JP2011017798A - Acid-transfer resin composition, production method of biochip, and biochip - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an acid-transfer resin composition for achieving more accurate and proper polymer synthesis on a substrate, and to provide a method for producing a biochip, and the biochip.SOLUTION: The acid-transfer resin composition contains (A) a polymer and (B) a radiation-sensitive acid generator, wherein the acid generator (B) generates an acid having a sulfonyl anion in the structure, by irradiation with radiation, and the proportion of carbon atoms in the chemical structure of the sulfonyl anion with respect to the total number of atoms is not less than 30%. The method includes steps of: forming a first film by coupling a first compound having an acid dissociable group to a substrate; forming a second film by using the composition; exposing the second film to remove a protective group from the first film corresponding to an exposed portion; removing the second film; and coupling a second compound to the portion in the first film where the protective group is removed.

Description

  The present invention relates to an acid transferable resin composition, a biochip manufacturing method, and a biochip. More specifically, more specifically, an acid-transferable resin composition used when synthesizing various polymers such as DNA, RNA, PNA and LAN on a substrate, a method for producing a biochip using the same, and this bio The present invention relates to a biochip using a chip manufacturing method.

In recent years, a method of synthesizing a polymer such as a biopolymer on a substrate has attracted attention, and in particular, a biochip in which probes having different sequences and lengths are arrayed on a single substrate using nucleotides or the like as monomers, and A method for producing this has been widely studied.
As a method of synthesizing a polymer on a substrate, a nucleotide monomer having a protecting group unstable to light is arranged, and after this protecting group is dissociated from a specific portion by exposure through a mask, other nucleotides are synthesized. The method of repeating the operation | movement which couple | bonds a monomer is disclosed by the following patent documents 1-2.
Further, in the field of semiconductor manufacturing, the following Patent Documents 3 to 5 disclose techniques for utilizing a photoacid generator used in forming a fine pattern using a photolithography method and a resist containing the photoacid generator for polymer synthesis. ing.

US Pat. No. 5,445,934 US Pat. No. 5,744,305 US Pat. No. 5,658,734 JP-A-2005-0909005 Special table 2003-501640 gazette

According to the methods of Patent Documents 1 to 5, various polymers can be synthesized on the substrate, but a technique capable of synthesizing the polymer on the substrate more accurately and precisely is required.
The present invention has been made in view of the above circumstances, and is capable of synthesizing a polymer on a substrate more accurately and more accurately than in the past due to excellent selectivity when diffusing an acid. It is an object of the present invention to provide a transferable resin composition, a biochip manufacturing method using the acid transferable resin composition, and a biochip using the biochip manufacturing method.

〔式（１）中、Ｒ^１は水素原子又はメチル基を表す。Ｒ^２及びＲ^３はそれぞれ独立に、水素原子、炭素数１〜１０の直鎖状又は分枝状の炭化水素基、炭素数３〜１０の環状の炭化水素基を表す。また、Ｒ^２及びＲ^３は、互いに結合して３〜１０員環の単環式ヘテロ環、又は、窒素原子、酸素原子、硫黄原子、セレン原子の群から選ばれる少なくとも１種のヘテロ原子を介して結合して４〜１０員環の単環式ヘテロ環を形成してもよい。〕
［７］前記酸転写性樹脂組成物が、バイオチップ製造用である前記［１］乃至［６］に記載の酸転写性樹脂組成物。
［８］（ａ）酸に不安定な保護基を有する第１化合物を基板に直接的又は間接的に結合して第１膜を形成する第１膜形成工程、
（ｂ）前記第１膜上に、前記［１］乃至［７］のうちのいずれかに記載の酸転写性樹脂組成物を用いて第２膜を形成する第２膜形成工程、
（ｃ）前記第２膜を露光して、露光された部分に対応する前記第１膜から前記保護基を除去する保護基除去工程、
（ｄ）前記第２膜を除去する第２膜除去工程、及び、
（ｅ）前記第１膜のうち前記保護基が除去された部位に第２化合物を結合する第２化合物結合工程、を備えることを特徴とするバイオチップの製造方法。
［９］前記第２化合物は、（１）ヌクレオチド、アミノ酸及び単糖類からなる群より選ばれる化合物、又は、（２）ヌクレオチド、アミノ酸及び単糖類からなる群より選ばれる２以上の化合物が結合された結合体、である前記［７］に記載のバイオチップの製造方法。
［１０］前記［８］又は［９］に記載のバイオチップの製造方法により製造されたことを特徴とするバイオチップ。 The present invention is as follows.
[1] An acid transferable resin composition comprising (A) a polymer and (B) a radiation sensitive acid generator,
The radiation sensitive acid generator (B) generates an acid having a sulfonyl anion in the structure by irradiation with radiation,
The ratio of the number of carbon atoms (Y) to the total number of atoms (X) in the chemical structural formula of the sulfonyl anion [(Y / X) × 100 (%)] is 30% or more, acid transferability Resin composition.
[2] The acid transferable resin composition according to [1], wherein the sulfonyl anion does not contain a fluorine atom.
[3] The acid transferable resin composition according to [1] or [2], wherein the sulfonyl anion has an alicyclic hydrocarbon group.
[4] The acid transferable resin composition according to any one of [1] to [3], wherein the polymer (A) has a nitrogen-containing group in a side chain.
[5] The acid transferable resin composition according to any one of [1] to [4], wherein the polymer (A) does not have an acid dissociable group.
[6] The acid transferable resin composition according to any one of [1] to [5], wherein the polymer (A) includes a structural unit represented by the following formula (1).

Wherein (1), R ¹ represents a hydrogen atom or a methyl group. R ² and R ³ each independently represent a hydrogen atom, a linear or branched hydrocarbon group having 1 to 10 carbon atoms, or a cyclic hydrocarbon group having 3 to 10 carbon atoms. R ² and R ³ are bonded to each other to form a 3 to 10-membered monocyclic heterocycle, or at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom, and a selenium atom. To form a 4- to 10-membered monocyclic heterocycle. ]
[7] The acid-transferable resin composition according to [1] to [6], wherein the acid-transferable resin composition is for biochip production.
[8] (a) a first film forming step of forming a first film by directly or indirectly bonding a first compound having an acid-labile protecting group to a substrate;
(B) a second film forming step of forming a second film on the first film using the acid transferable resin composition according to any one of [1] to [7];
(C) Protecting group removing step of exposing the second film and removing the protecting group from the first film corresponding to the exposed portion;
(D) a second film removing step for removing the second film, and
(E) A method for producing a biochip, comprising: a second compound binding step of binding a second compound to a portion of the first film from which the protecting group has been removed.
[9] The second compound is (1) a compound selected from the group consisting of nucleotides, amino acids and monosaccharides, or (2) two or more compounds selected from the group consisting of nucleotides, amino acids and monosaccharides. The biochip production method according to [7], wherein the biochip is a combined body.
[10] A biochip manufactured by the biochip manufacturing method according to [8] or [9].

According to the acid-transferable resin composition of the present invention, it is possible to exhibit an excellent acid diffusion controllability by suppressing unnecessary diffusion of acid generated by exposure. As a result, polymer synthesis can be performed on the substrate more accurately and precisely than in the past.
When the sulfonyl anion does not contain a fluorine atom, the acid can be made to act on the first film more efficiently.
When the sulfonyl anion has an alicyclic hydrocarbon group, the acid can be more efficiently caused to act on the first film.
In the case where the polymer (A) has a nitrogen-containing group in the side chain, unnecessary acid diffusion can be suppressed and further excellent acid diffusion controllability can be exhibited.
When the polymer (A) does not have an acid dissociable group, the acid can be more efficiently caused to act on the first film.
When the polymer (A) includes the structural unit represented by the formula (1), unnecessary diffusion of the acid can be suppressed more effectively, and particularly excellent acid diffusion controllability can be exhibited.
When the acid transferable resin composition is for biochip production, the excellent acid diffusion controllability by the present composition can be exhibited particularly effectively.
According to the method for producing a biochip of the present invention, it is possible to exhibit an excellent diffusion controllability by suppressing unnecessary diffusion of an acid generated by exposure of the second film. As a result, the first film can be patterned more accurately and accurately than in the prior art, and the probe can be formed accurately and precisely, and a biochip with an improved probe integration rate can be manufactured.
The second compound is (1) a compound selected from the group consisting of nucleotides, amino acids and monosaccharides; or (2) a conjugate in which two or more compounds selected from the group consisting of nucleotides, amino acids and monosaccharides are bound; In this case, a biochip that can be used effectively in the pharmaceutical field can be obtained.
According to the biochip of the present invention, it is possible to form a biochip with which probe formation can be performed more accurately and precisely than before and the probe integration rate is improved.

It is explanatory drawing which illustrates the manufacturing method of the biochip of this invention typically. It is explanatory drawing which illustrates the manufacturing method of the biochip of this invention typically. It is explanatory drawing which illustrates the manufacturing method of the biochip of this invention typically.

  Hereinafter, the present invention will be described in detail. In the present specification, “(meth) acryl” means acryl and methacryl, and “(meth) acrylate” means acrylate and methacrylate.

[1] Acid-transferable resin composition The acid-transferable resin composition of the present invention is an acid-transferable resin composition containing (A) a polymer and (B) a radiation-sensitive acid generator. The radiation-sensitive acid generator (B) generates an acid having a sulfonyl anion in the structure upon irradiation with radiation, and the number of carbon atoms relative to the total number of atoms (X) in the chemical structural formula of the sulfonyl anion ( The ratio of (Y) [(Y / X) × 100 (%)] is 30% or more.

  The acid transferable resin composition can be formed into a film as described later. When the obtained film is exposed, an acid is selectively generated at a desired site, and the generated acid can be kept from being unnecessarily diffused in the film. In particular, the present acid transferable resin composition has a specific sulfonium anion in the structure as the acid, so that the upper surface of the film (the surface close to the first film in the second film in the production method described later) It is excellent in the effect of suppressing the uneven diffusion of acid to the lower surface and the opposite surface as the upper surface. Thereby, an acid is generated accurately and precisely at a desired site in the film, so that a pattern composed of a site where the acid is generated and a site where no acid is generated can be formed. Further, the acid generated in the film formed from the acid transferable resin composition can be accurately transferred to the adjacent layer. These characteristics are particularly effective when used in biochip manufacturing applications and biochip manufacturing methods described later.

<1-1> Radioactive acid generator (B)
The “(B) radiation sensitive acid generator” (hereinafter also simply referred to as “acid generator (B)”) generates an acid having a sulfonyl anion in the structure by irradiation with radiation. The type of radiation that exhibits this radiation sensitivity is not particularly limited, and includes, for example, LED lamps, ultraviolet rays (including g-rays, i-rays, etc.), deep ultraviolet rays (KrF excimer laser, ArF excimer laser, F ₂ excimer laser, etc.) ), X-rays, electron beams, γ-rays, molecular beams, ion beams, etc.

〔式（２）中、Ｒ^１は１価の有機基である。〕 The sulfonyl anion is represented by the following formula (2).

[In Formula (2), R ¹ is a monovalent organic group. ]

〔式（３）中、Ｒ^１は１価の有機基である。Ａはカチオンである〕 The acid having the sulfonyl anion in the structure is represented by the following formula (3).

[In Formula (3), R ¹ is a monovalent organic group. A is a cation.

In the formulas (2) and (3), R ¹ is a monovalent organic group, and this R ¹ may be composed of only carbon atoms and hydrogen atoms, or may contain other atoms. Examples of other atoms include an oxygen atom, a nitrogen atom, a sulfur atom, a selenium atom, and a halogen atom (such as a chlorine atom). However, as will be described later, it is preferable that a fluorine atom is not included among the halogen atoms.
The acid represented by formula (3) is an acid having a sulfonyl anion as an anion component and A ⁺ as a cation component. The acid is only required to function as an acid, and A may be a hydrogen atom (proton), and may contain other atoms or two or more elements.

  When the acid generated from the acid generator is a sulfonyl anion, the first compound is unnecessarily decomposed when used as an acid transferable resin composition layer as will be described later when producing a biochip. Etc. can be inhibited. Further, when used in biochip manufacturing applications, the protecting group of the first compound can be more accurately dissociated, and the probe can be formed more accurately and precisely without unnecessarily decomposing the first compound.

Although R ¹ in Formula (2) and Formula (3), which is a monovalent organic group, is selected so that the ratio of the number of carbon atoms to the total number of atoms in the chemical structural formula of the sulfonyl anion is 30% or more. , R ¹ is not particularly limited.
Examples of the monovalent organic group as R ¹ in the formula (2) and the formula (3) include an alkyl group, an aromatic group, and an alicyclic hydrocarbon group. Furthermore, these groups may or may not have a substituent.

When R ¹ in the formula (2) and the formula (3) has a substituent, the substituent is other than an alkyl group having 1 to 4 carbon atoms, an aryl group having 6 to 20 carbon atoms, and a hydrocarbon group. Examples include polar groups. Only 1 type may be used for a substituent and it may use 2 or more types together. Moreover, when it has 2 or more types of substituents, each substituent may be the same and may differ.
Among these, polar groups include alkoxy groups (methoxy groups, ethoxy groups, propoxy groups, butoxy groups, etc.), hydroxy groups, carboxyl groups, oxo groups (= O), cyano groups, halogen atoms (fluorine atoms, chlorine atoms, bromines). Atoms), alkyloxycarbonyl groups, and the like.

The alkyl group as R ¹ in the formula (2) and the formula (3) preferably has 5 to 20 carbon atoms. Examples of such an alkyl group include a pentyl group, a heptyl group, and an octyl group.

The aromatic group as R ¹ in the formula (2) and the formula (3) preferably has 6 to 20 carbon atoms. Such aromatic groups include tolyl groups (p-, m-, o-), xylyl groups (-2,4, -3,5 etc.), mesityl groups (-2,4,6 etc.), benzyl Group, cumenyl group (p-, m-, o-), methoxyphenyl group (p-, m-, o-), naphthyl group, and the like. Among these, p-tolyl group, 2,4-xylyl group and benzyl are preferable, and p-tolyl group is particularly preferable. The sulfonyl anion having this p-tolyl group (that is, p-tolyl) as R ¹ in the formula (3) is represented by the following formula (4).

The alicyclic group as R ¹ in the formula (2) and the formula (3) may or may not contain an unsaturated bond. Furthermore, the alicyclic part of the alicyclic group may be monocyclic or polycyclic, and may be condensed or non-condensed in the case of polycyclic. Good. Moreover, this alicyclic part may be a bridge type or a non-bridge type.

The alicyclic group preferably has 4 to 20 carbon atoms, and more preferably an alicyclic hydrocarbon group. Examples of such alicyclic hydrocarbon groups include alicyclic hydrocarbon groups having a norbornane skeleton, alicyclic hydrocarbon groups having a norbornene skeleton, alicyclic hydrocarbon groups having a tricyclodecane skeleton, and tetracyclododecane. Examples thereof include an alicyclic hydrocarbon group having a skeleton, an alicyclic hydrocarbon group having an adamantane skeleton, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclodecanyl group, and a cyclododecanyl group.
Among these, an alicyclic hydrocarbon group having a norbornane skeleton is preferable, an alicyclic hydrocarbon group having a norbornanone skeleton is more preferable, and an alicyclic hydrocarbon group having a camphor skeleton is particularly preferable.

Examples of the sulfonyl anion having an alicyclic hydrocarbon group having a camphor skeleton as R ¹ in the formula (3) include the following formula (5).

  The acid generated from the acid generator (B) contained in the acid transferable resin composition has the sulfonyl anion in the structure, and the sulfonyl anion has the total number of atoms in the chemical structural formula ( The ratio of the number of carbon atoms (Y) to (X) [(Y / X) × 100 (%)] is 30% or more.

  When the ratio of the number of carbon atoms to the total number of atoms in the chemical structural formula of the sulfonyl anion (hereinafter, also simply referred to as “carbon content”) is 30% or more, it is formed using the present acid transferable resin composition. The diffusion of acid to the upper surface of the formed film can be effectively suppressed, and as a result, a film excellent in acid transfer selectivity can be obtained. That is, as described above, when the anion component is a sulfonyl anion, inhibition of unnecessarily decomposing the first compound in biochip production is suppressed, and the carbon content of the anion component is 30% or more. As a result, excellent acid transfer selectivity can be obtained.

  The carbon content of the sulfonyl anion may be 30% or more, but the upper limit is preferably 80%, more preferably 60%, and particularly preferably 50%. The lower limit is preferably 30%, more preferably 35%, and particularly preferably 40%.

Specifically, the carbon content of the sulfonyl anion is calculated as follows. That is, for example, in the sulfonyl anion of the above formula (4), the number of carbon atoms is 7, the number of hydrogen atoms is 7, the number of oxygen atoms is 3 and the number of sulfur atoms is 1. The carbon content of formula (4) sulfonyl anion is 38.9%.
{7 / (7 + 7 + 3 + 1)} × 100 = 38.9%

Similarly, in the sulfonyl anion of the above formula (5), the number of carbon atoms is 10, the number of hydrogen atoms is 15, the number of oxygen atoms is 4, and the number of sulfur atoms is 1. (5) The carbon content of the sulfonyl anion is 33.3%.
{10 / (10 + 15 + 4 + 1)} × 100 = 33.3%

Furthermore, the sulfonyl anion is preferably substantially free of fluorine atoms. When no fluorine atom is contained, the ratio of the number of fluorine atoms (S) to the total number of atoms (X) in the chemical structural formula of the sulfonyl anion [(S / X) × 100 (%)] is less than 1%. Means that.
When the sulfonyl anion is substantially free of fluorine atoms, acid diffusion to the upper surface of the film formed using the acid-transferable resin composition can be effectively suppressed. An acid transfer film excellent in acid transfer selectivity can be formed.

前記式（６）中、Ｒ^１は前記式（２）におけるＲ^１をそのまま適用できる。Ｒ^２は光を吸収する基である。 The acid generator (B) is not particularly limited as long as it can generate an acid having the sulfonyl anion in the structure from the acid generator (B) by radiation irradiation. Examples of the acid generator (B) include an acid generator (B) represented by the following formula (6) and an acid generator (B) represented by the following formula (7).

In Formula (6), R ¹ can be the same as R ¹ in Formula (2). R ² is a group that absorbs light.

前記式（７）中、Ｒ^１は前記式（２）におけるＲ^１をそのまま適用できる。Ｒ^２は光を吸収するカチオンである。

In Formula (7), R ¹ can be the same as R ¹ in Formula (2). R ² is a cation that absorbs light.

R ² constituting the acid generator (B) represented by the formula (6) may be a group that absorbs light, and the structure thereof is not particularly limited. For example, a thiophene ring structure {formula (8 ) And the following (9)}, naphthalimide structure {refer to the following formula (12)}, and the like, it is preferable to have a structure including a conjugated double bond.

前記式（８）中、Ｒ^１は前記式（２）におけるＲ^１をそのまま適用できる。Ｒ^２は２価の有機基である。

前記式（９）中、Ｒ^１は前記式（２）におけるＲ^１をそのまま適用できる。Ｒ^２は２価の有機基である。 Among the acid generators (B) represented by the formula (6), as the acid generator (B) having R ² containing a thiophene ring structure, an acid generator (B) represented by the following formula (8) ) And the acid generator (B) represented by the following formula (9).

In the formula (8), R ¹ can be the same as R ¹ in the formula (2). R ² is a divalent organic group.

In Formula (9), R ¹ can be the same as R ¹ in Formula (2). R ² is a divalent organic group.

R ² in Formula (8) and Formula (9) is not particularly limited except that R ² is a divalent organic group. R ² may consist only of carbon atoms and hydrogen atoms, or may contain other atoms. Examples of other atoms include an oxygen atom, a nitrogen atom, a sulfur atom, a selenium atom, and a halogen atom (such as a chlorine atom).
Furthermore, these groups may or may not have a substituent. Examples of the substituent include a C1-C4 alkyl group, a C6-C20 aryl group, and a polar group other than a hydrocarbon group. Only 1 type may be used for a substituent and it may use 2 or more types together. Moreover, when it has 2 or more types of substituents, each substituent may be the same and may differ.
Among these, polar groups include alkoxy groups (methoxy groups, ethoxy groups, propoxy groups, butoxy groups, etc.), hydroxy groups, carboxyl groups, oxo groups (= O), cyano groups, halogen atoms (fluorine atoms, chlorine atoms, bromines). Atoms), alkyloxycarbonyl groups, and the like.

前記式（１０）中、Ｒ^１は前記式（２）におけるＲ^１をそのまま適用できる。 In particular, R ² in the formula (8) preferably has a benzene ring structure and a nitrile group, and the acid generator (B) represented by the formula (8) is represented by the following formula (10). The acid generator (B) having a structure is particularly preferable.

In the formula (10), R ¹ can be the same as R ¹ in the formula (2).

In the formula (10), as R ¹ , for example, the p-tolyl group described above is preferable. That is, the acid generator (B) represented by the following formula (11) is particularly preferable.

前記式（１２）中、Ｒ^１は前記式（２）におけるＲ^１をそのまま適用できる。 On the other hand, among the acid generators (B) represented by the formula (6), the acid generator (B) having R ² containing a naphthalimide structure is an acid generator represented by the following formula (12). (B) is mentioned.

In the formula (12), ^{R 1} is directly applicable to ^{R 1} in the formula (2).

In the formula (12), R ¹ is preferably, for example, the above-described alicyclic hydrocarbon group having a camphor skeleton. That is, the acid generator (B) represented by the following formula (13) is particularly preferable.

Further, R ² constituting the acid generator (B) represented by the formula (7) may be a cation that absorbs light, and its structure is not particularly limited, but is represented by the following formula (14). Acid generator (B).

In the formula (14), R ¹ is a hydrogen atom, a fluorine atom, a hydroxyl group, a linear or branched alkyl group having 1 to 10 carbon atoms, a linear or branched alkoxyl group having 1 to 10 carbon atoms, A linear or branched alkoxycarbonyl group having 2 to 11 carbon atoms is shown. R ² represents a linear or branched alkyl group having 1 to 10 carbon atoms, an alkoxyl group, or a linear, branched or cyclic alkanesulfonyl group having 1 to 10 carbon atoms. Further, R ³ independently represents a linear or branched alkyl group having 1 to 10 carbon atoms, an optionally substituted phenyl group or an optionally substituted naphthyl group, or two R ³ are bonded to each other to form a divalent group having 2 to 10 carbon atoms, the divalent group may be substituted, k is an integer of 0 to 2, and r is 0 to 10 And X ⁻ is a sulfonyl anion represented by the formula (2).

Examples of the linear or branched alkyl group having 1 to 10 carbon atoms of R ¹ , R ² and R ³ in the formula (14) include a methyl group, an ethyl group, an n-butyl group and a t-butyl group. It is done.
Examples of the linear or branched alkoxyl group having 1 to 10 carbon atoms of R ¹ and R ² in the formula (14) include a methoxy group, an ethoxy group, an n-propoxy group, and an n-butoxy group.
Examples of the linear or branched alkoxycarbonyl group having 2 to 11 carbon atoms of R ¹ in the formula (14) include a methoxycarbonyl group, an ethoxycarbonyl group, and an n-butoxycarbonyl group.
In the formula (14), as the linear, branched or cyclic alkanesulfonyl group having 1 to 10 carbon atoms of R ^2, a methanesulfonyl group, an ethanesulfonyl group, an n-propanesulfonyl group, an n-butanesulfonyl group, A cyclopentanesulfonyl group, a cyclohexanesulfonyl group, etc. are mentioned.
As r in said Formula (14), 0-2 are preferable.

Examples of the optionally substituted phenyl group represented by R ³ in the formula (14) include a phenyl group, a tolyl group, a dimethylphenyl group, a trimethylphenyl group, a 4-ethylphenyl group, a 4-t-butylphenyl group, 4- A phenyl group substituted with a phenyl group such as a cyclohexylphenyl group or 4-fluorophenyl group or a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms; And a group substituted with at least one group such as a group, a carboxyl group, a cyano group, a nitro group, an alkoxyl group, an alkoxyalkyl group, an alkoxycarbonyl group, and an alkoxycarbonyloxy group.

  Among the substituents for the phenyl group and the alkyl-substituted phenyl group, the alkoxyl group is preferably a linear, branched or cyclic alkoxyl group having 1 to 20 carbon atoms. The alkoxyalkyl group is preferably a linear, branched or cyclic alkoxyalkyl group having 2 to 21 carbon atoms. The alkoxycarbonyl group is preferably a linear, branched or cyclic alkoxycarbonyl group having 2 to 21 carbon atoms. The alkoxycarbonyloxy group is preferably a linear, branched or cyclic alkoxycarbonyloxy group having 2 to 21 carbon atoms.

Examples of the optionally substituted phenyl group represented by R ² in the formula (14) include a phenyl group, a 4-cyclohexylphenyl group, a 4-t-butylphenyl group, a 4-methoxyphenyl group, and a 4-t-butoxyphenyl group. Etc.
As the optionally substituted naphthyl group of R ³ in the above formula (14), a naphthyl group such as a naphthyl group, a methylnaphthyl group, a dimethylnaphthyl group, an ethylnaphthyl group, or a straight chain having 1 to 10 carbon atoms, A naphthyl group substituted with a branched or cyclic alkyl group; these naphthyl group or alkyl-substituted naphthyl group can be converted into a hydroxyl group, carboxyl group, cyano group, nitro group, alkoxyl group, alkoxyalkyl group, alkoxycarbonyl group, alkoxycarbonyl group; And a group substituted with at least one group such as an oxy group.
Among the substituents for the naphthyl group and the substituted naphthyl group, examples of the alkoxyl group, alkoxyalkyl group, alkoxycarbonyl group, and alkoxycarbonyloxy group include the groups exemplified for the phenyl group and the alkyl-substituted phenyl group.

Examples of the naphthyl group which may be substituted for R ³ in the formula (14) include a naphthyl group, a 1- (4-methoxynaphthyl) group, a 1- (4-ethoxynaphthyl) group, and a 1- (4-n- A propoxynaphthyl) group, a 1- (4-n-butoxynaphthyl) group, and the like.
In addition, the divalent group having 2 to 10 carbon atoms formed by bonding two R ³ to each other includes a 5- or 6-membered ring, particularly preferably a 5-membered ring, together with the sulfur atom in the formula (14). Examples include a group that forms a ring (that is, a tetrahydrothiophene ring).
Examples of the substituent for the divalent group include a hydroxyl group, a carboxyl group, a cyano group, a nitro group, an alkoxyl group, an alkoxyalkyl group, and an alkoxycarbonyl group exemplified as the substituent for the phenyl group and the alkyl-substituted phenyl group. And an alkoxycarbonyloxy group.
As R ³ in the formula (14), a methyl group, an ethyl group, a phenyl group, a 4-methoxyphenyl group, a 1-naphthyl group, and two R ³ are bonded to each other to form a tetrahydrothiophene ring structure together with a sulfur atom. A divalent group is preferred.

Preferable examples of the acid generator (B) represented by the formula (14) include acid generators represented by the following formulas (15-1) to (15-5). X in formula (15-1) - (15-5) ^- is a sulfonyl anion represented by the formula (2).

Only 1 type may be used for the acid generator (B) described so far, and it may use 2 or more types together.
Further, the content of the acid generator (B) contained in the acid transferable resin composition is not particularly limited, but usually 0.1 to 200 parts by mass is contained with respect to 100 parts by mass of the polymer (A). The Furthermore, in order to obtain excellent acid transfer selectivity by the combination of the polymer (A) and the acid generator (B), this content is preferably 10 to 150 parts by mass, and 20 to 150 parts by mass. Part is more preferable, and 20 to 100 parts by mass is particularly preferable.

  In addition to the acid generator (B), the acid transferable resin composition of the present invention can contain other acid generators. As other acid generators, onium salt compounds (including thiophenium salt compounds), halogen-containing compounds, diazoketone compounds, sulfone compounds, sulfonic acid compounds, diazomethane compounds, and the like can be used. This acid generator (B) may use only 1 type and may use 2 or more types together.

  Examples of the onium salt compounds include 4,7-di-n-butoxynaphthyltetrahydrothiophenium salt compounds, 1- (4-n-butoxynaphthalen-1-yl) tetrahydrothiophenium salt compounds, 1- (6- thiophenium salt compounds such as n-butoxynaphthalen-2-yl) tetrahydrothiophenium salt compound and 1- (3,5-dimethyl-4-hydroxyphenyl) tetrahydrothiophenium salt compound; bis (4-t-butylphenyl) ) Iodonium salt compounds such as iodonium salt compounds and diphenyliodonium salt compounds; triphenylsulfonium salt compounds, 4-t-butylphenyldiphenylsulfonium salt compounds, 4-cyclohexylphenyldiphenylsulfonium salt compounds, 4-methanesulfonylphenyldiphenyls Sulfonium salt compounds such as Honiumu salt compounds; phosphonium salt compound; diazonium salt compound; pyridinium salt compounds; and the like.

Examples of the halogen-containing compound include haloalkyl group-containing hydrocarbon compounds and haloalkyl group-containing heterocyclic compounds. Specific examples include (trichloromethyl) -s-triazine derivatives.
Examples of the diazoketone compound include 1,3-diketo-2-diazo compounds, diazobenzoquinone compounds, diazonaphthoquinone compounds, and the like.
Examples of the sulfonated product include β-ketosulfone, β-sulfonylsulfone, and α-diazo compounds of these compounds.
Examples of the sulfonic acid compounds include alkyl sulfonic acid esters, haloalkyl sulfonic acid esters, aryl sulfonic acid esters, and imino sulfonates.
Examples of the diazomethane compound include bis (trifluoromethylsulfonyl) diazomethane, bis (cyclohexylsulfonyl) diazomethane, bis (phenylsulfonyl) diazomethane, bis (p-toluenesulfonyl) diazomethane, methylsulfonyl-p-toluenesulfonyldiazomethane, cyclohexylsulfonyl- Examples include 1,1-dimethylethylsulfonyldiazomethane and bis (1,1-dimethylethylsulfonyl) diazomethane.

  When other acid generators other than these acid generators (B) are contained, the content is not particularly limited, but is preferably 200 parts by mass or less with respect to 100 parts by mass of the polymer (A). 0.1-100 mass parts is more preferable, and 0.1-50 mass parts is still more preferable.

<1-2> Polymer (A)
The polymer (A) may be any polymer, but usually a polymer (A) having a nitrogen-containing group in the side chain is used.
The “(A) polymer having a nitrogen-containing group in the side chain” (hereinafter, also simply referred to as “polymer (A)”) is used in combination with the predetermined acid generator (B) in the membrane ( In the film formed using the present acid transferable resin composition, unnecessary acid diffusion can be particularly effectively prevented (that is, it has an acid diffusion preventing function).

The nitrogen-containing group that the polymer (A) has means a substituent that contains a nitrogen atom in the group. Examples of the nitrogen-containing group include a group having a structure of —NR ¹ R ² (hereinafter simply referred to as “amine group”), an acid group, an imide group, a urea group, a urethane group, and a pyridine group.
Of these, amine groups are preferred. R ¹ and R ² of the amine group each independently represent a hydrogen atom, a linear or branched hydrocarbon group having 1 to 10 carbon atoms, or a cyclic hydrocarbon group having 3 to 10 carbon atoms. In addition, R ¹ and R ² of the amine group are bonded to each other, and at least 1 selected from the group consisting of a 3- to 10-membered monocyclic heterocycle, or a nitrogen atom, an oxygen atom, a sulfur atom, and a selenium atom. It may combine through a heteroatom of a species to form a 4-10 membered monocyclic heterocycle.

That is, when R ¹ and R ² of the amine group are linear or branched hydrocarbon groups having 1 to 10 carbon atoms, R ¹ and R ² of the amine group include methyl group, ethyl group , N-propyl group, i-propyl group, n-butyl group, 2-methylpropyl group, 1-methylpropyl group, t-butyl group and other aliphatic hydrocarbon groups.

Further, examples of R ¹ and R ² of the amine group is R ¹ and R ² of the amine group in the case where a cyclic hydrocarbon group having 3 to 10 carbon atoms, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloalkyl Alicyclic groups such as heptyl group and cyclooctyl group; aromatic groups such as phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, 4-t-butylphenyl group, 1-naphthyl group and benzyl group Groups.

Further, R ¹ and R ² of the amine group are bonded to each other to form a 3- to 10-membered monocyclic heterocycle (which may be an unsaturated ring or a saturated ring). In this case, examples of the amine group include an aziridino group, an azetino group, a pyrrolidino group, a pyrrole group, a piperidino group, and a pyridino group.

In addition, R ¹ and R ² of the amine group are bonded via at least one hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom, and a selenium atom to form a 4- to 10-membered monocyclic ring In the case of forming a heterocyclic ring (which may be an unsaturated ring or a saturated ring), the amine group may be a morpholino group, a thiomorpholino group, a selenomorpholino group, an isoxazolidino group, Examples include isoxazole group, isothiazolidino group, isothiazole group, imidazolidino group, piperazino group and triazino group.

〔式（１）中、Ｒ^１は水素原子又はメチル基を表す。Ｒ^２及びＲ^３はそれぞれ独立に、水素原子、炭素数１〜１０の直鎖状又は分枝状の炭化水素基、炭素数３〜１０の環状の炭化水素基を表す。また、Ｒ^２及びＲ^３は、互いに結合して３〜１０員環の単環式ヘテロ環、又は、窒素原子、酸素原子、硫黄原子、セレン原子からなる群より選ばれる少なくとも１種のヘテロ原子を介して結合して４〜１０員環の単環式ヘテロ環を形成してもよい。〕 The amino group may be included in the side chain of the polymer (A) in any form, but it is particularly preferable that the structural unit represented by the following formula (1) is included in the polymer (A).

Wherein (1), R ¹ represents a hydrogen atom or a methyl group. R ² and R ³ each independently represent a hydrogen atom, a linear or branched hydrocarbon group having 1 to 10 carbon atoms, or a cyclic hydrocarbon group having 3 to 10 carbon atoms. R ² and R ³ are bonded to each other to form a 3- to 10-membered monocyclic heterocycle, or at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom, and a selenium atom. To form a 4- to 10-membered monocyclic heterocycle. ]

  The structural unit represented by the formula (1) can be usually obtained by polymerizing the polymer (A) using a monomer (Am1) represented by the following formula (16).

〔式（１６）中、Ｒ^１は水素原子又はメチル基を表す。Ｒ^２及びＲ^３はそれぞれ独立に、水素原子、炭素数１〜１０の直鎖状又は分枝状の炭化水素基、炭素数３〜１０の環状の炭化水素基を表す。また、Ｒ^２及びＲ^３は、互いに結合して３〜１０員環の単環式ヘテロ環、又は、窒素原子、酸素原子、硫黄原子、セレン原子からなる群より選ばれる少なくとも１種のヘテロ原子を介して結合して４〜１０員環の単環式ヘテロ環を形成してもよい。〕

[In Formula (16), R ¹ represents a hydrogen atom or a methyl group. R ² and R ³ each independently represent a hydrogen atom, a linear or branched hydrocarbon group having 1 to 10 carbon atoms, or a cyclic hydrocarbon group having 3 to 10 carbon atoms. R ² and R ³ are bonded to each other to form a 3- to 10-membered monocyclic heterocycle, or at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom, and a selenium atom. To form a 4- to 10-membered monocyclic heterocycle. ]

Examples of the linear or branched hydrocarbon group having 1 to 10 carbon atoms that is R ² and / or R ³ in the formula (16) include a methyl group, an ethyl group, an n-propyl group, i- Examples thereof include aliphatic hydrocarbon groups such as propyl group, n-butyl group, 2-methylpropyl group, 1-methylpropyl group, t-butyl group.
That is, as the monomer (Am1) in which R ² and / or R ³ in formula (16) is a linear or branched hydrocarbon group having 1 to 10 carbon atoms, N, N-dimethyl ( Examples include meth) acrylamide, N, N-diethyl (meth) acrylamide, and N-isopropyl (meth) acrylamide.

Examples of the cyclic hydrocarbon group having 3 to 10 carbon atoms that is R ² and / or R ³ in the formula (16) include cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, and cyclooctyl group. Cyclic group; aromatic groups such as phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, 4-t-butylphenyl group, 1-naphthyl group, and benzyl group.
Furthermore, in the above formula (16), a 3 to 10-membered monocyclic heterocycle formed by bonding R ² and R ³ to each other, or R ² and R ³ are a nitrogen atom, an oxygen atom, As a monomer (Am1) having a 4- to 10-membered monocyclic heterocycle formed by bonding via at least one heteroatom selected from the group consisting of a sulfur atom and a selenium atom, N -(Meth) acryloylmorpholine etc. are mentioned.

  As the monomer (Am1), N, N-dimethylacrylamide, N, N-dimethylmethacrylamide, N-acryloylmorpholine, and N-methacryloylmorpholine are preferable among the various monomers. The polymer (A) obtained using these preferable monomers can more effectively prevent unnecessary diffusion of the acid generated from the acid generator (B) in the film.

  When the nitrogen-containing group is contained in the polymer (A) as the structural unit represented by the formula (1), the proportion of the structural unit represented by the formula (1) in the polymer (A) is not particularly limited. When the total structural unit of the polymer (A) is 100 mol%, it is preferably 1 to 50 mol%, more preferably 3 to 40 mol%, and 5 to 30 mol%. Particularly preferred. When the proportion of the structural unit represented by the formula (1) in the polymer (A) is within the above range, unnecessary diffusion of the acid generated from the acid generator (B) in the film is more effectively prevented. it can.

〔式（１７）中、Ｒ^１は水素原子又はメチル基を表す。Ｒ^２は１価の有機基を表す。〕 The polymer (A) can contain other structural units in addition to the structural unit represented by the formula (1). The other structural unit is preferably a structural unit represented by the following formula (17).

[In Formula (17), R ¹ represents a hydrogen atom or a methyl group. R ² represents a monovalent organic group. ]

  As the structural unit represented by the formula (17), the polymer (A) containing the structural unit represented by the formula (17) is usually obtained by using a monomer (Am2) represented by the following formula (18). Obtainable.

〔式（１８）中、Ｒ^１は水素原子又はメチル基を表す。Ｒ^２は１価の有機基を表す。〕

[In Formula (18), R ¹ represents a hydrogen atom or a methyl group. R ² represents a monovalent organic group. ]

Examples of the monovalent organic group represented by R ² in the formula (18) include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, a 2-methylpropyl group, a 1-methylpropyl group, a linear or branched alkyl group having 1 to 12 carbon atoms such as a t-butyl group;

  Phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, 2,4-xylyl group, 2,6-xylyl group, 3,5-xylyl group, mesityl group, o-cumenyl group, m-cumenyl A C6-C20 aromatic hydrocarbon group such as a group, p-cumenyl group, benzyl group, phenethyl group, 1-naphthyl group, 2-naphthyl group;

  Hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, 1-hydroxypropyl group, 2-hydroxypropyl group, 3-hydroxypropyl group, 1-hydroxybutyl group, 2-hydroxybutyl group, 3-hydroxybutyl A hydroxyalkyl group having 1 to 8 carbon atoms such as a group, 4-hydroxybutyl group, 3-hydroxycyclopentyl group, 4-hydroxycyclohexyl group;

  Cyanomethyl group, 1-cyanoethyl group, 2-cyanoethyl group, 1-cyanopropyl group, 2-cyanopropyl group, 3-cyanopropyl group, 1-cyanobutyl group, 2-cyanobutyl group, 3-cyanobutyl group, 4-cyanobutyl group A nitrogen atom-containing organic group such as a cyanoalkyl group having 2 to 9 carbon atoms such as 3-cyanocyclopentyl group and 4-cyanocyclohexyl group; and a cyano group;

A cyclic hydrocarbon group such as a cyclopentyl group and a cyclohexyl group;
And alicyclic groups such as bridged cyclic hydrocarbon groups such as bornyl group and isobornyl group.
In the formula (17) and the formula (18), R ² may be an acid-labile protecting group (P) {that is, formula (19)} described later, but R ² may be an acid. It is preferably not an unstable protecting group (P).

As the monomer (Am2), a (meth) acrylate compound is preferable. Specifically, methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, n-butyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, polyethylene glycol mono (meth) acrylate, polypropylene glycol mono (meth) acrylate, glycerol mono (meth) acrylate, phenyl (meth) acrylate, benzyl (meth) ) Acrylate, cyclohexyl (meth) acrylate, isobornyl (meth) acrylate, tricyclodecanyl (meth) acrylate, and the like. These (meth) acrylate compounds may be used alone or in combination of two or more.
Of these (meth) acrylate compounds, methyl methacrylate is particularly preferable.

  The proportion of the structural unit represented by the formula (17) in the polymer (A) is not particularly limited, but is 5 to 99 mol% when the total structural unit of the polymer (A) is 100 mol%. It is preferably 10 to 97 mol%, more preferably 15 to 95 mol%. When the proportion of the structural unit represented by the formula (17) in the polymer (A) is within the above range, unnecessary diffusion of the acid generated from the acid generator (B) in the film can be prevented.

  A polymer (A) can contain other structural units other than the structural unit shown to the said Formula (1), and the structural unit shown to the said Formula (17). The type of other structural unit is not particularly limited as long as it does not impair the object of the present invention. When other structural units are included, the ratio is not particularly limited, but is preferably 30 mol% or less, when the total structural units of the polymer (A) are 100 mol%, preferably 1 to 10 mol% It is more preferable that Within this range, the object of the present invention is not impaired.

  Further, when both the structural unit represented by the formula (1) and the structural unit represented by the formula (17) are included and other structural units are contained, the formula (1) ) And the content of each of the structural units represented by the formula (17) are 100 mol in total of the structural unit represented by the formula (1) and the structural unit represented by the formula (17). %, The structural unit represented by the formula (1) is preferably 1 to 50 mol%, more preferably 3 to 40 mol%, and particularly preferably 5 to 30 mol%. . In this range, unnecessary diffusion of acid generated from the acid generator (B) in the film can be more effectively prevented.

The molecular weight of the polymer (A) is not particularly limited and may be appropriately selected. The polystyrene-reduced weight molecular weight (hereinafter referred to as “Mw”) measured by gel permeation chromatography (GPC). Usually, it is 1,000 to 500,000, preferably 2,000 to 400,000, and more preferably 3,000 to 300,000.
Further, the ratio (Mw / Mn) between the Mw of the polymer (A) and the polystyrene-equivalent molecular weight (hereinafter referred to as “Mn”) measured by GPC is not particularly limited and can be appropriately selected. It is 1-10, Preferably it is 1-8, More preferably, it is 1-3.

  Moreover, it is preferable that a polymer (A) is a polymer which does not have a hydroxyl group substantially. “Substantially no hydroxyl group” means that the R—OH bond sound having a wavelength of 2000 to 2300 nm is determined in accordance with the method for determining the hydroxyl value of a plastic-polyurethane raw material polyol of JIS K1557 by near infrared (NIR) spectroscopy. And the hydroxyl value of the polymer (A) measured using two wavelength ranges of 1380 to 1500 nm R—OH first overtone {the hydroxyl group in 1 g of the polymer (A) and an equivalent amount of potassium hydroxide. Mass (mg)} means 1 or less.

  Similarly, the polymer (A) is preferably a polymer that does not substantially have an acid dissociable group (an acid-labile protecting group). “Substantially has no acid-dissociable group” means that the monomer obtained without using an acid-dissociable group is 95% by mole or more of all monomers used for polymer synthesis. It is a coalescence. That is, in other words, it means that the constituent unit having an acid-labile protecting group described below is less than 5 mol% in 100 mol% of all the constituent units constituting the polymer (A).

  The acid transferable resin composition of the present invention may be formed into a film in any way, but usually the liquid acid transferable resin composition is applied to the target surface (for example, the surface of the first film described later). It is formed by applying and drying {further, it can be heat-treated (baked) if necessary}. For this reason, in addition to the said polymer (A) and the said acid generator (B), this acid transferable resin composition can contain a solvent (C).

Although the kind of said solvent (C) is not specifically limited, For example, water and / or an organic solvent etc. can be used. These may use only 1 type and may use 2 or more types together.
Examples of the organic solvent include propylene glycol monomethyl ether, propylene glycol monoethyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol dimethyl ether, diethylene glycol. Diethyl ether, diethylene glycol ethyl methyl ether, dipropyl ether, diisopropyl ether, butyl methyl ether, butyl ethyl ether, butyl propyl ether, dibutyl ether, diisobutyl ether, tert-butyl methyl ether, tert-butyl ethyl ether, tert-butyl propyl ether, di-tert-butyl ether, dipentyl ether, diisoamyl ether, cyclopentyl methyl ether, cyclohexyl methyl ether, cyclopentyl ethyl ether, cyclohexyl ethyl ether, cyclopentyl propyl ether, cyclopentyl-2-propyl ether, cyclohexyl propyl ether, Alkyl ethers such as cyclohexyl-2-propyl ether, cyclopentyl butyl ether, cyclopentyl-tert-butyl ether, cyclohexyl butyl ether, cyclohexyl-tert-butyl ether;

1-propanol, n-butanol, 2-butanol, 1-pentanol, 2-pentanol, 3-pentanol, 2-methyl-1-propanol, neopentyl alcohol, tert-amyl alcohol, isoamyl alcohol, 3-methyl Alkyl alcohols such as 2-butanol, 2-methyl-1-butanol, 2-ethyl-1-butanol, 2-methyl-1-pentanol, 4-methyl-2-pentanol;
Examples include hydrocarbons such as decane, dodecane, undecane, benzene, toluene, and xylene.

In the present acid transferable resin composition, the solvent (C) is usually contained in an amount of 10 to 10000 parts by mass, preferably 20 to 8000 parts by mass, when the polymer (A) is 100 parts by mass. -6000 mass parts is more preferable, and 40-4000 mass parts is still more preferable.
Furthermore, the viscosity of the entire acid transferable resin composition is not particularly limited, and may be set to an appropriate viscosity by a method of applying the acid transferable resin composition. For example, the viscosity at a temperature of 25 ° C. is 1 to 100 mPa · s. This viscosity is preferably 2 to 80 mPa · s, more preferably 3 to 50 mPa · s.

  In addition to the solvent (C), the acid transferable resin composition may contain other components. Surfactant (D) is mentioned as another component. Examples of the surfactant (D) include nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, silicone surfactants, polyalkylene oxide surfactants, and fluorine-containing surfactants. Surfactant etc. are mentioned.

Specifically, polyoxyethylene lauryl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, polyoxyethylene n-octylphenyl ether, polyoxyethylene n-nonylphenyl ether, polyethylene glycol dilaurate, polyethylene glycol distearate NBX-7, NBX-8, NBX-15 (trade name, manufactured by Neos), SH8400 FLUID (trade name, manufactured by Toray Dow Corning Silicon Co.), KP341 (trade name, manufactured by Shin-Etsu Chemical Co., Ltd.) ), Polyflow No. 75, no. 95 (trade name, manufactured by Kyoeisha Chemical Co., Ltd.), F Top EF301, EF303, EF352 (trade name, manufactured by Tochem Products Co., Ltd.), Megafax F171, F172, F173, F471, R-07, R-08 (Trade name, manufactured by Dainippon Ink & Chemicals, Inc.), Florard FC430, FC431 (trade name, manufactured by Sumitomo 3M Limited), Asahi Guard AG710, Surflon S-382, SC-101, SC-102, SC-103, SC-104, SC-105, SC-106 (trade name, manufactured by Asahi Glass Co., Ltd.) and the like can be mentioned. In addition, these may use only 1 type and may use 2 or more types together.
When this surfactant (D) is used, the amount thereof is not particularly limited, but is usually 0.01 to 0.5 parts by mass, preferably 0 with respect to 100 parts by mass of the total amount of the polymer (A). 0.02 to 0.1 part by mass.

  In addition, a sensitizer, a crosslinking agent, an antihalation agent, a storage stabilizer, a colorant, a plasticizer, an antifoaming agent, and the like can be appropriately added to the acid transferable resin composition.

[2] Biochip manufacturing method The biochip manufacturing method of the present invention includes (a) a first film forming step, (b) a second film forming step, (c) a protecting group removing step, and (d) a second film. It comprises a removal step and (e) a second compound binding step (see FIGS. 1 to 3).

  In the “(a) first film forming step” (see PR1 in FIG. 1), a first compound having an acid-labile protecting group P is directly or indirectly bonded to the substrate 10 to form the first film 20. Is a process PR1 of forming

The “first compound” is a compound having an acid-labile protecting group P (hereinafter, also simply referred to as “protecting group”). The 1st compound should just have protecting group P, and another structure is not specifically limited, For example, the compound illustrated by following (1)-(3) is mentioned. That is,
(1) A coupling compound for bonding the substrate surface and the second compound. More specifically, a compound having a bond with the second compound protected by the protecting group and a bond with the substrate surface, that is, a compound having a protecting group and a silyl group, for example.
(2) A protecting group-introducing compound for introducing a protecting group. More specifically, a compound for introducing a protecting group for protecting an amino group or a hydroxyl group, that is, a compound having a group capable of peptide bonding to an amino group and a protecting group, for example.
(3) A spacer compound for separating the second compound from the substrate surface. That is, for example, a compound having a group capable of peptide bonding to an amino group separated by an alkyl chain and a protecting group.

  Among the first compounds exemplified above, (1) the coupling compound is usually directly bonded to the substrate surface, but may be indirectly bonded to the substrate surface via another compound. Further, (2) the protecting group-introducing compound and (3) the spacer compound are usually indirectly bonded to the substrate surface via another compound. Any compound may be interposed between the (2) protecting group-introducing compound and (3) the spacer compound and the substrate surface. For example, a coupling agent (coupling compound) may be interposed.

Among these, examples of the (2) protecting group-introducing compound include aminoalkylcarboxylic acids such as omega-aminocaproic acid compounds having a protecting group. Such compounds include 6-Nt-butoxycarbonylaminocaproic acid, 4-Nt-butoxycarbonylaminobutanoic acid, 5-Nt-butoxycarbonylaminopentanoic acid, 7-Nt-butoxycarbonyl. Examples thereof include carboxylic acid derivatives having a t-butoxycarbonyl group as a protective group such as aminoheptanoic acid.
In addition, when the protective group-introducing compound (2) is used as the first compound, the coupling rigging agent (coupling compound) that connects the substrate and the first compound (protecting group-introducing compound) is aminopropyltriethoxysilane or the like. And a coupling agent having an amino group and a silyl group, and a coupling agent having a hydroxyl group and a silyl group.

  In addition, as the first compound, a compound having a protecting group among various compounds mentioned as the second compound to be described later, a derivative having a protecting group introduced into various compounds mentioned as the second compound to be described later, and the like are used. You can also.

  The “acid-labile protecting group (P)” is a group that dissociates in the presence of an acid, more specifically an acidic group, and more specifically, a phenolic hydroxyl group, a carboxyl group, or a sulfonic acid. The group which substitutes the hydrogen atom in acidic groups, such as a group, a phosphoric acid group, and an acidic hydroxyl group is meant. As this acid dissociable group, t-butoxycarbonyl group, tetrahydropyranyl group, tetrahydrofuranyl group, (thiotetrahydropyranylsulfanyl) methyl group, (thiotetrahydrofuranylsulfanyl) methyl group, alkoxy-substituted methyl group, alkylsulfanyl Examples thereof include a substituted methyl group, an acetal group, a hemiacetal group, a group represented by the following general formula (19) (hereinafter referred to as “acid-dissociable group (19)”), and the like.

〔式（１９）中、Ｒ^１〜Ｒ^３は、各々独立に、炭素数１〜１４の直鎖状のアルキル基、炭素数１〜１４の分岐状のアルキル基、炭素数３〜２０の非有橋式の１価の脂環式炭化水素基、炭素数３〜２０の有橋式の１価の脂環式炭化水素基、又は炭素数６〜２０の１価の芳香族基を示すか、或いは、Ｒ^１〜Ｒ^３のうちの何れか２つが結合して、炭素数３〜２０の非有橋式の２価の脂環式炭化水素基、又は炭素数３〜２０の有橋式の２価の脂環式炭化水素基を形成すると共に、Ｒ^１〜Ｒ^３のうちの残りの１つが、炭素数１〜１４の直鎖状のアルキル基、炭素数１〜１４の分岐状のアルキル基、炭素数３〜２０の非有橋式の１価の脂環式炭化水素基、炭素数３〜２０の有橋式の１価の脂環式炭化水素基、又は炭素数６〜２０の１価の芳香族基を示し、これらの各基は置換されていてもよい。］

[In Formula (19), R ^{1 to} R ³ each independently represents a linear alkyl group having 1 to 14 carbon atoms, a branched alkyl group having 1 to 14 carbon atoms, or a non-carbon having 3 to 20 carbon atoms. Whether it represents a bridged monovalent alicyclic hydrocarbon group, a bridged monovalent alicyclic hydrocarbon group having 3 to 20 carbon atoms, or a monovalent aromatic group having 6 to 20 carbon atoms Alternatively, any two of R ^{1 to} R ³ are bonded to each other to form a non-bridged divalent alicyclic hydrocarbon group having 3 to 20 carbon atoms, or a bridged structure having 3 to 20 carbon atoms. And the remaining one of R ^{1 to} R ³ is a linear alkyl group having 1 to 14 carbon atoms, a branched alkyl group having 1 to 14 carbon atoms. An alkyl group, a non-bridged monovalent alicyclic hydrocarbon group having 3 to 20 carbon atoms, a bridged monovalent alicyclic hydrocarbon group having 3 to 20 carbon atoms, or a carbon number of 6 to 20 A monovalent aromatic group of And, each of these groups may be substituted. ]

  Examples of the linear alkyl group having 1 to 14 carbon atoms and the branched alkyl group having 1 to 14 carbon atoms in the formula (19) include a methyl group, an ethyl group, an n-propyl group, an I- Propyl group, n-butyl group, 2-methylpropyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, n-nonyl group, n-decyl group, n-undecyl group, n -Dodecyl group, n-tridecyl group, n-tetradecyl group and the like.

As the non-bridged monovalent alicyclic hydrocarbon group having 3 to 20 carbon atoms and the bridged monovalent alicyclic hydrocarbon group having 3 to 20 carbon atoms in the formula (19), A cycloalkyl group such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group; a bicyclo [2.2.1] heptyl group, a bicyclo [2.2.2] octyl group , Tetracyclo [4.2.0.1 ^2,5 . 1 ^7,10 ] dodecyl group, adamantyl group and the like.

  Examples of the monovalent aromatic group having 6 to 20 carbon atoms in the formula (19) include a phenyl group, a naphthyl group, and an anthracenyl group.

In Formula (19), each group of R ^{1 to} R ³ may independently have a substituent. Examples of the substituent include a hydroxyl group, a carboxyl group, an oxo group (═O), a cyano group, a halogen atom (for example, a fluorine atom and a chlorine atom), and a linear alkyl group having 1 to 14 carbon atoms (for example, Methyl groups, ethyl groups, n-propyl groups, n-butyl groups, etc.), branched alkyl groups having 1 to 14 carbon atoms (for example, i-propyl group, 2-methylpropyl group, 1-methylpropyl group, t-butyl group, etc.), linear alkoxyl group having 1 to 8 carbon atoms (for example, methoxy group, ethoxy group, n-propoxy group, n-butoxy group, etc.), branched alkoxyl having 1 to 8 carbon atoms. Groups (for example, i-propoxy group, 2-methylpropoxy group, 1-methylpropoxy group, t-butoxy group, etc.), linear alkoxyalkyl groups having 2 to 8 carbon atoms (for example, methoxymethyl group, Dimethyl group), a branched alkoxyalkyl group having 2 to 8 carbon atoms (for example, t-butoxymethyl group), a linear alkoxyalkoxy group having 2 to 8 carbon atoms (for example, methoxymethoxy group, ethoxymethoxy group, etc.) Group), a branched alkoxyalkoxyl group having 2 to 8 carbon atoms (for example, t-butoxymethoxy group), a linear alkylcarbonyloxy group having 2 to 8 carbon atoms (for example, methylcarbonyloxy group, Ethylcarbonyloxy group etc.), C2-C8 branched alkylcarbonyloxy group (eg t-butylcarbonyloxy group etc.), C2-C8 linear alkoxycarbonyl group (eg methoxycarbonyl). Group, an ethoxycarbonyl group, etc.), a branched alkoxycarbonyl group having 2 to 8 carbon atoms (for example, t-butoxycarbonyl) Etc.), a linear cyanoalkyl group having 2 to 14 carbon atoms (for example, cyanomethyl group, 2-cyanoethyl group, 3-cyanopropyl group, 4-cyanobutyl group, etc.), branched cyano having 2 to 14 carbon atoms Examples thereof include an alkyl group, a linear fluoroalkyl group having 1 to 14 carbon atoms (for example, a fluoromethyl group, a trifluoromethyl group, a pentafluoroethyl group, etc.), a branched fluoroalkyl group having 1 to 14 carbon atoms, and the like. It is done. These may use only 1 type and may use 2 or more types together.

  Examples of the alkoxy-substituted methyl group include a methoxymethyl group, an ethoxymethyl group, a methoxyethoxymethyl group, an n-propoxymethyl group, an n-butoxymethyl group, an n-pentyloxymethyl group, and an n-hexyloxymethyl group. And benzyloxymethyl group.

  Examples of the alkylsulfanyl-substituted methyl group include methylsulfanylmethyl group, ethylsulfanylmethyl group, methoxyethylsulfanylmethyl group, n-propylsulfanylmethyl group, n-butylsulfanylmethyl group, n-pentylsulfanylmethyl group, n- Examples thereof include a hexylsulfanylmethyl group and a benzylsulfanylmethyl group.

  The kind of the “substrate (10)” is not particularly limited, and may be made of an inorganic material, an organic material, or a composite material thereof. Moreover, the board | substrate 10 may consist of a material from which the surface side differs from the other surface side. Examples of the substrate material include inorganic materials mainly composed of silicon such as silicon, silicon dioxide, and glass (including borosilicate glass, surface-modified glass, and quartz glass). In addition, organic materials such as polypropylene and polyacrylamide (including polyacrylamide whose surface is activated by acrylamide) can be used. Other known in the art having a surface with a reactive site (eg, an active amino group) suitable for immobilizing a layer of a compound having a protecting group (not limited to the first membrane). These substrates can be used as appropriate.

  The first film 20 may be bonded on the substrate 10 in any way, but usually the liquid containing the first compound is the surface of the substrate 10 (including the substrate that has not been surface-treated and the substrate that has been surface-treated). The first compound and the surface of the substrate 10 are reacted and bonded to each other. The coating method in this case is not particularly limited, and various conventionally known methods such as spin coating, cast coating, roll coating, and printing can be used.

Further, the first compound may be directly bonded to the substrate 10 or indirectly bonded via another compound. That is, in other words, the first film (a film made of a plurality of aligned first compounds or residues thereof) 20 may be directly laminated on the substrate 10, or one or more other films may be formed. You may laminate | stack indirectly.
The first compound is bonded directly or indirectly to the substrate in the other part while maintaining the protective group. In addition, in the first compound, part of the structure of the first compound may or may not change upon this bonding. Examples of the change include a case where a bond generated by elimination of a part of the structure of the first compound is used.

  The “(b) second film forming step” (see PR2 in FIG. 1) is a step PR2 in which the second film 30 is formed on the first film 20 using the acid transfer resin composition.

The method for forming the second film 30 using the acid transferable resin composition is not particularly limited, and examples thereof include appropriate coating means such as spin coating, cast coating, roll coating, and printing.
Furthermore, after apply | coating this acid transferable resin composition, you may form the 2nd film | membrane 30 by volatilizing the solvent in a coating film by pre-baking (PB) as needed. The prebaking heating conditions are appropriately selected depending on the composition of the acid transferable resin composition, but the heating temperature is usually 30 to 150 ° C, preferably 50 to 130 ° C. Furthermore, the heating time is usually 30 to 300 seconds, preferably 60 to 180 seconds.
The thickness of the second film 30 is not particularly limited, but is usually preferably 1 to 10000 nm, more preferably 5 to 800 nm, and still more preferably 10 to 500 nm.

In the “(c) protecting group removal step”, as illustrated in FIGS. 1 and 2, the second film 30 is exposed to remove the protecting group P from the first film 30 corresponding to the exposed portion. Steps PR3 and PR4.
In this protective group removal step, usually, an exposure step PR3 for exposing the second film 30 to radiation, and a transfer for transferring (diffusing) the acid generated in the second film 30 by the exposure to the first film 20 And a process PR4.

Of these, the exposure step PR3 is a step of exposing the second film 30 through the mask 50 to generate the acid in the second film 30. As a result, as illustrated in FIG. 1, the exposed portion of the second film 30 becomes the acid generating portion 31.
The type of radiation used for exposure is not particularly limited, and is appropriately selected according to the type of acid generator (B) contained in the second film 30. Further, the exposure amount and the like are appropriately selected according to the type of the acid generator (B) contained in the second film 30.

The acid transfer process PR4 is a process of transferring the acid generated in the second film 30 to the first film 20. As a result, as illustrated in FIG. 2, by removing the protecting group P from the first compound constituting the first film 20 corresponding to the acid generation site 31, a part of the first film 20 becomes an acid transfer site. 21 (the acid transcription site 21 contains the residue of the first compound from which the protecting group P is dissociated).
The method for transferring the acid is not particularly limited. Specifically, (1) a method for transferring by heating, (2) a method for transferring by standing at room temperature, and (3) a transfer using osmotic pressure. The method etc. are mentioned. These methods may be used alone or in combination of two or more. Among these methods, (1) the method of transferring by heating is preferable because of excellent transfer efficiency.
The heating conditions for transferring by heating are not particularly limited, but the heating temperature is preferably 50 to 200 ° C, more preferably 70 to 150 ° C. Furthermore, the heating time is preferably 30 to 300 seconds, more preferably 60 to 180 seconds.
In addition, when transferring by heating, it may be completed by one heating depending on the above heating conditions, but as a result, two or more heatings may be performed so as to obtain the same result as the above heating conditions. it can.

  Note that (2) the method of transferring by allowing to stand at normal temperature is a method of transferring the acid generated in the second film 30 by leaving it in a normal temperature environment of 20 to 30 ° C. without heating. Is naturally diffused into the first film 20 and transferred.

The “(d) second film removing step” is a step PR5 of removing the second film 30 as illustrated in FIG. That is, it is a process PR5 for removing the second film 30 and exposing the first film 20 to which the acid is transferred below the second film 30.
The removal of the second film 30 may be performed by any method, but is usually performed by dissolving the second film 30 with an organic solvent. This organic solvent dissolves the second film 30 but does not dissolve the first film 20 to which the acid has been transferred.

  Such an organic solvent is preferably selected as appropriate depending on the components constituting each of the second film 30 and the first film 20, and the organic solvent in which the first film 20 is not dissolved and the second film 30 is dissolved. Specific examples include acetonitrile, acetone, tetrahydrofuran, and pyridine. These organic solvents may use only 1 type and may use 2 or more types together.

  The “(e) second compound binding step” is a step PR6 of binding the second compound to the site of the first film from which the protecting group has been removed. That is, this is a step of laminating the portion 41 containing the second compound on the portion 21 of the first film 20 where the acid transfer is performed and the protecting group P is dissociated.

  The type of the “second compound” is not particularly limited, and various compounds can be used. Examples of the second compound include (1) nucleotides {including nucleotides, deoxynucleotides and analogs excluding these (synthetic nucleotide analogs, synthetic deoxynucleotide analogs, etc.)}, (2) amino acids, (3) single A saccharide, or (4) a conjugate in which two or more compounds selected from these nucleotides, amino acids and monosaccharides are bound, and (5) a peptide nucleic acid-forming compound for synthesizing peptide nucleic acid (PNA) (peptide nucleic acid monomer) ) And (6) various end forming compounds. These second compounds may have a protecting group and an active group. Moreover, these 2nd compounds may use only 1 type, and may use 2 or more types together.

Examples of the nucleotide (1) include deoxynucleotides and synthetic nucleotide analogs.
Among these, examples of the nucleotide include adenosine phosphate, guanosine phosphate, cytidine phosphate, uridine phosphate and the like.
Examples of deoxynucleotides include deoxyadenosine phosphate, deoxyguanosine phosphate, deoxythidine phosphate, deoxythymidine phosphate, and the like.
Furthermore, the synthetic nucleotide analogs include 2′-4 ′ cross-linked nucleotide analogs, 3′-4 ′ cross-linked nucleotide analogs, 5′-amino-3 ′, 5 ′ cross-linked nucleotide analogs and the like. Etc.

The (2) amino acids (including L-form and D-form) have glycine / alanine / valine / leucine / isoleucine having an alkyl chain, serine / threonine having a hydroxy group, cysteine / methionine containing sulfur, and an amide group. Examples include asparagine / glutamine, proline having an imino group, phenylalanine / tyrosine / tryptophan having an aromatic group, and the like.
Examples of the (3) monosaccharide include glucose, galactose, mannose, fucose, xylose, N-acetylglucosamine, N-acetylgalactosamine and the like.
Examples of the conjugate of (4) include oligonucleotides that are conjugates of nucleotides, peptides and proteins that are conjugates of amino acids, and the like.

  Examples of the peptide nucleic acid-forming compound include N- (2-t-butyloxycarbonyl-aminoethyl) -N-thymin-1-ylacetyl) glycine, N- (N-4- (benzyloxycarbonyl) cytosine-1- Yl) acetyl-N- (2-t-butyloxycarbonyl-aminoethyl) glycine, N- (N-6- (benzyloxycarbonyl) adenine-9-yl) acetyl-N- (2-t-butyloxycarbonyl) -Aminoethyl) glycine and N- (N-4- (benzyloxycarbonyl) guanin-1-yl) acetyl-N- (2-t-butyloxycarbonyl-aminoethyl) glycine.

  The (5) end forming compound is a compound that forms a molecular chain end, and includes a protecting group forming compound having various protecting groups, various capping compounds, and a labeling compound. Of these, the labeling compounds include various fluorescent labeling compounds (fluorescein derivatives such as phloresin isothiocyanate) and radioisotope labeling compounds.

Furthermore, as the protecting group that the second compound can have, the acid-labile protecting group in the first compound can be applied as it is, and a light-labile protecting group can also be used.
Examples of the active group that the second compound can have include a phosphorus-containing group capable of reacting with a free hydroxyl group such as a phosphoramidite group, H-phosphonate, phosphodiester, phosphotriester, and phosphate triester. It is done. Thus, for example, activated nucleotides include phosphoramidite nucleotide molecules. In addition, examples of the photochemically active group and the thermochemically active group include an amino group, a thiol group, a maleimide group, an N-hydroxysuccinimidyl ester group, a formyl group, a carboxyl group, an acrylamide group, and an epoxy group.

  Then, as illustrated in FIG. 3, the same operations as those for dissociating the protecting group P from the first film (acid transferable resin composition layer formation step PR7, exposure step PR8, acid transfer step PR9, acid transfer) By performing the transferable resin composition layer removal step PR10), the protective group P is dissociated from the first film where the protective group remains (the portion where the second compound is not bonded), and then the third compound binding step. By applying PR11, the third compound can be bound to the residue of the first compound to form a site 42 consisting of the residue of the third compound.

Furthermore, as illustrated in the bottom diagram of FIG. 2, when the second compound has an acid-labile protecting group P, the second compound consists of a residue of the second compound by performing the same operation as described above. Another compound (fourth compound, fifth compound, etc.) can be bound on the site 41. By repeating the same operation in this way, a polymer can be synthesized with a high degree of freedom on the substrate.
The description regarding the second compound can be applied to the third compound, the fourth compound and the fifth compound as they are. Further, the first compound, the second compound, the third compound, the fourth compound, the fifth compound and the like may be the same or different.

  According to the production method of the present invention, a polymer can be designed with a high degree of freedom on a substrate. The polymer synthesized by this method is not particularly limited, but is particularly suitable for the synthesis of biopolymers and pseudo-biopolymers. Examples of such a polymer include nucleic acids and proteins. Examples of nucleic acids include DNA, RNA and PNA (Peptide Nucleic Acid), as well as artificial nucleic acids (LNA {Locked Nucleic Acid (trademark of Proligo LLC)}) and BNA synthesized using partially or fully cross-linked nucleotide analogs. Etc.]. Among these, PNA is a pseudo-biopolymer having a peptide bond skeleton, whereas DNA and RNA have a phosphate bond skeleton. This PNA is usually a polymer having an aminoethylglycine derivative as a monomer.

[3] Biochip The biochip of the present invention is formed by the biochip manufacturing method of the present invention. This biochip is obtained by forming several thousand to several tens of thousands of probes on a 1 to 10 mm square substrate, and can simultaneously analyze an expression pattern of DNA or the like serving as a specimen.
Examples of the probe include DNA, RNA, PNA, BNA, artificial nucleic acid, protein (peptide), sugar chain, and a combination of these. The contents described in the above-described biochip manufacturing method can be directly applied to the substrate. The biochip may be any of a DNA chip, an RNA chip, a protein chip, a sugar chain chip, and the like.
The biochip can also be suitably used for detection of gene expression patterning, novel gene schooling, gene polymorphism, gene mutation, and the like.

  Hereinafter, the embodiment of the present invention will be described more specifically with reference to examples. However, the present invention is not limited to this embodiment. Note that “parts” and “%” in Examples and Tables are based on mass unless otherwise specified.

[1] Preparation of acid transferable resin composition (Examples 1-4 and Comparative Examples 1-2)
(1) Synthesis of polymer (A) 5 g of N, N-dimethylacrylamide (monomer Am1, manufactured by Kojin Co., Ltd.) 5 g in a 500 mL beaker when the total of Am1 and Am2 is 100 mol% %), Methyl methacrylate (Am2, manufactured by Mitsubishi Materials Corporation), 95 g (95 mol% when the total of Am1 and Am2 is 100 mol%), 2,2′-azobisisobutyronitrile (polymerization initiator) ) 5.0 g was charged and stirred until the polymerization initiator was dissolved to obtain a uniform solution. Separately, 150 g of propylene glycol monomethyl ether acetate (solvent) was charged into a flask equipped with a nitrogen-substituted dry ice / methanol refluxer, gently stirred and heated to 80 ° C. Then, the said solution was dripped little by little over 2 hours at 80 degreeC. After the dropping, polymerization was further performed at 80 ° C. for 3 hours, and then the temperature was raised to 100 ° C. and stirred for 1 hour to complete the polymerization. Thereafter, the obtained reaction solution was dropped into a large amount of cyclohexane to solidify the product. Next, the obtained coagulated product was washed with water, redissolved in tetrahydrofuran having the same mass as the coagulated product, and dropped into a large amount of cyclohexane to be coagulated again. After performing the redissolving and coagulation cycle three times in total, the obtained coagulated product was vacuum dried at 40 ° C. for 48 hours to obtain a polymer (A).
The yield of the obtained polymer (A) was 90%, Mw was 11,000, and Mw / Mn was 2.3. The polymer (A) is a polymer having the structural unit represented by the formula (1) and the structural unit represented by the formula (17).

(2) Mixing with other components As shown in Table 1 below, 100 parts by mass of the polymer (A) obtained in (1) above, 30 parts by mass of the following acid generator (B), 100 parts by mass of the solvent (C). Part and 0.05 part by mass of surfactant (D) were mixed and stirred to obtain a uniform solution. This solution was filtered through a capsule filter having a pore size of 0.5 μm to obtain six types of acid transferable resin compositions (Examples 1 to 4 and Comparative Examples 1 and 2).

この酸発生剤Ｂ１からは酸が発生され、その酸は、下記式（４）で表されるスルホニルアニオン有する。

前記式（４）で表されるスルホニルアニオンは、炭素原子７個、水素原子７個、酸素原子３個、硫黄原子１個から構成されることから、その炭素含有率は３８．９％〔｛７／（７＋７＋３＋１）｝×１００＝３８．９％〕である。 The following acid generators B1 to B4 were used as the acid generator (B).
Acid generator B1 [Formula (11) below]; manufactured by Ciba Japan Co., Ltd., product name “PAG121”

An acid is generated from the acid generator B1, and the acid has a sulfonyl anion represented by the following formula (4).

Since the sulfonyl anion represented by the formula (4) is composed of 7 carbon atoms, 7 hydrogen atoms, 3 oxygen atoms and 1 sulfur atom, its carbon content is 38.9% [{ 7 / (7 + 7 + 3 + 1)} × 100 = 38.9%].

この酸発生剤Ｂ２からは酸が発生され、その酸は、下記式（５）で表されるスルホニルアニオンを有する。

前記式（５）で表されるスルホニルアニオンは、炭素原子１０個、水素原子１５個、酸素原子４個、硫黄原子１個から構成されることから、その炭素含有率は３３．３％〔｛１０／（１０＋１５＋４＋１）｝×１００＝３３．３％〕である。 Acid generator B2 [formula (13) below]; product name “NAI-106” manufactured by Midori Chemical Co., Ltd.

An acid is generated from the acid generator B2, and the acid has a sulfonyl anion represented by the following formula (5).

Since the sulfonyl anion represented by the formula (5) is composed of 10 carbon atoms, 15 hydrogen atoms, 4 oxygen atoms and 1 sulfur atom, its carbon content is 33.3% [{ 10 / (10 + 15 + 4 + 1)} × 100 = 33.3%].

Acid generator B3; triphenylsulfonium nonafluorobutanesulfonate From this acid generator B3, an acid having a nonafluorobutanesulfonate anion in its structure is generated. This nonafluorobutanesulfonic acid anion is composed of 4 carbon atoms, 9 fluorine atoms, 3 oxygen atoms and 1 sulfur atom, so that its carbon content is 23.5% [{4 / (4 + 9 + 3 + 1 )} × 100 = 23.5%].

この酸発生剤Ｂ４からは、プロパンスルホン酸アニオンを構造中に有する酸が発生される。このプロパンスルホン酸アニオンは、炭素原子３個、水素原子７個、酸素原子３個、硫黄原子１個から構成されることから、その炭素含有率は２１．４％〔｛３／（３＋７＋３＋１）｝×１００＝２１．４％〕である。 Acid generator B4 [Formula (20) below]; Ciba Japan Co., Ltd., product name “PAG103”

From this acid generator B4, an acid having a propanesulfonate anion in the structure is generated. This propanesulfonic acid anion is composed of 3 carbon atoms, 7 hydrogen atoms, 3 oxygen atoms and 1 sulfur atom, so that its carbon content is 21.4% [{3 / (3 + 7 + 3 + 1)}. × 100 = 21.4%].

Moreover, the mixed solvent of the following solvent C1 and the solvent C2 was used as a solvent (C). During mixing, out of a total of 100 parts by mass of the solvent C1 and the solvent C2, the solvent C1 was 80 parts by mass and the solvent C2 was 20 parts by mass.
Solvent C1; Propylene glycol monomethyl ether acetate Solvent C2; γ-butyrolactone Further, as a surfactant (D), trade name “DYNAFLOW” manufactured by JSR Corporation was used.

  Polymer 4 (100 parts by mass), acid generators B1 to B4 (30 parts by mass), solvent C (100 parts by mass), surfactant (0. (05 parts by mass) was mixed and stirred to obtain a uniform solution. This solution was filtered through a capsule filter having a pore size of 0.5 μm to obtain six types of acid transferable resin compositions (Examples 1 to 4 and Comparative Examples 1 to 2) having a solid content concentration of 10.0%. It was.

[2] Evaluation of Biochip Manufacturing Resin Composition In order to evaluate the characteristics of the biochip manufacturing resin composition obtained in [1] above, the protective groups of the first film were selectively removed using each, and fluorescence Label and perform sensitivity evaluation and spot shape evaluation.

(1) First film forming step The glass substrate is immersed in a cleaning solution (1 L of 95% ethanol aqueous solution, 12 mL of water, 120 g of sodium hydroxide) for 12 hours, washed with water several times, and dried in the air. Next, a surface treatment for fixing amino groups on the glass substrate is performed. That is, the glass substrate is immersed in an ethanol solution of 0.1% by volume aminopropyltriethoxysilane and stirred at room temperature for 5 minutes. Then, it was washed with ethanol three times, dried at 120 ° C. for 20 minutes using a vacuum oven, and further left in an argon gas atmosphere for 12 hours, and then N, N-dimethylformamide (hereinafter simply referred to as “DMF”). Then, the surface treatment is performed by washing with dichloromethane.

  Thereafter, the surface-treated glass substrate was immersed in 0.5 ml of a DMF solution containing 30 mM 6-Nt-butoxycarbonylaminocaproic acid (first compound) and 3 g of dicyclohexylcarbodiimide (DCC). The reaction is allowed to stir for 1 hour at 0 ° C. Thereafter, the unreacted amino group (amino group on the glass substrate due to the aminopropyltriethoxysilane, which is not bound to the 6-Nt-butoxycarbonylaminocaproic acid) is protected with an acetyl group. For this purpose, the reaction is carried out in a mixed solution of acetic anhydride and pyridine (1 part by volume of acetic anhydride + 3 parts by volume of pyridine) with stirring for 1 hour. As a result, a first film (linker layer) made of the first compound in which the amino group is protected with an acid-labile protecting group (acetyl group) is formed on the glass substrate.

(2) Second Film Forming Step Each acid transferable resin composition (Examples 1 to 4 and Comparative Examples 1 and 2) obtained in [1] above is obtained in [2] (1) above. The glass substrate on which the film is formed is coated using a spin coater and heated on a hot plate at 110 ° C. for 1 minute to form each second film having a thickness of 150 nm.

(3) Protecting group removal step An ultrahigh pressure mercury lamp (manufactured by OSRAM, model “HBO” is applied to the surface of the second film of the glass substrate obtained up to (2) above through a pattern mask (square pattern of 50 μm × 50 μm). ”, An output of 1,000 W) is irradiated with ultraviolet light of 100 to 1000 mJ / cm ² to generate an acid in the second film. The amount of exposure is confirmed by an illuminometer (manufactured by Oak Manufacturing Co., Ltd., model “UV-M10” (illuminance meter) connected to model “probe UV-35” (receiver)).
Next, the glass substrate after the exposure is again heated on a hot plate at 110 ° C. for 1 minute to transfer the acid generated in the second film to the first film.

(4) Second Film Removal Step The glass substrate obtained up to (3) is immersed in acetonitrile for 30 seconds to remove the second film.

(5) Second compound binding step A protective group is dissociated from the first film in the step (3) and is exposed to the glass substrate surface in the step (4). In addition, a fluorescent label is formed by reacting at room temperature for 1 hour in a DMF solution containing 1 mM floresin isothiocyanate (manufactured by Aldrich, second compound). Then, after wash | cleaning in order of ethanol, water, and ethanol, it is made to dry and stores in a dark room.

(6) Spot shape evaluation and sensitivity evaluation The glass substrate obtained up to the above (5) is isothiocyanate group for all spots formed on the surface of the glass substrate using a microscopic laser Raman spectrometer (manufactured by Renishaw). And confirm whether each spot shape is formed to 50 μm × 50 μm accurately corresponding to the pattern mask. And the number which a defect | deletion is recognized with respect to the shape whose said absorption area | region is 50 micrometers x 50 micrometers is converted, it evaluates based on the following reference | standard, and it writes together in the said Table 1.
Moreover, sensitivity evaluation shows the minimum exposure amount in said (3) formed in 50 micrometers x 50 micrometers.
“O”; no defect is observed in all spots.
“Δ”: Defects are observed in 50% or less of the total number of spots.
“×”: Defects are observed in spots exceeding 50% of the total number.

  In addition, in this invention, it can restrict to what is shown to said specific Example, It can be set as the Example variously changed within the range of this invention according to the objective and the use.

10; substrate,
20; first film (first compound film), 21; site where protecting group is dissociated, P: protecting group,
30; second film (acid transferable resin film), 31; acid generation site,
41; site consisting of residues of the second compound; 42; site consisting of residues of the third compound (other second compound); 50; mask;
PR1; first film formation step, PR2; second film formation step, PR3; exposure step (part of the protective group removal step), PR4; acid transfer step (part of the protective group removal step), PR5; second film Removal step, PR6; second compound binding step, PR7; acid transferable resin composition film formation step, PR8; exposure step, PR9; acid transfer step, PR10; acid transferable resin composition film removal step, PR11; Compound binding step.

Claims (10)

An acid transferable resin composition comprising (A) a polymer and (B) a radiation sensitive acid generator,
The radiation sensitive acid generator (B) generates an acid having a sulfonyl anion in the structure by irradiation with radiation,
The ratio of the number of carbon atoms (Y) to the total number of atoms (X) in the chemical structural formula of the sulfonyl anion [(Y / X) × 100 (%)] is 30% or more, acid transferability Resin composition.   The acid transferable resin composition according to claim 1, wherein the sulfonyl anion does not contain a fluorine atom.   The acid transferable resin composition according to claim 1, wherein the sulfonyl anion has an alicyclic hydrocarbon group.   The acid transferable resin composition according to any one of claims 1 to 3, wherein the polymer (A) has a nitrogen-containing group in a side chain.   The acid transferable resin composition according to any one of claims 1 to 4, wherein the polymer (A) does not have an acid dissociable group. The acid transferable resin composition according to claim 1, wherein the polymer (A) includes a structural unit represented by the following formula (1).

Wherein (1), R ¹ represents a hydrogen atom or a methyl group. R ² and R ³ each independently represent a hydrogen atom, a linear or branched hydrocarbon group having 1 to 10 carbon atoms, or a cyclic hydrocarbon group having 3 to 10 carbon atoms. R ² and R ³ are bonded to each other to form a 3 to 10-membered monocyclic heterocycle, or at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom, and a selenium atom. To form a 4- to 10-membered monocyclic heterocycle. ]   The acid transferable resin composition according to claim 1, wherein the acid transferable resin composition is for biochip production. (A) a first film forming step of forming a first film by directly or indirectly bonding a first compound having an acid-labile protecting group to a substrate;
(B) a second film forming step of forming a second film on the first film using the acid transferable resin composition according to any one of claims 1 to 7;
(C) Protecting group removing step of exposing the second film and removing the protecting group from the first film corresponding to the exposed portion;
(D) a second film removing step for removing the second film, and
(E) A method for producing a biochip, comprising a second compound binding step of binding a second compound to a portion of the first film from which the protecting group has been removed.   The second compound is (1) a compound selected from the group consisting of nucleotides, amino acids and monosaccharides, or (2) a conjugate in which two or more compounds selected from the group consisting of nucleotides, amino acids and monosaccharides are bound. The method for producing a biochip according to claim 8, wherein   A biochip manufactured by the biochip manufacturing method according to claim 8 or 9.

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