Sensor structure
The sensor structure with a magnetic sensor array and concentrators improves detection sensitivity and spatial resolution, addressing the limitations of conventional systems by concentrating magnetic flux for precise measurement of weak signals from cells and devices.
Patent Information
- Application Number
- JP2024042622
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-03-18
- Publication Date
- 2025-10-01
AI Technical Summary
Conventional magnetic detection systems struggle to achieve high detection sensitivity while maintaining spatial resolution of several tens of micrometers, particularly in applications involving cultured cells, biological tissues, and devices generating weak magnetic signals.
A sensor structure comprising a magnetic sensor array with magnetic sensor elements and magnetic material concentrators arranged two-dimensionally, forming a magnetic circuit to concentrate magnetic flux and improve detection sensitivity and spatial resolution.
The sensor structure enhances detection sensitivity and spatial resolution, enabling precise measurement of magnetic signals from individual cells and devices by concentrating magnetic flux and suppressing attenuation.
Smart Images

Figure 2025142967000001_ABST
Abstract
Description
[Technical Field]
[0001] The present disclosure relates to sensor structures. [Background technology]
[0002] In recent years, iPS cell-based drug testing has attracted attention as an ethically sound drug testing method in the fields of preclinical research and pharmaceutical development. Specifically, cardiomyocytes and neurons derived from human iPS cells provide models that reflect the patient's genetic information and pathology, and are therefore widely used for drug efficacy analysis and toxicity evaluation. Previously, in vivo cell-based research, such as drug screening, mainly relied on electrophysiological measurements using electrodes such as patch clamping and microelectrode arrays (MEAs), as well as fluorescence microscopy.
[0003] However, the patch clamp method carries the risk of damaging cells, and measurement results are highly dependent on the experimenter's skill. Microelectrode arrays (MEAs) require specialized culture dishes, and measurement results are highly sensitive to the adhesion state of cells on the electrodes. Furthermore, the uptake of fluorescent dyes into cells when using a fluorescence microscope, or the excitation light used for cell observation, can cause stress and damage to cells, disrupting their homeostasis.
[0004] One possible method that can solve at least some of the problems of the above-mentioned conventional methods is to detect magnetic signals generated by cells. When an electric current flows in the cells, causing a change in membrane potential as an electrical signal, a magnetic field is generated accordingly. Therefore, if the magnetic field can be detected, it becomes possible to understand the state of the cells. Magnetic signals are vector signals that contain directional information and have the characteristics of being less susceptible to attenuation in the microenvironment of tissue and exhibiting less distortion. Furthermore, since the state of cultured cells can be detected without contact, it becomes possible to perform measurements while minimizing stress and damage to the cells.
[0005] As a conventional technique for detecting a magnetic field, for example, Patent Document 1 discloses a configuration in which a horizontal Hall sensor is arranged below the surface of a substrate and a spherical magnetic concentrator is arranged above the surface of the substrate. Also, Non-Patent Document 1 discloses a tunneling magnetoresistance (TMR) sensor based on a magnetic tunnel junction (MTJ). In this sensor, a pair of T-shaped flux concentrators (MFCs) are arranged on both sides of an MTJ array in which 74 MTJs are arranged. [Prior art documents] [Patent documents]
[0006] [Patent Document 1] Special Publication No. 2022-547945 [Non-patent literature]
[0007] [Non-Patent Document 1] Mikihiko Oogane et al., Sub-pT magnetic field detection by tunnel magneto-resistive sensors,2021 Appl. Phys. Express 14, 123002 (2021) Summary of the Invention [Problem to be solved by the invention]
[0008] In experiments using cultured cells, for example, to identify firing signals at the single-cell level (magnetic fields generated by electrical signals that cause membrane potential changes), higher detection sensitivity is required, as well as a spatial resolution of several tens of micrometers in detecting magnetic signals. However, in conventional magnetic detection systems, there was no known technology that could achieve a spatial resolution of several tens of micrometers while maintaining detection sensitivity.
[0009] For example, in the configuration described in Patent Document 1, a spherical magnetic concentrator is placed between the magnetic signal source and the sensor element. Although this configuration allows for increased detection sensitivity by using a spherical magnetic concentrator, which allows magnetic signals to be input from a wide space outside the concentrator, it is difficult to improve the spatial resolution of the sensor, which receives the magnetic signal via the concentrator. Furthermore, in the configuration described in Non-Patent Document 1, the magnetic signal input to the T-shaped flux concentrator is converged by the concentrator, and the converged magnetic signal is transmitted from the T-shaped flux concentrator to the MTJ array. Therefore, each sensor constituting the MTJ array detects the average value of the magnetic signal converged from a relatively wide area by the concentrator, making it difficult to improve the spatial resolution of the sensor. Thus, with regard to magnetic signal detection, there has been insufficient research into technologies that improve spatial resolution while also increasing detection sensitivity.
[0010] Improvements in spatial resolution in magnetic sensors are desired not only when cultured cells as described above are used as measurement targets, but also when, for example, biological tissues composed of cardiac muscle cells or nerve cells that generate magnetic signals, or living organisms that contain such biological tissues, are used as measurement targets. Furthermore, improvements in spatial resolution in magnetic sensors are desired not only when the measurement targets include cells as described above, but also when investigating and analyzing the state of devices that can generate weak magnetic signals, such as electrical circuit boards inside machines or the internal structure of batteries. [Means for solving the problem]
[0011] The present disclosure can be realized in the following forms. (1) According to one aspect of the present disclosure, there is provided a sensor structure including a magnetic sensor array in which a plurality of magnetic sensor elements are arranged two-dimensionally, a substrate arranged on the magnetic sensor array, and a plurality of magnetic material concentrators provided in the substrate corresponding to the plurality of magnetic sensor elements, each of the plurality of magnetic material concentrators having magnetic anisotropy, the magnetic sensor elements and the magnetic material concentrators provided corresponding to the magnetic sensor elements being arranged to form a magnetic circuit in which a magnetic signal is input to the magnetic sensor elements via the magnetic material concentrators. According to this type of sensor structure, a magnetic concentrator is provided corresponding to each magnetic sensor element. Therefore, magnetic signals can be applied to the magnetic sensor elements while concentrating magnetic flux in the magnetic concentrator and suppressing attenuation, thereby improving detection sensitivity. In this case, the magnetic concentrator has magnetic anisotropy, and the magnetic sensor elements and the magnetic concentrator are arranged to form a magnetic circuit in which a magnetic signal is input to the magnetic sensor elements via the magnetic concentrator. This allows only magnetic flux from a signal source arranged on the magnetic concentrator to be primarily converged, enabling high-sensitivity detection of the magnetic flux from the signal source. Furthermore, because the magnetic sensor elements and the magnetic concentrators are arranged two-dimensionally, the size of the magnetic concentrators and the distance between adjacent magnetic concentrators can be appropriately set depending on the signal source to be measured, enabling measurements with higher spatial resolution. (2) In the sensor structure of the above embodiment, the magnetic sensor element may be arranged on an extension of the easy axis of magnetization of a magnetic material concentrator provided corresponding to the magnetic sensor element. With this configuration, the signal source to be measured is arranged on an extension of the easy axis of magnetization, which makes it possible to easily increase the detection sensitivity. (3) In the sensor structure of the above aspect, each of the plurality of magnetic concentrators may be arranged so that the direction perpendicular to the surface direction of the substrate is the axis of easy magnetization, and each of the magnetic sensor elements may be arranged at a position overlapping the corresponding magnetic concentrator in the direction perpendicular to the surface direction of the substrate. With this configuration, the signal source to be measured can be arranged on the substrate at a position perpendicular to the surface direction of the magnetic concentrator, thereby easily increasing the detection sensitivity. (4) In the sensor structure of the above aspect, each of the plurality of magnetic concentrators may be embedded in the substrate or may be disposed so as to penetrate the substrate, thereby simplifying the structure of the sensor structure. (5) In the sensor structure of the above aspect, each of the plurality of magnetic concentrators may be made of a soft magnetic material having one or more of shape magnetic anisotropy, induced magnetic anisotropy, stress magnetic anisotropy, and magnetocrystalline anisotropy. With this configuration, the magnetic concentrator can easily converge the magnetic flux. (6) In the sensor structure of the above aspect, each of the plurality of magnetic concentrators may have shape magnetic anisotropy and may be formed in a shape selected from the group consisting of a cylindrical shape, a rectangular parallelepiped shape, a capsule shape having an elliptical cross section parallel to the central axis, a pyramidal shape, and a conical shape. With this configuration, the magnetic concentrator can be configured with a relatively simple structure. (7) In the sensor structure of the above aspect, each of the plurality of magnetic material concentrators may have magnetic anisotropy and a closed-circuit magnetic domain structure in an outer periphery including a surface of the magnetic material concentrator that suppresses the penetration of magnetic flux from directions other than the easy axis of magnetization related to the magnetic anisotropy. With this configuration, it is possible to enhance the effect of suppressing the penetration of magnetic flux into the magnetic material concentrator from directions other than the easy axis of magnetization of the magnetic material concentrator. (8) In the sensor structure of the above aspect, the magnetic concentrator and at least a part of the magnetic sensor element provided corresponding to the magnetic concentrator may be integrally formed, which simplifies the overall structure of the sensor structure. (9) In the sensor structure of the above aspect, a coating layer containing a cell adhesive component may be provided on a second surface of the substrate, the second surface being different from the first surface facing the magnetic sensor array, so as to cover an area including the region in the substrate where the plurality of magnetic concentrators are formed, and the diameter of a cross section of each of the plurality of magnetic concentrators parallel to the surface direction of the substrate may be 5 μm or more and 1000 μm or less. With this configuration, it is possible to detect magnetic signals from individual cells cultured on the second surface of the substrate. (10) In the sensor structure of the above aspect, the magnetic concentrator may be exposed on the second surface of the substrate, and the difference in height between the second surface of the substrate and the portion of the magnetic concentrator exposed on the second surface may be 10 μm or less. With this configuration, when cells cultured on the second surface of the substrate are to be detected, cell culture on the second surface can be performed more effectively. (11) In the sensor structure of the above aspect, a shield portion may be provided on a second surface of the substrate, the second surface being different from the first surface facing the magnetic sensor array, the shield portion protruding from the second surface and surrounding the entire area where the plurality of magnetic concentrators are arranged, to prevent the passage of magnetic flux. With this configuration, environmental noise from around the sensor structure can be blocked, thereby further increasing the sensitivity of the magnetic sensor element. (12) In the sensor structure of the above aspect, a shield portion may be provided on a second surface of the substrate, the second surface being different from the first surface facing the magnetic sensor array, protruding from the second surface and surrounding the area where each magnetic concentrator is disposed, to prevent the passage of magnetic flux. This configuration can improve reliability in blocking environmental noise from around the sensor structure and further increase the sensitivity of the magnetic sensor element. The present disclosure can be realized in various forms other than those described above, such as a method for manufacturing a sensor structure, a method for measuring cell firing signals, a drug testing method using a sensor structure, and a method for investigating the internal state of machinery that generates magnetic signals. [Brief explanation of the drawings]
[0012] [Figure 1] FIG. 1 is an explanatory diagram illustrating a schematic configuration of a sensor structure according to a first embodiment. [Figure 2] FIG. 2 is a perspective view showing a part of the external appearance of the sensor structure. [Figure 3] FIG. 10 is an explanatory diagram showing the magnetization curve of a cylindrical magnetic concentrator. [Figure 4] 10 is a flowchart showing a method for manufacturing the sensor structure. [Figure 5] FIG. 3 is an enlarged cross-sectional view showing a portion of a substrate including a magnetic concentrator. [Figure 6] 10 is a flowchart showing a method for manufacturing the sensor structure. [Figure 7] FIG. 10 is an explanatory diagram showing the state of a magnetic signal when a magnetic concentrator is provided. [Figure 8] FIG. 10 is an explanatory diagram showing the state of a magnetic signal when a magnetic concentrator is not provided. [Figure 9] 10A to 10C are explanatory diagrams showing substrates with magnetic concentrators of different shapes; [Figure 10] 10A to 10C are explanatory diagrams showing substrates with magnetic concentrators of different shapes; [Figure 11] 10A to 10C are explanatory diagrams showing substrates with magnetic concentrators of different shapes; [Figure 12] FIG. 10 is an explanatory diagram showing the configuration of a magnetic concentrator according to a third embodiment. [Figure 13] FIG. 2 is an explanatory diagram showing a magnetization curve for a magnetic concentrator. [Figure 14] FIG. 10 is an explanatory diagram showing the results of a simulation of magnetic flux density distribution. [Figure 15] FIG. 10 is an explanatory diagram showing the relationship between the Z-axis magnetic flux density attenuation rate and the distance from the signal source. [Figure 16] FIG. 10 is an explanatory diagram illustrating a schematic configuration of a sensor structure according to a fourth embodiment. [Figure 17] FIG. 10 is an explanatory diagram illustrating a schematic configuration of a sensor structure according to a fifth embodiment. [Figure 18] FIG. 2 is a perspective view showing a part of the external appearance of the sensor structure. [Figure 19] FIG. 10 is an explanatory diagram showing the state of a magnetic signal when a magnetic concentrator is provided. [Figure 20] FIG. 10 is an explanatory diagram showing the state of a magnetic signal when a magnetic concentrator is not provided. [Figure 21] FIG. 10 is an explanatory diagram illustrating a schematic configuration of a sensor structure according to a sixth embodiment. [Figure 22] FIG. 13 is an explanatory diagram illustrating a schematic configuration of a sensor structure according to a seventh embodiment. [Figure 23] FIG. 10 is an explanatory diagram showing a photograph of the sensor structure. [Figure 24] FIG. 4 is an explanatory diagram showing the results of examining the surface roughness of the second surface of the substrate. [Figure 25] FIG. 4 is an explanatory diagram showing the results of examining the surface roughness of the second surface of the substrate. [Figure 26] FIG. 10 is an explanatory diagram showing the results of fluorescence observation of cells after culturing. DETAILED DESCRIPTION OF THE INVENTION
[0013] A. First embodiment: (A-1) Configuration of sensor structure: FIG. 1 is an explanatory diagram illustrating a schematic configuration of a sensor structure 10 according to a first embodiment of the present disclosure, and FIG. 2 is a perspective view illustrating a portion of the exterior of the sensor structure 10. In FIGS. 1 and 2, as well as FIGS. 9 to 11, 14 to 18, 21, and 22 (described later), mutually orthogonal X, Y, and Z axes are shown to identify directions. The X, Y, and Z axes shown in each figure each indicate the same direction. In this specification, the Z axis indicates the vertical direction, and the X and Y axes indicate the horizontal direction. The vertical and horizontal directions are specified for convenience of explanation and do not necessarily correspond to the orientation of the sensor structure 10 when in use. In FIG. 2 and the perspective views shown in FIGS. 9 to 11, 18, and 22 (described later), internal structures that cannot be seen from the outside are indicated by dashed lines. Note that FIGS. 1 and 2 schematically illustrate the layout of each component and do not accurately represent the dimensional ratios of each component.
[0014] As shown in FIG. 1, the sensor structure 10 includes a magnetic sensor array 20 having a plurality of magnetic sensor elements 22, a substrate 30 disposed on the magnetic sensor array 20, and a plurality of magnetic concentrators 40 provided within the substrate 30, each of which is individually connected to one of the plurality of magnetic sensor elements 22.
[0015] The magnetic sensor array 20 is composed of a plurality of magnetic sensor elements 22 arranged two-dimensionally. There are no particular limitations on the type of magnetic sensor element 22 as long as it can be sufficiently miniaturized. For example, a magnetic impedance sensor composed of a magnetic impedance element, a GSR (GHz-Spin-Rotation Sensor), a giant magnetoresistance element, a ferromagnetic tunnel junction element, or the like can be used. In particular, a magnetic impedance sensor or a GSR sensor is desirable. FIG. 1 shows a schematic diagram of a magnetic impedance sensor or a GSR sensor in use.
[0016] The substrate 30 is formed in a plate shape with an array structure of multiple magnetic concentrators 40 provided inside. The substrate 30 is made of a non-magnetic material, preferably a highly transparent material. There are no particular restrictions on the material from which the substrate 30 is made as long as it is a non-magnetic material, but considering the convenience of microscope observation, it is preferable to make it from glass or resin. Furthermore, the substrate 30 does not need to be a single member made from a solid material; for example, thin-film members may be provided on the surface layers of the upper and lower surfaces of the substrate 30, and the rest of the surface layers may be made from a vacuum layer or air layer.
[0017] The magnetic concentrator 40 is made of a magnetic material (ferromagnetic material). The material constituting the magnetic concentrator 40 is preferably a soft magnetic material with high magnetic permeability. The material constituting the magnetic concentrator 40 can be, for example, nickel (Ni), cobalt (Co), iron (Fe), NiFe-based soft magnetic material, CoNiFe-based soft magnetic material, CoTaZr-based soft magnetic material, or a combination of multiple materials selected from these, or may be an amorphous magnetic material.
[0018] The magnetic concentrator 40 of this embodiment has magnetic anisotropy. Specifically, the magnetic concentrator 40 is made of a soft magnetic material having one or a combination of shape magnetic anisotropy, induced magnetic anisotropy, stress magnetic anisotropy, and magnetocrystalline anisotropy, and has an easy axis, which is a specific direction in which magnetization is easy. As an example, FIGS. 1 and 2 show a cylindrical magnetic concentrator 40 having at least shape magnetic anisotropy.
[0019] 3 is an explanatory diagram showing the magnetization curve of a cylindrical magnetic concentrator 40 having shape magnetic anisotropy. In the graph of FIG. 3, the horizontal axis represents the magnetic field H (Oe), and the vertical axis represents the magnetization strength M (emu / cm 31, the vertical direction (Z-axis direction) is the easy axis direction, and the horizontal direction (direction parallel to the XY plane) is the hard axis direction.
[0020] 2, the plurality of magnetic concentrators 40 included in the sensor structure 10 of this embodiment have an array structure arranged two-dimensionally within the substrate 30. The magnetic concentrators 40 may be arranged, for example, so as to penetrate the substrate 30, or may be arranged so as to be embedded within the substrate 30. FIG. 2 shows how cylindrical magnetic concentrators 40 are provided so as to penetrate the highly transparent substrate 30.
[0021] As described above, a magnetic sensor element 22 is provided corresponding to each magnetic material concentrator 40. Hereinafter, a combination of a magnetic material concentrator 40 and a corresponding magnetic sensor element 22 will also be referred to as a sensor unit 12. In each sensor unit 12, the magnetic sensor element 22 and the magnetic material concentrator 40 are arranged to form a magnetic circuit in which a magnetic signal is input to the magnetic sensor element 22 via the magnetic material concentrator 40. In this embodiment, the magnetic sensor element 22 is arranged on an extension of the easy axis of magnetization of the corresponding magnetic material concentrator 40. That is, since the easy axis of the magnetic material concentrator 40 of this embodiment is the Z-axis direction, the magnetic sensor element 22 is arranged directly below the magnetic material concentrator 40 so as to overlap with the magnetic material concentrator 40 in the Z-axis direction (the direction perpendicular to the surface direction of the substrate 30).
[0022] 1, in the substrate 30, the surface facing the magnetic sensor array 20 is designated as a first surface 32, and the surface different from the first surface is designated as a second surface 34. When performing a measurement using the sensor structure 10, the sensor structure 10 is disposed so that a signal source 50, which is the measurement target, is located on the second surface 34. FIG. 1 shows a state in which a cell is used as the signal source 50. When the signal source 50 is located on the magnetic material concentrator 40, i.e., on an extension of the easy axis of the magnetic material concentrator 40, the magnetic flux emitted from the signal source 50 is converged by the magnetic material concentrator 40 and applied to the corresponding magnetic sensor element 22.
[0023] In the magnetic material concentrator 40, which has magnetic anisotropy, magnetic flux easily passes through the easy axis direction inside the magnetic material, resulting in high magnetic permeability. Other hard axes are difficult to magnetize. Therefore, by arranging the signal source 50, the magnetic material concentrator 40, and the magnetic sensor element 22 in this order on the easy axis of the magnetic material concentrator 40, the weak magnetic signal generated by the signal source 50 can be mainly converged within the magnetic material concentrator 40 and narrowed to a single direction in which the magnetic sensor element 22 is arranged. In this case, magnetic signals containing noise from directions other than the easy axis direction (hard axis direction) are significantly attenuated (see FIG. 3), which prevents the magnetic sensor element 22 from receiving magnetic signals from the hard axis direction. In general, magnetic signals have the property of attenuating depending on the distance from the signal source, in proportion to the cube of the distance. Therefore, from the viewpoint of suppressing attenuation of the magnetic signal from the signal source 50 input to the magnetic sensor element 22, it is desirable that the distance between the signal source 50 and the magnetic concentrator 40, and the distance between the magnetic concentrator 40 and the magnetic sensor element 22, be short, and it is more desirable that they be in contact with each other.
[0024] The size of each magnetic material concentrator 40 and the distance between adjacent magnetic material concentrators 40 may be appropriately set depending on the spatial resolution desired to be achieved when performing measurements using the sensor structure 10. For example, in order to achieve a spatial resolution that enables distinguishing and detecting signals from individual cells using cells as signal sources 50 as shown in FIG. 1, the diameter of the cylindrical magnetic material concentrator 40 is preferably 1 mm or less, more preferably 100 μm or less. The distance between adjacent magnetic material concentrators 40 is preferably 1 mm or less, more preferably 100 μm or less. The length of the magnetic material concentrator 40 can be, for example, 0.1 mm or more and 2 mm or less.
[0025] (A-2) Method for manufacturing sensor structure: FIG. 4 is a flowchart showing a first manufacturing method as an example of a manufacturing method for the sensor structure 10 of this embodiment. When manufacturing the sensor structure 10 according to the first manufacturing method, first, a plurality of concentrator members for forming the magnetic material concentrator 40 are prepared (step T100). The concentrator members may be made of the magnetic material already described as a constituent material of the magnetic material concentrator 40, and may be shaped (e.g., cylindrical) according to the desired shape of the magnetic material concentrator 40. Then, the prepared concentrator members are subjected to a heat treatment such as magnetic annealing (step T110). The heat treatment performed in step T110 can be a treatment to improve the magnetic properties of the concentrator members or a treatment to remove and alleviate residual stress caused by processing (e.g., pressing, welding, bending, cutting, etc.) performed to fabricate the concentrator members. Magnetic annealing is a heat treatment performed primarily for the purposes of improving the magnetic properties of the concentrator members and removing and alleviating the residual stress in the concentrator members. Magnetic annealing also has the effect of increasing the magnetic permeability of the magnetic material. The heat treatment performed in step T110 may be, in addition to or instead of the magnetic annealing described above, a magnetic field heat treatment, a tension heat treatment, or Joule annealing (current annealing). The magnetic field heat treatment generates magnetic anisotropy, including induced magnetic anisotropy and stress magnetic anisotropy, thereby improving the magnetic properties.
[0026] Separately from steps T100 and T110, a substrate plate for forming the substrate 30 is prepared (step T120). The substrate plate may be a plate-shaped member made of the material already described as the constituent material of the substrate 30. Then, the prepared substrate plate is drilled to form a plurality of holes arranged in an array (arranged two-dimensionally) (step T130). The positions of the arrayed holes formed in step T130 correspond to the positions where the magnetic concentrators 40 should be arranged on the substrate 30 of the sensor structure 10. The size of the holes formed in step T130 may be slightly larger than the cross-sectional size of the concentrator member that has undergone step T110.
[0027] Thereafter, the concentrator members that have undergone step T110 are inserted into each of the holes formed in the substrate plate in step T130 (step T140). Then, the substrate plate and the concentrator members are bonded together using an adhesive to integrate them (step T150). After step T150, the surface of the substrate plate integrated with the concentrator members is polished (step T160), and then integrated with the magnetic sensor array 20 (step T170), completing the sensor structure 10.
[0028] FIG. 5 is an enlarged cross-sectional view of a portion of the substrate 30 including the magnetic material concentrator 40 in the sensor structure 10 obtained by the first manufacturing method shown in FIG. 4 . As shown in FIG. 5 , the inner wall of a hole formed in the substrate 30 and the magnetic material concentrator 40 are bonded together with an adhesive 35. In the sensor structure 10, the magnetic material concentrator 40 generally has a larger thermal expansion coefficient than the substrate 30. Therefore, it is desirable to select an adhesive 35 that has a high ability to absorb stress generated between the substrate 30 and the magnetic material concentrator 40 due to thermal expansion of the magnetic material concentrator 40, taking into account the thermal expansion coefficient of the magnetic material concentrator 40, for example. The adhesive 35 may be selected appropriately depending on the material of the magnetic material concentrator 40. Examples of the adhesive 35 that can be used include silica-based adhesives, alumina-based adhesives, magnesia-based adhesives, and α-cyanoacrylate-based adhesives. When the sensor structure 10 is used to measure cells, it is desirable that the adhesive 35 be biocompatible.
[0029] Fig. 6 is a flowchart showing a second manufacturing method as an example of a manufacturing method of the sensor structure 10 of this embodiment. In Fig. 6, steps common to those in Fig. 4 are assigned the same step numbers. When manufacturing the sensor structure 10 according to the second manufacturing method, as in the first manufacturing method, first, a plurality of concentrator members are prepared (step T100), and the prepared concentrator members are subjected to a heat treatment such as magnetic annealing (step T110). Furthermore, a substrate plate is prepared (step T120) separately from steps T100 and T110.
[0030] Then, in the second manufacturing method, without processing the substrate plate, each concentrator member is heated to a temperature equal to or higher than the melting point of the material constituting the substrate plate. Then, each concentrator member is pressed against a location on the substrate plate where the magnetic concentrator 40 is to be arranged, and the concentrator member penetrates the substrate plate while melting the substrate plate with the heat of the concentrator member (step T145). Thereafter, the surface of the substrate plate integrated with the concentrator member is polished (step T160), and further integrated with the magnetic sensor array 20 (step T170), completing the sensor structure 10.
[0031] The polishing process in step T160 shown in FIGS. 4 and 6 may be performed as appropriate to achieve a desired surface roughness for the substrate plate integrated with the concentrator member, depending on the purpose and manner of use of the sensor structure 10, or the signal source 50 to be measured. For example, if cells are cultured on the second surface 34 of the substrate 30 in the fabricated sensor structure 10 and individual cultured cells are used as the signal source 50, it is desirable to minimize the surface roughness of the substrate 30 so as not to hinder the growth of the cultured cells. From this perspective, for example, it is desirable that the height difference between the highest and lowest points on the second surface 34 be 10 μm or less. Furthermore, if the end of the magnetic concentrator 40 is exposed on the second surface 34 of the substrate 30, it is desirable that the height difference between the second surface 34 of the substrate 30 and the exposed portion of the magnetic concentrator 40 on the second surface 34 (the height difference between the highest and lowest points) be 10 μm or less.
[0032] Furthermore, when cells are cultured on the second surface 34 of the substrate 30 of the sensor structure 10 as described above, the second surface 34 may be subjected to a surface treatment suitable for cell culture after the polishing process in step T160 of FIGS. 4 and 6 . Specifically, for example, the entire second surface 34, including the area where the magnetic concentrator 40 is to be disposed, may be coated with a cell adhesion coating agent. Examples of the cell adhesion coating agent that can be used include extracellular matrices such as collagen, laminin, fibronectin, and proteoglycan. This configuration facilitates the growth of cultured cells on the substrate 30, enabling longer-term culture. Furthermore, the coating process may involve coating with a resin that readily adheres to cells, in addition to the biomolecules described above. In this case, a thin film having a thickness of about 1 nm to 100 μm may be formed using, for example, polystyrene, polyethylene terephthalate, polycarbonate, polymethyl methacrylate, polydimethylsiloxane, cycloolefin polymers and copolymers thereof, or biocompatible metal compounds such as titania, which are used in tissue culture plates and cover glasses for cell observation.
[0033] Furthermore, when cells are cultured on the second surface 34 of the substrate 30 of the sensor structure 10 as described above, it is desirable that the diameter of the cross section of each of the magnetic concentrators 40 parallel to the surface direction of the substrate 30 be 5 μm or more and 1000 μm or less. Setting the diameter to 1000 μm or less facilitates detection of magnetic signals from individual cells. From this perspective, it is more desirable that the diameter be 800 μm or less, and even more desirable that the diameter be 500 μm or less. However, the diameter may exceed 1000 μm and may be appropriately set depending on the type of cultured cells. Furthermore, setting the diameter to 5 μm or more facilitates the manufacture of the sensor structure 10.
[0034] Whether the first or second manufacturing method described above is adopted, the sensor structure 10 having an array structure can be manufactured while maintaining the magnetic domain structure and magnetic properties of the components constituting the magnetic material concentrator 40. Furthermore, the second manufacturing method eliminates the need for drilling in step T130, simplifying the manufacturing process and eliminating the need for adhesive 35. However, in the second manufacturing method, the temperature to which the concentrator components are heated in step T145 must be set sufficiently lower than the Curie temperature of the magnetic material constituting the concentrator components. Therefore, the type of magnetic material constituting the concentrator components must be selected depending on the melting temperature of the substrate plate. Therefore, the first manufacturing method allows for greater freedom in selecting the components of the substrate 30 and the magnetic material concentrator 40.
[0035] According to the sensor structure 10 of this embodiment configured as described above, a magnetic material concentrator 40 having a higher magnetic permeability than the surrounding area is provided for each magnetic sensor element 22. Therefore, by disposing the sensor structure 10 so that the signal source 50 is located above the magnetic material concentrator 40 on the second surface 34 of the substrate 30 and performing a measurement, the magnetic flux emitted from the signal source 50 can be converged by the magnetic material concentrator 40 to suppress attenuation and applied to the magnetic sensor element 22, thereby improving detection sensitivity. In this case, the magnetic material concentrator 40 has magnetic anisotropy, and the magnetic sensor element 22 and the magnetic material concentrator 40 are disposed so as to form a magnetic circuit in which a magnetic signal is input to the magnetic sensor element 22 via the magnetic material concentrator 40. Therefore, the direction of the magnetic flux converged by the magnetic material concentrator 40 is limited to one direction corresponding to the easy axis of the magnetic material concentrator 40, and each magnetic material concentrator 40 mainly converges the magnetic flux from a specific signal source 50 arranged thereon, allowing the corresponding magnetic sensor element 22 to detect the magnetic flux from the specific signal source 50 with high sensitivity. Furthermore, since the sensor unit 12, which is composed of the magnetic sensor element 22 and the magnetic material concentrator 40, is arranged two-dimensionally, measurements with higher spatial resolution can be achieved by appropriately setting the size of the magnetic material concentrators 40 arranged within the substrate 30 and the distance between adjacent magnetic material concentrators 40 according to the signal source 50 to be measured. By achieving high spatial resolution while increasing detection sensitivity as described above, it becomes possible to distinguish and detect weak signals, such as magnetic signals from individual cardiomyocytes or neurons, for each cell.
[0036] 7 and 8 are explanatory diagrams showing the results of a simulation comparing the behavior of magnetic signals between a configuration including a magnetic material concentrator 40 having magnetic anisotropy, such as the sensor structure 10 of this embodiment, and a configuration not including the magnetic material concentrator 40. FIG. 7 shows the results of investigating the behavior of magnetic signals for a configuration including the magnetic material concentrator 40 having magnetic anisotropy, and FIG. 8 shows the results of investigating the behavior of magnetic signals for a configuration not including the magnetic material concentrator 40. FIGS. 7(A) and 8(B) show gray color maps of magnetic signal strength. FIGS. 7(B) and 8(B) show the magnetic flux density distribution in the longitudinal direction of the magnetic sensor element 22 (the Z-axis direction in FIG. 1 ), illustrating the magnetic signal attenuation suppression effect. In FIGS. 7(B) and 8(B), the horizontal axis represents the longitudinal distance of the magnetic sensor element 22, i.e., the distance from the upper end of the magnetic sensor element 22 (the contact portion with the magnetic material concentrator 40 or the substrate 30), and the vertical axis represents the magnetic flux density (T). The above simulation was performed using COMSOL Multiphysics, a general-purpose physical simulation software.
[0037] In the simulation shown in FIG. 7, a magnetic flux was generated from an ellipsoidal signal source (semiaxes: 20 μm × 20 μm × 10 μm) equivalent in size to a single cell, placed on a glass substrate 30. A cylindrical magnetic concentrator 40 (height: 300 μm, diameter: 100 μm) made of permalloy (NiFe alloy) was embedded in the glass substrate 30, and the magnetic signal attenuation suppression effect of this flux concentrator structure was simulated. FIG. 8 shows the results of a simulation performed under the same conditions as FIG. 7, except that the magnetic concentrator 40 was not provided. The results shown in FIGS. 7 and 8 indicate that the provision of the magnetic concentrator 40 of this embodiment forms a magnetic circuit from the signal source 50 through the magnetic concentrator 40 to the magnetic sensor element 22, increasing the magnetic flux density in the magnetic sensor element 22 by more than 50 times compared to a case where the magnetic concentrator 40 is not provided.
[0038] In the sensor structure 10 of the first embodiment, the magnetic material concentrator 42 is disposed so that the direction perpendicular to the surface direction of the substrate 30 (the Z-axis direction) is the easy axis, and the magnetic sensor element 22 is disposed so that it is located on an extension of the easy axis of the magnetic material concentrator 42, that is, so that the magnetic material concentrator 42 and the magnetic sensor element 22 overlap in the Z-axis direction. However, the arrangement of the magnetic material concentrator 42 and the magnetic sensor element 22 may be different from the above. For example, the magnetic material concentrator 42 may be disposed in the substrate 30 so that the easy axis of the magnetic material concentrator 42 is oblique to the surface direction of the substrate 30, and the magnetic sensor element 22 may be disposed on an extension of the easy axis of the magnetic material concentrator 42. It is sufficient that the magnetic sensor element 22 and the magnetic material concentrator 42 provided corresponding to this magnetic sensor element 22 are disposed so as to form a magnetic circuit in which a magnetic signal is input to the magnetic sensor element 22 via the magnetic material concentrator 42. This makes it possible to obtain the same effect as in the first embodiment, that is, to improve the detection sensitivity of the magnetic sensor element while realizing high spatial resolution.
[0039] Furthermore, when using the sensor structure 10 of this embodiment, as described above, it becomes easy to culture cells on the second surface 34 of the substrate 30 by reducing the surface roughness of the second surface 34 of the substrate 30 or by coating the second surface 34 with a cell adhesive coating agent. In this way, when cells are cultured on the second surface 34 and measurements are performed using the cultured cells as the signal source 50, it becomes possible to shorten the distance between the magnetic concentrator 40 and the signal source 50, for example, to bring them into substantial contact. In this way, shortening the distance between the magnetic concentrator 40 and the signal source 50 makes it possible to further increase the sensitivity of detecting a magnetic signal from the signal source 50.
[0040] B. Second embodiment: In the first embodiment, a cylindrical magnetic material concentrator having at least shape magnetic anisotropy is used as the magnetic material concentrator 40, but a different shape may be used. In the following, as a second embodiment, another example of the magnetic material concentrator 40 having at least shape magnetic anisotropy will be described.
[0041] 9 to 11 are explanatory diagrams showing the configuration of a substrate having an array structure formed by magnetic concentrators having a shape different from that of the first embodiment. FIGS. 9(A), 10(A), and 11(A) are cross-sectional views, while FIGS. 9(B), 10(B), and 11(B) are perspective views. In FIGS. 9(B), 10(B), and 11(B), the position of the cross section of the corresponding FIG. 9(A), 10(A), or 11(A) is shown as an AA cross section. Each of the substrates 130, 230, and 330 shown in FIGS. 9 to 11 can be used in place of the substrate 30 of the first embodiment shown in FIG. 1, and can have the same configuration as the first embodiment except for the shapes of the magnetic concentrators 140, 240, and 340 provided in the substrates 130, 230, and 330.
[0042] FIG. 9 shows each magnetic material concentrator 140 in a conical shape, FIG. 10 shows each magnetic material concentrator 240 in a capsule shape with an elliptical cross section parallel to the central axis, and FIG. 11 shows each magnetic material concentrator 340 in a rectangular parallelepiped shape. In all of FIGS. 9 to 11, each magnetic material concentrator is arranged so that the Z-axis direction (thickness direction of the substrate 30) is the easy axis direction, and in the sensor structure, the magnetic sensor element 22 is arranged below each magnetic material concentrator on an extension of the easy axis of the magnetic material concentrator. Even with this configuration, the same effect as in the first embodiment can be obtained. Note that the magnetic material concentrator having shape magnetic anisotropy with the Z-axis direction as the easy axis direction may have a different shape, such as a pyramidal shape with a polygonal base.
[0043] C. Third embodiment: FIG. 12 is an explanatory diagram showing the configuration of a magnetic material concentrator 440 according to a third embodiment. Note that FIG. 12 shows a portion of the magnetic material concentrator 440 in a cutaway view. The magnetic material concentrator 440 according to the third embodiment can be used in place of the magnetic material concentrator 40 in the sensor structure 10 according to the first embodiment. Like the magnetic material concentrator 40, the magnetic material concentrator 440 has a cylindrical shape, with the longitudinal direction of the cylindrical shape being the formal easy axis direction of the magnetic material concentrator. However, the magnetic material concentrator 440 differs from the magnetic material concentrator 40 in that a portion including its surface (side surface) has a closed-circuit magnetic domain structure in a direction perpendicular to the easy axis direction. That is, the magnetic material concentrator 440 has a closed-circuit magnetic domain structure in the circumferential direction in a portion including the surface (side surface) of the cylindrical shape. In FIG. 12, the direction of the local easy axis in the outer periphery including the side surface of the cylindrical magnetic material concentrator 440 is indicated by an arrow. 12, in the cylindrical magnetic material concentrator 440, an easy axis is formed in the circumferential direction (perpendicular to the longitudinal direction of the cylindrical shape) along the outer periphery at the outer periphery including the side surfaces, and this prevents magnetic flux from penetrating into the magnetic material concentrator 440 from directions other than the easy axis (the longitudinal direction of the cylindrical shape). Such a closed-circuit magnetic domain structure can be formed, for example, by performing tension heat treatment or Joule annealing on the cylindrical member that will become the magnetic material concentrator 440.
[0044] FIG. 13 is an explanatory diagram showing the magnetization curve of the magnetic material concentrator 440. FIG. 13(A) shows the magnetization curve in the longitudinal direction of the cylindrical shape, and FIG. 13(B) shows the magnetization curve in the circumferential direction. The magnetic material concentrator 440 has a closed-circumferential magnetic domain structure, which generates a ferromagnetic hysteresis curve as shown in FIG. 13(B). As shown in FIG. 13(B), a large coercive force is generated and the magnetic permeability near zero magnetic field is small. Therefore, in the magnetic material concentrator 440, magnetic flux is less likely to enter from the side, and the direction in which magnetic flux converges, i.e., the detection direction, can be limited to the easy axis direction (the longitudinal direction of the cylindrical shape). Therefore, a sensor structure having such an array structure of magnetic material concentrators 440 can further improve the spatial resolution for detection.
[0045] 14A and 14B are explanatory diagrams showing the results of simulating the Z-axis magnetic flux density distribution when a magnetic dipole signal source is placed near the end of the magnetic concentrator on the second surface 34 of the substrate 30 for magnetic concentrators of various configurations that can be placed within the substrate 30. Fig. 14A shows an example using the magnetic concentrator 440 having the closed-circuit magnetic domain structure shown in Fig. 12, Fig. 14B shows an example using the cylindrical magnetic concentrator 40 having shape magnetic anisotropy without the closed-circuit magnetic domain structure described in the first embodiment, and Fig. 14C shows an example using a spherical magnetic concentrator formed in an isotropic spherical shape and having substantially no magnetic anisotropy.
[0046] Here, the magnetic dipole signal source on the second surface 34 was positioned at a position offset from the central axis of each magnetic concentrator in the Z-axis direction, i.e., the easy axis of the magnetic concentrator in Figures 14(A) and 14(B). The substrate 30 was a glass substrate, and each magnetic concentrator was made of permalloy (NiFe alloy). The cylindrical magnetic concentrators shown in Figures 14(A) and 14(B) had a length of 300 μm and a diameter of 20 μm, and the spherical magnetic concentrator shown in Figure 14(C) had a diameter of 300 μm. Simulations were performed under these conditions: these magnetic concentrators were embedded in the substrate 30. Compared with the spherical magnetic concentrator of FIG. 14(C), the magnetic concentrator 40 having magnetic anisotropy of FIG. 14(B) suppresses the penetration of magnetic flux from a signal source located off the easy axis, and the magnetic concentrator 440 having a closed-circuit magnetic domain structure of FIG. 14(A) further suppresses the penetration of magnetic flux from the signal source.
[0047] 15A to 15C are explanatory diagrams showing the results of a simulation of the relationship between the Z-axis magnetic flux density attenuation rate (attenuation rate relative to the average value of the Z-axis magnetic flux density) in each magnetic material concentrator and the distance between the magnetic dipole signal source and the magnetic material concentrator when a magnetic field is generated in the magnetic dipole signal source for each of the configurations shown in FIGS. 14A to 14C. FIG. 15A is an explanatory diagram of the "signal source distance," which is the distance between the magnetic material concentrator and the magnetic dipole signal source, and FIG. 15B is an explanatory diagram showing the results of the simulation. The "signal source distance" refers to the distance between the end of the magnetic material concentrator and the center of the magnetic dipole signal source on the second surface 34 of the substrate 30. As shown in Figure 15(B), in the spherical magnetic concentrator of Figure 14(C), even if the distance from the signal source increases, the degree of attenuation of the magnetic flux density is relatively gradual, whereas in the magnetic concentrators having magnetic anisotropy of Figure 14(B) and Figure 14(A), the magnetic flux density rapidly attenuates when the distance from the signal source increases slightly, and it was confirmed that this tendency is particularly strong in the magnetic concentrator 440 having the closed-circuit magnetic domain structure of Figure 14(A).
[0048] D. Fourth embodiment: Fig. 16 is an explanatory diagram showing the schematic configuration of a sensor structure 510 of the fourth embodiment in the same manner as Fig. 1. In the sensor structure 510, parts common to the sensor structure 10 of the first embodiment are given the same reference numerals.
[0049] In the sensor structure, the magnetic sensor element or a portion of the magnetic sensor element can be used as a magnetic concentrator, and the magnetic sensor element and the magnetic concentrator can be integrated. FIG. 16 shows an example of such a configuration, in which a magnetic sensor element, which is a magnetic impedance element, is configured using a portion of the components constituting the magnetic concentrator. Specifically, instead of the magnetic concentrator 40, the sensor structure 510 includes a magnetic concentrator 540, which is a magnetic wire having magnetic anisotropy with the easy axis in the Z-axis direction. The magnetic concentrator 540 extends further in the −Z-axis direction from the first surface 32 of the substrate 30. This portion extending in the −Z-axis direction is combined with a pickup coil to configure the magnetic sensor element 522.
[0050] This configuration not only provides the same effects as the sensor structure 10 of the first embodiment, but also simplifies the overall configuration of the sensor structure by eliminating the need for a connection structure between the magnetic material concentrator and the magnetic sensor element. Furthermore, the absence of a magnetic circuit gap between the magnetic material concentrator and the magnetic sensor element reduces attenuation of the magnetic signal reaching the magnetic sensor element, thereby improving the detection sensitivity of the magnetic sensor element. In the sensor structure 510 shown in FIG. 16, the magnetic material concentrator 540 may further have a closed-circuit magnetic domain structure as described in the third embodiment.
[0051] E. Fifth embodiment: Fig. 17 is an explanatory diagram showing the schematic configuration of a sensor structure 610 of the fifth embodiment in the same manner as Fig. 1, and Fig. 18 is a perspective view showing a part of the appearance of the sensor structure 610 in the same manner as Fig. 2. In the sensor structure 610, parts common to the sensor structure 10 of the first embodiment are given the same reference numerals.
[0052] In the sensor structure 10 of the first embodiment described above, one magnetic material concentrator 40 and one magnetic sensor element 22 constitute the sensor unit 12, and within the sensor unit 12, the magnetic sensor element 22 is arranged on an extension of the easy axis of magnetization of the magnetic material concentrator 40, but a different configuration may be used. The sensor structure 610 of the fifth embodiment differs from the first embodiment in that the sensor unit includes two magnetic material concentrators corresponding to each sensor element. In the sensor structure, the magnetic sensor element and the magnetic material concentrator corresponding to this magnetic sensor element may be arranged to form a magnetic circuit in which a magnetic signal generated by a signal source is input to the magnetic sensor element via the magnetic material concentrator. In the sensor structure 610 shown in Figures 17 and 18, a pair of magnetic concentrators 640 arranged adjacent to each other within the substrate 30 and a magnetic sensor element 622 arranged magnetically connected to both of the pair of magnetic concentrators 640 on the first surface 32 side of the substrate 30 constitute a sensor unit 612, and multiple sensor units 612 are arranged in an array.
[0053] 17 and 18, each of the pair of magnetic material concentrators 640 constituting the sensor unit 612 has shape magnetic anisotropy and is formed in a quadrangular pyramidal truncated shape. Also, in Fig. 17 and 18, a magnetic sensor element 622, which is a magnetic impedance element in which a pickup coil is wound around a magnetic wire, is arranged horizontally (in a direction parallel to the XY plane) and magnetically connected to each of the pair of magnetic material concentrators 640.
[0054] In such a sensor structure 610, when the signal source 50 is disposed between a pair of magnetic concentrators 640 on the second surface 34 of the substrate 30, magnetic flux flows in from the signal source 50 to one of the magnetic concentrators 640 and flows out of the other magnetic concentrator 640 via the magnetic sensor element 622. In this way, the magnetic circuit formed by the sensor unit 612 including the signal source 50 has two flows, a clockwise flow and a counterclockwise flow, as shown in FIG.
[0055] 19 and 20 are explanatory diagrams showing the results of a simulation comparing the behavior of magnetic signals between a configuration including a pair of magnetic material concentrators 640 having magnetic anisotropy, such as the sensor structure 610 of the fifth embodiment, and a configuration not including the pair. FIG. 19 shows the results of investigating the behavior of magnetic signals for a configuration including the magnetic material concentrators 640 having magnetic anisotropy, and FIG. 20 shows the results of investigating the behavior of magnetic signals for a configuration not including the magnetic material concentrators 640. FIGS. 19(A) and 20(B) show gray color maps of magnetic signal strength. FIGS. 19(B) and 20(B) show the magnetic flux density distribution in the longitudinal direction of the magnetic sensor element 622 (the X-axis direction in FIG. 17, where the longitudinal length of the magnetic sensor element 622 is 0.1 mm), showing the magnetic signal attenuation suppression effect. 19(B) and 20(B), the horizontal axis represents the longitudinal distance of the magnetic sensor element 622, that is, the distance from the left end of the magnetic sensor element 622 in the figure, and the vertical axis represents the magnetic flux density (T). The above simulation was performed using COMSOL Multiphysics, which is general-purpose physical simulation software.
[0056] In the simulation shown in FIG. 19 , magnetic flux was generated from an ellipsoidal signal source (semiaxes: 20 μm × 20 μm × 10 μm) equivalent in size to a single cell, placed on a glass substrate 30. A truncated-pyramidal Permalloy magnetic concentrator 640 was embedded in the glass substrate 30, and a simulation was performed to assess the magnetic signal attenuation suppression effect of this flux concentrator structure. The magnetic concentrator 640 measured 0.2 mm in width, 0.3 mm in height, and 0.02 mm in depth. FIG. 20 shows the results of a simulation performed under the same conditions as FIG. 19 , except that the magnetic concentrator 640 was not provided. The results shown in FIGS. 19 and 20 indicate that by adopting the structure of the sensor unit 612 according to this embodiment, a magnetic circuit is formed from the signal source 50 to the magnetic sensor element 622 via the magnetic concentrator 640, and the magnetic flux density in the magnetic sensor element 622 is increased by more than 50 times compared to when the magnetic concentrator 640 is not provided.
[0057] F. Sixth embodiment: FIG. 21 is an explanatory diagram showing a schematic configuration of a sensor structure 710 of the sixth embodiment. FIG. 21(A) is a perspective view, and FIG. 21(B) is a cross-sectional view. In the sensor structure 710, parts common to the sensor structure 10 of the first embodiment are given the same reference numerals. Note that in FIG. 21, the internal structure of the magnetic sensor array 20 is not shown.
[0058] In addition to the same configuration as the sensor structure 10, the sensor structure 710 further includes a shield portion 760 provided on the second surface 34 of the substrate 30, protruding from the second surface 34 and surrounding the entire area where the multiple magnetic concentrators 40 are arranged. FIG. 21 shows a cylindrical shield portion 760 provided along the outer periphery of the substrate 30. The shield portion 760 is a structure for blocking magnetic flux and may be made of a material that blocks the passage of magnetic flux, such as a high-permeability magnetic material such as a ferromagnetic material that absorbs magnetic force. With this configuration, environmental noise from around the sensor structure can be blocked in each sensor unit 12, further increasing the sensitivity of the magnetic sensor element 22.
[0059] G. Seventh embodiment: FIG. 22 is an explanatory diagram showing a schematic configuration of a sensor structure 810 of the seventh embodiment. FIG. 22(A) is a top view of one sensor unit 12, FIG. 22(B) is a perspective view of the sensor structure 810, and FIG. 22(C) is a cross-sectional view of the sensor structure 810. In the sensor structure 810, parts common to the sensor structure 10 of the first embodiment are given the same reference numerals. Note that in FIG. 22, the internal structure of the magnetic sensor array 20 is not shown.
[0060] In addition to the same configuration as the sensor structure 10, the sensor structure 810 further includes a shield portion 860 provided on the second surface 34 of the substrate 30, protruding from the second surface 34 and surrounding the area where each magnetic concentrator 40 is disposed. FIG. 22 shows a cylindrical shield portion 860 provided to surround each magnetic concentrator 40. The shield portion 860 is a structure for blocking magnetic flux and may be made of a material that blocks the passage of magnetic flux, such as a high-permeability magnetic material such as a ferromagnetic material that absorbs magnetic force. This configuration improves the reliability of blocking environmental noise from around the sensor structure in each sensor unit 12, further improving the sensitivity of the magnetic sensor element 22.
[0061] H. Other Embodiments: In the above-described embodiments, examples have been described in which cultured cells growing on the second surface 34 of the substrate 30 are used as the signal source 50 when measuring magnetic signals using the sensor structure. However, measurements may also be performed using a different type of measurement target as the signal source 50. For example, when cultured cells prepared separately from the sensor structure are used as the signal source 50, the sensor structure can be inverted and the second surface 34 of the substrate 30 can be brought close to or in contact with the signal source 50 to perform measurement. Furthermore, the measurement target may be, in addition to cultured cells, biological tissue composed of cardiac muscle cells or nerve cells that generate magnetic signals, or a living organism that includes such biological tissue. Furthermore, the sensor structure may be used not only when the measurement target includes cells as described above, but also for the purpose of investigating and analyzing the state of devices that may generate magnetic signals due to the flow of weak currents, such as electrical circuit boards inside machines or the internal structure of batteries. Even in these cases, the same effect of detecting magnetic signals with improved detection accuracy and spatial resolution can be achieved. Even in these cases, by reducing the distance between the magnetic concentrator of the sensor structure and the signal source, for example by bringing them into contact with each other, it is possible to suppress attenuation of the magnetic signal and increase the detection sensitivity. [Example]
[0062] A substrate 30 including the magnetic concentrator 40 in the sensor structure 10 described in the first embodiment was fabricated, and it was confirmed that it could be suitably used in applications where cells cultured on the second surface 34 of the substrate 30 were used as a signal source 50 to be measured. Here, the manufacturing method shown in FIG. 4 was followed. A cylindrical member (diameter 0.6 mm) made of permalloy (NiFe alloy) was used as the concentrator member prepared in step T100. A glass plate (thickness 1 mm) was used as the substrate plate prepared in step T120. A silica-based adhesive was used as the adhesive used in step T150.
[0063] Fig. 23 is an explanatory diagram showing a photograph of the fabricated sensor structure 10. Fig. 23(A) shows a photograph of the sensor structure 10 viewed from above, and Fig. 23(B) is a photograph of a perspective view of the sensor structure 10. As shown in Fig. 23, a plurality of magnetic concentrators 40 were provided in an array within a highly transparent glass substrate 30, penetrating the substrate 30 so that their ends were exposed on a second surface 34 of the substrate 30.
[0064] 24 and 25 are explanatory diagrams showing the results of a non-contact measurement of the surface roughness of the second surface 34 of the substrate 30 using a 3D measuring laser microscope after the polishing process (mechanical polishing) in step T160. FIG. 24(A) shows the surface height display (2D), and FIG. 24(B) shows the surface height display (3D). Height profiles were also acquired along two orthogonal lines shown as "Line 1" and "Line 2" in FIG. 23(A). That is, height profiles were continuously acquired along "Line 1" and "Line 2" on the second surface 34, from outside the outer periphery of the magnetic concentrator 40, across the edge of the magnetic concentrator 40 so as to pass through the center of the magnetic concentrator 40, and beyond the outer periphery of the magnetic concentrator 40. FIG. 25(A) shows the height profile along "Line 1," and FIG. 25(B) shows the height profile along "Line 2." 25(A) and 25(B), the horizontal axis indicates the distance from the starting point of the profile acquisition for each line, and the vertical axis indicates the height profile. As shown in FIGS. 24 and 25, the difference in height between the highest and lowest points on the second surface 34 was 10 μm or less, specifically 4 μm or less.
[0065] After polishing in step T160, a coating layer made of a cell adhesion coating agent was formed on the second surface 34 of the substrate 30, covering the area including the region in the substrate 30 where the magnetic concentrators 40 were formed. Specifically, the coating layer was formed so as to cover the entire second surface 34 of the substrate 30, in which the magnetic concentrators 40 were formed. Two types of cell adhesion coating agents were used: collagen and Matrigel. Specifically, the substrate 30 was placed in a 6-well plate, 2 mL of phosphate buffered saline was added, and 20 μL of Cellmatrix type IA (Nitta Gelatin Co., Ltd.), which contains collagen, or typically 20 μL of Matrigel (Corning Incorporated; Matrigel is a registered trademark) (variable depending on the lot) was added. The plate was stirred and then allowed to stand in a CO2 incubator for 1 hour, thereby carrying out the coating process. After the above coating process, the liquid containing the cell adhesive coating agent was removed by suction from the substrate 30, and then cells were seeded and cultured on each substrate 30 on which the coating layer had been formed. First, to disinfect bacteria present on the surface of the substrate 30, the substrate was placed in a well of a 12-well multiwell plate and treated with 70% ethanol for 15 minutes. Then, the ethanol was removed, and the surface of the substrate 30 was rinsed with sterilized water to completely remove the cleaning solution, and then air-dried. HEK293 cells were used for seeding the cells at a density of 1.5 x 104 cells / cm. 2 The cells were seeded at a density of 1000 x g in a suspension in a medium (RPMI1640-10% FBS).
[0066] Figure 26 is an explanatory diagram showing the results of fluorescent observation of cells after culture. Figure 26 shows the results of a substrate 30 with magnetic concentrators 40 formed thereon, using collagen or Matrigel as a cell adhesion coating agent, as well as the results of similar cell seeding and culture using a slide glass coated with collagen or Matrigel as a comparative example. Figure 26 shows a bright-field image, fluorescently stained images of live cells, and fluorescently stained images of dead cells. In the image of the substrate 30 with magnetic concentrators 40 formed thereon, the area where the magnetic concentrators 40 are formed is enclosed by a dashed line. As shown in Figure 26, cells adhered and proliferated on the substrate 30 with magnetic concentrators 40 as well as on a slide glass, and the coated surface was efficiently covered by cells. Furthermore, like a slide glass, the substrate 30 with magnetic concentrators 40 formed thereon exhibited no cytotoxicity, confirming its suitability for use in applications where cells cultured on the substrate 30 are used as a signal source 50.
[0067] The present disclosure is not limited to the above-described embodiments, and can be realized in various configurations without departing from the spirit thereof. For example, the technical features in the embodiments corresponding to the technical features in each aspect described in the Summary of the Invention section can be appropriately replaced or combined to solve some or all of the above-described problems or achieve some or all of the above-described effects. Furthermore, if a technical feature is not described as essential in this specification, it can be appropriately deleted.
[0068] The present disclosure can also be realized in the following forms. [Application example 1] A sensor structure comprising: a magnetic sensor array in which a plurality of magnetic sensor elements are arranged two-dimensionally; a substrate disposed on the magnetic sensor array; a plurality of magnetic concentrators provided in the substrate corresponding to the plurality of magnetic sensor elements; Equipped with each of the plurality of magnetic concentrators has magnetic anisotropy; The magnetic sensor element and a magnetic concentrator provided corresponding to the magnetic sensor element are arranged to form a magnetic circuit in which a magnetic signal is input to the magnetic sensor element via the magnetic concentrator. Sensor structure. [Application example 2] The sensor structure according to Application Example 1, The magnetic sensor element is disposed on an extension of the axis of easy magnetization of a magnetic concentrator provided corresponding to the magnetic sensor element. Sensor structure. [Application example 3] The sensor structure according to Application Example 2, each of the plurality of magnetic concentrators is arranged such that the direction perpendicular to the surface direction of the substrate is the axis of easy magnetization; Each of the magnetic sensor elements is disposed at a position where it overlaps with the corresponding magnetic concentrator in a direction perpendicular to the surface direction of the substrate. Sensor structure. [Application example 4] The sensor structure according to any one of Application Examples 1 to 3, Each of the plurality of magnetic concentrators is disposed embedded in the substrate or disposed through the substrate. Sensor structure. [Application example 5] The sensor structure according to any one of Application Examples 1 to 4, Each of the plurality of magnetic concentrators is made of a soft magnetic material having one or more properties of shape magnetic anisotropy, induced magnetic anisotropy, stress magnetic anisotropy, and magnetocrystalline anisotropy. Sensor structure. [Application Example 6] The sensor structure according to Application Example 5, Each of the plurality of magnetic concentrators has shape magnetic anisotropy and is formed in a shape selected from a cylindrical shape, a rectangular parallelepiped shape, a capsule shape in which the cross section parallel to the central axis is an ellipse, a pyramidal shape, and a conical shape. Sensor structure. [Application Example 7] The sensor structure according to any one of Application Examples 1 to 6, Each of the plurality of magnetic concentrators has magnetic anisotropy, and has a closed-circuit magnetic domain structure in an outer periphery including a surface of the magnetic concentrator that suppresses the penetration of magnetic flux from directions other than the easy magnetization direction related to the magnetic anisotropy. Sensor structure. [Application Example 8] The sensor structure according to any one of Application Examples 1 to 7, The magnetic concentrator and at least a part of the magnetic sensor element provided corresponding to the magnetic concentrator are integrally formed. Sensor structure. [Application Example 9] The sensor structure according to any one of Application Examples 1 to 8, a coating layer including a cell adhesive component is provided on a second surface of the substrate, the second surface being different from a first surface facing the magnetic sensor array, so as to cover an area including a region in the substrate where the plurality of magnetic concentrators are formed; The diameter of a cross section of each of the plurality of magnetic concentrators parallel to the surface direction of the substrate is 5 μm or more and 1000 μm or less. Sensor structure. [Application Example 10] The sensor structure according to Application Example 9, the magnetic concentrator is exposed on the second surface of the substrate; The difference in height between the second surface of the substrate and the portion of the magnetic concentrator exposed at the second surface is 10 μm or less. Sensor structure. [Application Example 11] The sensor structure according to any one of Application Examples 1 to 10, further comprising: a shield portion that protrudes from a second surface of the substrate, different from a first surface facing the magnetic sensor array, and that is provided so as to surround an entire region in which the plurality of magnetic concentrators are arranged, and that prevents passage of magnetic flux; Sensor structure. [Application Example 12] The sensor structure according to any one of Application Examples 1 to 11, further comprising: a shield portion that is provided on a second surface of the substrate, different from a first surface facing the magnetic sensor array, protruding from the second surface and surrounding an area where the magnetic concentrator is arranged for each magnetic concentrator, and that prevents passage of magnetic flux; Sensor structure. [Explanation of symbols]
[0069] 10,510,610,710,810...Sensor structure 12,612...Sensor unit 20...Magnetic sensor array 22,522,622...Magnetic sensor element 30, 130, 230, 330... PCB 32...First side 34...Second side 35...Adhesive 40, 140, 240, 340, 440, 540, 640...Magnetic concentrator 50…Signal source 760,860...Shield part
Claims
1. A sensor structure comprising: a magnetic sensor array in which a plurality of magnetic sensor elements are arranged two-dimensionally; a substrate disposed on the magnetic sensor array; a plurality of magnetic concentrators provided in the substrate corresponding to the plurality of magnetic sensor elements; Equipped with each of the plurality of magnetic concentrators has magnetic anisotropy; The magnetic sensor element and a magnetic concentrator provided corresponding to the magnetic sensor element are arranged to form a magnetic circuit in which a magnetic signal is input to the magnetic sensor element via the magnetic concentrator. Sensor structure.
2. 2. The sensor structure according to claim 1, The magnetic sensor element is disposed on an extension of the axis of easy magnetization of a magnetic concentrator provided corresponding to the magnetic sensor element. Sensor structure.
3. 3. The sensor structure according to claim 2, each of the plurality of magnetic concentrators is arranged such that the direction perpendicular to the surface direction of the substrate is the axis of easy magnetization; Each of the magnetic sensor elements is disposed at a position where it overlaps with the corresponding magnetic concentrator in a direction perpendicular to the surface direction of the substrate. Sensor structure.
4. 2. The sensor structure according to claim 1, Each of the plurality of magnetic concentrators is disposed embedded in the substrate or disposed through the substrate. Sensor structure.
5. 2. The sensor structure according to claim 1, Each of the plurality of magnetic concentrators is made of a soft magnetic material having one or more properties of shape magnetic anisotropy, induced magnetic anisotropy, stress magnetic anisotropy, and magnetocrystalline anisotropy. Sensor structure.
6. The sensor structure according to claim 5, Each of the plurality of magnetic concentrators has shape magnetic anisotropy and is formed in a shape selected from a cylindrical shape, a rectangular parallelepiped shape, a capsule shape in which the cross section parallel to the central axis is an ellipse, a pyramidal shape, and a conical shape. Sensor structure.
7. 2. The sensor structure according to claim 1, Each of the plurality of magnetic concentrators has magnetic anisotropy, and has a closed-circuit magnetic domain structure in an outer periphery including a surface of the magnetic concentrator that suppresses the penetration of magnetic flux from directions other than the easy magnetization direction related to the magnetic anisotropy. Sensor structure.
8. 2. The sensor structure according to claim 1, The magnetic concentrator and at least a part of the magnetic sensor element provided corresponding to the magnetic concentrator are integrally formed. Sensor structure.
9. 2. The sensor structure according to claim 1, a coating layer including a cell adhesive component is provided on a second surface of the substrate, the second surface being different from a first surface facing the magnetic sensor array, so as to cover an area including a region in the substrate where the plurality of magnetic concentrators are formed; The diameter of a cross section of each of the plurality of magnetic concentrators parallel to the surface direction of the substrate is 5 μm or more and 1000 μm or less. Sensor structure.
10. 10. The sensor structure according to claim 9, the magnetic concentrator is exposed at the second surface of the substrate; The difference in height between the second surface of the substrate and the portion of the magnetic concentrator exposed at the second surface is 10 μm or less. Sensor structure.
11. 2. The sensor structure according to claim 1, further comprising: a shield portion that protrudes from a second surface of the substrate, the second surface being different from a first surface facing the magnetic sensor array, and that is provided so as to surround an entire region in which the plurality of magnetic concentrators are arranged, and that prevents passage of magnetic flux; Sensor structure.
12. 2. The sensor structure according to claim 1, further comprising: a shield portion that is provided on a second surface of the substrate, different from a first surface facing the magnetic sensor array, protruding from the second surface and surrounding an area where the magnetic concentrator is disposed for each magnetic concentrator, and that prevents passage of magnetic flux; Sensor structure.
Citation Information
Patent Citations
Flux concentrators for out-of-plane magnetic field concentration.
JP2022547945A