Transistor sensor and biological material detection method

Abstract

To provide a transistor sensor with high sensitivity and low detection limit capable of detecting biological substances quickly and easily while achieving high detection stability at low cost.SOLUTION: A transistor sensor includes: a substrate; a channel layer formed over one surface of the substrate; a solid electrolyte layer formed between the substrate and the channel layer or over a surface at a side opposite to the substrate side of the channel layer; in which the channel layer contains inorganic semiconductors and the solid electrolyte layer contains inorganic solid electrolytes, at least a part of either one or both of the channel layers and the solid electrolyte layer has an exposed part exposed to an outside.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a transistor sensor and a method for detecting a biological material. [Background technology]

[0002] DNA sensors using transistor sensors such as thin film transistor (TFT) sensors are widely known, and various DNA sensors using transistor sensors have been reported. For example, a method has been reported in which a homo-oligomer DNA chain is immobilized using 3-aminopropylethoxysilane, and hybridization with the oligomer chain is directly detected by the change in gate potential under a constant drain current (Non-Patent Document 1).

[0003] Conventional methods for measuring mRNA / DNA include the use of PCR (polymerase chain reaction) and next-generation sequencing. PCR is a method for amplifying a specific region (target region) on a DNA sequence using a heat-resistant DNA polymerase, and since it is possible to detect a specific DNA sequence from a single DNA molecule, it is possible to detect the specific DNA sequence with high sensitivity. Next-generation sequencing is a method in which DNA is fragmented to prepare a library, and the DNA fragments of the library are sequenced in parallel, making it possible to comprehensively decipher the entire DNA sequence from a single molecule. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] J.Phys.Chem.B,1997,101,2980-2985 Summary of the Invention [Problem to be solved by the invention]

[0005] However, the technology of Non-Patent Document 1 has a detection limit of about 1 μg / mL, which is not very high, and the detection value changes depending on the coexisting substances in the actual sample, so the detection limit and selectivity are insufficient. In addition, DNA sensors using conventional transistors are easily affected by moisture and salt, and detection becomes unstable in the presence of moisture and salt.

[0006] In order to increase the detection limit, it is necessary for the sensor to have high sensitivity or low noise. The sensitivity of a transistor sensor is determined by (mobility) x (gate capacitance) and the S factor, but the sensitivity of conventional transistor sensors is not very high. Therefore, in order to increase the detection limit, stability of detection at low concentrations is important, but conventional transistor sensors have low stability in aqueous solutions, especially in real biological sample solutions in which proteins and other substances coexist.

[0007] On the other hand, the PCR method is highly sensitive and can detect even a single DNA molecule, but requires amplification, which requires time, effort, and cost for detection. In addition, the next-generation sequencing method requires even more time and cost for detection. In recent years, the need for clinical testing in the medical field has been increasing year by year, and rapid and highly sensitive detection and measurement are required, especially in the analysis of infectious diseases, new cancer markers, individual genes, exosomes, mRNA in white blood cells, cell-free RNA / DNA, etc.

[0008] An object of the present invention is to provide a transistor sensor and a biological substance detection method which have high sensitivity, a low detection limit, and high detection stability, and further which can detect biological substances quickly, easily, and at low cost. [Means for solving the problem]

[0009] As a result of extensive research, the inventors have found that in a transistor sensor having a substrate, a channel layer provided on one surface of the substrate, and a gate insulating layer (solid electrolyte layer) provided between the substrate and the channel layer or on the surface of the channel layer opposite the substrate, wherein at least one of the channel layer and the solid electrolyte layer or both have exposed portions exposed to the outside, the channel layer contains an inorganic semiconductor and the solid electrolyte layer contains an inorganic solid electrolyte, thereby enabling detection of biological substances with high sensitivity, a low detection limit, improved detection stability, and further enabling detection of biological substances to be performed quickly and easily at low cost. In addition, the present inventors have found that by using a composite metal oxide containing multiple specific metal elements as the gate insulation layer (solid electrolyte layer) of a transistor sensor, and using a metal oxide (inorganic semiconductor) containing one or more specific metal elements as the channel layer, and further setting the carbon and hydrogen contents in the gate insulation layer (solid electrolyte layer) within predetermined ranges, it is possible to achieve higher sensitivity and a significantly lower detection limit value than conventional transistor sensors, as well as higher stability in the presence of moisture, etc., and further reducing detection time, effort, and cost compared to conventional methods, thereby completing the present invention.

[0010] That is, in order to solve the above problems, the present invention provides the following means.

[0011] [1] A semiconductor device comprising: a substrate; a channel layer provided on one surface of the substrate; and a solid electrolyte layer provided between the substrate and the channel layer or on a surface of the channel layer opposite to the substrate side, the channel layer including an inorganic semiconductor; the solid electrolyte layer comprises an inorganic solid electrolyte, A transistor sensor comprising an exposed portion in which at least a portion of either or both of the channel layer and the solid electrolyte layer is exposed to the outside.

[0012] [2] The transistor sensor according to [1] above, wherein the solid electrolyte layer is formed of either a metal oxide containing a rare earth element and zirconium (Zr) or a metal oxide containing a rare earth element and tantalum (Ta), the channel layer is formed of a metal oxide containing at least indium (In), the carbon (C) content in the solid electrolyte layer is 0.5 atom% or more and 15 atom% or less, and the hydrogen (H) content in the solid electrolyte layer is 2 atom% or more and 20 atom% or less.

[0013] [3] The solid electrolyte layer has an ionic conductivity of 1×10 -8 The transistor sensor according to the above [1] or [2], characterized in that it has a resistivity of 1.5 S / cm or more.

[0014] [4] The transistor sensor according to any one of the above [1] to [3], wherein the surface of the exposed portion has a capture field that directly or indirectly captures a biological material.

[0015] [5] The transistor sensor according to [4] above, wherein the capture field has a probe molecule fixed thereto for capturing the biological material.

[0016] [6] The transistor sensor according to any one of the above [1] to [5], further comprising a holding portion on the exposed portion, capable of holding a liquid containing a biological material.

[0017] [7] The transistor sensor according to any one of the above [1] to [6], further comprising a conductive material layer in contact with at least a portion of the solid electrolyte layer, the conductive material layer being electrically insulated from layers other than the solid electrolyte layer.

[0018] [8] Further, a source electrode and a drain electrode connected to the channel layer; a reference electrode that is inserted into a liquid containing a biological material when the liquid containing a biological material is placed so as to contact the exposed portion; The transistor sensor according to any one of the above [1] to [7], further comprising a detection unit that detects the biological substance based on a voltage between the source electrode and a current between the source electrode and the drain electrode.

[0019] [9] A method for detecting a biological substance using the transistor sensor according to [8] above, supplying a liquid containing a biological material to the exposed portion; inserting the reference electrode into a liquid containing the biological material; applying a voltage between the reference electrode and the source electrode of the transistor sensor while measuring a current between the source electrode and the drain electrode of the transistor sensor, and detecting the biological substance based on the voltage between the reference electrode and the source electrode and the current between the source electrode and the drain electrode. Effect of the Invention

[0020] According to the present invention, it is possible to realize high sensitivity, a low detection limit, and high stability of detection, and further to detect biological materials quickly, easily, and at low cost. [Brief description of the drawings]

[0021] [Figure 1] FIG. 1(a) is a cross-sectional view (a cross-sectional view taken along line II in FIG. 1(b)) showing an example of the configuration of a transistor sensor according to a first embodiment of the present invention, and FIG. 1(b) is a plan view. [Diagram 2] 2(a) to 2(d) are cross-sectional views showing an example of a process for producing the transistor sensor of FIG. 1(a). [Diagram 3] FIG. 3 is a schematic diagram showing a method for detecting DNA using the transistor sensor of FIG. [Figure 4] FIG. 4 is a graph showing the VTG-IDS characteristics of the transistor sensor of Example 1 of the present invention. [Diagram 5] FIG. 5 is a graph showing the VTG-IDS characteristics of a conventional transistor sensor. [Figure 6] FIG. 6 is a cross-sectional view of a transistor sensor for explaining the function of the gate insulating layer (solid electrolyte layer) and the back gate electrode (conductive material layer). [Figure 7] 7(a) to 7(d) are schematic diagrams showing an example of a detection method in which the detection of target DNA is repeatedly performed using the transistor sensor of FIG. [Figure 8] 8(a) and 8(b) are graphs showing the relationship between the top gate voltage VTG and the drain current IDS when the width of the channel layer in the transistor sensor of FIG. 1 is changed. [Figure 9] 9(a) to 9(d) are schematic diagrams showing an example of a comparative experiment in which target DNA is detected without immobilizing probe DNA on the channel layer. [Figure 10] FIG. 10 is a graph showing the relationship between the top gate voltage VTG and the drain current IDS when the concentration of the target DNA is changed using the comparative experiment of FIG. [Figure 11] FIG. 11(a) is a cross-sectional view (a cross-sectional view taken along line II-II in FIG. 11(b)) showing another example of the configuration of the transistor sensor according to the first embodiment of the present invention, and FIG. 11(b) is a plan view. [Figure 12] FIG. 12 is a cross-sectional view showing yet another example of the configuration of the transistor sensor according to the first embodiment of the present invention. [Figure 13] FIG. 13 is a cross-sectional view showing still another example of the configuration of the transistor sensor according to the first embodiment of the present invention. [Figure 14] FIG. 14 is a cross-sectional view showing still another example of the configuration of the transistor sensor according to the first embodiment of the present invention. [Figure 15] FIG. 15 is a cross-sectional view showing still another example of the configuration of the transistor sensor according to the first embodiment of the present invention. [Figure 16] FIG. 16 is a cross-sectional view showing yet another example of the configuration of the transistor sensor according to the first embodiment of the present invention. [Figure 17] FIG. 17 is a cross-sectional view showing yet another example of the configuration of the transistor sensor according to the first embodiment of the present invention. [Figure 18] 18(a) to 18(f) are schematic diagrams showing the process of carrying probe DNA for capturing a biological substance to be measured on a transistor sensor in the embodiment. [Figure 19] FIG. 19(a) is a graph showing the stability evaluation of the transistor sensor in an example in a phosphate buffer, and FIG. 19(b) is a graph showing the stability evaluation in serum. [Figure 20] FIG. 20 is a graph showing the VTG-IDS characteristics measured using the transistor sensor produced in the example. [Figure 21] FIG. 21 is a graph in which the target DNA concentration of the sample in the graph of FIG. 20 is plotted on the horizontal axis, and the VTG value at which the IDS read from the graph of FIG. 20 reached 1 μA is plotted on the vertical axis. [Figure 22] FIG. 22 is a plan view of the transistor sensor fabricated in Example 12 of the present invention. [Figure 23] FIG. 23 is a graph showing a Cole-Cole plot of the impedance of the solid electrolyte measured in Example 15 of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings. The drawings used in the following description may show characteristic parts in an enlarged scale for the sake of convenience in order to make the characteristics of the embodiment easier to understand, and the dimensional ratios of each component may differ from the actual ones.

[0023] [Transistor sensor configuration] FIG. 1(a) is a cross-sectional view (a cross-sectional view taken along line II in FIG. 1(b)) showing an example of the configuration of a transistor sensor according to a first embodiment of the present invention, and FIG. 1(b) is a plan view. As shown in Fig. 1(a) and Fig. 1(b), the transistor sensor 10 includes a substrate 11, a back gate electrode (conductive material layer) 12, a gate insulating layer (solid electrolyte layer) 13, a channel layer 14, a source electrode 15, and a drain electrode 16, in this order. In the transistor sensor 10 of this embodiment, a gate insulating layer (solid electrolyte layer) 13 of a solid electrolyte is formed between the substrate 11 or the back gate electrode (conductive material layer) 12 and the channel layer 14, particularly between the back gate electrode (conductive material layer) 12 and the channel layer 14. The gate insulating layer (solid electrolyte layer) 13 and the channel layer 14 form an exposed portion 17 exposed to the outside. The back gate electrode (conductive material layer) 12 may be omitted.

[0024] The substrate 11 can be made of various insulating substrates such as, for example, high heat resistant glass, a SiO2 / Si substrate (i.e., a substrate in which a silicon oxide film is formed on a silicon substrate. Hereinafter, simply referred to as "substrate"), an alumina (Al2O3) substrate, an STO (SrTiO) substrate, an insulating substrate in which an STO (SrTiO) layer is formed on the surface of a Si substrate via a SiO2 layer and a Ti layer, a semiconductor substrate (for example, a Si substrate, a SiC substrate, a Ge substrate, etc.) The thickness of the substrate 11 is not particularly limited, but is, for example, 10 μm or more and 1 mm or less.

[0025] The back gate electrode 12 is a conductive material layer containing a conductive material. The back gate electrode (conductive material layer) 12 may be formed only from a conductive material. The back gate electrode (conductive material layer) 12 can be formed from any of metals such as platinum (Pt), gold (Au), silver (Ag), copper (Cu), aluminum (Al), molybdenum (Mo), palladium (Pd), ruthenium (Ru), iridium (Ir), tungsten (W), titanium (Ti), metal materials such as alloys containing the metals, and metal oxides such as indium tin oxide (ITO) and ruthenium oxide (RuO2). The back gate electrode (conductive material layer) 12 can be formed from a single layer formed from any of the above metals, metal materials such as alloys, and metal oxides, or a multilayer formed by laminating them. The thickness of the back gate electrode (conductive material layer) 12 is not particularly limited, but is, for example, 50 nm or more and 200 nm or less. The back gate electrode (conductive material layer) 12 may be electrically insulated from everything except the gate insulating layer (solid electrolyte layer) 13.

[0026] The gate insulating layer 13 is a solid electrolyte layer containing a solid electrolyte. The gate insulating layer (solid electrolyte layer) 13 may be formed only from a solid electrolyte. The gate insulating layer (solid electrolyte layer) 13 may be formed from, for example, any one of a metal oxide containing a rare earth element and zirconium (Zr) and a metal oxide containing a rare earth element and tantalum (Ta). The content of carbon (C) in the gate insulating layer (solid electrolyte layer) 13 may be 0.5 atom% or more and 15 atom% or less, and the content of hydrogen (H) in the gate insulating layer (solid electrolyte layer) 13 may be 2 atom% or more and 20 atom% or less. When the gate insulating layer (solid electrolyte layer) 13 is made of the above metal oxide and the contents of carbon (C) and hydrogen (H) in the gate insulating layer (solid electrolyte layer) 13 are both within the above ranges, the transistor sensor 10 becomes highly sensitive and the detection limit is significantly lowered by a combination with a metal oxide described later that constitutes the channel layer 14, and the stability of detection in the presence of moisture or the like is also increased.

[0027] The gate insulating layer (solid electrolyte layer) 13 has an ionic conductivity of 1×10 -8 The ionic conductivity of the gate insulating layer (solid electrolyte layer) 13 is preferably 1×10 -2 S / cm or less. Specifically, the gate insulating layer (solid electrolyte layer) 13 can be formed of, for example, any one of the following (A1) to (A5). (A1) Metal oxide containing lanthanum (La) and zirconium (Zr) (A2) Metal oxides containing lanthanum (La) and tantalum (Ta) (A3) A metal oxide containing any metal element selected from the group consisting of cerium (Ce), praseodymium (Pr), neodymium (Nd), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), lutetium (Lu), and yttrium (Y), and zirconium (Zr) or tantalum (Ta). (A4) Metal oxide containing at least one metal element selected from the group consisting of hafnium (Hf), zirconium (Zr) and aluminum (Al) (A5) Oxides containing lanthanum (La), hafnium (Hf), and zirconium (Zr)

[0028] For example, when the gate insulating layer (solid electrolyte layer) 13 is formed of a metal oxide containing lanthanum (La) and zirconium (Zr) (A1), the atomic ratio of lanthanum (La) to zirconium (Zr) in the gate insulating layer (solid electrolyte layer) 13 is not particularly limited, but for example, when lanthanum (La) is 1, zirconium (Zr) is preferably 0.43 or more and 2.33 or less, and more preferably 1 or more and 2.33 or less. By having the atomic ratio of lanthanum (La) to zirconium (Zr) in the gate insulating layer (solid electrolyte layer) 13 within the above range, high sensing performance (typically high field effect mobility and high gate capacitor capacity) can be obtained. In addition, when the gate insulating layer (solid electrolyte layer) 13 is formed of a metal oxide containing lanthanum (La) and tantalum (Ta) (A2), the atomic ratio of lanthanum (La) to tantalum (Ta) in the gate insulating layer (solid electrolyte layer) 13 is not particularly limited. Furthermore, even when the gate insulating layer (solid electrolyte layer) 13 is formed of any of the metal oxides (A3) to (A5) above, the atomic ratio of each metal element is not particularly limited.

[0029] The above-mentioned atomic composition ratios are determined by elemental analysis using Rutherford backscattering spectrometry (RBS method), etc. In particular, the carbon (C) and hydrogen (H) contents are determined by elemental analysis using Rutherford backscattering spectrometry (RBS analysis method), hydrogen forward scattering spectrometry (HFS analysis method), and nuclear reaction analysis (NRA analysis method) using Pelletron 3SDH manufactured by National Electrostatics Corporation.

[0030] The gate insulating layer (solid electrolyte layer) 13 can be composed of a single layer made of, for example, any of the above metal oxides. When the gate insulating layer (solid electrolyte layer) 13 is composed of a layer of a metal oxide made of lanthanum (La) and zirconium (Zr), it is also called an LZO layer. When the gate insulating layer (solid electrolyte layer) 13 is composed of a layer of a metal oxide made of lanthanum (La) and tantalum (Ta), it is also called an LTO layer.

[0031] The thickness of the gate insulating layer (solid electrolyte layer) 13 is not particularly limited, but is, for example, 50 nm to 300 nm. If the thickness of the gate insulating layer (solid electrolyte layer) 13 exceeds 300 nm, it is not preferable because it may affect the interface characteristics of the channel layer 14. On the other hand, if the thickness is less than 50 nm, it is not preferable from the viewpoints of an increase in leakage current and deterioration of the coverage of the film to the substrate.

[0032] The channel layer 14 is an inorganic semiconductor layer containing an inorganic semiconductor. The channel layer 14 may be formed only from an inorganic semiconductor. In addition to widely used Si, the inorganic semiconductor may be, for example, zinc oxide or an In-containing metal oxide containing at least indium (In). By forming the channel layer 14 from the above zinc oxide or In-containing metal oxide, the sensitivity of the transistor sensor 10 can be significantly improved by a combination with the above metal oxide of the gate insulating layer (solid electrolyte layer) 13, particularly the content of carbon (C) and hydrogen (H) in the gate insulating layer (solid electrolyte layer) 13, and the stability of detection in the presence of moisture or the like can be increased.

[0033] Examples of In-containing metal oxides include the following oxides (B1) to (B6). (B1) Metal oxide made of indium (In) (B2) Metal oxide containing indium (In) and tin (Sn) (B3) Metal oxide containing indium (In) and zinc (Zn) (B4) Metal oxide containing indium (In), zirconium (Zr), and zinc (Zn) (B5) Metal oxide containing indium (In) and gallium (Ga) (B6) Metal oxide containing indium (In), zinc (Zn) and gallium (Ga)

[0034] For example, when the channel layer 14 is formed of a metal oxide containing indium (In) and tin (Sn) (B2), it can contain tin (Sn) having an atomic ratio of 0.001 to 0.03 when indium (In) is taken as 1. When the channel layer 14 is formed of a metal oxide containing indium (In) and zinc (Zn) (B3), it can contain zinc (Zn) having an atomic ratio of 0.001 to 0.75 when indium (In) is taken as 1. When the channel layer 14 is formed of a metal oxide containing indium (In), zirconium (Zr), and zinc (Zn) (B4), it can contain zinc (Zn) having an atomic ratio of 0.001 to 0.75 when indium (In) is taken as 1, and zirconium (Zr) having an atomic ratio of 0.015 to 0.075.

[0035] Furthermore, when the channel layer 14 is formed of a metal oxide containing indium (In) and gallium (Ga) (B5), it can contain gallium (Ga) having an atomic ratio of 0.001 to 0.75 when indium (In) is taken as 1. When the channel layer 14 is formed of a metal oxide containing indium (In), zinc (Zn) and gallium (Ga) (B6), it can contain zinc (Zn) having an atomic ratio of 0.001 to 0.75 when indium (In) is taken as 1, and gallium (Ga) having an atomic ratio of 0.001 to 0.75.

[0036] It has also been confirmed that the above-mentioned metal oxide, which is the material of the channel layer 14, is in an amorphous phase or a nanocrystalline phase. Therefore, it is considered that a good interface state can be obtained with the gate insulating layer (solid electrolyte layer) 13, which is in an amorphous phase and in contact with the channel layer 14. As a result, a transistor sensor 10 with good electrical characteristics can be formed.

[0037] The channel layer 14 may be composed of a single layer made of, for example, the metal oxide. The thickness of the channel layer 14 is not particularly limited, but is preferably, for example, 5 nm to 80 nm from the viewpoint of covering the gate insulating layer (solid electrolyte layer) 13 with high accuracy and from the viewpoint of facilitating modulation of the conductivity of the channel layer 14.

[0038] In addition, when the channel layer 14 is made of a metal oxide layer containing indium (In) (B1), it is also called an InO layer. When the channel layer 14 is made of a metal oxide layer containing indium (In) and tin (Sn) (B2), it is also called an ITO (Indium Tin Oxide) layer. When the channel layer 14 is made of a metal oxide layer containing indium (In) and zinc (Zn) (B3), it is also called an IZO layer. When the channel layer 14 is made of a metal oxide layer containing indium (In), zinc (Zn), and zirconium (Zr) (B4), it is also called a ZIZO layer.

[0039] The width W (FIG. 1(b)) of the channel layer 14 is preferably as large as possible from the standpoint of noise, and is, for example, 100 μm or more and, for example, 1000 μm or less. The length L of the channel layer 14 is, for example, 50 μm or more and 200 μm or less.

[0040] In addition, in this embodiment, the channel layer 14 has a thickness thinner than both the source electrode 15 and the drain electrode 16, but this is not limited thereto, and the source electrode 15 and the drain electrode 16 may have the same thickness or may have a thickness thicker than them.

[0041] The source electrode 15 and the drain electrode 16 are disposed, for example, on the gate insulating layer (solid electrolyte layer) 13 and on both sides of the channel layer 14. The source electrode 15 and the drain electrode 16 can be formed, for example, from any of a high-melting point metal such as platinum (Pt), a metal material such as an alloy containing the high-melting point metal, and a metal oxide such as indium tin oxide (ITO) or ruthenium oxide (RuO2), without being particularly limited thereto. The source electrode 15 can be formed of a single layer formed of any of the above-mentioned metals, metal materials such as alloys thereof, and metal oxides, or a multi-layer formed by stacking them. The drain electrode 16 can also be formed of a single layer formed of any of the above-mentioned metals, metal materials such as alloys thereof, and metal oxides, or a multi-layer formed by stacking them. In this embodiment, the source electrode 15 is formed of a multi-layer formed by stacking a first source electrode 15x and a second source electrode 15y. The drain electrode 16 is formed of a multi-layer formed by stacking a first drain electrode 16x and a second drain electrode 16y. The thickness of the source electrode 15 and the drain electrode 16 is not particularly limited, but is, for example, not less than 50 nm and not more than 1000 nm.

[0042] [Manufacturing method of transistor sensor] 2(a) to 2(d) are cross-sectional views showing an example of a process for manufacturing the transistor sensor 10 of FIG. 1(a). (1) Formation of the back gate electrode (conductive material layer) First, as shown in FIG. 2(a), a back gate electrode (conductive material layer) 12 is formed on a base material, a SiO2 / Si substrate (hereinafter, simply referred to as the "substrate") 11, by known sputtering, photolithography and etching methods.

[0043] (2) Formation of gate insulating layer (solid electrolyte layer) Next, a precursor solution for a gate insulating layer (solid electrolyte layer) containing a precursor containing a rare earth element and a precursor containing zirconium (Zr) as solutes, or a precursor solution for a gate insulating layer (solid electrolyte layer) containing a precursor containing a rare earth element and a precursor containing tantalum (Ta) as solutes is formed on the back gate electrode (conductive material layer) 12 by a known spin coating method. In this embodiment, for example, a precursor layer for a gate insulating layer (solid electrolyte layer) is formed using a precursor solution for a gate insulating layer (solid electrolyte layer) containing a precursor containing lanthanum (La) and a precursor containing zirconium (Zr) as solutes as a starting material.

[0044] At this time, the precursor solution for the gate insulating layer (solid electrolyte layer) may be adjusted so that the carbon (C) content in the finally formed gate insulating layer (solid electrolyte layer) 13 is 0.5 atom % or more and 15 atom % or less, and the hydrogen (H) content in the gate insulating layer (solid electrolyte layer) 13 is 2 atom % or more and 20 atom % or less. Specifically, the precursor solution for the gate insulating layer (solid electrolyte layer) may be adjusted by the following methods (2-1) to (2-3). (2-1) Dissolve lanthanum acetate in propionic acid by heating at 110°C for 30 minutes to obtain a 0.2 mol / kg solution. (2-2) Dissolve zirconium butoxide in propionic acid by heating at 110°C for 30 minutes to obtain a 0.2 mol / kg solution. (2-3) The above solutions (2-1) and (2-2) are mixed at room temperature. From the viewpoint of further improving the characteristics as a transistor sensor, the above-mentioned carbon (C) content may be 1 atom % or more and 10 atom % or less, and the hydrogen (H) content in the gate insulating layer (solid electrolyte layer) 13 may be 5 atom % or more and 18 atom % or less.

[0045] An example of a precursor containing lanthanum (La) is lanthanum acetate. Other examples include lanthanum nitrate, lanthanum chloride, or various lanthanum alkoxides (e.g., lanthanum isopropoxide, lanthanum butoxide, lanthanum ethoxide, lanthanum methoxyethoxide). Also, an example of a precursor containing zirconium (Zr) is zirconium butoxide. Other examples include zirconium nitrate, zirconium chloride, or various other zirconium alkoxides (e.g., zirconium isopropoxide, zirconium butoxide, zirconium ethoxide, zirconium methoxyethoxide).

[0046] An example of a precursor containing tantalum (Ta) is tantalum butoxide. Other examples include tantalum nitrate, tantalum chloride, or various other tantalum alkoxides (e.g., tantalum isopropoxide, tantalum butoxide, tantalum ethoxide, tantalum methoxyethoxide).

[0047] Examples of precursors containing cerium (Ce) include Ce octylate and Ce nitrate. Examples of precursors containing praseodymium (Pr) include Pr octylate and Pr nitrate. Examples of precursors containing neodymium (Nd) include Nd octylate and Nd nitrate. Examples of precursors containing samarium (Sm) include Sm octylate and Sm nitrate. Examples of precursors containing europium (Eu) include Eu octylate and Eu nitrate. Examples of precursors containing gadolinium (Gd) include Gd octylate and Gd nitrate. Examples of precursors containing terbium (Tb) include Tb octylate and Tb nitrate. Examples of precursors containing dysprosium (Dy) include Dy octylate and Dy nitrate. Examples of precursors containing holmium (Ho) include Ho octylate and Ho nitrate. Examples of precursors containing erbium (Er) include Er octylate, Er nitrate, etc. Examples of precursors containing thulium (Tm) include Tm octylate, Tm nitrate, etc. Examples of precursors containing ytterbium (Yb) include Yb octylate, Yb nitrate, etc. Examples of precursors containing lutetium (Lu) include Lu octylate, Lu nitrate, etc. Examples of precursors containing yttrium (Y) include Y octylate, Y nitrate, etc.

[0048] Examples of precursors containing hafnium (Hf) include Hf octylate, Hf nitrate, Hf butoxide, etc. Examples of precursors containing aluminum (Al) include Al octylate, Al nitrate, Al butoxide, etc.

[0049] Thereafter, the pre-baking is performed by heating at 80°C or higher and 250°C or lower for a predetermined time. This pre-baking allows the solvent in the precursor layer for the gate insulating layer (solid electrolyte layer) to be sufficiently evaporated, and also allows a preferable gel state (presumably a state before thermal decomposition in which organic chains remain) to be formed in order to develop properties that enable future plastic deformation. From the viewpoint of achieving the above-mentioned viewpoint with a higher degree of certainty, the pre-baking temperature is preferably 100°C or higher and 250°C or lower. This temperature range is also the preferable temperature range for pre-baking of other materials. This pre-baking is performed in an oxygen atmosphere or in the air (hereinafter, also collectively referred to as an "oxygen-containing atmosphere"). In this embodiment, in order to finally obtain a sufficient thickness (e.g., 120 nm) of the gate insulating layer (solid electrolyte layer) 13, the formation of the precursor layer for the gate insulating layer (solid electrolyte layer) by the spin coating method and the pre-baking are repeated multiple times.

[0050] Thereafter, as the main firing, the precursor layer for the gate insulating layer (solid electrolyte layer) is heated in an oxygen-containing atmosphere (for example, but not limited to, an oxygen content of 100 volume %. The same applies to the "oxygen-containing atmosphere" below) at a temperature in the range of 250°C to 450°C for a predetermined time. As a result, as shown in FIG. 2(b), a gate insulating layer (solid electrolyte layer) 13 which is either a metal oxide containing a rare earth element and zirconium (Zr) or a metal oxide containing a rare earth element and tantalum (Ta) is formed on the back gate electrode (conductive material layer) 12.

[0051] (3) Formation of source and drain electrodes Then, a resist film (not shown) patterned by a known photolithography method is formed on the gate insulating layer (solid electrolyte layer) 13. Then, a first electrode layer and a second electrode layer are formed on the gate insulating layer (solid electrolyte layer) 13 and the resist film by a known sputtering method. In this embodiment, for example, an ITO layer and a Pt layer are formed in this order on the gate insulating layer (solid electrolyte layer) 13 to form a first electrode layer composed of an ITO layer and a Pt layer, and a second electrode layer composed of an ITO layer and a Pt layer. When forming the ITO layer, for example, an ITO layer target material containing 5 wt% tin oxide (SnO2) can be used. Then, the resist film is removed, and as shown in FIG. 2(c), a source electrode 15 composed of a first source electrode (ITO layer) 15x and a second source electrode (Pt) 15y and a drain electrode 16 composed of a first drain electrode (ITO layer) 16x and a second drain electrode (Pt) 16y are formed on the gate insulating layer (solid electrolyte layer) 13.

[0052] (4) Formation of the channel layer Further, after that, a channel layer precursor layer is formed by a known spin coating method using a channel layer precursor solution containing at least indium (In) as a solute as a starting material on the gate insulating layer (solid electrolyte layer) 13. In this embodiment, for example, a channel layer precursor layer is formed using a channel layer precursor solution as a starting material shown in any one of the following (C1) to (C6). (C1) Precursor solution for channel layer containing indium (In) as a solute (C2) A precursor solution for a channel layer containing a precursor containing indium (In) and a precursor containing tin (Sn) as solutes (C3) A precursor solution for a channel layer containing a precursor containing indium (In) and a precursor containing zinc (Zn) as solutes (C4) A precursor solution for a channel layer containing a precursor containing indium (In), a precursor containing zirconium (Zr), and a precursor containing zinc (Zn) as solutes (C5) A precursor solution for a channel layer containing a precursor containing indium (In) and a precursor containing gallium (Ga) as solutes (C6) A precursor solution for a channel layer containing a precursor including indium (In), a precursor including zinc (Zn), and a precursor including gallium (Ga) as solutes

[0053] In addition, the above-mentioned channel layer precursor solution further contains at least one baking promoter selected from the group consisting of acetylacetonate, urea, and ammonium acetate, and an oxidizing agent, examples of which include nitrates, peroxides, and perchlorates.

[0054] Examples of precursors containing indium (In) include indium nitrate. Other examples include indium acetylacetonate, indium acetate, indium chloride, or various indium alkoxides (e.g., indium isopropoxide, indium butoxide, indium ethoxide, indium methoxyethoxide). An example of a precursor containing tin (Sn) is tin chloride. Other examples include tin nitrate, tin acetate, or various tin alkoxides (e.g., tin isopropoxide, tin butoxide, tin ethoxide, tin methoxyethoxide). Examples of the precursor containing zinc (Zn) include zinc chloride. Other examples include zinc nitrate, zinc acetate, or various zinc alkoxides (e.g., zinc isopropoxide, zinc butoxide, zinc ethoxide, zinc methoxyethoxide).

[0055] An example of a precursor containing zirconium (Zr) is zirconium butoxide. Other examples include zirconium nitrate, zirconium chloride, or various other zirconium alkoxides (e.g., zirconium isopropoxide, zirconium butoxide, zirconium ethoxide, zirconium methoxyethoxide).

[0056] An example of a precursor containing gallium (Ga) is gallium isopropoxide. Other examples include gallium methoxide, gallium ethoxide, gallium n-propoxide, gallium butoxide, gallium nitrate, and gallium octoate.

[0057] Then, the channel layer precursor layer is pre-baked at a temperature in the range of 80° C. to 250° C. for a predetermined time. Then, the channel layer precursor layer is pre-baked at a temperature in the range of 250° C. to 400° C. for a predetermined time in an oxygen-containing atmosphere. As a result, a channel layer 14, which is a metal oxide containing at least indium (In), is formed on the gate insulating layer (solid electrolyte layer) 13, as shown in FIG. 2(d).

[0058] FIG. 3 is a schematic diagram showing a method of detecting DNA using the transistor sensor 10 of FIG. 3, first, if necessary, a wall portion 22 is placed so as to surround the exposed portion 17 (channel layer 14) of the transistor sensor 10. This makes it possible to form a liquid holding portion 18 capable of holding a liquid Lq containing a biological material at least on the upper portion of the channel layer 14 and inside the wall portion 22. The wall portion 22 is disposed so as to surround, for example, the channel layer 14, at least a portion of the source electrode 15, and at least a portion of the drain electrode 16.

[0059] Next, a probe molecule for capturing a specific biological substance (biomolecule) is immobilized on the channel layer 14. The probe molecule is not particularly limited, but may be, for example, an antibody or single-stranded DNA. At this time, the probe molecule may be immobilized not only on the channel layer 14 but also on the gate insulating layer (solid electrolyte layer) 13. In this way, the transistor sensor 10 has a capture field that indirectly captures the biological material to be measured (e.g., target DNA) on the channel layer 14. This capture field can also be called a capture surface that captures the biological material, and the capture surface is formed on the surface of the channel layer 14. Probe molecules (e.g., probe DNA) for capturing the biological material are fixed to the capture field or the capture surface.

[0060] The above-mentioned method for immobilizing the probe molecules is merely an example, and the probe molecules may be immobilized on the transistor sensor 10 by a method other than the above. Also, a capture field may be formed on the channel layer 14 by a method other than the above.

[0061] After immobilizing the biological material on the probe molecule as described above, it is preferable to perform a blocking treatment on the channel layer 14 (or on the channel layer 14 and the gate insulating layer (solid electrolyte layer) 13) to suppress non-specific binding.

[0062] Next, a liquid containing a biological material is placed so as to contact the channel layer 14 (or the channel layer 14 and the gate insulating layer (solid electrolyte layer) 13), and the biological material contained in the liquid that is to be measured is specifically bound to the probe molecule. The biological material is not particularly limited, but is, for example, nucleic acid such as DNA or mRNA. In this embodiment, for example, a liquid Lq containing a biological material (such as a mixture of a buffer solution and serum containing nucleic acid) is supplied onto the channel layer 14, and the liquid Lq is held in the liquid holding portion 18.

[0063] Thereafter, it is preferable to wash away with a washing solution the biological material not bound to the probe molecule, the biological material not to be measured, or the biological material bound nonspecifically. After washing, a measurement solution such as a buffer solution is supplied onto the channel layer 14 (or onto the channel layer 14 and the gate insulating layer (solid electrolyte layer) 13). This allows the channel layer 14 and the reference electrode 21 to be electrically connected via the measurement solution.

[0064] Next, the reference electrode 21 is inserted into the liquid Lq to electrically connect the reference electrode 21 and the source electrode 15, and a voltage V is applied between the reference electrode 21 and the source electrode 15 using a second voltage supply unit 24. TG Then, the source electrode 15 and the drain electrode 16 of the transistor sensor 10 are electrically connected to each other, and a voltage V is applied between the source electrode 15 and the drain electrode 16 using the first voltage supply unit 23. DS When a current I flows between the source electrode 15 and the drain electrode 16,DS Then, the voltage V between the reference electrode 21 and the source electrode 15 is measured. TG (hereinafter, also referred to as top gate voltage) and the current I between the source electrode 15 and the drain electrode 16 DS (hereinafter also referred to as drain current) and a biological substance is detected based on the drain current.

[0065] In this transistor sensor 10, a so-called top gate structure is formed, and a voltage V TG When the biological substance to be measured specifically binds to the probe molecule captured on the channel layer 14, a change in charge occurs, causing a current I DS changes, and the current I DS Depending on the change in V TG -I DS The change in the property is detected, which allows the amount of the particular biological substance being measured to be determined.

[0066] In this embodiment, no voltage is applied to the back gate electrode (conductive material layer) 12. However, this is not limiting. A voltage V BG may be applied. The back gate electrode (conductive material layer) 12 may be configured as a floating electrode. Furthermore, the back gate electrode (conductive material layer) 12 itself does not have to be provided.

[0067] FIG. 4 shows the V TG -I DS 4 is a graph showing the characteristics of a thin-film transistor of Example 1 of the present invention, which is fabricated under the conditions shown in Table 1 as an example of the transistor sensor 10, and a voltage V TG and current I DS V obtained from the measured value TG -I DS The characteristics are as follows. The method for producing the transistor sensor according to the first example of the present invention will be described later in the Examples section.

[0068] [Table 1]

[0069] As shown in FIG. 4, in the transistor sensor 10 of this embodiment, when the heating temperature during the formation of the gate insulating layer (solid electrolyte layer) 13 and the heating temperature during the formation of the channel layer 14 are 300° C. and 400° C., respectively, and the carbon (C) and hydrogen (H) contents in the gate insulating layer (solid electrolyte layer) 13 are 2.3 atom % and 10.8 atom %, respectively, the top gate voltage V TG V ranges from 0.6V to 1.5V, and V TG -I DS It was found that the curve shifted to the lower voltage side and responded almost linearly. In particular, even when the target DNA was 1 pg / mL, the drain current I DS is the top gate voltage V TG This shows that the transistor sensor 10 has high detection stability in liquid even in the low concentration range of the target DNA, and the concentration range in which the target DNA can be detected is at least 1 pg / mL or more.

[0070] Figure 5 shows the V TG -I DS In FIG. 5, as an example of a conventional transistor sensor, a transistor (TFT sensor) was fabricated under the conditions shown in Table 1, and the voltage V TG and current I DS V obtained from the measured value TG -I DS The characteristics are as follows. A method for manufacturing a conventional TFT sensor will be described in the examples below. As shown in Fig. 5, in the conventional transistor sensor, the heating temperatures for forming the gate insulating layer (insulator layer) and the channel are 550°C and 500°C, respectively, and the carbon (C) and hydrogen (H) contents in the gate insulating layer (insulator layer) are 0.4 atom% and 1.8 atom%, respectively. TG -I DSThe curves were scattered. In particular, when the concentrations of target DNA were 1ng / mL, 100pg / mL, 10pg / mL, and 1pg / mL, the V TG -I DS The curve was distorted. This shows that with the conventional transistor sensor, detection of target DNA in liquids below 1 ng / mL was unstable, and the concentration range in which target DNA can be detected was greater than 1 ng / mL.

[0071] In other words, whereas the detection limit of target DNA in conventional transistor sensors (conventional TFT sensors) is approximately 1 ng / mL, the detection limit of target DNA in the transistor sensor 10 of this embodiment (Example 1 of the present invention) is 1 pg / mL, which shows that the detection limit of the transistor sensor 10 is approximately 1,000 times higher than the detection limit of the conventional transistor sensors.

[0072] In this manner, it is presumed that in the transistor sensor 10 of this embodiment, by setting each of the carbon (C) and hydrogen (H) contents in the gate insulating layer (solid electrolyte layer) 13 to fall within a specific range, it may be possible to realize extremely sensitive detection and measurement.

[0073] In addition, in the transistor sensor 10 of this embodiment, the gate insulating layer (solid electrolyte layer) 13 is provided, thereby improving the sensitivity to the target DNA 32 and the stability of detection by widening the detectable range of the target DNA. The function of the gate insulating layer (solid electrolyte layer) will be described with reference to FIG. 6. FIG. 6 is a cross-sectional view of a transistor sensor for explaining the function of the gate insulating layer (solid electrolyte layer) and the back gate electrode (conductive material layer). In the conventional transistor sensor, when the probe DNA 31 fixed on the surface of the channel layer 14 captures the target DNA 32, the electric field generated by the charge of the target DNA 32 changes the electric current flowing through the channel layer 14 or the electric characteristics such as the IV characteristics. In this case, only the target DNA 32 captured on the surface of the channel layer 14 can contribute to the change. On the other hand, in the transistor sensor 10 of the present embodiment, the electric field (arrow D1) generated by the charge of the target DNA 32 captured on the probe DNA 31 fixed on the surface of the channel layer 14 and the electric field (arrow D2) generated by the charge of the target DNA 32 captured on the probe DNA 31 fixed on the surface of the gate insulating layer (solid electrolyte layer) 13 are transmitted to the channel layer 14 by ions moving inside the gate insulating layer (solid electrolyte layer) 13, and can contribute to the change in the electric characteristics (antenna effect). As a result, the electric field generated by the charge of more target DNA 32 is accumulated in the channel layer 14, improving the sensitivity and stability. The transistor sensor 10 of this embodiment can also have an electronically conductive back gate electrode (conductive material layer) 12 in contact with the gate insulating layer (solid electrolyte layer) 13. This has the effect of transmitting the electric field created by the charges of the captured target DNA 32 to the channel faster, farther, and in greater quantities.

[0074] 7(a) to 7(d) are schematic diagrams showing an example of a detection method in which the detection of target DNA is repeatedly performed using the transistor sensor 10 of FIG.

[0075] A liquid in which the concentration of the probe DNA has been adjusted to a predetermined value is supplied onto the channel layer 14, and the probe DNA 31 is immobilized on the channel layer 14 by the method shown in FIG. 3 (FIG. 7(a)). When the probe DNA 31 is immobilized on the channel layer 14, the probe DNA 31 may also be immobilized on the gate insulating layer (solid electrolyte layer) 13. Next, the target DNA 32 is captured by hybridization (FIG. 7(b)). Thereafter, V TG -I DS Measure the characteristics.

[0076] When measurements are to be performed repeatedly, a buffer solution such as PBS may then be supplied onto the channel layer 14, and the target DNA 32 may be released into the buffer solution by, for example, heating at 90°C for 5 minutes (FIG. 7(c)). The surface of the channel layer 14 may then be washed with pure water to remove the target DNA 32 from the channel layer 14 (FIG. 7(d)). In this case, liquids with different concentrations of the probe DNA 31 may be supplied onto the channel layer 14, and the V TG -I DS By repeating these steps, the characteristics can be measured using multiple liquids with different concentrations of the probe DNA 31. TG and the drain current I DS It is possible to measure the following:

[0077] 8(a) and 8(b) show the top gate voltage V when the width W of the channel layer 14 in the transistor sensor 10 of FIG. TG and the drain current I DS 8(a) is a graph showing the relationship between the gate insulating layer (solid electrolyte layer) 13 and the channel layer 14. In FIG. 8(a), a transistor sensor 10 is used in which the gate insulating layer (solid electrolyte layer) 13 is made of LZO and the channel layer 14 is made of indium oxide (In2O3). The width W of the channel layer 14 is 200 μm, the length L is 50 μm, and the concentrations of the target DNA are 1 pg / mL, 10 pg / mL, 100 pg / mL, and 1000 pg / mL. In FIG. 8(b), measurements are performed under the same conditions as in FIG. 8(a), except that the width W of the channel layer 14 is changed to 400 μm.

[0078] As shown in Fig. 8(a), the top gate voltage V TG is in the range of 0 or more (0≦V TG ), V TG -I DS It can be seen that the characteristics generally shift to the lower right as the concentration of the target DNA increases. In particular, when the concentration of the target DNA is an extremely small amount of 1 pg / mL, TG -I DS The characteristics are different for other concentrations of V TG -I DS The characteristics show a similar trend, and the top gate voltage VTG As the drain current I DS is increasing.

[0079] In addition, as shown in FIG. 8(b), when the width W of the channel layer 14 is twice as large as the width W of the channel layer 14 in FIG. 8(a), the top gate voltage V TG is in the range of 0 or more (0≦V TG ), V TG -I DS It can be seen that the characteristics generally shift downward and to the right with increasing concentration of target DNA.

[0080] 8(a) and 8(b), it can be seen that the detection range of hybridization is at least 1 pg / mL to 1 ng / mL in the transistor sensor 10. The fact that the detection limit of the transistor sensor 10 configured as described above is extremely high at 1 pg / mL is presumably due to, for example, a high product of electron mobility and gate capacitance.

[0081] 9(a) to 9(d) are schematic diagrams showing an example of a comparative experiment in which target DNA is detected without immobilizing probe DNA on the channel layer 14. In FIG.

[0082] In a comparative experiment, a transistor sensor 10 is fabricated by a method similar to that shown in FIG. 2 (FIG. 9(a)), and a liquid containing a biological material such as target DNA 32 is supplied onto the channel layer 14 (or onto the channel layer 14 and the gate insulating layer (solid electrolyte layer) 13) using a pipette or the like (FIG. 9(b)). Thereafter, if necessary, the biological material is cultured for, for example, 30 minutes. At this time, the biological material such as target DNA 32 is adsorbed onto the surface 14a of the channel layer 14 by physical adsorption (FIG. 9(c)).

[0083] The transistor sensor 10 configured as described above does not have a capture field that directly captures biological materials on the channel layer 14. Therefore, when the channel layer 14 is subsequently washed with pure water or the like, biological materials such as the target DNA 32 are easily detached from the surface 14a of the channel layer 14 (FIG. 9(d)).

[0084] Figure 10 shows the top gate voltage V when the concentration of the target DNA is changed using the comparative experiment of Figure 9. TG and the drain current I DS 10 is a graph showing the relationship between the gate insulating layer (solid electrolyte layer) 13 and the channel layer 14 of a transistor sensor 10 formed of LZO and indium oxide (In2O3), respectively. The concentrations of the target DNA are 1 nM / mL and 1 μM / mL.

[0085] As shown in Figure 10, when the concentration of target DNA is 1 nM / mL, V TG -I DS The characteristics are V TG -I DS The characteristics are almost the same as those of the target DNA at a concentration of 1 nM / mL. TG -I DS There is almost no change in the characteristics. This indicates that non-specifically bound biological substances and the like are removed from the channel layer 14 by washing the channel layer 14, and as a result, non-specifically bound biological substances and the like are not detected, and only specifically bound biological substances are detected.

[0086] As described above, according to this embodiment, the channel layer 14 contains an inorganic semiconductor, and the gate insulating layer (solid electrolyte layer) 13 contains an inorganic solid electrolyte. Therefore, no amplification is required, and high sensitivity with a low detection limit value and high stability of detection are achieved. Furthermore, it becomes possible to detect biological substances quickly and easily at low cost. When the gate insulating layer (solid electrolyte layer) 13 is formed of either a metal oxide containing a rare earth element and zirconium (Zr) or a metal oxide containing a rare earth element and tantalum (Ta), the channel layer 14 is formed of a metal oxide containing at least indium (In), the carbon (C) content in the gate insulating layer (solid electrolyte layer) 13 is 0.5 atom% or more and 15 atom% or less, and the hydrogen (H) content in the gate insulating layer (solid electrolyte layer) 13 is 2 atom% or more and 20 atom% or less, it is possible to detect target DNA in single molecule units in a shorter time than before due to high sensitivity and low detection limit value, and it is possible to realize high-precision detection in a short time when analyzing infectious diseases, new cancer markers, individual genes, exosomes, mRNA in white blood cells, cell-free RNA / DNA, etc. In addition, in the medical field, it is possible to detect biological substances related to the patient during the examination of the patient, and it is possible to perform prompt and appropriate diagnosis and treatment based on the detection results. Furthermore, the above manufacturing method makes it possible to provide a transistor sensor 10 that is excellent in industrial applicability and mass productivity.

[0087] Furthermore, according to this embodiment, a liquid containing a biological material such as target DNA is supplied onto the channel layer 14 of the transistor sensor 10, a voltage is applied between the reference electrode 21 inserted into the liquid containing the biological material and the source electrode 15 of the transistor sensor 10, and the current between the source electrode 15 and the drain electrode 16 of the transistor sensor 10 is measured, and the biological material is detected based on the voltage between the reference electrode 21 and the source electrode 15 and the current between the source electrode 15 and the drain electrode 16. Therefore, this detection method makes it possible to detect biological materials with high sensitivity in a short time with the same simple operation and at the same cost as conventional methods.

[0088] It is also possible to provide a biological substance detection device having a multi-structure or array structure in which a plurality of the transistor sensors 10 of this embodiment are arranged. Furthermore, it is also possible to provide a biological substance detection device including both the transistor sensor 10 of this embodiment and other electrochemical sensors such as a known carbon sensor. This makes it possible to achieve highly accurate detection in a short time, and to simultaneously detect both biological substances such as mRNA / DNA and other biological substances such as biomarkers, and to perform analysis from various viewpoints using the detection results of a plurality of biological substances obtained in one detection operation.

[0089] Although the embodiments of the present invention have been described in detail above, the present invention is not limited to the above-described embodiments, and various modifications and variations are possible within the scope of the gist of the present invention as described in the claims.

[0090] For example, in the transistor sensor 10 of this embodiment, the reference electrode 21 is configured to be separated from the source electrode 15 and the drain electrode 16, but the arrangement of the reference electrode 21 is not limited to this. The reference electrode 21 may be arranged in the same member as the source electrode 15 and the drain electrode 16.

[0091] An example of a transistor sensor 10 in which a reference electrode 21 is disposed on the same member as the source electrode 15 and the drain electrode 16 on the substrate 11 is shown in Fig. 11. Fig. 11(a) is a cross-sectional view (cross-section taken along line II-II in Fig. 11(b)) showing another example of the configuration of the transistor sensor according to the first embodiment of the present invention, and Fig. 11(b) is a plan view.

[0092] As shown in FIG. 11(a) and FIG. 11(b), the transistor sensor 10a has three back gate electrodes (conductive material layers) 12 provided on a substrate 11, and a gate insulating layer (solid electrolyte layer) 13 covering the back gate electrodes (conductive material layers) 12. A reference electrode 21 is provided on the gate insulating layer (solid electrolyte layer) 13. Three sensor pieces each including a source electrode 15, a drain electrode 16, and a channel layer 14 are provided on the gate insulating layer (solid electrolyte layer) 13. The three sensor pieces are respectively disposed above the three back gate electrodes (conductive material layers) 12. In order to keep the distance from the reference electrode 21 to each sensor piece constant, the sensor pieces and the back gate electrodes (conductive material layers) 12 are disposed on a concentric circle centered on the reference electrode 21. The reference electrode 21 is connected to a reference electrode lead wire 21a. The source electrode 15 of each sensor piece is connected to a source electrode lead wire 15a. The drain electrodes 16 of the sensor pieces are connected to separate drain electrode lead wires 16a.

[0093] In addition, the transistor sensor 10 of this embodiment includes a substrate 11, a back gate electrode (conductive material layer) 12, a gate insulating layer (solid electrolyte layer) 13, a channel layer 14, a source electrode 15, and a drain electrode 16 in this order, and the exposed portion 17 is at least a part of the channel layer 14, but is not limited to this configuration. Figs. 12 to 17 show still another example of the configuration of the transistor sensor according to the first embodiment of the present invention. The transistor sensors 10b to 10d shown in Figs. 12 to 14 are configured such that the exposed portion 17 can be at least a part of the channel layer 14 or at least a part of the channel layer 14 and the gate insulating layer (solid electrolyte layer) 13. The transistor sensors 10e to 10g shown in Figs. 15 to 17 are configured such that the exposed portion 17 is at least a part of the gate insulating layer (solid electrolyte layer) 13.

[0094] 12, a gate insulating layer (solid electrolyte layer) 13 is disposed on a substrate 11. A channel layer 14 is disposed on the gate insulating layer (solid electrolyte layer) 13, and a source electrode 15 and a drain electrode 16 are formed on the channel layer 14. The source electrode 15 and the drain electrode 16 are sized so that their ends are located inside the ends of the gate insulating layer (solid electrolyte layer) 13.

[0095] In a transistor sensor 10c shown in FIG. 13, a source electrode 15 and a drain electrode 16 are disposed on a substrate 11. The source electrode 15 and the drain electrode 16 are covered with a gate insulating layer (solid electrolyte layer) 13. A channel layer 14 is formed on the gate insulating layer (solid electrolyte layer) 13. The channel layer 14 is connected to the source electrode 15 and the drain electrode 16 via a through hole 20 provided in the gate insulating layer (solid electrolyte layer) 13. In addition, the gate insulating layer (solid electrolyte layer) 13 is provided with a through hole 20 for connecting the source electrode 15 and the drain electrode 16 to an external power supply.

[0096] 14, a gate insulating layer (solid electrolyte layer) 13 is disposed on a substrate 11. A source electrode 15 and a drain electrode 16 are disposed on the gate insulating layer (solid electrolyte layer) 13. A transistor sensor 10e shows a configuration in which the back gate electrode (conductive material layer) 12 is not provided in the transistor sensor 10 shown in FIG.

[0097] 15, a channel layer 14 is disposed on a substrate 11, and a source electrode 15 and a drain electrode 16 are formed on the channel layer 14. The channel layer 14, the source electrode 15 and the drain electrode 16 are covered with a gate insulating layer (solid electrolyte layer) 13. The gate insulating layer (solid electrolyte layer) 13 is provided with a through hole 20 for connecting the source electrode 15 and the drain electrode 16 to an external power supply.

[0098] In a transistor sensor 10f shown in Fig. 16, a channel layer 14 is disposed on a substrate 11. The channel layer 14 is covered with a gate insulating layer (solid electrolyte layer) 13. A source electrode 15 and a drain electrode 16 are formed on the gate insulating layer (solid electrolyte layer) 13. The source electrode 15 and the drain electrode 16 are connected to the channel layer 14 via a through hole 20 provided in the gate insulating layer (solid electrolyte layer) 13.

[0099] 17, a source electrode 15 and a drain electrode 16 are disposed on a substrate 11, and a channel layer 14 is formed on the source electrode 15 and the drain electrode 16. The channel layer 14, the source electrode 15, and the drain electrode 16 are covered with a gate insulating layer (solid electrolyte layer) 13. The gate insulating layer (solid electrolyte layer) 13 is provided with a through hole 20 for connecting the source electrode 15 and the drain electrode 16 to an external power supply.

[0100] In the transistor sensor 10 of this embodiment, the backgate electrode (conductive material layer) 12 is disposed between the substrate 11 and the gate insulating layer (solid electrolyte layer) 13, but the arrangement of the backgate electrode (conductive material layer) 12 is not limited to this. However, it is preferable that the backgate electrode (conductive material layer) 12 is in contact with at least a part of the gate insulating layer (solid electrolyte layer) 13. The backgate electrode (conductive material layer) 12 may be electrically insulated from layers other than the gate insulating layer (solid electrolyte layer) 13. The backgate electrode (conductive material layer) 12 may be disposed, for example, inside the gate insulating layer (solid electrolyte layer) 13.

[0101] Furthermore, the transistor sensor 10 of the present embodiment may be a thin-film transistor sensor in which a gate insulating layer (solid electrolyte layer) 13 of a solid electrolyte is formed between the substrate 11 or the back gate electrode (conductive material layer) 12 and the channel layer 14, the gate insulating layer (solid electrolyte layer) 13 being formed of either a metal oxide containing a rare earth element and zirconium (Zr) or a metal oxide containing a rare earth element and tantalum (Ta), the channel layer 14 being formed of a metal oxide containing at least indium (In), and the carbon (C) content in the gate insulating layer (solid electrolyte layer) 13 being 0.5 atom% or more and 15 atom% or less, and the hydrogen (H) content in the gate insulating layer (solid electrolyte layer) 13 being 2 atom% or more and 20 atom% or less. EXAMPLES

[0102] EXAMPLES Examples of the present invention will be described below, but the present invention is not limited to the following examples.

[0103] [Examples 1-2] Using the above-mentioned manufacturing method, a substrate, gate electrode, gate insulating layer (solid electrolyte layer), channel layer, source electrode, and drain electrode were formed in the shape shown in Figure 1 with the materials and thicknesses shown in Table 1 to fabricate a transistor sensor. The material of the gate insulating layer (solid electrolyte layer) was LZO, the material of the channel layer was indium oxide (In2O3), and the width W of the channel layer was 300 μm and the length L was 50 μm. The heating temperature when forming the gate insulating layer (solid electrolyte layer) was 400°C, and the heating temperature when forming the channel layer was 300°C.

[0104] The carbon (C) and hydrogen (H) contents in the gate insulating layer (solid electrolyte layer) were measured by Rutherford Backscattering Spectrometry (RBS analysis), Hydrogen Forward Scattering Spectrometry (HFS analysis), and Nuclear Reaction Analysis (NRA analysis) (Pelletron 3SDH, National Electrostatics Corporation), and the water content of carbon (C) was found to be 2.0 atom%, and the hydrogen (H) content was found to be 10.1 atom%.

[0105] Next, after forming the channel layer according to the above-mentioned manufacturing method (Fig. 18(a)), the surface of the channel layer was washed with ethanol and pure water. Next, the surface was treated with a solution of hydrogen peroxide, ammonium water, and water mixed at a volume ratio (v / v) of 1:1:5 at room temperature for 10 minutes, and then rinsed with pure water and dried at 110°C for 10 minutes (Fig. 18(b)).

[0106] Next, the surface was treated with an ethanol solution containing 10% by volume of 3-aminopropyltriethoxysilane in ethanol at room temperature for 30 minutes, then washed with pure water and dried at 120°C for 20 minutes (Fig. 18(c)). Then, the surface was treated with a solution containing 2.5% by volume of glutaraldehyde in phosphate buffer at room temperature for 30 minutes, and washed with pure water (Fig. 18(d)). Then, a liquid containing a probe DNA was supplied to the surface of the channel layer, and the probe DNA was fixed by chemical bonding (Fig. 18(e)). This formed a capture field on the channel layer that indirectly captures biological materials such as single-stranded target DNA via the probe DNA. A single-stranded probe DNA (also called 6C-DNA) with an amino group and a linker consisting of six carbons attached to the 5' side was used, and the probe DNA had a molecular weight of 20 bases; 6232 MW; Tm 57 o It was confirmed that the amino acid sequence of this product is "AmC6-CC TA TC GC TG CT AC CG TG AA-3'".

[0107] Then, a target DNA (also called cDNA) that constitutes a complementary DNA to the probe DNA was supplied, and the target DNA was captured on the channel layer by hybridization between the probe DNA and the target DNA (Figure 18(f)). The target DNA was "20 bases; 6182 MW; Tm 57 o It was confirmed that the gene had the sequence shown in Figure 1C, 5'-TT CA CG GT AG CA GC GA TA GG-3'.

[0108] Example 1 Phosphate buffer (PBS) is supplied onto the channel layer, and a voltage V is applied between the source electrode and the back gate electrode (conductive material layer). BG The voltage V applied between the source and drain electrodes is 1.0 V. DS is set to 0.5V, and V TG -I DS The characteristics were measured, and the results are shown in Figure 19(a). From the results of Fig. 19(a), even when the measurement was repeated 10 times, V TG -I DS Almost no change in characteristics was observed, indicating that the transistor sensor exhibits high detection stability in phosphate buffer.

[0109] Example 2 A number of mixtures of serum and phosphate buffer with concentrations of 1%, 2%, 3%, 5%, and 7% were supplied onto the channel layer, and a voltage V BG to 1.0V, voltage V DS is 0.2V, and V TG -I DS The characteristics were measured, and the results are shown in Figure 19(b). From the results in Figure 19(b), even if the serum concentration in the mixture was changed in the range from 1% to 7%, V TG -I DS There was almost no change in the characteristics. Therefore, it was found that the transistor sensor exhibits high detection stability even in a mixed solution containing serum.

[0110] In the examples, the transistor sensor exhibits high detection stability both in phosphate buffer and in a mixed solution containing serum. This is presumably because the transistor sensor is very stable in aqueous solution and effectively suppresses non-specific binding in the gate insulating layer (solid electrolyte layer) and / or channel layer.

[0111] [Example 3] (Example 1 of the present invention) The transistor was fabricated under the conditions shown in Table 1. Specifically, the transistor was fabricated as follows. A SiO2 / Si substrate was prepared by forming a 500 nm thick silicon oxide (SiO2) film on a silicon substrate. A 10 nm thick titanium (Ti) layer and a 100 nm thick platinum (Pt) layer were formed in that order on the silicon oxide film of the SiO2 / Si substrate by sputtering to form a back gate electrode (conductive material layer) consisting of a Pt / Ti two-layered conductive material layer.

[0112] On the obtained back gate electrode (conductive material layer), a gate insulating layer (solid electrolyte layer) was formed by the sol-gel method. First, La 0.5 Zr 0.5 The precursor layer for the gate insulating layer (solid electrolyte layer) was then pre-baked at 250°C in an oxygen-containing atmosphere, and then baked at 400°C to form a 120 μm-thick LaO solution. 0.5 Zr 0.5 The gate insulating layer (solid electrolyte layer) was formed from a LaO layer (solid electrolyte layer). 0.5 Zr 0.5 The O solution was prepared as follows. Lanthanum acetate 1.5-hydrate and zirconium butoxide were mixed in a 1:1 (molar ratio) ratio, and the resulting mixture was treated with La 0.5 Zr 0.5The resulting mixed solution was refluxed in an oil bath at 110°C for 30 minutes, and then filtered through a membrane filter with a pore size of 0.2 μm to obtain a 0.2 mol / kg LaO concentration. 0.5 Zr 0.5 O solution was obtained.

[0113] A resist film patterned into the shape of the source electrode and the drain electrode was formed on the obtained gate insulating layer (solid electrolyte layer) by photolithography. Next, a 50 nm thick ITO layer and a 100 nm thick platinum (Pt) layer were formed in this order by sputtering on the gate insulating layer (solid electrolyte layer) on which the resist film was formed, and then the resist film was removed. A source electrode and a drain electrode with a two-layer structure of Pt / ITO were formed. The size of the source electrode and the drain electrode was 320 μm wide x 200 μm long, respectively, and the distance between the source electrode and the drain electrode was 50 μm.

[0114] Next, a resist film patterned into the shape of the channel layer was formed on the gate insulating layer (solid electrolyte layer) by photolithography. Next, an In2O3 solution was applied as a channel layer precursor solution by spin coating on the gate insulating layer (solid electrolyte layer) on which the resist film was formed, to form a channel layer precursor layer. Next, the channel layer precursor layer was pre-baked at 250°C, and then baked at 300°C in an oxygen-containing atmosphere to form a channel layer made of In2O3 (inorganic semiconductor) with a thickness of 20 μm. The size of the channel layer was 300 μm wide x 50 μm long. The In2O3 solution was prepared as follows. Indium nitrate trihydrate was dissolved in 2-methoxyethanol to give an In2O3 concentration of 0.2 mol / kg. The resulting solution was refluxed in an oil bath at 110°C for 30 minutes, and then filtered through a membrane filter with a pore size of 0.2 μm to obtain an In2O3 solution with a concentration of 0.2 mol / kg.

[0115] (Conventional TFT sensor) A conventional TFT sensor was fabricated in the same manner as in Example 1 of the present invention, except that the temperature for the main baking of the precursor layer for the gate insulating layer (solid electrolyte layer) was 550°C and the temperature for the main baking of the precursor layer for the channel layer was 500°C.

[0116] (Example 2 of the present invention) Sm as a precursor solution for the gate insulating layer (solid electrolyte layer) 0.1 Zr 0.9 Using O solution, Sm 0.1 Zr 0.9 A transistor sensor of Example 2 of the present invention was fabricated in the same manner as in Example 1 of the present invention, except that a gate insulating layer (solid electrolyte layer) made of an O layer was formed. 0.1 Zr 0.9 The O solution was prepared as follows. Samarium acetate tetrahydrate and zirconium butoxide were mixed in a molar ratio of 1:9, and the resulting mixture was treated as Sm 0.1 Zr 0.9 The resulting mixture was refluxed in an oil bath at 110°C for 30 minutes, and then filtered through a membrane filter with a pore size of 0.2 μm to obtain a 0.2 mol / kg Sm 0.1 Zr 0.9 O solution was obtained.

[0117] (Example 3 of the present invention) Sm as a precursor solution for the gate insulating layer (solid electrolyte layer) 0.3 Zr 0.7 Using O solution, Sm 0.3 Zr 0.7 A transistor sensor of Example 3 of the present invention was fabricated in the same manner as in Example 1 of the present invention, except that a gate insulating layer (solid electrolyte layer) made of an O layer was formed. 0.3 Zr 0.7 The O solution was prepared in the same manner as in Invention Example 3, except that samarium acetate tetrahydrate and zirconium butoxide were mixed in a molar ratio of 3:7.

[0118] (Example 4 of the present invention) Dy as a precursor solution for the gate insulating layer (solid electrolyte layer)0.1 Zr 0.9 DyO solution was used. 0.1 Zr 0.9 A transistor sensor of Example 4 of the present invention was fabricated in the same manner as in Example 1 of the present invention, except that a gate insulating layer (solid electrolyte layer) made of an O layer was formed. 0.1 Zr 0.9 The O solution was prepared as follows. Dysprosium acetate tetrahydrate and zirconium butoxide were mixed in a molar ratio of 1:9, and the resulting mixture was treated with Dy 0.1 Zr 0.9 The resulting mixture was refluxed in an oil bath at 110°C for 30 minutes, and then filtered through a membrane filter with a pore size of 0.2 μm to obtain a DyO concentration of 0.2 mol / kg. 0.1 Zr 0.9 O solution was obtained.

[0119] (Example 5 of the invention) Dy as a precursor solution for the gate insulating layer (solid electrolyte layer) 0.3 Zr 0.7 DyO solution was used. 0.3 Zr 0.7 A transistor sensor of Example 5 of the present invention was fabricated in the same manner as in Example 1 of the present invention, except that a gate insulating layer (solid electrolyte layer) made of an O layer was formed. 0.3 Zr 0.7 The O solution was prepared in the same manner as in Invention Example 5, except that dysprosium acetate tetrahydrate and zirconium butoxide were mixed in a molar ratio of 3:7.

[0120] (Example 6) La as a precursor solution for the gate insulating layer (solid electrolyte layer) 0.3 Ta 0.7 LaO solution was used. 0.3 Ta 0.7 A transistor sensor of Example 6 of the present invention was fabricated in the same manner as in Example 1 of the present invention, except that a gate insulating layer (solid electrolyte layer) made of a La O layer was formed. 0.3 Ta 0.7 The O solution was prepared as follows. Lanthanum acetate 1.5 hydrate and tantalum butoxide were mixed in a molar ratio of 3:7, and the resulting mixture was treated as La 0.3 Ta 0.7 The mixture was refluxed in an oil bath at 110°C for 30 minutes, and then filtered through a membrane filter with a pore size of 0.2 μm to obtain a LaO concentration of 0.2 mol / kg. 0.3 Ta 0.7 O solution was obtained.

[0121] (Example 7) La as a precursor solution for the gate insulating layer (solid electrolyte layer) 0.3 Ta 0.7 LaO solution was used. 0.3 Ta 0.7 A transistor sensor of Example 7 of the present invention was fabricated in the same manner as in Example 1 of the present invention, except that a gate insulating layer (solid electrolyte layer) made of a LaO layer was formed, a channel layer made of a ZnO layer was formed using a ZnO solution as a precursor solution for the channel layer, and the size of the channel layer was 50 μm wide × 10 μm long. 0.3 Ta 0.7 The O solution was prepared in the same manner as in Invention Example 1, except that lanthanum acetate 1.5 hydrate and zirconium butoxide were mixed in a molar ratio of 3:7. The ZnO solution was prepared as follows. Zinc acetate dihydrate, acetylacetone, and ammonium acetate were mixed in a molar ratio of 1:1:1, and the resulting mixture was dissolved in 2-methoxyethanol to a ZnO concentration of 0.4 mol / kg. The resulting solution was refluxed in an oil bath at 110°C for 30 minutes, and then filtered through a membrane filter with a pore size of 0.2 μm to obtain a ZnO solution with a concentration of 0.4 mol / kg.

[0122] (Example 8) A transistor sensor of Example 8 of the present invention was produced in the same manner as in Example 7 of the present invention, except that the size of the channel layer was 300 μm wide×50 μm long.

[0123] (Example 9) The precursor solution for the channel layer was In 0.33 Ga 0.33 Zinc 0.33 Using InO solution, 0.33 Ga 0.33 Zinc 0.33 A transistor sensor of Example 10 of the present invention was fabricated in the same manner as in Example 7 of the present invention, except that a channel layer made of an InO layer was formed. 0.33 Ga 0.33 Zinc 0.33 The O solution was prepared as follows. Indium nitrate trihydrate, gallium nitrate n-hydrate (n = 7 to 9), and zinc acetate dihydrate were mixed in a molar ratio of 1:1:1, and the resulting mixture was treated as In 0.33 Ga 0.33 Zinc 0.33 The resulting solution was refluxed in an oil bath at 110°C for 30 minutes, and then filtered through a membrane filter with a pore size of 0.2 μm to obtain an In concentration of 0.4 mol / kg. 0.33 Ga 0.33 Zinc 0.33 O solution was obtained.

[0124] (Example 10) A transistor sensor of Example 10 of the present invention was produced in the same manner as in Example 9 of the present invention, except that the size of the channel layer was 300 μm wide×50 μm long.

[0125] Comparative Example 1 The transistor sensor of Comparative Example 1 was fabricated in the same manner as in Example 1 of the present invention, except that a back gate electrode (conductive material layer) and a gate insulating layer (solid electrolyte layer) were not provided, i.e., a source electrode, a drain electrode, and a channel layer were formed on the silicon oxide film of the SiO2 / Si substrate.

[0126] (evaluation) The carbon (C) and hydrogen (H) contents in the gate insulating layer (solid electrolyte layer) of the transistor sensors fabricated in Inventive Examples 2 to 10 were measured by the method described above. The sensing characteristics of the transistor sensors fabricated in Inventive Examples 2 to 10 and Comparative Example 1 were measured by the method described below. The results are shown in Table 2 below.

[0127] (Method of measuring sensing characteristics) A resist film is formed by photolithography, mainly on the channel layer. A square DNA probe carrying area (carrying portion) of 750 μm×750 μm was formed. The DNA probe carrying area (carrying portion) includes a gate insulating layer (solid electrolyte layer) and a channel layer. Furthermore, a wall was provided on the outer periphery of the DNA probe carrying area (carrying portion) to form a liquid holding portion including the channel layer and the gate insulating layer (solid electrolyte layer). Next, a probe DNA for capturing a biological material to be measured was carried on the DNA probe carrying area (carrying portion) by the above-mentioned method.

[0128] As samples, target DNA solutions with target DNA concentrations of 10ag / mL, 1fg / mL, and 100fg / mL and a blank were prepared. Each sample was supplied to the liquid holder and V TG -I DS The characteristics were measured. TG -I DS The characteristics are measured by applying a voltage V between the source and drain electrodes. DS The measurement was performed under the condition of 0.2 V. TG -I DS An example of the characteristics is shown in Figure 20. From the graph in Figure 20, I DS V when reaches 1μA TG The value of V was read. Then, the target DNA concentration of the sample was plotted on the horizontal axis. TGA graph in which the values ​​are plotted on the vertical axis is shown in FIG. 21. The slope of the line connecting the plotted points shown in FIG. 21 was taken as the sensing characteristic (unit: mV / decade). A high value of the sensing characteristic indicates high sensitivity. From the viewpoint of improving the sensitivity to the target DNA and the stability of detection by widening the detectable range of the target DNA, the sensing characteristic is preferably 10 mV / decade or more, and particularly preferably 20 mV / decade or more.

[0129] [Table 2]

[0130] The results shown in Table 2 show that the transistor sensors of Examples 2 to 10 of the present invention, in which the gate electrode layer is a solid electrolyte layer containing an inorganic solid electrolyte, have sensing characteristics of 10 mV / decade or more, and have improved sensitivity to target DNA and detection stability.

[0131] (Examples 11 to 14) La as a precursor solution for the gate insulating layer (solid electrolyte layer) 0.3 Zr 0.7 LaO solution was used. 0.3 Zr 0.7 The transistor sensors of Examples 11 to 14 of the present invention were fabricated in the same manner as in Example 1 of the present invention, except that a gate insulating layer (solid electrolyte layer) made of an O layer was formed. 0.3 Zr 0.7 The O solution was prepared as follows. Lanthanum acetate 1.5 hydrate and zirconium butoxide were mixed in a molar ratio of 3:7, and the resulting mixture was treated as La 0.3 Zr 0.7 The mixture was refluxed in an oil bath at 110°C for 30 minutes, and then filtered through a membrane filter with a pore size of 0.2 μm to obtain a concentration of 0.2 mol / kg La. 0.3 Zr 0.7 O solution was obtained.

[0132] In Examples 11 to 14 of the present invention, the size of the DNA probe carrying area (carrying portion) for capturing the target DNA by carrying the probe DNA was changed, that is, the size of the portion in contact with the target DNA solution, and the sensing characteristics were measured for the obtained transistor sensor. The size of the DNA probe carrying area was adjusted by forming a resist film on the surface of the transistor sensor by photolithography. FIG. 22 is a plan view of the transistor sensor fabricated in Example 12 of the present invention. As shown in FIG. 22, the transistor sensor 10h includes a channel layer 14, and a source electrode 15 and a drain electrode 16 connected to the channel layer 14. The source electrode 15 is connected to a source electrode lead wire 15a, and the drain electrode 16 is connected to a drain electrode lead wire 16a. The periphery of the channel layer 14, the source electrode 15 and the source electrode lead wire 15a, and the drain electrode 16 and the drain electrode lead wire 16a are covered with a resist film 19a, and the portion not covered with the resist film 19a is the DNA probe carrying area 19b, that is, the portion in contact with the target DNA solution. The size of the channel layer 14 is 300 μm×50 μm, and the size of the DNA probe carrying area 19b is 500 μm×500 μm. In the present invention example 11, the size of the DNA probe carrying area 19b was set to 300 μm×50 μm, and the area other than the channel layer 14 was covered with the resist film 19a. In the present invention example 13, the size of the DNA probe carrying area 19b was set to 750 μm×750 μm. In the present invention example 14, the area was not covered with the resist film 19a.

[0133] [Table 3]

[0134] From the results shown in Table 3, it can be seen that the sensing characteristics improve as the area of ​​the DNA probe carrying area 19b (carrying portion) increases. This is believed to be because the effect of increasing the amount of change in electrical characteristics (antenna effect) due to the electric field created by the charge of the target DNA captured by the probe DNA in the gate insulating layer (solid electrolyte layer) being transmitted to the channel layer.

[0135] (Example 14 of the invention) It was confirmed by AC impedance measurement as follows that the metal oxide (RZrO) containing a rare earth element (R) and zirconium (Zr) used in this example was a solid electrolyte membrane, i.e., exhibited ionic conductivity. The measurement sample was prepared as follows. First, a Ti / Pt electrode film (lower electrode film) was formed on a SiO2 / Si substrate by sputtering in the same manner as in Example 1 of the present invention. Next, a RZrO film was formed to a thickness of 120 nm on the lower electrode film by the sol-gel method. The SiO2 / Si substrate with the RZrO film was placed on a 20×20 mm 2 and place a 5×5 mm square on the RZrO film. 2 A stainless steel contact mask with a square hole of 5 × 5 mm was placed on the substrate. 2 A square ITO / Pt electrode film (upper electrode film) was formed by sputtering. In this way, a measurement sample was fabricated in which the SiO2 / Si substrate, lower electrode film, RZrO film, and upper electrode film were laminated in this order.

[0136] The measurements were performed using an AC impedance measuring device (SP-300, manufactured by Biologic). The lower and upper electrode films of the above-mentioned measurement sample were connected to the AC impedance measuring device using Al tab electrode tape, and the lower and upper electrode films were bonded to the Al tab electrode tape using Ag paste. The measurement conditions were AC frequency range: 0.1 to 7 MHz, AC voltage amplitude: 0.1 mV. Figure 23 shows a graph of a Cole-Cole plot of the real and imaginary parts of the AC impedance measured for a sample in which the RZrO film was a LaZrO film (LaZrO, La:Zr=3:7) containing rare earth elements La and Zr. As shown in Figure 23, an arc appears in the profile, and analysis of the arc revealed that the conductivity was 6.0 × 10 -7 The ionic conductivity of the other RZrO films was measured in the same manner. The RZrO films used in the present invention all had an ionic conductivity of 1.0×10 -8 It was confirmed that the value was ≥ 1.0 S / cm. [Explanation of symbols]

[0137] 10, 10a, 10b, 10c, 10e, 10f, 10g, 10h Transistor Sensor 11 Substrate 12 Back gate electrode (conductive material layer) 13 Gate insulation layer (solid electrolyte layer) 14 Channel Layer 14a surface 15 Source electrode 15a Source electrode lead 16 Drain electrode 16a Drain electrode lead 17 Exposed part 18 Liquid holding part 19a Resist film 19b DNA probe carrying area 20 Through hole 21 Reference electrode 21a Reference electrode lead wire 22 Wall 23 First voltage supply unit 24 Second voltage supply unit 31 Probe DNA 32 Target DNA

Claims

1. A semiconductor device comprising: a substrate; a channel layer provided on one surface of the substrate; and a solid electrolyte layer provided between the substrate and the channel layer or on a surface of the channel layer opposite to the substrate; the channel layer comprises an inorganic semiconductor; the solid electrolyte layer comprises an inorganic solid electrolyte, A transistor sensor comprising an exposed portion in which at least a portion of either or both of the channel layer and the solid electrolyte layer is exposed to the outside.

2. 2. The transistor sensor according to claim 1, wherein the solid electrolyte layer is formed of any one of a metal oxide containing a rare earth element and zirconium (Zr) and a metal oxide containing a rare earth element and tantalum (Ta), the channel layer is formed of a metal oxide containing at least indium (In), a carbon (C) content in the solid electrolyte layer is 0.5 atom % or more and 15 atom % or less, and a hydrogen (H) content in the solid electrolyte layer is 2 atom % or more and 20 atom % or less.

3. The solid electrolyte layer has an ionic conductivity of 1×10 －８ 3. The transistor sensor according to claim 1, wherein the resistivity is 1.0 S / cm or more.

4. 4. The transistor sensor according to claim 1, wherein a surface of the exposed portion has a capture field that directly or indirectly captures a biological material.

5. The transistor sensor according to claim 4 , wherein a probe molecule for capturing the biological material is immobilized in the capture field.

6. 6. The transistor sensor according to claim 1, further comprising a holding portion capable of holding a liquid containing a biological material, on an upper portion of the exposed portion.

7. The transistor sensor according to any one of claims 1 to 6, further comprising a conductive material layer in contact with at least a portion of the solid electrolyte layer, the conductive material layer being electrically insulated from layers other than the solid electrolyte layer.

8. Furthermore, a source electrode and a drain electrode connected to the channel layer; a reference electrode that is inserted into a liquid containing a biological material when the liquid containing a biological material is placed so as to contact the exposed portion; 8. The transistor sensor according to claim 1, further comprising a detection section that detects the biological material based on a voltage between the source electrode and the current between the source electrode and the drain electrode.

9. A method for detecting a biological material using the transistor sensor according to claim 8, supplying a liquid containing a biological material to the exposed portion; inserting the reference electrode into a liquid containing the biological material; applying a voltage between the reference electrode and the source electrode of the transistor sensor while measuring a current between the source electrode and the drain electrode of the transistor sensor, and detecting the biological substance based on the voltage between the reference electrode and the source electrode and the current between the source electrode and the drain electrode.

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