Biosensor based on exchange coupling effect and magneto-elastic coupling effect and preparation method thereof

Abstract

The application provides a biosensor based on exchange coupling effect and magnetic elastic coupling effect and a preparation method thereof, and belongs to the field of biosensors. The biosensor comprises, from bottom to top, a flexible substrate, a silver interdigital electrode prepared by a magnetron sputtering process arranged on the surface of the flexible substrate, a PDMS stress transfer layer arranged on the interdigital electrode, a magnetic sensitive unit composed of magnetostrictive layers and soft magnetic layers alternately stacked, and a gold biological interface layer arranged on the topmost layer. The application significantly reduces the interface impedance and optimizes the signal collection efficiency by introducing the silver interdigital electrode. The weak surface stress generated by the combination of biological molecules is efficiently converted into a significant change in magnetic anisotropy by utilizing the synergistic effect of exchange coupling and magnetostrictive effect in the magnetic multilayer film. The biosensor not only solves the problem of slow response to surface stress of traditional devices, but also has excellent mechanical flexibility, high signal-to-noise ratio and high sensitivity, and is suitable for label-free detection of complex biological samples.

Description

Technical Field

[0001] This application relates to the field of biosensor technology, and in particular to a biosensor based on exchange coupling effect and magnetoelastic coupling effect and its fabrication method. Background Technology

[0002] Biosensors are a core technology in fields such as disease diagnosis and environmental monitoring. While mainstream optical (such as surface plasmon resonance) and electrochemical biosensors perform well in laboratory environments, their signals are easily interfered with by complex sample matrices (such as ionic strength and turbidity), and the devices are often difficult to miniaturize and integrate at low cost, which severely restricts their widespread application in point-of-care testing scenarios.

[0003] To overcome these problems, mass-sensitive sensors (such as quartz crystal microbalances) and emerging magnetoelastic sensors have attracted attention. However, these sensors mainly rely on detecting the mass load resulting from biomolecular binding, and their signals are significantly attenuated in liquid environments. More importantly, they are extremely insensitive to another key physical change in biorecognition—surface stress—which is a more direct and sensitive dimension characterizing intermolecular interactions. This leads to fundamental limitations in the detection sensitivity and dimensionality of existing technologies.

[0004] Specifically, in the field of magnetic sensors, existing designs mostly employ a single magnetostrictive material or a simple bilayer structure. This simplistic configuration fails to fully utilize the magnetic anisotropy in the magnetic thin film—a physical quantity highly sensitive to stress—as a detection signal. Furthermore, it lacks the ability to synergistically combine exchange coupling and magnetostrictive effects through microstructural design, resulting in low stress-magnetic signal conversion efficiency and hindering performance improvement. Therefore, there is an urgent need in this field for a novel magnetic sensing element structure capable of efficiently sensing surface stress and possessing a high signal-to-noise ratio and excellent anti-interference capabilities. Summary of the Invention

[0005] To address the issues of sluggish response and low sensitivity of existing magnetic sensors to surface stress induced by biomolecule binding, this application proposes a biosensor based on exchange coupling and magnetoelastic coupling effects and its fabrication method. This approach effectively overcomes the shortcomings of existing technologies and has significant development potential.

[0006] The technical solution adopted in this application is: a biosensor based on exchange coupling effect and magnetoelastic coupling effect, comprising a substrate layer, a stress sensing layer, a magnetic sensitive unit and a bio-interface layer arranged sequentially from bottom to top, wherein the magnetic sensitive unit is composed of a periodic multilayer film of alternating stacked magnetostrictive layer and soft magnetic layer.

[0007] Furthermore, the total number of periods in the periodic multilayer film of the magnetic sensing unit is 3 to 20, and the total thickness is 50-300 nm.

[0008] Furthermore, the magnetostriction coefficient λS of the magnetic sensitive unit is ≥70ppm, and the surface roughness Ra is <2nm.

[0009] Furthermore, the magnetostrictive layer is made of FeGa alloy with a high magnetostriction coefficient, and the soft magnetic layer is made of CoFe alloy or NiFe alloy with low coercivity.

[0010] Furthermore, the substrate layer is a flexible electrode substrate on which interdigitated electrodes are deposited.

[0011] Furthermore, the stress sensing layer uses a highly elastic PDMS film with a thickness of 5-20 micrometers.

[0012] Furthermore, the bio-interface layer uses a gold film, which immobilizes bio-recognition molecules through chemical bonding and undergoes surface modification treatment, resulting in a surface roughness Ra < 1 nm.

[0013] A method for fabricating a biosensor based on exchange coupling and magnetoelastic coupling effects includes the following steps: S1. Forming interdigitated electrodes in flexible thin film processing; S2. Preparation of stress transfer layer: Mix PDMS A and B adhesives according to the set weight ratio, degas, spin coat onto the substrate and cure. S3, Magnetic Sensitive Unit Deposition: Alternating deposition of magnetostrictive and soft magnetic layers on the stress transfer layer; S4. Preparation of bio-interface layer: Deposition of gold film on magnetic sensitive unit; S5. Biofunctionalization: Immobilize biorecognition molecules on the surface of a gold film in a biointerface layer.

[0014] Furthermore, in steps S3 and S4, magnetron sputtering is used to deposit a magnetostrictive layer, a soft magnetic layer, and a gold film.

[0015] Furthermore, in step S3, a magnetostrictive layer is first deposited on the stress transfer layer, followed by a soft magnetic layer, and then the magnetostrictive layer and the soft magnetic layer are deposited alternately.

[0016] The advantages of this application over the prior art are as follows: 1. Ultra-high sensitivity based on synergistic amplification of "exchange coupling" and "magnetic elastic coupling": This application creatively utilizes the synergistic gain mechanism of exchange coupling and magnetostriction effects in magnetic multilayer films. Through the strong exchange coupling between the soft magnetic layer (CoFe / NiFe) and the magnetostrictive layer (FeGa) at the interface, the low coercivity of the soft magnetic layer effectively "softens" the hard magnetic phase and reduces the overall magnetic anisotropy field, making the magnetic moment highly susceptible to external perturbations. Simultaneously, the FeGa layer utilizes its high magnetostriction coefficient to capture the weak surface stress generated by the binding of biomolecules. The synergistic effect of these two effects efficiently "amplifies" nano-Newton (nN) level micro-stress into significant macroscopic magnetic anisotropy changes, thereby achieving ultra-high sensitivity detection without the need for complex circuit amplification.

[0017] 2. Extremely high signal-to-noise ratio and excellent anti-interference stability: This application achieves extremely low interface roughness through optimized processes and combines it with the characteristics of a soft magnetic layer, effectively suppressing the magnetic domain wall pinning effect at the microscopic level, significantly improving signal linearity and signal-to-noise ratio. Simultaneously, the detection mechanism based on the intrinsic magnetic properties of the material makes it naturally immune to sample color, turbidity, ionic strength, and pH value. Combined with the aforementioned low-noise characteristics, this ensures extremely high detection accuracy and stability of the sensor in complex biological samples such as serum and whole blood.

[0018] 3. Excellent flexibility and integration potential: By introducing PDMS as a stress transfer layer, not only can its low Young's modulus properties enable efficient transfer and buffering of biological stress, but it also endows the sensor with excellent mechanical flexibility. Combined with a flexible substrate, this sensor can adapt to curved surfaces and is easily integrated into wearable devices or microfluidic chips to meet the needs of real-time detection.

[0019] 4. Optimized electrode structure and performance: The interdigitated electrode structure is used as the bottom conductive network, which significantly increases the effective contact area between the electrode and the functional layer above (fingertip edge effect) compared with traditional planar electrodes, thereby effectively reducing interface impedance and improving signal collection efficiency. At the same time, the silver electrode prepared by magnetron sputtering has excellent conductivity and density, and strong adhesion to the PET flexible substrate. It can still maintain stable electrical performance when the sensor undergoes bending deformation, further enhancing the reliability of the device in flexible wearable scenarios. Attached Figure Description

[0020] The following description, in conjunction with the accompanying drawings, further illustrates this application: Figure 1 This is a schematic diagram of the sensor structure provided in an embodiment of this application; In the figure: 1 is the base layer, 2 is the stress transmission layer, 3 is the magnetic sensitive unit, 4 is the biological interface layer, 31 is the magnetostrictive layer, and 32 is the soft magnetic layer. Detailed Implementation

[0021] like Figure 1 As shown, this application provides a biosensor based on exchange coupling effect and magnetoelastic coupling effect, comprising: Substrate 1: Employs a flexible electrode substrate to support the sensor structure and provide conductive connections; Stress transfer layer 2: Located above the base layer 1, it is composed of polydimethylsiloxane (PDMS) and is used to transfer surface stress; Magnetic sensitive unit 3: Covered on stress transmission layer 2, it is composed of a multilayer film consisting of alternating stacks of magnetostrictive layer 31 and soft magnetic layer 32; Bio-interface layer 4: Located on the top layer of magnetic sensitive unit 3, it is composed of a gold film and is used to immobilize bio-recognition molecules.

[0022] The flexible electrode substrate of the base layer 1 is made of PET or other equivalent electrodes.

[0023] The stress transfer layer 2 is a highly elastic PDMS film with a thickness of 5-20 micrometers, prepared by spin coating at a speed of 1500-3000 rpm and cured at 110-130℃ for 10-15 minutes. This stress transfer layer 2, prepared by spin coating, has a thickness sufficient to effectively transfer surface stress generated by biomolecule bonding to the magnetically sensitive unit 3, and has a smooth surface.

[0024] The magnetic sensing unit 3 is a periodic multilayer film structure, wherein the magnetostrictive layer 31 is made of FeGa alloy with a high magnetostriction coefficient, and the soft magnetic layer 32 is made of CoFe alloy or NiFe alloy with low coercivity. This structure utilizes the exchange coupling effect at the interlayer interface and the magnetostrictive effect of the FeGa layer to synergistically enhance the magnetic response capability to force.

[0025] In this embodiment, the total number of cycles of the magnetic sensing unit 3 is 3 to 20, and the total thickness is 50-300 nm (the specific number of layers and thickness can be adjusted according to the biomolecules being detected, as long as the number of cycles and the total thickness of the multilayer film can generate a significant ferromagnetic resonance signal). Furthermore, the magnetostriction coefficient λS of the magnetic sensing unit 3 is ≥70 ppm, and the surface roughness Ra is <2 nm. The low surface roughness of the magnetic sensing unit 3 reduces the domain wall pinning effect, ensuring soft magnetic properties and stress sensitivity.

[0026] The bio-interface layer 4 is an ultrathin gold film deposited on the surface of the magnetically sensitive unit 3. The gold film fixes the bio-recognition molecules through chemical bonding and undergoes surface modification treatment to reduce non-specific adsorption.

[0027] Biofunctionalization processes include amination, antibody fixation, and blocking on the surface of biointerface layer 4, thereby constructing a biosensing surface with specific recognition functions.

[0028] In this embodiment, the thickness of the gold film in the bio-interface layer 4 is 50-200 nm, and the surface roughness Ra<1 nm.

[0029] This application also proposes a method for fabricating a biosensor based on exchange coupling and magnetoelastic coupling effects, comprising the following steps: S1, Substrate 1 Processing: A silver layer is deposited on a PET film by magnetron sputtering and patterned into interdigitated electrodes.

[0030] S2, Preparation of stress transfer layer 2: Mix PDMS A and B adhesives at a weight ratio of 10:1, degas, spin coat onto base layer 1 and cure; By controlling the spin coating speed and curing temperature, a stress transfer layer 2 with uniform thickness and complete curing can be obtained.

[0031] S3, Magnetic Sensing Unit 3 Deposition: Magnetostrictive layer 31 and soft magnetic layer 32 are alternately deposited on stress transfer layer 2 by magnetron sputtering process; The interface quality between the magnetostrictive layer 31 and the soft magnetic layer 32 can be controlled by optimizing the sputtering power, gas pressure and substrate temperature to enhance the exchange coupling between the layers.

[0032] S4, Bio-interface layer 4 preparation: A gold film is deposited on the magnetically sensitive unit 3 by magnetron sputtering; a low-temperature deposition process can be used to prepare the gold film to prevent high temperature from damaging the microstructure of the underlying magnetic film.

[0033] S5. Biofunctionalization: Immobilize biorecognition molecules on the gold film surface of biointerface layer 4.

[0034] This embodiment provides a specific preparation method, including: S1. Preparation of the flexible electrode substrate, including: S1.1 Take a clean, flexible PET (polyethylene terephthalate) film with a thickness of approximately 100-200 micrometers.

[0035] S1.2. A silver (Ag) film is deposited on the surface of a PET film as a conductive layer using a magnetron sputtering process, and then patterned into interdigitated electrodes using a mask or photolithography lift-off process to form the substrate layer 1.

[0036] The preparation and curing of S2 and PDMS stress transfer layer 2 include: S2.1 Using Sylgard 184 and Dow Corning as raw materials, accurately weigh and mix A glue and B glue in a weight ratio of 10:1 in a beaker and stir evenly. S2.2 Place the mixture in a degassing machine for degassing treatment until no obvious bubbles are generated in the container. Let the degassed mixture stand for 10-15 minutes. S2.3. Fix substrate 1 onto the base of the spin coater. Drop an appropriate amount of PDMS mixture onto the center of substrate 1, and then start the single-step spin coating program. By controlling the rotation speed and time, a PDMS film of the target thickness (approximately 8 μm) can be obtained. S2.4 Transfer the spin-coated sample to a horizontal baking table and cure at 110-130℃ for 10-15 minutes. After curing, allow it to cool naturally to room temperature.

[0037] The fabrication of S3 and magnetic sensitive unit 3 (magnetron sputtering) includes: S3.1. FeGa / CoFe alloy was alternately sputtered onto the sample spin-coated with PDMS using a magnetron sputtering process.

[0038] S3.2, Magnetron sputtering parameters: Target material: Fe 0.8 Ga 0.2 Alloy target (purity 99.99%); sputtering gas: Ar (purity 99.999%), pressure 3 mTorr; power: DC 200W, substrate temperature 50℃; thin film characteristics: deposition thickness 200nm, magnetostriction coefficient λS=70ppm, surface roughness Ra<2nm.

[0039] S3.3 Repeat the above steps, alternating between depositing FeGa and CoFe layers, up to 3 to 20 layers. (Alternative: FeGa / NiFe multilayer films can be used with a NiFe alloy target, and the deposition parameters are the same as those for the CoFe layers described above).

[0040] S4. Preparation of the bio-interface layer (gold film) (magnetron sputtering), including: S4.1 Sputtering of a gold target onto a sample on which magnetic sensitive unit 3 has been prepared using magnetron sputtering.

[0041] S4.2 Magnetron sputtering parameters: Target material: Au metal target (purity 99.99%); Sputtering gas: Ar (purity 99.999%), gas pressure 3mTorr; Power: DC 50W, substrate temperature 200℃; Thin film characteristics: deposition thickness 50nm, surface roughness Ra<1nm.

[0042] S5. Biomodification of the sensor surface, including: S5.1 Amination Treatment: The biosensor was immersed in a 4 mmol / L aqueous solution of mercaptoethylamine and reacted at 4°C for 8 hours. After completion, it was washed with deionized water and dried.

[0043] S5.2 Antibody fixation: The antibody solution activated by EDC / NHS was dropped onto the sensor surface and incubated at 37°C for 2 hours. Then, excess solution was removed and the sensor was washed and dried.

[0044] S5.3 Sealing: Add 0.1% bovine serum albumin (BSA) solution dropwise to the sensor surface and react at 37°C for 1 hour. Finally, clean and dry.

[0045] This application significantly reduces interfacial impedance and optimizes signal collection efficiency by introducing silver interdigitated electrodes. Utilizing the synergistic effect of exchange coupling and magnetostriction in a magnetic multilayer film, it efficiently converts the weak surface stress generated by biomolecule bonding into a significant change in magnetic anisotropy. This sensor not only solves the problem of sluggish response to surface stress in traditional devices but also possesses excellent mechanical flexibility, high signal-to-noise ratio, and high sensitivity, making it suitable for label-free detection of complex biological samples.

[0046] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A biosensor based on exchange coupling effect and magnetoelastic coupling effect, characterized in that: It includes a base layer, a stress sensing layer, a magnetic sensing unit, and a bio-interface layer arranged sequentially from bottom to top. The magnetic sensing unit is composed of a periodic multilayer film consisting of alternating layers of magnetostrictive and soft magnetic layers.

2. A biosensor based on exchange coupling effect and magnetoelastic coupling effect according to claim 1, characterized in that: The total number of periods in the periodic multilayer film of the magnetic sensing unit is 3 to 20, and the total thickness is 50-300 nm.

3. A biosensor based on exchange coupling effect and magnetoelastic coupling effect according to claim 2, characterized in that: The magnetostriction coefficient λS of the magnetic sensitive unit is ≥70ppm, and the surface roughness Ra is <2nm.

4. A biosensor based on exchange coupling effect and magnetoelastic coupling effect according to claim 3, characterized in that: The magnetostrictive layer is made of FeGa alloy with a high magnetostriction coefficient, and the soft magnetic layer is made of CoFe alloy or NiFe alloy with low coercivity.

5. A biosensor based on exchange coupling effect and magnetoelastic coupling effect according to any one of claims 2-4, characterized in that: The substrate is a flexible electrode substrate on which interdigitated electrodes are deposited.

6. A biosensor based on exchange coupling effect and magnetoelastic coupling effect according to claim 5, characterized in that: The stress sensing layer uses a highly elastic PDMS film with a thickness of 5-20 micrometers.

7. A biosensor based on exchange coupling effect and magnetoelastic coupling effect according to claim 6, characterized in that: The bio-interface layer uses a gold film, which immobilizes bio-recognition molecules through chemical bonding and undergoes surface modification treatment, resulting in a surface roughness Ra < 1 nm.

8. A method for fabricating a biosensor based on exchange coupling effect and magnetoelastic coupling effect as described in any one of claims 1-7, characterized in that: Includes the following steps: S1. Forming interdigitated electrodes in flexible thin film processing; S2. Preparation of stress transfer layer: Mix PDMS A and B adhesives according to the set weight ratio, degas, spin coat onto the substrate and cure. S3, Magnetic Sensitive Unit Deposition: Alternating deposition of magnetostrictive and soft magnetic layers on the stress transfer layer; S4. Preparation of bio-interface layer: Deposition of gold film on magnetic sensitive unit; S5. Biofunctionalization: Immobilize biorecognition molecules on the surface of a gold film in a biointerface layer.

9. The method for fabricating a biosensor based on exchange coupling effect and magnetoelastic coupling effect according to claim 8, characterized in that: In steps S3 and S4, magnetron sputtering is used to deposit a magnetostrictive layer, a soft magnetic layer, and a gold film.

10. The method for fabricating a biosensor based on exchange coupling effect and magnetoelastic coupling effect according to claim 9, characterized in that: In step S3, a magnetostrictive layer is first deposited on the stress transfer layer, followed by a soft magnetic layer, and then the magnetostrictive layer and the soft magnetic layer are deposited alternately.

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