KR101767573B1 - Biosensor and Manufacturing Method of Biosensor - Google Patents

Abstract

A biosensor according to an embodiment of the present invention includes: a thin-film transistor (TFT) including a gate electrode, a source electrode, a drain electrode, a source electrode, an active pattern connected to the drain electrode and having a channel formed therein, and a gate insulating pattern for insulating the active pattern and the gate electrode; a probe arranged on a surface of the active pattern and specifically reacting to a target material; and a medium for bringing the probe in contact with an active surface, wherein the probe is printed while being coupled to the medium, and is arranged on the active surface. Accordingly, the present invention is able to reduce a process time when compared to an existing technology, and also maintain the sensitivity for sensing and accuracy.

Description

TECHNICAL FIELD [0001] The present invention relates to a method of manufacturing a biosensor,

The present invention relates to a biosensor and a method of manufacturing the biosensor.

The conventional biosensors detect the inclusion of a target substance and / or its concentration using optical instruments. Since the use of optical equipment is complicated and uneconomical, a lot of research is underway on transistor-based biosensors to solve these problems. A transistor-based biosensor performs a number of preprocessing steps such as immersing a transistor in a probe-dispersed solution to attach the probe to the electrode or active layer.

The conventional biosensor requires a long time in a pre-process for attaching a probe to an electrode or an active layer. During the pre-process, the transistor is damaged or deteriorated in function, thereby reducing sensing sensitivity and accuracy. Further, since a long time is consumed in the pretreatment process to form the biosensor, it is required to reduce the time consumed to form the biosensor.

The present embodiment is for solving the problems of the above-described prior arts. The present embodiment provides a biosensor manufacturing method and a biosensor capable of improving sensing sensitivity and accuracy while reducing the process time for forming the biosensor One of the main purposes is.

The biosensor according to the present embodiment includes a gate electrode, a source electrode, a drain electrode, a thin film transistor including an active pattern formed by a channel formed by being connected to a source electrode and a drain electrode, and a gate insulating pattern insulating the active pattern from the gate electrode A thin film transistor (TFT), a probe disposed on the surface of the active pattern and specifically reacting with the target material, and a medium for adhering the probe to the active surface, wherein the probe is printed in an active state, .

A method of forming a biosensor according to an embodiment of the present invention includes the steps of (a) forming a thin film transistor (TFT) on a substrate, (b) preprocessing the probe and the medium specifically reacting with the target, , and (c) arranging a probe coupled to the medium by printing on the active pattern surface of the thin film transistor.

According to the present embodiment, since the biosensor is formed using a printing process, an advantage that the process time can be reduced compared to the prior art, and an advantage that the sensing sensitivity and accuracy can be maintained can be provided.

FIGS. 1 to 4 and 6 are sectional views showing the outline of each step of the method for manufacturing a biosensor according to the present embodiment.
5 is a view schematically showing a process of printing and arranging a probe P coupled with the medium 210 on the surface of the active pattern 130. As shown in FIG.
7 is a view for explaining a biosensor according to the present embodiment.
8 to 12 are graphs showing experimental data obtained by experimenting the biosensor according to the present embodiment.

Hereinafter, a biosensor and a manufacturing method thereof according to the present embodiment will be described with reference to the accompanying drawings. 1 to 4 are cross-sectional views showing the outline of each step of the method for manufacturing a biosensor according to the present embodiment. Referring to FIG. 1, a gate electrode G is formed on a substrate 110, and a gate insulating film 120 is formed to electrically isolate the gate electrode G.

In one embodiment, the substrate 110 is an extensible substrate that is stretchable. In another embodiment, the substrate 110 is a hardened glass or silicon substrate.

The gate electrode G is formed of a conductive metal such as aluminum or gold and a channel is formed in the active pattern 130 by an electrical signal provided to the gate electrode G. The gate insulating film 120 electrically insulates the gate electrode G from the source electrode S, the drain electrode D and the active pattern 130. [ For example, the gate insulating film 120 may be formed of an insulating material such as PMMA.

2 is a view schematically showing a state in which the active pattern 130 is formed. Referring to FIG. 2, an active pattern 130 is formed. A channel for electrically connecting the source electrode S (see FIG. 3) and the drain electrode D (see FIG. 3) is formed in the active pattern 130 by an electrical signal provided to the gate electrode G. For example, the active pattern 130 may be formed by forming a material layer such as graphene, pentacene, or the like, and patterning the material layer.

3 is a view showing a state in which a thin film transistor (TFT) is formed by forming a source electrode S and a drain electrode D. Referring to FIG. 3, a source electrode S and a drain electrode D are formed to be electrically connected to one end and the other end of the active pattern 130, respectively. In one embodiment, the source electrode S and the drain electrode D may be formed of a conductive metal pattern such as gold or aluminum.

4 is a view showing a state in which a probe P attached to the medium 210 is disposed on the surface of the active pattern 130. In FIG. Referring to FIG. 4, a probe P attached to the medium 210 is disposed on the surface of the active pattern 130. The probe P is coupled to or reacts with a target (Target, T) to be detected by the biosensor according to the present embodiment. For example, the probe P may be a substance that specifically binds to a target T to be detected using a biosensor. In one embodiment, if the target (T) is a deoxyribonucleic acid (DNA) having a specific base sequence, the probe (P) is a substance having a sequence complementary to a base sequence of the target. DNA, RNA, Ribonucleic Acid, Protein, Hormone, Antigen and so on, it is possible to detect substances that specifically bind to each of these DNA, RNA, proteins, hormones and antigens Is used as a probe (P). The medium 210 may, in one embodiment, be a graphene oxide.

The medium 210 has a property of being easily combined with the probe P and the medium 210 to which the probe P is coupled is also physically and chemically bonded to the active pattern 130. Therefore, when it is difficult to fix the probe P to the active pattern 130, the probe 210 can be used to immobilize the probe P to the medium 210. [

In an embodiment, the medium 210 and the probe P may be coupled through a preprocessing process. As an example, a process of immobilizing HER2, which forms an antigen-antibody reaction with SkBr3, which is a breast cancer cell, using medium of Graphene Oxide (Graphene Oxide) The mediator 210, graphene oxide, is reacted with NaOH, Cl-COONa to form graphene oxide-COOH. After the formation of GO-PEG-NH2 by reacting the formed graphene oxide-COOH with EDC and 6-arm PEG amine, GO-PEG-NH2 was reacted with HS as a half antibody to form graphene oxide and probe HER2.

5 is a view schematically showing a process of printing and arranging a probe P coupled with the medium 210 on the surface of the active pattern 130. As shown in FIG. In one embodiment, the process of disposing the probes P attached to the medium 210 in the active pattern 130 is performed in a printing process, and a mold (mold) Transfer printing in which a probe P attached to the medium 210 is applied to the active pattern 130 and then printing on the active pattern 130 is performed on the medium 210 with the nozzle illustrated in FIG. A probe P attached to the medium 210 in the active pattern 130 using a roller as illustrated in Fig. 5 (c), inkjet printing to eject the attached probe P, A gravure printing process and a roll-to-roll printing process may be used. In another embodiment not shown, the probes P attached to the medium 210 may be sprayed to dispose the probes P in the active pattern 130.

FIG. 6 is a view showing a state in which a fluid channel (C) through which a solution containing a target to be detected is contacted with a probe is formed by the biosensor according to the present embodiment. Referring to FIG. 6, PDMS is formed to form a fluid tube C so that a solution containing a target can flow to the surface of the active pattern 130. According to an embodiment not shown, an inlet for injecting a solution containing a target material is formed at one end of the fluid tube, and an outlet for discharging a solution containing a target material may be formed at the other end.

Hereinafter, the operation of the biosensor according to the present embodiment will be described with reference to FIG. For the sake of brevity and clarity, the description of the same or similar parts to those of the above-described embodiment may be omitted. When the solution containing the target T to be detected by the biosensor flows into the fluid pipe C, the target T reacts specifically with the probe P while flowing in the solution.

For example, the target T and the probe P react in the form of coupling each other, cutting a part of the probe P, or the like, and change the electrical properties of the active pattern 130 as a result of the reaction. The current-voltage characteristic of the thin film transistor included in the biosensor changes due to a change in the electrical property of the active pattern 130 due to the combination of the target T and the probe P, The presence or absence of the target T and / or the concentration of the target T in the solution can be detected.

The biosensor according to the present embodiment provides a predetermined voltage between the drain electrode D and the source electrode S and supplies a predetermined voltage between the drain electrode D and the source electrode S depending on the voltage provided between the gate electrode G and the source electrode S. [ D) and the source electrode (S) to detect the presence or absence of the target (T) in the solution and / or the concentration of the target (T) in the solution.

According to another embodiment of the present invention, the biosensor is provided with a predetermined voltage between the gate electrode G and the source electrode S and supplies a predetermined voltage between the drain electrode D and the source electrode S, A change in the current flowing between the electrode D and the source electrode S can be detected and detected to detect the presence of the target T in the solution and / or the concentration of the target T in the solution.

Experimental Example

Hereinafter, an experimental example of the biosensor according to the present embodiment will be described with reference to FIGS. 8 to 12. FIG. In this experiment, a thin film transistor in which an active pattern 130 is formed of pentacene and a probe P coupled to a graphene oxide medium on the active pattern 130 of the thin film transistor are disposed, Sensor was formed. In addition, a voltage of -20 V was applied to both the drain electrode and the source electrode of the biosensor of the biosensor.

The black curve in FIG. 8 is a curve showing a change in current flowing between the drain electrode and the source electrode while changing the gate-source voltage in the thin film transistor having the pentacene active layer, In which a probe (P) coupled with an oxide (graphene oxide) medium is arranged on a substrate. Referring to FIG. 8, it can be seen that the current change (red) of the biosensor according to this embodiment is similar to that of the current change (black) of the thin film transistor.

9 is a graph showing changes in current-voltage characteristics before and after providing the buffer solution to the fluid tube C of the biosensor. Referring to FIG. 9, a biosensor used in the present experiment is formed, and a black curve is formed by measuring the current change by providing the voltage to each electrode. Next, an RPMI buffer solution not containing the target T is flown into the fluid tube C, and the electric characteristic of the active pattern is measured after one hour is passed to show a current-voltage characteristic like a red curve.

10 (a) is a biosensor in which a probe P coupled with a graphene oxide medium is arranged on an active pattern 130 formed of pentacene, and a SkBr3 cancer cell as a target (T) is detected 10 (b) is a photograph of a state in which a SkBr3 cancer cell as a target (T) and a probe (P) have reacted with each other. As the probe (P), SkBr3, which is a target (T), and HER2 antigen (angtigen), which forms an antigen-antibody reaction, were used. In Fig. 10 (a), the points distinguished by s1 are combined with HER2 where SkBr3, which is the target T, is the probe, and the points distinguished by s2 are HER2, which is the probe not combined with the target. In Fig. 10 (b), it can be seen that SkBr3 as the target (T) binds to HER2 as the probe (P).

FIG. 11 shows the current-voltage curve (red) measured with the biosensor in the state of detecting the target (T) SkBr3 cancer cells and the current-voltage curve (black) measured without providing the buffer solution in the fluid tube together Fig.

When the black curve and the red curve are compared, it can be seen that a lower current flows when the target T and the probe P are coupled even though the same voltage is provided between the gate electrode and the source electrode. The probe P coupled with the target T and / or the target T has an electrical influence on the active pattern and the carrier mobility in the channel of the thin film transistor formed in the active pattern is changed .

Fig. 12 is a graph showing changes in carrier mobility before and after the reaction of the target (T) and the probe (P). 12 (a) is a diagram showing a change in carrier mobility that occurs when a reaction time of one hour elapses after flowing only a buffer solution into a fluid tube C of the biosensor according to the present embodiment. Referring to the left side of FIG. 12, it can be seen that when the buffer solution is flowed through the biosensor fluid tube C, the mobility of the carrier is reduced by about 15% to 47% as compared with the case where nothing is supplied to the fluid tube. On the contrary, when the buffer solution containing the target T is provided to the fluid tube C of the biosensor, the mobility of the carrier is reduced by 68% to 85% as compared with the case where nothing is flowed into the fluid tube have.

The biosensor according to the present embodiment can provide an advantage that the target can be detected with high accuracy. In addition, although the conventional technique requires a long time in the process of forming the biosensor, in the present embodiment, since the probe is formed on the active pattern using the printing method, the time required for forming the biosensor can be shortened .

110: substrate 120: gate insulating film
130: active pattern 210: medium

Claims (11)

1. A biosensor for detecting a target material,
1. A thin film transistor (TFT) comprising a gate electrode, a source electrode, a drain electrode, an active pattern connected to the source electrode and the drain electrode to form a channel, and a gate insulating film for insulating the active pattern from the gate electrode );
A probe disposed on a surface of the active pattern and specifically reacting with the target material; And
And an agent for adhering the probe to the surface of the active pattern,
Wherein the probe is disposed on a surface of the active pattern using a printing process while being immobilized in advance in association with the medium,
The printing process may be performed using one of the following methods: spray, transfer printing, inkjet printing, gravure printing, and roll-to-roll printing. Biosensor. The method according to claim 1,
Wherein the probe corresponds to a substance that specifically binds to one of DNA, RNA, protein, hormone and antigen to be detected. delete The method according to claim 1,
Wherein the active pattern comprises pentacene. The method according to claim 1,
Wherein the biosensor further comprises a fluid tube through which a solution containing the target material flows in contact with the probe. The method according to claim 1,
Wherein the medium comprises graphene oxide. A method of forming a biosensor for detecting a target material,
A thin film transistor (TFT) comprising a gate electrode, a source electrode, a drain electrode, an active pattern connected to the source electrode and the drain electrode to form a channel, and a gate insulating film for insulating the active pattern from the gate electrode, ;
A preprocessing step of immobilizing a probe that specifically reacts with the target material and an agent for bonding the probe to the surface of the active pattern;
Placing the probe in association with the medium on the surface of the active pattern using a printing process,
The printing process may be performed using one of the following methods: spray, transfer printing, inkjet printing, gravure printing, and roll-to-roll printing. A method of forming a biosensor. 8. The method of claim 7,
Wherein the probe is a substance that specifically binds to one of DNA, RNA, protein, hormone and antigen to be detected. 8. The method of claim 7,
Wherein the medium comprises graphene oxide. 8. The method of claim 7,
Wherein the active pattern comprises pentacene. 8. The method of claim 7,
And forming a fluid tube through which a solution containing the target material flows in contact with the probe.

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