Method for amine functionalization of magnetic nanoparticles through surface pretreatment and formation of silica interlayer

Abstract

According to an embodiment of the present invention, a method for amine functionalization of magnetic nanoparticles is provided, comprising the steps of: (a) pre-treating magnetic iron oxide nanoparticles through a basic aqueous solution; and (b) adding a silanizing agent to the pre-treated magnetic iron oxide nanoparticles and reacting them.

Description

Technology Field

[0001] The present invention relates to a method for amine functionalization of magnetic nanoparticles comprising a pretreated surface layer and a silica intermediate layer, and more specifically, to a method for immobilizing amine groups on the surface of iron oxide nanoparticles. Background Technology

[0002] Magnetic particles are utilized in various fields for medical purposes, including the diagnosis and treatment of diseases such as cancer, immunoassays, contrast agents used in medical imaging, drug delivery systems (DDS), genetic engineering such as RNA isolation, biosensors for analyzing bioanalytes, wastewater purification, catalysts, information storage, and anti-counterfeiting marking technologies.

[0003] Conventionally, methods for introducing silane compounds onto the surface of magnetic iron oxide (γ-Fe2O3) or iron oxide (Fe2O3) nanoparticles have generally been used, such as treatment with APTES (3-Aminopropyltriethoxysilane) alone or pretreatment with acid (HCl, etc.) followed by a silanization reaction.

[0004] However, this method has the following technical limitations.

[0005] First, acid-based pretreatment processes involve the dehydration condensation of some hydroxyl groups (-OH) or Cl - In some cases, inducing ion substitution reactions actually hinders the efficiency of the silanization reaction.

[0006] Second, when APTES is treated alone, the silane coupling reaction proceeds unevenly, which reduces the density and uniformity of surface amine group introduction.

[0007] Third, in the absence of a silica layer, the covalent stability of APTES is low, and there are limitations to long-term dispersion stability and maintenance of function due to the detachment or rearrangement of functional groups.

[0008] Due to these problems, the aforementioned conventional technology faced difficulties in ensuring the efficiency of functional group introduction and structural stability in the design of high-performance nanoparticles. Consequently, its applicability in application fields requiring polymer or biomolecular binding was also limited.

[0009] Therefore, nanoparticle surface modification technology capable of ensuring uniformity of functional group introduction, binding stability, and dispersibility is required. The problem to be solved

[0010] The purpose of the present invention is to solve the problems of the aforementioned prior art.

[0011] The objective of the present invention is to improve functional group binding efficiency and dispersion stability simultaneously by immobilizing amine groups through a multi-step process that combines NH4OH-based basic pretreatment, the formation of a silica interface layer using TEOS, and an APTES silanization reaction, as a surface modification technology for immobilizing amine groups (-NH2) on the surface of magnetic iron oxide (γ-Fe2O3) nanoparticles.

[0012] The objective of the present invention is to provide amine group functionalized magnetic iron oxide nanoparticles that can be utilized in various high-performance industrial fields such as semiconductor CMP (Chemical Mechanical Planarization) slurries, biosensors, precision catalyst supports, and magnetic resonance imaging (MRI) contrast agents, and to expect various application effects such as molecular bonding control through surface functionalization, improved dispersion characteristics, and recyclability.

[0013] The objectives of the present invention are not limited to those mentioned above, and other unmentioned objectives will be clearly understood from the description below. means of solving the problem

[0014] According to one embodiment of the present invention for achieving the above-mentioned purpose, a method for amine functionalization of magnetic nanoparticles is provided, comprising the steps of: (a) pre-treating magnetic iron oxide nanoparticles through a basic aqueous solution; and (b) adding a silanizing agent to the pre-treated magnetic iron oxide nanoparticles and reacting them.

[0015] The above step (a) may include a step of removing impurities from magnetic iron oxide nanoparticles.

[0016] The above step (a) may include the step of dispersing the iron oxide nanoparticles in distilled water and washing them.

[0017] The above cleaning can be performed through ultrasonic treatment.

[0018] The above washing can be performed two or more times.

[0019] The above step (a) may further include a step of recovering washed iron oxide nanoparticles using a magnet.

[0020] The above step (a) may further include the step of introducing washed magnetic iron oxide nanoparticles into a basic aqueous solution and then reacting them.

[0021] The above basic aqueous solution may be an aqueous NH4OH solution.

[0022] The reaction with the above basic aqueous solution can be carried out while stirring at 60 to 100°C for 1 hour.

[0023] The above stirring is performed at 200 to 400 rpm.

[0024] The above step (a) may further include a step of natural cooling after the reaction.

[0025] The above step (b) may include a step of dispersing pretreated magnetic oxide nanoparticles.

[0026] The above dispersion can be achieved in a mixture of distilled water and ethanol.

[0027] The above dispersion can be achieved using ultrasound.

[0028] The above step (b) may further include a step of adding a silanizing agent and reacting after dispersion.

[0029] The step of adding the above silanizing agent and reacting it can be carried out at 50 to 90°C for 48 hours.

[0030] The above silanizing agent may be APTES.

[0031] The above step (b) may further include a step of recovering the magnetic iron oxide nanoparticles, after the reaction with the silanizing agent is complete, using a magnet.

[0032] The above step (b) may further include a step of washing the recovered magnetic iron oxide nanoparticles.

[0033] The above washing can be performed using ethanol washing and distilled water washing.

[0034] The above step (b) may further include a step of forming an SiO2 intermediate layer on the surface of magnetic iron oxide nanoparticles prior to the step of adding and reacting the silanizing agent.

[0035] The step of forming the SiO2 intermediate layer may include the step of dispersing pretreated magnetic iron oxide nanoparticles in a mixture of distilled water and ethanol.

[0036] The step of forming the above SiO2 intermediate layer may further include the step of introducing a TEOS solution into a mixture in which magnetic iron oxide nanoparticles are dispersed.

[0037] The above TEOS solution can be administered dropwise through a syringe pump.

[0038] The above TEOS solution may be a mixture of 0.1 to 0.3 mL of TEOS and ethanol.

[0039] The step of forming the SiO2 intermediate layer may further include a step of proceeding with a stirring reaction after adding a TEOS solution.

[0040] The above stirring reaction can be carried out for 15 to 20 hours.

[0041] According to another embodiment of the present invention, a core-shell nanoparticle having a γ-Fe2O3 / SiO2-NH2 structure is provided, formed such that an amine group is immobilized on the surface through basic pretreatment, the formation of a silica intermediate layer, and a synranification reaction.

[0042] The core diameter of the above core-shell nanoparticles may be 150 to 300 nm. Effects of the invention

[0043] According to an embodiment of the present invention, by applying a multi-stage surface modification process to magnetic iron oxide nanoparticles, it is possible to simultaneously secure amine group (-NH2) introduction efficiency and structural stability.

[0044] According to an embodiment of the present invention, in particular, by forming abundant hydroxyl groups (-OH) on the particle surface through pretreatment using basic conditions (aqueous NH4OH solution) and uniformly growing a silica (SiO2) intermediate layer through TEOS hydrolysis based on this, the efficiency of the silane coupling reaction of APTES can be significantly improved thereafter. This structural basis exhibits superior characteristics in terms of high-precision introduction of amine groups, stability of surface bonding, and uniformity of functional group distribution compared to a single silanization treatment method.

[0045] According to an embodiment of the present invention, amine groups (-NH2) can be precisely and stably immobilized on the surface of magnetic iron oxide nanoparticles, and through the primary amine groups introduced on the surface, covalent bonding with various functional groups or biomolecules is possible, and it can be utilized in high-performance nanoparticle platforms such as CMP slurries, biosensors, precision catalysts, and medical contrast agents. Brief explanation of the drawing

[0046] Figure 1 is an FT-IR spectrum to confirm the change in functional groups before and after surface modification of magnetic iron oxide nanoparticles. Figure 2 shows the results of the zeta potential and PDI (Polydispersity Index) analysis measured to quantitatively analyze the change in dispersion stability before and after surface modification of magnetic iron oxide nanoparticles. Figure 3 is an FT-IR spectrum to confirm the change in functional groups after stepwise application of TEOS and APTES surface modifications to magnetic iron oxide nanoparticles. Figure 4 is a TEM image to confirm the structural characteristics and shape stability of magnetic iron oxide nanoparticles before and after surface modification. Figure 5 shows the results of zeta potential, particle size distribution (PSD), average particle size, and PDI analysis to confirm changes in dispersion stability and particle size characteristics following TEOS and APTES-based surface modification of magnetic iron oxide nanoparticles. Figure 6 shows the results of VSM analysis performed to confirm the effect of APTES-based amine group functionalization of magnetic iron oxide nanoparticles on magnetic properties. Specific details for implementing the invention

[0047] The following detailed description of the invention refers to the accompanying drawings, which illustrate specific embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention. It should be understood that various embodiments of the invention are different but need not be mutually exclusive. For example, specific shapes, structures, and characteristics described herein with respect to one embodiment may be implemented in other embodiments without departing from the spirit and scope of the invention. It should also be understood that the location or arrangement of individual components within each disclosed embodiment may be changed without departing from the spirit and scope of the invention. Accordingly, the following detailed description is not intended to be limiting, and the scope of the invention is limited only by the appended claims, including all equivalents to those claimed therein, provided appropriately described. Similar reference numerals in the drawings refer to the same or similar functions across various aspects.

[0048] Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the attached drawings in order to enable a person skilled in the art to easily practice the present invention.

[0049] Surface pretreatment of magnetic iron oxide nanoparticles

[0050] First, before introducing functional groups into the magnetic iron oxide (γ-Fe3O4) nanoparticles according to the present invention, a pretreatment process is performed to remove impurities present on the surface and induce the formation of reactive receivers (-OH).

[0051] Specifically, 2g of iron oxide nanoparticles are dispersed in distilled water and washed using ultrasonic treatment. The washing process is repeated multiple times, and then the particles are recovered using an external magnet.

[0052] Afterward, the washed nanoparticles are introduced into 500 mL of a 2N basic (NH4OH) aqueous solution (or an aqueous solution containing an HCl aqueous solution) and reacted at a stirring speed of 200 to 400 rpm at 60 to 100°C for 1 hour. After the reaction is complete, the temperature is lowered to room temperature (25°C) through natural cooling. Preferably, using a basic (NH4OH) aqueous solution is more effective for improving dispersion stability, as will be explained later.

[0053] This pretreatment step increases the hydroxyl group density on the surface of magnetic nanoparticles, thereby establishing foundational conditions that enhance the reactivity and uniformity of functional group bonding in the subsequent silanization reaction. In other words, surface hydroxylation can be induced through this pretreatment.

[0054] Amine functionalization by APTES

[0055] A functionalization process is performed to introduce amine groups (-NH2) to the surface of magnetic iron oxide nanoparticles pretreated through the process described above.

[0056] This can be done in the following two ways.

[0057] 1. Silanization by APTES treatment alone

[0058] Pre-treated magnetic iron oxide nanoparticles are dispersed in a mixture of DIW (distilled water) and ethanol using ultrasound. Subsequently, 0.026 mol of APTES is added as a silanizing agent, and the mixture is reacted at 50–90°C for 48 hours.

[0059] After the reaction is complete, the nanoparticles are recovered using a magnet, and impurities are removed through washing with ethanol and distilled water.

[0060] 2. Silanization through the formation of a TEOS-based silica interlayer

[0061] To achieve a more precise functionalization effect, a thin SiO2 intermediate layer is formed on the magnetic iron oxide surface prior to APTES treatment.

[0062] Specifically, magnetic iron oxide nanoparticles are dispersed in a mixture of DIW and ethanol. A pre-mixed solution of 0.1–0.3 ml of TEOS (Tetraethyl orthosilicate) and ethanol is prepared and then dropwise added to the dispersion using a syringe pump. After addition, a stirring reaction is carried out for 15–20 hours. Consequently, a uniform silica layer is formed on the iron oxide nanoparticles. Subsequently, APTES is added under the same conditions as in the preceding method 1, and the reaction is carried out for an additional 48 hours.

[0063] According to an embodiment of the present invention, only the first processing step may be performed, or the second method may be performed first, and then the first processing step may be performed.

[0064] Figure 1 is an FT-IR spectrum to confirm the change in functional groups before and after surface modification of magnetic iron oxide nanoparticles.

[0065] Approximately 570 cm in all analyzed and evaluated samples -1 Commonly observed Fe-O stretching vibration peaks in the vicinity indicate that the iron oxide nanoparticles maintain their crystal structure.

[0066] For samples treated with acid (HCl) and base (NH4OH), respectively, 3000-3700 cm -1 OH stretching vibration peak in the range and about 1600 cm -1 The intensity of the nearby HOH bending vibration peak increased, suggesting the presence of surface hydroxyl groups and adsorbed water molecules.

[0067] In particular, -OH and HOH peaks appeared most distinctly in the samples treated with base (NH4OH), which is OH - This is interpreted as a result of the hydroxide reaction being induced more effectively due to the provision of ions. On the other hand, acids (HCl) can react with some hydroxyl groups to induce dehydration condensation or substitution reactions, which relatively limits the increase of OH groups.

[0068] Therefore, it is determined that the NH4OH-based basic modification process on the surface of magnetic iron oxide nanoparticles is effective in increasing the density of -OH groups and promoting the adsorption of water molecules.

[0069] Figure 2 shows the results of the zeta potential and PDI (Polydispersity Index) analysis measured to quantitatively analyze the change in dispersion stability before and after surface modification of magnetic iron oxide nanoparticles.

[0070] The prepared magnetic iron oxide exhibits a low zeta potential of -1.6±2mV and a high PDI value of 0.824±0.13, which means that the electrical repulsion between particles is weak, leading to aggregation and consequently reduced dispersion stability.

[0071] A-γ-Fe3O4 and B-γ-Fe3O4 samples surface-modified with HCl and NH4OH exhibited zeta potentials of -11.9±3 mV and -26.1±3 mV, respectively, and PDI values ​​of 0.522±0.097 and 0.367±0.061, which indicates that the particle surface charge density increased through surface modification, and the resulting electrostatic repulsion improved, thereby enhancing dispersion stability.

[0072] In particular, B-γ-Fe3O4 modified with NH4OH exhibited the highest absolute zeta potential and the lowest PDI, suggesting that the formation of -OH groups on the surface was actively induced, resulting in the most excellent electrical stability.

[0073] This trend is consistent with the FT-IR analysis results in Figure 1, and it can be experimentally confirmed that basic treatment conditions are more effective in improving particle dispersion stability compared to acidic treatment.

[0074] Figure 3 is an FT-IR spectrum to confirm the change in functional groups after stepwise application of TEOS and APTES surface modifications to magnetic iron oxide nanoparticles.

[0075] In the BT-γ-Fe3O4 sample with added TEOS after NH4OH treatment, the Fe-O peak (570 cm⁻¹) -1 While ) is maintained, 1220 and 1070 cm -1 A new peak corresponding to a siloxane (Si-O-Si) bond was observed, confirming the formation of a thin SiO2 layer due to the TEOS hydrolysis / condensation reaction. Along with this, the intensity of the OH and HOH vibration peaks increased, indicating that numerous Si-OH groups were introduced to the surface.

[0076] For APTES-treated BA-γ-Fe3O4 and BTA-γ-Fe3O4 samples, 3000–3700 cm -1 (NH stretching), approximately 2900cm -1 (CH stretching), 1635 cm -1 A distinct peak corresponding to (NH bending) appeared, which means that amine groups (-NH2) were successfully introduced onto the surface of the nanoparticles.

[0077] In particular, in the BTA-γ-Fe3O4 sample pre-treated with TEOS, the intensity of the amine group peak increased while the siloxane bond peak was maintained, so it is believed that the SiO2 layer induced stable silane bonding of APTES and improved the uniformity of functional group immobilization.

[0078] The results of this analysis demonstrate that combined treatment with TEOS and APTES is an effective modification strategy that simultaneously improves the surface hydrophilicity and amine group introduction efficiency of magnetic iron oxide nanoparticles.

[0079] Figure 4 is a TEM image to confirm the structural characteristics and shape stability of magnetic iron oxide nanoparticles before and after surface modification.

[0080] Figure 4(a) is a TEM image of the prepared γ-Fe3O4, Figure 4(b) is an NH4OH-modified BA-γ-Fe3O4, Figure 4(c) is a TEOS-treated BTA-γ-Fe3O4, and Figure 4(d) is a BTA-γ-Fe3O4 sample with added APTES functionality.

[0081] The average particle size in all samples was measured to be approximately 270–290 nm, confirming that the basic modification, TEOS coating, and APTES functionalization processes were stably performed without structural damage to the γ-Fe3O4 core.

[0082] In addition, in the samples of Fig. 4(c) and (d), no clear shell structure or phase-separated layer was observed despite the application of TEOS and APTES treatments, so it is interpreted that the SiO2 and organic layers were adsorbed very thinly and uniformly on the surface.

[0083] All samples maintained a spherical or semi-spherical shape even after surface modification, indicating that the effect of the treatment process applied according to the embodiment of the present invention on the shape stability of γ-Fe3O4 nanoparticles is negligible.

[0084] Therefore, NH4OH-based pretreatment, TEOS coating, and APTES silanization reaction suggest that these are conditions that can effectively perform surface modification while maintaining the structural stability of the particles.

[0085] Figure 5 shows the results of zeta potential, particle size distribution (PSD), average particle size, and PDI analysis to confirm changes in dispersion stability and particle size characteristics following TEOS and APTES-based surface modification of magnetic iron oxide nanoparticles.

[0086] As a result of the zeta potential analysis in Fig. 5(a), the BA-γ-Fe3O4, BT-γ-Fe3O4, and BTA-γ-Fe3O4 samples showed values ​​of 7.1±2mV, -48.3±2mV, and 35.4±3mV, respectively, which is the result of increased surface charge density and electrical stability as APTES amine groups were effectively adsorbed through TEOS treatment.

[0087] In particular, BTA-γ-Fe3O4 exhibits the highest positive zeta potential, indicating a relatively large amount of amine groups introduced, which is consistent with the FT-IR results in Figure 3.

[0088] In the PSD and particle size analysis of Figures 5(b) and (c), the prepared γ-Fe3O4 showed a distinct double peak distribution with an average size of 827.4±16.4 nm and a high PDI of 0.824±0.13, whereas all surface-modified samples showed an average size of about 270–290 nm and a low PDI of 0.18–0.28, suggesting that dispersion stability was significantly improved.

[0089] In particular, BTA-γ-Fe3O4 with both TEOS and APTES applied showed a single-peak PSD distribution with good aggregation inhibition, which means that electrostatic repulsion due to increased surface charge effectively inhibits aggregation.

[0090] These results demonstrate that a combined treatment process of NH4OH, TEOS, and APTES is an effective strategy for effectively improving surface properties while maintaining the dispersion stability and structural consistency of γ-Fe3O4 nanoparticles.

[0091] Figure 6 shows the results of VSM analysis performed to confirm the effect of APTES-based amine group functionalization of magnetic iron oxide nanoparticles on magnetic properties.

[0092] All samples exhibited linear hysteresis curves without residual magnetization or coercivity, confirming that the nanoparticles maintain superparamagnetic properties even after surface modification.

[0093] The prepared γ-Fe3O4 exhibited a high saturation magnetization value (Ms) of 121.48 emu / g, while slightly reduced values ​​of 111.24 and 109.81 emu / g were observed in the APTES-introduced BA-γ-Fe3O4 and BTA-γ-Fe3O4 samples, respectively.

[0094] This reduction in magnetization value is due to the introduction of non-magnetic APTES and TEOS-based SiO2 layers on the particle surface, which lowers the relative proportion of magnetic material within the entire nanoparticle.

[0095] However, the reduction in Ms is limited and all samples maintain a superparamagnetic state, proving that the surface functionalization process of the present invention does not essentially impair the magnetic properties of γ-Fe3O4.

[0096] Therefore, the introduction of APTES amine groups suggests that it is an effective treatment condition that enables surface functionalization while minimizing the impact on magnetic retention properties.

[0097] According to an embodiment of the present invention, by applying a multi-stage surface modification process to magnetic iron oxide nanoparticles, it is possible to simultaneously secure amine group (-NH2) introduction efficiency and structural stability.

[0098] According to an embodiment of the present invention, in particular, by forming abundant hydroxyl groups (-OH) on the particle surface through pretreatment using basic conditions (aqueous NH4OH solution) and uniformly growing a silica (SiO2) intermediate layer through TEOS hydrolysis based on this, the efficiency of the silane coupling reaction of APTES can be significantly improved thereafter. This structural basis exhibits superior characteristics in terms of high-precision introduction of amine groups, stability of surface bonding, and uniformity of functional group distribution compared to a single silanization treatment method.

[0099] According to an embodiment of the present invention, amine groups (-NH2) can be precisely and stably immobilized on the surface of magnetic iron oxide nanoparticles, and through the primary amine groups introduced on the surface, covalent bonding with various functional groups or biomolecules is possible, and it can be utilized in high-performance nanoparticle platforms such as CMP slurries, biosensors, precision catalysts, and medical contrast agents.

[0100] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical spirit or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single unit may be implemented in a distributed manner, and components described as distributed may likewise be implemented in a combined form.

[0101] The scope of the present invention is defined by the claims set forth below, and all modifications or variations derived from the meaning and scope of the claims and equivalent concepts thereof should be interpreted as being included within the scope of the present invention.

Claims

Claim 1 A method for amine functionalization of core-shell magnetic nanoparticles, comprising: (a) a step of pretreating magnetic iron oxide nanoparticles through a basic aqueous solution; (b) a step of adding a silanizing agent to the pretreated magnetic oxide nanoparticles and reacting them, wherein step (a) comprises a step of dispersing the magnetic iron oxide nanoparticles in distilled water and washing them; and a step of introducing the washed magnetic iron oxide nanoparticles into an aqueous NH4OH solution and reacting them, wherein the reaction with the aqueous NH4OH solution is carried out while stirring at 60 to 100°C for 1 hour, and step (b) comprises a step of dispersing the pretreated magnetic iron oxide nanoparticles in a mixture of distilled water and ethanol; and a step of forming an SiO2 intermediate layer on the surface of the magnetic iron oxide nanoparticles by adding a TEOS solution to the mixture in which the magnetic iron oxide nanoparticles are dispersed and reacting them. Claim 2 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein step (a) comprises removing impurities from magnetic iron oxide nanoparticles. Claim 3 delete Claim 4 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein the washing is performed through ultrasonic treatment. Claim 5 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein the washing is performed two or more times. Claim 6 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein step (a) further comprises the step of recovering washed iron oxide nanoparticles using a magnet. Claim 7 delete Claim 8 delete Claim 9 delete Claim 10 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein the stirring is performed at 200 to 400 rpm. Claim 11 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein step (a) further comprises the step of natural cooling after the reaction is completed. Claim 12 delete Claim 13 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein the dispersion is carried out in a mixture of distilled water and ethanol. Claim 14 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 13, wherein the dispersion is achieved using ultrasound. Claim 15 delete Claim 16 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein the step of adding and reacting the silanizing agent is carried out at 50 to 90°C for 48 hours. Claim 17 A method for amine functionalization of core-shell magnetic nanoparticles, wherein the silanizing agent is APTES in claim 1. Claim 18 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein step (b) further comprises the step of recovering the magnetic iron oxide nanoparticles, after the reaction with the silanizing agent is completed, with a magnet. Claim 19 A method for amine functionalization of core-shell magnetic nanoparticles, wherein step (b) further comprises the step of washing the recovered magnetic iron oxide nanoparticles. Claim 20 In claim 19, the above washing is a method for amine functionalization of core-shell magnetic nanoparticles, wherein the washing is performed by carrying out an ethanol washing process and a distilled water washing process. Claim 21 delete Claim 22 delete Claim 23 delete Claim 24 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein the TEOS solution is dropwise administered through a syringe pump. Claim 25 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein the TEOS solution is a mixture of 0.1 to 0.3 mL of TEOS and ethanol. Claim 26 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 1, wherein the step of forming the SiO2 intermediate layer further comprises the step of carrying out a stirring reaction after adding a TEOS solution. Claim 27 A method for amine functionalization of core-shell magnetic nanoparticles according to claim 26, wherein the stirring reaction proceeds for 15 to 20 hours. Claim 28 delete Claim 29 delete

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