dropwise to the NdFeB dispersion to obtain a mixed reactant A;

[0086] The mixed reactant A is repeatedly washed with ethanol and then water to obtain a precipitate;

[0087] The precipitate is dried at 50-60°C to obtain NdFeB@SiO2 magnetic nanoparticles;

[0088] The NdFeB@SiO2 magnetic nanoparticles were mixed with a 1% sodium alginate precursor solution and a 7% polyvinyl alcohol precursor solution, and the mixture was stirred at high speed for 15-30 minutes to obtain a mixed reactant B;

[0089] The mixed reactant B is subjected to vacuum degassing treatment for 15-30 minutes to obtain a hydrogel precursor;

[0090] The hydrogel precursor is magnetized under a magnetic field of 2.5 T, and the magnetized hydrogel precursor is frozen at -20°C for 12-48 hours, thawed at 25°C for 2-4 hours, and the cycle is repeated 3-5 times to obtain a magnetic hydrogel.

[0091] The electron microscope image of the magnetic hydrogel in Example 1 is shown in Figure 4 shown.

[0092] 2. In vitro experiments

[0093] The magnetic hydrogel obtained in Example 1 was injected into an object, which was a biological simulation sample. A magnetic field of 60 mT was applied to the object for 0.5 min, and the magnetic moment change of the material was continuously detected by a vibrating sample magnetometer (VSM).

[0094] Embodiment 2:

[0095] The other steps were the same, except that the applied magnetic field was 80 mT.

[0096] Embodiment 3:

[0097] The other steps were the same, except that the applied magnetic field was 100 mT.

[0098] Embodiment 4:

[0099] The other steps were the same, except that the applied magnetic field was 150 mT.

[0100] Embodiment 5:

[0101] The other steps were the same, except that the applied magnetic field was 200 mT.

[0102] Embodiment 6:

[0103] The other steps were the same, except that the applied magnetic field was 500 mT.

[0104] Results Figure 5 By detecting the change in the magnetic moment of the material after in-situ reorientation, it was found that the magnetic moment of the material could be stably detected within 5 days, and the degree of reduction was small.

[0105] As can be seen from the examples, the present invention actually proposes a technical solution for stabilizing the residual magnetism of a magnetic fluid in a biological body under an in-situ reorientation method. Specifically, after injecting an injectable magnetic fluid with a three-dimensional network structure into a biological body, the residual magnetism is stabilized (for about one week) through an in-situ reorientation method of a weak magnetic field, and can be used for a variety of biological applications.

[0106] In order to solve biological applications, the present invention has brought about a huge breakthrough in achieving the residual magnetic stability of fluid materials, which is equivalent to getting rid of the constraints of the need for a continuous external magnetic field. Its five-day residual magnetic stability has brought huge potential to organisms, in vivo tracing, biological measurement, etc., which are difficult to break through in biological applications and have high application value.

[0107] Through the preparation method of the magnetic colloidal fluid of this embodiment, the preparation process is simple, the whole preparation temperature does not exceed 60°C, the lowest preparation temperature is not lower than -20°C, and the reactants are common and easily available, and easy to prepare; at the same time, a three-dimensional network is constructed through a hydrogel cross-linked network. After magnetization by a magnetic field, the magnetic particles show directional links in the three-dimensional network structure and still maintain a fluid state. The permanent magnetic particles are structurally fixed in the matrix, showing hysteresis, thereby achieving long-term existence of magnetism in the magnetic fluid after the external magnetic field disappears.

[0108] The magnetic colloidal fluid of this embodiment has a stable structure and is easy to recover. After the magnetic moment disappears, the stable fluid structure can be restored by simply applying a weak magnetic field (greater than 150 mT), and the residual magnetic field can be stable for at least several days, which is convenient for application in the field of in vivo tracing and biometry, thereby broadening its application range.

[0109] The present invention discloses a method for stabilizing the residual magnetism of an injectable magnetic fluid. The method performs in-situ reorientation on a structurally stable magnetic hydrogel, stabilizes the magnetic orientation links disrupted by injection and other operations with a weak magnetic field, and makes the magnetic fluid exhibit an outward macroscopic net magnetic moment again, thereby achieving long-term existence of magnetism in the magnetic fluid after the external magnetic field disappears. The magnetic hydrogel can be used for continuous tissue marking in vivo, biological signal measurement, and the like. The in-situ reorientation magnetic field is weak, has low damage to the organism, and is easy to promote and use.

[0110] The above embodiments are only exemplary embodiments of the present application and are not intended to limit the present application. The protection scope of the present application is defined by the claims. Those skilled in the art may make various modifications or equivalent substitutions to the present application within the essence and protection scope of the present application, and such modifications or equivalent substitutions shall also be deemed to fall within the protection scope of the present application.

Claims

1. A method for stabilizing the residual magnetism of an injectable magnetic fluid, wherein the magnetic fluid is an injectable magnetic hydrogel having a three-dimensional network structure, characterized in that: The method comprises the following steps: After the uniformity of the magnetic moment inside the magnetic hydrogel is disrupted, a weak magnetic field is applied to the magnetic hydrogel or an object containing the magnetic hydrogel to perform in-situ reorientation of the magnetic hydrogel with a weak magnetic field, so that the magnetic moment of the magnetic particles inside the magnetic hydrogel is unified, presenting fluid magnetism with stable remanent magnetism.

2. A method for stabilizing the residual magnetism of an injectable magnetic fluid according to claim 1, characterized in that: In the weak magnetic field in-situ reorientation, the strength of the weak magnetic field is 100-500 mT, and the magnetization time is 0.1 min to 1 min.

3. A method for stabilizing the residual magnetism of an injectable magnetic fluid according to claim 2, characterized in that: After in situ reorientation in the weak magnetic field, the magnetic hydrogel maintained stable magnetism for at least 5 days.

4. A method for stabilizing the residual magnetism of an injectable magnetic fluid according to claim 1, characterized in that: The magnetic hydrogel is prepared by cross-linking NdFeB@SiO2 magnetic nanoparticles with a sodium alginate precursor solution and a polyvinyl alcohol precursor.

5. A method for stabilizing the residual magnetism of an injectable magnetic fluid according to claim 1, characterized in that: The preparation method of the magnetic hydrogel comprises the following steps: The NdFeB@SiO2 magnetic nanoparticles are mixed with the sodium alginate precursor solution and the polyvinyl alcohol precursor solution, and stirred at high speed to obtain a mixed reactant B; The mixed reactant B is subjected to vacuum degassing treatment to improve the cross-linking tightness of the three-dimensional network in the hydrogel to obtain a hydrogel precursor; The hydrogel precursor is magnetized under a magnetic field of 2 to 3 T, and then subjected to repeated freeze-thaw treatment to promote the close cross-linking of sodium alginate chains and polyvinyl alcohol chains to form a polymer aggregation area, and promote the formation of hydrogen bonds and crystals to provide a three-dimensional network for the directional linking of magnetic particles, so as to obtain the magnetic colloidal fluid.

6. A method for stabilizing the residual magnetism of an injectable magnetic fluid according to claim 5, characterized in that: The repeated freeze-thaw treatment comprises the following steps: The magnetized hydrogel precursor was frozen at -20°C for 12-48 hours, and thawed at 25°C for 2-4 hours, and the cycle was repeated 3-5 times.

7. A method for stabilizing the residual magnetism of an injectable magnetic fluid according to claim 5, characterized in that: The high-speed stirring time is 15-30min; The vacuum degassing time is 15-30min.

8. A method for stabilizing the residual magnetism of an injectable magnetic fluid according to claim 5, characterized in that: The preparation steps of the NdFeB@SiO2 magnetic nanoparticles are as follows: The NdFeB particles are mixed with an ethanol aqueous solution and stirred for 15-30 minutes to obtain a NdFeB dispersion; Adding ammonia water and tetraethyl orthosilicate to the NdFeB dispersion successively to obtain a mixed reactant A; The mixed reactant A is repeatedly washed with ethanol and then water to obtain a precipitate; The precipitate is dried to obtain the NdFeB@SiO2 magnetic nanoparticles.

9. A method for stabilizing the residual magnetism of an injectable magnetic fluid according to claim 5, characterized in that: For every 1g of NdFeB, the amount of ethanol aqueous solution is 100-200ml; In the NdFeB dispersion, for every 1g of NdFeB, the amount of ammonia water is 4-8ml, and the amount of ethyl orthosilicate is 2-4ml; The drying temperature is 50-60°C; The concentration of the sodium alginate precursor solution is 0.5-2%; The concentration of the polyvinyl alcohol precursor solution is 5-10%.

10. The method for stabilizing the residual magnetism of an injectable magnetic fluid according to any one of claims 1 to 9, characterized in that: The magnetic hydrogel is used for biological tissue labeling and in vivo tracing.

Images