JP5488372B2 - Biosensor - Google Patents

Description

The present invention relates to a biosensor, and more particularly to a biosensor using a field effect transistor.

Biosensors using electrochemical detection means have been put to practical use as methods for quickly and simply measuring concentrations and the like of biological samples such as blood and cells and specific components therein. As one of them, a biosensor using a field effect transistor (hereinafter referred to as FET) is known, and particularly called an ISFET (Ion-sensitive FET). Application to detection systems using biological components such as DNA and protein using ISFET, cells, and the like has been actively studied.

For example, Patent Document 1 discloses a sensor in which a biosensing portion is provided on a gate electrode portion of a transistor formed on a semiconductor substrate in order to amplify a signal when biosensing. However, since the bio-sensing part is provided on the transistor, the semiconductor substrate, which is the base substrate, is opaque, and the transistor itself is also opaque. Therefore, the state of cells or DNA to be sensed is observed with a microscope. However, the sensing signal cannot be confirmed.

In Patent Document 2, a chemical reaction layer is formed on a thin film transistor formed on a transparent substrate such as glass or plastic. However, even in Patent Document 2, since the transistor portion and the wiring layer are opaque, the object to be sensed cannot be observed with a microscope.

JP 2001-281213 A JP 2006-250928 A

In research fields such as molecular cell biology and molecular biology, which are the foundation of medicine, it is necessary to compare observation results using a phase contrast microscope, a fluorescence microscope, and the like with data obtained by biosensing. However, conventional biosensors do not satisfy such requirements.

In view of the above circumstances, an object of the present invention is to provide a biosensor capable of observing an object to be sensed with a microscope or the like simultaneously with sensing.

According to one embodiment of the present invention, a transparent substrate, a gate electrode formed of a transparent conductive material on the transparent substrate, and a semiconductor film formed of a transparent semiconductor material covering the gate electrode A source electrode and a drain electrode disposed in ohmic contact with the semiconductor film, a first insulating film covering the source electrode and the drain electrode, respectively, and a semiconductor film on the gate electrode. There is provided a biosensor comprising an FET sensor comprising a second insulating film on which a device under test is disposed.

The biosensor may further include an electrode disposed on the semiconductor film via a first insulating film with respect to the source electrode and the drain electrode.

According to one embodiment of the present invention, a transparent substrate, a gate electrode formed of a transparent conductive material on the transparent substrate, and a semiconductor film formed of a transparent semiconductor material covering the gate electrode A source electrode and a drain electrode disposed in ohmic contact with the semiconductor film, a first insulating film covering each of the source electrode and the drain electrode, and the semiconductor film on the gate electrode to the semiconductor Provided is a biosensor comprising an FET sensor comprising: an electrode that is drawn out toward the outside of the film; and a second insulating film that is disposed on the electrode and on which an object to be measured is disposed. Is done.

The biosensor may include a partition wall disposed around at least the object to be measured in the second insulating film.

The biosensor may include a reference electrode that is insulated from the source electrode and the drain electrode and applies a variable voltage to the object to be measured.

In the biosensor, a hydrophilic region having hydrophilicity may be provided on the second insulating film.

In the biosensor, the second insulating film may be an ion sensitive film.

According to an embodiment of the present invention, a transparent base material, a first gate electrode formed of a transparent conductive material covering the transparent base material, and a transparent conductivity on the first gate electrode . A first semiconductor film formed of a material; a first source electrode and a first drain electrode disposed in ohmic contact with the first semiconductor film; and the first source electrode and the first source electrode. An FET sensor comprising: a first insulating film that covers each drain electrode; and a second insulating film that is disposed on the first semiconductor film on the first gate electrode and on which an object to be measured is disposed And a second gate electrode on the transparent substrate, a second semiconductor film covering the second gate electrode, and a second semiconductor electrode disposed in ohmic contact with the second semiconductor film, respectively. A source electrode and a second drain electrode; Biosensor comprising: the T, is provided.

In the biosensor, the FET sensor and the FET may constitute a current mirror circuit.

In the biosensor, the FET sensor and the FET may constitute an inverter circuit.

The biosensor may include a plurality of inverter circuits, and a ring oscillator circuit may be configured by connecting the plurality of inverter circuits in series.

The biosensor may include a partition wall disposed around at least the biological substance in the second insulating film.

The biosensor may include a reference electrode that is insulated from the source electrode and the drain electrode and applies a variable voltage to the object to be measured.

In the biosensor, a hydrophilic region having hydrophilicity may be provided on the second insulating film.

In the biosensor, the second insulating film may be an ion sensitive film.

According to the present invention, a biosensor capable of observing an object to be sensed with a microscope or the like simultaneously with sensing is provided.

It is a figure explaining the biosensor 100 of this invention which concerns on one Embodiment, (a) is a circuit diagram of the biosensor 100, (b) is a top view of the biosensor 100, (c) is (b) It is sectional drawing of the biosensor 100 in AA 'of (). It is a figure explaining the structure of the biosensor 200 of this invention which concerns on one Embodiment, (a) is a circuit diagram of the biosensor 200, (b) is a top view of the biosensor 200, (c) is It is sectional drawing of the biosensor 200 in AA 'of FIG.1 (b). 1A and 1B are diagrams showing a biosensor 300 according to an embodiment of the present invention, in which FIG. 1A is a circuit diagram of the biosensor 300, and FIG. FIG. 4 is a cross-sectional view of the biosensor 300 at AA ′ in FIG. It is a figure explaining the structure of the biosensor 400 of this invention which concerns on one Embodiment, (a) is a top view of the biosensor 400, (b) is sectional drawing of the biosensor 400 in AA 'of (a). It is. (A) is a circuit diagram of the biosensor 500 of the present invention according to an embodiment, and (b) is a top view of the biosensor 500. It is sectional drawing of the biosensor 500 in AA 'of FIG.6 (b). (A) is a circuit diagram of biosensor 600 of the present invention concerning one embodiment, and (b) is a figure showing influence on an output voltage by FET sensor 600a. It is a circuit diagram of biosensor 700 of the present invention concerning one embodiment. It is a circuit diagram of biosensor 800 of the present invention concerning one embodiment. It is a figure which shows the characteristic of the biosensor 100 of this invention which concerns on one Embodiment. It is a circuit diagram of biosensor 500 of the present invention concerning one example. It is a figure which shows the simulation result of an input current and an output current. It is a simulation result which shows the relationship between pH of a sample, and output current. (A) is a circuit diagram showing one inverter circuit of the biosensor 800 according to the present invention used in the simulation, (b) is a table showing frequencies at typical pH, and (c) is pH and ring. It is a figure which shows an oscillator frequency characteristic. It is a figure which shows the ring oscillator frequency characteristic in typical pH.

Hereinafter, a biosensor and a manufacturing method thereof according to the present invention will be described with reference to the drawings. However, the biosensor of the present invention can be implemented in many different modes and should not be construed as being limited to the description of the embodiments and examples shown below. Note that in the drawings referred to in this embodiment mode and examples, the same portions or portions having similar functions are denoted by the same reference numerals, and repetitive description thereof is omitted.

As a result of intensive studies to solve the above-mentioned problems, an inverted stagger type (bottom gate type) FET in which an active layer and an electrode are formed using a transparent material is used, and a protective layer is substituted on the active layer. By forming an ion-sensitive film, we have come to the idea of observing the sensing object with a microscope at the same time as sensing.

(Embodiment 1)
First, the structure of the biosensor 100 according to Embodiment 1 of the present invention will be described. FIG. 1 is a diagram for explaining the structure of a biosensor (FET sensor) 100 according to the present embodiment, FIG. 1 (a) is a circuit diagram of the biosensor 100, and FIG. 1 (b) is an upper surface of the biosensor 100. FIG. 1C is a cross-sectional view of the biosensor 100 taken along AA ′ in FIG.

The biosensor 100 according to the present embodiment includes a gate electrode 111, a gate insulating film 121, an active layer 131 that is a semiconductor film, a drain electrode 113 and a source electrode 115, and a protective film 141 on an upper surface that is an element formation surface of the substrate 101. And the structure of the reverse stagger type FET sensor which laminated | stacked the ion sensitive film | membrane 151 sequentially. The drain electrode 113 and the source electrode 115 are placed in ohmic contact with the active layer 131, and the ion sensitive film 151 on which the object to be measured is placed has a drain electrode 113 in a region sandwiched between the drain electrode 113 and the source electrode 115. Further, the protective film 141 is disposed with respect to the source electrode 115. In the biosensor 100, since the measurement region 191 is disposed above the protective film 141 that is the first insulating film and the ion sensitive film 151 that is the second insulating film, the object to be measured is disposed above the protective film 141. A partition wall 161 is further formed around the periphery.

A transparent base material is used as the base material 101. For example, a glass substrate, a quartz substrate, a substrate made of a transparent organic resin such as a plastic substrate, polypropylene, polyester, vinyl, polyvinyl fluoride, vinyl chloride, polyester, polyamide, etc. A transparent film or the like can be used. The thickness of the base material 101 can be appropriately selected within a range of 1 μm to 1 mm.

A transparent conductive material is used for the gate electrode 111, the drain electrode 113, and the source electrode 115. For example, indium tin oxide (ITO), zinc oxide (ZnO), indium zinc oxide (IZO), zinc oxide added with gallium is used. (GZO) or the like can be used. In addition, any of the gate electrode 111, the drain electrode 113, and the source electrode 115 can be formed using a material other than a transparent material. In that case, aluminum, gold, copper, or the like can be used as the material of the gate electrode 111, and as the material of the drain electrode 113 and the source electrode 115, titanium, aluminum, gold, copper, titanium, aluminum, and the like are stacked. It can also be used. The thicknesses of the gate electrode 111, the drain electrode 113, and the source electrode 115 are preferably 20 nm to 200 nm.

For the gate insulating film 121 and the protective film 141, a transparent insulating material is used, and for example, silicon oxide, silicon nitride, silicon oxynitride, or the like can be used. Further, a substrate made of a transparent organic resin such as a plastic substrate, a transparent film such as polypropylene, polyester, vinyl, polyvinyl fluoride, vinyl chloride, polyester, and polyamide may be used. The thicknesses of the gate insulating film 121 and the protective film 141 can be appropriately selected within a range of 50 nm to 1 μm.

The active layer 131 is made of a transparent semiconductor material, for example, an amorphous oxide whose main component is InMZnO (M is at least one of gallium (Ga), aluminum (Al), and iron (Fe)). it can. In particular, an InGaZnO-based amorphous oxide in which M is Ga is preferable. Moreover, when the active layer 131 has IGZO as a main component, if necessary, Al, Fe, Sn, or the like may be added as a constituent element. An IGZO semiconductor is suitable for a plastic substrate or a glass substrate having poor heat resistance because it can be formed at room temperature to a low temperature of about 150 ° C. The thickness of the active layer 131 is preferably 20 nm to 100 nm.

  Further, the active layer 131 may be formed of an oxide semiconductor containing zinc oxide (ZnO) as a main component. When ZnO is the main component, in addition to intrinsic oxide zinc, p-type dopants such as lithium (Li), sodium (Na), nitrogen (N) and carbon (C), and boron, if necessary (B), zinc oxide doped with n-type dopants such as aluminum (Al), gallium (Ga), indium (In), and zinc oxide doped with magnesium (Mg), beryllium (Be), etc. It may be. Further, the active layer 131 may be formed of an oxide semiconductor such as indium oxide to which tin is added (indium tin oxide: ITO), indium zinc oxide (IZO), or magnesium oxide (MgO).

The ion-sensitive membrane 151 can arrange an object to be measured, for example, a cell, DNA, sugar chain, protein, or the like included in a sample added to the measurement region 191. The ion sensitive film 151 is made of a transparent insulating material such as silicon oxide, silicon nitride, silicon oxynitride, tantalum oxide, or aluminum oxide.

The partition wall 161 is used to hold (store) a sample in the measurement region 191. For example, glass, plastic, or the like can be used.

When measurement using the biosensor 100 is performed, the drain electrode 113 and the reference electrode 117 insulated from the source electrode 115 are used. In addition, a power source 193 a and an ammeter 195 are connected to the drain electrode 113. When the biosensor 100 is an enhancement type, the power source 193b is connected to the reference electrode 117. A sample including an object to be measured is added to the measurement region 191, and a voltage V _DS of about 0.1 V to 1 V is applied between the drain electrode 113 and the source electrode 115, and the sample is variable via the reference electrode 117. applying a voltage _{V G.} At this time, the channel region formed in the active layer 131 changes due to the change in potential generated in the ion sensitive film 151 in accordance with the electrical characteristics of the object to be measured, and the change in the drain current _ID is detected. At this time, the gate electrode 111 may be in a floating state, but a power source 193c may be connected. By applying a voltage to the gate electrode 111, stable measurement is possible. In the biosensor 100, when a channel is formed in the active layer 131 by the potential of the sample itself and a current flowing between the drain electrode 113 and the source electrode 115 can be measured, the reference electrode 117 is not used. It is also possible to do.

In the conventional biosensor, the biosensing part is formed on the gate insulating film and the gate electrode, and the gate electrode is electrically floated or used in common with the function of the reference electrode for use as the biosensing part. It was necessary to use it. The biosensor according to the present embodiment has an inverted staggered FET structure, and an ion-sensitive film is formed on the active layer in place of the protective layer. In the biosensor according to the present embodiment, each electrode of the FET can be freely set without being restricted as in the conventional biosensor, and by providing a biosensing unit in the back gate of the FET, the ISFET can be directly used as a circuit. It can be incorporated. Moreover, the biosensor according to the present invention makes it possible to observe the sample of the biosensing unit with a microscope or the like by making the active layer and the electrode transparent.

(Embodiment 2)
In the present embodiment, a biosensor (FET sensor) 200 in which a floating electrode 217 is disposed on the active layer 131 will be described. 2A and 2B are diagrams for explaining the structure of the biosensor 200 according to the second embodiment of the present invention. FIG. 2A is a circuit diagram of the biosensor 200 and FIG. 2B is a top view of the biosensor 200. FIG. 2 (c) shows a cross-sectional view of the biosensor 200 at AA ′ in FIG. 1 (b).

The biosensor 200 according to the present embodiment has the same structure as the biosensor 100 except that the floating electrode 217 and the ion sensitive film 151 are sequentially stacked on the active layer 131. The floating electrode 217 is disposed with respect to the drain electrode 113 and the source electrode 115 via a protective film 141. In the biosensor 200, by disposing the floating electrode 217 on the active layer 131, the information of the sensing unit can be uniformly transmitted to the active layer. Since the operation principle of the biosensor 200 is the same as that of the biosensor 100, description thereof is omitted.

Next, the biosensor 300 will be described as a modification. FIG. 3A is a circuit diagram of the biosensor 300, and FIG. 3B is a top view of the biosensor 300. FIG. 4 is a cross-sectional view of the biosensor 300 taken along AA ′ in FIG. As shown in FIG. 3B, the biosensor 300 is disposed on the electrode, and the second insulating film biosensor 300 on which the object to be measured is disposed is disposed on the active layer 131. A floating electrode 317 is drawn outside a region sandwiched between the drain electrode 113 and the source electrode 115. Thereby, the biosensor 300 can arrange | position the ion sensitive film | membrane 151 and the measurement area | region 191 outside the area | region pinched | interposed by the drain electrode 113 and the source electrode 115 by arrange | positioning the floating electrode 317. FIG. In general, the measurement region 191 is larger than the region where the gate electrode 111, the drain electrode 113, and the source electrode 115 are formed, and thus the floating electrode 317 is drawn and arranged to increase the degree of freedom in designing the biosensor. Therefore, it is preferable. In this embodiment, the structure in which the floating electrode 317 formed in the same manner as the drain electrode 113 and the source electrode 115 is drawn is described, but the present invention is not limited to this. For example, a contact hole may be formed so as to be drawn out from the floating electrode 317 disposed above the active layer 131 to the measurement region 191 with a wiring formed in a layer different from the drain electrode 113 and the source electrode 115.

For the floating electrode 217 and the floating electrode 317, a transparent conductive material is used like the other electrodes. For example, indium tin oxide (ITO), zinc oxide (ZnO), indium zinc oxide (IZO), zinc oxide to which gallium is added (GZO) or the like can be used. The thickness of the floating electrode 217 and the floating electrode 317 is preferably 20 nm to 200 nm, and the shape and area of the floating electrode 217 and the floating electrode 317 can be appropriately set in consideration of the measurement region 191 to be arranged.

When measurement is performed using the biosensor 300, the drain electrode 113 and the reference electrode 117 insulated from the source electrode 115 are used. In addition, a power source 193 a and an ammeter 195 are connected to the drain electrode 113. When the biosensor 300 is an enhancement type, the power source 193b is connected to the reference electrode 117. A sample including an object to be measured is added to the measurement region 191, and a voltage V _DS of about 0.1 V to 1 V is applied between the drain electrode 113 and the source electrode 115, and the sample is variable via the reference electrode 117. applying a voltage _{V G.} At this time, the change in potential generated in the ion sensitive film 151 according to the electrical characteristics of the object to be measured is transmitted to the active layer 131 via the floating electrode 317, and the channel region formed in the active layer 131 is changed. A change in _ID is detected. At this time, the gate electrode 111 may be in a floating state, but may be connected to a power source 193c. By applying a voltage to the gate electrode 111, stable measurement is possible. In the biosensor 300, when a channel is formed in the active layer 131 by the potential of the sample itself and a current flowing between the drain electrode 113 and the source electrode 115 can be measured, the reference electrode 117 is not used. It is also possible to do.

The biosensor according to the present embodiment has an inverted staggered structure, and a floating electrode is formed on the active layer. In the biosensor according to the present embodiment, the measurement region can be freely arranged by arranging the floating electrode so as to be drawn out from the gate electrode, the drain electrode, and the source electrode. Moreover, the biosensor according to the present invention makes it possible to observe the sample of the biosensing portion with a microscope or the like by making the active layer and the floating electrode transparent.

(Embodiment 3)
In this embodiment, a biosensor (FET sensor) 400 in which an affinity layer 455 is disposed on the ion sensitive film 151 will be described. FIG. 5 is a view for explaining the structure of a biosensor 400 according to Embodiment 3 of the present invention, FIG. 5 (a) is a top view of the biosensor 400, and FIG. 5 (b) is a view of FIG. It is sectional drawing of the biosensor 400 in AA '. It is sectional drawing.

The biosensor 400 according to the present embodiment has the same structure as that of the biosensor 100 except that the affinity layer 455 is disposed on the ion sensitive membrane 151. The affinity layer 455 provides the ion sensitive film 151 with affinity for the object to be measured, and improves the detection efficiency of the ion sensitive film 151. In order to impart affinity to the object to be measured, the affinity layer 455 forms, for example, a hydrophilic region having hydrophilicity. The affinity layer 455 can be formed of a hydrophilic polymer, and can also be formed by chemically modifying a hydrophilic functional group on the ion sensitive membrane 151. Further, the affinity layer 455 may be formed using a transparent material having a binding property to the object to be measured. The material of the affinity layer 455 can be appropriately set in consideration of the binding characteristics with the object to be measured.

Conversely, without forming the affinity layer 455, a hydrophobic material is used for the protective film 141 other than the ion sensitive film 151, a cell adhesion inhibition layer is formed, and a hydrophobic film is formed on the upper surface of the protective film 141. May be. For example, the protective film 141 may be coated with silicone. In addition, the protective film 141 may be provided with a cell adhesion inhibition layer using a material having binding inhibition characteristics with respect to the measurement object, for example, cell adhesion inhibition characteristics.

As the material of the affinity layer 455, for example, a water-soluble polymer, a water-soluble oligomer, a water-soluble organic compound, a surfactant, an amphiphilic substance, or the like can be used. Water-soluble polymer materials include polyalkylene glycol and derivatives thereof, polyacrylic acid and derivatives thereof, polymethacrylic acid and derivatives thereof, polyacrylamide and derivatives thereof, polyvinyl alcohol and derivatives thereof, zwitterionic polymers, polysaccharides , Etc. Examples of the molecular shape include a straight chain, a branched one, and a dendrimer. Specifically, polyethylene glycol, a copolymer of polyethylene glycol and polypropylene glycol, such as Plonic F108, Plonic F127, poly (N-isopropylacrylamide), poly (N-vinyl-2-pyrrolidone), poly (2-hydroxy). Ethyl methacrylate), poly (methacryloyloxyethylphosphorylcholine), copolymers of methacryloyloxyethylphosphorylcholine and acrylic monomers, dextran, and heparin, but are not limited thereto. Examples of water-soluble oligomer materials and water-soluble low-molecular compounds include alkylene glycol oligomers and derivatives thereof, acrylic acid oligomers and derivatives thereof, methacrylic acid oligomers and derivatives thereof, acrylamide oligomers and derivatives thereof, saponified vinyl acetate oligomers and derivatives thereof, Examples include oligomers composed of zwitterionic monomers and derivatives thereof, acrylic acid and derivatives thereof, methacrylic acid and derivatives thereof, acrylamide and derivatives thereof, zwitterionic compounds, water-soluble silane coupling agents, and water-soluble thiol compounds. . Specifically, ethylene glycol oligomer, (N-isopropylacrylamide) oligomer, methacryloyloxyethylphosphorylcholine oligomer, low molecular weight dextran, low molecular weight heparin, oligoethylene glycol thiol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol , 2- [methoxy (polyethyleneoxy) -propyltrimethoxysilane, and triethyleneglycol-terminated-thiol, but are not limited thereto.

The average thickness of the affinity layer 455 is preferably 0.8 nm to 500 μm, more preferably 0.8 nm to 100 μm, more preferably 1 nm to 10 μm, and most preferably 1.5 nm to 1 μm. An average thickness of 0.8 nm or more is preferable because it is difficult to be affected by a region not covered with the affinity layer 455 in protein adsorption or cell adhesion. Moreover, if the average thickness is 500 μm or less, coating is relatively easy. The shape and area of the affinity layer 455 can be appropriately set in consideration of the measurement region 191 to be arranged and the object to be measured. For example, when the object to be measured is a cell, measurement from only one cell is possible by setting the size of the concave portion of the affinity layer 455 to a size that allows one cell to be arranged. Since the operation principle of the biosensor 400 is the same as that of the biosensor 100, description thereof is omitted.

Although not shown, the affinity layer 455 according to the present embodiment is also applicable to the biosensor 200 and the biosensor 300 described in the second embodiment. That is, the affinity layer 455 may be formed on the upper surface of the ion sensitive film 151 formed on the floating electrode 217 and the floating electrode 317.

The biosensor according to the present embodiment has an inverted staggered structure, and an affinity layer is formed. In the biosensor according to the present embodiment, the affinity to the object to be measured is imparted to the ion-sensitive film by the affinity layer, so that the object to be measured contained in the sample added to the measurement region is selectively formed on the ion-sensitive film. It can be installed in a high-precision measurement.

(Embodiment 4)
In the present embodiment, a current mirror type biosensor 500 provided with an FET sensor and an FET will be described. 6A and 6B are diagrams for explaining the structure of the biosensor 500 according to Embodiment 4 of the present invention. FIG. 6A is a circuit diagram of the biosensor 500, and FIG. 6B is a top view of the biosensor 500. FIG. 7 is a cross-sectional view of the biosensor 500 taken along AA ′ in FIG. 6A is an example in which the arrangement of the FET sensor 500a and the FET 500b is symmetrical.

The biosensor 500 according to the present embodiment has at least one set of ISFETs including two elements, the FET sensor 500a and the FET 500b, on the element forming surface of the same base material 101. Each of the FET sensors 500a and 500b has an inverted staggered structure in which a gate electrode 111, a gate insulating film 121, an active layer 131, a drain electrode 113 and a source electrode 115, and a protective film 141 are sequentially stacked. In the FET sensor 500a, in place of the protective film 141, an ion sensitive film 151 in which an object to be measured is disposed on the active layer 131a which is a first semiconductor film is a first drain electrode 113a and a first source electrode 115a. In the sandwiched region, the drain electrode 113a and the source electrode 115a are disposed with a protective film 141 interposed therebetween. In order to dispose the measurement region 191 above the protective film 141 and the ion sensitive film 151, a partition wall 161 is further disposed above the protective film 141.

The gate electrodes 111 of the FET sensor 500a and the FET 500b are electrically connected. The gate electrode 111, the gate insulating film 121, the active layer 131, the drain electrode 113 and the source electrode 115, and the protective film 141 of the FET sensors 500a and 500b are integrally formed, and the materials described in the first embodiment are applied as the respective materials. Therefore, the description is omitted. In the biosensor 500, the first gate electrode 111a of the FET sensor 500a and the second gate electrode 111b of the FET 500b are connected to the first drain electrode 113a of the FET sensor 500a and connected to the power source 193a connected to the FET sensor 500a. Connecting. Further, the first source electrode 115a of the FET sensor 500a and the second source electrode 115b of the FET 500b are connected. A power source 193b is connected to the second drain electrode 113b of the FET 500b. This connection forms a current mirror circuit. The arrangement of the drain electrode 113 and the source electrode 115 of the FET sensor 500a and FET 500b is an example, and the drain electrode 113 and the source electrode 115 of the FET sensor 500a and FET 500b can be arranged adjacent to each other.

When measurement using the biosensor 500 is performed, the drain electrode 113a and the reference electrode 117 insulated from the source electrode 115a are used for the FET sensor 500a. The drain electrode 113a is connected to the power source 193a, and the source electrode 115a is connected to the ammeter 195. When the biosensor 500 is an enhancement type, the power source 193c is connected to the reference electrode 117. Adding a sample containing the object to be measured in the measurement region 191, while applying a voltage _{V DS} of about 0.1V~1V between the drain electrode 113a and the source electrode 115a, the variable in the sample through the reference electrode 117 applying a voltage _{V G.} At this time, the channel region formed in the active layer 131a changes due to the change in potential generated in the ion sensitive film 151 in accordance with the electrical characteristics of the object to be measured, and the change in the drain current _ID is detected. Note that in the biosensor 500, when the channel is formed in the active layer 131 by the potential of the sample itself and the current flowing between the drain electrode 113 and the source electrode 115 can be measured, the reference electrode 117 is not used. It is also possible to do.

In the biosensor 500, one FET of the current mirror circuit is an FET sensor 500a, and the other is an FET 500b. Therefore, according to the biosensor 500, the measurement result of the FET sensor 500a can be obtained as a current value. Further, since the biosensor 500 can determine whether the current mirror circuit is good or bad at the manufacturing stage, it is possible to easily select defective products. Therefore, the biosensor 500 can be manufactured using only an appropriate current mirror circuit.

The configuration of the second embodiment and the third embodiment described above can also be applied to the biosensor 500. That is, the floating electrode 217 and the ion sensitive film 151 may be sequentially stacked on the active layer 131 of the biosensor 500, or the floating electrode 317 may be drawn out. Further, an affinity layer 455 may be disposed on the ion sensitive film 151 of the biosensor 500.

The biosensor according to the present embodiment has a current mirror circuit, and can obtain the measurement result of the FET sensor of the biosensing unit as a current value. In addition, since the biosensor according to the present embodiment can determine whether the current mirror circuit is good or bad at the manufacturing stage, it can provide a highly accurate biosensor.

(Embodiment 5)
In this embodiment, a biosensor 600 using one FET of a differential amplifier circuit as an FET sensor will be described. FIG. 8A is a circuit diagram of a biosensor 600 according to Embodiment 5 of the present invention, and FIG. 8B is a diagram showing the influence of the FET sensor 600a on the output voltage.

The biosensor 600 according to the present embodiment has five elements, an FET sensor 600a, an FET 600b, an FET 600c, an FET 600d, and an FET 600e on the element forming surface of the same base material 101. Since the FET sensor 600a, the FET 600b, the FET 600c, the FET 600d, and the FET 600e have the same structure as the FET sensor 500a and the FET 500b, details are omitted. Although not shown, the FET sensor 600a, FET 600b, FET 600c, FET 600d, and FET 600e are each an inverted staggered type in which a gate electrode 111, a gate insulating film 121, an active layer 131, a drain electrode 113, a source electrode 115, and a protective film 141 are sequentially stacked. It has a structure. In the FET sensor 600a, instead of the protective film 141, an ion sensitive film 151 is disposed on the active layer 131a that is the first semiconductor film, and a measurement region 191 is disposed on the protective film 141 and the ion sensitive film 151. Therefore, a partition wall 161 is further disposed on the protective film 141.

The gate electrode 111, the gate insulating film 121, the active layer 131, the drain electrode 113, the source electrode 115, and the protective film 141 of the FET sensor 600a, FET 600b, FET 600c, FET 600d, and FET 600e are integrally formed. Since the materials described in (1) can be applied, the description is omitted.

In the biosensor 600, the first source electrode 115a of the FET sensor 600a of the biosensing unit connected in parallel and the source electrode 115b of the second FET 600b are connected to the fifth drain electrode 113e of the FET 600e. The source electrode 115e of the FET 600e is grounded to GND. Further, the drain electrode 113a of the FET sensor 600a and the drain electrode 113b of the FET 600b are connected to the third source electrode 115c and the fourth source electrode 115d of the current mirror circuit formed by the FET 600c and FET 600d, respectively. The biosensor 600 formed in this way functions as a differential amplifier, and can output the measurement result of the FET sensor 600a to Vout as a voltage difference. In addition, since the biosensor 600 can select elements having variations at the manufacturing stage and can determine the quality of the differential amplifier circuit, it is possible to easily select defective products. Therefore, the biosensor 600 can be manufactured using only an appropriate differential amplifier circuit.

When measurement using the biosensor 600 is performed, a reference electrode 117 that is insulated from the drain electrode 113a and the source electrode 115a and grounded is used for the FET sensor 600a. The power source 193a is connected to the third drain electrode 113c and the fourth drain electrode 113d of the FET 600c and FET 600d, and the ammeter 195 is connected to the fifth source electrode 115e of the FET 600e. When the biosensor 600 is an enhancement type, the power source 193b is connected to the reference electrode 117. A sample including the object to be measured is added to the measurement region 191, and while applying the power supply voltage V _DD , a constant voltage V _DD / 2 is applied to the second gate electrode 111 b of the FET 600 b, and the first voltage of the FET sensor 600 a is applied. The output current I _out is measured by sweeping a voltage from 0 V to V _DD to one gate electrode 111a. At this time, if through the reference electrode 117 for applying a variable voltage V _G to the sample, as shown in FIG. 8 (b), the change in potential occurring in the ion-selective membrane 151 in accordance with the electrical characteristics of the object to be measured, the activity The channel region formed in the layer 131a changes, and the characteristic of the detected I _out centered around V _DD / 2 is shifted to the left or right. Note that in the biosensor 600, when the channel is formed in the active layer 131 by the potential of the sample itself and the current flowing between the drain electrode 113 and the source electrode 115 can be measured, the reference electrode 117 is not used. It is also possible to do.

The configuration of the second embodiment and the third embodiment described above can also be applied to the biosensor 600. That is, the floating electrode 217 and the ion sensitive film 151 may be sequentially stacked on the active layer 131 of the biosensor 600, and the floating electrode 317 may be drawn out. In addition, an affinity layer 455 may be disposed on the ion sensitive film 151 of the biosensor 600.

The biosensor according to the present embodiment has a differential amplifier circuit, and can obtain an output voltage using the measurement result of the FET sensor of the biosensing unit as a voltage difference. Moreover, since the biosensor according to the present embodiment can determine the quality of the differential amplifier circuit at the manufacturing stage, a highly accurate biosensor can be provided.

(Embodiment 6)
In the present embodiment, a biosensor 700 using one FET of an inverter circuit as an FET sensor will be described. FIG. 9 is a circuit diagram of a biosensor 700 according to Embodiment 6 of the present invention. Note that the left diagram and the right diagram in FIG. 9 are examples in which the arrangements of the FET sensors 700a and 700b are reversed.

The biosensor 700 according to the present embodiment has at least one ISFET including two elements, the FET sensor 700a and the FET 700b, on the element forming surface of the same base material 101. Since the FET sensor 700a and the FET 700b have the same structure as the FET sensor 500a and the FET 500b, the details are omitted. Although not shown, each of the FET sensors 700a and 700b has an inverted staggered structure in which a gate electrode 111, a gate insulating film 121, an active layer 131, a drain electrode 113 and a source electrode 115, and a protective film 141 are sequentially stacked. In the FET sensor 700a, instead of the protective film 141, an ion sensitive film 151 is disposed on the active layer 131 that is the first semiconductor film, and a measurement region 191 is disposed on the protective film 141 and the ion sensitive film 151. Therefore, a partition wall 161 is further disposed on the protective film 141.

The gate electrode 111, the gate insulating film 121, the active layer 131, the drain electrode 113 and the source electrode 115, and the protective film 141 of the FET sensors 700a and 700b are integrally formed, and the materials described in the first embodiment are applied as the respective materials. Therefore, the description is omitted.

In the biosensor 700, the FET sensor 700a and the FET 700b of the biosensing unit are connected in series. The biosensor 700 formed in this manner functions as an inverter and can detect the measurement result of the FET sensor 700a as an output voltage.

When measurement using the biosensor 700 is performed, a reference electrode 117 insulated from the first drain electrode 113a and the first source electrode 115a is used for the FET sensor 700a. Further, the power source 193a is connected to the drain electrode 113 of the FET sensor 700a or FET 700b on the upstream side of the biosensor 700, and the ammeter 195 is connected to the source electrode 115 of the FET sensor 700a or FET 700b on the downstream side of the biosensor 700. . When the biosensor 700 is an enhancement type, the power source 193b is connected to the reference electrode 117. Adding a sample containing the object to be measured in the measurement region 191, while applying a voltage _{V DS} of about 0.1V~1V between the drain electrode 113a and the source electrode 115a, the variable in the sample through the reference electrode 117 applying a voltage _{V G.} At this time, the channel region formed in the active layer 131a changes due to the change in potential generated in the ion sensitive film 151 in accordance with the electrical characteristics of the object to be measured, and the change in the drain current _ID is detected. Note that in the biosensor 700, when a channel is formed in the active layer 131 by the potential of the sample itself and a current flowing between the drain electrode 113a and the source electrode 115b can be measured, the reference electrode 117 is not used. It is also possible to do.

The configuration of the second embodiment and the third embodiment described above can also be applied to the biosensor 700. That is, the floating electrode 217 and the ion sensitive film 151 may be sequentially stacked on the active layer 131 of the biosensor 700, and the floating electrode 317 may be drawn out. Further, the affinity layer 455 may be disposed on the ion sensitive film 151 of the biosensor 700.

The biosensor according to the present embodiment can detect the measurement result of the FET sensor of the biosensing unit as an output voltage by providing the biosensing unit in a part of the inverter circuit.

(Embodiment 7)
In this embodiment, a biosensor 800 using one FET of each inverter circuit of a ring oscillator as an FET sensor will be described. FIG. 10 is a circuit diagram of a biosensor 800 according to Embodiment 7 of the present invention.

The biosensor 800 according to the present embodiment has a plurality of sets of ISFETs including two elements, an FET sensor 800a and an FET 800b, on the element forming surface of the same base material 101. Since the FET sensor 800a and the FET 800b have the same structure as the FET sensor 500a and the FET 500b, the details are omitted. Although not shown, each of the FET sensors 800a and 800b includes an inverted staggered type in which a gate electrode 111, a gate insulating film 121, an active layer 131, a first drain electrode 113a and a first source electrode 115b, and a protective film 141 are sequentially stacked. It has a structure. In the FET sensor 800a, instead of the protective film 141, an ion sensitive film 151 is disposed on the active layer 131a, and a measurement region 191 is disposed on the protective film 141 and the ion sensitive film 151. A partition wall 161 is further disposed on the top.

The gate electrode 111, the gate insulating film 121, the active layer 131, the drain electrode 113 and the source electrode 115, and the protective film 141 of the FET sensor 800a and the FET 800b are integrally formed, and the materials described in the first embodiment are applied as the respective materials. Therefore, the description is omitted.

Similarly to the biosensor 700, the biosensor 800 has an odd number of inverter circuits in which FET sensors 800a and 800b of the biosensing unit are connected in series, and the odd number of inverter circuits are connected in a ring shape. The connection terminal of the FET sensor 800a and FET 800b of the inverter circuit is connected to the gate electrode 111 of either the FET sensor 800a or FET 800b of the adjacent inverter circuit. Since the biosensor 800 measures one sample by all the FET sensors 800a, the measurement region 191 may be formed as one common region, or a plurality of the measurement regions 191 may be formed and the same sample may be dispensed. In addition, when the number of measurement regions 191 is one, the number of reference electrodes 117 may be one. In the biosensor 800, the arrangement of the FET sensor 800a and the FET 800b may be reversed as in the biosensor 700 described in the sixth embodiment. Note that in the biosensor 800, when the channel is formed in the active layer 131 by the potential of the sample itself and the current flowing between the drain electrode 113a and the source electrode 115b can be measured, the reference electrode 117 is not used. It is also possible to do.

The biosensor 800 formed in this manner oscillates, and the characteristics of the liquid sample can be detected as a difference in oscillation frequency. Specifically, as shown in the examples described later, the pH and the like of the liquid sample can be detected as a difference in oscillation frequency.

The configuration of the second embodiment and the third embodiment described above can also be applied to the biosensor 800. That is, the floating electrode 217 and the ion sensitive film 151 may be sequentially stacked on the active layer 131 of the biosensor 800, and the floating electrode 317 may be drawn out. In addition, an affinity layer 455 may be disposed on the ion sensitive film 151 of the biosensor 600.

The biosensor according to the present embodiment can detect the measurement result of the FET sensor of the biosensing unit based on the difference in oscillation frequency by using one FET of each inverter circuit of the ring oscillator as the FET sensor.

The measurement using the biosensor according to the present invention described above will be described below with a specific example. In addition, the Example shown below is an example, The biosensor which concerns on this invention is not limited to a following example.

(FET sensor simulation)
As Example 1, a simulation using the biosensor 100 described in Embodiment 1 was performed. FIG. 11 is a diagram illustrating the characteristics of the biosensor 100. The horizontal axis indicates the voltage of the reference electrode 117, and the horizontal axis indicates the output current. In the simulation, a circuit characteristic in which voltages are applied to the gate electrode 111, the drain electrode 113, and the source electrode 115 of the biosensor 100, a solution of pH 3.3, pH 6.7, and pH 10 is added as a sample in the measurement region 191, and The characteristics when a voltage was applied to were measured.

As is clear from FIG. 11, the voltage applied to the biosensor 100 and the output current have a positive correlation above the threshold voltage, and the output current decreases as the pH in the sample increases. This simulation result shows that the biosensor according to the present invention can accurately measure the pH of the sample.

(Simulation of current mirror type biosensor)
As Example 2, a simulation using the biosensor 500 described in Embodiment 4 was performed. FIG. 12 is a circuit diagram of the biosensor 500 according to the present invention used for the simulation. In the simulation, the threshold voltage Vth is set to 0.15 V / pH, voltage characteristics are applied to the gate electrode 111, the drain electrode 113, and the source electrode 115 of the biosensor 500, and the sample in the measurement region 191 is pH 3.3, pH 6. 7 and pH 10 solutions were added, and the characteristics when a voltage was applied to the reference electrode were measured. FIG. 13 is a diagram illustrating simulation results of input current and output current. The biosensor 500 shows a positive correlation between the input current and the output current, and it can be seen that the output current decreases as the pH of the sample increases.

FIG. 14 is a simulation result showing the relationship between the pH of the sample and the output current. The horizontal axis indicates the pH of the sample, and the vertical axis indicates the output current. The pH and output current showed a linear negative correlation. These simulation results indicate that the biosensor according to the present invention can accurately measure the pH of the sample.

(Simulation of ring oscillator type biosensor)
As Example 3, a simulation using the biosensor 800 described in Embodiment 7 was performed. In the simulation, circuit characteristics in which voltages are applied to the gate electrode 111, the drain electrode 113, and the source electrode 115 of the biosensor 800, a solution of pH 2.5, pH 5, and pH 10 is added as a sample in the measurement region 191, and the voltage is applied to the reference electrode. The characteristics were measured when applied. FIG. 15 (a) is a circuit diagram showing one inverter circuit of the biosensor 800 according to the present invention used for the simulation, and FIG. 15 (b) is a table showing frequencies at typical pHs. c) is a diagram showing pH and ring oscillator frequency characteristics. In FIG.15 (c), a horizontal axis shows the pH of a sample and a vertical axis | shaft shows a ring oscillator frequency. FIG. 16 is a diagram showing the ring oscillator frequency characteristics at a typical pH, in which the horizontal axis represents elapsed time (seconds) and the vertical axis represents voltage.

From the simulation results, pH and ring oscillator frequency characteristics showed a linear negative correlation. These simulation results indicate that the biosensor according to the present invention can accurately measure the pH of the sample.

As described above, the biosensor according to the present invention has an inverted staggered structure and can freely set each electrode of the FET by forming an ion-sensitive film on the active layer instead of the protective layer. In addition, by providing a biosensing unit at the back gate of the FET sensor, the ISFET can be incorporated into the circuit as it is. In addition, the biosensor according to the present invention makes it possible to observe the sample of the biosensing unit with a microscope or the like by making the active layer and the electrode transparent, and enables highly accurate detection of the object to be measured. is there.

100 Biosensor 101 Base material 111 Gate electrode 111a Gate electrode 111b Gate electrode 113 Drain electrode 113a Drain electrode 113b Drain electrode 115 Source electrode 117 Reference electrode 121 Gate insulating film 131 Active layer 141 Protective film 151 Ion sensitive film 161 Partition 191 Measurement area 193a Power supply 193b power supply 193c power supply 193d power supply 195 ammeter 200 biosensor 217 floating electrode 300 biosensor 317 floating electrode 400 biosensor 455 affinity layer 500 biosensor 500a FET sensor 500b FET
600 Biosensor 600a FET sensor 600b FET
600c FET
600d FET
600e FET
700 Biosensor 700a FET sensor 700b FET
800 Biosensor 800a FET sensor 800b FET

Claims (15)

A transparent substrate;
A gate electrode formed of a transparent conductive material on the transparent substrate;
A semiconductor film formed of a transparent semiconductor material covering the gate electrode;
A source electrode and a drain electrode disposed in ohmic contact with the semiconductor film,
A first insulating film covering each of the source electrode and the drain electrode;
A second insulating film disposed on the semiconductor film on the gate electrode and on which the object to be measured is disposed;
A biosensor comprising: an FET sensor comprising: The biosensor according to claim 1, further comprising an electrode disposed on the semiconductor film with a first insulating film interposed between the source electrode and the drain electrode. A transparent substrate;
A gate electrode formed of a transparent conductive material on the transparent substrate;
A semiconductor film formed of a transparent semiconductor material covering the gate electrode;
A source electrode and a drain electrode disposed in ohmic contact with the semiconductor film,
A first insulating film covering each of the source electrode and the drain electrode;
An electrode arranged to be drawn out from the semiconductor film on the gate electrode toward the outside of the semiconductor film;
A second insulating film disposed on the electrode and on which the object to be measured is disposed;
A biosensor comprising: an FET sensor comprising: The biosensor according to any one of claims 1 to 3, further comprising a partition wall disposed around at least the device to be measured in the second insulating film. The biosensor according to claim 1, further comprising a reference electrode that is insulated from the source electrode and the drain electrode and applies a variable voltage to the object to be measured. The biosensor according to any one of claims 1 to 5, characterized in that a hydrophilic region having a hydrophilic on the second insulating film. The biosensor according to any one of claims 1 to 6 , wherein the second insulating film is an ion-sensitive film. A transparent substrate;
A first gate electrode formed of a transparent conductive material covering the transparent substrate;
A first semiconductor film formed of a transparent semiconductor material on the first gate electrode;
A first source electrode and a first drain electrode disposed in ohmic contact with the first semiconductor film,
A first insulating film covering each of the first source electrode and the first drain electrode;
A second insulating film disposed on the first semiconductor film on the first gate electrode and on which a device under test is disposed;
An FET sensor comprising:
A second gate electrode on the transparent substrate;
A second semiconductor film covering the second gate electrode;
A second source electrode and a second drain electrode disposed in ohmic contact with the second semiconductor film,
FET comprising:
A biosensor comprising: The biosensor according to claim 8 , wherein the FET sensor and the FET constitute a current mirror circuit. The biosensor according to claim 9 , wherein the FET sensor and the FET constitute an inverter circuit. 11. The biosensor according to claim 10 , wherein a ring oscillator circuit is configured by having a plurality of the inverter circuits and connecting the plurality of inverter circuits in series. The biosensor according to any one of claims 8 to 11 , further comprising a partition wall disposed around at least the biological substance in the second insulating film. Insulated from the first source electrode and first drain electrode, and the described comprise a reference electrode for applying a variable voltage to any one of claims 8 to 12, wherein the object to be measured bio Sensor. The biosensor according to any one of claims 8 to 13, characterized in that a hydrophilic region having a hydrophilic on the second insulating film. The second insulating film, biosensor according to any one of claims 8 to 14, characterized in that the ion sensitive membrane.