Integrated piezoelectric sensing module based on immunoaffinity reaction and application
By integrating magnetic layers and immune magnetic beads in the piezoelectric sensor, and using magnetic fields and sound waves to achieve sensor reuse, the problem of traditional piezoelectric sensors being unreusable is solved, reducing costs and improving sensitivity and separation capabilities.
Patent Information
- Application Number
- CN202411541916.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-31
- Publication Date
- 2025-01-10
AI Technical Summary
Traditional piezoelectric sensors based on immune affinity reactions cannot be reused and have high manufacturing and use costs, which limits their widespread promotion in hospitals and clinics.
An integrated piezoelectric sensing module based on immune affinity reaction was designed, using magnetic layers to integrate them inside the piezoelectric sensor, using magnetic field force to make the immune magnetic beads come into contact with the sensor surface, and removing the magnetic beads through liquid erosion and sound waves. Implement sensor multiplexing.
It reduces the manufacturing and use costs of the sensor, improves sensitivity, and achieves separation of target objects and mass sensing and simplifies the module structure.
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Figure CN119290993A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of piezoelectric sensors, and in particular relates to an integrated piezoelectric sensing module based on immunoaffinity reaction and its application. Background Art
[0002] Piezoelectric sensors are devices that convert received acoustic signals into electrical signals through the piezoelectric effect. Piezoelectric sensors can characterize a variety of physical quantities such as temperature, stress, and mass. The principle is that when sound waves pass through the target medium, changes in the medium will affect the sound wave characteristics such as sound velocity and sound intensity. By measuring the changes in acoustic characteristics, the physical quantities that affect sound propagation can be indirectly characterized. With the advancement of micro-nano processing technology and the increasing perfection of piezoelectric material preparation technology, piezoelectric sensors based on piezoelectric resonators have significant advantages in miniaturization and integration, and are widely used in the fields of medical health and biological sciences. Piezoelectric resonators used in the field of sensing are mainly surface acoustic wave resonators and bulk acoustic wave resonators. Surface acoustic wave resonators usually select piezoelectric single crystal substrates such as lithium niobate, lithium tantalate, and bismuth germanate, and use interdigital electrodes to excite sound waves on the surface of the piezoelectric single crystal substrate. Bulk acoustic wave resonators usually select piezoelectric thin films such as aluminum nitride, and use top and bottom electrodes to excite sound waves in the piezoelectric thin film. The electrode materials of surface acoustic wave resonators and bulk acoustic wave resonators are usually gold, aluminum, copper, titanium, palladium, chromium, molybdenum, and platinum.
[0003] Immunoaffinity reaction is the reaction process of specific binding between antigen and antibody. Antigen and antibody with strong affinity can react quickly at low concentrations. This property makes it the basis of many biological experiments and clinical tests. Immunomarkers can bind to the target through immunoaffinity reaction. Immunomarkers can be fixed on the surface of the substrate or on the surface of microbeads. They are free in the liquid with the microbeads. Such microbeads are called immunomagnetic beads. Immunobeads with magnetic particles as the core are called immunomagnetic beads, which can be attracted by magnetic materials.
[0004] Traditional piezoelectric sensors based on immunoaffinity reactions fix immune markers on the surface of the piezoelectric substrate. The mass loading effect caused by the capture of the target by the immune marker will affect the resonant frequency of the sound wave, and the offset of the resonant frequency is used to characterize the total mass of the target. The disadvantages of the above sensors are that there is a saturation effect in the capture of the target, the sensors are difficult to reuse, the manufacturing and use costs are high, and they cannot be widely promoted in hospitals and clinics. Therefore, a new piezoelectric sensing module with reusable sensors is needed. Summary of the invention
[0005] In order to solve the technical problem that piezoelectric sensors based on immunoaffinity reactions in the prior art are not reusable, the present invention provides an integrated piezoelectric sensing module based on immunoaffinity reactions and applications.
[0006] In order to achieve the above object, the present invention adopts the following technical solutions:
[0007] An integrated piezoelectric sensing module based on immunoaffinity reaction includes a piezoelectric sensor and a plurality of immunomagnetic beads that bind to a target object. A flow channel is provided on the upper surface of the piezoelectric sensor, and the plurality of immunomagnetic beads that bind to the target object flow into the flow channel with the liquid. More than one magnetic layer is integrated on the piezoelectric sensor, and the direction of the magnetic field force of the magnetic layer acting on the immunomagnetic beads that bind to the target object points to the surface of the piezoelectric sensor.
[0008] Furthermore, the piezoelectric sensor includes a surface acoustic wave resonator or a bulk acoustic wave resonator.
[0009] Furthermore, the surface acoustic wave resonator includes interdigitated electrodes and a piezoelectric substrate, and the interdigitated electrodes are arranged on the upper surface of the piezoelectric substrate; if the interdigitated electrodes are two groups, the projection of the flow channel on the upper surface of the piezoelectric substrate is between the two groups of interdigitated electrodes, and one or more magnetic layers are prepared on the upper surface of the piezoelectric substrate and are located below the flow channel; if the interdigitated electrodes are one group, the projection of the flow channel on the upper surface of the piezoelectric substrate overlaps with the interdigitated electrodes, and the interdigitated electrodes are composed of one or more magnetic layers, or are composed of one or more magnetic layers and one or more highly conductive films.
[0010] Furthermore, the BAW resonator includes a top electrode, a piezoelectric film, a bottom electrode, an acoustic reflection layer and a substrate stacked in sequence from top to bottom, the flow channel is arranged on the upper surface of the top electrode, and the top electrode and / or the bottom electrode contain one or more magnetic layers.
[0011] Furthermore, the top electrode is composed of more than one magnetic layer, and the corresponding bottom electrode is composed of more than one magnetic layer, or is composed of more than one magnetic layer and more than one high conductive film, or is composed of more than one high conductive film; the bottom electrode is composed of more than one magnetic layer, and the corresponding top electrode is composed of more than one magnetic layer, or is composed of more than one magnetic layer and more than one high conductive film, or is composed of more than one high conductive film; the top electrode is composed of more than one magnetic layer and more than one high conductive film, and the corresponding bottom electrode is composed of more than one magnetic layer and more than one high conductive film, or is composed of more than one high conductive film; the bottom electrode is composed of more than one magnetic layer and more than one high conductive film, and the corresponding top electrode is composed of more than one magnetic layer and more than one high conductive film, or is composed of more than one high conductive film.
[0012] Furthermore, the piezoelectric film is composed of more than one layer of piezoelectric material, and the piezoelectric material includes any one or more combinations of aluminum nitride, scandium-doped aluminum nitride, lithium niobate, lithium tantalate and lead zirconate titanate.
[0013] Furthermore, the material of the magnetic layer includes a combination of one or more of iron, cobalt, nickel and alloys thereof, and the material of the highly conductive film includes a combination of one or more of gold, aluminum, copper, titanium, palladium, chromium, molybdenum and platinum.
[0014] Furthermore, the thickness of each magnetic layer is 0.03-12 μm, and the thickness of each highly conductive film is 5-1000 nm.
[0015] Furthermore, the immunomagnetic beads binding to the target include the target and the immunomagnetic beads, the immune markers on the immunomagnetic beads bind to the target through immune affinity reaction, and the diameter of the circumscribed sphere of the immunomagnetic beads is greater than 10 nm and smaller than the diameter of the circumscribed sphere of the target.
[0016] An application of the integrated piezoelectric sensing module based on immunoaffinity reaction comprises the following steps:
[0017] Step 1: The immunomagnetic beads bound to the target object flow into the flow channel above the piezoelectric sensor along with the liquid;
[0018] Step 2: Under the action of the magnetic field generated by the magnetic layer, the immunomagnetic beads bound to the target object come into contact with the upper surface of the piezoelectric sensor;
[0019] Step 3: Use a piezoelectric sensor to measure the total mass of the immunomagnetic beads bound to the target, and analyze and obtain the concentration of the target;
[0020] Step 4: Under the combined action of the liquid flushing in the flow channel and the sound waves generated by the piezoelectric sensor, the immunomagnetic beads bound to the target object that are in contact with the upper surface of the piezoelectric sensor are removed.
[0021] Compared with the prior art, the present invention has the following beneficial effects:
[0022] Compared with traditional piezoelectric sensors based on immune affinity reactions, the present invention does not need to fix immune markers on the surface of the piezoelectric sensor, but only uses immune magnetic beads as immune marker carriers. When the immune magnetic beads bound to the target enter the integrated piezoelectric sensing module, they contact the surface of the piezoelectric sensor under the action of the magnetic field generated by the magnetic layer; the piezoelectric sensor is then used to measure the total mass of the immune magnetic beads bound to the target, and the concentration of the target is obtained by analysis; after the measurement is completed, the immune magnetic beads bound to the target on the surface of the piezoelectric sensor are removed under the combined action of liquid flushing in the flow channel and sound waves generated by the piezoelectric sensor, thereby realizing the reuse of the sensor and reducing the manufacturing cost and use cost of the device.
[0023] The mass of the target increases after combining with the immunomagnetic beads, and the mass loading effect caused when it contacts the surface of the piezoelectric sensor becomes more significant, the offset of the resonant frequency increases, and the sensitivity of the piezoelectric sensor module improves.
[0024] When there are other impurities in the flow channel besides the target object and the immunomagnetic beads, the present invention can simultaneously achieve separation of the target object from the impurities and sensing of the target object quality.
[0025] The magnetic layer is integrated inside the piezoelectric sensor, eliminating the need for an external magnetic field source and simplifying the structure of the piezoelectric sensor module.
[0026] The integrated piezoelectric sensing module described in the present invention can be integrated with other conventional microfluidic modules, such as an acoustophoresis module and an acoustofluidic mixing module, to form a microfluidic system-on-chip, thereby realizing system integration and miniaturization, reducing the manufacturing cost of the system, and effectively reducing the loss caused by the transfer of the target object between different modules. BRIEF DESCRIPTION OF THE DRAWINGS
[0027] Figure 1 is a cross-sectional schematic diagram of the structure of an integrated piezoelectric sensing module based on immunoaffinity reaction, wherein A is the direction of the magnetic field force;
[0028] Figure 2 Schematic diagram of the top view (a) and the central cross-section of the flow channel (b) of the integrated piezoelectric sensing module structure based on surface acoustic wave resonator including two sets of interdigitated electrodes;
[0029] Figure 3 is a cross-sectional schematic diagram of an integrated piezoelectric sensing module structure based on a surface acoustic wave resonator including a group of interdigitated electrodes;
[0030] Figure 4 is a cross-sectional schematic diagram of the structure of an integrated piezoelectric sensing module based on a bulk acoustic wave resonator;
[0031] In the figure, 1, piezoelectric sensor, 2, magnetic layer, 3, immunomagnetic beads bound to the target, 4, flow channel, 11, surface acoustic wave resonator, 12, bulk acoustic wave resonator, 111, interdigitated electrodes, 112, piezoelectric substrate, 121, top electrode, 122, piezoelectric film, 123, bottom electrode, 124, acoustic reflection layer, 125, substrate. DETAILED DESCRIPTION
[0032] The technical solution of the present invention will be clearly and completely described below in conjunction with the drawings and embodiments. Obviously, the described embodiments are only part of the embodiments of the invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. Specific implementation method 1
[0034] An integrated piezoelectric sensing module based on immunoaffinity reaction includes a piezoelectric sensor 1 and a plurality of immunomagnetic beads 3 binding to a target object. A flow channel 4 is provided on the upper surface of the piezoelectric sensor 1, and a plurality of immunomagnetic beads 3 binding to a target object flow into the flow channel 4 along with a liquid; more than one magnetic layer 2 is integrated on the piezoelectric sensor 1, and the direction of the magnetic field force of the magnetic layer 2 acting on the immunomagnetic beads 3 binding to a target object points to the surface of the piezoelectric sensor 1. The structural schematic diagram is shown in FIG. Figure 1 shown.
[0035] Furthermore, the target-binding immunomagnetic beads 3 include a target and immunomagnetic beads, the immune markers on the immunomagnetic beads bind to the target through immunoaffinity reaction, and the diameter of the circumscribed sphere of the immunomagnetic beads is greater than 10 nm and smaller than the diameter of the circumscribed sphere of the target.
[0036] Furthermore, the piezoelectric sensor 1 is a surface acoustic wave resonator 11 .
[0037] Furthermore, the surface acoustic wave resonator 11 includes interdigital electrodes 111 and a piezoelectric substrate 112, wherein the interdigital electrodes 111 are arranged on the upper surface of the piezoelectric substrate 112; the piezoelectric substrate 112 is a piezoelectric single crystal substrate, the interdigital electrodes 111 are in two groups, the projection of the flow channel 4 on the upper surface of the piezoelectric substrate 112 is between the two groups of interdigital electrodes 111, and one or more magnetic layers 2 are prepared on the upper surface of the piezoelectric substrate 112 and are located below the flow channel 4, such as Figure 2 As shown in (a) and (b). When the piezoelectric sensor is working, the electrical signal is input into the left interdigital electrode, and the left interdigital electrode generates a sound wave propagating to the right through the piezoelectric effect. The right interdigital electrode receives the sound wave propagated through the flow channel 4, converts it into an electrical signal and outputs it. By analyzing the admittance curve of the output electrical signal, the total mass of the immunomagnetic beads 3 bound to the target is measured.
[0038] Furthermore, the material of the magnetic layer includes one or more combinations of iron, cobalt, nickel and alloys thereof.
[0039] Furthermore, the material of the interdigital electrodes 11 includes any one or more conductive elements selected from the group consisting of gold, aluminum, copper, titanium, palladium, chromium, molybdenum and platinum.
[0040] Furthermore, the thickness of the interdigital electrodes is between 40-3000 nm.
[0041] Furthermore, the thickness of each magnetic layer is between 0.03-12 μm.
[0042] The workflow includes the following steps:
[0043] Step 1: The immunomagnetic beads 3 bound to the target object flow into the flow channel 4 above the piezoelectric sensor 1 along with the liquid;
[0044] Step 2: Under the action of the magnetic field generated by the magnetic layer 2, the immunomagnetic beads 3 binding to the target object come into contact with the upper surface of the piezoelectric sensor 1;
[0045] Step 3: Use the piezoelectric sensor 1 to measure the total mass of the immunomagnetic beads 3 bound to the target, and analyze and obtain the concentration of the target;
[0046] Step 4: Remove the immunomagnetic beads 3 of the binding target in contact with the upper surface of the piezoelectric sensor 1 under the combined action of the liquid flushing in the flow channel 4 and the sound waves generated by the piezoelectric sensor 1. The sound waves generated by the piezoelectric sensor 1 act on the immunomagnetic beads 3 of the binding target in contact with the upper surface of the piezoelectric sensor 1, and will generate an acoustic radiation force on the immunomagnetic beads 3 of the binding target away from the upper surface of the piezoelectric sensor 1. Under the combined action of the force generated by the liquid flushing, the immunomagnetic beads 3 of the binding target are moved away from the upper surface of the piezoelectric sensor 1 and flow out of the integrated piezoelectric sensing module based on the immunoaffinity reaction along with the liquid.
[0047] After completing step 4, step 1 can be performed to achieve the reuse of the piezoelectric sensor.
[0048] This specific embodiment shows that the admittance curve is obtained based on the surface acoustic wave resonator parameters, and the expression of the piezoelectric equation for obtaining the admittance curve is:
[0049] T=cS-eE
[0050] D=εE-eS
[0051] Among them, T is the stress matrix, c is the stiffness matrix of the piezoelectric material, S is the strain matrix, e is the piezoelectric stress matrix, E is the electrostatic field intensity, D is the electric displacement, and ε is the dielectric matrix of the piezoelectric material. The resonant frequency and electromechanical coupling coefficient of the surface acoustic wave resonator are adjusted according to the piezoelectric stress matrix e. The piezoelectric stress matrix is:
[0052]
[0053] Among them, e15, e22, e24, e31, and e33 are piezoelectric coefficients of the piezoelectric materials in corresponding directions respectively; based on the above equation, the theoretical admittance curve of the surface acoustic wave resonator is determined by finite element simulation method and the geometric parameters are adjusted; the surface acoustic wave resonator is manufactured, and the actual admittance curve of the surface acoustic wave resonator is obtained by testing, and the geometric dimensions and process parameters are further adjusted according to the actual admittance curve, and finally the geometric dimensions and process parameters of the surface acoustic wave resonator that meets the requirements are determined. Specific implementation method 2
[0055] The difference from the first embodiment is that the number and arrangement of the interdigitated electrodes 111 are different; the interdigitated electrodes 111 are a group, the projection of the flow channel 4 on the upper surface of the piezoelectric substrate 112 overlaps with the interdigitated electrodes 111, and the interdigitated electrodes 111 include more than one magnetic layer 2.
[0056] In an exemplary embodiment, the interdigital electrodes 111 are composed of more than one magnetic layer 2 , that is, the material of the interdigital electrodes 111 includes a combination of one or more of iron, cobalt, nickel and alloys thereof.
[0057] In an exemplary embodiment, the interdigitated electrode 111 is composed of one or more magnetic layers 2 and one or more highly conductive films. The material of the magnetic layer 2 includes one or more combinations of iron, cobalt, nickel and alloys thereof, and the material of the highly conductive film includes one or more combinations of gold, aluminum, copper, titanium, palladium, chromium, molybdenum and platinum, and the thickness of each layer of the highly conductive film is between 5-1000 nm.
[0058] When the piezoelectric sensor is working, the electric signal is input into the interdigital electrodes 111, and the mass load effect caused by the contact between the immunomagnetic beads 3 bound to the target and the interdigital electrodes 111 will affect the admittance curve of the electric signal, and the total mass of the immunomagnetic beads 3 bound to the target can be measured by analyzing the change in the admittance curve. The rest is the same as the first embodiment. Specific implementation method three
[0060] An integrated piezoelectric sensing module based on immunoaffinity reaction includes a piezoelectric sensor 1 and a plurality of immunomagnetic beads 3 that bind to a target object. A flow channel 4 is provided on the upper surface of the piezoelectric sensor 1, and the plurality of immunomagnetic beads 3 that bind to a target object flow into the flow channel 4 along with the liquid. More than one magnetic layer 2 is integrated on the piezoelectric sensor 1, and the direction of the magnetic field force of the magnetic layer 2 acting on the immunomagnetic beads 3 that bind to a target object points to the surface of the piezoelectric sensor 1.
[0061] Furthermore, the target-binding immunomagnetic beads 3 include a target and immunomagnetic beads, the immune markers on the immunomagnetic beads bind to the target through immunoaffinity reaction, and the diameter of the circumscribed sphere of the immunomagnetic beads is greater than 10 nm and smaller than the diameter of the circumscribed sphere of the target.
[0062] Furthermore, the piezoelectric sensor 1 is a bulk acoustic wave resonator 12 .
[0063] Furthermore, the BAW resonator 12 includes a top electrode 121, a piezoelectric film 122, a bottom electrode 123, an acoustic reflection layer 124 and a substrate 125 stacked in sequence from top to bottom, the flow channel 4 is arranged on the upper surface of the top electrode 121, and the top electrode 121 and / or the bottom electrode 123 contain one or more magnetic layers 2.
[0064] Further, the top electrode 121 is composed of more than one magnetic layer 2, and the corresponding bottom electrode 123 is composed of more than one magnetic layer 2, or is composed of more than one magnetic layer 2 and more than one high conductive film, or is composed of more than one high conductive film; the bottom electrode 123 is composed of more than one magnetic layer 2, and the corresponding top electrode 121 is composed of more than one magnetic layer 2, or is composed of more than one magnetic layer 2 and more than one high conductive film, or is composed of more than one high conductive film; the top electrode 121 is composed of more than one magnetic layer 2 and more than one high conductive film, and the corresponding bottom electrode 123 is composed of more than one magnetic layer 2 and more than one high conductive film, or is composed of more than one high conductive film; the bottom electrode 123 is composed of more than one magnetic layer 2 and more than one high conductive film, and the corresponding top electrode 121 is composed of more than one magnetic layer 2 and more than one high conductive film, or is composed of more than one high conductive film.
[0065] In an exemplary embodiment, the top electrode 121 is composed of one or more magnetic layers 2, and the bottom electrode 123 is composed of one or more highly conductive films; the material of the magnetic layer 2 includes a combination of one or more of iron, cobalt, nickel and their alloys, and the material of the highly conductive film includes any one or more of the following conductive elements: gold, aluminum, copper, titanium, palladium, chromium, molybdenum and platinum; the thickness of each magnetic layer is between 0.03-12 μm, and the thickness of each highly conductive film is between 5-1000 nm.
[0066] In an exemplary embodiment, the top electrode 121 is composed of one or more magnetic layers 2 and one or more highly conductive films, and the bottom electrode 123 is composed of one or more highly conductive films; the material of the magnetic layer 2 includes a combination of one or more of iron, cobalt, nickel and their alloys; the material of the highly conductive film includes any one or more of the following conductive elements: gold, aluminum, copper, titanium, palladium, chromium, molybdenum and platinum; the thickness of each magnetic layer is between 0.03-12 μm, and the thickness of each highly conductive film is between 5-1000 nm.
[0067] In an exemplary embodiment, the bottom electrode 123 is composed of one or more magnetic layers 2, and the top electrode 121 is composed of one or more highly conductive films; the material of the magnetic layer 2 includes one or more combinations of iron, cobalt, nickel, and alloys thereof. The material of the highly conductive film includes any one or more of the following conductive elements: gold, aluminum, copper, titanium, palladium, chromium, molybdenum, and platinum; the thickness of each magnetic layer is between 0.03-12 μm, and the thickness of each highly conductive film is between 5-1000 nm.
[0068] In an exemplary embodiment, the bottom electrode 123 is composed of one or more magnetic layers 2 and one or more highly conductive films, and the top electrode 121 is composed of one or more highly conductive films; the material of the magnetic layer 2 includes a combination of one or more of iron, cobalt, nickel and their alloys; the material of the highly conductive film includes any one or more of the following conductive elements: gold, aluminum, copper, titanium, palladium, chromium, molybdenum and platinum; the thickness of each magnetic layer is between 0.03-12 μm, and the thickness of each highly conductive film is between 5-1000 nm.
[0069] Furthermore, the piezoelectric film 122 is composed of one or more layers of piezoelectric materials, and the piezoelectric materials include any one or more combinations of aluminum nitride, scandium-doped aluminum nitride, lithium niobate, lithium tantalate, and lead zirconate titanate. The thickness of the piezoelectric film is between 100-5000 nm.
[0070] The acoustic reflection layer is a Bragg reflection layer, which is formed by alternately stacking multiple layers of materials with different acoustic impedances. This design enables incident sound waves within a specific frequency range to be efficiently reflected, thereby reducing the leakage of acoustic energy and improving the quality factor of the bulk acoustic wave resonator.
[0071] The substrate material is silicon or silicon carbide.
[0072] The workflow includes the following steps:
[0073] Step 1: The immunomagnetic beads 3 bound to the target object flow into the flow channel 4 above the piezoelectric sensor 1 along with the liquid;
[0074] Step 2: Under the action of the magnetic field generated by the magnetic layer 2, the immunomagnetic beads 3 binding to the target object come into contact with the upper surface of the piezoelectric sensor 1;
[0075] Step 3: Use the piezoelectric sensor 1 to measure the total mass of the immunomagnetic beads 3 bound to the target, and analyze and obtain the concentration of the target;
[0076] Step 4: Under the combined action of the liquid flushing in the flow channel 4 and the sound waves generated by the piezoelectric sensor 1 , the immunomagnetic beads 3 bound to the target object in contact with the upper surface of the piezoelectric sensor 1 are removed.
[0077] After completing step 4, step 1 can be performed to achieve the reuse of the piezoelectric sensor.
[0078] When the piezoelectric sensor 1 is working, the electrical signal is input into the top electrode 121 and the bottom electrode 123. The mass load effect caused by the contact between the immunomagnetic beads 3 bound to the target and the top electrode 121 will affect the admittance curve of the electrical signal. The change in the admittance curve can be analyzed to measure the total mass of the immunomagnetic beads 3 bound to the target.
[0079] This specific embodiment shows that the admittance curve is obtained based on the bulk acoustic wave resonator parameters, and the expression of the piezoelectric equation for obtaining the admittance curve is:
[0080] T=cS-eE
[0081] D=εE-eS
[0082] Among them, T is the stress matrix, c is the stiffness matrix of the piezoelectric material, S is the strain matrix, e is the piezoelectric stress matrix, E is the electrostatic field intensity, D is the electric displacement, and ε is the dielectric matrix of the piezoelectric material. The resonant frequency and electromechanical coupling coefficient of the BAW resonator are adjusted according to the piezoelectric stress matrix e. The piezoelectric stress matrix is:
[0083]
[0084] Among them, e15, e22, e24, e31, and e33 are piezoelectric coefficients in corresponding directions of piezoelectric materials respectively; based on the above equation, the theoretical admittance curve of the BAW resonator is determined by finite element simulation method and the geometric parameters are adjusted; the BAW resonator is manufactured, and the actual admittance curve of the BAW resonator is obtained by testing, and the geometric dimensions and process parameters are further adjusted according to the actual admittance curve, and finally the geometric dimensions and process parameters of the BAW resonator that meet the requirements are determined.
[0085] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.
Claims
1. An integrated piezoelectric sensing module based on immunoaffinity reaction, characterized in that: The invention comprises a piezoelectric sensor (1) and a plurality of immunomagnetic beads (3) for binding to a target object, wherein a flow channel (4) is arranged on the upper surface of the piezoelectric sensor (1), and the plurality of immunomagnetic beads (3) for binding to a target object flow into the flow channel (4) along with a liquid; and the piezoelectric sensor (1) is integrated with one or more magnetic layers (2), wherein the direction of the magnetic field force of the magnetic layer (2) acting on the immunomagnetic beads (3) for binding to a target object points to the surface of the piezoelectric sensor (1).
2. The integrated piezoelectric sensing module based on immunoaffinity reaction according to claim 1, characterized in that: The piezoelectric sensor (1) comprises a surface acoustic wave resonator (11) or a bulk acoustic wave resonator (12).
3. The integrated piezoelectric sensing module based on immunoaffinity reaction according to claim 2, characterized in that: The surface acoustic wave resonator (11) comprises interdigital electrodes (111) and a piezoelectric substrate (112), wherein the interdigital electrodes (111) are arranged on the upper surface of the piezoelectric substrate (112); if the interdigital electrodes (111) are in two groups, the projection of the flow channel (4) on the upper surface of the piezoelectric substrate (112) is between the two groups of interdigital electrodes (111), and one or more magnetic layers (2) are prepared on the upper surface of the piezoelectric substrate (112) and are located below the flow channel (4); if the interdigital electrodes (111) are in one group, the projection of the flow channel (4) on the upper surface of the piezoelectric substrate (112) overlaps with the interdigital electrodes (111), and the interdigital electrodes (111) are composed of one or more magnetic layers (2), or are composed of one or more magnetic layers (2) and one or more highly conductive thin films.
4. The integrated piezoelectric sensing module based on immunoaffinity reaction according to claim 2, characterized in that: The bulk acoustic wave resonator (12) comprises a top electrode (121), a piezoelectric film (122), a bottom electrode (123), an acoustic reflection layer (124) and a substrate (125) which are stacked in sequence from top to bottom, the flow channel (4) is arranged on the upper surface of the top electrode (121), and the top electrode (121) and / or the bottom electrode (123) contain one or more magnetic layers (2).
5. The integrated piezoelectric sensing module based on immunoaffinity reaction according to claim 4, characterized in that: The top electrode (121) is composed of one or more magnetic layers (2), and the corresponding bottom electrode (123) is composed of one or more magnetic layers (2), or is composed of one or more magnetic layers (2) and one or more highly conductive films, or is composed of one or more highly conductive films; the bottom electrode (123) is composed of one or more magnetic layers (2), and the corresponding top electrode (121) is composed of one or more magnetic layers (2), or is composed of one or more magnetic layers (2) and one or more highly conductive films, or is composed of one or more highly conductive films; the top electrode (121) is composed of one or more magnetic layers (2) and one or more highly conductive films, and the corresponding bottom electrode (123) is composed of one or more magnetic layers (2) and one or more highly conductive films, or is composed of one or more highly conductive films; the bottom electrode (123) is composed of one or more magnetic layers (2) and one or more highly conductive films, and the corresponding top electrode (121) is composed of one or more magnetic layers (2) and one or more highly conductive films, or is composed of one or more highly conductive films.
6. The integrated piezoelectric sensing module based on immunoaffinity reaction according to claim 4, characterized in that: The piezoelectric film (122) is composed of one or more layers of piezoelectric material, and the piezoelectric material includes any one or more combinations of aluminum nitride, scandium-doped aluminum nitride, lithium niobate, lithium tantalate and lead zirconate titanate.
7. An integrated piezoelectric sensing module based on immunoaffinity reaction according to claim 3 or 5, characterized in that: The material of the magnetic layer includes one or more combinations of iron, cobalt, nickel and alloys thereof, and the material of the highly conductive film includes one or more combinations of gold, aluminum, copper, titanium, palladium, chromium, molybdenum and platinum.
8. An integrated piezoelectric sensing module based on immunoaffinity reaction according to claim 3 or 5, characterized in that: The thickness of each magnetic layer (2) is 0.03-12 μm, and the thickness of each highly conductive film is 5-1000 nm.
9. The integrated piezoelectric sensing module based on immunoaffinity reaction according to claim 1, characterized in that: The immunomagnetic beads (3) for binding to the target include the target and the immunomagnetic beads. The immune markers on the immunomagnetic beads bind to the target through immunoaffinity reaction. The diameter of the circumscribed sphere of the immunomagnetic beads is greater than 10 nm and smaller than the diameter of the circumscribed sphere of the target.
10. An application of the integrated piezoelectric sensing module based on immunoaffinity reaction according to any one of claims 1 to 9, characterized in that: The following steps are involved: Step 1: The immunomagnetic beads (3) bound to the target object flow into the flow channel (4) above the piezoelectric sensor (1) along with the liquid; Step 2: Under the action of the magnetic field generated by the magnetic layer (2), the immunomagnetic beads (3) bound to the target object come into contact with the upper surface of the piezoelectric sensor (1); Step 3: Using the piezoelectric sensor (1) to measure the total mass of the immunomagnetic beads (3) bound to the target, and analyzing to obtain the concentration of the target; Step 4: Under the combined action of the liquid flushing in the flow channel (4) and the sound waves generated by the piezoelectric sensor (1), the immunomagnetic beads (3) bound to the target object in contact with the upper surface of the piezoelectric sensor (1) are removed.