JP2022069292A - Biological substance adhesion prevention base material and instrument comprising the base material - Google Patents

Abstract

To provide a base material having a coating film of which deficiency is suppressed on a surface when exposed to a physiological buffer solution, as well as, to provide an instrument and the like comprising the base material.SOLUTION: The present disclosure relates to a biological substance adhesion prevention base material having a surface covered with an amorphous fluoropolymer, and an apparatus planned to be brought into contact with a biological substance.SELECTED DRAWING: None

Description

The present disclosure relates to a base material for preventing adhesion of a biological substance, an instrument scheduled to come into contact with a biological substance, and the like.

Glass is used as the material for base materials, instruments, etc. (for example, medical base materials, medical containers, experimental base materials, experimental containers, inspection base materials, inspection containers, etc.) used in fields such as biochemistry. Was adopted in many cases, and hard resin was also adopted. However, even with glass and resin base materials, instruments, etc., biochemical materials such as cells and components in blood may adhere to the surface, and more biochemical materials may adhere to the surface. There has been a demand for a base material, an instrument, etc. having a suppressed surface. In order to suppress this adhesion, it has been reported that the surface of a base material, an instrument, etc. is coated with an amorphous fluororesin (Patent Document 1).

International Publication No. 2013/179514

In the field of biochemistry, physiological buffers are often used for storage of biochemical materials, cell culture, etc., so they are applied to the surface of substrates, instruments, etc. used in the field of biochemistry, etc. The coated coating film is required to be free from defects or small even when exposed to a physiological buffer for a long period of time. In addition, substrates, instruments, etc. used in fields such as biochemistry are often heated to 200 ° C or higher for sterilization, and therefore the coating film applied to the surface is exposed to such high temperatures. May also be required to be non-defective or small.

One object of the present disclosure is to provide a base material, an instrument, or the like having a coating film on the surface whose defects are suppressed when exposed to a physiological buffer solution. One object of the present disclosure is to provide a base material, a container, or the like having a liquid-repellent coating film on the surface capable of suppressing the adhesion of biochemical materials. One object of the present disclosure is to provide a base material, an instrument, or the like having a coating film on the surface in which defects are suppressed when exposed to a high temperature of about 250 ° C.

The present inventors have solved the above-mentioned problems with a substrate having a surface coated with an amorphous fluoropolymer (particularly, a fluoropolymer containing a monomer unit represented by the formula (1) described later as a main component). I found that.

［式中、Ｒ^１～Ｒ^４はそれぞれ独立して、フッ素原子、フルオロアルキル基、又はフルオロアルコキシ基である。］
で表される単量体単位を主成分として含む、
項１又は２に記載の基材。
項４．
前記フッ素ポリマー中の全ての単量体単位における前記式（１）で表わされる単量体単位の割合が８０モル％以上である、項３に記載の基材。
項５．
前記フッ素ポリマーがフルオロオレフィン単位をさらに含む、項３又は４に記載の基材。
項６．
前記フルオロオレフィン単位が含フッ素パーハロオレフィン単位、フッ化ビニリデン単位、トリフルオロエチレン単位、ペンタフルオロプロピレン単位、及び１，１，１，２－テトラフルオロ－２－プロピレン単位からなる群から選択される少なくとも１種である項５に記載の基材。
項７．
前記含フッ素パーハロオレフィン単位が、クロロトリフルオロエチレン単位、テトラフルオロエチレン単位、ヘキサフルオロプロピレン単位、パーフルオロ（メチルビニルエーテル）単位、パーフルオロ（エチルビニルエーテル）単位、パーフルオロ（プロピルビニルエーテル）単位、パーフルオロ（ブチルビニルエーテル）単位、及びパーフルオロ（２，２－ジメチル－１，３－ジオキソール）単位からなる群から選択される少なくとも１種である項６に記載の基材。
項８．
前記フルオロオレフィン単位が、クロロトリフルオロエチレン単位、テトラフルオロエチレン単位、ヘキサフルオロプロピレン単位、パーフルオロ（メチルビニルエーテル）単位、及びパーフルオロ（プロピルビニルエーテル）単位からなる群から選択される少なくとも１種である項５～７のいずれかに記載の基材。
項９．
平均膜厚が10ｎｍ以上である項１～８のいずれかに記載の基材。
項１０．
以下の耐リン酸緩衝食塩水特性を備えた表面を有する生体由来物質付着防止基材。
塩化ナトリウム、リン酸水素二ナトリウム、塩化カリウム及びリン酸二水素カリウムを含有するリン酸緩衝食塩水に９０℃及び３時間条件で前記基材を浸漬する試験の前にＸ線光電子分光法で測定される前記表面のフッ素原子濃度（F）及び炭素原子濃度（C）、並びに同試験の後にＸ線光電子分光法で測定される前記表面のフッ素原子濃度（F1s）及び炭素原子濃度（C1s）を次の式（Ａ）：
100×（F1s/C1s）/（F/C） （Ａ）
に適用して得られる値が９５以上である。
項１１．
前記式（Ａ）に適用して得られる値が９７以上である、項１０に記載の基材。
項１２．
前記表面が、アモルファスなフッ素ポリマーを含有する膜である項１０又は１１に記載の基材。
項１３．
前記フッ素ポリマーが、
含フッ素脂肪族環を有する単量体単位を主成分として含み、前記含フッ素脂肪族環は環構成原子として１、２、又は３個のエーテル性酸素原子を有し、
前記含フッ素脂肪族環が当該エーテル性酸素原子を複数含むときは当該エーテル性酸素原子は互いに隣り合わない、
項１２に記載の基材。
項１４．
前記フッ素ポリマーが、式（１）：

［式中、Ｒ^１～Ｒ^４はそれぞれ独立して、フッ素原子、フルオロアルキル基、又はフルオロアルコキシ基である。］
で表される単量体単位を主成分として含む、
項１３に記載の基材。
項１５．
材質がガラス又は樹脂である項１～１４のいずれかに記載の基材。
項１６．
材質がガラス、ポリスチレン又はポリメチルメタクリレートである項１～１５のいずれかに記載の基材。
項１７．
項１～１６のいずれかに記載の基材を含む、生体由来物質との接触が予定される器具。
項１８．
医療用、生体由来物質分析用又は生体由来物質試験用である項１７に記載の器具。
項１９．
生体由来物質収容容器、細胞培養容器、マイクロ流路デバイス、カテーテル、コンタクトレンズケース、血液浄化器、血液回路、血液保存バッグ、又はバイオチップである項１７に記載の器具。
項２０．
式（１）：

［式中、Ｒ^１～Ｒ^４はそれぞれ独立して、フッ素原子、フルオロアルキル基、又はフルオロアルコキシ基である。］
で表される単量体単位を主成分として含むアモルファスなフッ素ポリマー、及び
非プロトン性溶媒
を含有する、生体由来物質付着防止表面形成用コーティング剤。
項２１．
前記フッ素ポリマーの含有量が、コーティング剤全質量に対して、１０質量％～６５質量％である項２０に記載のコーティング剤。
項２２．
前記非プロトン性溶媒が、パーフルオロ芳香族化合物、パーフルオロトリアルキルアミン、パーフルオロアルカン、ハイドロフルオロカーボン、パーフルオロ環状エーテル、ハイドロフルオロエーテル、及び少なくとも一つの塩素原子を含むオレフィン化合物からなる群から選択される少なくとも１種の溶媒である項２０又は２１に記載のコーティング剤。
項２３．
前記非プロトン性溶媒が、ハイドロフルオロエーテルの少なくとも１種である項２０～２２のいずれかに記載のコーティング剤。 The present disclosure typically includes the following aspects:
Item 1.
An anti-adhesion substrate for biological substances having a surface coated with an amorphous fluoropolymer.
Item 2.
The fluoropolymer is
The fluorine-containing aliphatic ring contains a monomer unit having a fluorine-containing aliphatic ring as a main component, and the fluorine-containing aliphatic ring has 1, 2, or 3 ethereal oxygen atoms as ring-constituting atoms.
When the fluorine-containing aliphatic ring contains a plurality of the ethereal oxygen atoms, the ethereal oxygen atoms are not adjacent to each other.
Item 1. The base material according to Item 1.
Item 3.
The fluoropolymer has the formula (1):

[In the formula, R ¹ to R ⁴ are independently fluorine atoms, fluoroalkyl groups, or fluoroalkoxy groups. ]
Contains the monomeric unit represented by, as the main component,
Item 2. The base material according to Item 1 or 2.
Item 4.
Item 3. The substrate according to Item 3, wherein the proportion of the monomer unit represented by the formula (1) in all the monomer units in the fluoropolymer is 80 mol% or more.
Item 5.
Item 3. The substrate according to Item 3 or 4, wherein the fluoropolymer further contains a fluoroolefin unit.
Item 6.
The fluoroolefin unit is selected from the group consisting of a fluorine-containing perhaloolefin unit, a vinylidene fluoride unit, a trifluoroethylene unit, a pentafluoropropylene unit, and a 1,1,1,2-tetrafluoro-2-propylene unit. Item 2. The substrate according to Item 5, which is at least one kind.
Item 7.
The fluorine-containing perhaloolefin unit is a chlorotrifluoroethylene unit, a tetrafluoroethylene unit, a hexafluoropropylene unit, a perfluoro (methyl vinyl ether) unit, a perfluoro (ethyl vinyl ether) unit, a perfluoro (propyl vinyl ether) unit, or a per. Item 6. The substrate according to Item 6, which is at least one selected from the group consisting of fluoro (butyl vinyl ether) units and perfluoro (2,2-dimethyl-1,3-dioxol) units.
Item 8.
The fluoroolefin unit is at least one selected from the group consisting of chlorotrifluoroethylene units, tetrafluoroethylene units, hexafluoropropylene units, perfluoro (methyl vinyl ether) units, and perfluoro (propyl vinyl ether) units. Item 5. The base material according to any one of Items 5 to 7.
Item 9.
Item 2. The substrate according to any one of Items 1 to 8, which has an average film thickness of 10 nm or more.
Item 10.
A bio-derived substance adhesion-preventing base material having a surface having the following phosphate-buffered saline properties.
Measured by X-ray photoelectron spectroscopy before the test in which the substrate is immersed in a phosphate buffered saline solution containing sodium chloride, disodium hydrogen phosphate, potassium chloride and potassium dihydrogen phosphate at 90 ° C. for 3 hours. The fluorine atom concentration (F) and carbon atom concentration (C) of the surface to be measured, and the fluorine atom concentration (F1s) and carbon atom concentration (C1s) of the surface measured by X-ray photoelectron spectroscopy after the test. The following equation (A):
100 × (F1s / C1s) / (F / C) (A)
The value obtained by applying to is 95 or more.
Item 11.
Item 2. The substrate according to Item 10, wherein the value obtained by applying to the formula (A) is 97 or more.
Item 12.
Item 2. The substrate according to Item 10 or 11, wherein the surface is a film containing an amorphous fluoropolymer.
Item 13.
The fluoropolymer is
The fluorine-containing aliphatic ring contains a monomer unit having a fluorine-containing aliphatic ring as a main component, and the fluorine-containing aliphatic ring has 1, 2, or 3 ethereal oxygen atoms as ring-constituting atoms.
When the fluorine-containing aliphatic ring contains a plurality of the ethereal oxygen atoms, the ethereal oxygen atoms are not adjacent to each other.
Item 12. The base material according to Item 12.
Item 14.
The fluoropolymer has the formula (1):

[In the formula, R ¹ to R ⁴ are independently fluorine atoms, fluoroalkyl groups, or fluoroalkoxy groups. ]
Contains the monomeric unit represented by, as the main component,
Item 13. The base material according to Item 13.
Item 15.
Item 2. The base material according to any one of Items 1 to 14, wherein the material is glass or resin.
Item 16.
Item 2. The base material according to any one of Items 1 to 15, wherein the material is glass, polystyrene or polymethylmethacrylate.
Item 17.
An instrument scheduled to come into contact with a biological substance, which comprises the substrate according to any one of Items 1 to 16.
Item 18.
Item 6. The instrument according to Item 17, which is for medical use, analysis of biological substances, or testing of biological substances.
Item 19.
Item 17. The device according to Item 17, which is a biological substance storage container, a cell culture container, a microchannel device, a catheter, a contact lens case, a blood purifier, a blood circuit, a blood storage bag, or a biochip.
Item 20.
Equation (1):

[In the formula, R ¹ to R ⁴ are independently fluorine atoms, fluoroalkyl groups, or fluoroalkoxy groups. ]
A coating agent for forming a surface for preventing adhesion of a biological substance, which contains an amorphous fluoropolymer containing a monomer unit represented by 1 as a main component and an aprotic solvent.
Item 21.
Item 2. The coating agent according to Item 20, wherein the content of the fluoropolymer is 10% by mass to 65% by mass with respect to the total mass of the coating agent.
Item 22.
The aprotic solvent is selected from the group consisting of perfluoroaromatic compounds, perfluorotrialkylamines, perfluoroalkanes, hydrofluorocarbons, perfluorocyclic ethers, hydrofluoroethers, and olefin compounds containing at least one chlorine atom. Item 6. The coating agent according to Item 20 or 21, which is at least one solvent to be used.
Item 23.
Item 2. The coating agent according to any one of Items 20 to 22, wherein the aprotic solvent is at least one kind of hydrofluoro ether.

One embodiment of the present disclosure can provide a substrate, an instrument or the like having a coating film on the surface whose defects are suppressed even when exposed to a physiological buffer solution. One embodiment of the present disclosure can provide a substrate, a container, or the like having a liquid-repellent coating film on the surface capable of suppressing the adhesion of a biochemical material. One embodiment of the present disclosure can provide a base material, a container, or the like having a coating film on the surface whose defects are suppressed even when exposed to a high temperature of about 250 ° C.

The above summary of the present disclosure is not intended to describe each disclosed embodiment or all implementations of the present disclosure.
The following description of the present disclosure exemplifies the embodiments of the examples more specifically.
Guidance is provided through illustrations in some parts of this disclosure, and these examples can be used in various combinations.
In each case, the exemplary group can serve as a non-exclusive and representative group.
All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety.

Terms Symbols and abbreviations herein are in the context of this specification and can be understood in the context commonly used in the art to which this disclosure belongs, unless otherwise specified.
In the present specification, the phrase "contains" is used with the intention of including the phrase "consisting of" and the phrase "consisting of".
The steps, treatments, or operations described herein may be performed at room temperature unless otherwise noted. In the present specification, room temperature can mean a temperature in the range of 10 ° C to 40 ° C.
In the present specification, the notation "Cn-Cm" (where n and m are numbers, respectively) has a carbon number of n or more and m or less, as is usually understood by those skilled in the art. Represents.

In the present specification, when the film is expressed as "thickness" or simply "film thickness", it means "average film thickness". The average film thickness is determined as follows.
Average film thickness
The average film thickness is an average value obtained by measuring the thickness five times with a micrometer. When it is difficult to measure the thickness of the film itself, such as when the film formed on a substrate such as a substrate cannot be peeled off, the thickness of the substrate before film formation and the thickness of the film-formed substrate are microscopically measured. The average film thickness is calculated by subtracting the average value of the thickness before film formation from the average value of the thickness after film formation by measuring 5 times each with a meter.
If it cannot be measured with a micrometer, the film thickness obtained by measuring the line profile of the cut surface of the film to be measured with an atomic force microscope (AFM) is taken as the average film thickness.
Specifically, it is a value determined by the method described in the specific example of the present disclosure.

In the present specification, when simply expressed as "molecular weight", it means "mass average molecular weight". The mass average molecular weight is determined as follows.
Mass average molecular weight
The mass average molecular weight is measured by the following GPC analysis method. Specifically, it is a value determined by the method described in the specific example of the present disclosure.
GPC analysis method <Sample preparation method>
The polymer is dissolved in perfluorobenzene to prepare a 2% by mass polymer solution, which is passed through a membrane filter (0.22 μm) to prepare a sample solution.
<Measurement method>
Standard sample of molecular weight: Polymethylmethacrylate Detection method: RI (Differential Refractometer)

In the present specification, "phosphate-buffered saline solution characteristics" are determined as follows.
Phosphate buffered saline resistance
Phosphate buffered saline and samples dissolved in water at 137 mmol / L sodium chloride, 10 mmol / L disodium hydrogen phosphate, 2.68 mmol / L potassium chloride and 2 mmol / L potassium dihydrogen phosphate. prepare. Fluorine atom concentration (F) and carbon atom concentration (C) are measured on the sample surface before immersion by X-ray photoelectron spectroscopy. After the measurement, the sample is immersed in the phosphate buffered saline (liquid temperature 90 ° C.) for 3 hours, and the fluorine atom concentration (F1s) and carbon atom concentration (C1s) are measured on the surface of the sample after immersion by X-ray photoelectron spectroscopy. do. The obtained fluorine atom concentration and carbon atom concentration are expressed in the following formula (A):
100 × (F1s / C1s) / (F / C) (A)
Calculate the numerical value by applying to. The calculated numerical value indicates the degree of surface defect after immersion. Therefore, when the calculated numerical value exceeds 100, it is evaluated as 100. The larger the calculated value, the higher the resistance of the sample surface to phosphate buffered saline.

In the present specification, the "glass transition temperature" is determined as follows.
Glass transition temperature (Tg)
Using DSC (Differential Scanning Calorimeter: Hitachi High-Tech Science, DSC7000), the temperature range of 30 ° C to 200 ° C is raised (first run) -lower temperature-higher (second run) under the condition of 10 ° C / min. The middle point of the endothermic curve in the second run is the glass transition temperature (° C).

Unless otherwise specified in the present specification, the "contact angle" is a "water repellency evaluation method" (Fukuyama) using a commercially available contact angle meter, for example, a contact angle meter of the DropMaster series manufactured by Kyowa Interface Science Co., Ltd. Written by Beniyo, Surface Technology, vol. 60, No.1, 2009, p21-26; hereinafter, also referred to simply as "water repellency evaluation method") as "4.1 Droplet method". It can be measured based on the method. The contact angle is specifically a value determined by the method described in the specific examples of the present disclosure.

In the present specification, the "sliding angle" is the tilt angle of the substrate when water droplets start rolling, and unless otherwise specified, a commercially available contact angle meter, for example, a contact angle meter of the DropMaster series manufactured by Kyowa Interface Science Co., Ltd. Can be measured based on the method described as "4.3 Sliding method (falling method)" in "Evaluation method of water repellency". The sliding angle is specifically a value determined by the method described in the specific examples of the present disclosure.

In the present specification, "sliding speed" is the speed at which 20 μL of water droplets roll on a film covering a substrate tilted at an inclination angle of 30 °, and unless otherwise specified, a commercially available contact angle meter, for example, Kyowa Interface Science It can be measured based on the method described as "4.4 Dynamic sliding down method" in "Evaluation method of water repellency" using the contact angle meter of DropMaster series manufactured by Co., Ltd. The sliding speed is specifically a value determined by the method described in the specific examples of the present disclosure.

Unless otherwise specified in the present specification, the "fluorinated aliphatic ring" has a plurality of carbon atoms and 1, 2, or 3 ethereal oxygen atoms as ring-constituting atoms. When the "fluorine-containing aliphatic ring" contains a plurality of oxygen atoms as ring-constituting atoms, the oxygen atoms are not adjacent to each other.
The "fluorinated aliphatic ring" includes a saturated aliphatic monocycle containing a fluorine atom.
The "fluorinated aliphatic ring" includes a ring having 4 or more members (eg, a 4-membered ring, a 5-membered ring, a 6-membered ring, a 7-membered ring).
The "fluorine-containing aliphatic ring" includes a perfluoroalkyl group (eg, a linear or branched C1-C5 perfluoroalkyl group) and a perfluoroalkoxy group (eg, a linear or branched C1-C5 par). It may have at least one selected from the group consisting of (fluoroalkoxy groups) as a substituent. The number of substituents can be 1 or more, and can be, for example, 1 to 4, 1 to 3, 1 to 2, 1, 2, 2, 3, or 4.
In the "fluorine-containing aliphatic ring", the ring-constituting carbon atom may have a fluorine atom.
An example of a "fluorinated aliphatic ring" is perfluorooxetane, which may have one or more substituents, perfluorotetra, which may have one or more substituents, and one or more substituents. Perfluorodioxolane, which may have a group, perfluorotetrahydropyran, which may have one or more substituents, and perfluoro-1,3-, which may have one or more substituents. Dioxane Perfluorooxepan which may have one or more substituents Perfluoro-1,3-dioxepan which may have one or more substituents and which has one or more substituents Includes perfluoro-1,4-dioxepan which may be and perfluoro-1,3,5-trioxepan which may have one or more substituents.

Unless otherwise noted herein, examples of "alkyl groups" include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl. , Nonyl, and decyl, which are linear or branched, can include C1-C10 alkyl groups.

Unless otherwise specified in the present specification, the "fluoroalkyl group" is an alkyl group in which at least one hydrogen atom is substituted with a fluorine atom. The "fluoroalkyl group" can be a linear or branched fluoroalkyl group.
The carbon number of the "fluoroalkyl group" is, for example, 1 to 12 carbon atoms, 1 to 6 carbon atoms, 1 to 5 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, 6 carbon atoms, and 5 carbon atoms. It can have 4 carbon atoms, 3 carbon atoms, 2 carbon atoms, or 1 carbon atom.
The number of fluorine atoms contained in the "fluoroalkyl group" is 1 or more (eg, 1 to 3, 1 to 5, 1 to 9, 1 to 11, and the maximum number that can be replaced from 1). be able to.
The "fluoroalkyl group" includes a perfluoroalkyl group.
A "perfluoroalkyl group" is a group in which all hydrogen atoms in the alkyl group are substituted with fluorine atoms.
Examples of perfluoroalkyl groups are trifluoromethyl group (CF _3- ), pentafluoroethyl group (C ₂ F _5- ), heptafluoropropyl group (CF ₃ CF ₂ CF _2- ), and heptafluoroisopropyl group (CF 3 CF 2 CF 2-). (CF ₃ ) ₂ CF-) is included.
Specific examples of the "fluoroalkyl group" include a monofluoromethyl group, a difluoromethyl group, a trifluoromethyl group (CF _3- ), and a 2,2,2-trifluoroethyl group (CF ₃ CH _2- ). , Perfluoroethyl group (C ₂ F _5- ), tetrafluoropropyl group (eg HCF ₂ CF ₂ CH _2- ), hexafluoropropyl group (eg (CF ₃ ) ₂ CH-), perfluorobutyl group (eg) Examples: CF ₃ CF ₂ CF ₂ CF _2- ), octafluoropentyl group (eg HCF ₂ CF ₂ CF ₂ CF ₂ CH _2- ), perfluoropentyl group (eg CF ₃ CF ₂ CF ₂ CF ₂ CF ₂ ). -) And a perfluorohexyl group (eg, CF ₃ CF ₂ CF ₂ CF ₂ CF ₂ CF _2- ) and the like.

Unless otherwise specified in the present specification, the "alkoxy group" is RO- [in the formula, R is an alkyl group (eg, C1-C10 alkyl group). ] Can be a group represented by.
Examples of "alkoxy groups" are methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy. , And linear or branched, C1-C10 alkoxy groups such as decyloxy.

Unless otherwise specified in the present specification, the "fluoroalkoxy group" is an alkoxy group in which at least one hydrogen atom is substituted with a fluorine atom. The "fluoroalkoxy group" can be a linear or branched fluoroalkoxy group.
The carbon number of the "fluoroalkoxy group" is, for example, 1 to 12 carbon atoms, 1 to 6 carbon atoms, 1 to 5 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, 6 carbon atoms, and 5 carbon atoms. It can have 4 carbon atoms, 3 carbon atoms, 2 carbon atoms, or 1 carbon atom.
The number of fluorine atoms contained in the "fluoroalkoxy group" is 1 or more (eg, 1 to 3, 1 to 5, 1 to 9, 1 to 11, and the maximum number that can be replaced from 1). be able to.
The "fluoroalkoxy group" includes a perfluoroalkoxy group.
A "perfluoroalkoxy group" is a group in which all hydrogen atoms in the alkoxy group are substituted with fluorine atoms.
Examples of perfluoroalkoxy groups are trifluoromethoxy group (CF ₃ O-), pentafluoroethoxy group (C ₂ F ₅ O-), heptafluoropropyloxy group (CF ₃ CF ₂ CF ₂ O-), and hepta. Includes a fluoroisopropyloxy group ((CF ₃ ) ₂ CFO-).
Specific examples of the "fluoroalkoxy group" include a monofluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, a 2,2,2-trifluoroethoxy group (CF ₃ CH ₂ O-), and a perfluoroethoxy group. Group (C ₂ F ₅ O-), tetrafluoropropyloxy group (eg HCF ₂ CF ₂ CH ₂ O-), hexafluoropropyloxy group (eg (CF ₃ ) ₂ CHO-), perfluorobutyloxy group (Example: CF ₃ CF ₂ CF ₂ CF ₂ O-), octafluoropentyloxy group (eg HCF ₂ CF ₂ CF ₂ CF ₂ CH ₂ O-), perfluoropentyloxy group (eg CF ₃ CF ₂ CF) ₂ CF ₂ CF ₂ O-) and a perfluorohexyloxy group (eg, CF ₃ CF ₂ CF ₂ CF ₂ CF ₂ CF ₂ O-) and the like can be mentioned.

Bio-derived substance adhesion-preventing substrate In one embodiment, the biological substance adhesion-preventing substrate has a surface coated with an amorphous fluoropolymer. The base material has a surface on which the adhesion of substances derived from a living body is suppressed. Substances derived from living organisms are not particularly limited, but include nucleic acids, proteins, cells, microorganisms, chromosomes, liposomes, mitochondria, organelles (organelles), proteins, various components in body fluids such as blood, and the like. The material of the base material includes glass, resin and the like, and preferred materials include glass, polystyrene and polymethylmethacrylate.

Amorphous fluoropolymer The amorphous fluoropolymer is, for example, a fluoropolymer containing a monomer unit having a fluoroaliphatic ring as a main component (here, the fluoroaliphatic ring is 1, 2, 2 as a ring-constituting atom. Or, when the fluoropolymer having three ethereal oxygen atoms and the fluoroaliphatic ring contains a plurality of the ethereal oxygen atoms, the ethereal oxygen atoms are not adjacent to each other), and is simply represented by the formula (1). Includes a fluoropolymer containing a weight unit as a main component (in the present specification, it may be referred to as "fluoropolymer (1)") and the like.
In the present specification, "containing a monomer unit as a main component" means that the ratio of a specific monomer unit to all the monomer units in the polymer is 50 mol% or more. The ratio of the specific monomer unit can be, for example, 70 mol% or more, preferably 80 mol% or more, more preferably 90 mol% or more, and particularly preferably 100 mol%.

The fluoropolymer containing a monomer unit having a fluoroaliphatic ring as a main component includes a fluoropolymer (1), Cytop ^(R) , Teflon ^TM AF and the like.
The type of the monomer unit having a fluorine-containing aliphatic ring in the fluoropolymer may be one or more, preferably 1 to 3, more preferably 1 or 2, and particularly preferably 1 type.

A monomer unit having a fluorine-containing aliphatic ring has 1, 2, or 3 ethereal oxygen atoms as ring-constituting atoms, and when the fluorine-containing aliphatic ring contains a plurality of the ethereal oxygen atoms. The etheric oxygen atoms are not adjacent to each other.
The fluorine-containing aliphatic ring contains two or more carbon atoms (eg, two, three, four) as ring constituent atoms, and one or more carbon-carbon bonds formed between adjacent carbon atoms (eg, two, three, four). Example: 1 piece, 2 pieces, 3 pieces, 4 pieces, 5 pieces, 6 pieces) can be included.
The fluorine-containing aliphatic ring preferably contains two or more carbon atoms and 1, 2, or 3 oxygen atoms as ring-constituting atoms, and does not contain other atoms.
The fluorine-containing aliphatic ring preferably does not contain a hydrogen atom.
The fluorine-containing aliphatic ring is preferably an aliphatic ring in which all hydrogen atoms are substituted with fluorine atoms.

The fluorinated aliphatic ring can be a 4-membered ring, a 5-membered ring, a 6-membered ring, or a 7-membered ring. From the viewpoint of various physical properties of the fluoropolymer, the fluoroaliphatic ring is preferably a 4-membered ring, a 5-membered ring, or a 6-membered ring, and more preferably a 5-membered ring.
The fluorine-containing aliphatic 4-membered ring can contain three carbon atoms and one oxygen atom as ring-constituting atoms. Examples of fluorine-containing aliphatic 4-membered rings include perfluorooxetane rings.
The fluorine-containing aliphatic 5-membered ring may contain 4 carbon atoms and 1 oxygen atom as ring-constituting atoms, or may contain 3 carbon atoms and 2 oxygen atoms. Examples of fluorine-containing aliphatic 5-membered rings include perfluorotetrahydrofuran rings and perfluorodioxolane rings.
The fluorine-containing aliphatic 6-membered ring may contain 5 carbon atoms and 1 oxygen atom as ring-constituting atoms, or may contain 4 carbon atoms and 2 oxygen atoms. Examples of fluorine-containing aliphatic 6-membered rings include perfluorotetrahydropyran rings and perfluoro-1,3-dioxane rings.
The fluorine-containing aliphatic 6-membered ring may contain 5 carbon atoms and 1 oxygen atom as ring-constituting atoms, or may contain 4 carbon atoms and 2 oxygen atoms. Examples of fluorine-containing aliphatic 6-membered rings include perfluorotetrahydropyran rings and perfluoro-1,3-dioxane rings.
The fluorine-containing aliphatic 7-membered ring may contain 6 carbon atoms and 1 oxygen atom as ring-constituting atoms, may contain 5 carbon atoms and 2 oxygen atoms, or may contain 4 oxygen atoms. It may contain a carbon atom and three oxygen atoms. Examples of fluorine-containing aliphatic 7-membered rings include perfluorooxepang rings, perfluoro-1,3-geoxepang rings, perfluoro-1,4-dioxepang rings, and perfluoro-1,3,5-trioxepang rings. Include.

The fluorine-containing aliphatic ring may have one or more substituents. When there are a plurality of substituents, they may be the same or different.
Substituents are from perfluoroalkyl groups (eg, linear or branched C1-C5 perfluoroalkyl groups) and perfluoroalkoxy groups (eg, linear or branched C1-C5 perfluoroalkoxy groups). Can be at least one selected from the group of The number of substituents can be 1 or more, and can be, for example, 1 to 4, 1 to 3, 1 to 2, 1, 2, 2, 3, or 4.
As the substituent, at least one group selected from the group consisting of trifluoromethyl, perfluoroethyl, perfluoropropyl, perfluoroisopropyl, trifluoromethoxy, and perfluoroethoxy is preferable, and trifluoromethyl and perfluoro are preferable. At least one group selected from the group consisting of ethyl, perfluoropropyl, and perfluoroisopropyl is more preferred, and at least one group selected from the group consisting of trifluoromethyl, perfluoroethyl, and trifluoromethoxy. Is particularly preferable.

［式中、Ｒ^１～Ｒ^４はそれぞれ独立して、フッ素原子、フルオロアルキル基、又はフルオロアルコキシ基である。］
で表される単量体単位（本明細書中、「単位（１）」と称することがある。）が好ましい。
式（１）で表わされる単量体単位を主成分として含むフッ素ポリマーで被覆された表面は、生体由来物質等の生化学的材料の付着を抑制できる点、生理学的緩衝液にさらされても表面の欠損が生じにくい点、又は、250℃程度の高温にさらされても表面の欠損が生じにくい点で有利である。 The monomer unit having a fluorine-containing aliphatic ring is represented by the formula (1):

[In the formula, R ¹ to R ⁴ are independently fluorine atoms, fluoroalkyl groups, or fluoroalkoxy groups. ]
A monomer unit represented by (in the present specification, it may be referred to as “unit (1)”) is preferable.
The surface coated with a fluoropolymer containing the monomer unit represented by the formula (1) as a main component can suppress the adhesion of biochemical materials such as biological substances, and even when exposed to a physiological buffer solution. It is advantageous in that surface defects are unlikely to occur, or surface defects are unlikely to occur even when exposed to a high temperature of about 250 ° C.

In each of R ¹ to R ⁴ , the fluoroalkyl group is, for example, a linear or branched C1-C5 fluoroalkyl group, a linear or branched C1-C4 fluoroalkyl group, a linear or branched group. It can be a C1-C3 fluoroalkyl group or a linear or branched C1-C2 fluoroalkyl group.
As the linear or branched C1-C5 fluoroalkyl group, a linear or branched C1-C5 perfluoroalkyl group is preferable.
As the linear or branched C1-C4 fluoroalkyl group, a linear or branched C1-C4 perfluoroalkyl group is preferable.
As the linear or branched C1-C3 fluoroalkyl group, a linear or branched C1-C3 perfluoroalkyl group is preferable.
As the C1-C2 fluoroalkyl group, a C1-C2 perfluoroalkyl group is preferable.

In each of R ¹ to R ⁴ , the fluoroalkoxy group is, for example, a linear or branched C1-C5 fluoroalkoxy group, a linear or branched C1-C4 fluoroalkoxy group, a linear or branched C1-C4 fluoroalkoxy group. It can be a C1-C3 fluoroalkoxy group or a C1-C2 fluoroalkoxy group.
As the linear or branched C1-C5 fluoroalkoxy group, a linear or branched C1-C5 perfluoroalkoxy group is preferable.
As the linear or branched C1-C4 fluoroalkoxy group, a linear or branched C1-C4 perfluoroalkoxy group is preferable.
As the linear or branched C1-C3 fluoroalkoxy group, a linear or branched C1-C3 perfluoroalkoxy group is preferable.
As the C1-C2 fluoroalkoxy group, a C1-C2 perfluoroalkoxy group is preferable.

R ¹ to R ⁴ may be independently a fluorine atom, a linear or branched C1-C5 fluoroalkyl group, or a linear or branched C1-C5 fluoroalkoxy group.
R ¹ to R ⁴ may be independently a fluorine atom, a linear or branched C1-C5 perfluoroalkyl group, or a linear or branched C1-C5 perfluoroalkoxy group.
R ¹ to R ⁴ may be independently a fluorine atom, a linear or branched C1-C4 fluoroalkyl group, or a linear or branched C1-C4 fluoroalkoxy group.
R ¹ to R ⁴ may be independently a fluorine atom, a linear or branched C1-C4 perfluoroalkyl group, or a linear or branched C1-C4 perfluoroalkoxy group.
R ¹ to R ⁴ may be independently a fluorine atom, a linear or branched C1-C3 fluoroalkyl group, or a linear or branched C1-C3 fluoroalkoxy group.
R ¹ to R ⁴ may be independently a fluorine atom, a linear or branched C1-C3 perfluoroalkyl group, or a linear or branched C1-C3 perfluoroalkoxy group.
R ¹ to R ⁴ may be independently a fluorine atom, a C1-C2 fluoroalkyl group, or a C1-C2 fluoroalkoxy group.
R ¹ to R ⁴ may be independently a fluorine atom, a C1-C2 perfluoroalkyl group, or a C1-C2 perfluoroalkoxy group.
R ¹ to R ⁴ may be independently fluorine atoms, trifluoromethyl, pentafluloethyl, or trifluoromethoxy.

In R ¹ to R ⁴ , at least one group is a fluorine atom, and the remaining groups are independent C1-C2 perfluoroalkyl groups or C1-C2 perfluoroalkoxy groups when there are a plurality of the remaining groups. May be.
In R ¹ to R ⁴ , at least two groups are fluorine atoms, and the remaining groups are independent C1-C2 perfluoroalkyl groups or C1-C2 perfluoroalkoxy groups when there are a plurality of the remaining groups. May be.
In R ¹ to R ⁴ , at least three groups are fluorine atoms, and the remaining groups may be C1-C2 perfluoroalkyl groups or C1-C2 perfluoroalkoxy groups.
In R ¹ to R ⁴ , at least three groups may be fluorine atoms, and the remaining groups may be C1-C2 perfluoroalkyl groups.
All of R ¹ to R ⁴ may be fluorine atoms.

［式中、Ｒ^１はフッ素原子、フルオロアルキル基、又はフルオロアルコキシ基である。］
フッ素ポリマーを構成する単量体単位は、単位（１－１）の１種単独又は２種以上を含んでよい。 The unit (1) may be a monomer unit represented by the following formula (1-1) (in the present specification, it may be referred to as “unit (1-1)”).

[In the formula, R ¹ is a fluorine atom, a fluoroalkyl group, or a fluoroalkoxy group. ]
The monomer unit constituting the fluoropolymer may contain one type of unit (1-1) alone or two or more types.

In unit (1-1), R ¹ may be a fluorine atom, a linear or branched C1-C5 perfluoroalkyl group, or a linear or branched C1-C5 perfluoroalkoxy group.
In unit (1-1), R ¹ may be a fluorine atom, a linear or branched C1-C4 fluoroalkyl group, or a linear or branched C1-C4 fluoroalkoxy group.
In unit (1-1), R ¹ may be a fluorine atom, a linear or branched C1-C4 perfluoroalkyl group, or a linear or branched C1-C4 perfluoroalkoxy group.
In unit (1-1), R ¹ may be a fluorine atom, a linear or branched C1-C3 fluoroalkyl group, or a linear or branched C1-C3 fluoroalkoxy group.
In unit (1-1), R ¹ may be a fluorine atom, a linear or branched C1-C3 perfluoroalkyl group, or a linear or branched C1-C3 perfluoroalkoxy group.
In unit (1-1), R ¹ may be a fluorine atom, a C1-C2 fluoroalkyl group, or a C1-C2 fluoroalkoxy group.
In unit (1-1), R ¹ may be a fluorine atom, a C1-C2 perfluoroalkyl group, or a C1-C2 perfluoroalkoxy group.
In unit (1-1), R ¹ may be a fluorine atom, trifluoromethyl, pentafluoroethyl, or trifluoromethoxy.
In unit (1-1), R ¹ may be a C1-C2 perfluoroalkyl group or a C1-C2 perfluoroalkoxy group.
In unit (1-1), R ¹ may be a C1-C2 perfluoroalkyl group.

Preferred examples of the unit (1-1) include a monomer unit represented by the following formula (1-11) (in the present specification, it may be referred to as "unit (1-11)"). ..

The fluoropolymer (1) may contain a fluoroolefin unit in addition to the unit (1).
The fluoroolefin unit may be used alone or in combination of two or more.
The ratio of the fluoroolefin unit can be 50 mol% or less of all the monomer units, preferably 30 mol% or less, more preferably 20 mol% or less, further preferably 10 mol% or less, and particularly preferably 0%.

The fluoroolefin unit is a monomer unit formed after polymerization by a monomer containing a fluorine atom and a carbon-carbon double bond.
The atoms constituting the fluoroolefin unit may be only a fluorine atom, a halogen atom other than the fluorine atom, a carbon atom, a hydrogen atom, and an oxygen atom.
The atoms constituting the fluoroolefin unit may be only a fluorine atom, a halogen atom other than the fluorine atom, a carbon atom, and a hydrogen atom.
The atoms constituting the fluoroolefin unit may be only a fluorine atom, a carbon atom, and a hydrogen atom.
The atoms constituting the fluoroolefin unit may be only fluorine atoms and carbon atoms.

Fluoroolefin units include fluorine-containing perhaloolefin units, vinylidene fluoride units (-CH ₂ -CF _2- ), trifluoroethylene units (-CFH-CF _2- ), and pentafluoropropylene units (-CFH-CF (CF)). ₃ )-, -CF ₂ -CF (CHF ₂ )-), and 1,1,1,2-tetrafluoro-2-propylene unit (-CH ₂ -CF (CF ₃ )-), etc. Includes at least one unit to be made.

The fluorine-containing perhaloolefin unit is a monomer unit formed after polymerization by a monomer containing a fluorine atom and a carbon-carbon double bond and may contain a halogen atom other than the fluorine atom.
The fluorine-containing perhaloolefin unit is chlorotrifluoroethylene unit (-CFCl-CF _2- ), tetrafluoroethylene unit (-CF ₂ -CF _2- ), hexafluoropropylene unit (-CF ₂ -CF (CF ₃ )). -), Perfluoro (methyl vinyl ether) unit (-CF ₂ -CF (OCF ₃ )-), Perfluoro (ethyl vinyl ether) unit (-CF ₂ -CF (OC ₂ F ₅ )-), Perfluoro (propyl vinyl ether) ) Units (-CF ₂ -CF (OCF ₂ C ₂ F ₅ )-), Perfluoro (butyl vinyl ether) units (-CF ₂ -CF (O (CF ₂ ) ₂ C ₂ F ₅ )-), and Perfluoro (2,2-Dimethyl-1,3-dioxol) Unit (-CF-CAF- (in the formula, A is a perfluorodioxolan ring formed with the adjacent carbon atom shown in the formula, which is a dioxolan ring. It shows a structure in which two trifluoromethyls are bonded to a carbon atom at the 2-position.) Includes at least one selected from the group consisting of)).

The fluoroolefin unit includes at least one selected from the group consisting of chlorotrifluoroethylene units, tetrafluoroethylene units, hexafluoropropylene units, perfluoro (methyl vinyl ether) units, and perfluoro (propyl vinyl ether) units. ..

The fluoropolymer (1) may contain one or more other monomer units in addition to the unit (1) and the fluoroolefin unit, and is preferably not contained.
Such other monomer units include CH ₂ = CHRf (Rf represents a C1-C10 fluoroalkyl group) unit, an alkyl vinyl ether unit (eg, cyclohexyl vinyl ether unit, ethyl vinyl ether unit, butyl vinyl ether unit, methyl vinyl ether unit). ), Alkenyl vinyl ether unit (eg, polyoxyethylene allyl ether unit, ethyl allyl ether unit), organic silicon compound unit having reactive α, β-unsaturated group (eg, vinyltrimethoxysilane unit, vinyltriethoxysilane unit) , Vinyl tris (methoxyethoxy) silane unit), acrylic acid ester unit (eg, methyl acrylate unit, ethyl acrylate unit), methacrylic acid ester unit (eg, methyl methacrylic acid unit, ethyl methacrylate unit), vinyl ester It includes units (eg, vinyl acetate unit, vinyl benzoate unit, "Beova" (vinyl ester manufactured by Shell) unit) and the like.

The ratio of the other monomer units can be, for example, 0 to 20 mol%, 0 to 10 mol%, or the like of all the monomer units.

The mass average molecular weight of the fluoropolymer is, for example, 10,000 to 1,000,000, preferably 30,000 to 500,000, and more preferably 50,000 to 300,000. Having a molecular weight within these ranges is advantageous in terms of the durability of the fluoropolymer film.

The glass transition temperature (Tg) of the fluoropolymer is preferably 110 ° C. or higher, more preferably 110 ° C. to 300 ° C., still more preferably 120 ° C. to 300 ° C., and particularly preferably 125 ° C. to 200 ° C. When the glass transition temperature is within these ranges, it is advantageous in that the bending durability of the fluoropolymer film formed on the surface of the substrate is high.

The sliding speed (inclination angle 30 °) of the surface coated with the amorphous fluoropolymer in the bio-derived substance adhesion prevention substrate is, for example, 150 mm / s or more, 150 mm / s to 250 mm / s, etc., preferably 160 mm / s. It is ~ 250 mm / s, more preferably 170 mm / s to 250 mm / s.

The sliding angle of the surface of the biological substance adhesion-preventing substrate coated with the amorphous fluoropolymer is, for example, 20 ° or less, preferably 15 ° or less.

The contact angle of the surface of the bio-derived substance adhesion-preventing substrate coated with the amorphous fluoropolymer is, for example, 100 ° to 130 °, preferably 100 ° to 120 °, and 110 ° to 120 °. Is more preferable. The contact angle of the existing superhydrophobic surface is approximately 150 ° or more. The surface of the substrate of the present disclosure can exhibit good sliding property (low sliding angle or high sliding speed) even when the contact angle is 100 ° to 130 °.

The fluoropolymer can be produced, for example, by polymerizing a monomer corresponding to a monomer unit constituting the fluoropolymer by an appropriate polymerization method. For example, it can be produced by polymerizing one type of monomer corresponding to the unit (1) alone or two or more types.

Further, in the fluoropolymer (1), at least one of the monomers corresponding to the unit (1) alone or two or more thereof is selected from the group consisting of fluoroolefins and other monomers, if necessary. It can be produced by polymerizing with a seed monomer.

［式中、Ｒ^１～Ｒ^４は、前記と同意義である。］
で表される化合物（本明細書中、「単量体（Ｍ１）」と称することがある。）である。 Those skilled in the art can understand the monomers corresponding to the monomer units constituting the fluoropolymer (1). For example, the monomer corresponding to the unit (1) is the formula (M1) :.

[In the formula, R ¹ to R ⁴ have the same meaning as described above. ]
It is a compound represented by (in the present specification, it may be referred to as "monomer (M1)").

［式中、Ｒ^１は、フッ素原子、フルオロアルキル基、又はフルオロアルコキシ基である。］
で表される化合物（本明細書中、「単量体（Ｍ１－１）」と称することがある。）である。 For example, the monomer corresponding to the unit (1-1) is represented by the formula (M1-1) :.

[In the formula, R ¹ is a fluorine atom, a fluoroalkyl group, or a fluoroalkoxy group. ]
It is a compound represented by (in the present specification, it may be referred to as "monomer (M1-1)").

で表される化合物（本明細書中、「単量体（Ｍ１－１１）」と称することがある。）である。 For example, the monomer corresponding to the unit (1-11) is represented by the formula (M1-11) :.

It is a compound represented by (in the present specification, it may be referred to as "monomer (M1-11)").

For example, the monomers corresponding to the tetrafluoroethylene unit, hexafluoropropylene unit, and vinylidene fluoride unit are tetrafluoroethylene (CF ₂ = CF ₂ ), hexafluoropropylene (CF ₃ CF = CF ₂ ), and foot, respectively. It is vinylidene compound (CH ₂ = CF ₂ ).

As a polymerization method, it is necessary to dissolve or disperse an appropriate amount of the monomer corresponding to the monomer unit constituting the fluoropolymer (1) in a solvent (eg, an aprotonic solvent or the like) as necessary. A method of adding a polymerization initiator according to the above and performing radical polymerization, bulk polymerization, solution polymerization, suspension polymerization, emulsification polymerization and the like can be mentioned.
Preferred polymerization methods are solution polymerization, which has a high yield because a liquid in which the fluoropolymer (1) is dissolved at a high concentration can be produced, which is advantageous for thick film formation and purification, and bulk polymerization, which tends to improve the molecular weight. As the fluoropolymer (1), a fluoropolymer (1) produced by solution polymerization is preferable. A fluoropolymer (1) produced by solution polymerization in which the monomer is polymerized in the presence of an aprotic solvent is more preferable.

In the solution polymerization of the fluoropolymer (1), the solvent used is preferably an aprotic solvent. The amount of the aprotonic solvent used in the production of the fluoropolymer (1) is, for example, 80% by mass or less, less than 80% by mass, 75% by mass or less, 70% by mass or less, based on the sum of the monomer mass and the solvent mass. 35% by mass to 95% by mass, 35% by mass to 90% by mass, 35% by mass to 80% by mass, 35% by mass to 70% by mass, 35% by mass or more and less than 70% by mass, 60% by mass to 80% by mass, etc. Can be done. It can be preferably 35% by mass or more and less than 80% by mass, more preferably 40% by mass to 70% by mass, and particularly preferably 50% by mass to 70% by mass.

Examples of the aprotonic solvent used for the polymerization of the fluoropolymer (1) include perfluoroaromatic compounds, perfluorotrialkylamines, perfluoroalkanes, hydrofluorocarbons, perfluorocyclic ethers, hydrofluoroethers, and at least. At least one selected from the group consisting of olefin compounds containing one chlorine atom can be mentioned.

The perfluoroaromatic compound is, for example, a perfluoroaromatic compound which may have one or more perfluoroalkyl groups. The aromatic ring contained in the perfluoroaromatic compound may be at least one ring selected from the group consisting of a benzene ring, a naphthalene ring, and an anthracene ring. The perfluoroaromatic compound may have one or more aromatic rings (eg: one, two, three).
The perfluoroalkyl group as a substituent is, for example, a linear or branched C1-C6, C1-C5, or C1-C4 perfluoroalkyl group, which is a linear or branched C1-C3 perfluoro. Alkyl groups are preferred.
The number of substituents is, for example, 1 to 4, preferably 1 to 3, and more preferably 1 to 2. When there are a plurality of substituents, they may be the same or different.
Examples of perfluoroaromatic compounds include perfluorobenzene, perfluorotoluene, perfluoroxylene, perfluoronaphthalene.
Preferred examples of perfluoroaromatic compounds include perfluorobenzene and perfluorotoluene.

Perfluorotrialkylamines are, for example, amines substituted with three linear or branched perfluoroalkyl groups. The perfluoroalkyl group has, for example, 1 to 10, preferably 1 to 5, and more preferably 1 to 4. The perfluoroalkyl groups may be the same or different, and are preferably the same.
Examples of perfluorotrialkylamines are perfluorotrimethylamine, perfluorotriethylamine, perfluorotripropylamine, perfluorotriisopropylamine, perfluorotributylamine, perfluorotrisec-butylamine, perfluorotritert-butylamine, perfluoro. Includes trypentylamine, perfluorotriisopentylamine, and perfluorotrineopentylamine.
Preferred examples of perfluorotrialkylamines include perfluorotripropylamine, perfluorotributylamine.

The perfluoroalkane is, for example, a linear, branched or cyclic C3-C12 (preferably C3-C10, more preferably C3-C6) perfluoroalkane.
Examples of perfluoroalkanes are perfluoropentane, perfluoro-2-methylpentane, perfluorohexane, perfluoro-2-methylhexane, perfluoroheptane, perfluorooctane, perfluorononane, perfluorodecane, perfluoro. Includes cyclohexane, perfluoro (methylcyclohexane), perfluoro (dimethylcyclohexane) (eg, perfluoro (1,3-dimethylcyclohexane)), perfluorodecalin.
Preferred examples of perfluoroalkanes include perfluoropentane, perfluorohexane, perfluoroheptane, perfluorooctane.

The hydrofluorocarbon is, for example, C3-C8 hydrofluorocarbon.
Examples of hydrofluorocarbons are CF ₃ CH ₂ CF ₂ H, CF ₃ CH ₂ CF ₂ CH ₃ , CF ₃ CHFCHFC ₂ F ₅ , 1,1,2,2,3,3,4-heptafluorocyclopentane, CF. Includes ₃ CF ₂ CF ₂ CF ₂ CH ₂ CH ₃ , CF ₃ CF ₂ CF ₂ CF ₂ CF ₂ CHF ₂ , and CF ₃ CF ₂ CF ₂ CF ₂ CF ₂ CF ₂ CH ₂ CH ₃ .
Preferred examples of hydrofluorocarbons include CF ₃ CH ₂ CF ₂ H, CF ₃ CH ₂ CF ₂ CH ₃ .

The perfluorocyclic ether is, for example, a perfluorocyclic ether which may have one or more perfluoroalkyl groups. The ring of the perfluorocyclic ether may be a 3- to 6-membered ring. The ring of the perfluorocyclic ether may have one or more oxygen atoms as ring-constituting atoms. The ring preferably has one or two, more preferably one oxygen atom.
The perfluoroalkyl group as a substituent is, for example, a linear or branched C1-C6, C1-C5, or C1-C4 perfluoroalkyl group. Preferred perfluoroalkyl groups are linear or branched C1-C3 perfluoroalkyl groups.
The number of substituents is, for example, 1 to 4, preferably 1 to 3, and more preferably 1 to 2. When there are a plurality of substituents, they may be the same or different.
Examples of perfluorocyclic ethers include perfluorotetrahydrofuran, perfluoro-5-methyltetrahydrofuran, perfluoro-5-ethyltetrahydrofuran, perfluoro-5-propyltetrahydrofuran, perfluoro-5-butyltetrahydrofuran, perfluorotetrahydropyran. do.
Preferred examples of perfluorocyclic ethers include perfluoro-5-ethyltetrahydrofuran, perfluoro-5-butyltetrahydrofuran.

The hydrofluoroether is, for example, a fluorine-containing ether.
The global warming potential (GWP) of the hydrofluoroether is preferably 600 or less, more preferably 400 or less, and particularly preferably 300 or less. The lower limit of the global warming potential (GWP) of the hydrofluoroether may be 1 or more or 5 or more.
Examples of hydrofluoroethers are CF ₃ CF ₂ CF ₂ CF ₂ OCH _3, CF ₃ CF ₂ CF (CF ₃ ) OCH _3, CF ₃ CF (CF ₃ ) CF ₂ OCH _3, CF ₃ CF ₂ CF ₂ CF ₂ OC ₂ H ₅ , CF ₃ CH ₂ OCF ₂ CHF ₂ , C ₂ F ₅ CF (OCH ₃ ) C ₃ F ₇ , (CF ₃ ) ₂ CHOCH ₃ , (CF ₃ ) ₂ CFOCH ₃ , CHF ₂ CF ₂ OCH ₂ CF ₃ , CHF ₂ CF ₂ CH ₂ OCF ₂ CHF ₂ , CF ₃ CHFCF ₂ OCH ₃ , CF ₃ CHFCF ₂ OCF ₃ , Trifluoromethyl 1,2,2,2-tetrafluoroethyl ether (HFE-227me), difluoro Methyl 1,1,2,2,2-pentafluoroethyl ether (HFE-227mc), trifluoromethyl 1,1,2,2-tetrafluoroethyl ether (HFE-227pc), difluoromethyl 2,2,2- Trifluoroethyl ether (HFE-245mf), 2,2-difluoroethyltrifluoromethyl ether (HFE-245pf), 1,1,2,3,3-hexafluoropropylmethyl ether (CF ₃ CHFCF ₂ OCH ₃ ), 1,1,1,2,2-tetrafluoroethyl 2,2,2-trifluoroethyl ether (CHF ₂ CF ₂ OCH ₂ CF ₃ ), 1,1,1,3,3,3-hexafluoro-2 -Methoxypropane ((CF ₃ ) ₂ CHOCH ₃ ) and 1, 1, 1, 2, 2, 3, 4, 5, 5, 5-decafluoro-3-methoxy-4- (trifluoromethyl) -pentane including.
Preferred examples of hydrofluoroethers are CF ₃ CF ₂ CF ₂ CF ₂ OCH _3, CF ₃ CF ₂ CF ₂ CF ₂ OC ₂ H ₅ , CF ₃ CH ₂ OCF ₂ CHF ₂ , C ₂ F ₅ CF (OCH ₃ ). Includes C ₃ F ₇ 1, 1, 1, 2, 2, 3, 4, 5, 5, 5-decafluoro-3-methoxy-4- (trifluoromethyl) -pentane.
The hydrofluoroether has the following formula (B1):
R ²¹ -OR ²² (B1)
[In the formula, R ²¹ is linear or branched perfluorobutyl, and R ²² is methyl or ethyl. ]
The compound represented by 1,1, 1, 2, 2, 3, 4, 5, 5, 5-decafluoro-3-methoxy-4- (trifluoromethyl) -pentane is more preferable.

The olefin compound containing at least one chlorine atom is a C2-C4 (preferably C2-C3) olefin compound containing at least one chlorine atom in its structure. An olefin compound containing at least one chlorine atom is a carbon atom in a hydrocarbon having 1 or 2 (preferably 1) carbon atom-carbon atom double bond (C = C) and having 2 to 4 carbon atoms. A compound in which at least one of the hydrogen atoms bonded to is substituted with a chlorine atom. A compound in which at least one of the hydrogen atoms bonded to the two carbon atoms constituting the carbon atom-carbon atom double bond in a hydrocarbon having 2 to 4 carbon atoms is replaced with a chlorine atom is preferable.
The number of chlorine atoms is 1 to the maximum number that can be replaced. The number of chlorine atoms can be, for example, 1, 2, 3, 4, 5, or the like.
The olefin compound containing at least one chlorine atom may contain at least one (eg, 1, 2, 3, 4, 5, etc.) fluorine atom.
Examples of chloroform compounds containing at least one chlorine atom are CH ₂ = CHCl, CHCl = CHCl, CCl ₂ = CHCl, CCl ₂ = CCl ₂ , CF ₃ CH = CHCl, CHF ₂ CF = CHCl, CFH ₂ CF = CHCl. , CF ₃ CCl = CFCl, CF ₂ HCl = CFCl, CFH ₂ Cl = CFCl.
Preferred examples of olefin compounds containing at least one chlorine atom include CHCl = CHCl, CHF ₂ CF = CHCl, CF ₃ CH = CHCl, CF ₃ CCl = CFCl.

As the aprotic solvent, hydrofluoroether is preferable because it has a small environmental load during use and can dissolve a polymer at a high concentration.

Preferred examples of polymerization initiators used in the production of fluoropolymers are di-n-propyl peroxydicarbonate, diisopropylperoxydicarbonate, diisobutyryl peroxide, di (ω-hydro-dodecafluoroheptanoid) peroxide. , Di (ω-hydro-hexadecafluorononanoyl) peroxide, ω-hydro-dodecafluoroheptanoyl-ω-hydrohexadecafluorononanoyl-peroxide, benzoyl peroxide, peroxypivalate tert-butyl, peroxypivalate tert -Includes hexyl, ammonium persulfate, sodium persulfate, potassium persulfate.
More preferred examples of the polymerization initiator are di-n-propylperoxydicarbonate, diisopropylperoxydicarbonate, diisobutyryl peroxide, di (ω-hydro-dodecafluoroheptanoyl) peroxide, benzoyl peroxide, peroxypivalic acid. Includes tert-butyl, tert-hexyl peroxypivalate, ammonium persulfate.

The amount of the polymerization initiator used in the polymerization reaction can be, for example, 0.0001 g to 0.05 g, preferably 0.0001 g to 0.01 g, based on 1 g of all the monomers subjected to the reaction. It may be preferably 0.0005 g to 0.008 g.

The temperature of the polymerization reaction can be, for example, −10 ° C. to 160 ° C., preferably 0 ° C. to 160 ° C., and more preferably 0 ° C. to 100 ° C.

The reaction time of the polymerization reaction may be preferably 0.5 hours to 72 hours, more preferably 1 hour to 48 hours, still more preferably 3 hours to 30 hours.

The polymerization reaction can be carried out in the presence or absence of an inert gas (eg, nitrogen gas), preferably in the presence.

The polymerization reaction can be carried out under reduced pressure, atmospheric pressure, or pressurized conditions.

The polymerization reaction can be carried out by adding a monomer to an aprotic solvent containing a polymerization initiator and then subjecting it to polymerization conditions. Further, it can be carried out by adding a polymerization initiator to an aprotic solvent containing a monomer and then subjecting it to polymerization conditions.

If desired, the fluoropolymer (1) produced by the polymerization reaction may be purified by conventional methods such as extraction, dissolution, concentration, filter filtration, precipitation, dehydration, adsorption, chromatography, or a combination thereof. Alternatively, a liquid in which the fluoropolymer produced by the polymerization reaction is dissolved, a liquid obtained by diluting the liquid, a liquid in which other components are added as necessary to these liquids, etc. are applied to the substrate and then dried or heated (eg,). : 30 ° C to 150 ° C) to form a bio-derived substance adhesion-preventing substrate having a surface coated with the fluoropolymer (1). Alternatively, the base material is immersed in a solution in which a fluoropolymer produced by a polymerization reaction is dissolved, a solution obtained by diluting the solution, a solution in which other components are added as necessary to these solutions, and then dried or heated (). Example: 30 ° C to 150 ° C) to form a bio-derived substance adhesion-preventing substrate having a surface coated with the fluoropolymer (1).

The film formed of the fluoropolymer constituting the surface of the bio-derived substance adhesion prevention substrate contains the fluoropolymer, for example, 50% by mass to 100% by mass, preferably 60% by mass to 100% by mass, based on the total mass of the film. %, More preferably 80% by mass to 100% by mass, and particularly preferably 90% by mass to 100% by mass.

The film formed of the fluoropolymer constituting the surface of the bio-derived substance adhesion prevention base material may contain other components. The other component may be a component conventionally used on the surface of the biological substance adhesion prevention base material. For example, it may be a wetting agent, a leveling agent, a colorant, a light diffusing agent, a filler, a plasticizer, a viscosity adjusting agent, a flexibility imparting agent, a light resistance stabilizing agent, a reaction inhibitor, an adhesion accelerator and the like.
The film formed of the fluoropolymer constituting the surface of the bio-derived substance adhesion prevention base material can contain other components in an appropriate amount as long as the effects of the present disclosure can be obtained. The content of the other components is, for example, 0% by mass to 50% by mass, preferably 0% by mass to 40% by mass, more preferably 0% by mass to 20% by mass, and particularly preferably 0% by mass, based on the total mass of the film. It can be 0% by mass to 10% by mass.

The bio-derived substance adhesion-preventing base material can be produced, for example, by removing the solvent from a liquid in which a fluoropolymer is dissolved or dispersed in a solvent by drying, heating or the like. The electret material can preferably be produced by removing the solvent from the coating agents of the present disclosure described below.

In addition, the surface of the bio-derived substance adhesion prevention substrate is surface-treated with a surface treatment agent such as a silane coupling agent (including a hydrolyzate of the silane coupling agent) before the amorphous fluoropolymer is applied. May be. The surface treatment improves the fixation of the amorphous fluoropolymer to the substrate. Examples of the silane coupling agent include methyltrimethoxysilane, methyltriethoxysilane, ethyltrimethoxysilane, ethyltriethoxysilane, 3-aminopropyltrimethoxysilane (APTMS), 3-aminopropyltriethoxysilane, and 3-aminopropyl. Methyldimethoxysilane, 3-aminopropylmethyldiethoxysilane, 2-aminoethyl-3-aminopropyltrimethoxysilane, 2-aminoethyl-3-aminopropyltriethoxysilane, 2-aminoethyl-3-aminopropylmethyldimethoxy Examples include silane, 2-aminoethyl-3-aminopropylmethyldiethoxysilane, 2-aminoethyltrimethoxysilane, 2-aminoethyltriethoxysilane, 4-aminobutyltrimethoxysilane, 4-aminobutyltriethoxysilane and the like. It can be used alone or in combination of two or more. Preferred silane coupling agents include methyltrimethoxysilane, methyltriethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminoethyltrimethoxysilane, and 3-aminopropyltriethoxysilane. In particular, 3-aminopropyltriethoxysilane is suitable.
Silane coupling agents are usually used in solution form. The solution can be prepared by diluting the silane coupling agent with water or a mixed solvent of water and alcohol, and if necessary, using an acid catalyst such as acetic acid. The concentration of the silane coupling agent is usually 0.1 to 10% by mass, preferably 0.2 to 5% by mass, and more preferably 0.4 to 3% by mass. Examples of the alcohol include C1 to C3 alcohols such as methanol, ethanol, propanol and isopropyl alcohol.
In a solution containing a silane coupling agent and / or a partial hydrolyzate thereof, an alkoxide of a metal such as silicon, titanium, or zirconium (for example, tetraalkoxysilane, etc.), as required, to the extent that the effect of the present invention is exhibited. A silane coupling agent other than the above and / or a hydrolyzate thereof may be contained.

The thickness of the film formed of the fluoropolymer constituting the surface of the bio-derived substance adhesion prevention base material can be appropriately selected depending on the application to which the base material is applied, for example, 10 nm or more, 10 nm to 1000 μm, and 30 nm. It can be up to 500 μm, 50 nm to 500 μm, etc., preferably 100 nm to 500 μm or less, more preferably 500 nm to 300 μm, still more preferably 800 nm to 200 μm or less, and particularly preferably 10 μm to 200 μm. When the average film thickness is within the above range, it is advantageous in that the peeling of the film from the substrate can be suppressed.

The surface of the bio-derived substance adhesion-preventing substrate composed of a film made of a fluoropolymer suppresses film defects even when exposed to a physiological buffer solution. The surface can suppress the adhesion of biological substances. Even if the surface is exposed to a high temperature of about 250 ° C., film defects are suppressed.

One embodiment of the present disclosure is a biogenic substance adhesion-preventing substrate having a surface having a phosphate buffered saline resistance of 95 or more. The base material is not particularly limited as long as the surface thereof has a phosphate buffered saline resistance of 95 or more, but the surface thereof is preferably a film containing the amorphous fluoropolymer described above.

Instruments The above-mentioned various base materials suppress the adhesion of biological substances, have excellent phosphate buffered saline resistance, and suppress surface defects even at high temperatures of about 250 ° C (for example, sterilization temperature), so that biological substances are suppressed. It is useful as a base material that constitutes an instrument (preferably its surface) that is expected to come into contact with.
The device is not particularly limited as long as it is a device containing the above-mentioned base material. The instruments include instruments for various purposes such as medical instruments, biological substance analysis instruments, and biological substance testing instruments.
Examples of instruments include biological material storage containers, cell culture containers, microchannel devices, catheters, contact lens cases, blood purifiers, blood circuits, blood storage bags, biochips and the like.
Preferred examples of the device include a biological substance storage container, a cell culture container, a microchannel device and the like.

Coating Agent One embodiment of the present disclosure is a coating agent containing a fluoropolymer (1) and an aprotic solvent used to form a surface such as a substrate in which the adhesion of a biological substance is suppressed. ..

The fluoropolymer (1) in the coating agent may be the fluoropolymer (1) described in the bio-derived substance adhesion prevention substrate. Therefore, unless otherwise specified, the details of the fluoropolymer (1) in the bio-derived substance adhesion-preventing substrate can be applied to the details of the fluoropolymer (1) in the coating agent.
In the coating agent, the content of the fluoropolymer (1) is, for example, 5% by mass to 65% by mass, 10% by mass to 65% by mass, 20% by mass to 65% by mass, and 30% by mass with respect to the total mass of the coating agent. It can be up to 65% by mass, more than 30% by mass to 65% by mass, 20% by mass to 40% by mass, and the like. It is preferably more than 20% by mass to 65% by mass, more preferably 25% by mass to 60% by mass, and particularly preferably 30% by mass to 50% by mass.

The aprotic solvent in the coating agent may be the aprotic solvent described in the bio-derived substance adhesion prevention substrate. Therefore, unless otherwise specified, the details of the aprotic solvent in the bio-derived substance adhesion prevention substrate can be applied to the details of the aprotic solvent in the coating agent.
In the coating agent, the content of the aprotic solvent is, for example, 35% by mass to 95% by mass, 35% by mass to 90% by mass, 35% by mass to 80% by mass, and 35% by mass to the total mass of the coating agent. It can be 70% by mass, 35% by mass to less than 70% by mass, 60% by mass to 80% by mass, and the like. It is preferably 35% by mass to less than 80% by mass, more preferably 40% by mass to 75% by mass, and particularly preferably 50% by mass to 70% by mass.

The coating agent may contain a polymerization initiator. The polymerization initiator in the coating agent may be the polymerization initiator described above. Therefore, unless otherwise specified, the details of the polymerization initiator in the coating agent can be applied.
In the coating agent, the content of the polymerization initiator is, for example, 0.00001% by mass to 10% by mass, preferably 0.00005% by mass to 10% by mass, more preferably, with respect to the total mass of the coating agent. It is 0.0001% by mass and 10% by mass.

The coating agent may contain a fluoropolymer (1), an aprotic solvent, optionally a polymerization initiator, and optionally other components in appropriate amounts. Other components may be, for example, colorants, light diffusing agents, fillers, plasticizers, viscosity modifiers, flexibility-imparting agents, light resistance stabilizers, reaction inhibitors, adhesion promoters and the like. The content of the other components is, for example, 0.01% by mass to 50% by mass, preferably 0.01% by mass to 30% by mass, and more preferably 0.01% by mass to 20% by mass with respect to the total mass of the coating agent. %can.

The coating agent can be produced by mixing a fluoropolymer (1), an aprotic solvent, optionally a polymerization initiator, and optionally other components.
The coating agent is a polymerization reaction solution obtained by solution polymerization of the fluoropolymer (1) described above (the solution contains at least the fluoropolymer (1) and an aprotic solvent), and if necessary, an aprotic solvent and an aprotic solvent. / Or can be produced by mixing other components. Since solution polymerization can increase the concentration of the fluoropolymer (1) or the amount of the fluoropolymer (1) dissolved in the polymerization reaction solution and the step of isolating the fluoropolymer from the polymerization reaction solution can be omitted, the coating agent is a polymerization reaction of solution polymerization. It preferably contains a liquid.

The content of the polymerization reaction solution for solution polymerization in the coating agent can be appropriately selected depending on the concentration of the fluoropolymer (1) in the polymerization reaction solution, the function of the film to be produced, the thickness and the like. The content of the polymerization reaction solution for solution polymerization in the coating agent is, for example, 5% by mass to 100% by mass, preferably 20% by mass to 100% by mass, and more preferably 30% by mass to 100% by mass with respect to the total mass of the coating agent. Can be%.

A coating agent containing an aprotic solvent in which a fluoropolymer (1) is dissolved or dispersed can be used, for example, by an appropriate method (eg, spray coating, dip coating method, bar coating) on a portion where suppression of adhesion of a biological substance is required. , Gravure coat, roll coat, inkjet, spin coat, etc.), and then the solvent is removed by drying, heating, etc. to form a film. It is preferable to heat after applying the coating agent. The drying or heating temperature is, for example, 30 ° C to 150 ° C, preferably 30 ° C to 80 ° C.
For example, a film can be formed by coating the substrate with the coating agent of the present disclosure and then drying it in a dryer at 80 ° C.
As described above, the portion to which the coating agent is applied may be surface-treated in advance with a surface treatment agent such as a silane coupling agent.

Although the embodiments have been described above, it will be understood that various modifications of the embodiments and details are possible without departing from the spirit and scope of the claims.

Hereinafter, one embodiment of the present disclosure will be described in more detail by way of examples and the like, but the present disclosure is not limited thereto. In Examples and the like, Mw means mass average molecular weight. Next, the measurement method and the like used in the examples and the like will be shown.

GPC analysis method (measurement of mass average molecular weight of fluoropolymer)
<Sample preparation method>
The polymer was dissolved in perfluorobenzene to prepare a 2% by mass polymer solution, which was passed through a membrane filter (0.22 μm) to prepare a sample solution.
<Measurement method>
Standard sample of molecular weight: Polymethylmethacrylate Detection method: RI (Differential Refractometer)

Glass transition temperature (Tg)
Using DSC (Differential Scanning Calorimeter: Hitachi High-Tech Science, DSC7000), the temperature range of 30 ° C to 200 ° C is raised (first run) -lower temperature-higher (second run) under the condition of 10 ° C / min. The middle point of the endothermic curve in the second run is the glass transition temperature (° C).

Average film thickness The average film thickness was an average value obtained by measuring the thickness five times with a micrometer. When it is difficult to measure the thickness of the film itself, such as when the film formed on a substrate such as a substrate cannot be peeled off, the thickness of the substrate before film formation and the thickness of the film-formed substrate (film). The sum of the thickness and the thickness of the substrate) was measured 5 times each with a micrometer, and the average film thickness was calculated by subtracting the average value of the thickness before film formation from the average value of the thickness after film formation.
When it was not possible to measure with a micrometer, the film thickness obtained by measuring the line profile of the cut surface of the film to be measured with an atomic force microscope (AFM) was taken as the average film thickness.

Phosphate Buffered Saline Characteristics Evaluation Sodium chloride was dissolved in water at 137 mmol / L, disodium hydrogen phosphate at 10 mmol / L, potassium chloride at 2.68 mmol / L, and potassium dihydrogen phosphate at 2 mmol / L. Phosphate buffered saline and a sample were prepared. The fluorine atom concentration (F) and the carbon atom concentration (C) were measured on the surface of the sample before immersion by X-ray photoelectron spectroscopy (XPS). After the measurement, the sample is immersed in the phosphate buffered saline at a liquid temperature of 90 ° C. or room temperature for 3 hours, and the surface of the sample after immersion is subjected to X-ray photoelectron spectroscopy to obtain fluorine atom concentration (F1s) and carbon atom concentration (C1s). Was measured. The obtained fluorine atom concentration and carbon atom concentration are expressed in the following formula (A):
100 × (F1s / C1s) / (F / C) (A)
The numerical value was calculated by applying to. The calculated numerical value indicates the degree of surface defect after immersion. Therefore, when the calculated numerical value exceeds 100, it is evaluated as 100. The larger the calculated value, the higher the resistance of the sample surface to phosphate buffered saline.
For the measurement, PHI5000 VersaProbe II, a surface analyzer manufactured by ULVAC-PHI, INC., Was used, and monochromatic X-ray AlKα was irradiated, and the emission angle was 45 °.

Contact angle A DropMaster 701 (manufactured by Kyowa Interface Science Co., Ltd.) was used as a measuring device for measuring the contact angle. The same sample was measured 5 times, and the average value was taken as the contact angle.
A coating placed on a horizontal sample stage after forming 2 μL or 5 μL water droplets on the tip of an injection needle [Kyowa Surface Science, Product No. 506 “Needle 22G”, outer diameter / inner diameter: 0.71 mm / 0.47 mm]. By moving the sample stage side, the distance between the substrate surface and the water droplet at the tip of the injection needle is gradually brought closer, and when the two come into contact, the sample stage and the injection needle are temporarily stopped, and then the sample stage side is moved. By slowly separating the sample stage and the injection needle, water droplets were made to drip on the surface of the coated substrate, and a still image of the water droplet image was taken 1 second after the drip. The shooting was performed with the setting of 1000 ms after dripping and the zoom magnification "STD" set in advance by the DropMaster control program "FAMAS". Based on the still image, the contact angle was determined by the θ / 2 method assuming that the contour shape of the water droplet was a perfect circle.
When the water droplets did not adhere to the surface of the coated substrate with a water droplet capacity of 2 μL and could not be deposited, the measurement was performed with a water droplet capacity of 5 μL.

A DropMaster701 (manufactured by Kyowa Interface Science Co., Ltd.) was used as a measuring device for measuring the sliding angle and the 5 mm moving-sliding angle sliding angle. The same sample was measured three times, and the average values were taken as the sliding angle and the moving-sliding angle of 5 mm.
After forming a 20 μL water droplet on the tip of the injection needle [Kyowa Surface Science Product No. 508 “Needle 15G”, outer diameter / inner diameter: 1.80 mm / 1.30 mm], the surface of the coated substrate placed on a horizontal sample stage The distance between the tip of the injection needle and the water droplet is gradually brought closer by moving the sample stage side, and when the two come into contact, the sample stage and the injection needle are temporarily stopped, and then the sample stage and the injection needle are moved to the sample stage side. By moving it and slowly releasing it, water droplets were deposited on the surface of the coated substrate. Within approximately 5 seconds after landing, the sample stage is tilted at an inclination speed of 2 ° / sec, and the still image of the water droplet image on the substrate surface is tilted at a zoom magnification of "W1" at every 1 ° of inclination angle (the width of the still image is It is 12 mm.) Was photographed. The tilt angle of the sample stage when the contact line on the receding side of the water droplet starts to move (when it moves 0.1 mm to 1 mm on the measurement screen; the actual movement distance of the droplet corresponds to 10 μm to 100 μm) is defined as the sliding angle. bottom.
The tilt angle when the water droplet moved and disappeared from the measurement screen of the zoom magnification "W1" was recorded as "5 mm movement-sliding angle" in order to distinguish it from the above-mentioned "sliding angle". 5mm movement-sliding angle is included in the roll-off angle specified in ISO 19403-7: 2017 "Paints and varnishes --Wettability --Part 7: Measurement of the contact angle on a tilt stage (roll-off angle)". It is a thing. ISO 19403-7: 2017 defines a drop movement distance of 1 mm or more, and a 5 mm movement-sliding angle is the tilt angle when a droplet moves 5 mm or more.

Sliding speed A DropMaster 701 (manufactured by Kyowa Interface Science Co., Ltd.) was used as a measuring device to measure the sliding speed. The same sample was measured three times, and the average value was taken as the sliding speed.
An injection needle [Kyowa Interface Science Product No. 506 "Needle 22G", outer diameter / inner diameter: 0.71 mm / 0.47 mm] was brought close to the surface of the coated substrate placed on the sample stage tilted at 30 ° in advance until just before contact. Later, 20 μL of water droplets were formed. At this point, the water droplets are stopped by the injection needle on the sloping coated substrate. Next, within approximately 5 seconds after forming the water droplet, move the injection needle side to slide the water droplet down by pulling the injection needle away from the water droplet, and the behavior of the water droplet is observed with a high-speed camera for 5 milliseconds (200 frames / sec). ) Was taken with a still image. The zoom magnification at the time of shooting was set to "W2". Only when the contact line on the forward side of the water droplet could move 15 to 20 mm per second, it was considered to have slipped. The horizontal axis is the sliding time (seconds) of the water droplets, and the vertical axis is the moving distance (mm) of the water droplets. / S).

Production Example 1: A compound (2- (difluoro) represented by the above formula (M1-11) as a synthetic monomer of a fluoropolymer (dioxolane skeleton polymer (1-11)) containing a unit (1-11) as a main component. Polymer containing the unit (1-11) as the main component using methylene) -4,4,5-trifluoro-5- (trifluoromethyl) -1,3-dioxolane) (fluoropolymer (1-11) Also referred to as) was manufactured. The details are as follows.
In a 50 mL glass container, 10 g of the monomer, 15 g of the solvent (methyl nonafluorobutyl ether), and 0.017 g of the initiator solution (methanol solution containing 50% by mass of di-n-propylperoxydicarbonate). After charging, the polymerization reaction was carried out for 20 hours while heating so that the internal temperature became 40 ° C. to obtain a reaction solution containing 36% by mass of the fluoropolymer (1-11) composed of the unit (1-11). rice field. The reaction solution was distilled off by vacuum drying at 120 ° C. to obtain the desired fluoropolymer (8.5 g (Mw: 273268)).
The glass transition temperature (Tg) of the polymer was 129 ° C.

Example 1: Glass substrate coated with a fluoropolymer (1-11) A glass substrate (length 4 cm, width 4 cm, thickness 1 mm) was washed with a solvent (ethanol), and an aqueous solution of 3-aminopropyltrimethoxysilane (APTMS) (APTMS) was washed. The glass substrate was immersed in (concentration: 0.5% by mass), taken out, left for a whole day and night, the glass substrate was ultrasonically washed in water for 5 minutes, and then air-dried to prepare a glass substrate for coating.
The fluoropolymer (1-11) obtained in Production Example 1 is used as an aprotic solvent (1, 1, 1, 2, 2, 3, 4, 5, 5, 5-decafluoro-3-methoxy-4- (tri)). Fluoromethyl) -pentane (Novec7300, 3M Japan Co., Ltd .; also referred to as HFE7300) was diluted to 1% by mass to obtain a fluoropolymer solution (coating solution).
The glass substrate for coating was immersed in the coating liquid, taken out, and heat-treated at 180 ° C. for 10 minutes to obtain a glass substrate coated with the fluoropolymer (1-11). As a result of measuring the obtained substrate by AFM, the average film thickness was 100 nm.

Reference Example 1: A commercially available fluoropolymer-coated glass substrate fluoropolymer (1-11) has a monomer unit represented by the following formula (10) and a monomer unit represented by (20) 65. A coated glass substrate was prepared by the same method as in Example 1 except that the fluoropolymer (also referred to as fluoropolymer (B)) (Mw: 229738) contained at 35 (molar ratio) was replaced.

Test Example 1: Evaluation of resistance of the coating film to phosphate buffered saline The coated glass substrates prepared in Example 1 and Comparative Example 1 were subjected to the evaluation of the characteristics of the phosphate buffered saline. The results are shown in Table 1.

The values of the glass substrate produced in Example 1 were 99 and 100 calculated by the formula (A), which were higher than the values (92) calculated by the glass substrate produced in Reference Example 1. From this, it was confirmed that the coating film of the glass substrate produced in Example 1 had almost no defects in the phosphate buffered saline (room temperature and 90 ° C.) immersion treatment and was excellent in resistance to the phosphate buffered saline. rice field.

Test Example 2: Evaluation of resistance of the coating film to heat sterilization conditions The coated glass substrates prepared in Example 1 and Comparative Example 1 were allowed to stand at 250 ° C. for 30 minutes in a constant temperature bath. When the film surface of the glass substrate after the heat treatment was visually observed, no change was observed in any of them.

Test Example 3: Evaluation of Adhesion Suppressing Function of Substrate Surface A coated glass substrate prepared in the same manner as in Example 1 and Comparative Example 1 has a contact angle (2 μL), a sliding angle (20 μL), and a 5 mm movement-sliding. The angle (roll-off angle) and sliding speed (20 μL) were measured. The average film thickness of the coating film on the glass substrate is 5 nm and 100 nm. The results are shown in Table 2.

Compared with the glass substrate prepared in Reference Example 1, the glass substrate prepared in Example 1 has a small sliding angle and a 5 mm movement-sliding angle, and a large sliding speed, so that the adhesion of droplets is small. Was confirmed.

Claims (23)

An anti-adhesion substrate for biological substances having a surface coated with an amorphous fluoropolymer. The fluoropolymer is
The fluorine-containing aliphatic ring contains a monomer unit having a fluorine-containing aliphatic ring as a main component, and the fluorine-containing aliphatic ring has 1, 2, or 3 ethereal oxygen atoms as ring-constituting atoms.
When the fluorine-containing aliphatic ring contains a plurality of the ethereal oxygen atoms, the ethereal oxygen atoms are not adjacent to each other.
The base material according to claim 1. The fluoropolymer has the formula (1):

[In the formula, R ¹ to R ⁴ are independently fluorine atoms, fluoroalkyl groups, or fluoroalkoxy groups. ]
Contains the monomeric unit represented by, as the main component,
The base material according to claim 1 or 2. The substrate according to claim 3, wherein the proportion of the monomer unit represented by the formula (1) in all the monomer units in the fluoropolymer is 80 mol% or more. The substrate according to claim 3 or 4, wherein the fluoropolymer further contains a fluoroolefin unit. The fluoroolefin unit is selected from the group consisting of a fluorine-containing perhaloolefin unit, a vinylidene fluoride unit, a trifluoroethylene unit, a pentafluoropropylene unit, and a 1,1,1,2-tetrafluoro-2-propylene unit. The substrate according to claim 5, which is at least one type. The fluorine-containing perhaloolefin unit is a chlorotrifluoroethylene unit, a tetrafluoroethylene unit, a hexafluoropropylene unit, a perfluoro (methyl vinyl ether) unit, a perfluoro (ethyl vinyl ether) unit, a perfluoro (propyl vinyl ether) unit, or a per. The substrate according to claim 6, which is at least one selected from the group consisting of fluoro (butyl vinyl ether) units and perfluoro (2,2-dimethyl-1,3-dioxol) units. The fluoroolefin unit is at least one selected from the group consisting of chlorotrifluoroethylene units, tetrafluoroethylene units, hexafluoropropylene units, perfluoro (methyl vinyl ether) units, and perfluoro (propyl vinyl ether) units. The base material according to any one of claims 5 to 7. The substrate according to any one of claims 1 to 8, which has an average film thickness of 10 nm or more. A bio-derived substance adhesion-preventing base material having a surface having the following phosphate-buffered saline properties.
Measured by X-ray photoelectron spectroscopy before the test in which the substrate is immersed in a phosphate buffered saline solution containing sodium chloride, disodium hydrogen phosphate, potassium chloride and potassium dihydrogen phosphate at 90 ° C. for 3 hours. The fluorine atom concentration (F) and carbon atom concentration (C) of the surface to be measured, and the fluorine atom concentration (F1s) and carbon atom concentration (C1s) of the surface measured by X-ray photoelectron spectroscopy after the test. The following equation (A):
100 × (F1s / C1s) / (F / C) (A)
The value obtained by applying to is 95 or more. The base material according to claim 10, wherein the value obtained by applying to the formula (A) is 97 or more. The substrate according to claim 10 or 11, wherein the surface is a film containing an amorphous fluoropolymer. The fluoropolymer is
The fluorine-containing aliphatic ring contains a monomer unit having a fluorine-containing aliphatic ring as a main component, and the fluorine-containing aliphatic ring has 1, 2, or 3 ethereal oxygen atoms as ring-constituting atoms.
When the fluorine-containing aliphatic ring contains a plurality of the ethereal oxygen atoms, the ethereal oxygen atoms are not adjacent to each other.
The base material according to claim 12. The fluoropolymer has the formula (1):

[In the formula, R ¹ to R ⁴ are independently fluorine atoms, fluoroalkyl groups, or fluoroalkoxy groups. ]
Contains the monomeric unit represented by, as the main component,
The base material according to claim 13. The base material according to any one of claims 1 to 14, wherein the material is glass or resin. The base material according to any one of claims 1 to 15, wherein the material is glass, polystyrene or polymethylmethacrylate. An instrument scheduled to come into contact with a biological substance, which comprises the substrate according to any one of claims 1 to 16. The instrument according to claim 17, which is for medical use, analysis of a biological substance, or test of a biological substance. 17. The device according to claim 17, which is a biological substance storage container, a cell culture container, a microchannel device, a catheter, a contact lens case, a blood purifier, a blood circuit, a blood storage bag, or a biochip. Equation (1):

[In the formula, R ¹ to R ⁴ are independently fluorine atoms, fluoroalkyl groups, or fluoroalkoxy groups. ]
A coating agent for forming a surface for preventing adhesion of a biological substance, which contains an amorphous fluoropolymer containing a monomer unit represented by 1 as a main component and an aprotic solvent. The coating agent according to claim 20, wherein the content of the fluoropolymer is 10% by mass to 65% by mass with respect to the total mass of the coating agent. The aprotic solvent is selected from the group consisting of perfluoroaromatic compounds, perfluorotrialkylamines, perfluoroalkanes, hydrofluorocarbons, perfluorocyclic ethers, hydrofluoroethers, and olefin compounds containing at least one chlorine atom. The coating agent according to claim 20 or 21, which is at least one solvent to be used. The coating agent according to any one of claims 20 to 22, wherein the aprotic solvent is at least one kind of hydrofluoro ether.