KR20090068724A - Fabricating method for bio sensor using nano-scale structure - Google Patents

Abstract

A biosensor and a manufacture method thereof are provided to respectively form a nanoscaled structure and a target molecule on different substrates, thereby continuously using a nanowire/carbon nanotube FET biosensor device. A biosensor using a nanoscaled structure comprises: a micro channel(220) which stores or flows a test solution containing target molecules(160); a receptor(150) which is connected to a chemical functioning unit(140) immobilized to a flexible thin film located on an upper part of the micro channel and which captures the target molecules; and a nanowire structure(130) which is located in a lower part of the micro channel in order to sense a field effect by an electric charge of the target molecules. The flexible thin film consists of a first upper thin film(240), a second upper thin film(250) and a pressure device(230).

Description

Fabrication method for bio sensor using nano-scale structure}

The present invention relates to a biosensor using a nanoscale structure including nanowires or carbon nanotubes, and more particularly, to a nanoscale structure including a receptor and a functional group for capturing a target molecule immobilized on a flexible thin film. It relates to a biosensor and a manufacturing method using the structure.

Nanowire FET is a device composed of an electrical device to measure the electrical properties of the nanowire by forming electrodes on both ends of the nanowire. In general, unlike the gate formed in the field effect transistor, the nanowire FET allows the gating electric field to be formed on the surface of the nanowire through the degree of adsorption or the adsorption of the charged particles.

Biosensors using nanowire FETs have the function of detecting specific biomolecules by surface-treating nanowires. In order to realize such a function, a receptor is formed by immobilizing a biomolecule such as a chemical functional group, an aptamer, or a protein that specifically acts on a specific biomolecule on the surface of the nanowire.

Chemical functional groups chemically treated on the nanowire surface selectively recognize and bind unknown target molecules present in the test solution as receptors. At this time, the charge of the unknown target molecules bound and captured induces an electric field effect on the nanowires, which gates the nanowire FETs. Through this, the conductivity change of the nanowire is sensed and operated as a biosensor. Receptors immobilized on the surface of the nanowires are designed to react specifically with the target molecule, thus detecting only molecules that are desired to be detected.

1 to 3 is a conceptual diagram of a biosensor using a nanoscale structure according to the prior art.

Conventional biosensors include an insulating layer 120 and nanowires 130 on a substrate 110 to detect target molecules in a test solution. A chemical functional group 140 having a predetermined length is attached to the surface of the nanowire 130, and a receptor 150 is formed at one end of the chemical functional group 140 (FIG. 1). Receptor 150 captures specific target molecules 160 in the test solution. The electric field effect by the charge of the target molecule 160 induces a change in carrier concentration that determines the amount of current in the channel 170 of the nanowire 130.

However, such conventional biosensors contain high concentrations of salts, ions, and other charged particles or protein molecules present in test solutions, such as blood, and the charges they contain are screened for the field effect by the target molecule. Decreases the sensing capability of the biosensor. As an example, when the receptor 150 fixed on the surface of the nanowire 130 is far from the surface of the nanowire 130 by a considerable distance, free target particles present in the test solution may be captured in the receptor 150. The gating effect may not occur by disturbing the field effect of the molecule 160. This is called a divide-by-shielding, a phenomenon in which the electric field effect of the charged particles is shielded due to the influence of the surrounding charges. As a result, the gating by the target molecule to be detected by the biosensor is likely to occur in a limited manner (FIG. 2).

FIG. 3 illustrates another conventional biosensor that reduces the effects of the device by shielding by forming the length of the chemical functional group 140 formed on the surface of the nanowire 130 within the device length to solve the problems caused by the device shielding. Conceptual diagram.

 In order to solve the device shielding, by shortening the length of the chemical functional group 140 connected to the receptor 150 attached to the surface of the nanowire 130 or reducing the size of the receptor 150 itself to prevent the occurrence of the device shielding.

In the case of a large-sized protein such as an antibody, it is relatively large compared to the dividing shielding length, and thus a method of removing the recognition portion of the antibody and immobilizing it on the surface of the nanowire 130 is not cumbersome and simple.

In addition, a method of using a shorter chemical functional group 140 or a receptor material such as an aptamer has been proposed. However, due to various limitations in terms of process, a fundamental solution for solving a divider shield is required.

In addition, there are various conventional techniques for maximizing the receptor activity of the biosensor in order to solve the problems caused by the device shielding.

In general, in order to maximize the activity of the receptor when the receptor is fixed on a solid substrate, it is advantageous to form it at a certain length or more from the bottom, and it is preferable to induce the maximization of the immune response through the directional control of the antibody. In this case, since several proteins must be used alternately, there is a necessity to secure a space over a certain length from the bottom, and thus there is a drawback that cannot be practically applied.

That is, it is difficult to apply a surface treatment technique for fixing a chemical functional group in order to detect target molecules within the length of the device, and there is a high possibility that the target molecules are inferior in sensitivity.

The present invention devised to solve the above problems of the prior art by using a pneumatic chamber having a thin film capable of bending by approaching the nanowires chemical functional groups trapping the target molecules, it is possible to prevent the divide-by shielding effect It is an object of the present invention to provide a biosensor and a manufacturing method using a nano-scale structure.

Another object of the present invention is to provide a biosensor and a manufacturing method using a nanoscale structure that can prevent a divider shielding effect by forming a spacer corresponding to the divider length under the nanowire.

In addition, another object of the present invention is to provide a biosensor and a manufacturing method using a nano-scale structure that can prevent the divide-by shielding effect by etching the insulating layer of the region adjacent to the nano-scale structure to a depth corresponding to the divider length. .

The object of the present invention is a micro channel for storing or flowing a test solution containing a target molecule; A receptor connected to a chemical functional group fixed to the flexible membrane located above the microchannel to capture the target molecule; And a nanoscale structure positioned under the microchannel and including a nanowire structure for sensing an electric field effect caused by the charge of the target molecule.

Another object of the present invention is to form a flexible thin film on a micro channel with a test solution containing a target molecule; Surface-treating the flexible thin film to attach a chemical functional group connected to a receptor to capture the target molecule; And forming a nanowire structure on the lower end of the microchannel to sense the electric field effect caused by the charge of the target molecule.

Therefore, the biosensor and the manufacturing method using the nanoscale structure of the present invention has the effect of preventing the dividing shielding phenomenon to improve the sensitivity of the sensor.

In addition, since the substrate on which the nanoscale structure is formed and the substrate on which the target molecules are captured are formed on different substrates, there is an advantage that the nanowire / carbon nanotube FET biosensor device can be used continuously. That is, the biosensor is used only as a sensing element due to the gating effect, and since the adsorption of the target molecule is performed on the upper surface of the microchannel containing the test solution, the biosensor can be used as a continuously detectable device by replacing the microchannel according to the test solution. It is possible.

Biosensor and manufacturing method using the nanoscale structure of the present invention is to access the target molecules trapped in the chemical functional groups fixed on the substrate surface to the nanowire surface, so there is no limitation in the surface treatment method used in the existing biochip technology There is an advantage that can be introduced as it is surface treatment technology.

The terms or words used in this specification and claims are not to be construed as being limited to their ordinary or dictionary meanings, and the inventors may appropriately define the concept of terms in order to best describe their invention. It should be interpreted as meaning and concept corresponding to the technical idea of the present invention based on the principle that the present invention.

Therefore, the embodiments described in the specification and the drawings shown in the drawings are only the most preferred embodiment of the present invention and do not represent all of the technical idea of the present invention, various modifications that can be replaced at the time of the present application It should be understood that there may be equivalents and variations.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings.

4 and 5 is a conceptual diagram of a biosensor using a nano-scale structure according to the first embodiment of the present invention.

The biosensor having the nanowire structure 130 formed on the insulating layer 120 formed on the substrate 110 is positioned in the microfluidic channel (chamber) 220. The microfluidic channel 220 is filled with a test solution.

According to the present invention, the nanowire structure 130 may use a FET device using silicon nanowires or carbon nanotubes 210.

The upper part of the biosensor is provided with a pressing device 230 having a flexible thin film that can be bent by an external pressure.

The pressurizing device 230 according to the present invention may use a pneumatic chamber (channel) using pneumatic pressure, the flexible thin film is composed of a plurality of upper layer thin film.

First, since the first upper layer thin film is made of a polymer material including PDMS, the central portion thereof is swollen by pneumatic pressure injected into the pressurizing device 230. As the second upper layer thin film 250, a material of a substrate used in a general biosensor, such as a metal including Au, silica, and a polymer, may be used. The chemical functional group 140 is attached to the surface of the second upper layer thin film 250 by surface treatment. A receptor 150 is formed at one end of the chemical functional group 140 to capture specific target molecules 160 in the test solution.

When the first upper layer thin film 240 and the second upper layer thin film 250 are bent by applying pressure to the pneumatic chamber (channel), the receptor 150 trapping the target molecule 160 and the chemical functional group connected thereto ( 140 approaches the substrate 110 on which the nanowires 130 are formed. The charge present in the target molecule 160 induces an electric field effect on the nanowire 130 to change the carrier concentration in the channel 170.

That is, unlike conventional biosensors using nanowires, pneumatic chambers (channels) in which a plurality of flexible thin films are formed to access biosensors while capturing biosensors and target molecules having nanowire structures are formed.

The receptor 150 for recognizing a specific target molecule 160 is fixed on the second upper layer thin film 250. In this case, it is preferable to increase the degree of freedom of surface treatment to maximize activation of the receptor 150. In addition, when detecting the charge of the target molecule 160 using the nanowire structure 130, it is preferable to approach the target molecule 160 to the surface of the nanowire 130 within a divide length.

6 is a conceptual diagram of a biosensor using a nanoscale structure according to a second embodiment of the present invention.

Anisotropic etching is performed on the insulating layer 120 to form a spacer 310 formed at a predetermined height under the nanowire structure 130. At this time, the height of the spacer 310 is preferably formed in consideration of the divide length. The chemical functional group 140 connected to the receptor 150 is fixed to the surface of the insulating layer 310 by surface treatment. Receptor 150 captures specific target molecules 160 in the test solution. The field effect generated by the charge of the captured target molecules 160 changes the carrier concentration in the channel 170 of the nanowire structure 130 and changes the amount of current flowing through the nanowire structure 130.

The spacer may be formed by etching the insulating layer 310 isotropically or anisotropically, as shown in FIG. 7.

By forming the spacer 310 at a height of about the length of the divider from the insulating layer 120, the divider shielding phenomenon is prevented so that the electric field effect due to the charge of the target molecule 160 is prevented from the nanowire structure 130. To influence the change in carrier concentration in channel 170

When using isotropic etching, an etching hole 410 is formed in the insulating layer. In this case, the depth of the etching hole 410 is formed in consideration of the length of the divide, and by attaching the chemical functional group 140 to the etching hole 410 through the surface treatment, it is preferable to prevent the divide-by shielding phenomenon.

8 is a conceptual diagram of a biosensor using a nanoscale structure according to a third embodiment of the present invention.

The insulating layer 120 and the nanowire structure 130 are formed on the substrate 110. An etching hole 410 is formed by etching a portion of the insulating layer 120 adjacent to the nanowire structure 130.

According to an embodiment of the present invention, the etching of the insulating layer 120 may use an isotropic or anisotropic view.

When the etching hole 140 is formed, the chemical functional group 150 is formed in the etching hole 410 through surface treatment. The electric field effect is induced on the nanoscale structure 130 by the charge of the target molecules 160 captured by the receptor 150 formed at one end of the chemical functional group 150, thereby changing the carrier concentration of the channel 170.

As in the first embodiment of the present invention, the electric field is applied to the nanowires through a series of processes in which the chemical functional group 150 is introduced and the receptors are fixed by surface treatment using the peripheral surface of the nanowires rather than the nanowires themselves. Can induce an effect.

The target molecules 160 directly adhered to the surface of the nanowire structure 130 are not detected due to the dividing shield, but the target molecules 160 combined with the receptor 150 processed on the bottom surface are detected due to the electric field effect. It is possible.

9 to 11 are process flowcharts of the nanowires according to the second and third embodiments of the present invention.

First, the silicon nanowires 130 floating on the substrate 110 are formed using a photolithography process (FIG. 9). Next, an insulating layer 120 having a thickness corresponding to the divide length is deposited on the substrate front surface 110 on which the nanowires 130 are formed (FIG. 10). After moving the bottom surface on which the insulating layer 120 is deposited by using a nanowire transfer, a nanowire biosensor is formed (FIG. 11). Finally, the biosensor that solves the divide-by shielding effect is completed by attaching chemical functionalities through surface treatment on the substrate bottom and adjusting the height of the spacer.

In the case of using the nanowire transfer, the insulating layer 120 to serve as a spacer in FIG. 9 may be formed in an appropriate thickness, about 10 nm in advance, and thus, there is no need to proceed with the etching process as in the above-described embodiment. After transferring the nanowires with the insulating layer formed on the substrate, the nanowire FET device may be made by a metal process, and the surface of the bottom substrate on which the nanowires are formed may be surface-treated to introduce a functional group, and the receptor may be immobilized to form a biosensor.

It is possible to form the deposition thickness of the insulating layer deposited on the upper part of the nanowire corresponding to the length of the device. The target molecule to which the receptor is held by adjusting the length of the functional group when the chemical functional group is introduced to the substrate surface by using the deposited thickness information It can be easily implemented so that is present close to the nanowire surface.

Although the present invention has been shown and described with reference to the preferred embodiments as described above, it is not limited to the above embodiments and those skilled in the art without departing from the spirit of the present invention. Various changes and modifications will be possible.

1 to 3 is a front view of the nanowire biosensor according to the prior art,

4 and 5 is a conceptual diagram of a biosensor using a nano-scale structure according to a first embodiment of the present invention,

6 is a conceptual diagram of a biosensor using a nanoscale structure according to a second embodiment of the present invention;

7 is a conceptual diagram of a spacer embodiment according to a second embodiment of the present invention;

8 is a conceptual diagram of a biosensor using a nanoscale structure according to a third embodiment of the present invention;

9 to 11 is a process flow diagram of a structure using a nano-scale structure according to the second and third embodiments of the present invention.

<Explanation of symbols for the main parts of the drawings>

110: substrate 120: insulating layer

130: nanowire 140: chemical functional group

150: receptor 160: target molecule

170: carrier 180: charge

210: carbon nanotube 220: micro fluid channel

230: pressure device 240: first upper layer thin film

250: second upper layer thin film 310: spacer

410: etching hole

Claims (15)

A micro channel for storing or flowing a test solution containing a target molecule; A receptor connected to a chemical functional group fixed to a flexible thin film located above the microchannel to capture the target molecule; And Located at the bottom of the micro-channel nanowire structure for detecting the electric field effect by the charge of the target molecule Biosensor using a nano-scale structure comprising a. The method of claim 1, wherein the flexible thin film, A first upper layer thin film capable of bending; A second upper layer thin film formed on the first upper layer thin film to fix the chemical functional group; And Pressing device for inducing bending by applying pressure to the first upper layer thin film Biosensor using a nano-scale structure comprising a. The method of claim 2, The first upper layer thin film is a biosensor using a nano-scale structure made of a polymer material. The method of claim 2, The second upper layer thin film is a biosensor using a nano-scale structure of any one of metal, silica and polymer. The method of claim 1, The nanowire structure is a biosensor using a nano-scale structure of silicon nanowires or carbon nanotubes. Nanowire structure for sensing the electric field effect by the charge of the following target molecules on the substrate on which the insulating layer is formed; A spacer formed at a height corresponding to the length of the divider at the bottom of the nanowire structure; And A chemical functional group fixed to a surface of the nanowire structure and having a receptor for trapping the target molecule Biosensor using a nano-scale structure comprising a. Nanowire structure for sensing the electric field effect by the charge of the following target molecules on the substrate on which the insulating layer is formed; The insulating layer in which a region adjacent to the nanowire structure is etched; And A chemical functional group fixed to a surface of the nanowire structure and having a receptor for trapping the target molecule Biosensor using a nano-scale structure comprising a. The method according to claim 6 or 7, The nanowire structure is a biosensor using a nanoscale structure having a wire shape using a material having a semiconductor characteristic including silicon nanowires or carbon nanotubes. The method according to claim 1, 6 or 7, The receptor is attached to the surface of the thin film substrate by the chemical functional group, biosensor comprising any one or more of the enzyme substrate, ligand, amino acid, peptide, protein, nucleic acid, lipid and carbohydrate. The method according to claim 1, 6 or 7, The chemical functional group biosensor comprising any one or more of an amine group, a carboxyl group and a thiol group. Forming a flexible thin film on a micro channel having a test solution including target molecules; Surface-treating the flexible thin film to attach a chemical functional group connected to a receptor to capture the target molecule; And  Forming a nanowire structure at the bottom of the microchannel to sense the electric field effect caused by the charge of the target molecule Method of manufacturing a biosensor using a nano-scale structure comprising a. The method of claim 11, Forming the nanowire structure is a method of manufacturing a biosensor using a nano-scale structure to form a structure in the form of a semiconductor wire. The method of claim 11, wherein forming the nanowire structure comprises: Forming a nanowire in an area spaced upward from the substrate using a photolithography process; Forming an insulating layer on the entire surface of the substrate and the nanowire; And Using the nanowire transfer to make the insulating layer deposition surface a bottom surface Method of manufacturing a biosensor using a nano-scale structure comprising a. The method of claim 13, A method of manufacturing a biosensor using a nano-scale structure comprising etching the insulating layer in a region adjacent to the nanowires. The method of claim 14, wherein etching the insulating layer comprises: The etching method of manufacturing a biosensor using a nano-scale structure using isotropic or anisotropic etching.

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