KR100549104B1 - Method for fabricating a bionanoarray with sub-10 nanometer feature size - Google Patents

Abstract

The present invention forms a groove-shaped or pillar-shaped pattern having a size of several nanometers or less by using self-assembly of organic molecules and selective chemical adsorption of metals, and then, a bio pattern is formed on the nanopattern. The present invention relates to a method for manufacturing a bio nanoarray, comprising fixing a bioreceptor that binds to a substance or biomaterial.

Nano Pattern, Organic Molecule, Self Assembly, Chemisorption, Bio, Nano Array

Description

Method for fabricating a bionano array with a size of less than 10 nanometers {Method for fabricating a bionanoarray with sub-10 nanometer feature size}             

1 is a diagram of a model of organic molecules self-assembly. FIG. 1A is a three-dimensional structure in which a disk- or disk-shaped dendrimer 1 and a fan-shaped organic molecule 2 form a cylindrical shape 3 through self-assembly, and the cylinders are arranged in a hexagon (4). ) Is shown. FIG. 1B shows that rod-chain or cone-shaped molecules 5 form spheres 6 through self-assembly, which spheres are gathered and arranged in a constant structure 7 in three-dimensional space.

Figure 2 is a schematic diagram of a nanopattern forming process for manufacturing a bio nanoarray according to the present invention.

3 is a transmission electron micrograph showing that the organic molecules form a regular structure in the form of a hexagonal column.

4 is a scanning electron micrograph of a nanopattern formed by the present invention.

5 is a schematic diagram of fabricating a nanopattern of a metal thin film.

6 is a schematic diagram of manufacturing a bio nanoarray by fixing a biomaterial or a bioreceptor to a nanopattern of a metal thin film.

The present invention relates to a method for manufacturing a bio nanoarray by fixing a bioreceptor or a bioreceptor that binds to a biomaterial to a submicron pattern formed at a submicron level formed by self-assembly of organic molecules and selective adsorption of metals.

Until now, surface pattern formation has been mainly performed by photolithography using a polymer thin film as a photoresist. However, in order to realize a nanometer-sized high-precision pattern, the wavelength of light available and As a result, it is difficult to secure devices and technologies and to limit the resolution of the polymer itself.

Since 1990, there have been attempts to increase the resolution of patterns using shorter wavelengths of light, along with attempts to use them as new photoresist in existing photoelectric methods. In addition, a whole new concept of patterning technology has emerged: nano-patterning of surfaces using soft lithography. This method has the advantage of being able to form patterns quickly and inexpensively and chain work, but in fact, the resolution limit is 100 nm, so it is difficult to expect an increase in resolution for further integration.

Meanwhile, in the method of forming a nanoscale micropattern of a semiconductor device using organic molecules as a material for forming a pattern (KR 10 / 263671B1), the thickness of the micropattern remaining in the groove by using one more buffer layer to secure an excessive etching margin is provided. The technique of applying spacers to the buffer layer in order to secure the size of the grooves and to reduce the size of the grooves, but the number of process steps and the size of the pattern is several tens of nanometers.

 Recently published self-assembly structure (KR 02 / 89528A) relates to a small-size structure to form a device widely used in the microelectronics industry, the self-assembly method proposed in the present invention is an array (array) While providing the ability to form, self-assembly itself does not determine the location of device formation within boundaries along the surface. Thus, the formation of devices within boundaries along the surface requires individual positioning techniques, where suitable positioning techniques are used in conjunction with self-assembly to form structures that can generally function as discrete components in integrated electronic circuits. do. The positioning method can delimit the structure using lithography, direct forming, or other positioning techniques such that a patterned substrate is formed, and the device is assembled by self-assembly on the substrate.

Self-assembled structures can be incorporated with structures formed by conventional chemical vapor deposition and physical vapor deposition techniques and integrated electronics can include integrated optical components. The self-assembled structure may be formed using a dispersion of nanoparticles by adjusting to obtain a desired structure formation according to the conditions of the material surface and the temperature and concentration conditions. Linkers, one end chemically bonded to the nanoparticles, on one surface of the substrate, and selective bonding with the linker may be used to move to the self-assembly process.

Another alternative is to use natural interactions, such as electrostatic and chemical interactions, to direct the self-assembly process, where the nanoparticles are placed in small pores to position the nanoparticles within the boundaries defined by the porous region. It is stacked. Small holes may be found in certain materials such as inorganic oxides or two-dimensional organic crystals, and suitable holes may be formed, for example, by ion milling or chemical etching. However, the process is complicated and the pattern spacing remains at the level of several tens to one hundred nanometers.

In addition, a method of forming a nanometer high precision pattern using a self-assembled monolayer (KR 03 / 23191A) is known, and the present invention forms an aromatic imine molecular layer having a substituted end ring on a substrate, and the aromatic imine molecular layer Selectively bonding-cutting the substituents, and hydrolyzing the aromatic imine molecular layer in which the substituents are selectively bonded-cut, thereby providing a method of forming a pattern in a short time, but still staying at several tens of nanometers.

On the other hand, the surface of the tip of an atomic force microscope is buried with a surface-active molecule having a chemical affinity for a solid substrate, and a nano-level pattern is formed on the substrate with the tip of the tip, as if writing letters on paper. The deep-pen nanolithography method (Science, 283: 661, 1999) has the advantage of achieving high resolution nanopatterns down to 5 nm by using highly precise tips, but the patterns must be drawn one after the other. Since there is a problem in that it takes a long time to obtain a desired design because of serial processing, there is a limit to applying it directly through mass production.

As described above, various methods such as photolithography, ultraviolet light, and X-ray etching have been introduced, but the pattern formation below 100 nm has reached its limit. Instead of top-down methods, methods for bottom-up methods have been widely studied.

Upward structure-forming methods are based on the formation of microstructures of molecules by self-assembly. This basic technique is used to analyze microstructures of organic molecules by scanning electron microscopy (Hudson, SD et al., Science, 278). : 449, 1997) and papers confirming that the orientation of organic molecules depends on the substrate surface properties (Jung, HT et al., Macromolecules, 35: 3717, 2002). Only the orientation of organic molecules is described.

In addition, as in the method of forming a regular pattern using a block copolymer and a method of forming a dot pattern through chemisorption of metal (Park M. et al., Science, 276: 1401, 1997) Research into making a pattern of less than 100nm using is in progress, but due to the molecular chain of the polymer is a situation that stays on the pattern formation of more than a few tens of nanometers. In addition, when the block copolymer is used, the aspect ratio of the pattern to be formed is not large, the structure of the thin film is complicated, and there is a problem in that it is not easy to give the structural direction of the thin film.

On the other hand, microarray protein chips (microarray) is currently occupying a large proportion of research on diagnostic protomics (diagnostic protomics). Early array techniques (USP 5,143,854A), which used photolithographics to array polypeptides on the surface of substrates, have recently been tried in various ways. In particular, the development of microarray-type formats is becoming increasingly important in a variety of immunoassays, including antigen-antibody pairs and enzyme-liked immunosorbent assays. have.

However, protein arrays are not as easy to integrate or array in a practical format that is smaller or more sensitive than DNA arrays. In other words, the lattice pattern of DNA oligonucleotide can be generated on the surface of the substrate by photoetching technique, but for a protein composed of hundreds of amino acids, the antibody should generally have about 1400 amino acids. In order to achieve a higher density of grid patterns are required, but it is not easy to succeed.

Another problem is that proteins can easily lose their tertiary structure when handled under denaturing conditions ( Anal. Chem . 14A-15A, 2001; Anal. Chem., 73 , 8-12, 2001). There are many limitations in the operation.

The solution to these problems depends on how high the protein is arranged without losing the tertiary structure of the protein. To date, inkjet printing, drop-on-demand Technology, microcontact printing, and IBM's soft lithography. However, these methods also have spacing sizes of several tens of micrometers to several millimeters and develop highly integrated diagnostic protein nanoarrays with high density of real-life samples without losing the tertiary structure of the protein. Has never been tried.

Accordingly, the present inventors have made diligent efforts to develop an ultra-high density pattern forming method of which the process is simpler and the pattern size is several nanometers. The present invention has been completed by forming a pattern or columnar pattern and combining a biomaterial or a bioreceptor to the formed nanopattern.

It is an object of the present invention to form grooves or pillar-shaped nanopatterns of several nanometers or less by using self-assembly of organic molecules and selective chemisorption of metals, and to fix the biomaterial or bioreceptor on the formed nanopatterns. It is to provide a method for producing a bio nano array characterized in.

Still another object of the present invention is to provide a bio nanoarray prepared by the above method.

In order to achieve the above object, the present invention, (a) forming a thin film of organic molecules causing self-assembly on the substrate; (b) forming a regular structure by self-assembling the organic molecules by increasing the temperature above the liquid crystal phase transition temperature of the organic molecules and then slowly cooling them; (c) selectively chemisorbing a metal to a regular structure formed by self-assembly of the organic molecules; (d) etching the selectively chemisorbed metal thin film to remove the non-metal adsorbed portions to form nanopatterns of organic molecules; (e) etching the substrate using the nanopattern of the organic molecules as a mask to form groove-shaped nanopatterns on the substrate; And (f) fixing the bioreceptor that binds the biomaterial or the biomaterial to the groove-shaped nanopattern, and is manufactured by the method, and the groove is formed by the method. Bio nanoarray characterized in that a biomaterial or bioreceptor selected from the group consisting of proteins, peptides, enzyme substrates, ligands, amino acids, cofactors, carbohydrates, DNA, oligonucleotides and RNAs is fixed to the substrate nanopattern ( nonoarray).

The present invention also includes the steps of (a) forming a thin film of a biomaterial or a material having affinity with a viro receptor that binds to the biomaterial; (b) forming a thin film of organic molecules causing self-assembly on a thin film of the biomaterial or a material having affinity with the bioreceptor; (c) forming a regular structure by self-assembling the organic molecules by increasing the temperature above the liquid crystal phase transition temperature of the organic molecules and then slowly cooling them; (d) chemisorbing the metal selectively to the regular structure formed by self-assembly of the organic molecules; (e) etching the thin film on which the metal is chemisorbed to selectively remove a portion where the metal is not adsorbed to form a nanopattern of organic molecules; (f) forming a pillar-shaped metal nanopattern by etching a thin film of a biomaterial or a material having affinity with a bioreceptor using the nanopattern of the organic molecule as a mask; And (g) fixing the biomaterial or the bioreceptor to the nanopattern of the biomaterial or the material having affinity with the bioreceptor. Bio-selected from the group consisting of proteins, peptides, enzyme substrates, ligands, amino acids, cofactors, carbohydrates, DNA, lipids, oligonucleotides and RNAs in nanopatterns of pillar-shaped biomaterials or materials that have affinity with bioreceptors It provides a bio nanoarray (nonoarray) characterized in that the substance or bioreceptor is fixed.

The present invention also provides a method for detecting a reaction between a biomaterial and a bioreceptor, wherein the bio nanoarray is used.

The term 'bio nanoarray' used in the present invention is a concept encompassing a biomaterial or a bioreceptor that binds or reacts with a biomaterial or a biomaterial to a nanopattern, and is defined as including a biochip and a biosensor.

According to one embodiment of the present invention, the organic molecule used the compound of the formula (1), but may be used without limitation as long as the organic molecule to self-assemble.

<Formula 1>

Organic molecules that self-assemble include disc or disc dendrimers 1, fan-shaped organic molecules 2, rod-chain or conical molecules 5 and the like. Examples of the wedge-shaped organic molecules include compounds of formula (2), examples of discotic organic molecules include compounds of formula (3), and examples of conical organic molecules include compounds of formula (4).

<Formula 2>

<Formula 3>

<Formula 4>

 Unlike organic polymers in which monomers are covalently linked, these organic molecules form a uniform structure by physical secondary bonds such as van der Waals attraction. These organic molecules are self-assembled by an appropriate temperature, an external magnetic field, or an electric field to form specific microstructures. The organic molecules of Chemical Formula 1 used in this experiment correspond to wedge-shaped dendrimers. The wedge-shaped molecules form a plate-like structure (1) through self-assembly, the plate-like structures gather to form a columnar shape (3), and again form a three-dimensional structure (4) in which the cylinders are arranged in a hexagon (Fig. 1A). ). In addition, in the case of cone-shaped organic molecules 5, the cones are self-assembled to form a sphere 6, and the spheres are arranged in a constant structure 7 in a three-dimensional space (Fig. 1B).

In the present invention, the substrate (substrate) may be used a variety of materials such as silicon, glass, molten silica, polymer.

According to an embodiment of the present invention, the organic molecular thin film is preferably formed by spin-coating, rubbing, or solution spreading by forming a thin film on the surface of the water.

According to an embodiment of the present invention, the step of forming a regular structure by self-assembling the organic molecules by annealing is preferably cooled slowly after raising the liquid crystal phase transition temperature of the organic molecules using the temperature.

According to an embodiment of the present invention, the step of selectively chemisorbing the metal may be characterized by using RuO₄ (Ruthenium tetraoxide) compound.

According to an embodiment of the present invention, the etching of the substrate or the material thin film having affinity with the biomaterial or the bioreceptor may use reactive ion etching and / or ion milling.

The biomaterial or bioreceptor may be any one selected from the group consisting of proteins, peptides, enzyme substrates, ligands, amino acids, cofactors, carbohydrates, lipids, DNA, oligonucleotides and RNA.

The fixing of the biomaterial or the bioreceptor to the nanopattern may be characterized in that it uses a binding aid, and the binding aid is characterized in that a chemical substance having an aldehyde, an amine or an imine group attached to the carbon group is used. In more detail, the aldehyde may be bonded to the surface of the substrate, the amine group may be attached to the terminal of the biomaterial or the bioreceptor, and then bonded using the amine-aldehyde reaction.

Hereinafter, the present invention will be described in more detail.

According to a preferred embodiment of the present invention, first, the organic molecule of <Formula 1> using tetrahydrofuran (THF) as a solvent to make a solution of 1wt% to form a thin film on the substrate. In forming a thin film, spin-coating, rubbing, or solution spreading is mainly used to form a thin film on the surface of the water. In the embodiment, a silicon wafer was used as the substrate, and surface modification was not performed (FIG. 2A).

Since the organic molecules are self-assembled to raise the temperature above the liquid crystal phase transition temperature. In the case of the organic molecules used in the present invention, since the liquid crystal phase transition temperature is about 230 ° C., the temperature is raised to 240 ° C. and then cooled slowly. The organic molecules form a microstructure having a columnar arrangement (FIG. 2b).

According to a preferred embodiment of the present invention, the organic molecules are self-assembled by heat treatment as follows.

The nature of the organic molecules can be modified by heat treatment, suitable starting materials for heat treatment include organic molecules produced by laser pyrolysis. In addition, organic molecules used as starting materials may undergo one or more pre-heating steps under different conditions. In the heat treatment of organic molecules formed by laser pyrolysis, further treatment improves crystallinity and contaminants such as elemental carbon. It is possible to alter the stoichiometry, possibly by incorporating additional oxygen or elements from other gaseous or non-gas compounds. The organic molecules are generally preferably heated in an oven or the like to provide uniform heating. Treatment conditions are generally mild, so that a significant amount of particle sintering does not occur. Therefore, the heating temperature is preferably lower than the melting point of both the starting material and the product material. If the heat treatment involves a composition change, the size and shape of the molecules may change even at mild heating temperatures.

Self-assembled structures are generated on and / or within the surface of the material / substrate. The self-assembled structure can be positioned within the boundary so that each structure can form an element as part of a plurality of elements of circuits or appliances in such a way that the structure forms a positioned island. In particular, each structure may be a component of an integrated electronic circuit, which component may include, for example, an electrical component, an optical element and a photonic crystal.

In order to form the structure within a predetermined boundary, the formation of the self-assembled structure of interest generally requires a process of defining a limit of the structure and a self-assembly separate from the process. The demarcation process generally uses external forces to limit the structure. The self-assembly process itself generally does not delimit the structure. Self-assembly is based on the natural sensing function of the composition / material which, when combined, causes natural ordering in the resulting structure. In general, the positioning step may be performed before or after the self-assembly process, but the nature of the processing step may indicate a particular order. The net effect results in a self-assembled structure having a correspondingly covered range of nanoparticles within the boundaries, and a region outside the boundaries without these covering ranges. A separate demarcation process is linked to the self-assembly process by activating the self-assembly process within the boundary or making the area outside the boundary inactive. In general, an external force must be applied to perform the activation process or the deactivation process.

Formation of a uniform structure on the bulk of organic molecules can be confirmed by transmission electron microscopy. As a result of manufacturing the sample through the process under the same conditions as used in this experiment, the results as shown in FIG. 3 were obtained, and it was found that the organic molecules formed a regular structure in the form of a hexagonal column.

According to a preferred embodiment of the present invention, a process of selectively chemisorbing a metal to a predetermined structure formed by self-assembly of the organic molecules is as follows.

First, the RuO ₄ solution and the substrate coated with the organic molecular thin film are placed together in a glass container so as not to directly contact the solution. In this process, Ru metal in the RuO ₄ solution diffuses into the gas phase and is adsorbed onto the organic thin film on the substrate. The adsorbed Ru metal selectively reacts with a specific part of the structure.

In the present invention, although RuO ₄ was used, all metals capable of selectively chemisorbing on the structure formed by OsO ₄ (osmium tetraoxide) or other organic molecules can be used.

After the chemical adsorption process according to a preferred embodiment of the present invention, when the etching process, the organic molecular layer on the surface is partially peeled to obtain a device in which the nanopattern is finally formed, such an etching process is a semiconductor Any method commonly used in device processing can be used without limitation. For example, an etching solution such as a KCN-KOH mixed solution or an HF aqueous solution may be used, or may be performed through reactive ion etching (RIE) or ion milling.

According to a preferred embodiment of the present invention, the nanopattern formed as described above may be used as an important surface substrate for reacting various kinds of biomaterials or bioreceptors to form an array of a desired shape, which is highly integrated and miniaturized. It will play a very important role in producing biochips.

In general, a biochip is manufactured by connecting a biomaterial or a bioreceptor directly to a substrate, or by connecting a biomaterial or a bioreceptor through a linker molecule. For example, in the case of a DNA chip, a protein chip or a protein sensor, in order to fix a biomaterial such as DNA, an antibody or an enzyme on a solid substrate, the aldehyde is bound to the substrate surface and the biomaterial or the biomaterial is bound to the substrate. The amine group may be bonded to a bioreceptor, and may be immobilized by chemical bonding of an amine-aldehyde to generate a desired bioarray.

The method of manufacturing a DNA chip in the bioarray according to the present invention includes a step of manufacturing a DNA chip by fixing a probe prepared in advance to a solid surface by a spotting method. The probe bound to the amine group is dissolved in 1X to 7X, preferably 2X to 5X, most preferably 3X SSC (0.45M NaCl, 15 mM C ₆ H ₅ Na ₃ O ₇ , pH 7.0) buffer, A layer (microarrayer) is used to spot the aldehyde-bonded substrate and then react to fix the probe to the substrate. At this time, the concentration of the probe is at least 10 pmol / μl, preferably at least 50 pmol / μl, most preferably at least 100 pmol / μl, 70 to 90% of the amine bound to the probe and the aldehyde bound to the substrate, preferably The reaction is allowed to react for 4 to 8 hours, preferably 5 to 7 hours, and most preferably 6 hours under 80% humidity.

The point-shaped structure obtained from the present invention is capable of converting the structure to the corresponding inverse phase. Silicon or silicon nitride (SiN) is deposited on the substrate on which the dot structure is formed to fill the exterior of the structure. Then, if the original point-shaped structure is selectively removed, it is possible to deform from the initial point-shaped structure to the hole-shaped structure.

Hereinafter, the present invention will be described with reference to Examples. However, embodiments according to the present invention can be modified in many different forms, the scope of the present invention should not be construed as limited to the following examples. Embodiments of the present invention are provided to more fully explain the present invention to those skilled in the art.

Example 1 Synthesis of Organic Molecules

The organic molecules of Chemical Formula 1 used in the present invention were synthesized by the same process as in <Scheme 1>. In the first step, potassium carbonate serving as a base was dissolved in diformamide at 65 ° C., followed by adding ethyl 4′-hydroxy-4-biphenyl carboxylate and perfluorododecyl bromide (1) for 18 hours. Reflux reaction was performed and compound (2) was obtained by esterification reaction.

     The compound (2) thus obtained was subjected to a reduction reaction at room temperature with purified aluminum lithium hydride in purified tetrahydrofuran, and then dissolved in a mixed solvent of dichloromethane and tetrahydrofuran, and then the amount of diformamide in the amount of catalyst. After the addition, the reaction was carried out for about 10 minutes at room temperature by thionyl chloride to obtain compound (3).

The last step, the esterification reaction, proceeded similarly to the first step. Methyl-3.4.5-trihydroxy benzoate and the compound (3) prepared in the previous step were added to a mixture of diformamide and tetrahydrofuran with a solvent of potassium carbonate, followed by reflux reaction at 70 ° C. for 24 hours. The organic molecule of Formula (1) was synthesized.

Scanning electron microscopy confirmed that these organic molecules form a regular cylindrical structure of less than nanometers.

<Scheme 1>

Example 2: Modification of the Substrate Surface

In the present invention, a silicon wafer was used that did not change the properties of the substrate. If necessary, metals, nonmetals and other thin films can be formed on the substrate.

Example 3: Formation of Organic Molecular Thin Film

The organic molecular sample was dissolved in tetrahydrofuran (THF) solvent and spin-coated on a silicon wafer to form a thin film (FIG. 2A). In the present invention, spin-coated for 10 to 30 seconds at a speed of 2000 ~ 3000 rpm, in this process can be appropriately changed the thickness of the thin film.

Example 4: Annealing

After raising the temperature to 240 ℃ was cooled slowly to form a regular microstructure (Fig. 2b). In the case of the organic molecules used in the present invention, self-assembly occurs at 240 ° C., which may vary depending on the organic molecules used. At this temperature, organic molecules have sufficient mobility for self-assembly and self-assembly with the most stable structure. In the case of the organic molecules used in the present invention, the three-dimensional structure in which the cylinders are arranged in a hexagonal shape is the most stable structure.

Example 5 Chemisorption with RuO₄ (ruthenium tetraoxide)

In the case of the present organic molecules, since the central portion can be selectively chemisorbed using the RuO ₄ compound, the sample was exposed to RuO ₄ for several minutes to chemisorb the Ru metal on the central portion (FIG. 2C).

When the sample is exposed to RuO ₄ , Ru metal diffuses into the air and is adsorbed onto the organic thin film. Ru metal chemically reacts with specific reactors (ether bond, alcohol, benzene ring, amine, etc.), and in the case of the organic molecules used in the present invention, the region corresponding to the central portion of the cylinder is chemisorbed by Ru metal.

Depending on the organic molecules used, it is possible to replace the chemisorbed metal. For example, OsO ₄ (osmium tetraoxide) is chemically adsorbed to a reactor such as carbon double bonds, alcohols, ether bonds, and amines.

Example 6 Etching

After the reactive ion etching process, the center part remains in accordance with the difference in the etching rate, thereby forming a dot form (FIG. 2D). 4 is a scanning electron micrograph showing the shape of the dots formed therefrom. In the present invention, the etching was performed for about 100 seconds using CF ₄ gas. Etching time varies from instrument to instrument, which is not universal in all cases and requires a test step to set conditions.

Example 7 Method of Forming Nanopattern on Substrate

The substrate was etched using the nanopattern of organic molecules obtained in the process of Examples 1 to 6 as a mask to form a nanopattern on the substrate. In the present invention, the intermediate layer is not used on the substrate, but when the other thin film layer is formed between the substrate and the organic molecular thin film, the formed nanostructure of the dot structure serves as a mask in the subsequent etching process. That is, the lower end of the portion where the dot pattern is formed is not etched, and the intermediate thin film layer whose surface is exposed is etched so that the pattern formed by the organic molecules is transferred to the intermediate thin film layer. This depends on the material used as the intermediate thin film layer, in the case of the metal thin film layer can be etched by ion milling (ion milling), in the case of other non-metal, organic thin film layer can be etched by reactive ion etching and ion milling. Etching conditions depend on the characteristics of each thin film layer.

Example 8 Fabrication of Bio Nanoarrays by Attaching Biomaterials or Viro Receptors to Grooved Nanopatterns

In order to bind a biomaterial or a bioreceptor that binds to the biomaterial to the groove-shaped substrate nanopattern obtained in Example 7, an aldehyde group was attached to the substrate and an amine group was attached to the terminal of the biomaterial or the bioreceptor, followed by an amine-aldehyde reaction. Through the biomaterial or bioreceptor was attached to the substrate.

Example 9 Fabrication of Bio Nanoarrays by Attaching Biomaterials or Bioreceptors to Columnar Nanopatterns

First, a thin film of a biomaterial or a material having excellent affinity with a bioreceptor which binds to the biomaterial is formed on the substrate, and then the processes of Examples 1 to 6 were performed. Using nanopatterns of organic molecules obtained as a mask, ion milling was performed to prepare nanopatterns of material thin films having affinity with biomaterials or bioreceptors (FIG. 6).

In this embodiment, gold (Au) was used as a material having affinity with a biomaterial or a bioreceptor. Gold may selectively bind to biomaterials or bioreceptors containing seed groups (-SH). By using these properties, biomolecules of high density may be fabricated by selectively binding biomolecules to gold nanopatterns (FIG. 6).

The present invention relates to a bio nanoarray by combining a biomaterial or a bioreceptor to a groove pattern or columnar pattern having a sub-nanometer size formed by self-assembly of organic molecules and selective chemical adsorption of metals. Has the effect of providing a breakthrough method of manufacturing.

Simple modifications and variations of the present invention can be readily used by those skilled in the art, and all such variations or modifications can be considered to be included within the scope of the present invention.

Claims (19)

Method for producing a bio nanoarray (nanoarray), characterized in that it comprises the following steps: (a) forming a thin film of organic molecules causing self-assembly on a substrate; (b) forming a regular structure by self-assembling the organic molecules by increasing the temperature above the liquid crystal phase transition temperature of the organic molecules and then slowly cooling them; (c) selectively chemisorbing a metal to a regular structure formed by self-assembly of the organic molecules; (d) etching the selectively chemisorbed metal thin film to remove the non-metal adsorbed portions to form nanopatterns of organic molecules; (e) etching the substrate using the nanopattern of the organic molecules as a mask to form groove-shaped nanopatterns on the substrate; And (f) binding a bioreceptor to the biomaterial or the biomaterial to the groove-shaped nanopattern. Method for producing a bio nanoarray (nanoarray), characterized in that it comprises the following steps: (a) forming a thin film of biomaterial or a material compatible with the bioreceptor binding to the biomaterial on the substrate; (b) forming a thin film of organic molecules causing self-assembly on a thin film of the biomaterial or a material having affinity with the bioreceptor; (c) forming a regular structure by self-assembling the organic molecules by increasing the temperature above the liquid crystal phase transition temperature of the organic molecules and then cooling them slowly; (d) chemisorbing the metal selectively to the regular structure formed by self-assembly of the organic molecules; (e) etching the thin film on which the metal is chemisorbed to selectively remove a portion where the metal is not adsorbed to form a nanopattern of organic molecules; (f) forming a pillar-shaped nanopattern by etching a thin film of a material having affinity with a biomaterial or a bioreceptor using the nanopattern of the organic molecule as a mask; And (g) binding the biomaterial or the bioreceptor to the nanopattern of the biomaterial or the material having affinity with the bioreceptor. The method of claim 1 or 2, wherein the organic molecule is a compound of formula (1). <Formula 1>

The method according to claim 1 or 2, wherein the thin film of organic molecules is formed by spin coating (coating), rubbing (rubbing), or by forming a thin film on the surface (solution spreading) How to. delete A method according to claim 1 or 2, wherein the chemisorption of the metal selectively comprises RuO ₄ (ruthenium tetraoxide). The method of claim 1, wherein etching the substrate to form grooved nanopatterns in the substrate uses reactive ion etching. The method of claim 2, wherein the etching of the thin film of the biomaterial or the bioreceptor to form a pillar-shaped nanopattern uses reactive ion etching and / or ion milling. The method according to claim 1 or 2, wherein the biomaterial or bioreceptor is any one selected from the group consisting of proteins, peptides, enzyme substrates, ligands, amino acids, cofactors, carbohydrates, lipids, DNA, oligonucleotides and RNA. How to. The method of claim 1, wherein the biomaterial or the bioreceptor is attached to the nanopattern of the substrate using a binding aid. The method of claim 10, wherein the binding aid is a chemical having an aldehyde, amine or imine group attached to the carbon group end. 12. The method of claim 11, wherein an amine group is attached to the end of the biomaterial or bioreceptor, and an aldehyde is applied to the surface of the substrate to bind the biomaterial or bioreceptor to the nanopattern of the substrate by reaction of the amine-aldehyde. The method of claim 2, wherein the biomaterial or material that is compatible with the bioreceptor is a metal. The method of claim 13, wherein the metal is gold (Au). A biomaterial or a biomaterial produced by the method of claim 1 and selected from the group consisting of proteins, peptides, enzyme substrates, ligands, amino acids, cofactors, carbohydrates, lipids, DNA, oligonucleotides, and RNA in the groove-shaped substrate nanopattern Bio nanoarray (nonoarray) characterized in that the receptor is coupled. Bio-produced by the method of claim 10, and selected from the group consisting of proteins, peptides, enzyme substrates, ligands, amino acids, cofactors, carbohydrates, lipids, DNA, oligonucleotides and RNA through binding aids to the groove-shaped nanopattern Bio nanoarrays characterized in that the substance or bioreceptor is coupled. The bio nanoarray of claim 16, wherein the binding aid is a chemical having an aldehyde, an amine or an imine group attached to a carbon group end. Prepared by the method of claim 2, the nanopattern of the biomaterial having a columnar shape or affinity with the bioreceptor, proteins, peptides, enzyme substrates, ligands, amino acids, cofactors, carbohydrates, lipids, DNA, oligonucleotides and Bio nanoarray (nonoarray) characterized in that the biomaterial or bioreceptor selected from the group consisting of RNA is combined. 19. A method for detecting a reaction between a biomaterial and a bioreceptor, wherein the bio nanoarray of claim 16 or 18 is used.

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