阅读说明：本技术 用于使聚合物基底的表面改性的方法以及具有由此改性的表面的聚合物基底 (Method for modifying the surface of a polymer substrate and polymer substrate having a surface modified thereby ) 是由 洪锺郁 申秀贞 金炫中 金弘徹 金正来 崔炳炅 金铁珉 于 2017-03-03 设计创作，主要内容包括：本发明涉及用于使聚合物基底的表面改性的方法。具体地,本发明提供了使用等离子体处理、亲水性底漆和包含疏水性氟化合物的涂覆剂来使聚合物基底的表面改性的方法。(The present invention relates to a process for modifying the surface of a polymeric substrate. In particular, the present invention provides a method of modifying the surface of a polymeric substrate using a plasma treatment, a hydrophilic primer, and a coating agent comprising a hydrophobic fluorine compound.)

1. A method for modifying a surface of a polymeric substrate, the method comprising:

Treating the surface of the polymeric substrate with plasma;

Applying a hydrophilic primer to the surface of the plasma-treated polymeric substrate; and

Coating the plasma-treated polymeric substrate with a coating agent comprising a hydrophobic fluorine compound.

2. The method of claim 1, wherein the polymer substrate is a siloxane-based polymer.

3. The method of claim 2, wherein the siloxane-based polymer is a silicone rubber.

4. The method of claim 1, wherein the plasma is a plasma of argon, nitrogen, oxygen, or a mixed gas in which two or more of these gases are mixed.

5. The method of claim 1, wherein, upon treating the surface of the polymeric substrate with plasma,

The plasma was formed from the mixed gas by applying power of 700W to 800W with an RF power supply in an apparatus in which the pressure was maintained at atmospheric pressure (760 torr).

6. The method of claim 1, wherein the hydrophobic fluorine compound comprises a condensation polymer of a fluorine-based polymer and a functional organic or inorganic silane compound.

7. The method of claim 6, wherein the fluorine-based polymer is selected from the group consisting of: a fluoroacrylate polymer; and a perfluoropolyether; and a polymer comprising: tetrafluoroethylene, hexafluoropropylene, chlorotrifluoroethylene, trifluoroethylene, vinylidene fluoride, octafluorobutene, pentafluorophenyl trifluoroethylene, pentafluorophenyl ethylene, and repeating units derived from the monomers.

8. The method of claim 6, wherein the functional organic or inorganic silane compound comprises one or more functional groups selected from the group consisting of: amino, vinyl, epoxy, alkoxy, halogen, mercapto, and thioether groups.

9. The method of claim 6, wherein the functional organic or inorganic silane compound is selected from the group consisting of: aminopropyltriethoxysilane; aminopropyltrimethoxysilane; amino-methoxysilane; phenylaminopropyl trimethoxysilane; n- (2-aminoethyl) -3-aminopropyltrimethoxysilane; n- (β -aminoethyl) - γ -aminopropylmethyldimethoxysilane; gamma-aminopropyl-tri-dimethoxysilane; gamma-aminopropyldimethoxysilane; gamma-aminopropyltriethoxysilane; gamma-aminopropyldiethoxysilane; vinyltriethoxysilane; vinyl trimethoxysilane; vinyltris (methoxyethoxy) silane; a dialkoxysilane, trialkoxysilane, or tetraalkoxysilane; vinylmethoxysilane; vinyl trimethoxysilane; a vinyl epoxy silane; vinyltriethoxysilane; 3-glycidoxypropyltrimethoxysilane; 3-methacryloxypropyltrimethoxysilane; gamma-glycidoxypropyltriethoxysilane; gamma-methacryloxypropyltrimethoxysilane; chlorotrimethylsilane; trichloroethylsilane; trichloromethylsilane; trichlorophenylsilane; a trichlorosilane; mercaptopropyltriethoxysilane; trifluoropropyltrimethoxysilane; bis (trimethoxysilylpropyl) amine; bis (3-triethoxysilylpropyl) tetrasulfide; bis (triethoxysilylpropyl) disulfide; (methacryloxy) propyltrimethoxysilane; 2- (3, 4-epoxycyclohexyl) ethyltrimethoxysilane; 3-glycidoxypropylmethyldiethoxysilane; 3-glycidoxypropyldiethoxysilane; 3-glycidoxypropyltriethoxysilane; p-styryl trimethoxysilane; and combinations thereof.

10. The method of claim 6, wherein the hydrophobic fluorine compound is selected from the group consisting of: polytetrafluoroethylene, ethylene-tetrafluoroethylene copolymer, perfluoropolyether group-containing silane, tetrafluoroethylene-hexafluoropropylene copolymer, partial hydrolysis condensate of a fluorine-containing oxyalkylene group-containing polymer composition, a fluoropolymer composition, polyvinylidene fluoride, and a fluorine-containing organopolysiloxane.

11. The method of claim 1, wherein the primer comprises a condensation polymer of a silicone-based polymer and a functional organic or inorganic silane compound.

12. The method of claim 11, wherein the functional organic or inorganic silane compound is selected from the group consisting of: aminopropyltriethoxysilane; aminopropyltrimethoxysilane; amino-methoxysilane; phenylaminopropyl trimethoxysilane; n- (2-aminoethyl) -3-aminopropyltrimethoxysilane; n- (β -aminoethyl) - γ -aminopropylmethyldimethoxysilane; gamma-aminopropyl-tri-dimethoxysilane; gamma-aminopropyldimethoxysilane; gamma-aminopropyltriethoxysilane; gamma-aminopropyldiethoxysilane; vinyltriethoxysilane; vinyl trimethoxysilane; vinyltris (methoxyethoxy) silane; a dialkoxysilane, trialkoxysilane, or tetraalkoxysilane; vinylmethoxysilane; vinyl trimethoxysilane; a vinyl epoxy silane; vinyltriethoxysilane; 3-glycidoxypropyltrimethoxysilane; 3-methacryloxypropyltrimethoxysilane; gamma-glycidoxypropyltriethoxysilane; gamma-methacryloxypropyltrimethoxysilane; chlorotrimethylsilane; trichloroethylsilane; trichloromethylsilane; trichlorophenylsilane; a trichlorosilane; mercaptopropyltriethoxysilane; trifluoropropyltrimethoxysilane; bis (trimethoxysilylpropyl) amine; bis (3-triethoxysilylpropyl) tetrasulfide; bis (triethoxysilylpropyl) disulfide; (methacryloxy) propyltrimethoxysilane; 2- (3, 4-epoxycyclohexyl) ethyltrimethoxysilane; 3-glycidoxypropylmethyldiethoxysilane; 3-glycidoxypropyldiethoxysilane; 3-glycidoxypropyltriethoxysilane; p-styryl trimethoxysilane; and combinations thereof.

13. A polymer substrate, the surface of which is modified by a method for modifying the surface of a polymer substrate according to any one of claims 1 to 12.

14. A biochip comprising the polymer substrate of claim 13.

Technical Field

The present invention relates to a method for modifying the surface of a polymer substrate, and in particular, to a method for modifying the surface of a polymer substrate using plasma, a hydrophilic primer, and a coating agent comprising a hydrophobic fluorine compound.

Background

The biochip means a hybrid device made in the form of an existing semiconductor chip by combining bio-organic materials (e.g., enzymes, proteins, antibodies, DNA, microorganisms, or animal and plant cells and organs, and nerve cells and organs derived from organisms) with inorganic materials (e.g., semiconductors or glass). The biochip diagnoses infectious diseases or analyzes genes by using unique functions of biomolecules and imitating functions of living organisms, and is used as a new functional device for information processing. Biochips can be broadly defined to include biosensors that can be used to detect and analyze various biochemical materials, such as lab-on-a-chip, which are tightly integrated and thus have an automatic analysis function to perform pretreatment, biochemical reaction, detection, and data analysis on a sample.

Biochips can be applied to various fields such as microchips, medical devices, medical materials, and SPF facilities, and a technique for modifying the surface of a polymer substrate (particularly, a silicone polymer substrate), which is one of constituent materials of biochips, is a very important basic technology.

Polydimethylsiloxane (PDMS) is one of silicone polymers, which is widely used as a basic material for manufacturing lab-on-a-chip fused biotechnology in addition to existing microarray and micro/nanofluidic systems due to various advantages such as transparency of materials, flexibility of materials, non-toxicity to cells, easy manufacturing, and low manufacturing cost.

However, in spite of these advantages of PDMS, PDMS has not been widely used as a material of a chip finally commercialized, and the problem of adsorption of a sample onto a PDMS chip is the biggest cause. PDMS is in-OSi (CH)₃)₂-repetitive forms and due to-CH therein₃The groups have a hydrophobic surface, but due to their unique viscosity, hydrophobic materials adsorb very strongly and once adsorbed, it is difficult to desorb the material. In order to analyze individual nanoparticles and trace substances, it is very necessary to prevent adsorption of noise that may be the result of an experiment, especially since biological samples such as proteins and cells contain a part of hydrophobic groups on their surface, and the following problems may occur in some cases: the biological sample is easily adsorbed onto the surface of PDMS and its unique 3-dimensional structure is deformed. In contrast, it is difficult to attach cells to the surface of PDMS and culture the cells due to its hydrophobic surface, and even when selectivity is imparted to its surface using a specific compound, antibody, or the like, it is necessary to include a plurality of stepsA surface treatment step.

In order to improve this problem, the following attempts have been continued to modify the surface of the polymer substrate: plasma treatment of the surface of a polymer substrate (e.g., PDMS), adsorption of non-specific proteins onto the surface of a polymer substrate, or use of materials containing Teflon or fluorocarbon groups similar to Teflon.

However, the most widely used oxygen plasma provides a super-hydrophilic surface, but the maintenance time of the hydrophilic surface is short, making the surface of PDMS rough, or even forming cracks, resulting in the following problems: oxygen plasma is not suitable for experiments using relatively small particles (e.g., nanoparticles) in microchips. Further, in the case of the fluorine compound-based coating agent for glass or plastic known in the related art, it is found that the coating agent forms a hard coating layer after drying, so that the flexibility of the polymer substrate is reduced or the coating layer is damaged by the movement of the polymer substrate.

The present invention was accomplished to lay the foundation of opening up the possibility of observing true single molecules by preventing adsorption of such nonspecific biomolecules and foreign substances (e.g., particles), and thus it is expected to increase the range of biological experiments in which polymer (e.g., silicone) -based biochips can be used as a platform.

Disclosure of Invention

Technical problem

The present invention provides a method for modifying the surface of a polymer substrate, in particular, a method for modifying the surface of a polymer substrate using a plasma treatment, a hydrophilic primer, and a coating agent comprising a hydrophobic fluorine compound.

Technical scheme

One aspect of the present invention provides a method for modifying the surface of a polymeric substrate, the method comprising: treating the surface of the polymeric substrate with plasma; applying a hydrophilic primer to the surface of the plasma-treated polymeric substrate; and coating the plasma-treated polymeric substrate with a coating agent comprising a hydrophobic fluorine compound.

Hereinafter, the polymer substrate will be described in detail.

According to an exemplary embodiment of the present invention, in the method of the present invention, the surface treatment of the polymeric substrate with plasma is first performed.

In this step, a polymer substrate is placed in a plasma reactor at room temperature under atmospheric pressure, a gas is injected therein, and then plasma of the gas is formed by applying electric power to electrodes present at both ends of the plasma reactor.

According to an exemplary embodiment of the present invention, the plasma may be a plasma of argon, nitrogen, oxygen, or a mixed gas in which two or more of these gases are mixed. Further, the plasma may be a low-temperature plasma or a high-temperature plasma, and is preferably a plasma generated at a low temperature. A hydrophilically modified surface can be obtained by treating the surface of a polymer substrate with plasma, and the subsequent bonding of a coating agent can be performed more firmly and safely.

According to an exemplary embodiment of the present invention, in treating the surface of the polymer substrate with plasma, the surface of the polymer substrate is reciprocally treated with plasma at a speed of 15 mm/sec by forming plasma by applying power of 700W to 800W using a mixed gas of argon and oxygen under atmospheric pressure (760 torr).

According to an exemplary embodiment of the present invention, the polymer substrate may include a natural or artificial polymer prepared by polycondensation or addition polymerization of one or more monomers, and may preferably include a siloxane-based polymer, more preferably a silicone rubber, an acrylic resin, a polystyrene resin, a polyvinyl chloride resin, a polyethylene resin, a polypropylene resin, a nylon, a phenol resin, a melamine resin, a urea resin, or an epoxy resin, and even more preferably a hydrophobic resin, a fluoropolymer, an acrylic resin, or a polyethylene resin, but is not limited thereto.

according to an exemplary embodiment of the present invention, after treating the surface of the polymer substrate with plasma, the method may further include applying a hydrophilic primer onto the surface of the polymer substrate.

According to an exemplary embodiment of the present invention, the applying of the hydrophilic primer onto the surface of the polymer substrate is performed after the surface of the polymer substrate is treated with plasma.

According to an exemplary embodiment of the present invention, the primer may include a condensation polymer of a silicone-based polymer and a functional organic or inorganic silane compound.

As used herein, a "primer" is a buffer coating applied in a nano-thickness between a substrate and a functional coating to improve adhesion, and may be a condensation polymerization reaction product of a silicone-based polymer and a functional organic or inorganic silane compound.

As used herein, the "silicone-based polymer" may be specifically selected from modified silicone polymers having one or more reactive groups selected from amino, epoxy, carboxyl, carbinol, methacryl, mercapto and phenyl groups, and combinations thereof, and may preferably be a polymer of an aminoalkylsilane.

The "functional organic or inorganic silane compound" used in the present specification as a component of the primer may be an organic or inorganic silane compound having one or more reactive groups, such as an amino group, a vinyl group, an epoxy group, an alkoxy group, a halogen group, a mercapto group, a thioether group, etc., which undergo a condensation polymerization reaction with the silicone-based polymer. In particular, the functional organic or inorganic silane compound may be selected from: aminopropyltriethoxysilane; aminopropyltrimethoxysilane; amino-methoxysilane; phenylaminopropyl trimethoxysilane; n- (2-aminoethyl) -3-aminopropyltrimethoxysilane; n- (β -aminoethyl) - γ -aminopropylmethyldimethoxysilane; gamma-aminopropyl-tri-dimethoxysilane; gamma-aminopropyldimethoxysilane; gamma-aminopropyltriethoxysilane; gamma-aminopropyldiethoxysilane; vinyltriethoxysilane; vinyl trimethoxysilane; vinyltris (methoxyethoxy) silane; a dialkoxysilane, trialkoxysilane, or tetraalkoxysilane; vinylmethoxysilane; vinyl trimethoxysilane; vinyl epoxy silane, vinyl triepoxy silane; 3-glycidoxypropyltrimethoxysilane; 3-methacryloxypropyltrimethoxysilane; gamma-glycidoxypropyltriethoxysilane; gamma-methacryloxypropyltrimethoxysilane; chlorotrimethylsilane; trichloroethylsilane; trichloromethylsilane; trichlorophenylsilane; a trichlorosilane; mercaptopropyltriethoxysilane; trifluoropropyltrimethoxysilane; bis (trimethoxysilylpropyl) amine; bis (3-triethoxysilylpropyl) tetrasulfide; bis (triethoxysilylpropyl) disulfide; (methacryloxy) propyltrimethoxysilane; 2- (3, 4-epoxycyclohexyl) ethyltrimethoxysilane; 3-glycidoxypropylmethyldiethoxysilane; 3-glycidoxypropyldiethoxysilane; 3-glycidoxypropyltriethoxysilane; p-styryl trimethoxysilane; and combinations thereof, may be preferably selected from aminopropyltriethoxysilane and combinations comprising the same, but are not limited thereto.

The primer is applied by a wet process, and is applied by completely dissolving a hydrophilic primer in a solvent (particularly, ethanol) and then applying the resulting solution onto the surface of the polymer substrate. Application includes brushing, spraying, dipping, and the like, and may preferably be performed by spraying.

Thereafter, coating of the surface of the polymer substrate with a coating agent comprising a hydrophobic fluorine compound is performed.

As used herein, the term "fluorine compound" broadly refers to a compound containing a fluorine (F) atom in the compound, and includes both single compounds and polymeric compounds. Preferably, the fluorine compound includes a fluorine-based organic component and exhibits hydrophobicity.

According to an exemplary embodiment of the present invention, the fluorine compound may be a product of a polycondensation reaction of the fluorine-based polymer and the functional organic or inorganic silane compound.

As used herein, a "fluorine-based polymer" may be a perfluorinated polymer. In particular, the fluorine-based polymer may be selected from: a fluoroacrylate polymer; a perfluoropolyether; and a polymer comprising: tetrafluoroethylene, hexafluoropropylene, chlorotrifluoroethylene, trifluoroethylene, vinylidene fluoride, octafluorobutene, pentafluorophenyl trifluoroethylene, pentafluorophenyl ethylene, and repeating units derived from the monomers, and may be preferably a perfluoropolyether, but is not limited thereto.

The "functional organic or inorganic silane compound" used in the present specification as a component of the fluorine compound may be an organic or inorganic silane compound having one or more reactive groups, such as an amino group, a vinyl group, an epoxy group, an alkoxy group, a halogen group, a mercapto group, a thioether group, etc., which undergo a condensation polymerization reaction with the fluorine-based polymer. Preferably, the functional organic or inorganic silane compound may be selected from: an organosilane comprising an alkoxy group, a silane compound comprising a functional organic group, and a partially hydrolyzed condensate of the organosilane composition. In particular, the functional organic or inorganic silane compound may be selected from: aminopropyltriethoxysilane; aminopropyltrimethoxysilane; amino-methoxysilane; phenylaminopropyl trimethoxysilane; n- (2-aminoethyl) -3-aminopropyltrimethoxysilane; n- (β -aminoethyl) - γ -aminopropylmethyldimethoxysilane; gamma-aminopropyl-tri-dimethoxysilane; gamma-aminopropyldimethoxysilane; gamma-aminopropyltriethoxysilane; gamma-aminopropyldiethoxysilane; vinyltriethoxysilane; vinyl trimethoxysilane; vinyltris (methoxyethoxy) silane; a dialkoxysilane, trialkoxysilane, or tetraalkoxysilane; vinylmethoxysilane; vinyl trimethoxysilane; a vinyl epoxy silane; vinyltriethoxysilane; 3-glycidoxypropyltrimethoxysilane; 3-methacryloxypropyltrimethoxysilane; gamma-glycidoxypropyltriethoxysilane; gamma-methacryloxypropyltrimethoxysilane; chlorotrimethylsilane; trichloroethylsilane; trichloromethylsilane; trichlorophenylsilane; a trichlorosilane; mercaptopropyltriethoxysilane; trifluoropropyltrimethoxysilane; bis (trimethoxysilylpropyl) amine; bis (3-triethoxysilylpropyl) tetrasulfide; bis (triethoxysilylpropyl) disulfide; (methacryloxy) propyltrimethoxysilane; 2- (3, 4-epoxycyclohexyl) ethyltrimethoxysilane; 3-glycidoxypropylmethyldiethoxysilane; 3-glycidoxypropyldiethoxysilane; 3-glycidoxypropyltriethoxysilane; p-styryl trimethoxysilane; and combinations thereof, may preferably be aminopropyltriethoxysilane and combinations comprising the same, but are not limited thereto.

The coating is preferably performed by a wet process, and is performed by completely dissolving the hydrophobic fluorine compound in a solvent, particularly, a fluorine-based solvent (HFE7200, 3M), and then applying the resulting solution to the surface of the polymer substrate. Application includes brushing, spraying, dipping, and the like, and may preferably be performed by spraying.

One aspect of the invention provides a polymer substrate having a surface modified by the method.

one aspect of the present invention provides a biochip comprising the polymer substrate. The biochip may be embodied as a microarray chip or a microfluidic chip. The biochip can be prepared by additionally attaching enzymes, proteins, antibodies, DNA, compounds, etc. capable of detecting various biomolecules and derived from organisms to the polymer substrate according to the present invention, and the biochip can detect the presence and absence and/or concentration of a target material to be detected by various physical and chemical methods (e.g., electrochemical, fluorescence, SPR, FET, and heat sensor).

Advantageous effects

By modifying the surface of the hydrophobic polymer substrate according to the present invention, the effect of preventing non-specific biomolecules and foreign substances (e.g., particles) from being adsorbed onto the surface of a device or the like can be significantly improved without impairing the transparency, flexibility, and the like of the material, which are advantages of the device, apparatus, and the like including the existing hydrophobic polymer substrate.

Further, while maintaining transparency and flexibility of materials, cell viability, and the like, which are advantages of devices, apparatuses, and the like including existing hydrophobic polymer substrates, it is possible to provide a polymer substrate in which the effect of preventing non-specific biomolecules (such as proteins and cells) and foreign substances (such as particles) from being adsorbed onto the devices, apparatuses, and the like is significantly improved, and a biochip including the same.

Drawings

Fig. 1 and 2 show fluorescence photographs showing the degree of adsorption of FITC-BSA protein and relative fluorescence intensities before and after the surface modification of each PDMS biochip according to the present invention and comparative example.

Fig. 3 shows the degree of adsorption of the oil-based ink before and after the surface modification of each PDMS biochip according to the present invention and comparative examples, and the left and right sides show graphs of the case of adsorption of BSA protein and the case of non-adsorption of BSA protein, respectively.

Fig. 4 shows light transmittance before and after surface modification of each PDMS biochip according to the present invention and comparative examples, and a) and b) are graphs showing the case of adsorption of BSA protein and the case of non-adsorption of BSA protein, respectively.

Fig. 5 shows the morphological observations (0 hours, 48 hours and 72 hours) of MDA cell lines cultured on petri dishes (control), PDMS whose surface was not modified, and PDMS biochips according to the invention.

Fig. 6 and 7 show the results of the survival and death determination test of cells attached to the bottom and cells floating in the culture medium in the MDA cell line cultured on the petri dish (control), PDMS whose surface was not modified, and the PDMS biochip according to the present invention. Green and red represent live and dead cells, respectively, and the number of corresponding cells is proportional to the fluorescence intensity. Fig. 8 shows a numerical comparison of cell viability by fluorescence intensity in fig. 6 and 7.

Fig. 9 shows the PEEL test results of a PDMS substrate according to the present invention during (a) the experiment and after b) the experiment was completed.

Detailed Description

one aspect of the present invention provides a method for modifying the surface of a polymeric substrate, the method comprising: treating the surface of the polymeric substrate with plasma; applying a hydrophilic primer to the surface of the plasma-treated polymeric substrate; and coating the plasma-treated polymeric substrate with a coating agent comprising a hydrophobic fluorine compound.

EMBODIMENTS FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in more detail by one or more examples. However, these embodiments are provided only for exemplarily explaining one or more embodiments, and the scope of the present invention is not limited by these embodiments.