Biphasic composite structure magnetic core and preparation method, orthogonal fluxgate probe, magnetic sensing test system and molecular test method

Abstract

The application discloses a two-phase composite structure magnetic core and a preparation method thereof, a normal magnetic flux gate probe, a magnetic sensing test system and a molecular test method. The two-phase composite structure magnetic core comprises a silver wire with a purity of 4N as a substrate and amorphous CoP deposited on the substrate; current annealing is performed on the magnetic core to make the CoP react with air to form partial crystallization. The normal magnetic flux gate probe comprises a U-shaped two-phase composite structure magnetic core, a voltage signal pickup coil, two glass tubes and a PCB printed circuit board, and the two glass tubes are penetrated to avoid mutual conduction. The magnetic sensing test system uses a reaction channel chip to carry a biological sample to be tested, and the biological sample to be tested has a magnetic marker and a voltage signal pickup coil magnetic field signal. The molecular test method comprises surface functionalization treatment, magnetic marker capture and signal detection, concentration gradient detection and quantitative analysis. The probe and the system have the advantages of low noise, high sensitivity, good stability and controllable structure, and realize single particle level magnetic bead detection and low concentration biological molecule detection.

Description

Technical Field

[0001] This invention belongs to the field of weak magnetic field measurement element technology, specifically relating to a method for preparing a magnetic core for an orthogonal fluxgate probe and the construction of a probe and biomolecular sensing and testing system. Background Technology

[0002] High-sensitivity detection technology for weak magnetic fields has significant application value in geomagnetic measurement, biomedical detection, non-destructive testing, and space exploration. Among these, orthogonal fluxgate magnetometers (EMGMs) are gradually becoming an important technical approach for weak magnetic field detection due to their miniaturization, high sensitivity, and low noise limit. Currently, commonly used core materials for EMGMs include homogeneous amorphous magnetic wires and composite cores. While homogeneous amorphous magnetic wires possess low coercivity and high permeability, their typical shell domain structure makes it difficult to fully magnetize the central region of the core, easily introducing significant noise under low-frequency conditions. Although FeNi-based electroplated composite cores have high conductivity, which helps reduce unsaturated regions and alleviate the skin effect, their large grain size and wide domain spacing limit effective permeability, making it difficult to simultaneously achieve both soft magnetic properties and low-frequency noise performance. Therefore, existing core structures cannot simultaneously meet the requirements of noise suppression, good soft magnetic properties, and process controllability, necessitating a novel composite core structure that can effectively reduce core noise while maintaining high permeability.

[0003] Furthermore, in the field of biomagnetic detection, detection methods based on immunomagnetic beads place even more stringent technical demands on the sensor's magnetic noise level and ability to resolve weak magnetic signals. Existing orthogonal fluxgate sensors still face challenges such as insufficient sensitivity, high detection limits, and limited stability when detecting magnetic markers at the nanometer to micrometer scale, hindering their further application in ultrasensitive biomolecule detection. Therefore, there is an urgent need for a novel orthogonal fluxgate core structure and its sensor technology solution that achieves synergistic optimization at the material structure design, fabrication process, and system integration levels to overcome the shortcomings of existing technologies in low-frequency noise control, soft magnetic property preservation, and biomagnetic detection sensitivity.

[0004] To address the aforementioned issues, this invention proposes and fabricates a CoP amorphous-nanocrystalline composite magnetic core based on a silver substrate. By introducing a nanocrystalline phase into the amorphous CoP magnetic layer, a dual-phase structure where amorphous and nanocrystalline phases coexist is achieved, thus balancing low noise characteristics and high magnetic permeability. Based on this magnetic core, this invention further constructs a magnetic sensing testing system. The magnetic core is used to sense the weak magnetic signals generated by target biomolecules labeled with superparamagnetic beads. The system is equipped with a reaction channel chip to carry the sample to be tested, and combines a pickup coil and signal conditioning circuitry to achieve highly sensitive acquisition and modulation output of the magnetic signal, thereby constructing a complete sensing platform capable of single-particle level detection and low-concentration biomolecule detection. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a method for preparing a two-phase composite magnetic core and a two-phase composite magnetic core, which are in view of the shortcomings of the prior art.

[0006] Another object of the present invention is to provide an orthogonal fluxgate probe containing a dual-phase composite magnetic core.

[0007] Another object of the present invention is to provide a magnetic sensing testing system for biomolecule detection containing an orthogonal fluxgate probe. This system achieves highly sensitive detection of weak magnetic signals generated by target biomolecules labeled with superparamagnetic beads, and is suitable for single-bead level detection and low-concentration biomolecule detection applications.

[0008] Another object of the present invention is to construct a molecular testing method using the aforementioned magnetic sensing testing system.

[0009] The following technical solution is adopted to solve the technical problem of the present invention:

[0010] A method for preparing a two-phase composite magnetic core, wherein the two-phase composite magnetic core uses a silver wire with a purity of 4N as a substrate, and the diameter of the silver wire is 20-140 μm; an amorphous phase CoP is electrochemically deposited on the silver wire to obtain the magnetic core; wherein the thickness of the CoP is 4-16 μm, and the electrolyte used for electrochemical deposition also contains Co. 2+ CoP and hypophosphate ions were used to anneal the magnetic core by electric heating in an air environment. CoP reacted with the air to form partial crystallization, resulting in a two-phase composite magnetic core.

[0011] Specifically, the electrolyte composition is: 0.05 mol / L NiSO4·6H2O, 0.5 mol / L CoSO4·6H2O, 0.2-0.8 mol / L NaH2PO2·6H2O, 0.2 mol / L Na3C6H5O7·2H2O, 0.15 mol / L C4H4Na2O6·2H2O, and 0.5 mol / L (NH4)2SO4. After the electrolyte is prepared, the pH value of the electrolyte is adjusted to 7 with NaOH, and electrochemical deposition is carried out using the constant potential deposition method.

[0012] During the electrochemical deposition, the electrolyte temperature is 65℃-95℃, the pH is 7-9.5, the deposition time is 3000-8500 seconds, and the deposition current density is 0.6-2 A / dm³. 2 .

[0013] When annealing the magnetic core, the magnetic core is vertically suspended in the air using an electrode clamp carrying a direct current. The CoP / Ag is stressed by the gravity of the electrode clamp itself. The annealing current is 1.6-2 A and the annealing time is 10-20 min. The annealing process causes 10-20 nm nanocrystals to form in the amorphous phase, thereby producing a two-phase structure.

[0014] Before electrochemical deposition, the silver wire is pretreated as follows: wash with deionized water for 5-10 min → wash with weak alkaline solution for 10-15 min → wash with deionized water for 5-10 min → wash with acid solution for 10-15 min → wash with deionized water for 5-10 min. The weak alkaline solution is a 40-45 g / L sodium carbonate solution, and the acid solution is a hydrochloric acid solution prepared by mixing 2 mL of concentrated hydrochloric acid with 50 mL of deionized water.

[0015] The dual-phase composite magnetic core prepared according to the above-described method is U-shaped, and CoP is not deposited in the U-shaped bend (the measure taken is to cover the U-shaped bend of the pretreated silver wire with a clamp).

[0016] An orthogonal fluxgate probe containing the aforementioned dual-phase composite magnetic core includes a U-shaped dual-phase composite magnetic core, a voltage signal pickup coil, a second glass tube and a first glass tube, and a PCB printed circuit board; the second glass tube is fitted inside the first glass tube, one side of the U-shaped dual-phase composite magnetic core passes through the second glass tube and the other side passes through the interlayer between the first and second glass tubes, the voltage signal pickup coil is wound on the first glass tube, and the voltage signal pickup coil, the U-shaped dual-phase composite magnetic core, and the PCB printed circuit board are soldered together.

[0017] A magnetic sensing testing system for biomolecule detection using the aforementioned orthogonal fluxgate probe includes an orthogonal fluxgate probe equipped with a signal conditioning circuit board connected to a PCB printed circuit board. A reaction channel chip is positioned directly above a U-shaped two-phase composite magnetic core. The signal conditioning circuit board, the U-shaped two-phase composite magnetic core, and the reaction channel chip are all housed inside a Helmholtz coil, collectively forming the magnetic sensing testing system for biomolecule detection. The reaction channel chip carries the biological sample to be tested, which contains magnetic markers. A voltage signal pickup coil is used to pick up the magnetic field signals before and after the placement of the magnetic markers in the biological sample. By recording the voltage difference before and after detecting the magnetic signal of the biological sample, the content of the detected molecules is obtained.

[0018] A molecular testing method using the aforementioned magnetic sensing testing system includes the following steps:

[0019] Step a: Surface functionalization treatment: A reaction channel chip is prepared using glass as a substrate. The glass is silanized using 3-aminopropyltriethoxysilane (APTES) solution to introduce amino functional groups into the glass surface. These amino functional groups are used to covalently couple the target biomarkers in the biological sample to be tested to form a stable active interface. Subsequently, the biological sample to be tested is introduced. After incubation, washing and sealing steps, only the specific recognition sites are retained, thereby effectively improving the detection signal-to-noise ratio.

[0020] Step b: Magnetic marker capture and signal detection: The magnetic marker is a magnetic bead. Based on the diameter of the magnetic bead and the concentration of the original stock solution of the biological sample to be tested, the working concentration of the magnetic bead suspension is determined by statistical methods (usually 10% of the highest concentration of the sample to be tested). 2 ~10 3 (Multiple times), magnetic beads coated with specific antibodies against the target biomarker are introduced into the reaction channel chip that has undergone surface functionalization in step a. After incubation and washing, the magnetic beads that bind only through specific recognition are captured and fixed on the chip surface. A Helmholtz coil is connected to a constant current power supply to generate an excitation magnetic field. First, when the reaction channel chip is not placed on the U-shaped biphase composite magnetic core, the voltage signal pickup coil of the orthogonal fluxgate probe is used to detect the background magnetic signal above the U-shaped biphase composite magnetic core, and the output voltage A is recorded. Then, the reaction channel chip with the fixed magnetic beads is placed above the U-shaped biphase composite magnetic core to magnetize the magnetic beads. The voltage signal pickup coil detects the magnetic signal again and records the output voltage B. By comparing the changes in output voltage A and B, the presence or concentration of the target biomarker is determined.

[0021] Step c: Concentration gradient detection and quantitative analysis: When the presence of the target biomarker is confirmed in step b, solutions of the target biomolecules at different concentrations are prepared. A reaction channel chip is fabricated according to step a, and magnetic bead suspensions of the same working concentration as in step b are added. After incubation and cleaning, under the condition that a Helmholtz coil generates an excitation magnetic field, the output voltage C is first detected using a voltage signal pickup coil when no reaction channel chip is placed. Subsequently, reaction channel chips incubated with different concentrations of target biomolecule solutions are sequentially replaced and placed above a U-shaped biphase composite magnetic core to magnetize the magnetic beads. The voltage signal pickup coil detects the magnetic signal. Each concentration of target biomolecule solution incubated with a reaction channel chip corresponds to an output voltage, recorded as D1, D2, D3, D4… Based on the changes in output voltage C and D1, D2, D3, D4…, a correspondence between the voltage signal change and the concentration of the target biomolecule solution is established, thereby achieving quantitative detection of the target biomarker.

[0022] Preferably, the magnetic beads are superparamagnetic beads with a diameter of 100 nm to 1 μm; the target biomarker is any biomolecule to be detected, and the captured molecule is an antibody or antigen corresponding to the target biomarker.

[0023] The beneficial effects of this invention are:

[0024] The proposed dual-phase composite magnetic core is a CoP amorphous-nanocrystalline dual-phase composite core. This composite core uses a highly conductive silver wire as a substrate, on which a CoP magnetic coating is formed through electrochemical deposition. Compared to traditional single amorphous magnetic cores, the silver substrate plays a major current-carrying role during core operation, effectively improving current distribution and reducing the unsaturated region of the core, thus facilitating the full magnetization of the magnetic coating. Furthermore, this invention introduces a nanocrystalline phase into the amorphous CoP magnetic layer through a controlled annealing process, creating a dual-phase structure where amorphous and nanocrystalline phases coexist. The amorphous phase, as a continuous matrix, exhibits low coercivity and low domain wall pinning characteristics; the dispersed nanocrystalline phase improves structural order while stabilizing the magnetic domain structure and improving magnetic flux transmission characteristics. This dual-phase structure design effectively suppresses core magnetization noise while maintaining high permeability.

[0025] Based on the aforementioned two-phase composite magnetic core, this invention further constructs an orthogonal fluxgate probe. Under the action of an alternating excitation magnetic field, the magnetic core of this probe can achieve a stable and symmetrical magnetization process, thereby significantly reducing the probe's background noise level and improving the detection sensitivity of low-frequency weak magnetic fields. Compared with orthogonal fluxgate probes using conventional magnetic cores, the probe of this invention exhibits superior noise performance and stability in the low-frequency range.

[0026] Furthermore, this invention applies the aforementioned orthogonal fluxgate probe to a magnetic bead and biomolecule sensing testing system, constructing a magnetic sensing testing system for biomolecule detection using an orthogonal fluxgate probe. The system includes a reaction channel chip to hold the biological sample to be tested. The target biomolecule binds to and is immobilized by the superparamagnetic magnetic bead through an immune reaction. When an external alternating magnetic field is applied to the magnetic bead, the weak magnetic signal generated by the bead is highly sensitively detected by the dual-phase composite magnetic core and modulated and amplified by a voltage signal pickup coil and signal conditioning circuit. The magnetic sensing testing system thus constructed can achieve stable detection of single-particle magnetic beads and low-concentration biomolecules. The magnetic sensing testing system of this invention uses a fundamental mode to test noise, as shown in the attached diagram. Figure 4As shown, the noise level of the pure amorphous magnetic core sensor at 1 Hz is 8 pT / √Hz, while that of the dual-phase magnetic core sensor is 500 pT / √Hz, significantly reducing the noise level of the orthogonal fluxgate magnetometer. Using the magnetic sensing testing system, this signal from a single magnetic bead can be identified, and when testing alpha-fetoprotein molecules, a detection limit of 50 fg / mL can be obtained using a 1-micron magnetic bead. The dual-phase composite magnetic core and its preparation method described in this invention have a simple process flow, controllable parameters, and low raw material costs, making them suitable for large-scale applications. Furthermore, the constructed orthogonal fluxgate magnetometer probe and magnetic sensing testing system have significant technical advantages and application prospects in the field of low-frequency weak magnetic detection, especially in high-sensitivity biomagnetic sensing applications. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the dual-phase composite magnetic core of the present invention used in an orthogonal fluxgate probe;

[0028] Figure 2 The images show SEM and TEM images of the two-phase composite magnetic core of this invention; a is a cross-sectional scan of the two-phase composite magnetic core, b is a surface scan of the two-phase composite magnetic core, c is a high-resolution transmission electron microscope image of the single-phase composite magnetic core, and d is a high-resolution transmission electron microscope image of the two-phase composite magnetic core.

[0029] Figure 3 This is a schematic diagram of the magnetic sensing testing system for biomolecule detection using an orthogonal fluxgate probe according to the present invention.

[0030] Figure 4 A noise comparison diagram of a single-phase amorphous composite magnetic core and a two-phase composite magnetic core of the present invention;

[0031] Figure 5 To test alpha-fetoprotein molecular data using the magnetic sensing testing system of this invention, the lowest detection limit of this magnetic sensing testing system is found to be 50 fg / mL. Detailed Implementation Example 1

[0032] A method for fabricating a two-phase composite magnetic core, comprising the following specific steps:

[0033] Step a: Fold a silver wire substrate with a purity of 4N and a length of 11cm into a U-shape, wherein the diameter of the silver wire is 120 micrometers;

[0034] Step b: The cathode silver wire is pretreated before electrochemical deposition, specifically: wash with deionized water for 10 min → wash with weak alkaline solution (40 g / L sodium carbonate solution) for 10 min → wash with deionized water for 10 min → wash with acid solution (prepared with 2 mL concentrated hydrochloric acid / 50 mL deionized water) for 15 min → wash with deionized water for 10 min.

[0035] Step c: Prepare an electrolyte solution for depositing the CoP amorphous magnetic layer. The solution composition is: 0.05 mol / L NiSO4·6H2O, 0.5 mol / L CoSO4·6H2O, 0.2 mol / L NaH2PO2·6H2O, 0.2 mol / L Na3C6H5O7·2H2O, 0.15 mol / L C4H4Na2O6·2H2O, and 0.5 mol / L (NH4)2SO4. After preparing the solution according to the above proportions, weigh out NaOH and add it to the solution to adjust the pH to 7. Electrochemical deposition is then performed using a potentiostatic deposition method.

[0036] Step d: Deposition was performed using a three-electrode method, with a deposition current density of approximately 2 A / dm³. 2 The electrolyte is heated to 65°C, and then the silver wire, calomel electrode and platinum sheet electrode clamped by the fixture are placed into the electrolyte. The deposition time is 5000 seconds and the thickness of each coating layer is 4 micrometers. During electrochemical deposition, the U-shaped bend of the pretreated silver wire is blocked by the fixture to prevent CoP from being deposited on the U-shaped bend.

[0037] Step e: After electrochemical deposition, the U-shaped composite magnetic core is removed, the surface solution is wiped clean with degreased cotton, and annealed with direct current. The magnetic core is vertically suspended in the air using electrode clamps carrying direct current for annealing. The gravity of the electrode clamps (10 g) is used to apply stress to the CoP / Ag. The annealing current is 1.6 A, and the annealing time is 10 min. By heating with current, the temperature of CoP is increased. The high-temperature CoP reacts with air to achieve partial crystallization, forming 10-20 nm nanocrystals in the amorphous phase, thus producing a two-phase structure.

[0038] An orthogonal fluxgate probe containing a dual-phase composite magnetic core comprises a U-shaped dual-phase composite magnetic core 2, a voltage signal pickup coil 3, a second glass tube 5, a first glass tube 4, and a PCB printed circuit board 6. The U-shaped dual-phase composite magnetic core 2 is made of 4N silver wire 1 deposited with dual-phase CoP. The second glass tube 5 is fitted inside the first glass tube 4. One side of the U-shaped dual-phase composite magnetic core 2 passes through the second glass tube 5, and the other side passes through the interlayer between the first and second glass tubes 4. The U-shaped dual-phase composite magnetic core 2 avoids mutual conductivity by passing through different glass tubes. The voltage signal pickup coil 3 is wound around the first glass tube 4. The voltage signal pickup coil 3, the U-shaped dual-phase composite magnetic core 2, and the PCB printed circuit board 6 are soldered together.

[0039] The magnetic sensing test system for biomolecule detection using the orthogonal fluxgate probe comprises a signal conditioning circuit board 9 connected to a PCB printed circuit board 6. A reaction channel chip 8 is positioned directly above the U-shaped two-phase composite magnetic core 2. The signal conditioning circuit board 9, the U-shaped two-phase composite magnetic core 2, and the reaction channel chip 8 are all housed inside a Helmholtz coil 7, forming the magnetic sensing test system for biomolecule detection. The reaction channel chip 8 carries the biological sample to be tested, which contains magnetic markers. A voltage signal pickup coil 3 is used to pick up the magnetic field signals before and after the placement of the magnetic markers in the biological sample. By recording the voltage difference before and after detecting the magnetic signal of the biological sample, the content of the detected molecules is obtained.

[0040] The molecular assay method using the aforementioned magnetic sensing assay system, employing 1 μm diameter superparamagnetic beads, with any biomolecule to be detected as the target biomarker and antibodies or antigens corresponding to the target biomarker as the capture molecules, includes the following steps:

[0041] Step a: Surface functionalization treatment: The reaction channel chip 8 is prepared on a glass substrate. The glass is silanized with 3-aminopropyltriethoxysilane (APTES) solution to introduce amino functional groups on the glass surface. These amino functional groups are used to covalently couple the target biomarkers in the biological sample to be tested to form a stable active interface. Subsequently, the biological sample to be tested is introduced. After incubation, washing and sealing steps, only the specific recognition sites are retained, thereby effectively improving the detection signal-to-noise ratio.

[0042] Step b: Magnetic marker capture and signal detection: The magnetic marker is magnetic bead 10. Based on the diameter of the magnetic bead 10 and the concentration of the original stock solution of the biological sample to be tested, the working concentration of the magnetic bead suspension (10 times the highest concentration of the sample to be tested) is determined by statistical methods. 2 (Multiple times), magnetic beads 10 coated with specific antibodies against the target biomarker are introduced into the reaction channel chip 8, which has undergone surface functionalization treatment in step a. After incubation and cleaning, the magnetic beads that bind only through specific recognition are captured and fixed on the chip surface. The Helmholtz coil 7 is connected to a constant current power supply to generate an excitation magnetic field. First, when the reaction channel chip 8 is not placed on the U-shaped biphase composite magnetic core 2, the voltage signal pickup coil 3 of the orthogonal fluxgate probe is used to detect the background magnetic signal above the U-shaped biphase composite magnetic core 2, and the output voltage A is recorded. Then, the reaction channel chip 8 with the fixed magnetic beads is placed above the U-shaped biphase composite magnetic core 2 to magnetize the magnetic beads. The voltage signal pickup coil 3 detects the magnetic signal again and records the output voltage B. By comparing the changes in output voltage A and B, the presence or concentration of the target biomarker is determined.

[0043] Step c: Concentration gradient detection and quantitative analysis: When the presence of the target biomarker is confirmed in step b, solutions of the target biomolecules at different concentrations are prepared. A reaction channel chip 8 is fabricated according to step a. Magnetic bead suspensions of the same working concentration as in step b are added dropwise, incubated, and then cleaned. Under the condition that the Helmholtz coil 7 is energized to generate an excitation magnetic field, the output voltage C is first detected using the voltage signal pickup coil 3 when the reaction channel chip 8 is not placed. Subsequently, reaction channel chips 8 incubated with different concentrations of target biomolecule solutions are sequentially replaced and placed above the U-shaped biphase composite magnetic core 2 to magnetize the magnetic beads. The voltage signal pickup coil 3 detects the magnetic signal. Each concentration of target biomolecule solution incubated with the reaction channel chip 8 corresponds to one output voltage, recorded as D1, D2, D3, D4… (ellipsis indicates more than 4 detections, limited to the number of times that a person skilled in the art can achieve the testing objective). Based on the changes in output voltage C and D1, D2, D3, D4…, a correspondence between the voltage signal change and the concentration of the target biomolecule solution is established, thereby achieving quantitative detection of the target biomarker. Example 2

[0044] A method for fabricating a two-phase composite magnetic core, comprising the following specific steps:

[0045] Step a: Fold a silver wire substrate with a purity of 4N and a length of 11cm into a U-shape, wherein the diameter of the silver wire is 100 micrometers;

[0046] Step b: The cathode silver wire is pretreated before electrochemical deposition, specifically: wash with deionized water for 10 min → wash with weak alkaline solution (45 g / L sodium carbonate solution) for 10 min → wash with deionized water for 10 min → wash with acid solution (prepared with 2 mL concentrated hydrochloric acid / 50 mL deionized water) for 15 min → wash with deionized water for 10 min.

[0047] Step c: Prepare an electrolyte solution for depositing the CoP amorphous magnetic layer. The solution composition is: 0.05 mol / L NiSO4·6H2O, 0.5 mol / L CoSO4·6H2O, 0.5 mol / L NaH2PO2·6H2O, 0.2 mol / L Na3C6H5O7·2H2O, 0.15 mol / L C4H4Na2O6·2H2O, and 0.5 mol / L (NH4)2SO4. After preparing the solution according to the above proportions, weigh out NaOH and add it to adjust the pH to 7. Electrochemical deposition is then performed using a potentiostatic deposition method.

[0048] Step d: Deposition was performed using a three-electrode method, with a deposition current density of approximately 1 A / dm³. 2The electrolyte is heated to 95°C. Then, the silver wire, calomel electrode, and platinum sheet electrode, which are clamped by a fixture, are placed into the electrolyte. The deposition time is 7500 seconds, and the thickness of each coating layer is 12 micrometers. During electrochemical deposition, the U-shaped bend of the pretreated silver wire is shielded by a fixture to prevent CoP from being deposited on the U-shaped bend.

[0049] Step e: After electrochemical deposition, the U-shaped composite magnetic core is removed, the surface solution is wiped clean with degreased cotton, and annealed with DC current. The magnetic core is vertically suspended in the air for annealing using an electrode clamp carrying DC current. The CoP / Ag is stressed by the weight of the electrode clamp (30 g). The annealing current is 1.8 A and the annealing time is 15 min. The CoP temperature is increased by heating with current. The high-temperature CoP reacts with air to achieve partial crystallization, forming 10-20 nm nanocrystals in the amorphous phase, thus producing a two-phase structure.

[0050] An orthogonal fluxgate probe containing a two-phase composite magnetic core has the same structure as in Example 1.

[0051] The magnetic sensing test system for detecting biomolecules using the orthogonal fluxgate probe has the same structure as in Example 1.

[0052] The molecular testing method using the magnetic sensing testing system described above follows the same steps as in Example 1, except that the diameter of the superparamagnetic beads used is 100 nm. Example 3

[0053] A method for fabricating a two-phase composite magnetic core, comprising the following specific steps:

[0054] Step a: Fold a silver wire substrate with a purity of 4N and a length of 11cm into a U-shape, wherein the diameter of the silver wire is 60 micrometers;

[0055] Step b: The cathode silver wire is pretreated before electrochemical deposition, specifically: wash with deionized water for 10 min → wash with weak alkaline solution (40 g / L sodium carbonate solution) for 10 min → wash with deionized water for 10 min → wash with acid solution (prepared with 2 mL concentrated hydrochloric acid / 50 mL deionized water) for 15 min → wash with deionized water for 10 min.

[0056] Step c: Prepare an electrolyte solution for depositing the CoP amorphous magnetic layer. The solution composition is: 0.05 mol / L NiSO4·6H2O, 0.5 mol / L CoSO4·6H2O, 0.8 mol / L NaH2PO2·6H2O, 0.2 mol / L Na3C6H5O7·2H2O, 0.15 mol / L C4H4Na2O6·2H2O, and 0.5 mol / L (NH4)2SO4. After preparing the solution according to the above proportions, weigh out NaOH and add it to adjust the pH to 7. Electrochemical deposition is then performed using a potentiostatic deposition method.

[0057] Step d: Deposition was performed using a three-electrode method, with a deposition current density of approximately 0.8 A / dm³. 2 The electrolyte is heated to 95°C. Then, the silver wire, calomel electrode, and platinum sheet electrode, which are clamped by a fixture, are placed into the electrolyte. The deposition time is 6500 seconds, and the thickness of each coating layer is 10 micrometers. During electrochemical deposition, the U-shaped bend of the pretreated silver wire is shielded by a fixture to prevent CoP from being deposited on the U-shaped bend.

[0058] Step e: After electrochemical deposition, the U-shaped composite magnetic core is removed, the surface solution is wiped clean with degreased cotton, and annealed with DC current. The magnetic core is vertically suspended in the air for annealing using an electrode clamp carrying DC current. The CoP / Ag is stressed by the weight of the electrode clamp (10 g). The annealing current is 1.7 A and the annealing time is 10 min. The CoP temperature is increased by heating with current. The high-temperature CoP reacts with air to achieve partial crystallization, forming 10-20 nm nanocrystals in the amorphous phase, thus producing a two-phase structure.

[0059] An orthogonal fluxgate probe containing a two-phase composite magnetic core has the same structure as in Example 1.

[0060] The magnetic sensing test system for detecting biomolecules using the orthogonal fluxgate probe has the same structure as in Example 1.

[0061] The molecular testing method using the magnetic sensing testing system described above follows the same steps as in Example 1, except that the diameter of the superparamagnetic beads used is 1 μm.

Claims

1. A method for preparing a two-phase composite magnetic core, characterized in that: The dual-phase composite magnetic core uses a 4N pure silver wire as a substrate, with a diameter of 20-140 μm. An amorphous CoP phase is electrochemically deposited on the silver wire to obtain the magnetic core; the CoP thickness is 4-16 μm, and the electrolyte used for electrochemical deposition contains Co. 2+ CoP and hypophosphate ions were used to anneal the magnetic core by electric heating in an air environment. CoP reacted with the air to form partial crystallization, resulting in a two-phase composite magnetic core.

2. The method for preparing a two-phase composite magnetic core according to claim 1, characterized in that: The electrolyte composition is: 0.05 mol / L NiSO4·6H2O, 0.5 mol / L CoSO4·6H2O, 0.2-0.8 mol / L NaH2PO2·6H2O, 0.2 mol / L Na3C6H5O7·2H2O, 0.15 mol / L C4H4Na2O6·2H2O, and 0.5 mol / L (NH4)2SO4. After the electrolyte is prepared, the pH value of the electrolyte is adjusted to 7 with NaOH, and electrochemical deposition is carried out using the constant potential deposition method.

3. The method for preparing a two-phase composite magnetic core according to claim 1, characterized in that: During the electrochemical deposition, the electrolyte temperature is 65℃-95℃, the pH is 7-9.5, the deposition time is 3000-8500 seconds, and the deposition current density is 0.6-2 A / dm³. 2 .

4. The method for preparing a two-phase composite magnetic core according to claim 1, characterized in that: When annealing the magnetic core, the magnetic core is vertically suspended in the air using an electrode clamp carrying a direct current. The CoP / Ag is stressed by the gravity of the electrode clamp itself. The annealing current is 1.6-2 A and the annealing time is 10-20 min. The annealing process causes 10-20 nm nanocrystals to form in the amorphous phase, thereby producing a two-phase structure.

5. The method for preparing a two-phase composite magnetic core according to claim 1, characterized in that: Before electrochemical deposition, the silver wire is pretreated as follows: wash with deionized water for 5-10 min → wash with weak alkaline solution for 10-15 min → wash with deionized water for 5-10 min → wash with acid solution for 10-15 min → wash with deionized water for 5-10 min. The weak alkaline solution is a 40-45 g / L sodium carbonate solution, and the acid solution is a hydrochloric acid solution prepared by mixing 2 mL of concentrated hydrochloric acid with 50 mL of deionized water.

6. The two-phase composite magnetic core prepared by the method for preparing a two-phase composite magnetic core according to claim 5, characterized in that: The dual-phase composite core is U-shaped, and CoP is not deposited in the U-shaped bend.

7. An orthogonal fluxgate probe containing the dual-phase composite magnetic core of claim 6, characterized in that: The device includes a U-shaped two-phase composite magnetic core (2), a voltage signal pickup coil (3), a second glass tube (5) and a first glass tube (4), and a PCB printed circuit board (6). The second glass tube (5) is fitted inside the first glass tube (4). One side of the U-shaped two-phase composite magnetic core (2) is inserted into the second glass tube (5), and the other side is inserted into the interlayer between the first glass tube (4) and the second glass tube (5). The voltage signal pickup coil (3) is wound on the first glass tube (4). The voltage signal pickup coil (3), the U-shaped two-phase composite magnetic core (2), and the PCB printed circuit board (6) are soldered together.

8. A magnetic sensing testing system for biomolecular detection using the orthogonal fluxgate probe of claim 7, characterized in that: The orthogonal fluxgate probe is equipped with a signal conditioning circuit board (9), which is connected to a PCB printed circuit board (6). A reaction channel chip (8) is set directly above the U-shaped two-phase composite magnetic core (2). The signal conditioning circuit board (9), the U-shaped two-phase composite magnetic core (2), and the reaction channel chip (8) are placed inside the Helmholtz coil (7) to form a magnetic sensing test system for biomolecule detection. The reaction channel chip (8) is used to carry the biological sample to be tested. The biological sample to be tested contains magnetic markers. The voltage signal pickup coil (3) is used to pick up the magnetic field signal before and after the magnetic markers in the biological sample to be tested are placed. By recording the voltage difference before and after the detection of the biological magnetic signal, the content of the detected molecules is obtained.

9. A molecular testing method using the magnetic sensing testing system of claim 8, characterized in that, Includes the following steps: Step a: Surface functionalization treatment: The reaction channel chip (8) is prepared on glass as a substrate. The glass is silanized by 3-aminopropyltriethoxysilane solution to introduce amino functional groups on the glass surface. The amino functional groups are used to covalently couple the target biomarkers in the biological sample to be tested to form a stable active interface. The biological sample to be tested is then introduced. After incubation, washing and sealing steps, only the specific recognition sites are retained. Step b: Magnetic marker capture and signal detection: The magnetic marker is a magnetic bead (10). Based on the diameter of the magnetic bead (10) and the concentration of the original stock solution of the biological sample to be tested, the working concentration of the magnetic bead suspension is determined by statistical methods. The magnetic beads (10) coated with the specific antibody of the biomarker to be tested are introduced into the reaction channel chip (8) that has undergone surface functionalization treatment in step a. After incubation and washing, the magnetic beads that bind only through specific recognition are captured and fixed on the chip surface. The Helmholtz coil (7) is connected to the constant current power supply, and an excitation magnetic field is generated when the power is turned on. First When no reaction channel chip (8) is placed on the U-shaped two-phase composite magnetic core (2), the voltage signal pickup coil (3) of the orthogonal fluxgate probe is used to detect the background magnetic signal above the U-shaped two-phase composite magnetic core (2) and record the output voltage A; then the reaction channel chip (8) with the magnetic bead fixed is placed above the U-shaped two-phase composite magnetic core (2) to magnetize the magnetic bead, and the voltage signal pickup coil (3) detects the magnetic signal again and records the output voltage B. By comparing the changes in output voltage A and B, the presence or concentration of the target biomarker can be determined. Step c: Concentration gradient detection and quantitative analysis: When the presence of the target biomarker is confirmed in step b, different concentrations of target biomolecule solutions are prepared, and reaction channel chips (8) are made according to step a. Magnetic bead suspensions with the same working concentration as in step b are added dropwise, incubated, and then cleaned. Under the condition that the Helmholtz coil (7) generates an excitation magnetic field, the voltage signal pickup coil (3) is first used to detect the output voltage C when no reaction channel chip (8) is placed. Then, the reaction channel chips (8) incubated with different concentrations of target biomolecule solutions are replaced in sequence and placed above the U-shaped biphase composite magnetic core (2) to magnetize the magnetic beads. The voltage signal pickup coil (3) detects the magnetic signal. Each concentration of target biomolecule solution incubated with the reaction channel chip (8) corresponds to an output voltage, recorded as D1, D2, D3, D4... According to the changes in output voltage C and D1, D2, D3, D4..., the correspondence between the voltage signal change and the concentration of the target biomolecule solution is established, thereby realizing the quantitative detection of the target biomarker.

10. The molecular testing method according to claim 9, characterized in that: The magnetic beads (10) are superparamagnetic beads with a diameter of 100 nm to 1 μm; the target biomarker is any biomolecule to be detected, and the captured molecule is an antibody or antigen corresponding to the target biomarker.

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