JP5531886B2 - Biosensor system - Google Patents

Description

  The present invention relates to a biosensor system including a biosensor and an electronic circuit that executes predetermined processing based on an output from the biosensor.

  In recent years, various methods have been developed for testing biologically relevant substances such as DNA, sugar chains, and proteins for the purpose of disease diagnosis, detection of individual differences in drug metabolism, or food or environmental monitoring. In particular, research on biosensors that detect biomolecules using electrical signals is in progress. Recently, a field effect transistor (hereinafter also referred to as “FET”) is used from the viewpoint that electrical signal conversion is fast and the connection between an integrated circuit and a MEMS (Micro Electro Mechanical System) is easy. Much research has been done on biosensors that are used to detect biological responses.

  A biosensor using an FET has a structure in which a gate electrode is removed from a MOSFET and an ion-sensitive film is deposited on an insulating film, and is called “ISFET (Ion Sensitive FET)”. And this ISFET functions as various biosensors by disposing oxidoreductases, various proteins, DNA, antigens or antibodies on the ion sensitive membrane (for example, Patent Document 1).

  Also known is an ISFET (multi-ISFET) in which a plurality of insulating regions are provided on the same substrate, and an ion sensitive film is separately formed on each insulating region (for example, Patent Document 2).

JP 2007-108160 A Japanese Patent Publication No. 5-44986

  However, in the biosensor described in Patent Document 1 or 2, since it is necessary to form a related part such as a source electrode or a drain electrode in accordance with the area of the ion sensitive film, the area of the ion sensitive film is increased. In this case, other related parts need to be enlarged and cannot be manufactured at low cost. In addition, in the biosensor described in Patent Document 1 or 2, a source electrode, a drain electrode and other circuit elements for functioning as an ISFET or a circuit including the circuit element is formed on a substrate together with an ion sensitive film. Therefore, when the circuit element or the circuit including the circuit element is defective, the biosensor itself is defective and the yield cannot be improved, resulting in an increase in manufacturing cost. To do.

  The present invention has been made to solve the above-described problems, and the object thereof is to increase the area of the sensitive membrane on which the biological substance contained in the fluid to be inspected is easily and inexpensively arranged. Another object is to provide a biosensor system capable of improving the yield and suppressing the manufacturing cost.

(1) In order to solve the above-described problem, a biosensor system of the present invention includes a base material, a semiconductor film formed on the base material, and at least a source electrode and a drain formed by the semiconductor film. An electronic circuit chip having an electronic circuit with electrodes;
An electronic circuit chip having an electronic circuit having at least a source electrode and a drain electrode, an insulating film stacked on the electronic circuit chip, an electrode layer stacked on the insulating film, and an electrode layer A sensitive film on which a biological substance contained in a fluid to be inspected is disposed, and the electronic circuit in the packaged electronic circuit chip and the electrode layer are electrically connected to each other. Yes.

  With this configuration, the biosensor system of the present invention can form the source electrode and the drain electrode that are essential as a biosensor system using an electronic circuit chip. Therefore, the source electrode and the drain electrode are independent of the size of the sensitive film. A drain electrode can be formed. In addition, the biosensor system of the present invention performs an inspection prior to disposing the electronic circuit chip on the base material, thereby improving the yield compared to the case of incorporating the source electrode and the drain electrode together with the sensitive film on the base material. As a result, the manufacturing cost can be reduced.

  (2) In addition, the biosensor system of the present invention has a configuration in which the area where the biological substance is arranged in the sensitive film is wider than the area of the laminated surface on which the sensitive film is laminated in the electronic circuit chip. doing.

  With this configuration, the biosensor system of the present invention can inspect a larger biological material and can form an essential source electrode and drain electrode as a biosensor system using an electronic circuit chip. It can be manufactured inexpensively without depending on the area of the sensitive film.

  (3) Moreover, the biosensor system of the present invention further includes a reference electrode provided adjacent to the sensitive film for applying a variable voltage to the fluid to be inspected, and the packaged electronic circuit and the package The reference electrode is electrically connected.

  With this configuration, the biosensor system of the present invention can retain the fluid to be inspected on the sensitive film without inserting the reference electrode into the fluid to be inspected after the fluid to be inspected is retained on the sensitive film. Since the reference voltage can be applied to the fluid to be inspected by the reference electrode, the inspection process can be simplified.

  (4) Moreover, the biosensor system of the present invention includes a single electronic circuit chip, a plurality of the sensitive films that are individually arranged with the biological substance and are configured independently of other sensitive films, A plurality of the electrode layers formed corresponding to the respective sensitive films, wherein the single electronic circuit chip and each of the electrode layers are electrically connected, and the single electronic circuit chip Has a configuration in which a signal generated by a biological substance disposed on each sensitive membrane is input.

  With this configuration, the biosensor system of the present invention can process a signal generated by the arrangement of a plurality of biological substances with a single electronic circuit chip, and thus can efficiently test the biological substance. At the same time, the manufacturing cost can be suppressed by an efficient structure.

  (5) Moreover, the biosensor system of the present invention has a configuration in which the substrate is formed with a recess that is open on the upper surface and accommodates the electronic circuit chip.

  With this configuration, the biosensor system of the present invention can accurately fix the electronic circuit chip on the base material, and can easily realize the flattening of the electrode layer.

  (6) Moreover, the biosensor system of this invention has the structure by which the said base material is formed with the flexible substrate.

  With this configuration, the biosensor system of the present invention can improve design flexibility without selecting an installation location for the biosensor system, and can also improve resistance to bending of the entire apparatus. While being able to provide a base material with a roll, manufacturing cost can be suppressed.

  (7) Moreover, the biosensor system of this invention has the structure by which the said base material is formed with the transparent electrode while the said base material is formed with the transparent base material.

  With this configuration, the biosensor system of the present invention is configured to irradiate light from the upper part of the fluid to be inspected (on the side opposite to the base material side) and to dispose the biological substance disposed on the sensitive film from the base material side to the microscope or other Since it can be observed with an optical observation device, it is possible to accurately and accurately observe the biological substance, compared to the case of observing the biological substance disposed on the sensitive film from the upper part of the fluid to be inspected. In addition, the detection of the electrical characteristics of the biological substance and the high-magnification observation of the biological substance can be made compatible.

  (8) In the biosensor system of the present invention, the packaged electronic circuit chip includes a signal amplification circuit, a current-voltage conversion circuit, a frequency conversion circuit, a differentiation circuit, an integration circuit, an analog-digital conversion circuit, It has a configuration including at least one of a memory circuit, a digital logic operation circuit, and a digital control circuit.

  With this configuration, the biosensor system of the present invention uses a signal amplification circuit, a current-voltage conversion circuit, a frequency conversion circuit, a differentiation circuit, an integration circuit, an analog-digital conversion circuit, and a memory circuit to detect a signal detected from a biological substance. It can be used for a digital logic operation circuit or a digital control circuit.

  (9) The biosensor system of the present invention has a configuration in which the electronic circuit chip is provided with a terminal for inspecting the operation of the electronic circuit.

  With this configuration, the biosensor system of the present invention can perform an inspection before disposing the electronic circuit chip on the base material, and also compared with the case where the source electrode and the drain electrode are incorporated on the base material together with the sensitive film. Thus, the yield can be improved, and as a result, the manufacturing cost can be suppressed.

  The biosensor system according to the present invention can form the source electrode and the drain electrode regardless of the size of the sensitive film, and compared with the case where the source electrode and the drain electrode are incorporated on the substrate together with the sensitive film. The yield can be improved and the manufacturing cost can be suppressed as a result.

It is sectional drawing in 1st Embodiment of the biosensor system which concerns on this invention. It is the example of sectional drawing and the top view which show the internal structure of the IC chip of the biosensor system in 1st Embodiment. It is a figure for demonstrating the principle of operation of the biosensor system in 1st Embodiment. It is sectional drawing of the modification in the biosensor system of 1st Embodiment. It is sectional drawing in 2nd Embodiment of the biosensor system which concerns on this invention. It is a figure for demonstrating the operation principle of the biosensor system in 2nd Embodiment. It is a top view in 3rd Embodiment of the biosensor system which concerns on this invention. It is a circuit diagram which shows the circuit structure in the biosensor system of 3rd Embodiment. It is sectional drawing of the modification in the biosensor system of 3rd Embodiment. It is a circuit diagram which shows the circuit structure of each cell in 4th Embodiment of the biosensor system which concerns on this invention.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  In the embodiment described below, the ISFET having a structure for detecting a signal from a sample contained in a fluid to be inspected arranged on a sensitive film, that is, a biological substance such as a cell, DNA, sugar chain, or protein. This is an embodiment in which the biosensor system of the present invention is applied to a biosensor system using an IC, in which an IC chip having a packaged electronic circuit is incorporated. In the biosensor system of the following embodiment, a pseudo top gate bottom contact ISFET is constituted by the sensitive film and the source electrode and drain electrode incorporated in the IC chip.

[First Embodiment]
First, a first embodiment of a biosensor system 100 according to the present invention will be described with reference to FIGS. 1 and 2.

(Configuration of biosensor system)
Next, the configuration of the biosensor system 100 according to the present embodiment will be described with reference to FIGS. 1 and 2. FIG. 1 is a cross-sectional view of the biosensor system 100 of the present embodiment, and FIG.

  As shown in FIG. 1, the biosensor system 100 of the present embodiment includes a base 110, a polymer layer 120 stacked on the base 110, an IC chip 200 formed on the polymer layer 120, and an IC chip. 200 based on insulating layer 130 that is laminated on polymer layer 120, electrode layer 140 that is laminated on insulating layer 130, and sample 300 that is laminated on electrode layer 140 and applied with reference electrode 400. A sensitive membrane 150 for detecting signals, and a partition wall 160 formed on both ends of the sensitive membrane 150 for retaining a fluid to be inspected such as an aqueous solution or a culture solution containing the sample 300 on the sensitive membrane 150, have.

  The substrate 110 is not particularly limited as long as it is formed of a material capable of laminating various layers such as the polymer layer 120, the insulating layer 130, and the electrode layer 140. Specifically, the substrate 110 is formed of a transparent or opaque material, and is made of an inorganic material such as glass, plastic such as PEN or PET (polyester resin, polyethylene resin, polypropylene resin, ABS resin, nylon, acrylic resin, fluorine Resin, polycarbonate resin, polyurethane resin, methylpentene resin, phenol resin, melamine resin, epoxy resin, vinyl chloride resin). The shape of the substrate 110 is not limited, and examples thereof include a flat shape such as a flat plate, a flat membrane, a film, and a porous membrane, and a three-dimensional shape such as a cylinder, a stamp, a multiwell plate, and a microchannel. It is done. When using a film, the thickness is not particularly limited, but is usually about 1 μm to 1 mm.

  In addition, said transparency should just be transparent so that the biological material arrange | positioned from the base material 110 to the sensitive film | membrane 150 can be observed using observation apparatuses, such as a microscope, and a translucent thing is included. I can't.

  The polymer layer 120 has adhesive properties and is thermosetting or thermoplastic. The polymer layer 120 may have elastomeric properties. Suitable polymer materials include epoxy functional polymers, polyimides, liquid crystal polymers, cycloolefins, polyurethanes, polyamides, benzocyclobutanes, polyamide-imides, polyarylene ethers, benzimidazoles, polyether ketones, polysiloxanes, polyether ether ketones. , Polyphenylquinosaline, polyimide iso-indoloquinazolinedione, fluoropolymer, cyanate ester, bismaleimide triazine (BT), sinate ester, and these compounds.

  The polymer layer 120 is formed of a single layer or an appropriate number of sublayers of the same composition or different compositions. For example, the polymer layer 120 includes a rigid core or a thermally stable flexible core covered with one or two polymer sublayers. The polymer layer 120 or one or more sublayers in the polymer layer 120 have a suitable thickness. Specifically, the thickness of the polymer layer 120 or one or more sublayers in the polymer layer 120 is about 1 μm to 3 μm.

  The polymer layer 120 may be transparent. This transparent is only required to be transparent to the extent that the biological material disposed on the sensitive film 150 can be observed from the base 110 using an observation device such as a microscope, and does not include a translucent material. For example, the transparent polymer material includes an acrylic resin of resin: V259 (manufactured by Nippon Steel Chemical Co., Ltd.). Further, instead of the polymer layer 120, a coating type inorganic insulating film such as polysilazane or siloxane may be used.

  In this embodiment, the polymer layer 120 is formed in order to bring the IC chip 200 into an adhesive and insulating state. However, the insulating layer 130 can be formed with a thickness that covers the IC chip 200. If it is.

  In the IC chip 200, a circuit (hereinafter referred to as “internal circuit”) for performing a predetermined process on a signal generated in the sensitive film 150 based on the reference electrode 400 and the sample 300 disposed therein is formed inside. That is, an integrated circuit chip with electronic circuitry. For example, the IC chip 200 of this embodiment constitutes the electronic circuit chip of the present invention.

  In particular, the IC chip 200 includes each circuit element constituting the internal circuit from the outside (that is, the outside of the IC chip 200 includes the biosensor system 100 other than the IC chip), humidity, heat, gas, light, etc. Packaged as a single component that protects against changes in the external environment, and has a connection terminal on the surface so that predetermined signal processing can be performed by appropriately transmitting and receiving predetermined signals and power to and from the outside. It has become. The IC chip 200 has a pad P formed on the upper surface thereof for electrical connection with the electrode layer 140 and the external electrode. The IC chip 200 is formed with at least a source electrode and a drain electrode for forming an ISFET together with the sensitive film 150, and the source electrode and the drain electrode are connected to an external electrode. However, the IC chip 200 may have a gate electrode in addition to the source electrode and the drain electrode. The IC chip 200 has a thickness of about 50 μm.

  Here, an example of the IC chip 200 including a gate electrode, a source electrode, and a drain electrode will be described with reference to FIG. 2A is a cross-sectional view of the IC chip 200 taken along the line AA in FIG. 2B, and FIG. 2B is a top view of the IC chip 200. FIG. FIG. 2C is a cross-sectional view showing the BB cross section of the IC chip 200 in FIG.

  In such a case, as shown in FIG. 2, the IC chip 200 includes a p-type silicon 210 functioning as a base, an insulating layer 220 formed of silicon oxide stacked on the p-type silicon 210, an oxidation The semiconductor layer 230 is stacked on the silicon film 220 and forms a channel region 231 and a source region 232 and a drain region 233. The IC chip 200 is formed so as to cover the gate insulating film 240 stacked on the semiconductor film 230, the channel region 231, and the gate insulating film 240 stacked on the gate insulating film 240. And the source and drain electrode pads P1 and P2 formed on the insulating film 260 and connected to the source region 232 and the drain region 233 through the contact holes H, respectively. Yes. Further, in the IC chip 200, an insulating layer 270, a contact hole H, and an electrode 280 are formed on the insulating film 260 in a region different from the source and drain electrode pads P1 and P2, and the gate electrode is formed on the uppermost portion. A pad P3 is formed.

  In particular, the semiconductor film 230 is formed of a semiconductor such as P-type silicon (silicon) or N-type silicon. In addition, the semiconductor film 230 functions as a channel, and a channel region 231 formed under the electrode layer 140 and the channel region 231 are physically juxtaposed in the horizontal direction, and boron or phosphorus is ion-implanted into the semiconductor film 230. And a source region 232 and a drain region 233 formed by diffusion by heat. The source region 232 and the drain region 233 are physically and electrically connected to pads P1 and P2 connected to the outside formed on the gate insulating film 240 through the contact holes H, respectively.

The gate electrode 250 and the other electrode 280 are formed of a conductive material such as indium tin oxide (ITO), zinc oxide (ZnO), tin oxide (SnO ₂ ), aluminum (Al), or copper (Cu).

The insulating layer 130 is laminated on the polymer layer 120 so as to cover the IC chip 200. Further, the insulating layer 130 is not particularly limited as long as it is formed of a material capable of laminating the sensitive film 150. Specifically, it is formed from silicon oxide or silicon nitride such as silicon oxide (SiO ₂ ), silicon nitride (SiNx), or silicon nitride oxide (SiOxNy) from the viewpoint of insulation. In particular, it is preferable to use silicon oxide for the insulating layer 130 of the present embodiment. The film thickness of the insulating film 40 can be appropriately selected according to various conditions, and is, for example, 10 μm or more.

The electrode layer 140 is not particularly limited as long as it is formed of a conductive film on which the sensitive film 150 can be laminated. Specifically, it is made of a transparent or opaque material, and has a conductive property such as indium tin oxide (ITO), zinc oxide (ZnO), tin oxide (SnO ₂ ), aluminum (Al), or copper (Cu). Formed from things. In particular, when the electrode layer 140 is formed of a transparent electrode, the electrode layer 140 is not particularly limited as long as the sensitive film 150 can be observed from the lower part of the substrate 110. In addition, the transparent material may be transparent to the extent that the biologically related substance disposed on the sensitive film 150 can be observed from the base material 110 using an observation device such as a microscope, like the base material 110. Translucent materials are not included.

  The electrode layer 140 is connected to an internal circuit in the IC chip 200 via a pad P formed on the upper surface of the IC chip 200. For example, when the internal circuit is formed of only the source electrode 250 and the drain electrode 260, it is connected to the pad P formed on the IC chip 200 as described above.

The sensitive film 150 is laminated on the electrode layer 140 and is formed of a sample 300 included in a fluid to be inspected, that is, a substance on which a biological substance such as a cell, DNA, sugar chain, or protein can be arranged. In particular, the sensitive film 150 has a region (hereinafter referred to as “arrangement region”) in which the sample 300 contained in the stayed fluid 300 to be inspected is disposed on a region where a channel is formed in the transparent semiconductor film. Have at least. The sensitive film 150 is an ion sensitive film, and is formed of a silicon oxide film (SiO ₂ ), a silicon nitride film (SiN ₄ ), a tantalum oxide film (Ta ₂ O ₅ ), or an aluminum oxide film (Al ₂ O ₃ ). Is done. What is necessary is just to employ | adopt suitably according to the ion species to measure these ion sensitive membranes. If necessary, surface modification for immobilizing DNA proteins and sugar chains may be performed.

  The partition wall 160 is formed on the sensitive film 150 and around the arrangement region, and has a predetermined height with respect to the stacking direction so that a fluid to be inspected such as an aqueous solution or a culture solution is retained on the sensitive film 150. Have. The barrier is not particularly limited as long as it is formed of a material for preventing leakage of the fluid to be inspected containing the sample 300 outside the arrangement region. Specifically, it is made of glass, plastic or metal.

(Operation principle of biosensor system)
Next, the operation principle of the biosensor system 100 in the present embodiment will be described with reference to FIG. FIG. 3 is a diagram for explaining the operation principle of the biosensor system 100 in the present embodiment.

The biosensor system 100 according to the present embodiment has the above-described configuration, so that the sample 300 included in the fluid to be inspected, that is, a biological substance such as a cell, DNA, sugar chain, or protein is placed on the sensitive film 150. It can be arranged. Therefore, as shown in FIG. 3, the reference electrode 400 inserted in the fluid to be inspected is applied while applying a voltage V _DS of about 0.1 V to 1 V between the source electrode 250 and the drain electrode 260 in the IC chip 200. When the variable voltage (reference voltage) V _G is applied to the fluid to be inspected via the IC chip 200 via the electrode layer 140 in accordance with a change in potential (hereinafter also referred to as “membrane potential”) generated in the sensitive film 150. The channel region 231 formed in the semiconductor film 230 changes so that the change of the drain current _ID can be detected. As a result, the change in the drain current _ID based on the reference voltage V _G , that is, the sample included in the fluid to be inspected by comparing the current-voltage characteristic as a transistor with the current-voltage characteristic in the biological substance measured in advance. 300 types can be specified.

(Function and effect)
As described above, since the biosensor system 100 according to the present embodiment can form the source electrode and the drain electrode essential as the biosensor system 100 using the IC chip 200, these sources can be used regardless of the size of the sensitive film 150. An electrode and a drain electrode can be formed. The biosensor system 100 according to the present embodiment performs the inspection before the electronic circuit chip is disposed on the base material 110, thereby incorporating the source electrode and the drain electrode together with the sensitive film 150 on the base material 110. In comparison with this, it is possible to improve the yield and to suppress the manufacturing cost as a result.

  In addition, the biosensor system 100 according to the present embodiment can inspect a larger sample 300 and can form essential source and drain electrodes as the biosensor system 100 using the IC chip 200. It can be manufactured inexpensively without depending on the area of the sensitive film 150.

  In addition, the biosensor system 100 according to the present embodiment makes each member such as the base material 110, the electrode layer 140, and the polymer layer 120 transparent so that light can be emitted from above the fluid to be inspected (on the side opposite to the base material 110 side). Can be observed from the substrate 110 side with a microscope or other optical observation equipment. Therefore, the biosensor system 100 of the present embodiment can accurately perform observation on the sample 300 at a high magnification as compared with the case of observing the sample 300 disposed on the sensitive film 150 from above the fluid to be inspected. In addition, the detection of the electrical characteristics of the sample 300 and the high-magnification observation of the sample 300 can be made compatible.

(Modification)
Next, the modification in the biosensor system 100 of this embodiment is demonstrated using FIG. FIG. 4 is a cross-sectional view of a modified example of the biosensor system 100 of the present embodiment.

  The base 110 of the above embodiment may be a thin film alloy flexible substrate made of stainless steel (SUS). In this case, since the flexible substrate can be provided by a roll, the manufacturing cost can be suppressed, and the design flexibility can be improved without selecting the location for the biosensor system 100. And the tolerance in the bending of the whole apparatus can also be improved.

  In the above embodiment, the recess 111 for fixing the IC chip 200 to the base 110 may be provided. For example, as shown in FIG. 4, the substrate 110 has a groove that is open to the top and has a larger area than the IC chip 200, and the IC chip 200 is placed and the IC layer 200 is formed when the polymer layer 120 is formed. The chip 200 is fixed to the substrate 110 with a polymer. Unlike the above-described embodiment, the insulating layer 130 may be formed on the polymer layer 120, or the insulating layer 130 may not be formed on the polymer layer 120 as in the above-described embodiment.

  With this configuration, the biosensor system 100 can accurately fix the IC chip 200 on the base material 110, easily flatten the electrode layer 140 formed on the IC chip 200, and As a result, the sensitive film 150 can be easily flattened.

  In addition, a terminal (pad) for confirming that the internal circuit performs normal operation may be provided on the upper surface of the IC chip 200 in the above embodiment. For example, this terminal is connected to each of the terminal to which the electrode layer 140 in the IC chip 200 is connected for confirmation of the gate electrode and each of the source electrode 250 and drain electrode 260 for confirmation of the source electrode 250 and drain electrode 260. The connected terminals are used when confirming normal operation before being formed on the substrate 110. Therefore, the inspection can be performed before the IC chip 200 is disposed on the base 110, and the yield is improved as compared with the case where the source electrode 250 and the drain electrode 260 are incorporated on the base 110 together with the sensitive film 150. As a result, the manufacturing cost can be suppressed.

[Second Embodiment]
Next, a second embodiment of the biosensor system 100 according to the present invention will be described with reference to FIGS. 5 and 6.

  In the biosensor system 100 of the present embodiment, instead of the reference electrode 400 being inserted into the fluid to be inspected (sample 300) in the first embodiment, the biosensor system 100 is adjacent to the sensitive membrane 150 and is used as the fluid to be inspected. It is characterized in that it has a reference electrode 500 formed in a region where a reference voltage can be applied. In addition, since the other structure is the same as 1st Embodiment, it attaches | subjects the same code | symbol to the same member, and abbreviate | omits the description.

(Configuration of biosensor system)
First, the configuration of the biosensor system 100 of the present embodiment will be described with reference to FIG. FIG. 5 is a cross-sectional view of the biosensor system 100 of the present embodiment.

  As shown in FIG. 5, the biosensor system 100 of the present embodiment includes a base 110, a polymer layer 120 laminated on the base 110, an IC chip 200 formed on the polymer layer 120, and an IC chip. An insulating layer 130 that covers 200 and is laminated on the polymer layer 120, an electrode layer 140 that is laminated on the insulating layer 130, and a sample 300 that is laminated on the electrode layer 140 and disposed with the application of the reference electrode 500. A sensitive membrane 150 for detecting a signal, a reference electrode 500 adjacent to the sensitive membrane 150 for applying a reference voltage to the fluid to be examined, and a partition wall 160 for retaining the fluid to be examined. ing.

The reference electrode 500 is formed adjacent to the arrangement region where the sample 300 is arranged in the sensitive film 150 in the horizontal direction perpendicular to the stacking direction, and the fluid to be inspected is in contact with the fluid to be inspected in part. It is formed in the area where it stays. The reference electrode 500 is provided so as to be insulated from the IC chip 200 and is laminated in a region other than the region where the sensitive film 150 is disposed. Furthermore, the reference electrode 500 is not particularly limited as long as it is formed of a conductive film. Specifically, it is made of a transparent or opaque material, and is made of a conductive material such as indium tin oxide (ITO), zinc oxide (ZnO), tin oxide (SnO ₂ ), aluminum (Al), or copper (Cu). Formed from things.

(Operation of biosensor system)
Next, the operation principle of the biosensor system 100 according to this embodiment will be described with reference to FIG. FIG. 6 is a diagram for explaining the operating principle of the biosensor system 100 in the present embodiment.

The biosensor system 100 according to the present embodiment has the above-described configuration, so that the sample 300 included in the fluid to be inspected, that is, a biological substance such as a cell, DNA, sugar chain, or protein is placed on the sensitive film 150. It can be arranged. Therefore, as shown in FIG. 6, the voltage V _DS of about 0.1 V to 1 V is applied between the source electrode 250 and the drain electrode 260 in the IC chip 200, and the reference electrode 500 is in contact with the fluid to be inspected. When the variable voltage (reference voltage) V _G is applied to the fluid to be inspected, the IC chip 200 is connected via the electrode layer 140 in accordance with a change in potential (hereinafter also referred to as “membrane potential”) generated in the sensitive film 150. The channel region 231 formed in the semiconductor film 230 is changed so that a change in the drain current _ID can be detected. As a result, the change in the drain current _ID based on the reference voltage V _G , that is, the sample included in the fluid to be inspected by comparing the current-voltage characteristic as a transistor with the current-voltage characteristic in the biological substance measured in advance. 300 types can be specified.

(Function and effect)
As described above, in addition to the first embodiment, the biosensor system 100 according to the present embodiment stores the fluid to be tested without inserting the reference electrode 500 into the fluid to be tested after the fluid to be tested is retained on the sensitive film 150. If it stays on the sensitive film 150, the reference voltage can be applied to the fluid to be inspected by the reference electrode 500, so that the inspection process can be simplified.

(Modification)
Next, a modified example of the biosensor system 100 of the present embodiment will be described.

  Similar to the first embodiment, the base material 110 of the above embodiment may be a thin film alloy flexible substrate made of stainless steel (SUS).

  Similarly to the first embodiment, in the above embodiment, a recess for fixing the IC chip 200 to the base 110 may be provided.

  Similarly to the first embodiment, a terminal (pad) for confirming that the internal circuit performs a normal operation may be provided on the upper surface of the IC chip 200 in the above embodiment. For example, this terminal is a terminal connected to the electrode layer 140 in the IC chip 200, a terminal connected to each of the source electrode and the drain electrode, and confirms normal operation before being formed on the substrate 110. Used when

[Third Embodiment]
Next, a third embodiment of the biosensor system 100 according to the present invention will be described with reference to FIGS.

  In the biosensor system 100 of the present embodiment, in the first embodiment, a plurality of sensitive membranes 150 are configured such that the samples 300 are individually arranged on a single IC chip 200 and configured independently of the other sensitive membranes 150. And a plurality of electrode layers 140 formed corresponding to the respective sensitive films 150. In addition, since the other structure is the same as 1st Embodiment, it attaches | subjects the same code | symbol to the same member, and abbreviate | omits the description.

(Configuration of biosensor system)
First, the configuration of the biosensor system 100 of the present embodiment will be described with reference to FIGS. 7 and 8. FIG. 7 is a top view showing the structure of the biosensor system 100 of this embodiment, and FIG. 8 is a circuit diagram showing the circuit configuration of the biosensor system 100 of this embodiment.

As shown in FIG. 7, the biosensor system 100 according to the present embodiment has a structure in which samples 300 are individually arranged on a single IC chip 200 and are independent of other sensitive membranes 150. It has the some sensitive film | membrane 150 and the some electrode layer 140 formed corresponding to each sensitive film | membrane 150. FIG. The IC chip 200 and each electrode layer 140 are electrically connected via a pad P provided on the upper surface of the IC chip 200 portion on which the electrode layer 140 is superimposed. Each signal generated by the sample 300 disposed on each sensitive film 150 is input. Note that the biosensor system 100 according to the present embodiment has a power supply line for applying the power supply voltage V _DD to each cell C (that is, the sensitive film 150) and each of the sensitive films 150 so that each sensitive film 150 functions as the cell C. A selection line for selecting the cell C is formed on the IC chip 200 and is connected to an internal circuit in the IC chip 200 by a contact hole.

Further, as shown in FIG. 8, the biosensor system 100 includes an ISFET 10 and a switching transistor 20 for each cell C as shown in FIG. Specifically, the biosensor system 100 includes the ISFET 10 other than the sensitive film 150 incorporated in the IC chip 200, the ISFET 10 formed by the sensitive film 150 formed in the IC chip 200 information, and the IC chip 200 circuit. And a switching transistor 20 built in. Then, in the switching transistor 20 in each cell C, when a power source voltage V _DD is applied to the source and a predetermined voltage is applied to the gate by the selection line, each signal in the sample 300 is detected by the ISFET 10 of each cell C. Be able to. In addition, each signal in the sample 300 detected by the ISFET 10 in each cell C is output to the outside through an output terminal (not shown), or used for a predetermined process by another circuit incorporated in the IC chip 200. It has become.

(Function and effect)
As described above, the biosensor system 100 according to the present embodiment can process signals generated by the arrangement of the plurality of samples 300 by the single IC chip 200 in addition to the effects of the first embodiment. In addition, the manufacturing cost can be suppressed by an efficient structure.

(Modification)
Next, the modification in the biosensor system 100 of this embodiment is demonstrated using FIG. FIG. 9 is a cross-sectional view of a modification of the biosensor system 100 of the present embodiment.

In this embodiment, the switching transistor 20 is formed in each cell C. However, the switching transistor 20 may be omitted and formed only from the ISFET 10. In this case, a source electrode in ISFET10 as shown in FIG. 9 is connected to the power supply voltage _{V DD,} is possible to detect the respective signals definitive sample 300 with the power supply voltage _{V DD} is applied by ISFET10 of each cell C It can be done.

  In the above embodiment, as in the second embodiment, instead of the point that the reference electrode 500 is inserted into the fluid to be inspected, the reference voltage is applied to the fluid to be inspected adjacent to the sensitive film 150. The reference electrode 500 may be formed in a region where it can be applied.

  Similarly to the first embodiment, the base material 110 of the above embodiment may be a thin film alloy flexible substrate made of stainless steel (SUS).

  Similarly to the first embodiment, in the above embodiment, a recess for fixing the IC chip 200 to the base 110 may be provided.

  Similarly to the first embodiment, a terminal for confirming that the internal circuit performs a normal operation may be provided on the upper surface of the IC chip 200 in the above embodiment.

[Fourth Embodiment]
Next, a fourth embodiment of the biosensor system 100 according to the present invention will be described with reference to FIG.

  The biosensor system 100 of the present embodiment is characterized in that the processing circuit 30 is incorporated in each cell C in the third embodiment. In addition, since the other structure is the same as 3rd Embodiment, it attaches | subjects the same code | symbol to the same member, and abbreviate | omits the description.

(Configuration of biosensor system)
First, the configuration of the biosensor system 100 of the present embodiment will be described with reference to FIG. FIG. 10 is a circuit diagram showing a circuit configuration of each cell C in the biosensor system 100 of the present embodiment.

  As shown in FIG. 10, each cell C of the biosensor system 100 according to the present embodiment includes an ISFET 10, a switching transistor 20, a resistance element R, and a processing circuit 30. Specifically, the biosensor system 100 includes the ISFET 10 other than the sensitive film 150 incorporated in the IC chip 200, the ISFET 10 formed by the sensitive film 150 formed in the IC chip 200 information, and the IC chip 200 circuit. And a switching transistor 20 built in. The biosensor system 100 includes a resistance element R and a processing circuit 30 incorporated in the IC chip 200. The drain of the ISFET 10 is connected to one end of the resistance element R and the input end to the processing circuit 30, the ground connection is connected to the other end of the resistance element R, and the output terminal is connected to the other end of the processing circuit 30. It is connected to the.

  The resistance element R is a resistance used to amplify the signal output from the ISFET 10 and input it to the processing circuit 30. The processing circuit 30 includes at least one of a signal amplification circuit, a current-voltage conversion circuit, a frequency conversion circuit, a differentiation circuit, an integration circuit, an analog-digital conversion circuit, a memory circuit, a digital logic operation circuit, and a digital control circuit. Is included.

(Function and effect)
As described above, the biosensor system 100 according to the present embodiment converts the signal detected from the sample 300 into a signal amplification circuit, a current-voltage conversion circuit, a frequency conversion circuit, a differentiation circuit, an integration circuit, an analog-digital conversion circuit, a memory circuit, and a digital circuit. It can be used for a logic operation circuit or a digital control circuit.

  In this embodiment, the IC chip 200 is incorporated in the biosensor system 100. However, the present invention is not limited to this, and an electronic circuit in which at least a source electrode and a drain electrode for forming an ISFET together with the sensitive film 150 are formed. If it is an electronic circuit component (electronic circuit chip) made into 1 chip, it will not be limited to this.

C ... Cell H ... Contact hole P ... Pad R ... Resistance element 20 ... Switching transistor 30 ... Processing circuit 40 ... Insulating film 100 ... Biosensor system 110 ... Base material 111 ... Recess 120 ... Polymer layer 130 ... Insulating layer 140 ... Electrode layer 150 ... Sensitive film 160 ... Partition 200 ... IC chip 210 ... P-type silicon 220 ... Silicon oxide film 230 ... Semiconductor film 231 ... Channel region 232 ... Low resistance region 240 ... Gate insulating film 250 ... Source electrode 260 ... Drain electrode 300 ... Sample (Inspected fluid)
400, 500 ... Reference electrode

Claims (8)

A substrate;
A packaged electronic circuit chip having a semiconductor film formed on the substrate and having an electronic circuit having at least a source electrode and a drain electrode formed by the semiconductor film;
An insulating film laminated on the electronic circuit chip;
An electrode layer laminated on the insulating film;
An arrangement region in which a biological substance contained in the fluid to be inspected is arranged on the electrode layer;
With
The electronic circuit in the packaged electronic circuit chip and the electrode layer are electrically connected ,
The placement region is formed of a sensitive film, and the placement region and the electrode layer are wider than an area of a stacking surface on which the placement region and the electrode layer of the electronic circuit chip are stacked. Biosensor system. The biosensor system according to claim 1, wherein
A reference electrode provided at an end of the placement region, for applying a variable voltage to the fluid to be inspected;
A biosensor system, wherein the packaged electronic circuit and the reference electrode are electrically connected. The biosensor system according to claim 1 or 2 ,
And a single of the electronic circuit chip, formed said biological substance arranged individually, and a plurality of the arrangement region juxtaposed configured independently of the other placement area, corresponding to each of the placement regions A plurality of the electrode layers,
The single electronic circuit chip and each electrode layer are electrically connected, and the single electronic circuit chip is input with a signal generated by a biological substance disposed in each placement region. Sensor system. In the biosensor system according to any one of claims 1 to 3 ,
The biosensor system, wherein the base material is formed with a recess that is open on an upper surface and accommodates the electronic circuit chip. In the biosensor system according to any one of claims 1 to 4 ,
A biosensor system, wherein the base material is formed of a flexible substrate. In the biosensor system according to any one of claims 1 to 4 ,
A biosensor system in which the substrate is formed of a transparent substrate and the electrode layer is formed of a transparent electrode. In the biosensor system according to any one of claims 1 to 6 ,
The packaged electronic circuit chip includes at least a signal amplification circuit, a current-voltage conversion circuit, a frequency conversion circuit, a differentiation circuit, an integration circuit, an analog-digital conversion circuit, a memory circuit, a digital logic operation circuit, or a digital control circuit. A biosensor system including any one circuit. In the biosensor system according to any one of claims 1 to 7,
The biosensor system, wherein the electronic circuit chip is provided with a terminal for inspecting the operation of the electronic circuit.

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