JPWO2015159945A1 - PHYSICAL / CHEMICAL SENSOR AND PHYSICAL / CHEMICAL Phenomenon Sensing Device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a physical / chemical sensor and a physical / chemical phenomenon sensing device capable of shortening a reaction time on a movable film, and to provide a manufacturing method therefor. A physical / chemical sensor forms a Fabry-Perot interferometer, and a flow path forming layer 4 is laminated on the surface of a movable film 3 to form a hollow portion 41 and a flow path 42 connected thereto. The physical / chemical phenomenon sensing device includes a plurality of physical / chemical sensors, and is divided into a detection sensor 100 and a reference sensor 200 so that a specimen and a reference sample can be supplied to the movable film by different flow paths and hollow portions. I made it. In these manufacturing methods, a sacrificial layer is stacked on a substrate, a flow path forming layer is formed of a resist, and then the sacrificial layer is etched as the last step. [Selection] Figure 1

Description

  The present invention relates to an optical interference type physical / chemical sensor, and more particularly to a sensor for detecting a molecule contained in a gas or a liquid without labeling, a physical / chemical phenomenon sensing device using the sensor, and these It relates to a manufacturing method.

  In recent years, as represented by fuel cells, techniques for using hydrogen gas as an energy source have been developed and spread, and along with this, sensors for detecting hydrogen gas are regarded as important. Gases that induce environmental pollution (such as carbon dioxide and nitrogen dioxide) must be detected for the purpose of environmental conservation, and components used in explosives (trinitrotoluene: TNT and trimethylenetrinitroamine) : Detection of gas containing RDX etc. is useful for finding landmines. Furthermore, in the medical field, a specific antigen (specific protein) is detected by an antigen-antibody reaction in order to determine that the patient is suffering from a specific disease by detecting a specific type of antibody or a specific type of antigen. Sensors that do this are also regarded as important.

  Therefore, in the medical field, as a method for specifying a protein to be detected, a fluorescent labeling technique using a fluorescent label has been used. This technology reacts proteins with activated fluorescent groups to label them, allowing multiple detections simultaneously and easy handling of fluorescent dyes. . However, with this fluorescent labeling technology, there is a concern that the protein structure will deteriorate as the fluorescent group reacts, and there is a problem with quantitative evaluation that it is difficult to control the position of the fluorescent group modification and the number of labels. It was.

  As a technique for solving the above problem, a sensor that does not use a label (non-labeled, so-called label-free) has been proposed. Therefore, as a label-free protein sensor using MEMS (Micro Electro Mechanical System) technology, a sensor that detects a change in surface stress due to molecular adsorption as a bend of a cantilever or a thin film has been proposed (non-patented). Reference 1 and 2). The change of the surface stress in the above technique is caused by electrostatic repulsion due to the charge of adsorbed molecules. As a transducer for outputting a static displacement signal, a method of detecting a reflection angle of a laser or a method of reading an output voltage signal using a piezoresistor is employed. In the method using a cantilever, a cantilever type sensor is mounted in a microchannel, and target molecules contained in a liquid fed by a syringe pump are detected in real time.

  However, a cantilever type sensor using a piezoresistor recognizes mechanical bending of the cantilever as a change in resistance value due to the piezo element, and conversion efficiency from the bending amount of the cantilever to the resistance value change amount is small. In addition, since the material of the cantilever is made of silicon, the Young's modulus is high (130 to 160 GPa), and it is impossible to obtain a deflection amount necessary and sufficient for detecting a minute intermolecular force caused by a biomolecule. Had.

WO2013 / 047799 gazette

G.H.Wu, R.H.Datar, K.M.Hansen, T.Thundat, R.J.Cote, A. Majumdar, Bioassay of prostate-specific antigen (PSA) using microcantilevers, Nat. Biotechnol. 19 (2001) 856-860. Y. Arntz, JDSeelig, HpLang, J. Zhang, P. Hunziker, JPRamseyer, E. Meyer, M. Hegner, C. Gerber “Label-free protein assay based on a nanomechanical cantilever array”, Nanotechnology 14, pp .86-90, 2003.

  In order to solve the above problems, the inventors of the present application have proposed a method using optical interference as a transducer for improving the sensitivity of the surface stress sensor (see Patent Document 1). In this technique, a Fabry-Perot interferometer is formed by a movable film made of a material having the ability to fix a specific substance and the surface of the light receiving element, and the fixed state of the specific substance is detected by a change in the intensity of transmitted light having a specific wavelength. That is, when a movable film having substance-fixing ability fixes a specific substance, the film part bends due to the intermolecular force of the substance, and the gap width of the gap part (air gap) constituting the Fabry-Perot interferometer changes. To do. Since the interference wavelength changes with this change, when a single wavelength laser beam is incident, the transmittance with respect to the incident wavelength changes, and this change in transmitted light intensity is read out as a change in photocurrent by the light receiving element. is there. If an antibody molecule is immobilized on the movable membrane, this antibody molecule and a specific protein are bound by an antigen-antibody reaction, and the change in intermolecular force due to the binding of the protein to be detected can be detected from the amount of deflection of the movable membrane. It can be done. In this way, not only the presence or absence of protein, but also the amount of adhesion can be quantitatively evaluated from the electrical signal. Further, if the transmission characteristics of the Fabry-Perot interferometer are controlled, the signal conversion efficiency with respect to the displacement of the movable film is improved. It is something that can be done.

  By the way, in the Fabry-Perot interference type sensor, in order to form a gap between the light receiving element and the movable film, an etchable material (sacrificial layer) is previously laminated on the light receiving surface of the light receiving element, and the movable film layer is formed on the surface. The sacrificial layer was fabricated by etching and then removing the sacrificial layer. Therefore, the movable film layer is formed with a communication hole for allowing the etching gas or the etchant to reach the sacrificial layer. After the etching is completed, the communication hole is sealed to prevent the liquid from flowing into the gap. Was. At this time, when the sealing film is patterned by photolithography, severe restrictions are imposed on the coating method, development and baking conditions, and the yield cannot be said to be good.

  In addition, as described above, a specific substance such as a protein to be detected is fixed (specific adsorption) to the movable film. Therefore, the surface of the movable film is opened and the specific substance is placed on the surface. The liquid (test object liquid) which may contain was dripped and the reaction was observed. For this reason, a reaction time of about several tens of minutes may be required until the specific substance specifically adsorbs on the surface of the movable film. However, when a quick diagnosis is to be performed, or for the purpose of molecular screening, the reaction time is required to be shortened. However, the conventional sensor has not yet reached the point where the request is satisfied. In addition, when the liquid is dropped on the surface of the movable film, the interference characteristics change depending on the total amount of the liquid. Therefore, the process of drying the surface of the movable film to remove the liquid such as the cleaning liquid before the dropping (before use) And the problem of increasing the overall processing time is inherent.

  The present invention has been made in view of the above points, and its object is to provide a physical / chemical sensor and a physical / chemical phenomenon sensing device capable of reducing the reaction time on the movable membrane, and therefore The manufacturing method is also provided.

  Therefore, the present invention according to the physical / chemical sensor includes a movable film provided on the light receiving surface of the light receiving element so as to face the light receiving surface while forming a gap, and the movable film is a substance on at least the outer surface. A physical / chemical sensor having a fixing ability and configured to form a Fabry-Perot interferometer together with the light receiving surface, comprising a flow path forming layer laminated on an outer surface of the movable film, the flow path forming layer Is characterized in that a hollow portion is formed on the outer surface of the movable membrane, and a flow path connected to the hollow portion is formed.

  According to the above configuration, the liquid to be inspected or the gas to be inspected (hereinafter collectively referred to as a specimen) can be supplied to the movable film by flowing into the flow path, and the reaction time can be reduced by concentrating the specimen in a narrow range. Shortening is possible. Here, the flow path is a micro flow path having a fine diameter, and the hollow portion is a fine space to which the movable film can be changed. By supplying the specimen to such a fine region, the reaction time can be shortened by a so-called size effect. In addition, the specimen is supplied to the movable membrane through the flow path, but by continuing the supply of the specimen, the specific substance to be fixed (specific adsorption) to the movable membrane is continuously maintained. Since it is supplied to the surface of the movable film, the efficiency of specific substance immobilization (specific adsorption) by the substance immobilization ability of the movable film can be improved. That is, when the surface of the movable membrane is opened and dropped onto the surface as in the past, even if a specific substance exists at a position away from the movable membrane (upper part in the liquid) Can not be fixed (specific adsorption), but when passing through a narrow area, a specific substance can be supplied to a position close to the surface of the movable membrane, and fixation (specific adsorption) by the movable membrane surface Since it becomes easy, the reaction time can be shortened.

  In the invention having the above-described configuration, the movable film includes a penetrating portion penetrating a part of a peripheral portion, and the flow path forming layer communicates with the penetrating portion at a position deviating from the hollow portion and the flow path. And a gap formed between the light receiving surface and the movable film communicates with the outside through the penetration and the communication portion. Is.

  In the case of such a configuration, the gap formed between the light receiving surface of the light receiving element and the movable film is eventually opened, and the gap is formed under atmospheric pressure. Become. This gives flexibility to the deformation of the movable film, which facilitates the deformation of the movable film due to the intermolecular force of the substance fixed (specific adsorption) on the surface of the movable film, and improves the measurement accuracy of the adsorbed substance. To get.

  In the invention of each configuration described above, the movable film may be formed of a material having a molecule fixing ability for fixing molecules contained in a gas or a liquid.

  According to the above configuration, a specific gas (for example, a combustible gas or a gas that affects the environment), a biopolymer, and the like can be measured. Here, examples of the flammable gas include hydrogen gas and gases contained in explosives such as TNT and RDX, and examples of the gas that affects the environment include carbon dioxide and nitrogen dioxide. it can. Examples of biopolymers include polymers containing amino acids, nucleic acids, polysaccharides, etc. (eg, antibodies, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), etc.). In addition, when the molecular immobilization ability has the ability to immobilize an antibody, the antibody is immobilized in advance on the surface of the movable membrane, and a state where a specific protein (antigen) that binds to the antibody binds to the antibody is detected.・ Measurement is also possible.

  On the other hand, as the movable film in the invention having the above-described structure, a film composed of a flexible base film and a molecular fixed film in which a material having a molecular fixing ability is laminated on the surface of the base film can be used.

In the case of the above configuration, various types of sensors can be configured according to the target substance to be detected and measured by stacking different types of molecular fixed films. Examples of the molecular immobilization membrane include Parylene (registered trademark) A or Parylene (registered trademark) AM manufactured by Japan Parylene LLC. (Registered trademark) A or AM. These are para-xylene-based polymers, which are structures in which benzene rings are connected via CH ₂ , and those that end with “A” have an amino group on the side chain, Since “AM” is a structure in which a methyl group-amino group is bonded in series to the side chain, an antibody can be bonded to the amino group.

  Note that when a plurality of films are stacked as described above, the movable film can also function as a half mirror by stacking metal films at the same time. This is because by configuring the half mirror, it is possible to improve the selectivity of wavelengths that interfere inside the Fabry-Perot interferometer. In this case, a metal film may be laminated on the light receiving surface of the light receiving element. This is because the half-value width of the interference wavelength can be narrowed.

  The present invention relating to a physical / chemical sensor array uses the physical / chemical sensor described above, wherein a plurality of the physical / chemical sensors are formed on a substrate, and the flow formed in the flow path layer is formed. The path is characterized in that a plurality of hollow portions formed on the outer surface of the movable film of each physical / chemical sensor are connected in series.

  According to the above configuration, the same specimen can be supplied from the flow path connected in series to the hollow part on the movable membrane constituting the physical / chemical sensor. Enables sensing of different materials. In other words, by varying the substance fixing conditions of the movable films constituting the individual sensors, it is possible to sense a plurality of different types of substances contained in the same specimen. Different substance fixation conditions for the movable membrane include when the specific substance that can be immobilized (specific adsorption) differs by the movable membrane, as well as by selecting a specific antibody that specifically adsorbs to a specific antigen. May be fixed.

  Further, the invention relating to the physical / chemical sensor array uses the physical / chemical sensor described above, and a plurality of units are provided by a plurality of the physical / chemical sensors formed on the substrate. The flow path formed in the path layer is formed so that a plurality of hollow portions formed on the outer surface of the movable film of each physical / chemical sensor are connected in series for each unit. There is something to do.

  According to the above configuration, different samples can be allowed to flow for each unit, and specific substances can be detected for a plurality of samples at the same time. In this case, some of the plurality of sensors constituting each unit can be used for reference. For example, when a specific substance (antigen) is detected by immobilizing an antibody on the surface of the movable membrane in advance and specifically adsorbing the antigen to the antibody, the antibody is immobilized on the surface of the movable membrane constituting the reference sensor. First, by preventing the specific adsorption of the antigen on the movable membrane, it is possible to measure the transmitted light intensity under conditions where the specific substance (antigen) is not fixed. That is, the same specimen supplied via the same flow path passes through both a sensor that can detect a specific substance and a sensor that cannot detect (for reference), and both sensors By comparing the intensity of transmitted light (the intensity of photocurrent), the change in the movable film can be clearly measured. On the other hand, a sample not containing a specific substance may be supplied to a part of the plurality of units, and the specific unit may be used for reference. Even in such a case, it is possible to compare the intensity of transmitted light (intensity of photocurrent) in units.

  Here, the flow path in the physical / chemical sensor array may include an inflow portion and an exhaust portion that are open at the edge of the substrate for each unit.

  In such a configuration, the specimen can be supplied from the outside of the substrate on which the sensor array is formed, and the specimen after passing through the flow path can be discharged outside the board. The supply system at this time can be configured by forming the flow path and the inlet on a chip different from the substrate on which the sensor array is formed, while the discharge system also includes the substrate on which the sensor array is formed. Can be constructed by forming channels and outlets on different chips.

  The present invention relating to a physical / chemical phenomenon sensing device is a sensing device using the physical / chemical sensor, wherein a plurality of the physical / chemical sensors are arranged on a substrate, a part of which is used for reference, A part or all of the above is used for detection.

  According to the above configuration, the reference sensor can have the same structure as the sensor for detecting a specific substance. In this case, for example, an antibody that causes an antigen-antibody reaction with a specific antigen is fixed to the detection sensor, and the antibody is not fixed to the reference sensor. By supplying, the movable film changes only in the detection sensor. This makes it possible to compare changes in the intensity of light detected by the light receiving elements of both sensors. In particular, the detection sensor and the reference sensor can be in the same condition for the inspection when the sample itself has a property of reducing the light transmittance, such as a sample having a dye. By comparing the change in the intensity of light detected by the light receiving element with the change in the intensity of light detected by the light receiving element of the reference sensor, it becomes possible to detect the change in light transmittance due to the fixation of the specific substance. .

  In addition, the invention relating to a physical / chemical phenomenon sensing device uses the above-described sensor array, and a plurality of the physical / chemical sensors of the plurality of physical / chemical sensors constituting each unit are used for the plurality of units. -Some of them are characterized by using a chemical sensor for reference and another physical / chemical sensor for detection.

  In the case of the above configuration, since some sensors can function as reference sensors for each unit, it is possible to compare the detection sensor and the reference sensor for each unit, which differs for each unit. Samples can be tested simultaneously. In addition, it is possible to detect several kinds of specific substances at the same time by changing the substance fixing conditions for a plurality of sensors constituting the unit, and the reference sensor should be in a condition that these specific substances are not fixed (specific adsorption). A reference value can be obtained.

  The invention relating to a physical / chemical phenomenon sensing device is a sensing device using the above-described sensor array, wherein a part of the plurality of units is used for reference, and part or all of the other is used. It may be for detection.

  In the case of the above configuration, a unit composed of a plurality of physical / chemical sensors can be divided into a unit for detection and a unit for reference, and the unit is provided by supplying the same specimen to both units. It is also possible to compare the intensity change of the transmitted light detected by the light receiving element in units of.

  On the other hand, the present invention according to the method of manufacturing a physical / chemical sensor includes a sacrificial layer generation step of generating a sacrificial layer by depositing an etchable material on a light receiving surface of a light receiving element, and an etching material among the sacrificial layer surfaces. A movable film layer generating step for generating a movable film layer by depositing a movable film constituent material in the movable film constituent region, excluding an etching material distribution region for allowing the gas to pass through, and a space portion on the outer surface of the movable film layer; And a flow path forming layer generating step of forming a flow path connected to the space and forming a communication area communicating with the etching material flow area and laminating the flow path forming layer on the surface of the movable film layer And sacrificial layer removal that causes the etching material to reach the sacrificial layer through the etching material flow region and the communication region, and removes the sacrificial layer by etching to form a void on the back side of the movable film layer. It is characterized in that comprises a step.

  According to the above configuration, the movable film is stacked using the surface of the sacrificial layer, and further, the hollow portion and the flow path are formed on the upper part of the movable film, and then the sacrificial layer is removed to thereby form the light receiving surface of the light receiving element. A gap is formed between the movable film and the Fabry-Perot interferometer. Here, the sacrificial layer is removed by etching. However, since the etching material reaches the sacrificial layer through the etching material flow region and the communication region after the flow path forming layer is constructed, the sacrificial layer is sacrificed. It is not necessary to form a structure by a wet process after removing the layer. This is because, in the conventional structure, when the flow path is formed after configuring the Fabry-Perot interferometer, the wet process is performed with the sacrificial layer removed, so that liquid can flow into the gap. However, if the manufacturing method has the above configuration, such liquid inflow can be prevented. Further, in the conventional structure, after removing the sacrificial layer, a process for sealing the etching material circulation region is required, but the process can be omitted. And even if the etching material distribution region is sealed by the sealing process, if the sealed state is insufficient, there is a possibility that the liquid (specimen) dropped on the movable film flows in, Since the region where the liquid (specimen) is supplied by the flow path forming layer is separated from the etching material flow area and the communication area, the liquid (specimen) supplied into the flow path forming layer flows into the gap. Can be prevented.

  In the above physicochemical sensor manufacturing method, the flow path forming layer generation step includes a wall surface forming area, a flow path forming area, and a wall surface forming process for forming a surrounding wall surface of the communication area, and the space portion forming area and the flow path. The flow path forming layer can be generated by dividing into a closing process for closing the upper opening of the constituent region.

  In the case of the above configuration, the flow path forming layer is composed of two layers, and can be constructed as a structure in which at least the space portion configuration area and the flow path configuration area are sealed. These can be formed by depositing a photoresist by photolithography. Even in the case of photolithography, since the sacrificial layer is not removed, the developer or the like does not affect the gap. Instead, after the flow path forming layer is formed from a resist, the adhesion between the substrate and the flow path forming layer is improved by post-baking.

  The invention relating to the method of manufacturing a physicochemical phenomenon sensing device includes a sacrificial layer generating step of generating an sacrificial layer by depositing an etchable material on each light receiving surface of a plurality of light receiving elements fabricated on a substrate, and the sacrificial layer A movable film layer generating step of generating a movable film layer by depositing the movable film constituent material in the movable film constituent region, excluding the etching material distribution region for allowing the etching material to pass through, On the outer surface, a space portion and a plurality of light receiving elements are divided into a plurality of units, and a flow path for connecting each space portion in series is formed for each unit and communicated with the etching material circulation region. A flow path forming layer generating step of laminating a flow path forming layer on the surface of the movable film layer while forming the communication area, and the etching material flowing through the etching material flow area and the communication area. To reach the serial sacrificial layer and is characterized in that it comprises a sacrificial layer removing step of forming a gap portion of the sacrificial layer is removed by etching on the back side of the movable layer.

  According to the said structure, the flow path which connects the some physical and chemical sensor divided into the some unit on the board | substrate, and the several space part which makes each unit a unit can be formed. By forming a plurality of the units, it is possible to manufacture a device that can test different specimens at the same time. Also in this manufacturing method, the sacrificial layer is the one in which the etching material reaches the sacrificial layer through the etching material flow region and the communication region after the flow path forming layer is constructed. This eliminates the need to form a structure.

  Also in the method for manufacturing a physical / chemical phenomenon sensing device as described above, the flow path forming layer generation step includes a wall surface forming step, a wall surface forming step that forms a surrounding wall surface of the space portion forming area, the flow path forming area, and the communication area; The flow path forming layer can be configured to be distinguished from the block forming step of closing the upper opening portion of the part configuration area and the flow path configuration area.

  According to the present invention relating to a physical / chemical sensor, a fine hollow portion is formed on the surface of a movable film constituting a Fabry-Perot interferometer, and a specimen (a gas to be inspected or a test object) is placed in a microchannel connected to the hollow portion. The liquid can be supplied to the movable film surface while concentrating the specimen in a narrow range. At this time, since there is a hollow part on the surface side of the movable membrane and a void part is formed on the back side, when a specific substance is immobilized (specific adsorption) on the surface, the intermolecular molecules of the fixed substance The movable film can be deformed in accordance with the force, and the intensity of transmitted light according to the deformed state of the movable film can be detected by irradiating the light receiving element with light through the movable film. As described above, by supplying the sample concentrated in a narrow range, the specific substance is fastened (specific adsorption) to the surface of the movable membrane, and as a result, the reaction time to be detected can be shortened. Will be. In particular, since the specimen is supplied to a minute space via the microchannel, the adsorption speed on the movable film surface can be promoted by the so-called size effect, and the reaction time can be greatly shortened.

  In addition, as described above, the specimen is supplied to the hollow portion on the surface of the movable membrane via the flow path, so that it can reach the portion to be detected while avoiding contact with the outside. On the other hand, although the specimen is supplied to the surface of the movable membrane, the gap formed on the back side of the movable membrane is because the movable membrane and the same type of thin film are interposed between the flow path and the hollow portion, The specimen does not flow into the gap. Therefore, a process such as drying the voids can be made unnecessary during use. In addition, the flow path and the hollow part into which the sample has flowed in can be easily cleaned by supplying a cleaning solution (such as physiological saline) after use, and then used without drying. Can do. If it is necessary to dry, it can be easily dried by flowing dry air into the flow path.

  The sensor array using the physical / chemical sensor has a single flow path because the flow path is connected in series with the hollow portions on the movable membrane constituting the plurality of physical / chemical sensors. The specimen supplied from can be sensed by a plurality of sensors. Therefore, it is not necessary to supply the same specimen to different flow paths, and substances can be detected simultaneously under different conditions for the same specimen. The different conditions at this time include a case where the movable film constituting a part of the sensors is a condition in which a specific substance cannot be fixed (specific adsorption), and can be used as a reference sensor. In addition, by using a plurality of sensors connected in series as a unit and forming a plurality of units, it is possible to supply different samples for each unit and simultaneously test a plurality of samples. With this configuration, measurement time can be shortened, and comparison results can be obtained at the same time by providing conditions for reference, making it possible to instantaneously determine the detection of specific substances. Become.

  Furthermore, according to the present invention relating to a physical / chemical phenomenon sensing device, a plurality of the physical / chemical sensors are formed on a substrate, and a unit is formed by the plurality of sensors, and a part of the plurality of sensors. Or by using a part of the plurality of units for reference, the state of deformation of the movable film in the sensor or unit for detecting the specimen, and the state of deformation of the movable film in the reference sensor or unit Can be compared. The comparison with the reference sensor or unit makes it possible to clearly grasp the presence of the specific substance to be detected. For comparison, it is only necessary to electrically detect the value of the photocurrent obtained by the light receiving element, and the detection result can be obtained very easily and quickly. In each of these sensors and units, the reaction time can be shortened by supplying the sample into the minute space and the inside of the microchannel.

  On the other hand, according to the present invention related to the manufacturing method of the physical / chemical sensor and the physical / chemical phenomenon sensing device, a fine hollow portion can be formed on the surface side of the movable film constituting the Fabry-Perot interferometer, A microchannel connected to the hollow portion can be formed. These hollow portions and flow paths can be formed by, for example, lithography technology, but when these hollow portions and flow paths are formed, a sacrificial layer is laminated on the back side of the movable membrane. The wet process will be performed prior to removing the sacrificial layer. Then, in the final step, the sacrificial layer is removed by allowing the etching material to reach the sacrificial layer via the etching material circulation region provided in the movable film and the communication region provided in the flow path forming layer. After the gap is formed in this final step and the Fabry-Perot interferometer is configured, a processing step by a wet process becomes unnecessary, and an inflow of unnecessary liquid such as a developer can be prevented in the gap. This kind of effect is the same when a sensor array and a sensing device are manufactured as well as when a single physical / chemical sensor is formed.

It is explanatory drawing which shows embodiment of a physical / chemical sensor. It is explanatory drawing which shows the state which isolate | separated the flow-path formation layer which comprises a physical and chemical sensor. (A) is sectional drawing in IIIA-IIIA of FIG. 1, (b) is sectional drawing in IIIB-IIIB of FIG. It is sectional drawing in IV-IV of FIG. It is explanatory drawing which shows embodiment of the physical and chemical phenomenon sensing device. It is explanatory drawing which shows 2nd embodiment of a physical and chemical phenomenon sensing device. It is explanatory drawing which shows the manufacturing method of a physical / chemical sensor. It is explanatory drawing which shows the manufacturing method of a physical / chemical sensor. It is explanatory drawing which shows the manufacturing method of a physical and chemical phenomenon sensing device. It is explanatory drawing which shows the manufacturing method of a physical and chemical phenomenon sensing device. It is a photograph of an actual physical / chemical sensor array. It is the photograph at the time of experimenting the preparation state of a space | gap part. It is a graph which shows the result of having measured the reflection spectrum with respect to a movable film. It is a graph which shows the characteristic of a photodiode.

  DESCRIPTION OF EMBODIMENTS Embodiments of a physical / chemical sensor, a physical / chemical sensor array, a physical / chemical phenomenon sensing device, and manufacturing methods thereof will be described below with reference to the drawings.

<Physical and chemical sensors>
FIG. 1 is a diagram showing an outline of an embodiment of the invention relating to a physical / chemical sensor, and FIG. 2 is a diagram showing a state where a part of a single physical / chemical sensor is separated. 3A is a cross-sectional view taken along IIIA-IIIA in FIG. 1, and FIG. 3B is a cross-sectional view taken along IIIB-IIIB. An embodiment of a physical / chemical sensor will be described based on these drawings. First, as shown in FIG. 1, in the present embodiment, a gap 2 is formed on a light receiving surface 11 of a light receiving element 10 (hereinafter referred to as a photodiode as an example of the light receiving element) 10 formed on a substrate 1. The movable film 3 is formed through the above, thereby forming the Fabry-Perot interferometer FP, and the flow path forming layer 4 is laminated on the surface side of the movable film 3.

  The gap 2 is formed by previously stacking a sacrificial layer between the light receiving surface 11 of the photodiode 10 and the movable film 3 and removing it by etching. Accordingly, the gap 2 is formed only in the range where the sacrificial layer is laminated and the movable film 3 is formed on the surface thereof.

  The movable film 3 is formed of a flexible thin film, and the distance between the light receiving surface 11 and the movable film 3 changes within a range where the gap 2 is formed by mechanically bending the movable film 3. The interference wavelength of light by the Fabry-Perot interferometer FP is different. Therefore, the state of bending of the movable film can be detected by detecting the intensity of light of a specific wavelength.

  Thus, in order to form the movable film 3 in a flexible thin film, the movable film constituting material can be exemplified by Parylene (registered trademark) C or Parylene (registered trademark) N manufactured by Japan Parylene LLC. For example, diX (registered trademark) C or diX (registered trademark) N manufactured by Co., Ltd. can be used. By depositing these materials, the movable film 3 having optical transparency and flexibility can be formed. In order to exert the substance fixing ability on the surface side of the movable film 3, a material (substance) having the substance fixing ability on the surface such as Parylene (registered trademark) C or N or diX (registered trademark) C or N. What is necessary is just to laminate | stack the material which can be fixed. In addition, when the movable film is formed from a single material, Parylene (registered trademark) A or AM, diX (registered trademark) A, or AM can be used. These materials are also light transmissive and flexible, and can be used for the movable film 3. In addition, since the side chain has an amino group, a probe molecule (specific antibody) that can be electrically bonded to the amino group can be immobilized (has substance immobilization ability). In this case, by fixing the probe molecule (antibody) to the surface of the movable film 3 in advance, it is possible to detect a specific protein (antigen) that is specially adsorbed to the probe molecule (antibody).

  The movable film 3 is laminated in a wider range than the area where the gap 2 is formed, and the range where the gap 2 is formed becomes a movable area where the movable film 3 can actually move (bend deformation). The peripheral portion is a fixed region that fixes the movable region. In addition, when the gap 2 is formed, an etching hole 31 is formed at an appropriate position of the movable film 3 so that the sacrificial layer can be etched. The etching hole 31 functions as an etching material distribution region in the manufacturing process described later (referred to as an etching hole in that sense). However, after manufacturing, the etching hole 31 functions as a through-hole for communicating the outside with the gap portion 2. It functions.

  By the way, the flow path forming layer 4 is laminated on the upper part of the movable film 3 (including the movable area and the fixed area), and has the same size as the area where the movable area is formed on the movable film 3. In addition, a hollow portion 41 having an appropriate height dimension (several tens of μm to 100 μm) is formed, and a space is formed so that the movable membrane 3 does not stick to the peripheral portion while allowing the movable membrane 3 to be deformed. Has been. A flow path 42 is formed in a portion where the fixed region of the movable film 3 is formed. The flow channel 42 is connected to the hollow portion 41, and is configured so that a gas or a liquid (specimen) to be examined can be supplied to the hollow portion 41 via the flow channel 42.

  Here, as shown in FIG. 2 (the movable film 3 in FIG. 2 is shown as transparent), the flow path forming layer 4 includes a hollow portion forming region 41A and a flow that are opened only on one side (lower surface) 40b. The path configuration region 42A is formed, and the single-sided (lower surface) 40b is laminated so as to be in close contact with the surface side of the movable film 3, whereby the hollow part 41 and the channel 42 (FIG. 1) are formed. Is formed. That is, since the open portions of the hollow portion constituting region 41A and the flow passage constituting region 42A are closed by the surface of the movable membrane 3, the sealed hollow portion 41 and the flow passage 42 are formed. is there.

  Since the movable film 3 is laminated on the surface of the substrate 1 in a wide range including the gap portion 2 and its peripheral portion, the hollow portion configuration is formed by both the movable region and the fixed region of the movable film 3. The area 41A and the flow path configuration area 42A are sealed, and the flow path 42 can be formed long.

  The flow path forming layer 4 is provided with a communication portion 43 that penetrates from the front surface 40a to the back surface 40b. The communicating portion 43 is for allowing an etching material to pass through when the sacrificial layer is removed by etching. Therefore, the communication portion 43 is provided at a position where it can communicate with the etching hole 31 formed in the movable film 3. A space portion 21 formed integrally with the space portion 2 is formed around the space portion 2 formed in the substrate 1. Etching holes are formed in the movable film 3 stacked on the surface of the space portion 21. 31 is formed. In FIG. 2, the space portion 21 is illustrated in a hollow state, but the space portion 21 is also initially in a hollow state when a sacrificial layer is stacked and removed by an etching material. In addition, the etching hole 31 is comprised by the comparatively fine through-hole, as FIG. 2 shows.

  As described above, the communication portion 43 is provided in the flow path forming layer 4, so that the gap portion 2 formed between the light receiving surface 11 of the photodiode 10 and the movable film 3 includes the etching hole 31 and the communication portion. It is configured to communicate with the outside air through 43. This state is shown in FIG. As shown in this figure, the movable region 3a of the movable film 3 has a hollow portion 41 into which a specimen can flow and a void portion 2 on the back surface side. The gap 2 is under atmospheric pressure because it communicates with the outside air through the etching hole 31 and the communication portion 43. Since both ends of the flow path 42 connected to the hollow portion 41 are open, after the specimen is supplied to the hollow portion 41 (after passing), the hollow portion 41 can be brought to atmospheric pressure. . Since the specimen supplied to the hollow portion 41 passes through the surface of the movable membrane 3, when a specific substance contained in the specimen is fixed (specific adsorption) on the surface of the movable membrane 3, it is deformed by the intermolecular force. To get.

  In addition, using the area | region in which the flow path 41 is not formed among the board | substrates 1, as shown in FIG.3 (b), the electrodes 12 and 13 are provided in the p-type area | region and n + type area | region of the photodiode 10, A bias electrode is applied. Further, by arranging the light source L on the surface side of the flow path forming layer 4, the irradiation light of the light source L is transmitted through each layer. Therefore, the intensity is detected by the photodiode 10 as a photocurrent, and the movable film 3 is bent. The degree of can be detected.

  The physical / chemical sensor of this embodiment can be configured as a single sensor as shown in FIG. 2 and FIG. 3, and also has a plurality of sensors as shown in FIG. 1 and FIG. Alternatively, a configuration may be adopted in which a flow path 42 that continuously connects a plurality of hollow portions 41 is provided, and the same specimen can be detected by a plurality of sensors.

  4 is a cross section taken along IV-IV in FIG. 1. As shown in FIG. 4, a plurality of photodiodes 10 are formed on the substrate 1, and the respective photodiodes 10 make independent fabrics. A Perot interferometer FP is formed. A hollow portion 41 is formed above the movable film 3 constituting the Fabry-Perot interferometer FP, and a plurality of physical / chemical sensors having the same configuration as described above are arranged in parallel.

  In this case, the flow paths 42a to 42d are formed so as to connect the respective hollow portions 41 in series, and when the flow path 42a formed at one end is the inflow side, the flow path formed at the other end. 42b becomes the discharge side, and the intermediate flow paths 42c and 42d function as a connection for connecting the adjacent hollow portions 41.

  In the case of the above-described configuration, the sample is sequentially supplied to the plurality of hollow portions 41 by flowing the sample from the flow channel 42a on the inflow side, and the surface of the movable film 3 in each hollow portion 41. Therefore, the specific substance can be detected by the plurality of movable films 3. That is, when the plurality of movable films 3 have the same fixing ability, the specific substance can be fixed to the plurality of movable films 3. For example, when the movable membrane 3 is made of a substance-immobilizable material (such as the above-mentioned parylene (registered trademark) A or AM, diX (registered trademark) A or AM), the antibody A serving as a probe molecule is formed on the surface thereof. The antigen P can be specifically adsorbed by causing an antigen-antibody reaction with the antibody A by allowing blood or body fluid to flow in.

  In addition, by making the type of antibody A immobilized on the plurality of movable membranes 3 different for each movable membrane 3, specific antigens P capable of causing antigen-antibody reactions individually with different types of antibodies A are specifically adsorbed. It is also possible. That is, by individually adsorbing proteins derived from various diseases contained in specimens such as blood and body fluids, it is possible to detect the proteins, and supplying the same specimen to a single flow path for a plurality of specific substances Sensing can be performed.

  In the present embodiment, the gap 2 formed on the back surface side of the movable film 3 is isolated from the hollow portion 41 in any case where a single sensor or a plurality of sensors are arranged. It can also be prevented from flowing into the portion 2. Furthermore, the range in which the hollow portion 41 is formed is approximately the same as the width of the movable region of the movable membrane 3 and has a predetermined height dimension, so that a specific substance is fixed on the surface of the movable membrane 3 ( It does not inhibit deformation due to specific adsorption.

  Therefore, when a specific substance is detected, the specimen is brought into contact with the surface of the movable membrane 3 by supplying the specimen to the hollow portion 41 via the flow path 42 and the specific substance can be fixed (specific adsorption). It will be good. At this time, since the specimen is supplied to a limited narrow space, the specific substance can be efficiently fixed (specific adsorption).

  In addition, when it is necessary to wash the hollow part 41 and the flow path 42 after use, it is only necessary to allow the cleaning liquid to flow in via the flow path 42. What is necessary is just to let dry air flow in after washing | cleaning. In any case, it is possible to test different specimens in a relatively short time.

<Physical / chemical sensor array>
By the way, in the embodiment shown in FIGS. 1 and 4, a plurality of physical / chemical sensors configured as described above are formed on the substrate 1. That is, the illustrated state is an example of an embodiment of a physical / chemical sensor array. In the illustrated case, a plurality of (three in the figure) physical / chemical sensors are formed, and the flow paths 42 are connected in series with the hollow portions 41 disposed above the respective movable membranes 3. The ends of the flow paths 42 a and 42 b at both ends are opened at the edge of the substrate 1. In this case, an injection means such as a syringe is connected to the open end of one flow path 42a, and a sample storage means is connected to the open end of the other flow path 42b.

  As a different configuration, there may be a case where individual flow paths 42 are connected to the hollow portions 41 of a plurality of physical / chemical sensors. In this case, different specimens are caused to flow into the respective flow paths 42, or the specimens and the reference sample are distinguished and caused to flow, whereby different sensors are detected. This makes it possible to detect the same substance for different specimens at the same time, and it is possible to detect the difference in photocurrent between the specimen and the reference sample by simultaneously flowing the reference sample. Become.

  Further, there may be a case where a plurality of the above-described physical / chemical sensor hollow portions 41 are connected in series by the flow path 42 as one unit, and a plurality of the units are formed. In the case of such a sensor array, the same specimen can be detected by a plurality of sensors, and different specimens or reference samples can be simultaneously detected.

<Physical and chemical sensing devices>
As an embodiment of a physical / chemical phenomenon sensing device, there is one using the sensing array. For example, as shown in FIG. 5, when a flow path 142 that connects hollow portions 141a, 141b, and 241 of a plurality of sensors (three sensors in the figure) is formed in series, a plurality of sensors positioned upstream thereof Are the detection sensors 100a and 100b, and the sensor located downstream is the reference sensor 200.

  In order for some of the sensors to function as the reference sensor 200, the movable film 203 forming the reference sensor 200 may be one that does not have a substance fixing ability, or a specific film as shown in the figure. There is a method in which the antibody A (or B) is fixed only to the movable films 103a and 103b of the detection sensors 100a and 100b, and the antibody A (or B) is not fixed to the movable film 203 of the reference sensor 200. That is, the reference sensor 200 has the same configuration as the detection sensor 100, but prevents the specific substance from being fixed (specific adsorption).

  In the case where different types of antibodies A and B are fixed to the movable films 103a and 103b of the detection sensors 100a and 100b, different types of antigens contained in the same specimen can be detected. . That is, one detection sensor 100a detects an antigen that specifically adsorbs to antibody A, and the other detection sensor 100b detects an antigen that specifically adsorbs to antibody B.

  Thus, by making the reference sensor 200 the same configuration as the detection sensors 100a and 100b, the comparison condition between the two can eliminate the structural difference between the sensors 100a, 100b, and 200. In addition, since the detection sensors 100a and 100b and the reference sensor 200 have the same configuration, any one can be selected as the reference sensor 200 during use. In other words, by arranging a plurality of sensors on the substrate, a specific sensor among them is used for reference 200, and the remaining sensors are used for detection 100a and 100b, it is possible to simultaneously test a plurality of specimens. On the other hand, by using a plurality of sensors as the reference 200, it is possible to obtain a plurality of reference values with different conditions. If a plurality of sensors 100a, 100b, and 200 as described above are used as a single unit, and a plurality of units are configured, different specimens can be tested for each unit.

  Next, FIG. 6 shows a second embodiment of the physical / chemical phenomenon sensing device. In the present embodiment, different flow path forming layers 104 and 204 are provided in both sensors 100 and 200, and individual flow paths (not shown) are connected to the hollow portions 141 and 241. It is configured. As shown in this figure, in the present embodiment, the detection sensor 100 and the reference sensor 200 are formed on the same substrate while being distinguished, and the reference sensor 200 is substantially the detection sensor 100. It is set as the same structure.

  Conventionally, since the movable film surface is in an open state, it is assumed that the specimen is also supplied to the reference sensor, and is different from the detection sensor so that the movable film constituting the reference sensor is not deformed. It was set as the structure (refer patent document 1). That is, the gap is not formed on the back side of the movable film, and the movable film is laminated on the light receiving surface of the light receiving element. However, when the detection sensor and the reference sensor are different from each other as described above, the production of the reference sensor becomes complicated, and a comparison condition (sample supplied to the reference sensor) is arbitrarily selected. I couldn't do that either.

  Therefore, in the present embodiment, the sealed hollow portions 141 and 241 are individually provided on the surfaces of the movable films 103 and 203 of the individual sensors (detection 100 and reference 200). The hollow portions 141 and 241 can be separated from each other by forming flow paths that can be individually supplied while distinguishing the specimen and the reference sample in the hollow portions 141 and 241. It can be done. As a result, only the specimen can be supplied to the detection sensor 100, and only the reference sample can be supplied to the reference sensor 200. As a result, the detection sensor 100 detects the transmitted light intensity for the specimen to be examined, while the reference sensor 200 determines the transmitted light intensity for any (to be compared) sample. Will be detected. By comparing these detection values, it is possible to detect the presence and concentration of the specific substance in the specimen.

  For example, when the detection target is hydrogen gas, the specimen (gas) is supplied to the detection sensor 100, and the reference sensor 200 is supplied with a gas having molecules that are not fixed by the movable film 203. The presence of hydrogen gas can be detected by comparing the detected values. Further, when the detection target is a specific protein contained in blood or body fluid, the blood or body fluid is supplied to the detection sensor 100, and the reference sensor 200 does not contain a specific protein such as physiological saline. A liquid is introduced and the two are compared. The sample for comparison can be appropriately changed depending on the specimen. For example, when the specimen is blood, a red liquid should be used for the specimen in consideration of changes in light intensity due to coloring. Is assumed. Also, depending on the case, there may be a case where nothing is supplied.

  Further, the detection sensor 100 may have a configuration in which a plurality of physical / chemical sensors are arranged in series. In this case, in order to supply the same sample to each hollow part 141, the flow path connected in series is comprised. Similarly, the reference sensor 200 is configured such that a plurality of physical / chemical sensors are arranged in series, and the hollow portion 241 is configured to be continuous by a flow path different from the detection sensor 100. To do. When a specific substance is detected by a plurality of sensors for the same specimen, a detection value of a reference sensor to be compared for each of the plurality of detection sensors can be obtained.

  In this way, by making the reference sensor 200 similar in configuration to the detection sensor 100, the comparison condition between the two can eliminate the structural difference between the sensors 100 and 200. When a plurality of sensors connected in series are used as a unit and a plurality of units are configured, detection and reference can be distinguished for each unit.

<Physical / chemical sensor manufacturing method>
Next, a method for manufacturing a physical / chemical sensor will be described. A light receiving element (photodiode) is formed by a semiconductor process, a Fabry-Perot interferometer is formed on the surface, and then a flow path forming layer is laminated. The process is shown in FIGS.

  First, as shown in FIG. 7A, a photodiode 10 is formed on a substrate 1 by a semiconductor process, and a silicon oxide film 5 as a protective layer is formed on the surface thereof. A sacrificial layer 6 is formed on the surface (sacrificial layer generation step, see FIG. 7B). The material used for the sacrificial layer 6 is a material (etchable material) that can be removed by later etching, and for example, polysilicon can be used. When polysilicon is used as the etchable material, for example, polysilicon is deposited on the entire surface of the silicon oxide film by CVD, and patterned by photolithography to generate the sacrificial layer 6 in a necessary range. be able to. Since polysilicon is used not only as the sacrificial layer 6 but also in the peripheral laminated portion 7, the polysilicon is patterned so as to leave the polysilicon deposited in the laminated portion 7.

  Subsequently, the movable film layer 30 is laminated on the surface of the sacrificial layer 6 (movable film layer generation process, see FIG. 7C). Before this process, the surface of the laminated portion 7 is protected. Electrodes and the like are configured. That is, the silicon oxide film 8 is laminated on the surface and side surfaces of the laminated portion 7 in order to protect it from an etching material (etching gas or the like) in later etching. A silicon oxide film 8 is also laminated on the side surface of the sacrificial layer 6 to form the periphery of the void formed after etching. Further, in these processes, a part of the surface of the photodiode is formed by etching the silicon oxide film 5 with a buffered hydrofluoric acid solution, wiring aluminum in the part, and providing electrodes in the p-type region and the n + -type region. I can leave.

  After the necessary steps are completed, the movable film layer 30 is laminated on the surface of the sacrificial layer 6. The movable film layer 30 functions as a movable film after the sacrificial layer 6 is removed by etching. Therefore, an etching hole 31 is provided in the movable film layer 30 so that the etching material can reach the sacrificial layer 6. That is, after the movable film constituent material is formed on the entire surface of the sacrificial layer 6, the etching material distribution region (the portion that becomes the etching hole 31) is removed. As the movable film constituting material, parylene (registered trademark) C or N, diX (registered trademark) C or N, parylene (registered trademark) A or AM, or diX (registered trademark) A or AM can be used. . This is because these materials have optical transparency and flexibility and can function as a movable film. Therefore, other materials can be used as long as they have light transparency and flexibility. In addition, when the above material ends with A or AM, since it has an amino group in the side chain, a movable membrane layer 30 (later movable) that can fix a molecule (specific antibody) that can be electrically bonded to the amino group. Membrane). In addition, since the movable film layer 30 (following movable film | membrane) should just be the structure which has molecule | numerator fixing ability at least on the surface side, a thin film having light permeability and flexibility is formed, and the molecule fixing ability is formed on the surface. You may laminate the thin film which has.

  By the way, when the above-mentioned movable film constituent material is used as the movable film constituent material, it is vapor-deposited on the surface of the sacrificial layer by a vapor deposition method, and then a part (etching material distribution region) is removed by etching. The movable film layer 30 can be generated. Also in this case, a predetermined region is removed after patterning by oxygen plasma by a photolithography technique.

  Thereafter, the flow path forming layer 4 is laminated on the movable film layer 30 and its periphery (refer to the flow path forming layer generation step, FIGS. 8A and 8B). The flow path forming layer generating step in the present embodiment is generated in two steps, a wall surface forming step (see FIG. 8A) and a closing step (see FIG. 8B). That is, first, it is possible to communicate with a range where the hollow portion is to be formed (hollow portion configuration region 41a), a range where the flow channel is to be formed (flow channel configuration region), and the etching material circulation region (etching hole 31). In the possible range (communication region 43a), only the lower layer 4a is laminated in order to form the surrounding wall surface. This is the wall surface construction process. And the upper layer 4b is laminated | stacked in order to block | close the upper opening part of the hollow part 41 (and flow path). This is the closing process. In the figure, the flow path and the flow path constituting area are not shown, but are continuous to the hollow part 41 or the hollow part constituting area 41a in the vertical direction of the drawing.

  The lower layer 4a and the upper layer 4b are both made of a resist or the like. In the wall surface forming step, a portion that should form the wall surface is left by a photolithography technique, and the hollow portion forming area 41a, the flow path forming area Further, the communication area 43a is removed. On the other hand, in the closing step, the same kind of resist is laminated to close the hollow portion constituting area 41a and the flow path constituting area while keeping the hollow, and the upper layer 4b is laminated on the surface of the surrounding wall surface. At this time, the communication region 43a is not blocked by the resist, and the communication region 43b is formed also in the upper layer 4b. The formation of the communication region 43b in the upper layer 4b can also be performed by a photolithography technique. As described above, when the flow path forming layer 4 is formed of a resist by photolithography, post-baking is performed after exposure, development, and the like. As a result, the flow path forming layer 4 and the substrate 1 are consequently obtained. Adhesiveness is ensured.

  In the state where the flow path forming layer 4 is laminated as described above, the communication portion 43 penetrating the flow path forming layer 4 is provided by both the communication regions 43a and 43b formed in the lower layer 4a and the upper layer 4b. The etching material distribution region (etching hole 31) formed in the film layer 30 is in communication with the etching layer. Therefore, the sacrificial layer 6 is etched using the communication portion 43 and the etching material flow region 31 (see the sacrificial layer removal step, see FIG. 8C). The removal of the sacrifice layer 6 is performed by causing an etching gas to reach the sacrifice layer 6 by dry etching. As described above, when the etching gas is supplied from the outside of the flow path forming layer 4, the etching gas passes through the communication portion 43 to the surface of the movable film layer 30 and further the etching material for the movable film layer 30. That is, the sacrificial layer 6 is reached via the distribution area 31.

  The sacrificial layer 3 on the back surface side of the movable film layer 30 is removed by the series of steps described above, and a part of the movable film layer 30 becomes a film to form the movable film 3. At the same time, the gap 2 is formed on the back side of the movable film 3, and a Fabry-Perot interferometer is constructed together with the surface 11 of the photodiode 10 and the movable film 3. Further, since the hollow portion 42 and the flow path formed in the flow path forming layer 4 become a space isolated from the periphery by the lower layer 4a and the upper layer 4b, the gas or liquid supplied to the inside leaks out to the periphery. There is no. Accordingly, the gap 2 formed on the back surface side of the movable film 3 can be used as it is opened through the communication portion 43 and the etching material flow region 31. That is, it is not necessary to close the opening used in the etching.

  Since this embodiment is configured as described above, the sacrificial layer 6 removal step can be performed last, and there is no need to perform a wet process after the fabrication of the Fabry-Perot interferometer. Further, a sealed hollow portion 41 can be formed on the surface of the movable film 3, and a physical / chemical sensor having a configuration capable of supplying the specimen via the flow path to the movable film 3 can be manufactured.

<Physical / chemical phenomenon sensing device manufacturing method>
Next, a method for manufacturing a physical / chemical phenomenon sensing device will be described. As shown in FIGS. 9 and 10, the physical / chemical phenomenon sensing device is manufactured by constructing a plurality of physical / chemical sensors on a substrate. Therefore, basically, the process is the same as the manufacturing method of the physical / chemical sensor described above, but the flow path forming layer is generated because the flow path is divided and connected to a plurality of physical / chemical sensors. It is a little different in the process.

  That is, a plurality (two in the figure) of photodiodes 110 and 210 are formed on the substrate 1 (see FIG. 9A). Sacrificial layers 106 and 206 are laminated on the light receiving surfaces 111 and 211 of the photodiodes 110 and 210, respectively (sacrificial layer generation step, see FIG. 9B). At this time, the stacked portions 107 and 207 are also configured at the same time. Then, after protecting the side surfaces of the sacrificial layers 106 and 206 and the surfaces and side surfaces of the stacked portions 107 and 207 with the silicon oxide films 108 and 208, the movable film layers 130 and 230 are formed (movable film layer generation step, (See FIG. 9C). Thereafter, the flow path forming layers 104 and 204 are generated (flow path forming layer generating step).

  Also in this embodiment, the flow path forming layer generation process is based on a wall surface forming process and a closing process. That is, the lower layers 104a and 204a are laminated on the surfaces of the movable film layers 130 and 230, and the surrounding wall surfaces of the hollow portion constituting regions 141a and 241a and the communication regions 143a and 243a are formed (wall surface forming step, see FIG. 10A). ) Further, the upper layers 104b and 204b are laminated thereon to construct the flow path forming layers 104 and 204 constituting the hollow portions 141 and 241 and the communication portions 143 and 243 (blocking step, FIG. 10B). reference). Although not shown, when the hollow portions 141 and 241 are formed, a flow path connected to the hollow portions 141 and 241 is formed in a direction perpendicular to the paper surface.

  Finally, the sacrificial layers 106 and 206 are removed by etching (sacrificial layer removal step, see FIG. 10C) to form the movable films 103 and 203, and the voids 102 and 202 are formed on the back side thereof. Thus, a Fabry-Perot interferometer is configured.

  According to this embodiment, as shown in the figure, two physical / chemical sensors 100, 200 are formed in adjacent photodiodes 110, 210, but the same including individual hollow portions 141, 241 respectively. A structure detection sensor 100 and a reference sensor 200 can be produced. For convenience of explanation, the hollow portions 141 and 241 adjacent to each other are illustrated as not being connected by a flow path, but the hollow portions 141 and 241 may be connected by a flow path. In this case, the movable film 203 of the reference sensor 200 may be made of a material that does not have substance fixing ability. In addition, a unit in which a plurality of hollow portions 141 and 241 are continuous in a flow path as described above may be used as a unit, and a plurality of units may be configured simultaneously.

  The embodiments of the present invention are as described above. However, these embodiments are merely examples, and the present invention is not limited to the above-described embodiments. Therefore, it is possible to modify these as appropriate.

  For example, in the embodiment of the physical / chemical sensor or the physical / chemical phenomenon sensing device, a metal film may be formed on the front or back surface of the movable films 3, 103, 203 to form a half mirror. In this case, a reflectance may be improved by forming a metal film on the light receiving surface side of the photodiodes 10, 110, and 210. In the manufacturing method for forming such a half mirror, a metal material such as gold, silver or copper is deposited by a sputtering method or a vapor deposition method before and after forming the movable films 3, 103, 203 and the like. The Rukoto.

  Hereinafter, a physical / chemical sensor having a Fabry-Perot interferometer was produced by the manufacturing method. The manufactured physical / chemical sensor is a sensor array in which 4 × 4 photodiodes are formed on a silicon substrate, and four units are connected in series to form four rows. Polysilicon was used for the sacrificial layer, and finally etching was performed with xenon difluoride gas. For the flow path forming layer, TMMF2000 manufactured by Tokyo Ohka Co., Ltd. was used as a resist having resistance to xenon difluoride. It was determined that the resist used here has high light transmittance and can be used as a flow path forming layer. FIG. 11 (a) shows a micrograph of the surface of the fabricated sensor, FIG. 11 (b) shows a photo of the entire substrate, and FIG. 11 (c) shows a state in which the substrate is mounted on an inspection apparatus (having an inlet and an outlet). ) Respectively.

<Experimental result>
In the final sacrificial layer removal step, xenon difluoride gas (etching gas) reaches the sacrificial layer via the communication portion (communication region) and the etching material flow region (etching hole), and the sacrificial layer is It was tested whether it was removed or not. The experiment confirmed the change in color due to light interference before and after etching. The result is shown in FIG. Although the photograph in this figure is not clear, it was actually confirmed that the vicinity of the center of the movable film (movable region) changed from green to red. This is considered to be due to the change in the light wavelength between the case where the sacrificial layer is present and the case where the gap is formed.

  Moreover, it experimented whether the produced space | gap part was functioning. In the experiment, the reflection spectrum was measured and the state of the movable film was evaluated. The sensor used in the experiment was the same as that described above, and after the liquid flowed into the flow path, the sensor was dried and then the reflection spectrum was measured when the same liquid was flowed. The liquid used was ethanol in consideration of surface tension. The result is shown in FIG. In addition, since there was a sensor suspected of liquid leakage, it is shown in FIG. 13B for comparison. In addition, what is described as “initial” and “stition” in the figure is shown for comparison, and “initial” is a state in which a normal void portion is formed and liquid is not allowed to flow in. The “spection” indicates the reflection spectrum when stiction (a defective state in which the movable film adheres to the light receiving surface of the photodiode) occurs.

  As is clear from this result, in the sensor produced by the experiment, four interference peaks were confirmed in the wavelength band of 450 nm to 750 nm as in the normal case. On the other hand, for the sensor suspected of liquid leakage, the interference peak is reduced to three as in the case where stiction occurs. Therefore, it has been found that the gap of the sensor used in the experiment does not leak even when liquid flows in and functions normally. For the sensor used in the experiment, the interference peak shifted about 20 nm to the long wavelength side, which is presumed that the movable film was slightly deformed due to non-specific adsorption of molecules in the liquid. The Also in this sense, by using the comparison target by the reference sensor, it is possible to clearly detect the state of specific adsorption of the specific substance.

  Finally, the photocurrent value of the photodiode with respect to the intensity change of the irradiation light emitted from the light source is measured, the output characteristics thereof are shown in FIG. 14A, and the photocurrent value when a reverse bias voltage is applied to the photodiode. FIG. 14B shows the characteristics thereof. As is clear from the above results, the output current has a linear response to the intensity of the irradiated light, and it has been found that the transmittance can be measured even when the flow path forming layer is laminated.

DESCRIPTION OF SYMBOLS 1 Substrate 2,101,202 Gap part 3,103,103a, 103b, 203 Movable film 3a Movable area | region 4,104,204 Flow path formation layer 4a, 104a, 204a Lower layer 4b, 104b of flow path formation layer 2014a Upper layer 5, 105, 205 silicon oxide film 6, 106, 206 Sacrificial layer 7, 107, 207 Laminated portion 8, 108, 208 Silicon oxide film 10, 110, 210 Photodiode (light receiving element)
11, 111, 211 Light-receiving surface 12, 13 Electrode 21 Spatial portion 30, 130, 230 Movable film layer 31 Etching hole (etching material distribution region)
40a Channel forming layer front surface 40b Channel forming layer back surface 41, 141, 141a, 141b, 241 Hollow part 41A Hollow part constituting area 42, 42a, 42b, 42c, 42d, 142 Channel 42A Channel constituting area 43, 143 243 Communication part (communication area)
43a, 43b, 143a, 143b, 243a, 243b Communication area 100, 100a, 100b Detection sensor 200 Reference sensor A, B Antibody L Light source FP Fabry-Perot interferometer

Claims (14)

A light-receiving surface of the light-receiving element is provided with a movable film provided to face the light-receiving surface while forming a gap, and the movable film has a substance fixing ability on at least an outer surface and is Fabry-Perot together with the light-receiving surface. In physical and chemical sensors configured to form an interferometer,
A flow path forming layer laminated on the outer surface of the movable membrane, the flow path forming layer forming a hollow portion on the outer surface of the movable membrane and a flow path connected to the hollow portion; Physical and chemical sensors characterized by   The movable membrane includes a through portion penetrating a part of a peripheral portion, and the flow path forming layer is formed so as to communicate with the through portion at a position deviating from the hollow portion and the flow path. The communication part which penetrates a layer is provided, The space part formed between the light-receiving surface and the movable film communicates with the outside via the penetration part and the communication part. Physical / chemical sensors.   The physical / chemical sensor according to claim 1, wherein the movable film is formed of a material having a molecular fixing ability for fixing molecules contained in a gas or a liquid.   4. The physical / chemical sensor according to claim 1, wherein the movable film includes a flexible base film and a molecular fixed film in which a material having a molecular fixability is laminated on a surface of the base film. 5. . A sensor array using the physical / chemical sensor according to claim 1,
A plurality of physical / chemical sensors are formed on a substrate, and a flow path formed in the flow path layer connects a plurality of hollow portions formed on the outer surface of the movable film of each physical / chemical sensor in series. A physical / chemical sensor array characterized by being formed to A sensor array using the physical / chemical sensor according to claim 1,
A plurality of units are provided by a plurality of the physical / chemical sensors formed on the substrate, and the flow path formed in the flow path layer is the outer surface of the movable film of each physical / chemical sensor for each unit. A physical / chemical sensor array formed by connecting a plurality of hollow portions formed in a series in series.   The physical / chemical sensor array according to claim 6, wherein the flow path includes an inflow portion and a discharge portion that open at an edge of the substrate for each unit. A sensing device using the physical / chemical sensor according to claim 1,
A physical / chemical phenomenon sensing device, wherein a plurality of the physical / chemical sensors are arranged on a substrate, part of which is used for reference, and part or all of the other is used for detection. A sensing device using the sensor array according to claim 6 or 7,
Among the plurality of units, some physical / chemical sensors among the plurality of physical / chemical sensors constituting each unit are used for reference, and other physical / chemical sensors are used for detection.・ Chemical phenomenon sensing devices. A sensing device using the sensor array according to claim 6 or 7,
A physical / chemical phenomenon sensing device, wherein a part of the plurality of units is used for reference and a part or all of the other is used for detection. A sacrificial layer generating step of generating a sacrificial layer by depositing an etchable material on the light receiving surface of the light receiving element;
A movable film layer generating step of generating a movable film layer by depositing the movable film constituent material in the movable film constituent region except for the etching material distribution region for allowing the etching material to pass through the surface of the sacrificial layer;
A space portion and a flow path connected to the space portion are formed on the outer surface of the movable film layer, and a communication region communicating with the etching material flow region is formed, and a flow region is formed on the surface of the movable film layer. A flow path forming layer generating step of laminating a path forming layer;
A sacrificial layer removing step of causing the etching material to reach the sacrificial layer through the etching material flow region and the communication region, and removing the sacrificial layer by etching to form a void on the back side of the movable film layer. A method of manufacturing a physical / chemical sensor characterized by the above.   The flow path forming layer generating step includes a wall surface forming step that forms a surrounding wall surface of the space portion forming region, the flow path forming region, and the communication region, and a blockage that closes an upper opening of the space portion forming region and the flow path forming region. The method for producing a physical / chemical sensor according to claim 11, comprising: a process. A sacrificial layer generating step of generating a sacrificial layer by depositing an etchable material on each light receiving surface of a plurality of light receiving elements fabricated on a substrate;
A movable film layer generating step of generating a movable film layer by depositing the movable film constituent material in the movable film constituent region except for the etching material distribution region for allowing the etching material to pass through the surface of the sacrificial layer;
The etching material is formed on the outer surface of the movable film layer with a space portion and a flow path connecting the space portions in series for each unit while dividing the plurality of light receiving elements into a plurality of units. A flow path forming layer generating step of laminating a flow path forming layer on the surface of the movable film layer while forming a communication area communicating with the flow area;
A sacrificial layer removing step of causing the etching material to reach the sacrificial layer through the etching material flow region and the communication region, and removing the sacrificial layer by etching to form a void on the back side of the movable film layer. A method of manufacturing a sensing device for physical / chemical phenomena.   The flow path forming layer generating step includes a wall surface forming step that forms a surrounding wall surface of the space portion forming region, the flow path forming region, and the communication region, and a blockage that closes an upper opening of the space portion forming region and the flow path forming region. The method for manufacturing a physical / chemical phenomenon sensing device according to claim 13, comprising: a process.

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