JPH10260156A - Sensor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a sensor whose sensitivity and selectivity are high by a method wherein a part to which a protein and an enzyme which are selectively reacted with, or absorbed to, a specific substance is used as a field-effect transistor(FET) or a single-electron transistor. SOLUTION: A glucose oxidation enzyme as a receptor 5 is adsorbed, via polypyrrole, to the part of the gate 4 of an FET which is formed by an ordinary semiconductor technique. The part of the gate 4 is immersed in a solution which contains glucose 6 as a ligand, and a selective reaction with the glucose 6 is caused. Then, a transistor output which is nearly proportional to the concentration of the glucose is obtained. That is to say, when the concentration of the glucose is increased, the transistor output is raised. Consequently, this structure functions as a sensor. In addition, when a plurality of FET's are connected in parallel, their sensitivity can be enhanced. In this manner, the glucose 6 in the solution can be detected with high sensitivity and with high selectively.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel structure of a so-called biosensor. About the sensor.

[0002]

2. Description of the Related Art A conventional biosensor has a method in which a membrane has a function of selectively reacting with a specific molecule, and a change in potential when the molecule is adsorbed is measured. For example, Aizawa, Chemical Communication,
945 (1989) (M. Aizawa, Chem. Soc. Chem.
Commun., 945 (1989)), a glucose oxidase was immobilized on the electrode surface, and the amount of glucose was detected by measuring the current accompanying the oxidation of glucose.
However, in this method, even if the electrode has selectivity by attaching a reactive group, the sensitivity is low and low-concentration glucose can be detected because the current value associated with the chemical reaction is directly detected. However, it was not always possible to take advantage of the high selectivity of biosensors, for example, it was impossible.

[0003]

SUMMARY OF THE INVENTION The present invention has been made to solve such problems of the present technology, and has a field effect type or single electron type transistor structure in which an enzyme is connected to a gate. It is intended to provide a highly selective sensor with much higher sensitivity than before. According to the present invention, a device capable of detecting one molecule can be realized, so that the technical effect of the present invention is great.

[0004]

FIG. 1 shows the basic structure of a device according to the present invention. In the figure, the potential of the gate 4 connected to the receptor 5 changes due to an electrode reaction that occurs when the ligand 6 selectively reacts with and adheres to the receptor 5 adhered to the gate 4. This potential change is
The conductance of a transistor including a source 2, a drain 3, and a gate 4 formed on a semiconductor substrate 1 is changed. Specifically, a channel current value flowing between the source 2 and the drain 3 changes according to the number of reactions between the receptor 5 and the ligand 6. In this manner, the number of the ligands 6 present in the solution can be detected from the channel current value with high selectivity and high sensitivity, which was impossible in the past, so that the technical effect of the present invention is large. is there.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION

(Embodiment 1) In this embodiment, an embodiment of the present invention having a field effect transistor structure will be described with reference to FIG. FIG.
Shows a state in which a gate 4, a source 2, and a drain 3 are formed on a silicon (100) substrate 1 by using a normal semiconductor technique to form a field effect transistor structure. In the figure, a silicon substrate 1 has a specific resistance of 10 ohm-cm doped with p-type, and a source 2 and a drain 3 have phosphorous of 1020 cm-cm.
-3 doped, and the junction depth was 2 microns.
The gate 4 is formed of polycrystalline silicon having a thickness of 200 nm, and has a gate length of 5 microns and a gate width of 10 nm.
Micron. Glucose oxidase was adsorbed as the receptor 5 to the gate 4 portion of the structure thus prepared. The glucose oxidase 5 is adsorbed on the gate 4 via polypyrrole, and is electrically connected to the gate 4. In this state, the portion where glucose oxidase was adsorbed as the receptor 5 was immersed in the gate 4 portion in a solution containing glucose 6 as a ligand to cause a selective reaction with glucose. As a result, a transistor output almost proportional to the glucose concentration was obtained. That is, when the glucose concentration is increased as shown in FIG. 2, the amount of glucose adsorbed on the glucose oxidase also increases in proportion thereto, and as a result, the gate voltage is effectively increased, and the conductance of the transistor is increased. The output increases. As is apparent from FIG. 2, the structure according to the present invention has a sufficient function as a sensor. Further, the field-effect transistors shown in FIG. 1 are arranged in parallel,
It is also possible to use as one sensor. With such a structure, for example, by operating five field effect transistors in parallel, it is possible to increase the sensitivity five times. The reason for this is that the effective gate width is increased, but the sensitivity can be improved because, for example, noise can be suppressed by paralleling a plurality of transistors rather than simply increasing the gate width of one transistor. .

[0006] In the present embodiment, examples of the combination of glucose oxidase and glucose have been given with respect to proteins and enzymes that selectively react with or adsorb to a specific substance. Combinations of enzymes and proteins that selectively react with the substance can be arbitrarily selected. That is, a feature of the present invention is that a combination of a receptor and a ligand having particularly high selectivity can be arbitrarily selected according to the purpose.

(Embodiment 2) In this embodiment, an embodiment of the present invention having a single electron transistor structure will be described with reference to FIG. FIG. 3 shows a quantum dot 1 having a single-electron transistor structure.
1 shows a state in which a protein or enzyme 13 that selectively reacts or adsorbs with a specific substance 15 via a gate 14 is added. In the figure, reference numeral 12 denotes a tunnel junction;
The current flowing through the quantum dot 11 is controlled by the potential. That is, when the substance 15 reacts or adsorbs to the protein or the enzyme 13 which selectively reacts or adsorbs with the substance 15, a current flowing through the quantum dot 11 is observed. When the substance 15 does not react or adsorb to the protein or enzyme 13 which selectively reacts or adsorbs, the current flowing through the quantum dot 11 is adjusted to be almost zero. On the contrary, when the substance 15 reacts or adsorbs to the protein or the enzyme 13 which selectively reacts or adsorbs with the substance 15, the current flowing through the quantum dot 11 becomes zero. If the substance 15 does not react or adsorb to the protein or enzyme 13 which selectively reacts or adsorbs with the substance 15, it is also possible to adjust so that the current flowing through the quantum dot 11 can be observed. Can select an appropriate shape arbitrarily according to the characteristics of the measurement system. Further, by sufficiently reducing the size of the quantum dot 11, the detection sensitivity is improved, and it is possible to detect a change when one molecule is adsorbed. In this embodiment, by reducing the quantum dots to 10 nm,
The potential of the gate 14 changed by 10 mV, whereby one molecule could be detected.

[0008] In the present embodiment, examples of the combination of glucose oxidase and glucose have been given with respect to proteins and enzymes that selectively react with or adsorb to a specific substance. Combinations of enzymes and proteins that selectively react with the substance can be arbitrarily selected. That is, a feature of the present invention is that a combination of a receptor and a ligand having particularly high selectivity can be arbitrarily selected according to the purpose.

FIG. 4 shows an example of a configuration in which the single-electron transistor structures 21 disclosed in FIG. 3 are arranged in parallel and used as one sensor. With such a parallel structure, for example, by operating five single-electron transistors in parallel as shown in FIG. 4, the sensitivity can be increased fivefold. This is because the effective current path is increased by a factor of five. If the quantum dot size of one single-electron transistor is simply reduced, the current becomes smaller and the sensitivity is rather lowered. On the other hand, when the quantum dot size is increased, thermal noise due to temperature increases,
Since the voltage change caused by one reaction is small, the sensitivity also decreases. Therefore, when a single-electron transistor is used, parallelization is indispensable for improving the sensitivity. According to the method of using a single-electron transistor, it is possible to achieve a sensitivity that is 100 times or more higher than that of the conventional method and 10 times or more that of the field effect transistor type. Therefore, the engineering effect of the present invention is great.

[0010]

As is clear from the above embodiments, according to the present invention, a highly selective sensor having much higher sensitivity than the conventional one can be realized. Further, according to the present invention, a device capable of detecting one molecule can be realized, so that the technical effect of the present invention is great.

[Brief description of the drawings]

FIG. 1 is a diagram illustrating the principle and an embodiment of the present invention.

FIG. 2 is a diagram showing the effect of the present invention.

FIG. 3 is a diagram showing an embodiment of the present invention.

FIG. 4 is a diagram showing an embodiment of the present invention.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Substrate, 2, 3 ... Diffusion layer, 4, 14 ... Gate, 5, 1
3. Receptor, 6, 15 Ligand, 11 Quantum dot, 12 Tunnel junction, 21 Single electron transistor sensor.

 ──────────────────────────────────────────────────続 き Continuing from the front page (72) Munehisa Miya 2520 Akanuma, Hatoyama-cho, Hiki-gun, Saitama Prefecture Basic Research Laboratory, Hitachi, Ltd.

Claims (5)

[Claims] 1. A sensor having a portion to which a protein or enzyme that selectively reacts or adsorbs with a specific substance is added. 2. The sensor according to claim 1, wherein the portion to which a protein or enzyme selectively reacting or adsorbing with the specific substance is added is a gate of a field effect transistor. 3. The sensor according to claim 1, wherein the portion to which a protein or enzyme that selectively reacts or adsorbs with the specific substance is added is a gate of a single-electron transistor. 4. The sensor according to claim 2, wherein a plurality of said field effect transistors are arranged in parallel. 5. The sensor according to claim 3, wherein a plurality of said single-electron transistors are arranged in parallel.