This application is entitled and claims the benefit of Japanese Patent Application No. 2010-089479, filed on Apr. 8, 2010, the disclosure of which including the specification, drawings and abstract is incorporated herein by reference in its entirety.
This disclosure relates to a biosensor having a field effect transistor device, and a detection method of a target substance using the same.
Biosensors that utilize a field effect transistor have heretofore been proposed (see Patent References 1 to 3). Generally, in such a field-effect transistor biosensor, source/drain electrodes and a channel are formed on an insulating film formed on a semiconductor substrate, and in many cases, a reaction field is disposed on the channel or insulating film on the semiconductor substrate. Target recognition molecules are often immobilized on the reaction field.
In such a biosensor, target recognition molecules immobilized on the reaction field are allowed to recognize a target substance. The biosensor then measures a source-drain current upon target recognition to determine the presence or concentration of the target substance provided to the reaction field.
As mentioned above, the field-effect transistor biosensor determines the presence or concentration of a target substance based on the source-drain current of a field effect transistor. A source-drain current of a field effect transistor greatly varies depending on the measurement environment. Examples of measurement conditions that cause variations in a source-drain current include ambient temperature and lightness (amount of light). Variations in source-drain current associated with changes in the measurement environment impede precise detection.
It is therefore an object of the present invention to provide a biosensor capable of precise target detection regardless of measurement conditions such as ambient temperature and lightness, even though the device has a field effect transistor.
The present invention is directed to a biosensor having at least two field effect transistor devices, one as a device for detecting a target substance and the other as a device for correcting noise associated with changes in the measurement environment. Specifically, a first aspect of the present invention relates to biosensors given below.
[1] A biosensor including:
at least two field effect transistor devices, each including a silicon substrate, a silicon oxide film formed on a surface of the silicon substrate, a source electrode disposed on the silicon oxide film, a drain electrode disposed on the silicon oxide film, a channel for connecting the source electrode and the drain electrode, and a gate electrode capable of controlling the channel,
wherein one of the at least two field effect transistor devices is provided with a reaction field on which a target recognition molecule is to be immobilized, and the other one of the at least two field effect transistor devices is provided with a reaction field on which a target recognition molecule is not to be immobilized.
[2] The biosensor according to [1], wherein the silicon substrates of the at least two field effect transistor devices are set apart from each other.
[3] The biosensor according to [1], wherein the at least two field effect transistor devices share the same silicon substrate, and the gate electrodes of the at least two field effect transistor devices are set apart from each other.
[4] The biosensor according to any one of [1] to [3], wherein a voltage applied to the gate electrode is +0.5 V to −0.5 V.
A second aspect of the present invention relates to a detection method given below.
[5] A detection method of a target substance with the biosensor according to claim 1, the method including:
providing a sample to the respective reaction fields of the at least two field effect transistor devices;
measuring a source-drain current of each of the at least two field effect transistor devices; and
correcting the source-drain current of one of the at least two field effect transistor devices with the source-current of the other one of the at least two field effect transistor devices.
[6] The detection method according to [5], wherein a voltage applied to the gate electrode upon measurement of the source-drain current of each of the at least two field effect transistor devices is +0.5V to −0.5V.
A field-effect transistor biosensor of the present invention is capable of high-precise target detection regardless of measurement conditions such as ambient temperature and lightness; therefore, the present invention contributes to the practical use of a field-effect transistor biosensor.
Moreover, the biosensor of the present invention eliminates the need to provide a detection apparatus with a noise cancelling mechanism and to store noise cancelling data in the detection apparatus, making it possible to simplify the detection apparatus.
A biosensor of the present invention has field effect transistor devices. The field effect transistor device includes a semiconductor substrate; an insulating film formed on a surface of the semiconductor substrate; a source electrode disposed on the insulating film; a drain electrode disposed on the insulating film; a channel for connecting the source and drain electrodes; and a gate electrode capable of controlling the channel. The semiconductor substrate and insulating film are usually, but not necessarily, a silicon substrate and a silicon oxide film, respectively.
Channel 16 is, for example, but not limited to, a polysilicon channel; for example, channel 16 may be a carbon nanotube channel. Channel 16 may be of NPN-type, PNP-type, NiN-type, or PiP type. When channel 16 is NPN type or PNP type, the band gap of the channel is large, and therefore, leakage current tend to be small compared to the NiN-type or PiP-type channel. Consequently, with an NPN-type or PNP-type channel, an electric circuit that can reduce current consumption in stand-by mode can be readily constructed. The NiN-type or PiP-type channel, on the other hand, may be manufactured in fewer steps than the NPN-type or PNP-type channel.
A biosensor having a single field effect transistor device, such as that illustrated in
As seen from
In contrast to such a biosensor, the biosensor of the present invention uses at least two field effect transistor devices, one as a detection device and the other as a correction device.
Every field effect transistor device contained in the biosensor of the present invention includes a semiconductor substrate; an insulating film formed on a surface of the semiconductor substrate; a source electrode disposed on the insulating film; a drain electrode disposed on the insulating film; a channel for connecting the source and drain electrodes; and a gate electrode capable of controlling the channel. All of the field effect transistors preferably have the same constituent components (except for reaction field) and have the same structure. This makes uniform device characteristics, especially I-V characteristics, among the field effect transistors.
The field effect transistor devices may have own separate silicon substrates (see
The field effect transistor devices contained in the biosensor of the present invention each have a reaction field. As used herein, the term “reaction field” means an area in which a sample (typically solution) which may contain a target substance is to be provided. The position of the reaction field is not particularly limited; it may be disposed on the surface of the semiconductor substrate (see
Field effect transistor device A, one of the field effect transistor devices contained in the biosensor of the present invention, includes a reaction field on which target recognition molecules are to be immobilized. Field effect transistor device A is a device for detecting a target substance. Examples of target recognition molecules include proteins such as antibodies, enzymes and lectin, nucleic acid, oligosaccharides or polysaccharides, and substances having the structure of the foregoing. Immobilizing target recognition molecules on the reaction field allows for specific detection of specific types of proteins or chemicals.
On the other hand, field effect transistor device B, the other one of the field effect transistor devices contained in the biosensor of the present invention, includes a reaction field on which no target recognition molecule are immobilized. Field effect transistor device B is a device for correcting detection data of field effect transistor device A.
Target Detection Flow Using Biosensor
Detection of a target substance using a biosensor of the present invention starts by providing a sample, which may contain a target substance, to the reaction field of field effect transistor device A (reaction field on which target recognition molecules are immobilized).
The same sample is also provided to the reaction field of field effect transistor device B (reaction field on which target recognition molecules are not immobilized). The target recognition molecules immobilized on the reaction field of field effect transistor device A react with a target substance in the sample. By contrast, no reaction takes place in the reaction field of field effect transistor device B because of the absence of target recognition molecules. Where necessary, the sample's solvent and other components are then removed from the respective reaction fields.
The same level of a given gate voltage is applied to the gate electrodes of field effect transistor devices A and B. For example, a voltage applied to the gate electrodes of field effect transistor devices A and B is +0.5 V to −0.5 V. At this time, source-drain currents of field effect transistor devices A and B are respectively measured. Due to slight changes in the measurement environment, such as changes in ambient temperature or lightness, noise may occur in both of the source-drain currents of field effect transistor devices A and B. The source-drain currents show similar noise patterns, because field effect transistors device A and B have the same device structure.
In
Thus, it can be seen that a noise-cancelled source-drain current can be obtained for field effect transistor device A by correcting the source-drain current of field effect transistor device A with the source-drain current of field effect transistor device B.
With reference to
Typical biosensor apparatus require a mechanism for suppressing noise in the measured values in the biosensor or a mechanism for cancelling the generated noise. The noise suppressing mechanism is, for example, a mechanism for keeping the measurement temperature constant or a light-shielding mechanism. The noise cancelling mechanism is, for example, a mechanism for correcting the measured values in the biosensor using predicted noise patterns stored in the mechanism in advance.
The biosensor of the present invention, on the other hand, requires neither a noise suppressing mechanism nor a noise cancelling mechanism, since the biosensor itself has a noise cancelling function. Thus, according to the present invention, a simple and small biosensor apparatus may be provided.
Because possible noise that occurs due to the measurement environment can be cancelled, the biosensor of the present invention is capable of highly sensitive and precise target detection even though the device has a field effect transistor.
Number | Date | Country | Kind |
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2010-089479 | Apr 2010 | JP | national |