WO2015088055A1 - Bio-sensor using single electron transistor operating at room temperature, method for manufacturing same, analysis system having same, and analysis method - Google Patents

Abstract

The present invention relates to a bio-sensor using a single electron transistor operating at room temperature, a method for manufacturing the same, an analysis system having the same, and an analysis method. More specifically, the preset invention relates to a bio-sensor using a single electron transistor operating at room temperature comprising: a single electron transistor that has a source and a drain formed on a substrate, a quantum point coulomb channel formed between the source and the drain, and a gate formed on the upper side of the quantum point coulomb channel; a metal oxide sensing layer formed on the upper side of the gate to form a chemical bond with target molecules; and an ion aqueous solution reservoir that has ion aqueous solution with target molecules stored therein and is provided on the upper side of the metal oxide sensing layer such that the ion aqueous solution is brought into contact with the metal oxide sensing layer.

Description

Biosensor using single-electron transistor at room temperature, manufacturing method of biosensor, analysis system having biosensor and analysis method

The present invention relates to a biosensor using a room temperature operating single-electron transistor, a method for manufacturing the biosensor, an analysis system having the biosensor, and an analysis method. More specifically, a T-shaped gate is formed on the quantum dot coulomb channel between the source and the drain of the room temperature operating single-electron transistor to float, and a metal oxide detection layer is formed on the gate. hydrogen ions (H +) that can be generated by chemical bonding reactions of target molecules to be detected in an aqueous solution of ions, including a structure of forming an oxide sensing layer and contacting its surface with an aqueous ionic solution. As other charges are adsorbed on the surface of the sensing layer, the T-type floating gate induces a change in the electrostatic potential of the quantum dot coulomb channel, causing a change in the current between the source and the drain, and detecting the current change to target molecules in the ion solution. The present invention relates to a biosensor capable of analyzing the identity of and a method of analyzing the same.

Detection and quantitative analysis of biopolymers, such as DNA, proteins and viruses, is an important area of healthcare and biotechnology research. The quantum dot single-electron transistor (SET) device technology applied to the present invention can change the distribution of the minute charges generated by the chemical bond reaction between the biomolecules-molecules at a level of 10E-4e / √Hz (one full charge per electron). Ultra-sensitivity sensing is possible to replace the existing FET biosensor.

In particular, when detecting a small amount of target molecules in the aqueous solution by the conventional method, the electrical noise generated to a serious level, there were many problems in the conventional FET method.

Conventional bio-sensing method that can be replaced by the present invention, as in the conventional FET type biosensor, by fixing the recognition material on the gate of the FET to measure the change in the electrical signal generated when the recognition material and the target molecules are combined It is in a form to say. For example, enzyme FETs immobilized on gates, Immuno FETs using antigen-antibody reactions, and ion-sensitive FETs (IS FETs), which are used as actual pH sensors, and similar nanowire FETs. Is possible.

Accordingly, the present invention has been made to solve the above problems, according to an embodiment of the present invention, the 10E-4e / √Hz (10,000 electron charge per million) level of the room temperature operating single-electron transistor technology To detect and analyze the identity of target molecules using ultra-sensitivity sensing characteristics related to the change in the distribution of fine charges in the nanowires, it overcomes the serious noise problem that occurs when detecting very small amount of target molecules in the aqueous solution. The purpose is to provide a biosensor and analysis method that can solve the difficulties of the FET method, including.

Other objects, specific advantages and novel features of the present invention will become more apparent from the following detailed description and preferred embodiments in conjunction with the accompanying drawings.

A first object of the present invention is a biosensor comprising: a single electron transistor having a source and a drain provided on a substrate, a quantum dot coulomb channel provided between the source and drain, and a gate provided on an upper side of the quantum dot coulomb channel; A metal oxide detection layer provided on an upper side of the gate and capable of chemically bonding to a target molecule; And an ion aqueous solution container in which an ion aqueous solution having a target molecule is stored therein and provided in an upper side of the metal oxide detecting layer so that the ion aqueous solution contacts the metal oxide detecting layer. It can be achieved as a biosensor used.

A second object of the present invention is a biosensor, comprising: a plurality of sources provided on a substrate, each of the plurality of drains provided on the substrate at a position spaced apart from the source, at a position opposite to the source and the source; A gate provided on an upper side of the plurality of quantum dot coulomb channels provided between each of the provided drains; A metal oxide detection layer provided on an upper side of the gate and capable of chemically bonding to a target molecule; And an ion aqueous solution container in which an ion aqueous solution having a target molecule is stored therein and provided in an upper side of the metal oxide detecting layer so that the ion aqueous solution contacts the metal oxide detecting layer. It can be achieved as a biosensor used.

A source oxide film layer having a source and a quantum dot coulomb channel and a drain connected to each other and disposed between the substrate, the source and the drain; And a first dielectric layer stacked on an upper side of the source, the quantum dot coulomb channel and the drain, and formed with a trench; And a second dielectric layer deposited over the first dielectric layer and the quantum dot coulomb channel, and the gate may be provided in a trench in which the second dielectric layer is deposited as a T-shaped floating gate.

A source, a quantum dot coulomb channel, and a drain are connected to each other to form a plurality of nanowire structures, and a buried oxide layer disposed between the substrate, the plurality of sources, and the plurality of drains; And a first dielectric layer stacked on an upper side of the plurality of nanowire structures and having trenches formed therein. And a second dielectric layer deposited over the first dielectric layer and the plurality of quantum dot coulomb channels, and the gate may be provided in a trench in which the second dielectric layer is deposited as a T-shaped floating gate.

The metal oxide detection layer may be composed of a tantalum oxide film, an aluminum oxide film, a silicon oxide film, or a silicon nitride film.

When the target molecule is a specific antigen, the upper surface of the metal oxide detection layer may be characterized by including a chemically treated surface layer for immobilizing a specific antibody reacting with the specific antigen.

A third object of the present invention is a method of manufacturing a room temperature operating single-electron transistor having a substrate on which at least one buried oxide layer and an upper silicon layer are stacked, the first step of forming a nanowire structure by etching the upper silicon layer. ; Forming a first dielectric layer on top of the substrate and the nanowire structure; Etching the first dielectric layer to form a trench and a quantum dot coulomb channel; A fourth step of forming a second dielectric layer thereon; Forming a gate in the trench; Depositing a metal oxide detection layer capable of chemically bonding to a target molecule on the gate; And a seventh step of storing an ion aqueous solution having a target molecule therein, and forming an ion aqueous container on the upper side of the metal oxide detection layer such that the ion aqueous solution contacts the metal oxide detection layer. It can be achieved as a method of manufacturing a biosensor using an electronic transistor.

A fourth object of the present invention is a method of manufacturing a biosensor using a single-electron transistor in a room temperature operation having a substrate on which at least one buried oxide layer and an upper silicon layer are stacked, wherein a plurality of nanowire structures are formed by etching the upper silicon layer. Forming a first step; Forming a first dielectric layer on top of the substrate and the plurality of nanowire structures; Etching the first dielectric layer to form a trench and a plurality of quantum dot coulomb channels; A fourth step of forming a second dielectric layer thereon; Forming a gate in the trench; Depositing a metal oxide detection layer capable of chemically bonding to a target molecule on the gate; And a seventh step of storing an ion aqueous solution having a target molecule therein, and forming an ion aqueous container on the upper side of the metal oxide detection layer such that the ion aqueous solution contacts the metal oxide detection layer. It can be achieved as a method of manufacturing a biosensor using an electronic transistor.

In the sixth step, when the target molecule is a specific antigen, the method may further include forming a chemically treated surface layer for immobilizing the upper surface of the metal oxide detection layer with a specific antibody reacting with the specific antigen.

Etching a portion of the second dielectric layer formed by the deposition process between the fourth and fifth steps to form a sidewall spacer; And etching a portion of the first dielectric layer and a portion of the second dielectric layer to form a source and a drain by doping impurities with a gate as a mask.

The seventh step may include depositing an dielectric layer on top of the metal oxide detection layer; Etching the insulating film layer into a container shape until the top surface of the metal oxide detection layer is exposed; And it may be characterized in that it comprises the step of introducing an ion solution containing a target molecule therein.

The first dielectric layer may be formed to have a thickness of 10 nm to 1000 nm through a deposition process, and the second dielectric layer may be formed by a deposition process after a thermal oxidation process or a thermal oxidation process.

The width of the nanowire structure formed by etching the upper silicon layer in the first step may be 1 to 50 nm, and the length may be 0.1 to 10 μm.

In the third step, the trench may be formed to have a width of 1 to 100 nm by etching, and a portion of the thickness of the upper silicon layer may be etched to form a thickness of the quantum dot of 1 to 50 nm.

A fifth object of the present invention is a target molecule analysis system having a biosensor, comprising: a biosensor according to the aforementioned first object; A voltage applying unit having a reference electrode serving as a gate voltage by applying a specific voltage to the ion aqueous solution stored in the ion aqueous solution container of the biosensor; Measuring means for measuring a current flowing between the source and the drain of the biosensor; And analytical means for analyzing the target molecule by measuring a change in current caused by a chemical bond between the target molecule included in the ion aqueous solution and the metal oxide detection layer of the biosensor, based on the data measured by the measurement means. It can be achieved as a target molecule analysis system having a biosensor.

A sixth object of the present invention is a target molecule analysis system having a biosensor, comprising: a biosensor according to the aforementioned second object; A voltage applying unit having a reference electrode serving as a gate voltage by applying a specific voltage to the ion aqueous solution stored in the ion aqueous solution container of the biosensor; Measuring means for measuring each of the currents flowing between the plurality of sources provided in the biosensor and the plurality of drains provided at positions opposite to the sources; And analytical means for analyzing the target molecule by measuring a change in current caused by a chemical bond between the target molecule included in the ion aqueous solution and the metal oxide detection layer of the biosensor, based on the data measured by the measurement means. It can be achieved as a target molecule analysis system having a biosensor.

A seventh object of the present invention is a target molecule analysis method using the analysis system according to the above-mentioned fifth or sixth object, the method comprising: applying a voltage to the ion aqueous solution by a voltage applying unit; Generating a chemical bond of the target molecule contained in the ion aqueous solution; The charges generated by the chemical bonding are adsorbed on the surface of the metal oxide detection layer; Changing the electrostatic potential of the gate of the biosensor by the amount of charge adsorbed on the surface of the metal oxide detection layer; Inducing a change in the electrostatic potential of the quantum dot coulomb channel of the biosensor to generate a current change between the source and the drain; And analyzing the target molecule by detecting a change in current based on the current value between the source and the drain measured by the measuring means by the analyzing means.

The target molecule is a specific antigen, the upper surface of the metal oxide detection layer includes a chemically treated surface layer for immobilizing a specific antibody that reacts with the specific antigen, and the step of adsorbing on the surface of the detection layer is that the specific antigen is applied to the chemically treated surface layer and the antigen. It may be characterized by the step of antibody reaction.

The amount of charge may be characterized as being a certain amount of positive or negative charge, including H ⁺ .

Accordingly, as described above, according to an embodiment of the present invention, the ultra-sensitivity sensing characteristic related to the distribution change of the minute charge amount of 10E-4e / √Hz (one million charge amount per electron) of the room temperature operation SET technology is used. This is to detect and analyze the identity of the target molecule, and it has the effect of solving the difficulty of the FET method including the nanowire by overcoming the serious noise problem that occurs when detecting the small amount of the target molecule in the test aqueous solution. .

Although the present invention has been described in connection with the above-mentioned preferred embodiments, it will be readily apparent to those skilled in the art that various other modifications and variations are possible without departing from the spirit and scope of the present invention. Are all within the scope of the appended claims.

1 is a perspective view of a biosensor using a room temperature operating single-electron transistor according to a first embodiment of the present invention;

2 is a flow chart of a biosensor manufacturing method using a room temperature operating single-electron transistor according to a first embodiment of the present invention,

3 is a perspective view showing an example of a substrate according to the first embodiment of the present invention;

4 is a perspective view showing a state in which the nanowire structure is formed according to the first embodiment of the present invention;

5 is a perspective view illustrating a state in which a first dielectric layer is formed according to a first embodiment of the present invention;

6 is a perspective view showing a state in which a trench is formed in the first dielectric layer according to the first embodiment of the present invention;

7 is a perspective view illustrating a state in which a quantum dot is formed according to a first embodiment of the present invention;

8 is a perspective view illustrating a state in which a second dielectric layer is formed according to the first embodiment of the present invention;

9 is a cross-sectional view taken along line A-A of FIG. 8;

10 is a perspective view showing an example in which a gate is formed according to a first embodiment of the present invention;

11 is a perspective view illustrating another example in which a sidewall spacer is formed by etching a planar layer of a second dielectric layer formed by a deposition process according to a first embodiment of the present invention;

12 is a perspective view showing a state in which a source and a drain are formed by doping impurities according to the first embodiment of the present invention;

13 is a perspective view of a metal oxide detection layer formed on top according to a first embodiment of the present invention;

14 is a perspective view of an insulating film layer formed on top according to a first embodiment of the present invention;

15 is a perspective view of a biosensor using a single-temperature transistor operating at room temperature according to a first embodiment of the present invention;

16 is a cross-sectional view taken along line B-B of FIG. 15;

17 is a perspective view of a biosensor using a room temperature operating single-electron transistor according to a second embodiment of the present invention;

18 is a plan view of a biosensor using a room temperature operating single-electron transistor according to a second embodiment of the present invention;

19 is a cross-sectional view schematically showing the configuration of a target molecule analysis system having a biosensor according to an embodiment of the present invention;

20 is a flowchart of an analysis method using a target molecule analysis system having a biosensor according to an embodiment of the present invention.

Fig. 21 shows the gate voltage (V _g ) applied by the voltage applying section before (indicated by the solid line) and after (indicated by the dashed line) the injection / chemical coupling of the target molecules contained in the ion aqueous solution and the current values measured by the measuring means. (I _ds ) Characteristic curve The graph shows the change in the amount of charges generated by chemical bonding after injection of the target molecule, or the Coulomb vibration current generated by chemical bonding of the target molecule to the metal oxide detection layer. Show the shift.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, in describing in detail the operating principle of the preferred embodiment of the present invention, if it is determined that the detailed description of the related known functions or configurations may unnecessarily obscure the subject matter of the present invention, the detailed description thereof will be omitted.

In addition, the same reference numerals are used for parts having similar functions and functions throughout the drawings. Throughout the specification, when a part is 'connected' to another part, this includes not only 'directly connected' but also 'indirectly connected' with another element in between. do. In addition, "including" a certain component does not exclude other components unless specifically stated otherwise, it means that may further include other components.

Hereinafter, the configuration and manufacturing method of the biosensor using the room temperature operating single-electron transistor according to the first embodiment of the present invention will be described. First, Figure 1 shows a perspective view of a biosensor using a room temperature operating single-electron transistor according to a first embodiment of the present invention.

As shown in FIG. 1, a biosensor using a single-electron transistor operating at room temperature according to a first embodiment of the present invention includes a source S and a drain D, a source S, and a drain provided on a substrate. A single electron transistor having a quantum dot coulomb channel 22 provided between the D) and a gate G provided on an upper side of the quantum dot coulomb channel 22; A metal oxide detecting layer 50 provided at an upper side of the gate G and capable of chemically bonding to the target molecule 62, and an ion aqueous solution 61 having the target molecule 62 therein are stored, and the ion aqueous solution ( It can be seen that 61 includes an ion aqueous solution 60 provided on the upper side of the metal oxide detection layer 50 so as to contact the metal oxide detection layer 50.

In addition, as shown in FIG. 1, in the biosensor using the single-electron transistor operating at room temperature according to the first embodiment of the present invention, the source S, the quantum dot coulomb channel 22, and the drain D are connected to each other. And a buried oxide layer 10 between the substrate and the source S and the drain D, and stacked on the upper side of the source S, the quantum dot coulomb channel 22 and the drain D, and formed with the trench 31. It can be seen that the first dielectric layer 30, the first dielectric layer 30, and the second dielectric layer 40 deposited on the quantum dot coulomb channel 22 are further included. In addition, the gate G is provided in the trench 31 in which the second dielectric layer 40 is deposited as the T-shaped floating gate G.

In addition, the metal oxide detection layer 50 has an adsorption rate of other charges including hydrogen ions (H +), which may be generated by a chemical coupling reaction of the target molecule 62 to be detected in the ion aqueous solution 61. It consists of metal oxides and electrical insulators, such as a large tantalum oxide film (Ta ₂ O ₅ ), aluminum oxide film (Al ₂ O ₃ ), silicon oxide film (SiO ₂ ) or silicon nitride film (Si 3 N 4).

In addition, in order to maximize the charge adsorption rate on the surface of the metal oxide detection layer 50, the surface may be chemically treated to form a chemically treated surface layer. In addition, when detecting the target molecule 62 using the antibody-antigen reaction, the metal oxide detection layer 50 may be chemically treated to immobilize a specific antibody that acts on a specific antigen. For example, when the target molecule 62 is a prostate specific antigen (PSA), the surface of the metal oxide detection layer 50 may be silanized and immobilized by reacting with an amine group (NH 2) present on the surface of the antibody. .

Hereinafter, each configuration will be described in detail with the biosensor manufacturing method using the room temperature operating single-electron transistor according to the first embodiment. First, FIG. 2 is a flowchart illustrating a method of manufacturing a biosensor using a single-temperature transistor operating at room temperature according to a first embodiment of the present invention.

3 is a perspective view showing an example of a substrate according to the first embodiment of the present invention. The substrate used in the preferred embodiment of the present invention may be a substrate in which the buried oxide layer 10 and the upper silicon layer 20 are repeatedly stacked, but for convenience of description, the silicon substrate 100 is illustrated in FIG. 3. ), An SOI substrate having a structure in which the buried oxide layer 10 and the upper silicon layer 20 are sequentially stacked will be described as an example (S1). In addition, although the silicon substrate 100 and the upper silicon layer 20 may use various kinds of conductors, silicon will be described as an example. The buried oxide film layer 10 will be described using an oxide film or an insulating film as an example.

4 is a partial cross-sectional perspective view showing a state in which the nanowire structure 21 according to the first embodiment of the present invention is formed. As shown in FIG. 4, the nanowire structure 21 is formed on the SOI substrate (S2). The nanowire structure 21 is formed by etching the upper silicon layer 20. To this end, after the photoresist is applied on the upper silicon layer, a pattern is formed by photolithography or electron beam lithography, and then the upper silicon layer 20 is etched using the formed pattern as a mask. The nanowire structure 21 defined as described above is preferably formed to have a width and a length of 1 to 50 nm and 0.1 to 10 μm, respectively, so as to minimize the overall size of the biosensor using the room temperature operating single-electron transistor. desirable.

5 is a partial cross-sectional perspective view showing a state in which the first dielectric layer 30 according to the first embodiment of the present invention is formed. As shown in FIG. 5, the next step is to form the first dielectric layer 30 on the substrate (S3). The first dielectric layer 30 may be formed to have a constant thickness, or may be formed to have a constant surface at an upper portion as shown in FIG. 5. The first dielectric layer 30 serves as an insulator for providing electrical insulation and may use various insulating materials. Examples of the first dielectric layer 30 may include a silicon oxide film and a silicon nitride film. In a preferred embodiment of the present invention, it is preferable to use a deposition method as the formation method of the first dielectric layer 30. This is because the first dielectric layer 30 can be deposited to a predetermined thickness on the entire surface of the substrate, and in particular, its thickness can be easily adjusted.

6 is a partial cross-sectional perspective view showing an example in which the trench 31 and the quantum dot coulomb channel 22 according to the first embodiment of the present invention are formed, and FIG. 7 is a quantum dot coulomb channel 22 according to the first embodiment of the present invention. Is a partial cross-sectional perspective view showing another example in which) is formed. 6 and 7, the next step is to form a quantum dot coulomb channel 22 (S4). The quantum dot coulomb channel 22 is defined by forming the trench 31 by etching the first dielectric layer 30 so that the nanowire structure 21 is exposed.

The trench 31 may form a first dielectric layer 30 by dry etching after forming a mask pattern to be orthogonal to the middle portion of the nanowire structure 21 or by using a focused ion beam method. ) Is formed by etching. Subsequently, the middle portion of the nanowire structure 21 exposed in the trench 31 may be partially etched to form the quantum dot coulomb channel 22. As shown in FIG. 6, the quantum dot coulomb channel 22 is formed by etching only the first dielectric layer 30 so that the nanowire structure 21 is exposed. In addition, as shown in FIG. 7, a portion of the thickness of the nanowire structure 21 may be etched to form a thin thickness of the quantum dot coulomb channel 22.

As the trench 31 is formed as described above, the quantum dot coulomb channel 22 formed by the nanowire structure 21 exposed to the outside may be formed to have a width of 1 to 50 nm and a thickness of 1 to 50 nm. . The width of the quantum dot coulomb channel 22 defined herein corresponds to the width of the nanowire structure 21. In addition, the quantum dot coulomb channel 22 is preferably formed to have a trench 31 width of 1 to 100nm to have a minimum size.

8 is a partial cross-sectional perspective view showing a state in which the second dielectric layer 40 is formed according to the first embodiment of the present invention. As shown in FIG. 8, the next step is to form the second dielectric layer 40 on the upper surface of the substrate (S5). The second dielectric layer 40 is a gate oxide film for insulating the quantum dot coulomb channel 22 and the T-type floating gate G to be described later. The first gate oxide film is an oxide film surrounding the quantum dot coulomb channel 22 through a thermal oxidation process. In this process, the size of the quantum dot coulomb channel 22 is miniaturized by 1 nm to 5 nm to allow room temperature operation. Thereafter, the deposition process is deposited on the upper portion of the first dielectric layer 30 and the trench 31 with a predetermined thickness.

As such, when the second dielectric layer 40 is formed, the width of the trench 31 is reduced by that much, so that the width of the T-type floating gate G formed in a later process, which will be described later, may be further narrowed. The second dielectric layer 40 having such a function is preferably formed through a thermal oxidation process or a deposition process after the thermal oxidation process. FIG. 8 illustrates an example in which the second dielectric layer 40 is formed through a thermal oxidation process and then a deposition process after the quantum dot coulomb channel 22 is formed. 9 is a cross-sectional view taken along line A-A of FIG. 8 showing a state in which the second dielectric layer 40 is formed according to the first embodiment of the present invention.

10 is a partial cross-sectional perspective view showing a state in which a T-type floating gate G is formed according to a first embodiment of the present invention. As shown in Figure 10, the next step is to form a T-type floating gate (G) (S6). The T-type floating gate G is formed to fill the trench 31 with a conductive material. That is, the quantum dot coulomb channel 22 is formed by fabrication of the trench 31, and the quantum dot coulomb channel 22 is wrapped with the second dielectric layer 40, and then a conductive material is filled thereon to fill the T-type floating gate (G). Will form.

Meanwhile, the manufacturing method of the first embodiment according to the present invention further includes etching a part of the formed third dielectric film 40 and doping impurities to form the source S and the drain D of the transistor. It can also be configured to include.

FIG. 11 is a cross-sectional view illustrating a state in which a sidewall spacer S1 is formed by etching a planar layer of the second dielectric layer 40 formed by the deposition process according to the first embodiment of the present invention. That is, as shown in FIG. 11, the planar layer of the second dielectric layer 40 is etched. The second dielectric layer 40 formed by the deposition process may be etched to exist only on the wall of the trench 31 to form a sidewall spacer S1. In this case, the gate oxide film has a first gate oxide film formed by a thermal oxidation process. 11 is a cross-sectional view illustrating a state in which sidewall spacers S1 are formed by etching a portion of the second dielectric layer 40 according to the first embodiment of the present invention.

In addition, it may include the step of doping with impurities to make the source (S) and drain (D). Through dry etching, the first dielectric layer 30 and the second dielectric layer 40 are partially or partially etched to a thickness capable of doping impurities, and then doped with impurities using the T-type floating gate G as a mask. According to a preferred embodiment of the present invention, the doping of impurities may be performed as follows according to the method of forming the T-type floating gate (G).

First, the first dielectric layer 30 and the second dielectric layer 40 are etched by forming a T-type floating gate G and then doped. Second, the gate G is formed only in the trench 31 to etch all or part of the first dielectric layer 30 and the second dielectric layer 40 and then doping. Third, the gate G is formed only in the trench 31 to etch the first dielectric layer 30 and the second dielectric layer 40, and then do the sidewall spacers S1. FIG. 12 is a cross-sectional perspective view showing a source S and a drain D formed by forming a T-type floating gate G to etch impurities to partially etch the first dielectric layer 30 and the second dielectric layer 40.

Next, after forming the T-type floating gate (G), the metal oxide detection layer 50 is deposited on the top (S7). FIG. 13 is a perspective view of a state in which a metal oxide detection layer 50 is formed thereon according to a first embodiment of the present invention.

The metal oxide detection layer 50 has a large adsorption rate of other charges including hydrogen ions (H +), which may be generated by a chemical coupling reaction of the target molecule 62 to be detected in the ion aqueous solution 61. It consists of metal oxides and electrical insulators, such as tantalum oxide film (Ta ₂ O ₅ ), aluminum oxide film (Al ₂ O ₃ ), silicon oxide film (SiO ₂ ) or silicon nitride film (Si 3 N 4).

In addition, in order to maximize the charge adsorption rate on the surface of the metal oxide detection layer 50, the surface may be chemically treated to form a chemically treated surface layer. In addition, when detecting the target molecule 62 using the antibody-antigen reaction, the metal oxide detection layer 50 may be chemically treated to immobilize a specific antibody that acts on a specific antigen. For example, when the target molecule 62 is a prostate specific antigen (PSA), the surface of the metal oxide detection layer 50 may be silanized and immobilized by reacting with an amine group (NH 2) present on the surface of the antibody. .

After the metal oxide detection layer 50 is formed, the ion aqueous solution container 60 is formed at the top (S8). The ion aqueous solution container 60 contains the ion aqueous solution 61 containing the target molecules 62. The ion aqueous solution 61 comes into contact with the surface of the metal oxide detection layer 50 mentioned above. Therefore, the target molecules 62 included in the ion aqueous solution 61 react with each other at the surface of the metal oxide detection layer 50 to generate H + and other charges Q.

As an example of a method of forming the ion-aqueous solution container 60, an insulating film layer that does not react with the target molecule 62 is deposited on the upper portion, and a portion of the insulating film is etched until the surface of the metal oxide detection layer 50 is exposed. Can be formed. 14 is a perspective view of a state in which an insulating film layer is formed in an upper portion according to the first embodiment of the present invention.

As shown in FIG. 14, after the insulating layer is deposited on the metal oxide detection layer 50, a portion of the insulating layer is exposed to the width and length of the T-type gate G to expose the surface of the metal oxide detection layer 50. Etch until it is configured to form a container 60 so that the ion solution 61 can be stored therein. FIG. 15 illustrates a perspective view of a biosensor using a room temperature operating single-electron transistor according to a first embodiment of the present invention. FIG. 16 illustrates a cross-sectional view taken along line B-B in FIG. 15.

Hereinafter, the configuration and manufacturing method of a biosensor using a room temperature operating single-electron transistor according to a second embodiment of the present invention will be described. Since the basic configuration and manufacturing method are the same as in the first embodiment described above, the differences will be mainly described. First, FIG. 17 illustrates a perspective view of a biosensor using a room temperature operating single-electron transistor according to a second embodiment of the present invention. 18 is a plan view of a biosensor using a room temperature operating single-electron transistor according to a second embodiment of the present invention.

As shown in FIG. 17 and FIG. 18, a biosensor using a single-electron transistor operating at room temperature according to a second embodiment of the present invention has a plurality of T-type floating gates G and a plurality of ion solution containers 60. It can be seen that the drain D, the plurality of sources S, and the plurality of quantum dot coulomb channels 22 are provided. In the manufacturing method according to the first embodiment, when the upper silicon layer 20 is etched to form the nanowire structure 21, the plurality of nanowire structures 21 are formed instead of one.

Therefore, as will be described later, one biosensor has a plurality of sources (S)-quantum dot coulomb channel (22)-drain (D) so that the current (I _ds ) flowing through the source (S)-drain (D), respectively. ) Can be measured to analyze the target molecule 62 more quickly and accurately. That is, by adding a single electron transistor integrated with a plurality of sources (S)-quantum coulomb channel 22-drain (D) by using one T-type floating gate (G) in common, T-type floating gate (G) / The source (S) -drain (D) current (I) of each single-electron transistor during the chemical reaction of the target molecules 62 present in the one ion aqueous solution 60 located above the metal oxide detection layer 50. By simultaneously measuring and decoding the change in _ds ), it is possible to greatly reduce the time required while increasing the reliability.

Hereinafter will be described the configuration of the target molecule 62 analysis system having a biosensor and the target molecule 62 analysis method according to an embodiment of the present invention. 19 is a cross-sectional view schematically showing the configuration of a target molecule 62 analysis system having a biosensor according to an embodiment of the present invention. And, Figure 20 shows a flow chart of the analysis method using a target molecule 62 analysis system having a biosensor according to an embodiment of the present invention. In addition, FIG. 21 shows the gate voltage V _g applied by the voltage applying unit 70 before and after chemical bonding of the target molecules 62 contained in the ion aqueous solution and the current value measured by the measuring means 80 ( I _ds ) Characteristic curve I _ds -V _g Shows the change in the graph. Coulomb vibration currents (indicated by solid lines) before the chemical bonding of the target molecules are charged by the chemical bonding of the target molecules, or the target molecules are coupled to the metal oxide detection layer 50 to shift the coulomb vibration currents. (Shown with a dashed line).

As shown in FIG. 19, it can be seen that the measuring means 80 measures the value of the current I _ds flowing between the source S and the drain D in real time as a function of the gate voltage V _g . In the method of analyzing the target molecules 62, first, a voltage applying unit 70 applies a gate voltage V _g to a reference electrode provided in the ion aqueous solution 61 before injection of the target molecules into the ion aqueous solution. In the measuring means 80, the current value I _ds is measured to obtain an I _ds -V _g characteristic curve prior to injection of the target molecule (S10).

Next, the target molecules 62 to be detected into the ion aqueous solution 61 are injected to allow the target molecules 62 to chemically react with the surface of the metal oxide detection layer 50 (S20). In addition, such chemical binding can be an antigen-antibody reaction. Such chemical reactions and bonds can be of any kind as long as they can adsorb charges on the detection layer 50 surface. When the target molecule 62 is a specific antigen, a chemical treatment is performed to immobilize a specific antibody that functions with the specific antigen on the surface of the metal oxide detection layer 50. For example, when the specific antigen is prostate specific antigen (PSA), the surface of the metal oxide detection layer 50 may be silanized and immobilized by reacting with an amine group (NH 2) present on the surface of the antibody.

Hydrogen ions and other charges (Q) generated by such chemical bonds are adsorbed onto the surface of the metal oxide detection layer 50 (S30).

Therefore, the electrostatic potential of the T-type floating gate G is changed by the amount of charge adsorbed on the surface of the metal oxide detection layer 50 (S40). In addition, the electrostatic potential of the T-type floating gate G is changed, thereby inducing a change in the electrostatic potential of the quantum dot coulomb channel 22 located at the lower end of the T-type floating gate G, thereby allowing the source S to drain D. The current I _{ds of the} liver is changed (S50, S60). The analytical means detects the change of the current (I _ds ) value after injection of the target molecule and measures the new I _ds -V _g characteristic (S70), and compares / analyzes the I _ds -V _g characteristic curve before the target molecule injection ( S80) The identity of the target molecules 62 in the ion aqueous solution 61 is deciphered.

In addition, when the target molecule 62 is analyzed using the biosensor according to the second embodiment described above, that is, one T-type gate G and the ion aqueous solution 60 are shared by several sources ( By adding single-electron transistors integrated into the S) -quantum dot coulomb channel 22-drain D, in one ion aqueous solution 61 located above the T-type floating gate G and the metal oxide detection layer 50 During the chemical reaction of the target molecules 62, the measuring means 80 provided in each of the plurality of sources S-drain D measures the current I _ds as a function of the gate voltage and Simultaneously measuring the change of I _ds ) and comparing / analyzing the I _ds -V _g characteristic curve prior to the injection of the target molecule can decode the target molecule to significantly reduce the time required while increasing the reliability.

Claims (19)

1. In the biosensor,

   A single electron transistor having a source and a drain provided on a substrate, a quantum dot coulomb channel provided between the source and the drain, and a gate provided on an upper side of the quantum dot coulomb channel;

   A metal oxide detection layer provided on an upper side of the gate and capable of chemically bonding to a target molecule; And

   An ion aqueous solution having a target molecule therein, the ion aqueous solution container is provided on the upper side of the metal oxide detection layer so that the ion aqueous solution is in contact with the metal oxide detection layer; Biosensor using transistors.
2. In the biosensor,

   A plurality of sources provided on the substrate, each of the plurality of drains provided on the substrate at specific intervals at positions opposed to the source, and a plurality of sources provided at each of the drains provided at the positions opposite to the source and the source; A gate provided on an upper side of the quantum dot coulomb channel and a plurality of quantum dot coulomb channels;

   A metal oxide detection layer provided on an upper side of the gate and capable of chemically bonding to a target molecule; And

   An ion aqueous solution having a target molecule therein, the ion aqueous solution container is provided on the upper side of the metal oxide detection layer so that the ion aqueous solution is in contact with the metal oxide detection layer; Biosensor using transistors.
3. The method of claim 1,

   The source and the quantum dot coulomb channel and the drain are connected to each other,

   A buried oxide layer disposed between the substrate, the source, and the drain; And

   A first dielectric layer stacked on an upper side of the source, the quantum dot coulomb channel, and a drain and having a trench; And

   And a second dielectric layer deposited on the first dielectric layer and the quantum dot coulomb channel.

   The gate is a T-shaped floating gate biosensor using a single-electron transistor operating at room temperature, characterized in that provided in the trench in which the second dielectric layer is deposited.
4. The method of claim 2,

   The source and the quantum dot coulomb channel and the drain are connected to each other to form a plurality of nanowire structures,

   A buried oxide layer disposed between the substrate and the plurality of sources and the plurality of drains; And

   A first dielectric layer stacked on top of the plurality of nanowire structures and having trenches formed therein; And

   And a second dielectric layer deposited on the first dielectric layer and the plurality of quantum dot coulomb channels.

   The gate is a T-shaped floating gate biosensor using a single-electron transistor operating at room temperature, characterized in that provided in the trench in which the second dielectric layer is deposited.
5. The method according to claim 1 or 2,

   The metal oxide detection layer,

   A biosensor using a room temperature operating single-electron transistor, comprising a tantalum oxide film, an aluminum oxide film, a silicon oxide film, or a silicon nitride film.
6. The method of claim 5,

   When the target molecule is a specific antigen

   The upper surface of the metal oxide detection layer is a biosensor using a room temperature operating single-electron transistor, characterized in that it comprises a chemical treatment surface layer for immobilizing the specific antibody reacts with the specific antigen.
7. A method for manufacturing a room temperature operating single-electron transistor having a substrate on which at least one buried oxide layer and an upper silicon layer are laminated,

   A first step of forming a nanowire structure by etching the upper silicon layer;

   A second step of forming a first dielectric layer on the substrate and the nanowire structure;

   A third step of forming a trench and a quantum dot coulomb channel by etching the first dielectric layer;

   A fourth step of forming a second dielectric layer thereon;

   Forming a gate in the trench;

   Depositing a metal oxide detection layer capable of chemically bonding to a target molecule on the gate; And

   A seventh step of storing an ion aqueous solution having a target molecule therein and forming an ion aqueous solution container on an upper side of the metal oxide detection layer such that the ion aqueous solution contacts the metal oxide detection layer; A method of manufacturing a biosensor using an operational single electron transistor.
8. A method of manufacturing a biosensor using a room temperature operating single-electron transistor having a substrate on which at least one buried oxide layer and an upper silicon layer are laminated,

   A first step of forming a plurality of nanowire structures by etching the upper silicon layer;

   A second step of forming a first dielectric layer on top of the substrate and the plurality of nanowire structures;

   Etching the first dielectric layer to form a trench and a plurality of quantum dot coulomb channels;

   A fourth step of forming a second dielectric layer thereon;

   Forming a gate in the trench;

   Depositing a metal oxide detection layer capable of chemically bonding to a target molecule on the gate; And

   A seventh step of storing an ion aqueous solution having a target molecule therein and forming an ion aqueous solution container on an upper side of the metal oxide detection layer such that the ion aqueous solution contacts the metal oxide detection layer; A method of manufacturing a biosensor using an operational single electron transistor.
9. The method according to claim 7 or 8,

   In the sixth step,

   When the target molecule is a specific antigen, the step of forming a chemical treatment surface layer for immobilizing the upper surface of the metal oxide detection layer with a specific antibody reacting with the specific antigen, characterized in that it further comprises a step Biosensor manufacturing method using.
10. The method according to claim 7 or 8,

    Etching a portion of the second dielectric layer formed by the deposition process between the fourth step and the fifth step to form a sidewall spacer; And

    And etching a portion of the first dielectric layer and a portion of the second dielectric layer to form a source and a drain by doping an impurity with a gate as a mask to form a source and a drain.
11. The method according to claim 7 or 8,

    The seventh step,

    Depositing an insulating layer on top of the metal oxide detection layer;

    Etching the insulating film layer into a container shape until the top surface of the metal oxide detection layer is exposed; And

    Method of manufacturing a biosensor using a single-electron transistor operating at room temperature, characterized in that it comprises the step of introducing an ion aqueous solution containing a target molecule therein.
12. The method according to claim 7 or 8,

    The first dielectric layer is formed to a thickness of 10nm ~ 1000nm through the deposition process,

    The second dielectric layer may be formed by a thermal oxidation process or a thermal oxidation process followed by a deposition process.
13. The method according to claim 7 or 8,

    The width of the nanowire structure formed by etching the upper silicon layer in the first step is 1 ~ 50nm, the length is 0.1 ~ 10㎛ manufacturing method of a biosensor using a single-electron transistor, characterized in that the formed.
14. The method according to claim 7 or 8,

    In the third step, the trench is formed to have a width of 1 to 100 nm by etching, and a portion of the thickness of the upper silicon layer is etched to form a thickness of the quantum dot of 1 to 50 nm. Method of manufacturing the sensor.
15. In the target molecule analysis system having a biosensor,

    A biosensor according to claim 1;

    A voltage applying unit for applying a specific voltage to the ion aqueous solution stored in the ion aqueous solution container of the biosensor through a reference electrode;

    Measuring means for measuring a current flowing between the source and the drain of the biosensor; And

    Based on the data measured by the measuring means, the current-gate (I _ds -V _g ) characteristic change due to chemical bonding between the target molecule contained in the ion aqueous solution and the metal oxide detection layer of the biosensor is measured to the target Target molecule analysis system having a biosensor, characterized in that it comprises an analysis means for analyzing the molecule.
16. In the target molecule analysis system having a biosensor,

    A biosensor according to claim 2;

    A voltage applying unit for applying a specific voltage to the ion aqueous solution stored in the ion aqueous solution container of the biosensor through a reference electrode;

    Measuring means for measuring each current flowing between a plurality of sources provided in the biosensor and a plurality of drains provided at positions opposite to the source; And

    Based on the data measured by the measuring means, the current-gate (I _ds -V _g ) characteristic change due to chemical bonding between the target molecule contained in the ion aqueous solution and the metal oxide detection layer of the biosensor is measured to the target Target molecule analysis system having a biosensor, characterized in that it comprises an analysis means for analyzing the molecule.
17. In the target molecule analysis method using the analysis system according to claim 15,

    Applying a voltage to the ion aqueous solution by a voltage applying unit;

    Measuring source-drain current prior to injecting target molecules into the ion aqueous solution;

    Injecting target molecules into the aqueous ion solution to generate chemical bonds of the target molecules;

    The charges generated by the chemical bonding are adsorbed on the surface of the metal oxide detection layer;

    Changing the electrostatic potential of the gate of the biosensor by the amount of charge adsorbed on the surface of the metal oxide detection layer;

    Inducing a change in the electrostatic potential of a quantum dot coulomb channel of the biosensor to generate a current change between a source and a drain; And

    And analyzing the target molecules by detecting an Ids-Vg characteristic change based on a current value between the source and the drain measured by the measuring means before and after the injection of the target molecule by the measuring means. Target molecule analysis method.
18. The method of claim 17,

    The target molecule is a specific antigen, the upper surface of the metal oxide detection layer includes a chemical treatment surface layer for immobilizing a specific antibody reacts with the specific antigen,

    Adsorbed on the surface of the detection layer,

    The specific antigen is a target molecule analysis method characterized in that the step of antigen-antibody reaction with the chemical treatment surface layer.
19. The method of claim 17,

    The charge amount is a target molecule analysis method, characterized in that the positive or negative charge of a certain amount including H ⁺ .

Images