JP2011112594A - Sensor chip and sensor device using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sensor chip for securely adsorbing or trapping a spherical substance, such as a particle or a cell, and also to provide a sensor device using the same. <P>SOLUTION: The sensor chip is equipped with a sheet and a frame body to support the periphery of the sheet, in which the sheet has at least a through-hole to penetrate a first surface and a second surface facing the first surface and a recess continuously provided from the through-hole has a diameter greater than the bore diameter of the through-hole and a narrow-down portion on the first surface side. The structure provides a sensor chip improving the adhesiveness between the spherical substance, such as an particle and a cell, and the recess. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a sensor chip for adsorbing or capturing spherical particles of particles such as cells and beads, a cell electrophysiological sensor for measuring the electrophysiological activity of cells using this sensor chip, and a sample such as a chemical substance. The present invention relates to a sensor device such as a chemical substance identification sensor to be measured.

  As shown in FIG. 11, a cell electrophysiological sensor which is an example of a conventional sensor device has a mounting substrate 2 having conduction holes 1 and silicon held at the lower ends of these conduction holes 1 as main components. Sensor chip 3 and electrodes 4 and 5 disposed above and below the mounting substrate 1, respectively. The sensor chip 3 includes a through hole 7 having a recess 6.

  Here, the upper and lower portions of the sensor chip 3 are filled with the electrolyte, and the cells are injected from the upper portion of the sensor chip 3, and the cells are injected from the upper portion of the through-hole 7 or sucked from the lower portion. Can be sucked and captured in the hollow portion 6.

  Then, in a state where the cells are captured, a drug is administered from above the cells, and the potential difference between the electrolyte solution above and below the sensor chip 3 is measured using the electrodes 4 and 5, so that the cells are activated. It is possible to measure a change in potential inside or outside the cell, a current value, or a physicochemical change caused by cell activity.

  For example, Patent Literature 1 is disclosed as an example similar to the above-described cell electrophysiological sensor.

JP 2005-156234 A

  The configuration as described above has a problem that the measurement accuracy of the sensor device is low. This is because the adhesion between the cells and the depression 6 of the through-hole 7 is low, and the cells cannot be reliably captured by the depression 6, so that the electrical insulation between the upper side and the lower side of the sensor chip 3 is sufficient. The cause is that it is not secured. As a result, the measurement accuracy is reduced.

  SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to solve the above problems and to realize a sensor chip and a sensor device using the sensor chip for reliably adsorbing or capturing spherical substances such as particles and cells.

  In order to achieve this object, a sensor chip according to the present invention includes a thin plate and a frame body that holds a peripheral portion of the thin plate, and the thin plate is between a first surface and a second surface facing the first surface. At least one through-hole that penetrates the through-hole, and a concave portion having a diameter larger than the diameter of the through-hole and having a throttle portion on the first surface side.

  The sensor device of the present invention includes a mounting substrate and a sensor chip held at a lower end portion of a conduction hole that conducts from the upper surface to the lower surface of the mounting substrate, and the sensor chip is a thin plate and a peripheral portion of the thin plate. The thin plate has at least one through-hole penetrating between the first surface and the second surface facing the first surface, and the through-hole has a through-hole in the through-hole. A recess having a diameter larger than the hole diameter and having a throttle portion on the first surface side is provided.

  In addition, another sensor device of the present invention includes a mounting substrate and a sensor chip held in a central portion of a conduction hole that conducts from the upper surface to the lower surface of the mounting substrate, and the sensor chip is a thin plate and the thin plate. The thin plate has at least one through-hole penetrating between the first surface and the second surface opposite to the first surface, and the through-hole includes the through-hole. A concavity having a diameter larger than the diameter of the hole and having a constricted portion on the first surface side, and a microsphere having a probe function disposed in the concavity, and the conduction divided by the microsphere One of the first region and the second region of the hole is filled with a liquid.

  Thereby, the sensor chip of this invention and the sensor device using the same can improve the adhesiveness of spherical substances, such as particle | grains and a cell, and a recessed part.

  This is because, as described above, spherical portions such as particles and cells easily bite into the recesses by having the constriction in the recesses.

  As a result, spherical substances such as particles and cells can be reliably adsorbed or captured.

Sectional drawing of the sensor chip in Embodiment 1 Sectional drawing of the principal part of the sensor chip in Embodiment 1. Top view of main parts of another sensor chip in the first embodiment AB cross section of FIG. Sectional drawing of the sensor device in Embodiment 2 Sectional drawing of the principal part of the sensor device in Embodiment 2. Partially cutaway perspective view of a sensor device according to Embodiment 3 Sectional drawing of the principal part of the sensor device in Embodiment 3. Sectional drawing of the principal part of the sensor device in Embodiment 3. Sectional drawing of the principal part of the sensor device in Embodiment 3. Partially cutaway perspective view of a conventional sensor device

(Embodiment 1)
Hereinafter, the sensor chip 11 in the present embodiment will be described. In addition, in each embodiment, what has the same configuration as the preceding embodiment is described with the same reference numeral, and detailed description may be omitted. The present invention is not limited to the following embodiments.

  As shown in FIGS. 1 and 2, the sensor chip 11 in the present embodiment includes a disk-shaped thin plate 12 mainly composed of silicon, and a cylindrical frame 13 that supports the outer periphery of the thin plate 12. The thin plate 12 has a through-hole 14 that penetrates the upper and lower surfaces thereof. By providing the frame 13, even when the thin plate 12 is thin, the mechanical strength of the entire sensor chip 11 can be kept high.

  A recess 15 having a diameter larger than the diameter of the through hole 14 is continuously provided in the through hole 14 on the first surface side of the thin plate 12, and an arc surface and an arc surface having different curvature radii of the recess 15 are provided. A diaphragm 16 is provided at the intersecting position. That is, as shown in FIG. 2, the curvature radius CR2 of the curved surface at the position P2 of the recess 15 is different from the curvature radius CR1 of the inner wall surface, which is a curved surface at a position P1 different from the position P2. Specifically, the position P1 is closer to the opening than the position P2, and the curvature radius CR1 is larger than the curvature radius CR2. When the sensor chip 11 is viewed from the vertical direction, the diameter of the position P1 is preferably larger than the diameter of the position P2. The position, depth, and size of the aperture can be changed as appropriate according to the purpose of use.

  Next, members of the sensor chip in the present embodiment will be described.

  The sensor chip 11 can be formed by etching a silicon single crystal substrate, an SOI (Silicon on Insulator) substrate, a glass substrate, a quartz substrate, or the like.

In the present embodiment, an SOI substrate in which a silicon dioxide layer is sandwiched between silicon layers is used as the sensor chip 11, and the concave portion 15 having the throttle portion 16 is first formed by etching. For the etching for forming the recess 15 having the narrowed portion 16, a process of repeatedly introducing and discharging the etching material is used. Specifically, first, an SOI substrate on which a mask is formed is placed in a chamber or the like, and a certain amount of etching material is introduced into the chamber. Then, the introduced etching material is reacted with the SOI substrate. And after making it react for a fixed time, reaction is once complete | finished, the etching material which reaction was completed is sucked using a pump etc., and is discharged | emitted. Thereafter, a new etching material is introduced into the chamber and reacted in the same manner. After the reaction, suction and discharge are performed. In this manner, the introduction of the etching material, the etching reaction, and the discharge of the etching material that has completed the reaction are repeatedly performed. At this time, since the size of the opening of the mask is 10 μm or less, it is difficult for the etching material that has entered the inside of the recess 15 to be completely discharged. Therefore, in particular, the etching material that has completed the etching reaction tends to stay in the lower portion of the recess 15 at a position away from the opening of the mask. Then, in the state where the etching material having completed the reaction stays in the recess 15, a new etching material is introduced and the etching reaction is started, so that the etching rate at the lower portion of the recess 15 where the new etching material has not reached much is increased. The curvature radius CR2 is decreased. On the other hand, in the upper part of the recess 15 near the opening of the mask, since it is close to the opening of the mask, it is relatively easy to discharge the etching material from the opening of the mask and to introduce the unreacted etching material. . Therefore, the etching rate does not decrease, and as a result, the radius of curvature CR1 becomes larger than CR2. Thus, since a change occurs in the etching rate during the etching reaction, a desired shape can be obtained. As an etching method at this time, dry etching is preferable because highly precise microfabrication is possible and the switching of the discharge and introduction of the etching material is easy. As an etching gas used at this time, a gas capable of etching Si, such as SF ₆ , CF ₄ , Cl ₂ , and XeF ₂ , can be used.

  Thereafter, fine through holes 14 were formed by dry etching. Note that an SOI substrate can use an intermediate silicon dioxide layer as an etching stop layer. Therefore, the depth of the through hole 14, the thickness of the thin plate 12, the height of the frame 13, and the like can be processed with high accuracy as designed.

  Although the sensor chip 11 is formed using an SOI substrate, for example, single crystal silicon, polycrystalline silicon, amorphous silicon, a mixture of polycrystalline silicon and amorphous silicon, glass, crystal, and the like, and silicon dioxide are the main components. You may form with a diaphragm with a base material.

  Thus, by providing the through-hole 14 with the concave portion 15 and having the constricted portion 16 in the concave portion 15, spherical substances such as particles and cells are firmly bitten into the concave portion 15, and the spherical substance 17 such as particles and cells. Can be reliably adsorbed or captured, and as a result, the adhesion between the spherical substance 17 and the recess 15 can be enhanced.

  It should be noted that at least one throttle part 16 may be provided in the recess 15, but it is desirable to have a plurality of throttle parts 16 in order to capture the spherical substance 17 more reliably.

  Although the sensor chip 11 is arranged below the frame 13 so that the thin plate 12 is the bottom surface, the mechanical strength of the entire sensor chip 11 is kept high even if the orientation of the sensor chip 11 is upside down. be able to.

  3 and 4, a plurality of through holes 14 are provided in the thin plate 12, and a concave portion 15 having a plurality of throttle portions 16 is connected to each through hole 14, and an inner wall of the adjacent concave portion 15 is formed. You may form so that it may mutually cross.

  That is, the inner walls of the adjacent recesses 15 intersect with each other, and the intersecting portion has a protruding shape formed with a curved surface. And even if the spherical substance 17 lands on this part, it is inclined to any one of the recesses 15 by gravity without being attached, and quickly rolls into the recesses 15 along its inner wall and is captured or adsorbed. The capture rate or adsorption rate of the spherical substance 17 in the recess 15 can be improved.

(Embodiment 2)
Hereinafter, a cell electrophysiological sensor which is a sensor device in the present embodiment will be described.

  As shown in FIG. 5, in the sensor device according to the present embodiment, a mounting substrate 19 having conductive holes 18 formed in an array and a sensor chip 11 inserted and fixed inside the conductive holes 18 are provided. I have. As shown in FIG. 6, the sensor chip 11 includes a disk-shaped thin plate 12 held at the lower end of the conduction hole 18 and a cylindrical frame 13 that supports the outer periphery of the thin plate 12. The thin plate 12 is formed with a through hole 14 penetrating the upper and lower surfaces thereof. Here, the thin plate 12 functions as a partition plate that partitions the upper surface side and the lower surface side of the mounting substrate 19, and the through hole 14 functions as a through path that penetrates the upper surface side and the lower surface side of the mounting substrate 19. Further, by providing the frame 13, the mechanical strength of the entire sensor chip 11 can be kept high even when the thin plate 12 is thin, and damage to the sensor chip 11 when mounted on the mounting substrate 19 is reduced.

  The through-hole 14 is continuously provided with a recess 15 having a diameter larger than the diameter of the through-hole 14 for capturing the substantially spherical subject 20 made of a cell or a living body-derived membrane on the upper surface side of the mounting substrate 19. In addition, the constricted portion 16 is provided at a position where the arc surface and the arc surface having different curvature radii of the concave portion 15 intersect. Specifically, the position P1 is closer to the upper surface side of the mounting substrate 19 than the position P2, and the curvature radius CR1 is larger than the curvature radius CR2. When the sensor chip 11 is viewed from the vertical direction, the diameter of the position P1 is preferably larger than the diameter of the position P2. In addition, the maximum opening diameter of the recess 15 is about 10 μm, the minimum opening diameter is the same as the opening diameter of the through hole 14, and when the subject 20 is a cell, it is suitable for holding the cell to be 5 μm or less. ing. Note that the position, depth, and size of the aperture 16 can be changed as appropriate according to the purpose of use.

  Further, the throttle part 16 may be at least one in the concave part 15, but it is desirable to have a plurality of throttle parts 16 in order to capture the spherical substance 17 more reliably.

  Although the sensor chip is disposed below the frame 13 so that the thin plate 12 is the bottom surface, the mechanical strength of the entire sensor chip can be kept high even if the orientation of the sensor chip is upside down. .

  The thin plate 12 has a thickness of 10 μm to 100 μm, a diameter of 1000 μm, the frame has a height of about 400 μm, the outer diameter is 1000 μm, and the through hole has an opening diameter of 1 μm to 3 μm (the depth is the same as the thickness of the thin plate 12).

  Moreover, it is preferable that the surface of the thin plate which has a recessed part is formed with a silicon dioxide layer. Since the silicon dioxide layer has high insulating properties, the subject 20 can be held in close contact. Thereby, the leakage current through the sensor chip can be reduced. Furthermore, since the silicon dioxide layer has high hydrophilicity, the adhesion between the subject 20 and the recess 15 is improved, and the measurement accuracy of the sensor device 11 can be improved.

  Further, as shown in FIG. 5, a probe-shaped measuring electrode 21 and a thin tubular dispenser 22 are inserted into the conduction hole 18 from above.

  The measurement electrode 21 measures the potential, current value, or resistance value of the electrolyte injected above the sensor chip 11. The dispenser 22 is for injecting an electrolyte solution, cells, drugs, and the like above the sensor chip 11.

  A reference electrode 23 is provided on the lower surface of the mounting substrate 19. Further, a flow path plate 25 for forming a flow path 24 is joined below the mounting substrate 19, and the flow path 24 can be filled with an electrolytic solution. The reference electrode 23 described above only needs to be able to measure the potential (or current value or resistance value) of the electrolytic solution, and the position and shape can be changed as appropriate. For example, it may have a probe shape and may be inserted into the space below the sensor chip 11.

  In addition, if the mounting substrate 19 and the flow path plate 25 are made of resin, it is easy to mold and assembly is also easy. More preferably, a thermoplastic resin is used, and by using means such as injection molding, a uniform molded body with high productivity can be obtained. In addition, these thermoplastic resins are preferably polycarbonate (PC), polyethylene (PE), olefin polymer, polymethyl methacrylate acetate (PMMA), or a combination thereof.

  Further, these thermoplastic resins may be cyclic olefin polymers, linear olefin polymers, cyclic olefin copolymers obtained by polymerizing them, or polyethylene (PE) from the viewpoint of workability, production cost, and material availability. preferable.

  In particular, the cyclic olefin copolymer is highly transparent and highly resistant to inorganic chemicals such as alkalis and acids, and is suitable for the production method or use environment of the present invention. In addition, since these materials can transmit ultraviolet rays, they are effective when adhered using an ultraviolet curable adhesive.

  Next, a measurement method in cell electrophysiology using the sensor device in the present embodiment will be described.

  As shown in FIG. 5, a dispenser 22 is inserted from above the conduction hole 18, and an extracellular fluid (electrolytic solution) is injected above the sensor chip 11. In addition, intracellular fluid (electrolytic solution) is injected into the flow path 24.

Here, for example, in the case of mammalian muscle cells, the extracellular fluid is typically an electrolytic solution containing about 4 mM K ⁺ ions, about 145 mM Na ⁺ ions, and about 123 mM Cl ⁻ ions. The solution is an electrolytic solution to which K ⁺ ions are added at about 155 mM, Na ⁺ ions at about 12 mM, and Cl ⁻ ions at about 4.2 mM.

  Next, the measurement electrode 21 is inserted from above the conduction hole 18. Thus, a conduction resistance value of about 100 kΩ to 10 MΩ can be observed between the measurement electrode 21 electrically connected to the extracellular fluid and the reference electrode 23 electrically connected to the intracellular fluid. . This is because the intracellular fluid or the extracellular fluid permeates through the through hole 14 and an electric circuit is formed between the measurement electrode 21 and the reference electrode 23. Next, when the subject 20 is introduced from above the sensor chip 11 via the dispenser 22 and the pressure is reduced by the pressure transmission tube, the subject 20 is attracted to the opening of the recess 15 as shown in FIG. Thus, when the subject 20 closes the opening of the recess 15, the electrical resistance between the extracellular fluid and the intracellular fluid is sufficiently high (referred to as a giga seal) of 1 GΩ or more. In this giga-seal state, if the potential inside and outside the cell changes due to the electrophysiological activity of the subject 20, even a slight potential difference or current can be measured with high accuracy. Here, at the time of this measurement, reducing bubbles in the intracellular fluid inside the flow path 24 as much as possible contributes to improvement in measurement accuracy.

  Next, a drug such as nystatin is injected into the space inside the flow path 24 in FIG. 5, or a hole is made in the cell membrane of the subject 20 closing the through hole 14 with a needle (referred to as a whole cell).

  Thereafter, a chemical solution is injected from above the sensor chip 11 via the dispenser 22 to stimulate the subject 20. At this time, the method for stimulating the subject 20 may be chemical stimulation such as a chemical solution as in the present embodiment, or other physical stimulation such as an electrical signal. When the ion channel of the subject 20 reacts due to these chemical or physical stimuli, the reaction is detected by the potential difference (or current value change or resistance value change) between the measurement electrode 21 and the reference electrode 23. be able to.

  Since the through hole 14 has the concave portion 15 and the concave portion 15 has the constricted portion 16, the subject 20 can easily bite into the concave portion 15, so that the subject 20 can be reliably adsorbed or captured. Thus, the adhesion between the subject 20 and the recess 15 can be improved.

  Note that the thin plate 12 of the sensor chip 11 of the present embodiment can be used upside down. That is, even when the subject 20 is adsorbed on the surface opposite to the surface having the recess 15 of the sensor chip 11, the flow path resistance from the solution flowing through the flow path 24 can be suppressed by the throttle portion 16. Therefore, the subject 20 can be held.

  As described above, the sensor device of the present embodiment is useful for measurement of cellular electrophysiology related to, for example, a high-precision and high-speed drug screening system.

  In addition, description about the same structure and effect as Embodiment 1 is abbreviate | omitted.

(Embodiment 3)
Hereinafter, a chemical substance identification sensor which is a sensor device in the present embodiment will be described.

  As shown in FIGS. 7 and 8, the sensor device according to the present embodiment includes a pair of bottomed cylindrical mounting substrates 19 constituting the cavity 26 and a pair of mounting substrates 19 so as to partition the cavity 26. The sensor chip 11 is fixed to the sensor chip 11. The sensor chip 11 includes a plate-like thin plate 12 that partitions the upper space 27 and the lower space 28 of the cavity 26, and a cylindrical frame 13 that supports the outer periphery of the thin plate 12. A through hole 14 penetrating the upper and lower surfaces is formed. Here, the thin plate 12 functions as a partition plate that separates a first region that is an upper space 27 of the cavity 26 and a second region that is a lower space 28 of the cavity 26, and the through hole 14 is an upper space of the cavity 26. It functions as a through path that penetrates the first region 27 and the second region 28 that is the lower space 28 of the cavity 26.

  The through-hole 14 is provided with a recess 15 for adsorbing particles (beads) 30 having probes 29 formed on the surface thereof in the upper space 27, and chemical substances are identified through the particles 30. Do. Further, the constricted portion 16 is provided at a position where the arc surface and the arc surface having different curvature radii of the concave portion 15 intersect each other. That is, the curvature radius CR2 of the curved surface at the position P2 of the recess 15 is different from the curvature radius CR1 of the inner wall surface that is the curved surface at the position P1 different from the position P2. Specifically, the position P1 is closer to the upper space 27 than the position P2, and the curvature radius CR1 is larger than the curvature radius CR2. When the sensor chip 11 is viewed from the vertical direction, the diameter of the position P1 is preferably larger than the diameter of the position P2. The maximum opening diameter of the recess 15 is about 10 μm, and the minimum opening diameter is the same as the opening diameter of the through hole 14. Note that the position, depth, and size of the aperture 16 can be changed as appropriate according to the purpose of use. Further, it is sufficient that the narrowed portion 16 is at least one in the concave portion 15.

  Although the sensor chip 11 is disposed below the frame 13 so that the thin plate 12 is the bottom surface, the mechanical strength of the entire sensor chip is kept high even if the orientation of the sensor chip 11 is upside down. Can do.

  The thin plate 12 has a thickness of 10 μm to 100 μm, a diameter of 1000 μm, the frame 13 has a height of about 400 μm, the outer diameter is 1000 μm, and the through hole 14 has an opening diameter of 1 μm to 3 μm (the depth is the same as the thickness of the thin plate 12). did.

  In addition, a light inlet 31 and a light detection port 32 such as an optical fiber are provided in the upper space 27 and the lower space 28, respectively. Connected).

  Further, the inside of the through hole 14 having the concave portion 15 having the upper space 27, the lower space 28 and the throttle portion 16 is filled with liquid. Here, the liquid is a liquid substance in which the target chemical substance to be measured exists. Further, the upper space 27 and the lower space 28 are configured to be covered with the mounting substrate 19, and thus the upper space 27 and the lower space 28 are isolated from the external atmosphere. As a result, the internal pressure can be controlled.

  In the present embodiment, the upper space 27 and the lower space 28 are both filled with the liquid. However, the light passing through the through hole 14 to the lower space 28 diffuses in the liquid filling the lower space 28. Therefore, there is an advantage that introduction into the light detection port 32 installed in the lower space 28 becomes easy. However, on the other hand, if it is not preferable to diffuse light in the lower space 28, the lower space 28 may not be filled with liquid. In this case, the light that has passed through the through hole 14 reaches the light detection port 32 directly.

  The material of the particles 30 is not particularly limited, but preferably has transparency with respect to the excitation light 33 and the detection light 34 used for identification, and has such transparency. Suitable materials include inorganic materials such as glass and ceramic materials, or resin materials such as polycarbonate, polystyrene, and polyolefin. Further, the size of the particles 30 is a spherical shape having a diameter of about 0.5 to 100 μm, so that the particles 30 can be stably held inside the concave portion 15 having the throttle portion 16 provided on the thin plate 12 of the sensor chip 11. . However, shapes other than the spherical shape are not excluded. For example, in order to increase the amount of the probe 29 attached to the surface, the present embodiment can be applied to an irregular shape having irregularities on the surface.

  Further, a probe 29 is attached to the surface of the particle 30, and this probe 29 is synthesized as a specific compound corresponding to the substance to be inspected 35. For example, a DNA probe is a DNA having a complementary base sequence that binds to a specific base sequence. When it is desired to determine the presence or absence of DNA having a specific sequence in a solution, it binds to this DNA probe (hybridization). Can be identified by whether or not

  In particular, in the present embodiment, the probe 29 is fluorescently labeled, and when the substance 35 to be examined is bound, fluorescence is emitted with respect to the excitation light 33 that is input light from the outside. As a result, the color of the detection light 34 that has passed through the surface of the particle 30 changes depending on the presence or absence of hybridization. In the sensor device of the present embodiment, only the detection light 34 that has passed through the through hole 14 is observed. Therefore, it is possible to reduce noise from others, which makes it possible to identify chemical substances with higher accuracy.

  In addition, RNA, protein, etc. other than DNA can be used for the kind of probe 29.

  Next, a method for identifying a chemical substance present in a liquid using the sensor device according to the present embodiment will be described.

  As shown in FIGS. 9 and 10, in the upper space 27, the particles 30 having the probe 29 formed on the surface are held inside the recess 15 having the throttle portion 16. Here, since the concave portion 15 is smaller than the particle 30, as a method for holding the particle 30, strong holding can be easily realized by decompressing the lower space 28 and sucking the through hole 14.

  In addition, since this holding method uses a pressure difference between the upper space 27 and the lower space 28, it is not necessary to provide a separate chemical bonding site for adsorbing the particles 30 in the recess 15 having the throttle portion 16. Has the advantage.

  Further, since the upper space 27 and the lower space 28 are partitioned by the thin plate of the sensor chip 11, the inside of the upper space 27 is pressurized by a pressurizing means (not shown), and the lower space is interposed via the through hole 14. While moving the liquid to the space 28, the particles 30 are moved to the recess 15 having the throttle portion 16, and the particles 30 can be steadily adsorbed and held in the recess 15.

  Thus, since it is set as the structure which can control the upper space 27 and the lower space 28 separately, the particle | grains 30 can be easily controlled using means, such as attraction | suction or pressurization. Furthermore, it is possible to realize a sensor structure that allows a liquid to be easily replaced with another chemical liquid or the like.

  Next, as shown in FIG. 9, when the excitation light 33 is introduced from the upper space 27 side, the light is scattered while passing through the liquid filling the interior of the upper space 27, and enters the through hole 14 having the recess 15. Also enters. At this time, since the particles 30 held in the recess 15 reliably block the through holes 14, the excitation light 33 transmitted through the through holes 14 is light transmitted through the surfaces of the particles 30. As shown in FIG. 9, when the inspection target substance 35 is not present in the upper space 27 or when the concentration is low, the probe 29 formed on the surface of the particle 30 does not hybridize with the inspection target substance 35. Light passing through the surface of the particle 30 in this state is detected as detection light 34, and a reference response is measured.

  On the other hand, as shown in FIG. 10, in the state where the inspection target substance 35 exists on the upper space 27 side, the probe 29 is hybridized with the inspection target substance 35, and the detection that has passed through the surface of the particle 30 in this state Light 34 is detected. At this time, in the state in which the probe 29 and the substance to be inspected 35 are hybridized, if the probe 29 is modified to emit fluorescence, the detected light 34 that has passed is accompanied by fluorescence, and the reference response Distinguished from In this way, it can be determined whether or not the inspection target substance 35 is present in the liquid present in the upper space 27.

  As described above, by providing the sensor chip 11 with the concave portion 15 having the narrowed portion 16 in the through hole 14, the particles 30 having the probe 29 on the surface can be reliably held, and the light that has passed through the through hole 14 must be in the form of particles. Since it passes through 30 surfaces, it is possible to measure with higher accuracy.

  Therefore, the material of the sensor chip 11 can be realized by other than the silicon described in the first embodiment, but it is more desirable that the sensor chip 11 be opaque (low transparency). As a result, only the light transmitted to the lower space 28 side passes through the through hole 14, and the light detection on the lower space 28 side becomes more accurate. Note that light detection is possible even if the lower space 28 side, which is the detection side, is not necessarily filled with liquid, but when it is filled with liquid, the light that has passed through the through hole 14 is liquid present on the lower space 28 side. It has the advantage that it can be easily scattered and is easily introduced into the light detection port 32.

  Furthermore, in the method for holding particles 30 in the present embodiment, if the upper space 27 side is in a reduced pressure atmosphere, the particles 30 once held can be released again, so that the particles 30 can be liquidated at any time. The reaction between the probe 29 and the substance to be inspected 35 can be promoted by dispersing in the medium. For example, after the reference response is measured by holding the particle 30 in the recess 15 in a state where the inspection target substance 35 is not in the liquid, the liquid containing the inspection target substance 35 is added, and then the holding of the particle 30 is released. The particles 30 are easily dispersed in the liquid to promote the reaction between the test target substance 35 and the probe 29. When the measurement is performed after the particles 30 are held again by suction, the test target substance 35 is compared with the reference response. This has the advantage that the presence / absence determination becomes more accurate.

  In addition, more reliable measurement is possible by providing a plurality of through-holes 14 provided with the recess 15 having the throttle portion 16.

  In addition, the mounting substrate 19 of the present embodiment is configured to cover the sensor chip 11, but when performing chemical substance identification that does not use a photoreaction, the mounting substrate having the conduction holes 18 opened up and down. The sensor chip 11 may be held inside 19 and the conduction hole 18 may be divided into an upper space 27 and a lower space 28.

  As described above, the sensor device according to the present embodiment detects a DNA sensor that detects a specific DNA sequence such as a virus or a food production area, or a SNP (single nucleotide polymorphism) sequence as a chemical substance identification sensor. It can be widely used in the agricultural field, medical field, environmental field, etc., such as an SNP sensor and an antigen sensor that detects the presence of allergen (allergic antigen).

  In addition, description about the same structure and effect as Embodiment 1 is abbreviate | omitted.

  As described above, the sensor device according to the present invention is useful for adsorbing spherical substances such as particles and cells, and can be used for cell electrophysiological sensors, chemical substance identification sensors, and the like.

DESCRIPTION OF SYMBOLS 11 Sensor chip 12 Thin plate 13 Frame body 14 Through-hole 15 Recessed part 16 Restriction part 17 Spherical substance 18 Conductive hole 19 Mounting substrate 20 Subject 21 Measuring electrode 22 Dispenser 23 Reference electrode 24 Channel 25 Channel plate 26 Cavity 27 Upper space 28 Lower space 29 Probe 30 Particle 31 Light inlet 32 Light detection port 33 Excitation light 34 Detection light 35 Substance to be inspected

Claims (4)

Comprising a thin plate and a frame for holding the periphery of the thin plate,
The thin plate has at least one through-hole penetrating between the first surface and the second surface facing the first surface;
A sensor chip in which the through hole has a recess having a diameter larger than the diameter of the through hole and having a throttle on the first surface side. 2. The sensor chip according to claim 1, wherein each of the recesses having a throttle portion provided continuously to each of the plurality of through holes is formed such that inner walls of adjacent recesses intersect each other. A mounting board;
A sensor chip held at the lower end of the conduction hole that conducts from the upper surface to the lower surface of the mounting substrate;
The sensor chip includes a thin plate and a frame body that holds the periphery of the thin plate,
The thin plate has at least one through-hole penetrating between the first surface and the second surface facing the first surface;
A sensor device in which the through-hole is continuously provided with a recess having a diameter larger than the diameter of the through-hole and having a throttle portion on the first surface side. A mounting board;
A sensor chip held inside a conduction hole that conducts from the upper surface to the lower surface of the mounting substrate,
The sensor chip includes a thin plate and a frame body that holds the periphery of the thin plate,
The thin plate has at least one through hole penetrating the first surface and the second surface facing the first surface;
The through hole is provided with a recess having a diameter larger than the diameter of the through hole and having a throttle portion on the first surface side,
While arranging a microsphere having a probe function in the recess,
A sensor device in which a liquid is filled in either the first region or the second region of the conduction hole divided by the microsphere.

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