JP2018102159A - Photosensitive composition for biochip and biochip production method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a photosensitive composition for a biochip on which a cell-non-adhesive membrane formed with a hole through the thickness direction or a groove can be formed with suitable patterning properties, and a production method for the biochip using the photosensitive composition for a biochip.SOLUTION: The photosensitive composition for a biochip comprises: a copolymer (A) with a unit (u1) having a cyclic ester group and a unit (u2) having -(R-O)-R, the molar ratio of unit (u1)/unit (u2) being 15/85 to 95/5, and the ratio of the sum of unit (u1) and unit (u2) with respect to all units being 65 mol% or more; a photoacid generator (B); and a solvent (C). Rindicates an alkylene group with a carbon number of 2-4, n indicates an integer of 1-30, Ris a hydrogen atom or R-X(where Rindicates an alkylene group and Xindicates a hydrogen group or a cyano group).SELECTED DRAWING: None

Description

  The present invention relates to a biochip photosensitive composition and a biochip manufacturing method.

In the life science field, cells are placed on a biochip and their behavior is observed.
If cells can be collected at a specific location on the biochip surface, observation can be performed more efficiently. As a technique for collecting cells at a specific location on the biochip surface, a method is considered in which a location on the biochip surface where cells adhere easily (cell adhesion portion) and a location where cells are difficult to adhere (cell non-adhesion portion) are provided. .

It is known that a polymer film having a poly (oxyalkylene) group or a phosphorylcholine group is difficult to adhere to proteins (Patent Documents 1 and 2).
If the protein is difficult to adhere, the cells are also difficult to adhere. Therefore, such a polymer film can function as a cell non-adhesive part.
However, Patent Documents 1 and 2 do not discuss patterning a polymer film.

For example, the following resin compositions have been proposed as materials that can form a patternable film.
In a polymer obtained by polymerizing polyethylene glycol mono (meth) acrylate and / or glycerol mono (meth) acrylate, glycidyl (meth) acrylate, etc., represented by a specific formula, a (meth) acryloyl group in one molecule or After reacting a compound having one vinyl group and one carboxyl group, a reaction product reacted with an acid anhydride of a polycarboxylic acid compound, a diluent, a photopolymerization initiator, a metal powder, and a metal oxide Or the resin composition containing 1 type, or 2 or more types selected from glass (patent document 3).
However, Patent Document 3 does not discuss suppression of cell adhesion.
In Patent Document 3, polyethylene glycol mono (meth) acrylate is used for the purpose of making the reaction product water-soluble and enabling development with water or an aqueous alkaline solution.

Japanese Patent Laid-Open No. 7-184990 International Publication No. 2016/010147 JP-A-9-194551

  An object of the present invention is to provide a biochip photosensitive composition capable of forming a cell non-adhesive film having a hole or groove penetrating in the thickness direction with good patterning properties, and the biochip photosensitive composition. It is to provide a method for producing the biochip used.

The present invention provides a biochip photosensitive composition and a biochip manufacturing method having the following configurations [1] to [6].
[1] having a unit (u1) having a cyclic ether group and a unit (u2) having a group represented by the following formula (1), wherein the molar ratio of the unit (u1) / the unit (u2) is A copolymer (A) having a ratio of 15/85 to 95/5 and a total ratio of the unit (u1) and the unit (u2) of 65 mol% or more based on the total units;
A photosensitive composition for biochips, comprising a photoacid generator (B).
-(R ¹ -O) _n -R ² (1)
However, ^{R 1} is an alkylene group having 2 to 4 carbon atoms, n represents an integer of 1 to 30, ^{R 2} is a hydrogen atom or ^R 3 -X ⁴ (provided that, ^{R 3} is an alkylene group, ^{X 4} Represents a hydrogen atom or a cyano group.
[2] The photosensitive composition for biochips according to [1], wherein the cyclic ether group is at least one selected from the group consisting of an epoxy group, an oxetane group and a 3,4-epoxycyclohexyl group.
[3] The photosensitive composition for biochips according to [1] or [2], wherein the unit (u1) is a unit derived from a monomer represented by the following formula (m1).
_{^{CH 2 = CR 11 -COO-R}} 12 -R 13 ··· (m1)
R ¹¹ represents a hydrogen atom, a halogen atom or an alkyl group, R ¹² represents an alkylene group or a group having an etheric oxygen atom between carbon atoms of the alkylene group, and R ¹³ represents the cyclic ether group.
[4] The photosensitive composition for biochips according to any one of [1] to [3], wherein the unit (u2) is a unit derived from a monomer represented by the following formula (m2).
_{^{CH 2 = CR 21 -Q 2 -}} (R 1 -O) n -R 2 ··· (m2)
^{However, R} 1, n and ^{R 2} are the same as defined ^{above, R 21} represents a hydrogen atom, a halogen atom or an alkyl group, ^{Q 2} is COO or ^COO-R 22 -NHCOO ^{(However, R 22} is an alkylene group Is shown.)
[5] The photosensitive composition for biochips according to any one of [1] to [4], wherein the photoacid generator has an extinction coefficient at a wavelength of 365 nm of 400 mL · g ⁻¹ · cm ⁻¹ or less.
[6] A method for producing a biochip having a base material and a cell non-adhesive film provided on the surface of the base material and having one or more holes or grooves penetrating in the thickness direction,
Applying the photosensitive composition for biochips according to any one of [1] to [5] to the surface of a substrate to form a photosensitive film;
Exposing a portion other than the portion corresponding to the hole or groove of the photosensitive film,
A method for producing a biochip, comprising developing the exposed photosensitive film to form the non-cell-adhesive film.

According to the photosensitive composition for a biochip of the present invention, a cell non-adhesive film in which holes or grooves penetrating in the thickness direction can be formed with good patternability.
According to the method for producing a biochip of the present invention, a cell non-adhesive film in which holes or grooves penetrating in the thickness direction are formed on the surface of a substrate can be formed with good patterning properties.

It is sectional drawing which shows each process in one Embodiment of the manufacturing method of the biochip of this invention.

The meanings of the following terms in this specification are as follows.
A “biochip” is a device that can detect biomolecules such as DNA, proteins, sugar chains, target compounds, etc. in large quantities simultaneously.
“Cyclic ether” means a ring structure having an etheric oxygen atom between some carbon atoms of a saturated hydrocarbon ring.
The “etheric oxygen atom” means an oxygen atom that exists between carbon and carbon atoms.
The “photo acid generator” means a compound that generates an acid when irradiated with light.
“Photosensitive film” means a film made of a photosensitive composition.
The “cell non-adhesive membrane” means a substrate exhibiting cell non-adhesiveness compared to a portion other than the membrane, specifically a membrane having a protein adsorption rate Q lower than that of the portion other than the membrane. The protein adsorption rate Q is measured by the method described in Examples described later.
The “(meth) acryloyloxy group” is a general term for an acryloyloxy group and a methacryloyloxy group.
“(Meth) acrylate” is a general term for acrylate and methacrylate.
“(Meth) acrylic acid” is a general term for acrylic acid and methacrylic acid.
“Light” is a general term for ultraviolet rays, visible rays, infrared rays, electron beams and radiation.
The “absorption coefficient at a wavelength of 365 nm” is a value calculated by the Lambert Beer equation from the relationship between the concentration and the absorbance of a 0.001 to 0.1% by mass methanol solution of a photoacid generator.

[Photosensitive composition for biochip]
The biochip photosensitive composition of the present invention (hereinafter also referred to as “the present photosensitive composition”) includes a copolymer (A) and a photoacid generator (B).
This photosensitive composition may contain other components other than a copolymer (A) and a photo-acid generator (B) in the range which does not impair the effect of this invention.

<Copolymer (A)>
The copolymer (A) has a specific unit (u1) and a specific unit (u2). The copolymer (A) may have a unit (u3) other than the unit (u1) and the unit (u2) as necessary.

(Unit (u1))
The unit (u1) is a unit having a cyclic ether group.
When the copolymer (A) has the unit (u1), the photosensitive composition has photosensitivity. When a part of the photosensitive film formed from the photosensitive composition is selectively exposed, the cyclic ether groups of the unit (u1) are bonded to each other by the action of the acid generated from the photoacid generator (B) in the exposed portion. React to form a crosslinked structure. For example, when epoxy groups react with each other, a —CH (OH) CH ₂ CH ₂ CH (OH) — structure is formed. By forming the cross-linked structure, the solubility of the exposed portion in the developer is lowered. Therefore, when the photosensitive film after exposure is developed, the unexposed part is dissolved and removed, while the exposed part remains as it is, and a cell non-adhesive film having a hole penetrating in the thickness direction is formed. The

The cyclic ether group only needs to be able to react by the action of an acid, such as a monocyclic or polycyclic cyclic ether group containing an epoxy ring, a monocyclic or polycyclic cyclic ether group containing an oxetane ring, etc. Is mentioned.
As the cyclic ether group, at least one selected from the group consisting of an epoxy group, an oxetane group and a 3,4-epoxycyclohexyl group is preferable in terms of excellent reactivity.

The cyclic ether group may be substituted with an alkyl group as long as the reactivity is not impaired. As for carbon number of an alkyl group, 1-6 are preferable.
The epoxy group and the 3,4-epoxycyclohexyl group are preferably unsubstituted. The oxetane group may be unsubstituted or substituted by an alkyl group, and a (3-alkyloxetane-3-yl) group is preferred.

The unit (u1) is also referred to as a monomer represented by the following formula (m1) (hereinafter referred to as “monomer (m1)”) in terms of ease of polymerization, variety of types, and availability. .) Are preferred.
_{^{CH 2 = CR 11 -COO-R}} 12 -R 13 ··· (m1)
R ¹¹ represents a hydrogen atom, a halogen atom or an alkyl group, R ¹² represents an alkylene group or a group having an etheric oxygen atom between carbon atoms of the alkylene group, and R ¹³ represents the cyclic ether group.

Examples of the halogen atom for R ¹¹ include a fluorine atom and a chlorine atom. As an alkyl group, a C1-C4 alkyl group is preferable. R ¹¹ is particularly preferably a hydrogen atom or a methyl group.
As the alkylene group for R ^12, an alkylene group having 1 to 6 carbon atoms is preferable, and a methylene group is particularly preferable from the viewpoint of easy availability of a raw material monomer.
In the group having an etheric oxygen atom between the carbon atoms of the alkylene group, the alkylene group has 2 or more carbon atoms, preferably 2-6. The number of etheric oxygen atoms is preferably one.
As the cyclic ether group for R ^13, the same groups as those described above can be mentioned, and preferred embodiments are also the same.

Examples of the monomer (m1) include glycidyl (meth) acrylate, (3-ethyloxetane-3-yl) methyl (meth) acrylate, 4-hydroxybutyl (meth) acrylate glycidyl ether, and 3,4-epoxycyclohexylmethyl. (Meth) acrylate etc. are mentioned.
A monomer (m1) may be used individually by 1 type, and may use 2 or more types together.
Note that the unit derived from the monomer (m1) has a structure in which the ethylenically unsaturated bond in the monomer (m1) is cleaved to form a single bond.

(Unit (u2))
The unit (u2) is a unit having a group represented by the following formula (1).
When the copolymer (A) has the unit (u2), a film formed from the photosensitive composition (photosensitive film, cell non-adhesive film obtained by exposing and developing the photosensitive film) is formed. Excellent cell non-adhesiveness.

-(R ¹ -O) _n -R ² (1)
However, ^{R 1} is an alkylene group having 2 to 4 carbon atoms, n represents an integer of 1 to 30, ^{R 2} is a hydrogen atom or ^R 3 -X ⁴ (provided that, ^{R 3} is an alkylene group, ^{X 4} Represents a hydrogen atom or a cyano group.

R ¹ may be linear or branched. Examples of R ¹ include CH ₂ , CH ₂ CH ₂ , CH ₂ CH ₂ CH ₂ , CH (CH ₃ ) CH ₂ , CH ₂ CH ₂ CH ₂ CH _{2 and the} like.
R ¹ is preferably a linear alkylene group, particularly preferably CH ₂ CH ₂ from the viewpoint of cell non-adhesiveness.
n is preferably an integer of 2 to 25, particularly preferably an integer of 3 to 25. When n is at least the lower limit of the above range, cell non-adhesiveness is excellent. In addition, the larger n is within the above range, the higher the excluded volume effect, and it is easier to obtain sufficient cell non-adhesiveness with a small amount. If n is below the upper limit of the said range, film forming property will be excellent.

When n is 2 or more, the plurality of types of (R ¹ —O) may be the same or different. If they are different, the arrangement may be random, block, or alternating.
Specific examples of (R ¹ -O) include (CH ₂ O), (CH ₂ CH ₂ O), (CH ₂ CH ₂ CH ₂ O), (CH (CH ₃ ) CH ₂ O), (CH ₂ CH ₂ CH ₂ CH ₂ O) and the like.

R ³ may be linear or branched, and is preferably linear from the viewpoint of non-cell adhesion. The number of carbon atoms of R ³ is preferably 1 to 25, more preferably 1 to 4, 1 or 2 are particularly preferred.
X ⁴ is preferably a hydrogen atom because it is difficult for proteins, and thus cells, to be adsorbed.
R ² is particularly preferably a hydrogen atom or R ³ —X ^{4 in} which X ⁴ is a hydrogen atom, that is, an alkyl group.

The unit (u2) is preferably a unit derived from a monomer represented by the following formula (m2) (hereinafter also referred to as “monomer (m2)”).
_{^{CH 2 = CR 21 -Q 2 -}} (R 1 -O) n -R 2 ··· (m2)
^{However, R} 1, n and ^{R 2} are the same as defined ^{above, R 21} represents a hydrogen atom, a halogen atom or an alkyl group, ^{Q 2} is COO or ^COO-R 22 -NHCOO ^{(However, R 22} is an alkylene group Is shown.)

Examples of R ²¹ include the same as R ^11, and preferred embodiments are also the same.
R ²² may be linear or branched, and is preferably linear from the viewpoint of non-cell adhesion. The number of carbon atoms of R ²² is 1 to 4 is preferred.
Q ² is preferably COO.

Specific examples of the monomer (m2) include the following compounds.
_{CH 2 = CH-COO- (C} 2 H 4 O) 9 -H,
_{CH 2 = CH-COO- (C} 2 H 4 O) 5 -H,
_{CH 2 = CH-COO- (C} 2 H 4 O) 4 -H,
_{CH 2 = CH-COO- (C} 2 H 4 O) 3 -H,
_{CH 2 = CH-COO- (C} 2 H 4 O) 9 -CH 3,
_{CH 2 = CH-COO- (C} 2 H 4 O) 5 -CH 3,
_{CH 2 = CH-COO- (C} 2 H 4 O) 4 -CH 3,
_{CH 2 = CH-COO- (C} 2 H 4 O) 3 -CH 3,
_{CH 2 = CH-COO- (C} 2 H 4 O) 3 -C 2 H 5,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) 9 -H,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) 5 -H,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) 4 -H,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) 3 -H,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) 9 -CH 3,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) 5 -CH 3,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) 4 -CH 3,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) 3 -CH 3,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) 3 -C 2 H 5,
_{CH 2 = CH-COO- (C} 2 H 4 O) g2 - (C 4 H 8 O) g3 -H,
_{CH 2 = CH-COO- (C} 2 H 4 O) g2 - (C 4 H 8 O) g3 -CH 3,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) g2 - (C 4 H 8 O) g3 -H,
_{CH 2 = C (CH 3)} -COO- (C 2 H 4 O) g2 - (C 4 H 8 O) g3 -CH 3 and the like.
In the above formula, g1 represents an integer of 1 to 20, g2 and g3 each independently represents an integer of 1 or more, and g2 + g3 represents an integer of 2 to 30.
A monomer (m2) may be used individually by 1 type, and may use 2 or more types together.

(Unit (u3))
The unit (u3) is a unit other than the unit (u1) and the unit (u2).
However, the copolymer (A) does not have a unit having an organic group having one or more fluorine atoms (hereinafter also referred to as “fluorinated organic group”). Therefore, the unit (u3) does not have a fluorine-containing organic group.

Examples of the unit (u3) include units derived from the monomer (m3) other than the monomer (m1) and the monomer (m2). However, as described above, the unit (u3) does not have a fluorine-containing organic group. Therefore, the monomer (m3) also has no fluorine-containing organic group.
Examples of the monomer (m3) include monomers having no fluorine-containing organic group. Examples of the monomer having no fluorine-containing organic group include methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, n-butyl (meth) acrylate, isobutyl (meth) acrylate, tert-butyl ( (Meth) acrylate, hexyl (meth) acrylate, cyclohexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, octyl (meth) acrylate, decyl (meth) acrylate, isodecyl (meth) acrylate, lauryl (meth) acrylate, stearyl ( Examples include meth) acrylate, benzyl (meth) acrylate, isobornyl (meth) acrylate, adamantyl (meth) acrylate, and dimethylaminoethyl (meth) acrylate.
A monomer (m3) may be used individually by 1 type, and may use 2 or more types together.

(Percentage of each unit)
In the copolymer (A), the molar ratio of unit (u1) / unit (u2) is 15/85 to 95/5, preferably 20/80 to 92/8, and 25/75 to 90/10. Particularly preferred. If this molar ratio is not less than the lower limit of the above range, the patternability of the photosensitive film formed from the photosensitive composition is excellent. When the molar ratio is not more than the upper limit of the above range, the cell non-adhesiveness of the film formed from the photosensitive composition is excellent.

The total ratio of the unit (u1) and the unit (u2) is 65 mol% or more, preferably 70 mol% or more, based on all units (100 mol%) constituting the copolymer (A), 75 Mole% or more is particularly preferable. When the total ratio is equal to or greater than the lower limit, the effects of the units (u1) and (u2) are sufficiently exhibited, and both excellent patterning properties and cell adhesiveness can be achieved.
The upper limit of the total ratio of the unit (u1) and the unit (u2) with respect to all units is not particularly limited, and may be 100 mol%.

In some cases, the sum of the proportion of the unit (u1) and the proportion of the unit (u2) may not be 100 mol%, but the balance in this case is the unit (u3).
Therefore, the ratio of the unit (u3) in the copolymer (A) is 35 mol% or less, preferably 30 mol% or less, particularly preferably 25 mol% or less, based on all units.
The ratio of each unit in the copolymer (A) can be determined, for example, from the integral ratio of peaks peculiar to each unit in the ¹ H-NMR (nuclear magnetic resonance) method.

(Various properties of copolymer (A))
The weight average molecular weight (Mw) of the copolymer (A) is preferably from 5,000 to 200,000, more preferably from 8,000 to 150,000, and particularly preferably from 10,000 to 100,000. When the mass average molecular weight is not less than the lower limit of the above range, the film forming property is more excellent. When the mass average molecular weight is not more than the upper limit of the above range, the flatness of the coating film is more excellent.
The mass average molecular weight (Mw) of the copolymer (A) is a value in terms of standard polymethyl methacrylate measured by gel permeation chromatography (GPC).

The glass transition temperature (Tg) of the copolymer (A) is preferably from -25 to 70 ° C, particularly preferably from -20 to 50 ° C. If the glass transition temperature is not less than the lower limit of the above range, the uniformity of the coating film thickness is more excellent. If the glass transition temperature is not more than the upper limit of the above range, cell non-adhesiveness is more excellent.
The glass transition temperature (Tg) of the copolymer (A) means a midpoint glass transition temperature when changing from a rubber state to a glass state measured by a differential scanning calorimetry (DSC) method.

(Production method of copolymer (A))
The copolymer (A) can be produced by a known polymerization method such as a solution polymerization method, a bulk polymerization method, or an emulsion polymerization method. As the polymerization method, a solution polymerization method is preferable.
A chain transfer agent may be used during the polymerization. By using a chain transfer agent, the mass average molecular weight of the copolymer (A) can be adjusted. Examples of the chain transfer agent include a thiol chain transfer agent represented by the following formula (S1).
HS-CR ⁵ R ⁶ R ⁷ (S1)
However, R ⁵ and R ⁶ are each independently a hydrogen atom or an alkyl group in which part of the hydrogen atom may be substituted, and R ⁷ is an alkyl in which part of the hydrogen atom may be substituted. A group, a cycloalkyl group in which part of the hydrogen atom may be substituted, an aryl group in which part of the hydrogen atom may be substituted, or a heteroaryl group in which part of the hydrogen atom may be substituted Yes, two or three of R ^{5 to} R ⁷ may be linked to form a ring structure.

When a part of hydrogen atoms in the alkyl group of R ^{5 to} R ⁷ are substituted, examples of the substituent include a hydroxyl group. When a part of hydrogen atoms in the cycloalkyl group, aryl group or heteroaryl group of R ⁷ is substituted, examples of the substituent include an alkyl group having 1 to 6 carbon atoms and a carbon atom having 1 to 6 carbon atoms. An alkoxy group, a halogen atom, etc. are mentioned.

R ⁵ and R ⁶ are each preferably a hydrogen atom or a linear or branched alkyl group having 1 to 20 carbon atoms, particularly preferably a hydrogen atom or a methyl group.
R ⁷ includes a straight or branched alkyl group having 1 to 20 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, and an aryl having 6 to 10 carbon atoms, in which part of the hydrogen atoms may be substituted with a hydroxyl group. And a heteroaryl group having 4 to 6 carbon atoms (for example, a furyl group, a pyridyl group, etc.) are preferable.
When two or three of R ^{5 to} R ⁷ are linked to form a ring structure, the ring structure may be an alicyclic structure or an aromatic ring structure. Further, it may be monocyclic or polycyclic. For example, as examples of two of the ring structure formed by combining one of R ⁵ to R ^7, include cycloalkane structure having 3 to 6 carbon atoms.

  Specific examples of the thiol chain transfer agent include dodecanethiol, octadecanethiol, thioglycerol, 2-ethylhexanethiol, cyclohexyl mercaptan, furfuryl mercaptan, and benzylthiol. From the viewpoint of low odor, thioglycerol is particularly preferred.

When a chain transfer agent is used during polymerization, at least one of the main chain ends of the copolymer (A) obtained has a group derived from the chain transfer agent. For example, when the thiol chain transfer agent is used, at least one of the ends of the main chain of the copolymer (A) obtained has a group represented by the following formula (IV).
^{-S-CR 5 R 6 R 7} (IV)
^However, R 5 to R ⁷ are as described above.

<Photoacid generator (B)>
As a photo-acid generator (B), what is necessary is just a compound which generate | occur | produces an acid by irradiating light, for example, a well-known photo-acid generator is mentioned.

As the photoacid generator (B), a photoacid generator having an extinction coefficient of 400 mL · g ⁻¹ · cm ⁻¹ or less at a wavelength of 365 nm is preferable, and a photoacid generator having a absorbance of 200 mL · g ⁻¹ · cm ⁻¹ or less is preferred. Agents are particularly preferred. If the extinction coefficient is equal to or less than the upper limit of the above range, light that becomes noise generated from the cell non-adhesive film of the biochip is suppressed when fluorescence analysis is performed on cells on the biochip. The light that becomes noise is light that is observed as fluorescence when measured by a laser beam excitation type fluorescence analyzer. Although the cause of the generation of such light is not clear, stray light due to autofluorescence or scattering can be considered.
The lower limit of the extinction coefficient at a wavelength of 365 nm of the photoacid generator (B) is not particularly limited, and may be, for example, 1 mL · g ⁻¹ · cm ⁻¹ or more, and 10 mL · g ⁻¹ · cm ⁻¹ or more Good.

  Examples of the photoacid generator (B) include triarylsulfonium salts, diaryliodonium salts, sulfonyldiazomethane, and the like.

  Specific examples of the cation moiety of the triarylsulfonium salt and diaryliodonium salt include triphenylsulfonium, diphenyl-4-methylphenylsulfonium, tris (4-methylphenyl) sulfonium, diphenyl-2,4,6-trimethylphenylsulfonium, 4- (phenylthio) phenyldiphenylsulfonium, diphenyliodonium, 4-isopropyl-4′-methyldiphenyliodonium, 4-methyl-4′-methylpropyldiphenyliodonium, bis (4-tert-butylphenyl) iodonium, 4-methoxyphenyl Examples thereof include phenyliodonium.

  Specific examples of the anion moiety of the triarylsulfonium salt and diaryliodonium salt include trifluoromethanesulfonate, nonafluorobutanesulfonate, hexafluorophosphate, tetrafluoroborate, tris (pentafluoroethyl) trifluorophosphate, and tris (heptafluoropropyl). Examples thereof include trifluorophosphate, tris (nonafluoroisobutyl) trifluorophosphate, bis (nonafluoroisobutyl) tetrafluorophosphate, and the like.

  Specific examples of the sulfonyldiazomethane include bis (phenylsulfonyl) diazomethane, bis (tert-butylsulfonyl) diazomethane, bis (cyclohexylsulfonyl) diazomethane, and bis (p-toluenesulfonyl) diazomethane.

  As the photoacid generator (B), 4- (phenylthio) phenyldiphenylsulfonium tris (heptafluoropropyl) trifluorophosphate, 4- (phenylthio) phenyldiphenylsulfonium tris (4-fluorophenyl) trifluorophosphate, (Phenylthio) phenyldiphenylsulfonium tris (nonafluoroisobutyl) trifluorophosphate, 4- (phenylthio) phenyldiphenylsulfonium bis (nonafluoroisobutyl) tetrafluorophosphate, 4- (phenylthio) phenyldiphenylsulfonium (pentafluoroethyl) trifluorophosphate Diphenyl-2,4,6-trimethylphenylsulfonium trifluoromethanesulfonate, diphenyl-2,4,6-trimethylphenylsulfonium nonafluor Butane sulfonate, bis (phenylsulfonyl) diazomethane, bis (p- toluenesulfonyl) diazomethane is preferred.

Commercially available photoacid generators may be used, such as IRGACURE (registered trademark) 250 manufactured by BASF; CPI (registered trademark) -100P, CPI (registered trademark) -210S manufactured by San Apro; manufactured by Wako Pure Chemical Industries, Ltd. WPAG199 and the like.
A photo-acid generator may be used individually by 1 type, and may use 2 or more types together.

  Examples of other components that can be included in the photosensitive composition include copolymers other than the copolymer (A), solvents, photosensitizers, antioxidants, thermal polymerization initiators, thermal polymerization inhibitors, Other additives such as adhesion promoters, leveling agents, antifoaming agents, suspending agents, dispersants, plasticizers, thickeners and the like can be mentioned.

Since the copolymer (A) is fluid at room temperature, the present photosensitive composition can be applied without containing a solvent, but may further contain a solvent for improving the applicability.
As a solvent, what is necessary is just to melt | dissolve or disperse | distribute a copolymer (A) and a photo-acid generator (B), and what dissolves is preferable.

Specific examples of the solvent include 1H-tridecafluorohexane (Asahi Glass Co., Ltd., ASAHIKLIN (registered trademark) AC2000), 1,1,1,2,2,3,3,4,4,5,5,6. , 6-Tridecafluorooctane (Asahi Glass Co., Ltd., Asahiklin (registered trademark) AC6000), 1,1,2,2-tetrafluoro-1- (2,2,2-trifluoroethoxy) ethane (Asahi Glass Co., Ltd.) , ASAHIKLIN (registered trademark) AE3000), dichloropentafluoropropane (Asahi Glass Co., Ltd., ASAHIKLIN (registered trademark) AK-225), 1, 1, 1, 2, 3, 4, 4, 5, 5, 5- Decafluoro-3-methoxy-2- (trifluoromethyl) pentane (Asahi Glass Co., Cytop (registered trademark) CT-solv100E), 1-methoxynonafluorobutane (3M Japan) Novec (registered trademark) 7100), 1-ethoxynonafluorobutane (manufactured by 3M Japan, Novec (registered trademark) 7200), 1,1,1,2,3,3-hexafluoro-4- (1, 1,2,3,3,3-hexafluoropropoxy) pentane (manufactured by 3M Japan, Novec (registered trademark) 7600), 2H, 3H-perfluoropentane (manufactured by Mitsui DuPont Fluorochemical Co., Ltd., Vertrel (registered trademark) XF) ), 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanol, 4,4,5,5,6,6,7, 7,8,8,9,9,9-tridecafluoro-1-nonanol, hexafluorobenzene, hexafluoro-2-propanol, 2,2,3,3,4,4,5,5-octa Fluoro-containing compounds such as luro-1-pentanol, 1H, 1H, 7H-dodecafluoro-1-heptanol; non-fluorine ketones such as cyclopentanone, cyclohexanone, methyl amyl ketone, 2-butanone; ethyl lactate, benzoic acid Esters such as methyl acid, ethyl benzoate, benzyl benzoate, methyl cellosolve acetate, ethyl cellosolve acetate, propylene glycol methyl ethyl acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene carbonate; diethylene glycol methyl ethyl Examples include ethers such as ether, tetrahydrofuran, dioxane, dimethoxyethane, diethoxyethane, anisole, diglyme, and triglyme. These solvents may be used alone or in combination of two or more.
Among these, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, diethylene glycol methyl ethyl ether, hexafluoro-2-propanol, 2,2,3 because of its high solubility, high boiling point and excellent film-forming properties , 3,4,4,5,5-octafluoro-1-pentanol, 1H, 1H, 7H-dodecafluoro-1-heptanol is preferred.

<Ratio of each component>
1-99.9 mass% is preferable with respect to the whole quantity (100 mass%) of this photosensitive composition, and, as for the ratio of a copolymer (A), 5-80 mass% is especially preferable.
0.1-10 mass% is preferable with respect to the whole quantity of this photosensitive composition, and, as for the ratio of a photo-acid generator (B), 1-5 mass% is especially preferable.
0-98.9 mass% is preferable with respect to the whole quantity of this photosensitive composition, and, as for the ratio of a solvent, 15-94 mass% is especially preferable.
The ratio of components other than the solvent is preferably 0 to 98.9% by mass and particularly preferably 0 to 94% by mass with respect to the total amount of the photosensitive composition.

<Effect>
In this photosensitive composition, since it contains a copolymer (A) having a specific proportion of units (u1) and units (u2) and a photoacid generator (B), it penetrated in the thickness direction. A cell non-adhesive film in which holes or grooves are formed can be formed with good patterning properties. For example, a non-cell-adhesive membrane having pores with a diameter of 50 μm or less can be formed.
In the biochip in which the cell non-adhesive membrane is provided on the surface of the base material, the portion of the cell non-adhesive membrane on the surface is defined as the cell non-adhesive portion, and the hole or groove portion of the cell non-adhesive membrane That is, the part where the substrate is exposed can be used as the cell adhesion part. Such a biochip has advantages such that cells arranged on the biochip gather at the cell adhesion portion, so that observation with a microscope or the like is easy, and the same cell can be observed over time.

[Production method of biochip]
In the biochip manufacturing method of the present invention, a biochip having a base material and a non-cell-adhesive membrane provided on the surface of the base material and having one or more holes or grooves penetrating in the thickness direction is provided. To manufacture.
The cell non-adhesive film is formed using the above-described photosensitive composition. Specifically, the photosensitive composition is applied to the surface of a substrate to form a photosensitive film, and a portion other than the portion corresponding to the hole or groove of the photosensitive film is exposed, and the exposed photosensitive film is exposed. The cell membrane is developed to form the non-cell-adhesive membrane.
Hereinafter, the manufacturing method of the manufacturing method of the biochip of the present invention will be described with reference to the attached drawings. However, the present invention is not limited to the following embodiments.

FIG. 1 is a cross-sectional view showing each step in one embodiment of the biochip manufacturing method of the present invention.
The biochip manufacturing method of the present embodiment includes the following steps.
Step (a): A step of applying the photosensitive composition to the surface of the substrate 10 to form the photosensitive film 12.
Step (b): A step of exposing the photosensitive film 12 in a predetermined pattern.
Step (c): A step of heat-treating the exposed photosensitive film 12 as necessary.
Step (d): A step of developing the exposed photosensitive film 12 with a developer to form a cell non-adhesive film 18 having a predetermined pattern.

(Process (a))
As shown in FIG. 1, the photosensitive composition is applied to the surface of a substrate 10 to form a wet photosensitive film (not shown), and is dried (hereinafter also referred to as pre-baking) as necessary. Thereby, the photosensitive film 12 in a dry state is formed.

As the base material 10, a base material in which cells are more easily adhered to the surface than the cell non-adhesive film 18 formed from the photosensitive composition is typically used.
Examples of the base material 10 include various glass plates; thermoplastic plastic sheets; silicon wafers; metal substrates such as stainless steel (SUS) and aluminum; resin substrates on which metal foils such as copper foils are attached to the surface. Examples of the material of the thermoplastic plastic sheet include polypropylene, polyethylene, polycarbonate, polymethyl methacrylate, and polystyrene. When the biochip is for fluorescence analysis, a substrate having a low fluorescence intensity is preferred.
The substrate 10 is preferably a glass plate, particularly a quartz glass plate, from the viewpoint of heat resistance.

Examples of the coating method include a spray method, a roll coating method, a spin coating method, and a bar coating method.
By prebaking the wet photosensitive film, the solvent (C) is volatilized, and a dry photosensitive film 12 having no fluidity is obtained. Although prebaking conditions change with kinds, compounding ratios, etc. of each component, 50-120 degreeC and 10-2,000 second are preferable.
The thickness of the photosensitive film 12 in a dry state is not particularly limited, but is preferably 0.01 to 100 μm, and more preferably 0.1 to 50 μm.

(Process (b))
After the step (a), as shown in FIG. 1, the photosensitive film 12 is irradiated (exposed) with light from the light source 22 through a mask 20 having a predetermined pattern.
In the exposed portion 14 of the exposed photosensitive film 12, an acid is generated from the photoacid generator (B), and by the action of this acid, the cyclic ether groups of the unit (u1) in the copolymer (A) are exchanged. Formation of a crosslinked structure by reaction, that is, curing proceeds.

The pattern of the mask 20 is a pattern corresponding to the hole or groove of the cell non-adhesive film 18 to be formed. When exposed through the mask 20, portions other than the portions corresponding to the holes or grooves of the photosensitive film 12 are exposed.
The light is preferably a light beam having a wavelength of 100 to 500 nm, more preferably a light beam having a wavelength of 200 to 450 nm, and particularly preferably i-line (365 nm).
As the light source, a high-pressure mercury lamp, (ultraviolet) LED, laser or the like is preferable.
The exposure amount is preferably in the range of 5 to 10,000 mJ / cm ² .

(Process (c))
After the step (b), if necessary, the exposed photosensitive film 12 is subjected to a heat treatment, so-called post-exposure heating (PEB) treatment. Thereby, formation (hardening) of the crosslinked structure in the exposed portion 14 is promoted.
The heat treatment can be performed using a known heating device such as a hot plate or an oven.
The conditions for the heat treatment are preferably 60 to 200 ° C. and 60 to 600 seconds.

(Process (d))
After the step (b) or after the step (c), as shown in FIG. 1, the exposed photosensitive film 12 is developed with a developer, and the unexposed portion 16 is removed to remove the non-exposed portion of the cell. An adhesive film 18 is formed.
Since the exposed portion 14 of the photosensitive film 12 is cured, the solubility in the developer is lower than that of the unexposed portion 16. Therefore, when the exposed photosensitive film 12 is developed, the unexposed portion 16 is dissolved and removed in the developer, while the exposed portion 14 remains undissolved. Thereby, the cell non-adhesive film | membrane 18 in which the hole or the groove | channel 24 was formed in the position of the unexposed part 16 is obtained. The cell non-adhesive film 18 is a cured film made of a cured product of the photosensitive composition.
The protein adsorption rate Q of the cell non-adhesive membrane 18 is preferably 2% or less, more preferably 1% or less, further preferably 0.6% or less, and particularly preferably 0.2% or less. The lower the protein adsorption rate Q, the better the non-cell adhesion.

The developer is not particularly limited as long as it dissolves the copolymer (A) (uncured), and examples thereof include the same solvents as those described above.
Examples of the developing method include a liquid piling method, a dipping method, and a shower method.
The development time is preferably 30 to 180 seconds.
After the development, the cell non-adhesive film 18 may be washed with water (rinse). The rinsing time is preferably 30 to 90 seconds.
After rinsing, the cell non-adhesive film 18 is preferably dried.

Although there is no restriction | limiting in the thickness of the cell non-adhesion film | membrane formed with the manufacturing method of the biochip of this invention, 0.01-100 micrometers is preferable and 0.1-50 micrometers is more preferable.
There are no particular restrictions on the shape of the holes or grooves formed in the non-cell-adhesive membrane.
Although there is no restriction | limiting in the size of a hole, For example, when it is circular shape by planar view, 1-1000 micrometers is preferable in diameter, and 10-500 micrometers is more preferable. Although there is no restriction | limiting in the space | interval of a hole, 1-1000 micrometers is preferable and, as for the distance between adjacent holes, 10-500 micrometers is more preferable.
Although there is no restriction | limiting in the width | variety of a groove | channel, 1-2000 micrometers is preferable and 10-1000 micrometers is more preferable. Although there is no restriction | limiting in the space | interval of a groove | channel, 1-2000 micrometers is preferable and 10-1000 micrometers is more preferable.

EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to these.
Of Examples 1 to 18, Examples 1 to 10 and 14 to 18 are examples, and Examples 11 to 13 are comparative examples.
The evaluation methods and materials used in each example are shown below.

<Evaluation method>
⁽¹ H-NMR)
The ¹ H-NMR spectrum of the compound was measured using an FT-NMR apparatus (manufactured by JEOL Ltd., JNM-AL300).

(Mass average molecular weight, number average molecular weight)
The weight average molecular weight (Mw) and the number average molecular weight (Mn) of the polymer were respectively determined from standard chromatograms with known molecular weights from chromatograms obtained by a high-speed gel permeation chromatography (GPC) apparatus (manufactured by Tosoh Corporation, HLC-8220). It calculated | required using the calibration curve created using the methylmethacrylate sample.

(Glass-transition temperature)
The glass transition temperature (Tg) of the polymer was determined by a differential scanning calorimeter (TA Instruments (DSC Q-100)).

(resolution)
A photosensitive composition was spin-coated on a 4-inch quartz glass substrate at 2,000 rpm for 30 seconds and heated at 100 ° C. for 300 seconds using a hot plate to form a dry coating film (photosensitive film). .
Next, using a high-pressure mercury lamp as a light source, the dried coating film is exposed through a mask (a mask capable of forming a circular hole pattern having a diameter of 50 μm) so that the exposure energy is 800 mJ / cm ² . A part (exposed part) was cured. Then, in order to accelerate | stimulate hardening of a dry coating film, it heated at 120 degreeC for 120 second using the hotplate.
The exposed dried coating film was subjected to dip development for 60 seconds using propylene glycol monomethyl ether acetate (PGMEA) as a developer to form a cured film (cell non-adhesive film) having a hole pattern corresponding to the mask. . The thickness of the cured film at the portion not removed by development was 3.0 μm.
The cured film was observed with a microscope (manufactured by KEYENCE, VHX DIGITAL MICROSCOPE), and it was determined that the resolution was good (◯) when a 50 μm hole was opened. When a 50 μm hole was not opened or a pattern did not remain, it was judged as defective (×).

(Protein adhesion)
The protein adsorption rate Q was determined by the following procedures (1) to (6).
(1) Well preparation:
Dispense 2.2 mL of the photosensitive composition into 3 wells of a 24-well microplate (manufactured by AGC Techno Glass Co., Ltd.) (leaving 2.2 mL for each well) and let stand for 1 day to evaporate the solvent. A dried coating film was formed, and the entire dried coating film was exposed to an exposure energy of 800 mJ / cm ² to form a coating layer (cell non-adhesive film) on the well surface.

(2) Preparation of coloring solution and protein solution:
The coloring solution was 50 mL of peroxidase coloring solution (3,3 ′, 5,5′-tetramethylbenzidine (TMBZ), manufactured by KPL) and 3,3 ′, 5,5′-tetramethylbenzidine peroxidase substrate (TMB). A mixture of 50 mL of Peroxidase Substrate (manufactured by KPL) was used. As the protein solution, a protein (POD-goat anti mouse IgG, Biorad) diluted 16,000 times with a phosphate buffer solution (D-PBS, Sigma) was used.

(3) Protein adsorption:
In the 24-well microplate formed with the coating layer obtained in (1) above, 2 mL of the protein solution was dispensed into each well in which the coating layer was formed (2 mL dispensing for each well), and 1 mL at room temperature. Left for hours. As a blank, in a 96-well microplate without any coating, 2 μL of the protein solution was dispensed into 3 wells (2 μL was dispensed per well).

(4) Well washing:
A phosphate buffer solution (D-PBS (Dulbeccolic acid) containing 0.05% by mass of a surfactant (Tween 20, manufactured by Wako Pure Chemical Industries, Ltd.) was added to the 24-well microplate subjected to protein adsorption in (3) above. Buffered saline), manufactured by Sigma) was washed 4 times (using 4 mL per well).

(5) Dispensing of coloring solution:
Dispense 2 mL of the chromogenic solution (use 2 mL per well) to the 24-well microplate that has been washed in (4) above, perform a color reaction for 7 minutes, and then add 1 mL of 2N sulfuric acid. The color reaction was stopped by using 1 mL per well. In the blank, 100 μL of the coloring solution was dispensed into each well of a 96-well microplate (use 100 μL for each well), color development reaction was performed for 7 minutes, and 50 μL of 2N sulfuric acid was added (per well). The color reaction was stopped.

(6) Absorbance measurement and calculation of protein adsorption rate Q:
150 μL of liquid is taken from each well of the 24-well microplate to which the color developing solution has been dispensed in (5) above, transferred to 3 wells of a 96-well microplate, and a wavelength of 450 nm using MTP-810Lab (Corona Electric Co., Ltd.). The absorbance was measured. Here, the average absorbance of the blank (N = 3) was A _0. The absorbance of the liquid is moved from the 24-well microplates in 96-well microplates and A _1, the protein adsorption rate Q ₁ was determined by the following equation. Three average protein adsorption rate Q ₁ obtained was protein adsorption rate Q. The protein adsorption rate is preferably 2% or less, particularly preferably 1% or less.
Q ₁ = A ₁ / {A ₀ × (100 / amount of dispensed blank protein solution)} × 100
= A ₁ / {A ₀ × (100/2 μL)} × 100 [%]

<Material>
(Monomer)
PEG9MA: methoxy polyethylene glycol methacrylate _{(CH 2 = C (CH 3} ) -COO- (C 2 H 4 O) 9 -CH 3) ( manufactured by NOF Corporation, Blemmer PME400).
PEG3MA: ethoxy polyethylene glycol methacrylate _{(CH 2 = C (CH 3} ) -COO- (C 2 H 4 O) 3 -C 2 H 5) ( manufactured by Polymer Science).
GMA: glycidyl methacrylate (manufactured by Tokyo Chemical Industry Co., Ltd.).
OXMA: (3-ethyloxetane-3-yl) methyl methacrylate (manufactured by Osaka Organic Chemical Industry Co., Ltd.).
ECHMA: 3,4-epoxycyclohexylmethyl methacrylate (manufactured by Daicel).
C12MA: n-dodecyl methacrylate (manufactured by Tokyo Chemical Industry Co., Ltd.).
C18MA: Stearyl methacrylate (manufactured by Tokyo Chemical Industry Co., Ltd.).

(solvent)
PGMEA: Propylene glycol monomethyl ether acetate.
(Polymerization initiator)
V65: 2,2′-azobis (2,4-dimethylvaleronitrile) (manufactured by Wako Pure Chemical Industries, V-65).
(Chain transfer agent)
Thioglycerol (manufactured by Tokyo Chemical Industry Co., Ltd.).
(Photoacid generator)
CPI210S: 4- (phenylthio) phenyldiphenylsulfonium tris (heptafluoropropyl) trifluorophosphate (manufactured by San Apro, CPI (registered trademark) -210S, extinction coefficient at wavelength 365 nm: 98 mL · g ⁻¹ · cm ⁻¹ ).

<Synthesis Example 1>
5.0 g of PEG9MA, 0.65 g of GMA, 0.06 g of V65 and 0.03 g of thioglycerol were dissolved in 8.4 g of PGMEA, and the mixture was stirred at 50 ° C. for 24 hours under a nitrogen atmosphere. And stirred for 2 hours to obtain a polymer PGMEA solution. The solid content (polymer content) of the obtained PGMEA solution, the copolymerization ratio of the polymer in the PGMEA solution, the mass average molecular weight (Mw), the molecular weight distribution (Mw / Mn), and the glass transition temperature (Tg) are shown. It is shown in 2.
However, the copolymerization ratio indicates the molar ratio of each unit constituting the copolymer, and was calculated from signals of 3.6 ppm and 3.8 ppm of ¹ H-NMR (d-acetone, TMS).

<Synthesis Examples 2-18>
A polymer was obtained in the same manner as in Synthesis Example 1 except that the type and amount (g) of the material used for the reaction were as shown in Table 1. Table 2 shows the solid content of the obtained PGMEA solution, the copolymerization ratio of the polymer in the PGMEA solution, the mass average molecular weight (Mw), the molecular weight distribution (Mw / Mn), and the glass transition temperature (Tg).

<Example 1>
Place 10.0 g of the PGMEA solution of the polymer obtained in Synthesis Example 1 and 0.4 g of CPI210S (absorption coefficient is 98 mL · g ⁻¹ · cm ⁻¹ ) as a photoacid generator into a glass vial (20 mL) Stir to a homogeneous solution. The obtained solution was filtered with a PTFE filter having a pore size of 0.20 μm to prepare a photosensitive composition.
Using this photosensitive composition, the resolution and protein adhesion were evaluated. The results are shown in Table 3.

<Examples 2 to 18>
A photosensitive composition was prepared in the same manner as in Example 1 except that the polymer PGMEA solution was changed to the polymer PGMEA solution obtained in Synthesis Examples 2 to 18. Using this photosensitive composition, resolution and protein adhesion were evaluated. The results are shown in Table 3.

In Examples 1-10 and 14-18, the film | membrane in which the hole penetrated in the thickness direction was formed with high resolution, and it was excellent in patterning property. The formed film had low protein adhesion, that is, low cell adhesion.
In Example 11 where the polymer did not have units (u1), the protein adhesion of the formed film was high.
Examples 12 to 13 in which the molar ratio of unit (u1) / unit (u2) in the polymer was less than 15/85 were inferior in patternability.

  The photosensitive composition for a biochip of the present invention is useful for producing a biochip having a patterned cell non-adhesive film.

  DESCRIPTION OF SYMBOLS 10 Base material, 12 Photosensitive film | membrane, 14 Exposure part, 16 Unexposed part, 18 Cell non-adhesion film | membrane, 20 Mask, 22 Light source, 24 Hole or groove | channel.

Claims (6)

It has a unit (u1) having a cyclic ether group and a unit (u2) having a group represented by the following formula (1), and the molar ratio of the unit (u1) / the unit (u2) is 15/85. A copolymer (A) having a ratio of the total of the unit (u1) and the unit (u2) of 65 mol% or more based on the total unit,
A photosensitive composition for biochips, comprising a photoacid generator (B).
-(R ¹ -O) _n -R ² (1)
However, ^{R 1} is an alkylene group having 2 to 4 carbon atoms, n represents an integer of 1 to 30, ^{R 2} is a hydrogen atom or ^R 3 -X ⁴ (provided that, ^{R 3} is an alkylene group, ^{X 4} Represents a hydrogen atom or a cyano group.   The photosensitive composition for biochips according to claim 1, wherein the cyclic ether group is at least one selected from the group consisting of an epoxy group, an oxetane group, and a 3,4-epoxycyclohexyl group. The photosensitive composition for biochips according to claim 1 or 2, wherein the unit (u1) is a unit derived from a monomer represented by the following formula (m1).
_{^{CH 2 = CR 11 -COO-R}} 12 -R 13 ··· (m1)
R ¹¹ represents a hydrogen atom, a halogen atom or an alkyl group, R ¹² represents an alkylene group or a group having an etheric oxygen atom between carbon atoms of the alkylene group, and R ¹³ represents the cyclic ether group. The photosensitive composition for biochips according to any one of claims 1 to 3, wherein the unit (u2) is a unit derived from a monomer represented by the following formula (m2).
_{^{CH 2 = CR 21 -Q 2 -}} (R 1 -O) n -R 2 ··· (m2)
^{However, R} 1, n and ^{R 2} are the same as defined ^{above, R 21} represents a hydrogen atom, a halogen atom or an alkyl group, ^{Q 2} is COO or ^COO-R 22 -NHCOO ^{(However, R 22} is an alkylene group Is shown.) The photosensitive composition for biochips as described in any one of Claims 1-4 whose extinction coefficient in wavelength 365nm of the said photo-acid generator is 400 mL * g <^-1> * cm <^-1> or less. A method for producing a biochip comprising a base material and a cell non-adhesive film provided on the surface of the base material and having one or more holes or grooves penetrating in the thickness direction,
A photosensitive film is formed by applying the photosensitive composition for a biochip according to any one of claims 1 to 5 to the surface of a substrate,
Exposing a portion other than the portion corresponding to the hole or groove of the photosensitive film,
A method for producing a biochip, comprising developing the exposed photosensitive film to form the non-cell-adhesive film.

Images