WO2012120852A1 - Puce de détection - Google Patents

Puce de détection Download PDF

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Publication number
WO2012120852A1
WO2012120852A1 PCT/JP2012/001436 JP2012001436W WO2012120852A1 WO 2012120852 A1 WO2012120852 A1 WO 2012120852A1 JP 2012001436 W JP2012001436 W JP 2012001436W WO 2012120852 A1 WO2012120852 A1 WO 2012120852A1
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Prior art keywords
hole
diaphragm
sensor chip
holes
silicon
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PCT/JP2012/001436
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English (en)
Japanese (ja)
Inventor
健樹 山本
中谷　将也
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パナソニック株式会社
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Publication of WO2012120852A1 publication Critical patent/WO2012120852A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
    • G01N33/48728—Investigating individual cells, e.g. by patch clamp, voltage clamp

Definitions

  • the present invention relates to a sensor chip used for a sensor device such as a chemical substance identification sensor or a cell electrophysiological sensor for measuring the electrophysiological activity of a cell.
  • Biosensors and biochips are used for biosensing proteins, genes, low molecular weight signal molecules, etc. based on the ecological molecular recognition mechanism. Specifically, biosensing can be performed by monitoring a selective specific reaction such as a receptor ligand and an antigen-antibody reaction and a selective catalytic reaction such as an enzyme using a predetermined device.
  • the patch clamp method is used as an example of a biosensing method.
  • the patch clamp method is one of methods for elucidating the function of ion channels existing in cell membranes or screening (inspecting) drugs using the electrical activity of cells as an index.
  • a minute portion (patch) of a cell membrane is gently sucked with a tip portion of a micropipette.
  • a current across the patch is measured at a fixed membrane potential by a microelectrode probe provided on the micropipette.
  • the patch clamp method is one of the few methods that can examine the physiological functions of cells in real time.
  • the patch clamp method requires special techniques and skills for the production and operation of micropipettes. Therefore, it takes a lot of time to measure one sample. Therefore, it is not suitable for use in screening a large amount of drug candidate compounds at high speed.
  • a flat-plate microelectrode probe using a microfabrication technique has been developed. Such microelectrode probes are suitable for automated systems that do not require the insertion of a micropipette for individual cells.
  • a cell electrophysiological sensor has been proposed as a method for electrophysiologically measuring an ion channel present in a cell membrane. This does not require the skill of inserting a micropipette into an individual cell like the patch clamp method. Therefore, it is suitable for a high-throughput automated system.
  • a method for measuring an averaged ion current from a cell population has been proposed.
  • a sensor device including a plate in which a plurality of through-holes are arranged in a lattice form in each well is used.
  • the ionic current from the cell population is measured. Therefore, the average current measured by this sensor device is uniform between the wells and has little variation. That is, the success rate of measurement with the sensor device is very high. As a result, measurement in a plurality of wells becomes unnecessary, and the throughput is improved.
  • the sensor chip includes a diaphragm including a first surface and a second surface facing the first surface, and a plurality of through holes penetrating the first surface and the second surface.
  • the diaphragm has a lower mechanical strength against stress from a specific direction than mechanical strength against stress from other directions.
  • the plurality of through holes have a first through hole and a second through hole closest to the first through hole. The direction along the first line segment connecting the center of the first through hole and the center of the second through hole is different from the specific direction.
  • FIG. 1 is a cross-sectional view of a sensor device according to an embodiment of the present invention.
  • FIG. 2 is a cross-sectional view of the sensor chip in the embodiment of the present invention.
  • FIG. 3 is a cross-sectional view for explaining the method for manufacturing the sensor chip in the embodiment of the present invention.
  • FIG. 4 is a cross-sectional view for explaining the method for manufacturing the sensor chip in the embodiment of the present invention.
  • FIG. 5 is a cross-sectional view for explaining the method for manufacturing the sensor chip in the embodiment of the present invention.
  • FIG. 6 is a cross-sectional view for explaining the method for manufacturing the sensor chip in the embodiment of the present invention.
  • FIG. 7 is a top view of the sensor chip in the embodiment of the present invention.
  • FIG. 8A is a diagram showing a cleavage plane of a silicon (100) substrate.
  • FIG. 8B is a diagram showing a cleavage plane of the silicon (110) substrate.
  • FIG. 8C is a diagram showing a cleavage plane of the silicon (111) substrate.
  • a cell electrophysiological sensor is used as an example of the sensor device, but the use is not particularly limited as long as the same sensor chip is used.
  • FIG. 1 is a cross-sectional view of a cell electrophysiological sensor which is an example of a sensor device.
  • a cell electrophysiological sensor 100 as a sensor device has a sensor chip 13 and a mounting substrate 11.
  • the sensor chip 13 has a diaphragm 12 and is mounted on the mounting substrate 11.
  • the cell electrophysiological sensor 100 further includes a first electrode tank 14, a first electrode 15, a second electrode tank 16, and a second electrode 17.
  • the first electrode tank 14 is disposed above the diaphragm 12.
  • the first electrode 15 is disposed inside the first electrode tank 14 and on the upper surface side that is the first surface of the diaphragm 12.
  • the second electrode tank 16 is disposed below the diaphragm 12.
  • the second electrode 17 is disposed inside the second electrode tank 16 and on the lower surface side that is the second surface side of the diaphragm 12.
  • the diaphragm 12 is provided with a plurality of through holes 18 penetrating between the first surface and the second surface.
  • the first electrolyte and the second electrolyte flow in the direction of the arrow shown in FIG.
  • the diaphragm 12 becomes a boundary surface between the first electrolytic solution and the second electrolytic solution.
  • the subject 19 and the first electrolytic solution are drawn into the through hole 18 by applying pressure from the first surface side of the diaphragm 12 through the through hole 18 or reducing pressure from the second surface side of the diaphragm 12. Then, the subject 19 is sucked and held on the surface of the diaphragm 12 so as to block the through hole 18. As a result, the subject 19 can be sampled.
  • aqueous solution containing about 155 mM K + ions, about 12 mM Na + ions, and about 4.2 mM Cl ⁇ ions as the first electrolyte. Further, it is preferable to use an aqueous solution containing about 4 mM of K + ions, about 14 mM of Na + ions, and about 123 mM of Cl ⁇ ions as the second electrolytic solution. Note that the first electrolytic solution and the second electrolytic solution may be different as in the present embodiment, or those having similar components may be used.
  • chemical stimuli include chemical stimuli such as chemicals and poisons
  • physical stimuli include mechanical displacement, light, heat, electricity, and electromagnetic waves.
  • the subject 19 becomes active with respect to these stimuli, for example, the subject 19 releases or absorbs various ions through channels held by the cell membrane. As a result, the potential gradient inside and outside the cell that is the subject 19 changes. This electrical change is detected by the first electrode 15 and the second electrode 17, and the pharmacological reaction of the cells can be examined.
  • mammalian muscle cells are used as an example of the subject 19, but the subject 19 is not limited to cells, and may be any object such as particles.
  • a DNA sensor that detects a specific DNA sequence such as a virus or a food production area
  • a SNP sensor that detects a SNP (single nucleotide polymorphism) sequence
  • an antigen sensor that detects the presence of an allergen (allergic antigen)
  • It can be widely used in the medical field, the environmental field, and the like.
  • the first electrode 15 does not necessarily have to be formed in the sensor device, and may be provided so as to be in contact with the solution filled in the first electrode tank 14.
  • the second electrode 17 does not necessarily have to be formed in the sensor device, and may be provided so as to be in contact with the solution filled in the second electrode tank 16.
  • FIG. 2 is a cross-sectional view of the sensor chip 13.
  • the sensor chip 13 has a diaphragm 12 and a silicon layer 22.
  • Diaphragm 12 has a first surface and a second surface opposite to the first surface.
  • the silicon layer 22 is bonded to the outer peripheral surface of the first surface of the diaphragm 12.
  • the diaphragm 12 is formed by laminating a silicon layer 20 which is a first layer containing silicon as a main component and a silicon oxide layer 21 which is a second layer containing silicon oxide as a main component.
  • the silicon layer 20 of the diaphragm 12 has a cleavage property in which the mechanical strength with respect to stress from a specific direction is lower than the mechanical strength from other directions.
  • the specific direction is the direction of the cleavage plane of the silicon layer 20.
  • the first surface, the second surface, and the surface of the silicon layer 22 of the diaphragm 12 are layers made of a silicon oxide film 23 that does not have a cleavage property, a crystalline material that has a cleavage property such as a diamond, or the like. Is preferably formed.
  • a silicon oxide film 23 is formed on the second surface of the diaphragm 12 and the surface of the silicon layer 22.
  • a crystalline material having a cleavage property such as diamond
  • it is preferably coated in a direction not parallel to the first or second surface of the diaphragm 12 and the surface direction of the silicon layer 22. That is, it is preferable that the cleavage direction of the crystalline material having cleavage properties is different from the cleavage direction of the silicon layer 22.
  • the diaphragm 12 is formed with a through hole 18 which is a surface bonded to the silicon layer 22 and communicates from the first surface holding the subject 19 to the second surface which is the opposite surface.
  • the silicon layer 20 has a weak cleaving property against a force applied in the direction of a specific surface because the connection between atoms is weak.
  • the silicon oxide layer 21 does not have a cleavage property, there is no low mechanical strength against stress from a specific direction. Therefore, it is possible to prevent the diaphragm 12 from being cracked by laminating the silicon oxide layer 21 that has cleavage properties and is relatively easy to crack on the silicon layer 20 that does not have cleavage properties.
  • the material laminated with the silicon layer 20 may be a material that does not have cleavage property or a material that has a cleavage plane direction different from the cleavage plane direction of silicon.
  • an insulating material having electrical insulating properties because noise during measurement can be reduced.
  • An example of a material that does not have a cleavage property is not limited to silicon oxide, but includes amorphous materials such as silicon nitride, silicon oxynitride, hafnium oxide, aluminum oxide, tantalum oxide, and titanium oxide, and various organic materials. Any material may be mentioned.
  • crystalline materials such as a diamond and a mica, are mentioned.
  • the silicon layer 20 is made of silicon (100).
  • SOI substrate has a three-layer structure of silicon layer-silicon oxide layer-silicon layer. Unlike the silicon layer, the silicon oxide layer does not have a cleavage property. For this reason, it becomes harder to break than forming a substrate with only a silicon layer.
  • the same effect as in the present embodiment can be obtained even if a silicon single crystal plate is used as the substrate.
  • silicon (100) is used, whether it is an SOI substrate or a silicon single crystal plate, the through holes 18 are formed so that the arrangement thereof does not follow the silicon (110). Yes.
  • the entire surface of the sensor chip 13 is covered with the silicon oxide film 23.
  • silicon (100) includes silicon (010) and silicon (001) that are equivalent due to symmetry of the crystal structure.
  • silicon doped with elements such as boron and phosphorus is also included.
  • the SOI substrate By using the SOI substrate, a large number of high-precision sensor chips 13 can be manufactured collectively by fine processing by photolithography and etching techniques.
  • the silicon oxide layer serves as an etching stop layer during the etching process in the process of manufacturing the sensor chip 13. Therefore, a highly accurate sensor chip 13 can be manufactured.
  • the silicon oxide layer is rich in hydrophilicity, the generation of bubbles during measurement can be suppressed, and the bubbles can be easily removed. Therefore, highly accurate measurement can be realized. If bubbles remain in the vicinity of the through-hole 18 at the time of measurement, the giga-seal property is greatly lowered, and the measurement accuracy is greatly adversely affected.
  • the thickness of the silicon oxide layer in the SOI substrate is preferably 0.5 to 10 ⁇ m from the viewpoint of use as an etching stop layer and productivity.
  • the diaphragm 12 may be as thin as several ⁇ m depending on the case. Therefore, the silicon layer 22 is formed on the outer peripheral portion of the diaphragm 12 in consideration of handling properties and mounting properties in the manufacturing process. That is, the silicon layer 22 has a function as a holding part of the sensor chip 13, a function of increasing mechanical strength, and a function of storing liquid.
  • the silicon layer 22 is not an indispensable requirement, and it is preferable to appropriately select a predetermined dimension depending on the shape and structure of the sensor chip 13.
  • the silicon layer 22 as the holding portion may be formed by etching from the SOI substrate, or a separately formed silicon layer 22 may be bonded to the diaphragm 12. However, it is preferable to form the SOI substrate by etching from the viewpoint of process consistency.
  • the thickness of the diaphragm 12 is desirably about 5 to 50 ⁇ m.
  • the silicon oxide layer functioning as an etching stop layer is generally formed by thermal oxidation.
  • other methods such as a CVD method, a sputtering method, and a CSD method may be used.
  • a silicon oxide layer a so-called PSG layer in which silicon oxide is doped with phosphorus, a so-called BSG layer in which silicon oxide is doped with boron, or a BPSG layer in which phosphorus and boron are doped may be used.
  • the number and the hole diameter of the through holes 18 are not particularly limited, and may be arbitrarily specified according to the size and shape of the sensor chip 13.
  • an SOI substrate having a silicon layer made of silicon (100) is prepared as a substrate for manufacturing the sensor chip 13.
  • a first resist mask 24 is formed on the surface of the silicon layer 20 as shown in FIG. At this time, a plurality of mask holes 25 having substantially the same shape as the cross-sections of the desired plurality of through holes 18 are patterned in the first resist mask 24.
  • the silicon layer 20 is etched to form the through holes 18.
  • dry etching capable of high-precision fine processing is desirable.
  • SF 6 is used as an etching gas for promoting etching
  • C 4 F 8 is used as a gas for suppressing etching.
  • plasma is generated by an inductive coupling method of an external coil, and when SF 6 as an etching gas is introduced therein, F radicals are generated. The F radicals react with the silicon layer 20 and the silicon layer 20 is chemically etched.
  • this fluorocarbon film serves as a protective film to suppress etching.
  • the protective film is formed not only on the wall surface portion of the through-hole 18 formed by etching but also on the bottom surface.
  • the protective film formed on the bottom surface is easily removed by the impact of ion collision in etching, as compared with the protective film formed on the wall surface.
  • etching in the wall surface direction of the through-hole 18 is suppressed, and etching proceeds only in the vertical direction (depth direction).
  • the through hole 18 eventually reaches the surface of the silicon oxide layer 21.
  • the silicon oxide layer 21 has a property that it is difficult to be etched under the above etching conditions.
  • etching in the vertical direction stops at the exposed surface of the silicon oxide layer 21.
  • etching ions are accumulated on the surface of the exposed silicon oxide layer 21.
  • the etching ions that have entered the through hole 18 and the etching ions accumulated on the surface of the silicon oxide layer 21 are repelled, and the etching ions proceed in the lateral direction. Therefore, in the vicinity of the silicon oxide layer 21, a concave portion 26 that gradually widens in a tapered shape is formed. This is because the diaphragm 12 has a structure in which two kinds of materials of a silicon layer 20 as a conductor and a silicon oxide layer 21 as an insulator are laminated.
  • etching ions are likely to be accumulated on the surface of the insulating layer of the silicon oxide layer 21. Moreover, the etching ions accumulated on the surface of the silicon oxide layer 21 and the etching ions that have entered easily repel. As a result, after the through-hole 18 reaches the silicon oxide layer 21, the etching easily proceeds in the lateral direction (direction parallel to the surface of the silicon oxide layer 21), and the tapered recess 26 is formed. . The depth of the recess 26 is about 1 ⁇ m. This depth can be controlled by the etching time.
  • CF 4 can be used as the etching gas
  • CHF 3 can be used as the suppression gas.
  • a depression may be provided at the end of the through hole 18 on the first surface side or the second surface side.
  • the silicon oxide layer 21 is dry-etched.
  • an etching gas used at this time for example, a mixed gas of CHF 3 and Ar is used.
  • the plasma-excited Ar gas becomes an etching gas with high straightness.
  • an etching component such as Ar ions that proceeds by sputtering advances straight from the opening of the through hole 18 and enters the through hole 18 to etch only the silicon oxide layer 21 that is an insulator.
  • CHF 3 hardly forms a polymer film on the surface of the silicon oxide layer 21, but forms a polymer film made of fluorocarbon on the surface of the silicon layer 20.
  • the fluorocarbon film when the through hole 18 is formed also functions as a protective film. Therefore, only the silicon oxide layer 21 can be easily selectively etched.
  • a mixed gas such as CF 4 / H 2 or CHF 3 / SF 6 / He may be used.
  • the two types of materials of the laminate of the diaphragm 12 have different etching rates for the same gas. Therefore, the silicon oxide layer 21 is not etched when the silicon layer 20 is etched, and the silicon layer 20 is not etched when the silicon oxide layer 21 is etched. Etching utilizing such properties makes it possible to easily form a through hole 18 having a desired shape.
  • a second resist mask 27 is formed on the surface of the silicon layer 22 in the same manner as the first resist mask 24 described above. Thereafter, the cavity 28 is formed by etching the silicon layer 22 under the same conditions as the etching of the silicon layer 20. Also in this case, the progress of etching in the depth direction stops at the exposed surface of the silicon oxide layer 21. As a result, the silicon oxide layer 21 is projected at the peripheral edge of the through hole 18 of the silicon oxide layer 21 (overhang state).
  • the sensor chip 13 is heated in an atmosphere containing oxygen in a heat treatment furnace in the air. Then, the silicon surface is oxidized, and the silicon oxide film 23 is uniformly formed on the exposed silicon surface. Thereby, the sensor chip 13 as shown in FIG. 2 is completed.
  • the thickness of the silicon oxide film 23 is 200 to 230 nm. At this time, strictly speaking, the thickness of the silicon oxide layer 21 increases simultaneously. However, since oxidation proceeds by oxygen diffusion, the amount of increase differs depending on the thickness of the silicon oxide layer 21 before oxidation. For example, when the thickness of the silicon oxide layer 21 before oxidation is 500 nm, the increase amount is about 50 nm.
  • FIG. 7 is a top view of the diaphragm 12 of the sensor chip 13.
  • a plurality of through holes 18 are formed in the diaphragm 12.
  • the direction along the line segment L1 connecting the centers of one through hole 18A of the plurality of through holes 18 and the other through hole 18B closest to the through hole 18A is the cleavage plane of the silicon layer 20.
  • the direction along the line connecting the centers of the adjacent through holes 18 that are closest to each other is different from the direction of the cleavage plane of the silicon layer 20.
  • the diaphragm 12 is arranged such that the direction along the line segment L1 that connects the centers of the adjacent through holes 18A and 18B that are closest to each other as in this embodiment is different from the direction of the cleavage plane. Cracking can be effectively prevented.
  • the meaning of being closest and adjacent to each other means that when attention is paid to an arbitrary through hole 18A among the plurality of through holes 18, the center is located closest to the center of the arbitrary through hole 18A. This means a relationship with the through hole 18B. And the positional relationship in which a through-hole does not exist in the position near the other of the through-hole 18B is represented.
  • the plurality of through holes 18 may be arranged so that the direction along the line segment connecting the centers of the adjacent through holes 18 that are closest to each other in the plurality of through holes 18 is different from the direction of the cleavage plane of the silicon layer 20.
  • a plurality of through holes are formed so that the direction along the line connecting the centers of the arbitrary through hole 18 and the other through hole 18B closest to the arbitrary through hole 18A is different from the direction of the cleavage plane of the silicon layer 20. It is preferable to arrange the holes 18. Thereby, the crack of the diaphragm 12 can be prevented more effectively. However, in this case, there may be a case where only some of the through holes 18 do not satisfy the above-mentioned condition due to an error in the manufacturing process or the like.
  • the diaphragm 12 is preferably formed in a circular shape when viewed from the top. If the shape of the diaphragm 12 is circular, the stress applied to the diaphragm 12 when adsorbing the specimen can be uniformly supported on the outer periphery. On the other hand, if the diaphragm 12 has a non-circular shape such as a square, a corner is formed on the outer periphery of the diaphragm 12, so that the corner is distorted and the diaphragm 12 is cracked. For this reason, cracking of the diaphragm 12 can be prevented by making the shape of the diaphragm 12 circular when viewed from above.
  • the diaphragm 12 or the silicon layer 20 is preferably provided with a mark 30 indicating the direction of the cleavage plane of the silicon layer 20.
  • the direction along the line segment connecting the centers of one through hole 18A among the plurality of through holes 18 and the one through hole 18A and the other through hole 18B closest to the through hole 18A is the silicon layer 20. It becomes easy to form the diaphragm 12 so as to be different from the direction of the cleavage plane. Further, since the direction of the cleavage plane can be visually recognized, the direction of the cleavage plane can be recognized during the mounting operation of the sensor chip 13, and the diaphragm 12 can be effectively prevented from cracking during the mounting operation.
  • the shape of the mark 30 is not particularly limited. However, it is preferable that the shape of the mark 30 has a line segment parallel to the direction of the cleavage plane because the cleavage plane can be easily identified. Further, if the mark 30 has a shape that does not have a point-symmetrical center, the directionality within the wafer can be understood, so that the work can be easily performed. Furthermore, by using different marks 30 for all the sensor chips 13 in the wafer, the position of the sensor chip 13 in the wafer can be tracked, which is advantageous in production management. However, the same effect can be obtained by using several sensor chips 13 as one group without using different marks 30 for all sensor chips 13 and using different marks for each group.
  • the same effect as that of providing the mark 30 can be obtained by arranging the through hole 18 so that the direction of the cleavage plane can be understood.
  • the direction of the cleavage plane may be determined by making the arrangement of the through holes 18 not point-symmetric with respect to the center of the diaphragm 12.
  • an SOI substrate in which the silicon layer 20 is made of silicon (100) is used.
  • Silicon (100) is a substrate excellent in workability and versatility.
  • silicon (110) or silicon (111) can be selected for the silicon layer 20.
  • FIG. 8A shows a cleavage plane of a silicon (100) substrate.
  • FIG. 8B shows a cleavage plane of the silicon (110) substrate
  • FIG. 8C shows a cleavage plane of the silicon (111) substrate.
  • the distance between the centers of the through holes 18 that are closest and adjacent to each other is preferably 20 ⁇ m or more from the viewpoint of preventing cracking of the diaphragm 12 and the success rate of measurement.
  • the size of the cell used as the specimen is generally about 20 ⁇ m. For this reason, if the distance between the centers of the through holes 18 is smaller than the size of the cells used as the subject, interference between cells occurs, and the success rate of the measurement decreases. Furthermore, when the distance between the centers of the through holes 18 is short, an area that receives stress applied to the diaphragm 12 when the subject is sucked and adsorbed is reduced, and the diaphragm 12 is easily broken.
  • the distance between the centers of the through holes 18 is increased, the structurally weak parts are difficult to gather. Therefore, the reliability of the sensor chip 13 is improved.
  • region required for formation of the through-hole 18 becomes large. This makes it difficult to reduce the size and cost of the sensor.
  • the durability of the diaphragm 12 is improved and interference between subjects is prevented. Therefore, the center of one through-hole 18 of the plurality of through-holes 18 arranged closest to the center of the diaphragm 12 and the other through-hole 18 closest to the one through-hole 18 is connected.
  • the distance of the line segment is 60 ⁇ m.
  • the shape formed by line segments connecting the centers of three adjacent through holes 18 may be arranged in a regular triangle shape. That is, a line segment connecting the centers of one through-hole 18C among the plurality of through-holes 18 and another through-hole 18D that is closest to one through-hole C and another through-hole 18E that is also closest to each other is correct. Arrange them in a triangular shape. Thereby, the several through-hole 18 can be arrange
  • the direction along the line segment connecting the through holes 18 arranged in a regular triangle shape is different from the direction of the cleavage plane of the silicon layer 20 as described above. Thereby, the crack of the diaphragm 12 can be prevented. However, this is not necessarily the case.
  • the direction of the diaphragm 12 so that the direction along the line connecting the centers of the adjacent through holes 18 that are closest to each other is different from the direction of the cleavage plane of the silicon layer 20. Can be designed and formed easily. Thereby, the diaphragm 12 which is hard to break can be formed.
  • the plurality of through holes 18 are not arranged near the center P of the diaphragm 12. That is, it is preferable that the plurality of through holes 18 be arranged in a region excluding the vicinity of the center P of the diaphragm 12.
  • the center P of the diaphragm 12 indicates a position where the distance from the outer periphery is equal when the diaphragm 12 is circular as viewed from above, and when the diaphragm 12 is a polygon, the distance from the corner of the outer periphery of the diaphragm 12 is equal. Represents the position. When the subject is aspirated and adsorbed, a particularly large stress is applied to the center P of the diaphragm 12.
  • the through hole 18 is disposed in the vicinity of the center P of the diaphragm 12, a large stress is applied to the through hole 18. Then, a crack from the through hole 18 is likely to occur, and the sensor chip 13 is easily cracked. Thus, by disposing the through hole 18 while avoiding the center P of the diaphragm 12, the diaphragm 12 can be effectively prevented from cracking.
  • the vicinity of the center P of the diaphragm 12 refers to a range of about 50 ⁇ m from the center of the diaphragm 12 when the diameter of the diaphragm 12 is about 500 ⁇ m.
  • the diaphragm 12 is difficult to break and cracking can be effectively prevented.
  • the vicinity of the outer periphery represents a range that is not the center of the diaphragm 12, particularly a range of about 10 ⁇ m from the outer periphery.
  • the diaphragm 12 is subjected to a greater stress at a position closer to the center. For this reason, from the viewpoint of preventing the diaphragm 12 from cracking, it is preferable that the length of the line connecting the centers of the adjacent through holes 18 that are closest to each other is longer in the vicinity of the center of the diaphragm 12 than in the vicinity of the outer periphery. As the distance from the center of the diaphragm 12 toward the outer periphery decreases, the distance between the centers of the adjacent through holes 18 that are closest to each other is shortened, so that the diaphragm 12 can be prevented from cracking, and a plurality of through holes can be efficiently penetrated on the diaphragm 12.
  • Holes 18 can be arranged. That is, a line segment that connects the centers of an arbitrary through hole 18 and another through hole 18 that is closest to the arbitrary through hole 18 is another line segment that is closest to the other arbitrary through hole 18 and the other arbitrary through hole 18. It is preferable that it is located on the outer peripheral side of the diaphragm 12 and shorter than the line segment connecting the center with the through hole 18. Thereby, the above-described effects can be obtained. For example, as shown in FIG. 7, when the distance between the centers of the adjacent through holes 18 that are closest to each other is L1, L2, and L3 in order from the closest to the center of the diaphragm 12, the distance between the line segments is L1> L2>. L3 is preferable.
  • the through hole 18 is provided point-symmetrically with respect to the center P of the diaphragm 12.
  • the shape of the through hole 18 is not particularly limited, and an optimal shape may be selected depending on the type and shape of the subject to be measured. However, in the case of cells or spherical particles, the subject has a shape relatively close to a true sphere. Therefore, it is desirable that the shape of the through hole 18 is close to a perfect circle because the subject can be aspirated isotropically.
  • the sensor chip according to the present invention is not easily broken even when the subject is sucked and sucked into the through hole, and has excellent durability. Therefore, it is effective in the medical / biological field where a sensor device with excellent durability is required.

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Abstract

La présente puce de détection comporte un diaphragme comprenant une première surface et une seconde surface faisant face à la première surface, ledit diaphragme comportant plusieurs trous traversant les première et seconde surfaces. Le diaphragme est caractérisé en ce qu'il présente une résistance mécanique inférieure lorsqu'une contrainte est appliquée selon une direction spécifique, par rapport à la résistance observée lorsque la contrainte est appliquée selon d'autres directions. Les trous traversants comportent un premier trou traversant et un second trou traversant qui se trouve à proximité immédiate du premier trou traversant. La direction correspondant à un premier segment linéaire reliant le centre du premier trou traversant et le centre du second trou traversant est différente de la direction spécifique susmentionnée.
PCT/JP2012/001436 2011-03-04 2012-03-02 Puce de détection WO2012120852A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106535484A (zh) * 2016-12-29 2017-03-22 奥士康科技股份有限公司 一种印刷导气板
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JPWO2017187588A1 (ja) * 2016-04-28 2018-10-25 株式会社日立製作所 メンブレンデバイス、計測装置、メンブレンデバイス製造方法
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