JP5534390B2 - Cyclic olefin resin processing method and molded body - Google Patents

Description

  The present invention relates to a biochemical non-adsorption treatment method for the surface of a molded body made of a material containing a cyclic olefin-based resin.

  Cyclic olefin resins are used in various applications because they are excellent in melt processability, fluidity, heat shrinkability, printing characteristics, and the like. In addition to the above properties, it is excellent in transparency, chemical resistance, moisture resistance, mechanical properties, and the like, so that its use is widespread in medical device applications, pharmaceutical applications, optical applications, and the like.

  In pharmaceutical or medical equipment applications, a molded body made of a material containing a cyclic olefin resin is used in a storage container, an analytical device, or the like that handles biological substances (biochemical substances) such as proteins. However, when a medicine or sample containing a relatively low concentration of biochemical substance is handled, problems may occur due to the biochemical substance adsorbed on the surface of the molded body. For example, in the case of a biopharmaceutical container, the drug may be adsorbed on the surface of the container, the concentration of the drug may decrease, and the effect of the drug may decrease. In order to reduce the effect of drugs and suppress the decrease in pharmaceutical production, a surface treatment method that is difficult for biopharmaceuticals to be adsorbed is required.

  In addition, in microanalysis of biological samples using microflow devices made of materials containing cyclic olefin resins, the influence of the adsorption of biochemical substances by cyclic olefin resins on the surface of plastic substrates for microflow devices cannot be ignored. There is a problem that it is difficult to obtain accurate analysis results.

  For this reason, development of the method of suppressing the adsorption | suction of a biochemical substance by giving a certain surface treatment to the surface of the molded object which consists of material containing cyclic olefin resin is desired.

  The microflow device is sometimes called a microchip, and Patent Document 1 reports a surface treatment method for a plastic substrate used for the microchip. In that report, as a method of performing surface treatment on a plastic substrate using a cyclic olefin resin, for example, a plastic substrate having a saturated cyclic polyolefin resin is subjected to ultraviolet treatment, corona discharge treatment, electron beam treatment, low frequency and high frequency. A method of introducing a hydroxyl group into the surface of a plastic substrate by performing a treatment using a low temperature plasma discharge treatment or a chemical treatment solution containing an oxidation reagent has been proposed.

  However, this surface treatment is a method of surface-treating the detection part of the plastic substrate for microflow devices for the purpose of improving the measurement sensitivity of the microflow device. And the method of processing the microchip surface-treated by the method described in Patent Document 1 with an aminosilane compound or the like effective for further immobilizing biochemical substances derived from living organisms such as proteins and DNA has been proposed. (Patent Document 2).

  In order to increase the accuracy of the microflow device, it is necessary to increase the sensitivity of the detection unit. However, if the sample is adsorbed on the surface of the flow path until it reaches the detection unit, there is a problem that the measurement accuracy decreases. In order to solve this problem, there is a need for a method of modifying the flow path of the microflow device to a surface on which biological substances are difficult to adsorb.

JP 2003-183425 A JP 2003-279572 A

  The present invention has been made in order to solve the above-described problems, and the object thereof is simple, can sufficiently realize non-adsorption of biochemical substances, and is formed of a material containing a cyclic olefin resin. An object of the present invention is to provide a non-adsorption treatment method for biochemical substances on the surface of a body.

  The inventors of the present invention have made extensive studies to solve the above problems. As a result, with respect to the surface of the molded body made of a material containing a cyclic olefin-based resin, 1) Step 1 of performing plasma discharge treatment on the surface of the molded body, and 2) After Step 1, the surface of the molded body is made strong acid. It has been found that adsorption of biochemical substances can be suppressed by performing a surface treatment including the step 2 of contacting. Furthermore, it was found that the same effect can be obtained by carrying out step 3 of reacting the surface of a molded article treated with a strong acid with a specific fluorine-containing silane compound, thereby completing the present invention. More specifically, the present invention provides the following.

(1) Non-adsorption treatment method for biochemical substances on the surface of a molded article made of a material containing a cyclic olefin resin, including the following step 1 and step 2:
1) Step 1 of plasma discharge treatment of the surface of the molded body;
2) The process 2 which makes the surface of the said molded object contact with a strong acid after the process 1.

(2) The non-adsorption treatment method of (1) including the process 3 of making the surface of the said molded object and the fluorine compound represented by the following Formula (1) react after the process 2.
(R ^a ) Si (R ^b ) ₃ (1)
[R ^a is ^a group selected from a fluorine-containing hydrocarbon group having 3 to 10 carbon atoms or a perfluoroalkyl group. R ^b is a group selected from chlorine, bromine, iodine, methoxy group, ethoxy group, n-propyloxy group, or isopropyloxy group. ]

  (3) The non-adsorption treatment method for biochemical substances according to (1) or (2), wherein the strong acid is dilute sulfuric acid.

  (4) A molded article made of a material containing a cyclic olefin-based resin that has been subjected to a non-adsorption treatment of a biochemical substance by the method according to any one of (1) to (3).

  (5) A plastic substrate for a microflow device, wherein the biochemical substance is non-adsorbed by the method according to any one of (1) to (3).

  According to the present invention, the surface of a molded body made of a material containing a cyclic olefin resin is treated with a plasma discharge device widely used in various applications, then treated with a strong acid, and optionally with a strong acid. By performing a treatment with a specific fluorine compound after the treatment, the surface of the molded body can be made difficult for the biochemical substance to be adsorbed.

It is a figure which shows the XPS measurement result of the binding energy area | region corresponding to the O1s peak of the plate by which plasma discharge processing (process 1) was carried out in Example 1. FIG. It is a figure which shows the XPS measurement result of the bond energy area | region corresponding to the O1s peak of the plate which carried out the dilute sulfuric acid process (process 2) in Example 1. FIG. It is a figure which shows the XPS measurement result of the binding energy area | region corresponding to the S2p peak of the plate which carried out the dilute sulfuric acid process (process 2) in Example 1. FIG. It is a figure which shows the XPS measurement result of the binding energy area | region corresponding to the O1s peak of the plate which reacted with the perfluorobutyl trichlorosilane in Example 1 (process 3). It is a figure which shows the XPS measurement result of the bond energy area | region corresponding to the F1s peak of the plate which reacted with the perfluorobutyl trichlorosilane in Example 1 (process 3). It is a figure which shows the XPS measurement result of the binding energy area | region corresponding to the O1s peak of the plate by which the plasma discharge process (process 1) was carried out in Example 2, and the plate by which the dilute sulfuric acid process (process 2) was carried out. XPS in the binding energy region corresponding to the Si2p peak of the plate treated with dilute sulfuric acid (Step 2) in Example 2 and reacted with 1H, 1H, 2H, 2H-perfluorooctyltrimethoxysilane (Step 3) It is a figure which shows a measurement result. XPS in the binding energy region corresponding to the F1s peak of the plate treated with dilute sulfuric acid (step 2) in Example 2 and reacted with 1H, 1H, 2H, 2H-perfluorooctyltrimethoxysilane (step 3) It is a figure which shows a measurement result. It is a figure which shows the atomic force microscope observation result of the untreated plate by which the surface was processed with the bovine serum albumin in Example 3. It is a figure which shows the atomic force microscope observation result of the plate by which the surface was processed with the bovine serum albumin in Example 3 and which carried out the dilute sulfuric acid process (process 2). It is a figure which shows the atomic force microscope observation result of the plate which made 1H, 1H, 2H, 2H-perfluoro octyltrimethoxysilane react the surface by bovine serum albumin in Example 3 (process 3).

  Hereinafter, embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments, and can be implemented with appropriate modifications within the scope of the object of the present invention. . In addition, although description may be abbreviate | omitted suitably about the location where description overlaps, the summary of invention is not limited.

  First, in the present specification, biochemical substances include proteins, enzymes, antibodies, polypeptides, oligopeptides, amino acids, oligonucleotides, polynucleotides, nucleic acids, lipids, polysaccharides, oligosaccharides, amino sugars, microorganisms, viruses, etc. Means. Biochemical substances are not limited to those obtained from biological materials by extraction or the like, but also include those chemically synthesized outside the organism.

  Next, a molded body made of a material containing a cyclic olefin resin used in the present invention will be described.

[Cyclic olefin resin]
The cyclic olefin-based resin is a polymer compound having a main chain composed of a carbon-carbon bond and having a cyclic hydrocarbon structure in at least a part of the main chain. This cyclic hydrocarbon structure is introduced by using a compound (cyclic olefin) having at least one olefinic double bond in the cyclic hydrocarbon structure as represented by norbornene or tetracyclododecene as a monomer. Is done.

  The cyclic olefin resin (A) is an addition (co) polymer of a cyclic olefin or a hydrogenated product thereof (1), an addition copolymer of a cyclic olefin and an α-olefin or a hydrogenated product thereof (2), It is classified as a ring-opening (co) polymer or a hydrogenated product (3) thereof.

  Specific examples of the cyclic olefin include cyclopentene, cyclohexene, cyclooctene; one-ring cyclic olefin such as cyclopentadiene and 1,3-cyclohexadiene;

  Bicyclo [2.2.1] hept-2-ene (common name: norbornene), 5-methyl-bicyclo [2.2.1] hept-2-ene, 5,5-dimethyl-bicyclo [2.2. 1] Hept-2-ene, 5-ethyl-bicyclo [2.2.1] hept-2-ene, 5-butyl-bicyclo [2.2.1] hept-2-ene, 5-ethylidene-bicyclo [ 2.2.1] hept-2-ene, 5-hexyl-bicyclo [2.2.1] hept-2-ene, 5-octyl-bicyclo [2.2.1] hept-2-ene, 5- Octadecyl-bicyclo [2.2.1] hept-2-ene, 5-methylidene-bicyclo [2.2.1] hept-2-ene, 5-vinyl-bicyclo [2.2.1] hept-2-ene Ene, 5-propenyl-bicyclo [2.2.1] hept-2-ene, etc. Cyclic olefin ring;

Tricyclo [4.3.0.1 ^2,5 ] deca-3,7-diene (common name: dicyclopentadiene), tricyclo [4.3.0.1 ^2,5 ] dec-3-ene; tricyclo [ 4.4.0.1 ^2,5 ] undeca-3,7-diene or tricyclo [4.4.0.1 ^2,5 ] undeca-3,8-diene or a partially hydrogenated product thereof (or cyclopentadiene) Tricyclo [4.4.0.1 ^2,5 ] undec-3-ene; 5-cyclopentyl-bicyclo [2.2.1] hept-2-ene, 5-cyclohexyl-bicyclo [2.2.1] hept-2-ene, 5-cyclohexenylbicyclo [2.2.1] hept-2-ene, 5-phenyl-bicyclo [2.2.1] hept-2-ene A cyclic olefin of the ring;

Tetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene (also simply referred to as tetracyclododecene), 8-methyltetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene, 8-ethyltetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene, 8-methylidenetetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene, 8-ethylidenetetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene, 8-vinyltetracyclo [4,4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene, 8-propenyl-tetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] tetracyclic olefins such as dodec-3-ene;

8-cyclopentyl-tetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene, 8-cyclohexyl-tetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene, 8-cyclohexenyl-tetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene, 8-phenyl-cyclopentyl-tetracyclo [4.4.0.1 ^2,5 . 1 ^7,10 ] dodec-3-ene; tetracyclo [7.4.1 ^3,6 . 0 ^1,9 . 0 ^2,7 ] tetradeca-4,9,11,13-tetraene (also referred to as 1,4-methano-1,4,4a, 9a-tetrahydrofluorene), tetracyclo [8.4.1 ^4,7 . 0 ^1,10 . 0 ^3,8 ] pentadeca-5,10,12,14-tetraene (also called 1,4-methano-1,4,4a, 5,10,10a-hexahydroanthracene); pentacyclo [6.6.1]. ^.1,3,6 . 0 ^2,7 . 0 ^9,14 ] -4-hexadecene, pentacyclo [6.5.1.1 ^3,6 . 0 ^2,7 . 0 ^9,13] -4-pentadecene, pentacyclo [7.4.0.0 ^2,7. 1 ^3,6 . 1 ^10,13] -4-pentadecene; heptacyclo [8.7.0.1 ^2,9. 1 ^4,7 . 1 ^{11, 17} . 0 ^3,8 . 0 ^12,16 ] -5-eicosene, heptacyclo [8.7.0.1 ^2,9 . 0 ^3,8 . 1 ^4,7 . 0 ^12,17 . 1 ^13,16 ] ^-14-eicosene ; and polycyclic cyclic olefins such as a tetramer of cyclopentadiene. These cyclic olefins can be used alone or in combination of two or more.

  Specific examples of the α-olefin copolymerizable with the cyclic olefin include ethylene, propylene, 1-butene, 1-pentene, 1-hexene, 3-methyl-1-butene, 3-methyl-1-pentene, 3 -Ethyl-1-pentene, 4-methyl-1-pentene, 4-methyl-1-hexene, 4,4-dimethyl-1-hexene, 4,4-dimethyl-1-pentene, 4-ethyl-1- Hexene, 3-ethyl-1-hexene, 1-octene, 1-decene, 1-dodecene, 1-tetradecene, 1-hexadecene, 1-octadecene, 1-eicosene, etc. 2 to 20, preferably carbon number Examples include 2 to 8 ethylene or α-olefin. These α-olefins can be used alone or in combination of two or more.

  The method for polymerizing the cyclic olefin or the cyclic olefin and the α-olefin and the method for hydrogenating the obtained polymer are not particularly limited, and can be carried out according to a known method.

  The cyclic olefin-based resin is preferably an addition copolymer of ethylene and norbornene or an addition copolymer of ethylene and tetracyclododecene.

  There is no restriction | limiting in particular in the structure of cyclic olefin resin, Although it may be chain | strand shape, a branched form, or bridge | crosslinking form, Preferably it is linear.

  Moreover, it is also possible to use a commercially available resin as the cyclic olefin resin containing the cyclic olefin component used in the present invention as a polymerization component. Examples of commercially available cyclic olefin-based resins include TOPAS (registered trademark) (Topas Advanced Polymers), Apel (registered trademark) (manufactured by Mitsui Chemicals), Zeonex (registered trademark) (manufactured by Nippon Zeon), Examples include ZEONOR (registered trademark) (manufactured by ZEON Corporation), ARTON (registered trademark) (manufactured by JSR Corporation), and the like.

[Other ingredients]
In the present invention, the cyclic olefin-based resin may be used as a composition blended with other thermoplastic resins in the range and type that do not impair the object of the present invention. A resin composition composed of a cyclic olefin-based resin and another thermoplastic resin can be prepared by, for example, melt-kneading using a single screw extruder or a twin screw extruder.

  In the present invention, the cyclic olefin-based resin includes various additives such as an antioxidant, a weathering stabilizer, an ultraviolet absorber, an antibacterial agent, a flame retardant, and a colorant in a range and amount that do not impair the object of the present invention. You may use what contains. When the cyclic olefin resin contains an additive, it can be prepared, for example, by melt-kneading the cyclic olefin resin and the additive using a single screw extruder or a twin screw extruder.

[Molded body]
The molded body subjected to the non-adsorption treatment of the biochemical substance by the method of the present invention is produced by molding the above cyclic olefin resin by a known method. Examples of known molding methods include injection molding, injection compression molding, gas assist injection molding, extrusion molding, multilayer extrusion molding, rotational molding, hot press molding, blow molding, foam molding, and the like.

  The shape of the molded body made of a material containing a cyclic olefin resin is not particularly limited. For example, the molded product may be a general-purpose product such as a film, a sheet, a tube, a pipe, or a bottle, or may be a molded product designed according to a specific application such as a plastic substrate for a microflow device.

  The shape of these molded bodies is preferably a plastic substrate for a microflow device used for analyzing a sample containing a biochemical substance. This is because when the molded body is a plastic substrate for a microflow device, the effect of non-specific adsorption of biochemical substances when the surface of the molded body is treated by the method of the present invention is remarkably exhibited.

  Hereinafter, according to embodiments of the present invention, 1) Steps 1 and 2 of performing plasma discharge treatment on the surface of the molded body, Step 2 and Step 2 of bringing the surface of the molded body into contact with a strong acid; and 3) of Step 2 Later, step 3 of reacting the surface of the molded body with the fluorine compound represented by the formula (1) will be described in order.

<Step 1>
Step 1 is a step of subjecting a molded body made of a material containing a cyclic olefin resin to plasma discharge treatment. By performing plasma discharge treatment on the surface of the molded body, the surface of the molded body can be activated.

[Plasma discharge treatment]
The plasma discharge device used in the present invention is not particularly limited as long as it can perform plasma discharge on the surface of the molded body, and plasma discharge devices conventionally used for various applications can be used.

  The plasma discharge treatment is preferably performed at a discharge output of 1 to 100 W, preferably under reduced pressure of 10 to 1000 Pa, and preferably performed for a time of 1 to 10 minutes.

<Process 2>
Step 2 is a step of treating the surface of the molded body that has been plasma-discharged in Step 1 with a strong acid. In the present invention, the surface of the molded body is treated with a strong acid for the purpose of introducing oxygen into the surface of the cyclic olefin resin activated by the plasma discharge treatment.

[Strong acid]
Examples of the strong acid include mineral acids such as sulfuric acid, hydrochloric acid and nitric acid, and organic sulfonic acids such as methanesulfonic acid, toluenesulfonic acid and p-toluenesulfonic acid. These strong acids are preferably used as aqueous solutions. The strong acid aqueous solution may contain a water-soluble organic solvent such as methanol, ethanol, and acetone as long as the object of the present invention is not impaired. Among these strong acids, it is preferable to use a mineral acid, and more preferable to use sulfuric acid because oxygen can be easily introduced into the surface of the molded body. When using sulfuric acid, it is preferable to use dilute sulfuric acid. The specific concentration of dilute sulfuric acid is 0.01M to 1M, more preferably 0.05M to 0.2M. If the concentration of sulfuric acid is too high, an undesirable reaction such as sulfonation may occur on the surface of the molded article. If the concentration of sulfuric acid is too low, the desired oxygen introduction effect may not be obtained.

[Treatment with strong acid]
In the step 2, the method for treating the surface of the molded body with a strong acid is not particularly limited as long as the strong acid solution can be brought into contact with the surface of the molded body activated in the step 1. For example, a method of immersing the compact in a strong acid solution, a method of flowing a strong acid solution on the surface of the compact, a method of applying a strong acid solution to the surface of the compact, a method of spraying a strong acid solution on the surface of the compact, etc. It is done. Among these methods, since the surface of the molded body can be uniformly treated, a method of immersing the molded body in a strong acid solution or a method of flowing a strong acid solution over the surface of the molded body is preferably used.

  After the treatment of the surface of the molded body with a strong acid, the surface of the molded body is preferably washed with water for the purpose of removing the acid component remaining on the surface of the molded body.

  In the present invention, adsorption of biochemical substances on the surface of a molded body made of a material containing a cyclic olefin-based resin can be sufficiently suppressed by the surface treatment in Step 1 and Step 2 described above. However, when oxygen is introduced into the surface of a molded body made of a material containing a cyclic olefin-based resin, adsorption of biochemical substances such as proteins to the surface of the molded body can be prevented by suppressing hydrophobic bonds. In some cases, biochemical analysis may be hindered by non-specific adsorption of metal ions or the like. In order to avoid such obstacles and improve the accuracy of biochemical analysis, in addition to the processing of Step 1 and Step 2, the processing of Step 3 described below is performed, and a fluorocarbon group is formed on the surface of the molded body. More preferably, is introduced.

<Step 3>
Step 3 is a step of reacting the surface of the molded body treated with the strong acid in Step 2 with the fluorine compound represented by the formula (1). In the present invention, the fluorine-containing group having a small polarity is introduced into the surface of the molded body by reacting the oxygen-containing group introduced into the surface of the molded body in Step 1 and Step 2 with the fluorine compound represented by the formula (1). Thus, non-adsorption of biochemical substances is realized.

[Fluorine compounds]
In this invention, the fluorine compound represented by the following Formula (1) is used as a surface treating agent of the molded object which consists of material containing cyclic olefin resin. A plurality of fluorine compounds represented by the formula (1) may be used in combination.
(R ^a ) Si (R ^b ) ₃ (1)
[R ^a is ^a group selected from a fluorine-containing hydrocarbon group having 3 to 10 carbon atoms or a perfluoroalkyl group. R ^b is a group selected from chlorine, bromine, iodine, methoxy group, ethoxy group, n-propyloxy group, and isopropyloxy group. ]

Specific examples of the ^Ra group include 3,3,3-trifluoropropyl group, 2,2,3,3,3-pentafluoropropyl group, 3,3,4,4,5,5,6,6. , 6-nonafluorohexyl group, perfluoropropyl group, perfluorobutyl group, perfluorohexyl group, perfluorooctyl group, perfluorodecyl group and the like.

  Preferred examples of the fluorine compound represented by the formula (1) include 3,3,3-trifluoropropyltrichlorosilane, 2,2,3,3,3-pentafluoropropyltrichlorosilane, 1H, and 1H. , 2H, 2H-perfluorodecyldimethylchlorosilane, 1H, 1H, 2H, 2H-perfluorodecylmethyldichlorosilane, 1H, 1H, 2H, 2H-perfluorodecyltrichlorosilane, 1H, 1H, 2H, 2H-perfluoro Octyldimethylchlorosilane, 1H, 1H, 2H, 2H-perfluorooctylmethyldichlorosilane, 1H, 1H, 2H, 2H-perfluorooctyltrichlorosilane, 3,3,4,4,5,5,6,6,6 -Nonafluorohexyltrichlorosilane, 3,3,4,4,5,5,6,6,6 Fluoroalkyltrihalosilanes such as nonafluorohexylmethyldichlorosilane; 3,3,3-trifluoropropyltriethoxysilane, 2,2,3,3,3-pentafluoropropyltriethoxysilane, perfluoromethyltriethoxysilane Fluoroalkyltri, such as 1H, 1H, 2H, 2H-perfluorodecyltriethoxysilane, 1H, 1H, 2H, 2H-perfluorooctyltriethoxysilane, 1H, 1H, 2H, 2H-perfluorooctyltrimethoxysilane Examples include alkoxysilanes.

[Treatment with fluorine compounds]
The method of reacting the surface of the molded body treated with strong acid obtained in step 2 with the fluorine compound represented by formula (1) is not particularly limited as long as the reaction proceeds well. The fluorine compound represented by the formula (1) is preferably used as a fluorine compound solution diluted with an organic solvent such as methanol or ethanol. The concentration of the fluorine compound solution is preferably in the range of 0.01 mM to 10 mM. If the concentration of the fluorine compound in the fluorine compound solution is too low, a sufficient effect of non-adsorption of biochemical substances may not be obtained, or the reaction may take a long time.

  Specific methods for reacting the surface of the molded body with the fluorine compound include, for example, a method of immersing the molded body in the fluorine compound solution, a method of flowing the fluorine compound solution over the surface of the molded body, and the method described above on the surface of the molded body. Examples include a method of applying a fluorine compound solution. Among these methods, since the operation is simple and the surface of the molded body can be uniformly treated, a method of immersing the molded body in the above-described fluorine compound solution or a method of flowing the fluorine compound solution over the surface of the molded body is preferable.

  The reaction conditions between the molded body surface and the fluorine compound are not particularly limited as long as the reaction proceeds well. Usually, the reaction between the molded body surface and the fluorine compound is carried out at a temperature of 0 ° C. to 50 ° C., more preferably 15 to 35 ° C., for 15 minutes to 12 hours, more preferably 30 minutes to 2 hours.

The bond of oxygen to the surface of the molded body and the bond of the fluorine compound of the formula (1) are measured by XPS (X-ray photoelectron spectroscopy), and the peak between 530 eV and 535 eV attributed to O1s and around 690 eV attributed to F1s Each can be confirmed by the presence or absence of a peak.

  In addition to the treatments in Step 1 and Step 2 on the surface of a molded body made of a material containing a cyclic olefin-based resin, the treatment in Step 3 is performed to introduce a fluorocarbon group into the surface of the molded body. Adsorption can be prevented and non-specific adsorption of the cationic substance on the surface of the molded body can be suppressed.

  The molded body whose surface has been treated by the method described above has a greatly reduced adsorptivity of biochemical substances that are polar materials. For this reason, the molded article surface-treated by the method of the present invention is a protein, enzyme, antibody, polypeptide, oligopeptide, amino acid, oligonucleotide, polynucleotide, nucleic acid, lipid, polysaccharide, oligosaccharide, amino sugar, microorganism, Or it is used suitably for the use which uses biochemical substances, such as a virus.

  In particular, when the surface of a substrate for a microflow device used for microanalysis of a sample containing a biochemical substance is processed by the method of the present invention, the adsorption of the biochemical substance in the sample to the substrate surface is greatly suppressed. Thus, a high-performance microflow device with high analysis accuracy can be obtained.

  Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1
Using TOPAS8007S-04 (manufactured by Polyplastics Co., Ltd.) as a cyclic olefin resin, a 1 mm × 70 mm × 70 mm plate (untreated) by injection molding in a mold having an average surface roughness (Za) of a cavity of about 3 nm Plate).
<Step 1>
An untreated plate made of cyclic olefin resin was set in a JFC-1500 type plasma discharge treatment apparatus manufactured by JEOL Datum Co., Ltd., and subjected to plasma discharge treatment at an output of 20 W and a pressure of 133 Pa for 3 minutes.
<Process 2>
The plate treated in step 1 was immersed in 0.1 M dilute sulfuric acid for 60 minutes and then thoroughly washed with pure water.
<Step 3>
The plate treated in step 2 was immersed in an ethanol solution of perfluorobutyltrichlorosilane having a concentration of 0.005 M at room temperature for 1 hour.

  Using the AXIS-165 type X-ray electron spectroscopy (XPS) apparatus manufactured by Shimadzu / KRATOS Seisakusho, XPS measurement was performed on the surface of the plate after the treatment in Step 1, Step 2 and Step 3.

  FIG. 1 shows the XPS measurement results of the plate after the treatment in Step 1, and FIG. 2 shows the XPS measurement result of the plate after the treatment in Step 2. 1 and 2, it was clearly shown that the O1s peak increased about 20 times in the plate after the treatment according to step 2, and oxygen was bound to the plate surface.

FIG. 3 shows the XPS measurement result of the binding energy region corresponding to S2p of the plate after the process 2. As is clear from FIG. 3, no peak corresponding to SO ₄ was observed, and no binding of sulfate ions was observed.

FIG. 4 shows the XPS measurement result of the binding energy region corresponding to the O1s peak of the plate after the processing in Step 3, and FIG. 5 shows the XPS measurement result of the binding energy region corresponding to the F1s peak of the plate after the processing in Step 3. Show. In FIG. 4, a peak corresponding to the O—Si bond was observed, and in FIG. 5, a peak corresponding to CF ₂ was observed, indicating that a fluorocarbon group was introduced on the plate surface.

(Example 2)
Examples except that the cyclic olefin resin is changed from TOPAS8007S-04 to ZEONOR1060R (manufactured by Nippon Zeon Co., Ltd.) and the perfluorobutyltrichlorosilane is changed to 1H, 1H, 2H, 2H-perfluorooctyltrimethoxysilane. In the same manner as in Example 1, plate preparation and surface treatment from Step 1 to Step 3 were performed.

  The XPS measurement results of the surface of each plate subjected to the surface treatment are shown in FIGS. From FIG. 6, it was shown that oxygen was bonded to the plate surface after the treatment in Step 2. 7 and 8 show that the fluorocarbon group was introduced to the plate surface by the step 3.

(Example 3)
Except that perfluorobutyltrichlorosilane was replaced with 1H, 1H, 2H, 2H-perfluorooctyltrimethoxysilane, plate preparation and surface treatments from Step 1 to Step 3 were performed in the same manner as in Example 1. XPS measurement was performed in the same manner as in Example 1, and it was confirmed that oxygen was bonded to the plate surface after the treatment in Step 2, and it was confirmed that a fluorocarbon group was introduced into the plate surface after the treatment in Step 3. .

  Using an untreated plate, a plate treated in step 2, and a plate treated in step 3, 1000 ppm bovine serum albumin (manufactured by Aldrich) diluted with a phosphate buffer was dropped onto the plate surface, and After standing for 1 hour, it was thoroughly washed with a phosphate buffer. The plate surface after washing was observed with an SPM-9500J3 type atomic force microscope (AFM) manufactured by Shimadzu Corporation. The AFM observation results of the untreated plate, the plate treated in step 2 and the plate treated in step 3 are shown in FIGS. 9, 10 and 11, respectively.

  FIG. 9 shows that aggregates of bovine serum albumin are observed on the untreated plate surface. It can be seen from FIG. 10 that no bovine serum albumin is observed on the surface of the plate treated in step 2, and that adsorption of bovine serum albumin is prevented by introducing oxygen into the surface of the cyclic olefin resin plate. From FIG. 11, bovine serum albumin aggregates are not observed on the plate treated according to step 3, and adsorption of bovine serum albumin is prevented by surface-treating the surface of the plate with a silane compound having a fluorocarbon group. I understand.

Claims (3)

A non-adsorption treatment method for biochemical substances on the surface of a molded article made of a material containing a cyclic olefin-based resin, including the following step 1 and step 2:
1) Step 1 of plasma discharge treatment of the surface of the molded body;
2) The process 2 which makes the surface of the said molded object contact with a strong acid after the process 1. The non-adsorption treatment method according to claim 1, further comprising a step 3 of reacting the surface of the molded body with the fluorine compound represented by the following formula (1) after the step 2.
(R ^a ) Si (R ^b ) ₃ (1)
[R ^a is ^a group selected from a fluorine-containing hydrocarbon group having 3 to 10 carbon atoms or a perfluoroalkyl group. R ^b is a group selected from chlorine, bromine, iodine, methoxy group, ethoxy group, n-propyloxy group, or isopropyloxy group. ]   The biochemical non-adsorption treatment method according to claim 1, wherein the strong acid is dilute sulfuric acid.