JP2002340914A - Micronozzle, method for manufacturing the same, spotting method and spotter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a micronozzle for discharging many kinds of solutions from a large number of discharge orifices at the same time through individual flow channels without generating contamination between the solutions to easily form a large number of spots at a stroke, a method for manufacturing the same, a spotting method and a spotter equipped with the micronozzle. SOLUTION: In the micronozzle having four or more mutually independent capillary flow channels and the discharge orifices and injection ports of the flow channels, the center to center distance of the adjacent discharge orifices is 4-10,000 times the diameter of each of the discharge orifices and the center to center distance of the adjacent injection ports is larger than the center to center distance of the adjacent discharge orifices and the diameter of each of the injection ports is larger than that of each of the discharge orifices. The method for manufacturing the micronozzle, the spotting method and the spotter having the micronozzle are also disclosed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a nozzle having a fine discharge port used for various applications, and simultaneously discharges a plurality of kinds of liquids from a plurality of discharge ports and a plurality of fine coating liquids. The present invention relates to a micro nozzle capable of being applied in a dot shape, a method for manufacturing the same, and a spotting method.
The present invention also relates to a spotter for manufacturing a microarray or the like in which a number of probes are fixed as a number of spots on a surface of a substrate.

The micronozzle of the present invention is particularly useful as a spotter nozzle for manufacturing a microarray used as an apparatus for manufacturing so-called DNA chips, immunodiagnostic agents, biosensors and the like.

[0003]

2. Description of the Related Art One of the steps of manufacturing a microarray,
As a method of applying (spotting) the solution of the probe on the substrate in a number of spots, an ink jet method, a photochemical method, a stamp method using a needle (contact method), and the like are known. However, it is quite difficult to spot a large number of different solutions, and only the method of forming spots sequentially or the method of forming a small number of spots at a time and performing them sequentially is known. Did not.

In order to form the desired number of spots at once,
It is expected that it is possible to use a method of simultaneously discharging many types of solutions from a micro nozzle having a required number of discharge ports.However, a different solution is applied to each discharge port of a fine nozzle having a plurality of discharge ports. There is no known method of supplying or connecting pipes to a large number of minute discharge ports, and the method has not been realized.

[0005]

A problem to be solved by the present invention is to simultaneously discharge a large number of coating liquids from a large number of discharge ports through individual flow paths without contamination between the coating liquids. It is an object of the present invention to provide a micro-nozzle capable of forming the above spots at once and easily, a manufacturing method thereof, a spotting method using the same, and a spotter equipped with the micro-nozzle.

[0006]

Means for Solving the Problems The present inventors have intensively studied means for solving the above-mentioned problems, and as a result, the above-mentioned problems were solved by setting the discharge port diameter, the discharge port interval, and the injection port interval to a specific relationship. What can be solved is that a micro nozzle having such a structure is easily formed by adopting a structure in which a member having a large number of discharge ports is fixed to a member having a surface or an inside having a cutout portion serving as a capillary channel. It has been found that these members can be formed by a method in which at least one of the members is adhered in a semi-cured state and irradiated with an active energy beam again to be laminated, using an active energy ray-curable composition as a raw material. Thus, the present invention has been completed. In addition, the present inventors, by using the above-mentioned micro nozzle, without connecting a pump to each inlet independently, to store the coating liquid independently in each inlet formed in a storage tank shape, The inventor has found that the above problem can be easily solved by contacting, pressing, and stamping the micro nozzle with an application object, and has completed the present invention.

That is, the present invention relates to a micro nozzle having four or more capillary channels independent of each other and an outlet and an inlet of each channel, wherein the distance between the centers of the adjacent outlets is reduced. 4 to 10000 times the diameter of the outlet, wherein the distance between the centers of adjacent inlets is larger than the center between adjacent outlets, and the diameter of the inlet is larger than the diameter of the outlet. Is provided.

Further, the present invention is a micro nozzle having four or more capillary channels independent of each other and an outlet and an inlet of each channel, wherein the distance between the centers of adjacent outlets is the same. Manufacture of a micro-nozzle that is 4 to 10000 times the diameter of an outlet, the center-to-center distance of each adjacent inlet is larger than the center-to-center distance of the adjacent outlet, and the diameter of the inlet is larger than the diameter of the outlet. The method

A member (A) having four or more independent capillary flow paths penetrating the member and discharge ports of each flow path
And a flow path in a member connected to the discharge port of the member (A) or a defective portion forming a flow path with the member (A), and is made of a semi-cured active energy ray-curable composition. The member (B) is laminated,

Next, the present invention provides a method for manufacturing a micro nozzle, which comprises irradiating an active energy ray to cure the member (B) and bonding the member (A) and the member (B).

The present invention is also a micro nozzle having four or more capillary channels independent of each other, and an outlet and an inlet of each channel, wherein the distance between the centers of adjacent outlets is the same. Manufacture of a micro-nozzle that is 4 to 10000 times the diameter of an outlet, the center-to-center distance of each adjacent inlet is larger than the center-to-center distance of the adjacent outlet, and the diameter of the inlet is larger than the diameter of the outlet. A method comprising: a member (A) comprising four or more independent capillary channels which penetrate the member and a discharge port of each channel, and comprising a semi-cured active energy ray-curable composition. And a member (B) having a defective portion forming a flow path with the flow path or the member (A) in the member connected to the discharge port of the member (A), and then irradiating with an active energy ray. While curing the member (A), the member (A) and the member ( ) And there is provided a method of manufacturing a micro nozzle, characterized in that adhering.

The present invention also provides a spotting method for applying a coating solution to an object to be coated in a dot-like manner using the micro nozzle. Further, the present invention provides a spotter having the micro nozzle.

[0013]

DESCRIPTION OF THE PREFERRED EMBODIMENTS First, a micro nozzle according to the present invention will be described. The micro-nozzle of the present invention is a micro-nozzle having four or more capillary channels independent of each other, and a discharge port and an injection port of each flow path. 4 to 10000 of outlet diameter
The distance between the centers of adjacent inlets is larger than the distance between the centers of adjacent outlets, and the diameter of the inlet is larger than the diameter of the outlet.

The outer shape of the micronozzle of the present invention is not particularly limited, and may take the shape of an object to be coated or a shape corresponding to an apparatus to which the micronozzle of the present invention is mounted.
For example, a sheet shape (including a film shape, a ribbon shape, and the like).
The same applies hereinafter), plate-like (including convex or concave curved plate-like; the same applies hereinafter), tubular (roller-like), and other molded products of complicated shapes. It is preferable that the shape has a parallel surface. Further, the surface provided with the discharge port (hereinafter, may be referred to as “nozzle surface”) is a convex curved surface (camel-shaped) that is a part of a cylinder, and the opposite side is a flat surface. Particularly preferred. At this time, the diameter of the nozzle surface is preferably 5 cm to 10 cm.
m, more preferably a part of a column of 10 cm to 1 m. The above-mentioned shape refers to the shape of a portion excluding an additional structure such as a spacer and a fixing structure described later.

By using the above-mentioned curved micro-nozzles having nozzle surfaces and sequentially moving the contact surface like a roller, spotting is performed one row at a time from one end of the discharge ports arranged in a matrix. Spotting can be performed accurately from the discharge port.

Alternatively, it is also preferable to form the entire micronozzle of the present invention in a flexible sheet shape. High resolution spotting by pressing a micro nozzle formed into a flexible sheet from the back of the nozzle with a flexible member, and bringing the nozzle surface into close contact with the application target to be spotted, and spotting in that state Becomes possible. In addition, a convex structure acting as a spacer at the time of spotting is provided on the nozzle surface, and when the micro nozzle is brought into contact with an application target (for example, a base material for a microarray), the distance between the discharge port and the application target is made close to a predetermined interval. It is also preferable to maintain the state in order to suppress variation between spots. The spacer preferably has a thickness of 3 to 100 μm,
More preferably, it is 50 μm.

The flow path of the micro nozzle of the present invention is formed as a defective portion of a cured product of the active energy ray curable composition constituting the micro nozzle. By forming a cured product of the active energy ray-curable composition, its formation is facilitated. However, the micro-nozzle of the present invention does not need to be entirely composed of a cured product of the active energy ray-curable composition, and may be partially composed of another material. May be configured.

Preferably, the flow path is connected to one injection port and one discharge port corresponding thereto by one non-branched flow path, but four or more independent flow paths are connected to each other. As long as one outlet is provided, one inlet may be connected to a plurality of, preferably 2 to 10, and more preferably 2 to 4 outlets in a branched flow path. Such a micronozzle is suitable for an application in which a plurality of microarrays are simultaneously manufactured by simultaneously performing four or more spotting operations on a plurality of application objects.

The diameter of the inlet is larger than the diameter of the outlet, and the center distance between the inlets is larger than the center distance between the outlets. This makes it possible to easily inject a plurality of different coating liquids, thereby facilitating connection of a pipe for injecting the coating liquid. The injection port referred to in the present invention refers to the one in which the other end of the flow path is opened on the surface of the micro nozzle, but a pipe may be connected. In this case, the size of the surface of the micro nozzle is defined as the size of the discharge port.

The micro-nozzle of the present invention has a structure in which discharge ports are opened in the same direction, and a plurality of dots can be applied to one application target from a plurality of discharge ports. For example, when the object to be applied is flat, a flat surface, when the object to be applied is a convex curved surface, a corresponding concave curved surface, and when the object to be applied has a step, a corresponding step is formed. Each discharge port is formed so as to open on the surface having the discharge port.

The number of discharge ports is four or more, but usually four to four.
It is preferably 10,000, more preferably 10 to 10,000, and even more preferably 30 to 1,000. When the number of discharge ports is 3 or less, the effect of the present invention is hardly exhibited, and when the number is excessive, manufacture becomes difficult.

The arrangement of the discharge ports is arbitrary, and may be, for example, a linear arrangement, a plurality of rows of a linear arrangement, a matrix arrangement, an alternating arrangement, a circular arrangement, a concentric arrangement, a radial arrangement, etc. , A plurality of rows in a linear arrangement, or a shape (matrix arrangement) arranged in the vertical and horizontal directions. However, the ejection openings in each row may be arranged at the same position, alternately, or obliquely.

Since the micro-nozzle of the present invention aims at spotting in a plurality of independent dots, the distance between the centers of the discharge ports is 4 times or more, preferably 5 times or more, more preferably 5 times or more the diameter of the discharge ports. Is 6 times or more, which is larger than that of a known composite fiber spinning nozzle. Further, the distance between the centers of the discharge ports is 10,000 times or less the diameter of the discharge ports,
Preferably it is 100 times or less, more preferably 10 times or less. If it is smaller than this range, it is difficult to perform spotting in an independent point shape. If it is larger than this range, the nozzle size tends to be large.

The distance between the centers of the discharge ports is arbitrary, and can be, for example, the distance between the centers of the spots of the microarray to be manufactured, but is preferably 2 to 1000 μm, more preferably 5 to 500 μm. . Of course, the center-to-center distance need not be constant, and may be different in the vertical and horizontal directions.

The shape of the discharge port is arbitrary, such as a circle, a hexagon,
It may be rectangular or slit-shaped, but is preferably circular or rectangular. The diameter of the discharge port is preferably from 1 to 500 μm, more preferably from 1 to 300 μm, and most preferably from 3 to 200 μm.
However, non-circular cross-sections are represented by the diameter of a circle having the same cross-sectional area. If it is too small, it will be difficult to manufacture, and if it is too large, it will be impossible to form minute spots.

The discharge port is a flat surface of the micro nozzle,
It may be formed on the upper surface of a curved surface or a trapezoidal convex structure, or may be a cylindrical shape in which the periphery of the discharge port is higher than these surfaces in a wall shape. In particular, when the target portion to be applied is the bottom of the groove-shaped concave portion, the discharge port is formed on the upper plane of the trapezoidal convex structure having a height just reaching the bottom of the groove. Or it is preferable to be formed in the said cylindrical shape.

As a preferred mode of the micro nozzle of the present invention, (1) a member having four or more independent capillary flow paths penetrating the member and a discharge port of each flow path (hereinafter referred to as a “member ( A) ”) and (2) a flow path in a member connected to the discharge port of the member (A), which is made of a cured product of the active energy ray-curable composition, or laminated with the member (A). And a member (hereinafter, referred to as a member (B)) having a deficient portion that forms a flow path on the bottom surface.

Hereinafter, the case where the micro nozzle of the present invention is composed of the above-mentioned member (A) and member (B) will be described, but the description is the same for other structures. Further, in this specification, the member (A) has a posture in which the opening (nozzle surface) of the discharge port is directed downward, and expresses the height, the height, and the like.

First, the independent 4 through the member
The member (A) having at least one capillary flow path and the discharge port of each flow path will be described. The discharge port is provided as an opening of a hole-shaped flow path penetrated through the member (A) (a flow path formed in the member (A) may be referred to as a “flow path (A)”). ing. The diameter and shape of the flow path (A) may be constant or different in the depth direction. Further, the direction of piercing is not necessarily perpendicular to the nozzle surface of the member (A), and the plurality of flow paths (A) may not be parallel to each other.

The outer shape of the member (A) can take any shape according to the shape of the micro nozzle, but can be the same as the preferable shape of the micro nozzle of the present invention described above.
Among them, for example, a planar shape, a trapezoidal shape, and a shape having a convex portion serving as a spacer on the surface are preferable.

The member (A) is preferably formed such that the whole or the nozzle surface is smaller than the member (B), and when used in a contact type, for example, only the vicinity of the discharge port is in contact with the object to be coated. . In particular, when the target portion to be spotted is the bottom of the groove-shaped concave portion, instead of the member (A) being trapezoidal, the width of the member (A) is smaller than the width of the groove of the application target. It is also preferable that the thickness is set to a thickness corresponding to the depth of the groove.

The thickness of the member (A) is arbitrary,
It is preferably from 500 to 500 m, more preferably from 3 to 100 m. If the thickness is too small, manufacturing becomes difficult. If the thickness is too large, it becomes difficult to form a fine discharge port, and the discharge amount during use decreases, making it impossible to form a spot at high speed. As described later, when the member (A) is formed of a hydrophobic material and the member (B) is formed of a hydrophilic material, the thickness of the member (A) is preferably thin. The member (A) may have a defective portion on the upper surface, that is, the back surface of the nozzle surface, which becomes a flow path when laminated with the member (B).

The member (A) may be composed of any material, and may be, for example, glass, crystal such as quartz, metal such as stainless steel, semiconductor such as silicon, ceramic, carbon, or polymer. The member (A) may be a composite formed of different materials, for example, a laminate, but may be composed entirely of the same material, or a laminate of thin film-like members as described below. It is preferable because it is easy to manufacture.

Among these materials, polymers are preferable because the nozzle surface is easily made hydrophobic. The polymer may be a homopolymer or a copolymer, and may be a thermoplastic polymer or a thermosetting polymer. From the viewpoint of productivity, the polymer is an active energy ray-curable composition (hereinafter, referred to as an active energy ray-curable composition).
The active energy ray-curable composition constituting the member (A) is preferably a cured product of the composition (A).

The material constituting the nozzle surface of the member (A) is
The contact angle with water is preferably 45 degrees or more.
It is more preferable that the angle is from about 110 to about 110, and most preferably from about 60 to about 95 (hereinafter, such surface characteristics are referred to as "hydrophobicity"). If the contact angle with water is less than this range, the nozzle surface becomes wet with the liquid introduced into each discharge port,
It tends to induce spot spread and contamination between liquids.

There is no inconvenience due to the high contact angle of the nozzle surface with water, and it may be, for example, 180 degrees.
When the contact angle of the nozzle surface is increased, the inner surface of the hole formed in the member (A), that is, the inner surface of the flow path (A) having the discharge port as an opening tends to increase at the same time. Becomes difficult. The smaller the contact angle of the inner surface of the flow path (A), the more preferable it is 90 degrees or less, and more preferable 70 degrees or less.

From this point, it is also preferable that the member (A) is a composite composed of a plurality of layers, an extremely thin layer on the surface is formed of a hydrophobic material, and the inner layer is formed of a hydrophilic material. . Alternatively, it is also preferable that the member (A) is formed into a thin film and laminated with the hydrophilic member (B). Member (A)
From the viewpoint of durability, it is preferable to use a material having high hardness or a material having good abrasion resistance at least for a portion to be a nozzle surface.

The polymer usable for the member (A) includes
For example, polystyrene, poly-α-methylstyrene, a copolymer of polystyrene and maleic acid, a styrene-based polymer such as a copolymer of polystyrene and acrylonitrile, and a polysulfone-based polymer such as porsulfone and polyethersulfone; (Meth) acrylic polymers such as polymethyl methacrylate and polyacrylonitrile, and polymaleimide polymers,

Polycarbonate polymers, polyolefin polymers, chlorine-containing polymers such as vinyl chloride and vinylidene chloride, cellulosic polymers such as cellulose acetate and methylcellulose, polyurethane polymers,
Polyamide-based polymers, polyimide-based polymers, fluorine-based polymers, polyether-based or polythioether-based polymers such as poly-2,6-dimethylphenylene oxide and polyphenylene sulfide;

Examples include polyether ketone polymers such as polyether ether ketone, polyester polymers such as polyethylene terephthalate and polyarylate, epoxy resins, urea resins, and phenol resins. Among these, styrene-based polymers, (meth) acrylic polymers, polycarbonate-based polymers, polysulfone-based polymers, and polyester-based polymers are preferred from the viewpoint of good adhesion to the member (B).

The polymer that can be used for the member (A) is also preferably a cured product of an active energy ray-curable composition (hereinafter, referred to as “composition (A)”). Forming the member (A) from the cured product of the composition (A) makes it easy to control flexibility, hydrophobicity and the like in a wide range, and the member (B)
It is preferable because it is easy to adhere to the substrate. The composition (A) is the same as the composition (B) described below, except that the ratio of preferred hydrophilicity to hydrophobicity and the preferred hardness are different.

The method of forming the discharge port and the flow path (A) is arbitrary, and includes drilling, laser drilling, lithography (etching), and photolithography (pattern hardening using active energy rays or pattern decomposition using active energy rays. Similarly, micro stereolithography can be used. Among these, the composition (A) is used as the material of the member (A), and the material (A) is obtained by photolithography.
Discharge port and flow path (A) when forming by on-site polymerization of
Is also preferable.

Subsequently, a flow path in a member made of a cured product of the active energy ray-curable composition and connected to the discharge port of the member (A), or a flow path on a surface laminated with the member (A) The member (B) having a defective portion forming the following will be described. Hereinafter, the member (B) will be described with reference to the simple schematic diagrams shown in FIGS. 8 and 9 as an example. Member (B) (2
2) The member (23) is laminated and fixed to the members (A) and (21) so that one end of each member (23) is connected to each of the flow paths (28, 28 ', 28 ", 28'") of the member (A). ), And the other end is provided on the surface of the member (B) (23) at the injection port (27, 2).
7 ', 27 ", 27'") and open capillary channels (25, 26, 25 ', 26', 25 ", 2").
6 ", 25"",26"") (hereinafter, only one of the four systems will be shown and described as necessary).

The flow path may be formed as a capillary tube inside the member (B), or provided with a deficient portion (25) on the surface, and the surface of the member (B) (22) having the deficient portion. Is laminated on the member (A) with the member (A) (21) side, so that the side surface of the defective portion (25) and the member (A) (2)
A capillary channel (25) may be formed on the surface laminated with 1). The member (B) may have both the defective portion (25) and the capillary channel (Example 1, FIGS. 1 to 1).
7).

The flow paths (25, 26) are for supplying liquid to be discharged to the flow paths (A) (28) connected to the discharge port (24), and have a diameter larger than the diameter of the discharge port. Is preferred. By doing so, the flow path resistance is reduced,
High-speed spotting becomes possible. The other end of the channel is opened as an inlet (27) in the members (B) and (23) or between the members (A) and (B).

The distance between the centers of the inlets (27) is
4) is larger than the center-to-center distance, and “the center-to-center distance of the injection port /
The ratio of the distance between the centers of the discharge ports is greater than 1 and the ratio is 3 to
It is preferably 300, more preferably 5 to 100, and most preferably 10 to 50. In the present invention, this ratio can be made large. If the ratio is too small, the effect of the present invention will not be exhibited, and if it is too large, the nozzle will be too large and disadvantageous.

By making the distance between the centers of the inlets larger than the distance between the centers of the outlets, a large-diameter flow path can be formed to reduce the pressure loss, and the connection of the piping to the large-diameter inlet can be reduced. This facilitates liquid supply to the inlet.

The cross-sectional area of the flow path (25, 26) is arbitrary, but is preferably larger than the area of the discharge port, and is smallest at the portion in contact with the members (A) and (21).
It is more preferable to make the largest in 7). With such a structure, the flow path resistance can be reduced.

Each flow path (25, 25 ', 25 ", 2
5 ′ ″) is also preferable to make the lengths the same, from the viewpoint of equalizing the pressure loss of each flow path. Alternatively, the flow path (25, 2
It is also preferable to adjust the cross-sectional area of 5 ′, 25 ″, 25 ′ ″) to equalize the pressure loss between the flow paths.

The inlet (27) may be open on any surface of the member (A), the member (B), or both, and the inlet (27) of the member (A) (21) and the member (B) (22) may be opened. An opening may be provided therebetween, but it is preferable that the opening is provided on the surface of the member (B) opposite to the surface of the member (A).

The discharge ports (24, 24 ', 24 ", 2
4 ′ ″) and the inlets (27, 27 ′, 27 ″, 27 ′ ″) are arbitrary. For example, an inlet is formed at the other end of the channel radially drawn from the outlet. A shape having an outlet group near the center of the nozzle, or a shape in which an inlet is formed at the other end of the flow path drawn in one direction from the outlet, and the outlet group and the inlet group are separated. When the outlets are arranged in a matrix, it is preferable that the inlet is an enlarged matrix arranged on the upper surface of the member (B) in the same order as the outlets.

The injection port (27) has a structure for connecting to a mechanism for sending the discharged liquid, for example, a driving mechanism of an ink jet system such as a piezo element or a heating mechanism, for example, a conical structure of the injection port, an injection port. It may be formed into a surrounding convex structure, O-ring holding structure, etc., or a mechanism for connecting piping, such as a hose port, a screw hole, a luer fitting (a standard that can fix a syringe in about 1/4 turn) A connector, an O-ring holding structure, or the like may be provided, or a pipe may be fixedly connected.

Alternatively, the inlet (27) may be in the form of a well. In the case of a well shape, the liquid is sent only by its own weight or movement by capillary action without a special liquid sending mechanism. A tube for applying pressure with a water column, a mercury column, an oil column, or the like may be connected to the well, or a pressurizing mechanism using a pressurized gas or the like may be provided. Further, the member (B) may be provided with other structures, for example, an ink-jet type driving mechanism such as a piezo element or a heating mechanism, a diaphragm pump, a base frame valve, a filtration mechanism connected to a flow path, and the like. good.

However, the above-mentioned inlet may be provided in the member (A) as an opening of a hole-shaped flow path (A) penetrated through the member (A).

The outer shape of the member (B) is arbitrary as long as it can be laminated and closely adhered to the member (A), and is the same as the shape shown in the case of the member (A). The height (thickness) of the member (B) is arbitrary, but is preferably 10 μm to 3 μm.
0 mm, and more preferably 100 μm to 10 mm. If the thickness is too small, the production becomes difficult. If the thickness is too large, it becomes difficult to form a fine channel, and the discharge amount during use decreases, making it impossible to form spots at high speed. In addition,
In this specification, the height of the member (B) is also expressed by the posture of the member (B) stacked on the member (A) placed with the nozzle face down.

The member (B) is formed of a cured product of an active energy ray-curable composition (hereinafter, referred to as “composition (B)”). By being formed from the cured product of the composition (B), it is easy to form a structure having a flow path inside,
Control of hydrophilicity and flexibility becomes easy.

The member (B) is preferably formed of a laminate in which a plurality of members each formed of a cured product of the composition (B) are laminated. As an example of the member (B) made of such a laminate, a member (B1) having an inlet and a flow path in a member connected to the inlet, a member (A) and a member (B1) are laminated. And a member (B2) having a flow path in the member or a defective portion forming a flow path with the formed surface.

More specifically, the member (B) is formed by laminating two members (member 22 and member 23), and the layers constituting the member (B) are formed by a capillary channel (25). It is preferable to have a defective portion (25).

When the member (B) is a laminate, the direction of lamination of the members constituting the member (B) is arbitrary, for example, parallel to, perpendicular to, or perpendicular to the contact surface with the members (A) and (21). The members (A) and (21) may be stacked at other angles.
It is preferable to be laminated in parallel on the contact surface with the substrate.

Hereinafter, the member (B) is a laminate, and a plurality of members (22, 23) constituting the member (B) are formed in parallel with the contact surface with the member (A). A description will be given of a state in which the members are stacked and fixed on the members (A) and (21) placed with the side down. Such a structure has, for example, a deficient portion (25) composed of a deficient portion of a layer constituent material in a member (22), and the member (22) is connected to another member (23).
The defective portion (25) becomes a capillary channel (25) by being sandwiched and laminated by one of the members (A) and (21).

The deficient portions (25, 26) may be, for example, linear, or have any shape that is a cross section of the flow path (26) penetrating the member (23) vertically (in the thickness direction). Is also good. When the defective portion is linear, the line is not limited to a straight line, and may be an arbitrary line such as a curve or a zigzag. In this case, the flow path is formed in the member (22) in parallel with the member (22).

When the defective portions (25, 26) have a cross-sectional shape of the flow path, they are preferably circular, but may have any shape such as a rectangle or a slit. In this case, the positions of the deficient portions of the respective members may be slightly shifted from each other to form a diagonally formed flow path.

When the member (22) is in contact with the members (A) and (21), the defective portion (25) is formed in the flow path (A) (28).
The member (B) is formed by stacking a plurality of members, and the member (B) is formed by stacking a plurality of members.
When it comes into contact with 3), it is provided so as to be connected to a defective portion (26) provided in another member (23). The formed channel may be opened as an inlet (27) at the edge of the member forming the member (B) (that is, the side surface of the nozzle),
An opening may be provided in the member (23) farthest from the member (A) (that is, the back surface of the nozzle).

In the case where the member (B) is formed by laminating a plurality of members, the number of members having a linear defect (25) is one.
Layers may be used, but when the number of discharge ports of the nozzle is large, a large number of layers having linear defect portions are laminated to form a large number of layers parallel to the contact surface between the member (A) and the member (B). It is preferable to form a flow path (Example 1 and FIGS. 1 to 7).
Specifically, the member (B) comprises (1) a member (B1 ′) having an inlet and a flow path in a member connected to the inlet.
(2) a member (B3 ') having a defective portion forming a flow path on a surface on which the members constituting the member (B) are laminated, a member (B3') having a flow path in the member, and (3) a member (A) and A member having a member (B2 ') having a defective portion that forms a flow path by the surface laminated with the member (B3') and a flow path in the member. In this case, the member (B3 ′) may be formed by laminating a large number of members, and the number of the member (B3 ′) is preferably 2 to 40, and more preferably 4 to 30. preferable.

The member (B2 ') is provided in each layer when a member having a linear defect and a member having a hole defect are alternately laminated (Example 1 and FIGS. 1 to 7). This is preferable because interference of the position of the flow path is avoided and the degree of freedom of design is increased. In this case, the number of members having a linear defect is two.
-20, more preferably 3-15. If it is less than this, it becomes difficult to form a nozzle having a large number of discharge ports, and if it is too large, it becomes difficult to manufacture.

In the case where the discharge ports are arranged in a matrix and the injection ports are arranged in an enlarged matrix (for example, in Example 1 and FIGS. 1 to 7), the member (B2) has a plurality of defective portions having a flow path. It is preferable that the flow path formed in the layer close to the member (A) communicates with the outer discharge port, and the member farther from the member (A) be assigned to the discharge port closer to the center. . Therefore, when N is a natural number, 2
When manufacturing a micro nozzle with N rows of discharge ports,
It is preferable to have a member having a defective portion serving as a horizontal flow path laminated on the N layer.

The shape of the defective portion (25) is linear, and the portion where the linear defective portion becomes a flow path is the defective portion (2).
The width of 5) becomes the width of the flow path, and the member (2
The thickness of 2) becomes the height of the flow path. When the member (B) is composed of a plurality of members, the thickness of each member is 1 to 1000, respectively.
μm is preferred. When the shape of the defective portion is a hole (26) and the hole-shaped defective portion is a cross section of the flow path (26), the diameter thereof is preferably 1 to 1000 μm.
m, more preferably 10 to 500 μm.

If the thickness is smaller or smaller, manufacturing becomes difficult, and the liquid supply speed to the discharge port is insufficient. If the thickness is larger or larger, the nozzle becomes excessively large. However, this is not always the case when the defective portion serving as the flow channel has another structure such as a well (26).

The members (B) and (22) and the members (A) and (21)
The lamination method with the discharge port (24) and the flow path (A) (28)
And the flow path (25) are connected to each other, and the member (A) and the member (B) are fixed in a relative position, for example, by screwing, caulking, fitting, compression by another member, or the like. Although possible, it may be adhesion, adhesion, fusion, integration by surface dissolution and drying, integration by polymerization, and the like.

The bonding includes, for example, the use of a solvent type adhesive, the use of a solventless type adhesive, and the use of a fusion type adhesive. The fusion includes fusion by heat, ultrasonic waves, high frequency, or the like. The integration by dissolution and drying may be performed by applying or absorbing a solvent to the surface of the member to be fixed. The integration by polymerization forms the member to be fixed as a semi-cured product of the active energy ray-curable composition, and then further irradiates the active energy ray in a state in which the member is in close contact with the other member to be cured and simultaneously bonded. Method. Among these, integration by polymerization using an active energy ray-curable composition is preferable because it does not block fine voids and has high productivity.

When the member (B) is composed of a plurality of members, the method of fixing the members constituting the member (B) is arbitrary, but the method of fixing the members (A) and (B) is not limited. A similar method can be used. Among them, integration by polymerization using the composition (B) is preferable because it does not block fine voids and has high productivity.

When the member to be fixed does not have a deficient portion, another preferable fixing method is to irradiate the active energy ray insufficiently with the composition (B) spread on the liquid surface. It is also preferable to form a cured or semi-cured product of the member to be bonded and bond the same by the same method as above. When it is necessary to provide a defective portion on the member, the defective portion can be formed by laser drilling or the like after fixing.

The liquid for developing the composition (B) is arbitrary, and examples thereof include water (including an aqueous solution; the same applies hereinafter), silicon oil, mercury, and halogenated naphthalene, but water is preferred. It is also preferable to add a solvent to the composition (B). For the liquid surface development, the composition (B) may be dropped or dropped from the liquid surface, or may be extruded into the liquid.

When the member (B) is composed of a plurality of members, each member may be formed continuously. For example, the composition (B)
Patterning irradiation of active energy rays on the uncured layer of
Without removing the uncured composition (B) in the non-irradiated portion, the second member (B2) made of the composition (B)
A layer is formed (or a member (B) is placed below the liquid level of the composition (B)).
The member (B1) is sunk to a depth corresponding to the thickness of 2)).
In 2), a method of irradiating an active energy ray with patterning and repeating this process (micro stereolithography) may be adopted.

At this time, in order to prevent the active energy rays irradiated by patterning from hardening only the surface layer and not from hardening the non-irradiated portion of the lower layer, the active energy ray absorption of the composition (B) should be increased. The method can be carried out by a method of preventing the light from reaching the lower layer, a method of using active energy rays which are easily absorbed, for example, an electron beam, a method of focusing only on the surface layer using an optical system having a large aperture ratio, and the like.

The composition (B) forms a cured resin by irradiation with active energy rays and contains an active energy ray-curable compound. The composition (B) may be an active energy ray-curable compound alone, a mixture of a plurality of types of active energy ray-curable compounds, or may contain a third component. The active energy ray-curable compound is arbitrary as long as it can be cured by an active energy ray, and may be any one such as radical polymerizable, anionic polymerizable, and cationic polymerizable.

The active energy ray-curable compounds are not limited to those which polymerize in the absence of a polymerization initiator, and those which polymerize with an active energy ray only in the presence of a polymerization initiator can also be used. The active energy ray-curable compound is preferably an addition polymerizable compound, preferably a compound having a polymerizable carbon-carbon double bond as an active energy ray-polymerizable functional group. ) Acrylic compounds, vinyl ethers, and maleimide compounds that cure even in the absence of a photopolymerization initiator are preferred.

Further, the active energy ray-curable compound is
From the viewpoint of high shape retention in a semi-cured state and high strength after curing, a compound that forms a crosslinked polymer by polymerization is preferable. Therefore, a compound having two or more polymerizable carbon-carbon double bonds in one molecule (hereinafter, “having two or more addition polymerizable functional groups in one molecule” is referred to as “polyfunctional”. Is more preferable.

Examples of the polyfunctional (meth) acrylic monomer which can be preferably used as the active energy ray-curable compound include diethylene glycol di (meth) acrylate, neopentyl glycol di (meth) acrylate, and 1,6-hexanediol diacrylate. (Meth) acrylate, 2,2'-bis (4- (meth) acryloyloxypolyethyleneoxyphenyl) propane,

2,2'-bis (4- (meth) acryloyloxypolypropyleneoxyphenyl) propane, neopentyl glycol dihydroxy dipivalate di (meth) acrylate, dicyclopentanyl diacrylate, bis (acryloxyethyl) hydroxy 2 such as ethyl isocyanurate and N-methylenebisacrylamide
Functional monomers,

Trimethylolpropane tri (meth) acrylate, trimethylolethanetri (meth) acrylate, tris (acryloxyethyl) isocyanurate,
Examples include trifunctional monomers such as caprolactone-modified tris (acryloxyethyl) isocyanurate, tetrafunctional monomers such as pentaerythritol tetra (meth) acrylate, and hexafunctional monomers such as dipentaerythritol hexa (meth) acrylate.

As the active energy ray-curable compound, a polymerizable oligomer (also referred to as a prepolymer) can be used.
50,000. Examples of such a polymerizable oligomer include (meth) acrylate of epoxy resin, (meth) acrylate of polyether resin, (meth) acrylate of polybutadiene resin, and (meth) acryloyl at the molecular terminal. And a polyurethane resin having a group.

Examples of the maleimide-based active energy ray-curable compound include 4,4'-methylenebis (N-
Phenylmaleimide), 2,3-bis (2,4,5-trimethyl-3-thienyl) maleimide, 1,2-bismaleimideethane, 1,6-bismaleimidehexane, triethyleneglycolbismaleimide, N, N ' -M-
Phenylenedimaleimide, m-tolylenedimaleimide,
N, N'-1,4-phenylenedimaleimide, N, N '
-Diphenylmethane dimaleimide, N, N'-diphenylether dimaleimide, N, N'-diphenylsulfone dimaleimide,

1,4-bis (maleimidoethyl) -1,
4-diazoniabicyclo- [2,2,2] octane dichloride, 4,4'-isopropylidenediphenyl dicyanate.N, N '-(methylenedi-p-phenylene)
Examples thereof include a bifunctional maleimide such as dimaleimide, and a maleimide having a maleimide group such as N- (9-acridinyl) maleimide and a polymerizable functional group other than the maleimide group. Maleimide monomers include vinyl monomers, vinyl ethers, and polymerizable carbons such as acrylic monomers.
It can be copolymerized with a compound having a carbon double bond.

These active energy ray-curable compounds can be used alone or in combination of two or more. Further, the active energy ray-polymerizable active energy ray-curable compound may be a mixture of a polyfunctional monomer and a monofunctional monomer for the purpose of adjusting the viscosity, increasing the adhesiveness or the tackiness in a semi-cured state, and the like. .

The monofunctional (meth) acrylic monomers include, for example, methyl methacrylate, alkyl (meth)
Acrylate, isobornyl (meth) acrylate, alkoxy polyethylene glycol (meth) acrylate, phenoxydialkyl (meth) acrylate, phenoxy polyethylene glycol (meth) acrylate,
Alkylphenoxy polyethylene glycol (meth) acrylate, nonylphenoxy polypropylene glycol (meth) acrylate, hydroxyalkyl (meth)
Acrylate,

Glycerol acrylate methacrylate, butanediol mono (meth) acrylate, 2-hydroxy-3-phenoxypropyl acrylate,
Acryloyloxyethyl-2-hydroxypropyl acrylate, ethylenoxide-modified phthalic acid acrylate, w-carboxyaprolactone monoacrylate,
2-acryloyloxypropyl hydrogen phthalate, 2-acryloyloxyethyl succinic acid,

Acrylic acid dimer, 2-acryloyloxypropylhexahydrohydrogen phthalate,
Fluorine-substituted alkyl (meth) acrylate, chlorine-substituted alkyl (meth) acrylate, sodium sulfonic acid (meth) acrylate, 2-methylpropane-2-acrylamide sulfonic acid, (meth) acrylate containing a phosphate group,

Sulfonate group-containing (meth) acrylates, silano group-containing (meth) acrylates, ((di)
(Alkyl) amino group-containing (meth) acrylate, quaternary ((di) alkyl) ammonium group-containing (meth) acrylate, (N-alkyl) acrylamide, (N, N-
Dialkyl) acrylamide, achloroyl morpholine and the like.

Examples of the monofunctional maleimide-based monomer include N-methylmaleimide, N-ethylmaleimide,
N-alkylmaleimides such as N-butylmaleimide and N-dodecylmaleimide, N-alicyclic maleimides such as N-cyclohexylmaleimide, N-benzylmaleimide, N-phenylmaleimide, N- (alkylphenyl) maleimide, N-dialkoxyphenylmaleimide, N- (2-chlorophenyl) maleimide,

2,3-dichloro-N- (2,6-diethylphenyl) maleimide, 2,3-dichloro-N- (2
N- such as -ethyl-6-methylphenyl) maleimide
(Substituted or unsubstituted phenyl) maleimide, maleimide having halogen such as N-benzyl-2,3-dichloromaleimide, N- (4'-fluorophenyl) -2,3-dichloromaleimide, and hydroxyphenylmaleimide A maleimide having a hydroxyl group, a maleimide having a carboxy group such as N- (4-carboxy-3-hydroxyphenyl) maleimide,

A maleimide having an alkoxy group such as N-methoxyphenylmaleimide, a maleimide having an amino group such as N- [3- (diethylamino) propyl] maleimide, and a polycyclic aromatic compound such as N- (1-pyrenyl) maleimide Group maleimide or N- (dimethylamino-4
And maleimides having a heterocyclic ring such as -methyl-3-coumarinyl) maleimide and N- (4-anilino-1-naphthyl) maleimide.

The composition (B) preferably contains an amphiphilic polymerizable compound copolymerizable with the active energy ray-curable compound which is an essential component of the composition. By containing the amphiphilic compound, it becomes possible to hardly swell the cured product in water, and to form a surface that is hydrophilic and has low adsorption to biological components.

The amphiphilic polymerizable compound contains both a hydrophilic group and a hydrophobic group in the molecule, and the active energy ray-curable compound contained in the active energy ray-curable composition is irradiated with the active energy ray. It has a polymerizable functional group that can be copolymerized. When the active energy ray-curable compound is a compound having two or more polymerizable carbon-carbon unsaturated bonds in one molecule, the amphiphilic polymerizable compound is one or more polymerizable compounds in one molecule. Preferably, the compound has a carbon-carbon unsaturated bond.

The amphiphilic polymerizable compound does not need to be a cross-linked polymer, but may be a cross-linked polymer. The amphiphilic polymerizable compound is also one that is uniformly compatible with the active energy ray-curable compound. Compatibility in this case refers to no macroscopic phase separation, and includes a state where micelles are formed and dispersed stably.

The amphiphilic polymerizable compound is a compound having a hydrophilic group and a hydrophobic group in the molecule and being compatible with both water and a hydrophobic solvent. In this case as well, the term "compatible" means that no phase separation occurs macroscopically, and also includes a state where micelles are formed and dispersed stably. The amphiphilic polymerizable compound has a solubility in water of 0.5% or more by mass at 0 ° C. and a solubility in a cyclohexane: toluene = 5: 1 (mass ratio) mixed solvent at 25 ° C. of 25% by mass. % Is preferable.

As used herein, the term “solubility” means, for example, that the solubility is 0.5% or more by mass percentage means that at least 0.5% by mass percentage of a compound can be dissolved. Although 0.5% of the compound does not dissolve in the solvent, it does not include those in which only a small amount of the solvent is soluble. When a compound having a solubility in water or a solubility in a mixed solvent of cyclohexane: toluene = 5: 1 (mass ratio) lower than these values is used, it is difficult to satisfy both high surface hydrophilicity and water resistance. Become.

When the amphiphilic polymerizable compound has a nonionic hydrophilic group, particularly a polyether-based hydrophilic group, the balance between hydrophilicity and hydrophobicity is determined by the Griffin's HLB value (HLB value). It is preferably 11 to 16 and more preferably 11 to 15. Outside this range, it is difficult to obtain a molded article having high hydrophilicity and excellent water resistance, or the combination and mixing ratio of the compounds for obtaining the molded article are extremely limited, and the performance of the molded article is poor. It tends to be stable.

The hydrophilic group possessed by the amphiphilic polymerizable compound is arbitrary, for example, a cationic group such as an amino group, a quaternary ammonium group and a phosphonium group, and an anionic group such as a sulfone group, a phosphate group and a carbonyl group. A nonionic group such as a hydroxyl group, a polyethylene glycol group or an amide group, or a zwitterionic group such as an amino acid group. The amphiphilic polymerizable compound is preferably a compound having, as a hydrophilic group, a polyether group, particularly preferably a polyethylene glycol chain having a repeating number of 6 to 20.

As the hydrophobic group of the amphiphilic polymerizable compound,
Examples include an alkyl group, an alkylene group, an alkylphenyl group, a long-chain alkoxy group, a fluorine-substituted alkyl group, and a siloxane group. The amphiphilic polymerizable compound is preferably a compound having an alkyl group or an alkylene group having 6 to 20 carbon atoms as a hydrophobic group. 6 to 2 carbon atoms
The 0 alkyl group or alkylene group may be contained, for example, in the form of an alkylphenyl group, an alkylphenoxy group, an alkoxy group, a phenylalkyl group, or the like.

The amphiphilic polymerizable compound has a polyethylene glycol chain having a repeating number of 6 to 20 as a hydrophilic group,
Further, it is preferable that the compound has an alkyl group or an alkylene group having 6 to 20 carbon atoms as a hydrophobic group.
Among these amphiphilic polymerizable compounds, nonylphenoxy polyethylene glycol (n = 8 to 17) (meth)
Acrylate and nonylphenoxy polypropylene glycol (n = 8 to 17) (meth) acrylate are particularly preferred.

The preferred ratio of the active energy ray-curable compound to the amphiphilic polymerizable compound varies depending on the type and combination of the active energy ray-curable compound and the amphiphilic polymerizable compound. The amount of the amphiphilic polymerizable compound is preferably at least 0.1 part by mass, more preferably at least 0.2 part by mass, per 1 part by mass. If it is less than this value, it becomes difficult to form a highly hydrophilic surface.

The proportion of the amphiphilic polymerizable compound is preferably at most 5 parts by mass, more preferably at most 3 parts by mass, per 1 part by mass of the other active energy ray-curable compound. . When the ratio of the amphiphilic polymerizable compound to 1 part by mass of the active energy ray-curable compound is 5
If the amount is larger than the parts by mass, the polymer tends to be swellable with water, and the polymer constituting the liquid contact portion tends to gel.

By appropriately selecting the mixing ratio of the active energy ray-curable compound and the amphiphilic polymerizable compound, it is possible to produce a cured product which does not gel in a wet state and has high hydrophilicity and low adsorptivity. Can be done. As the hydrophilicity of the amphiphilic polymerizable compound becomes relatively stronger, for example, as the HLB value of griffin becomes larger, the preferable addition amount becomes smaller.

In the composition (B), if necessary, a photopolymerization initiator, a polymerization retarder, a polymerization inhibitor, a solvent, a thickener, a modifier, a colorant, and the like may be mixed and used. it can. The photopolymerization initiator that can be mixed and used as necessary in the composition (B) is active with respect to the active energy ray used in the present invention, and can polymerize the active energy ray-curable compound. There is no particular limitation as long as it is a radical polymerization initiator, for example, a radical polymerization initiator, an anionic polymerization initiator or a cationic polymerization initiator.

As such a photopolymerization initiator, for example, p-tert-butyltrichloroacetophenone, 2,2
2'-diethoxyacetophenone, 2-hydroxy-2
Acetophenones such as -methyl-1-phenylpropan-1-one and benzophenone, 4,4'-bisdimethylaminobenzophenone, 2-chlorothioxanthone, 2-methylthioxanthone, 2-ethylthioxanthone and 2-isopropylthioxanthone. Ketones,

Benzoin, benzoin methyl ether,
Examples include benzoin ethers such as benzoin isopropyl ether and benzoin isobutyl ether, benzyl ketals such as benzyl dimethyl ketal and hydroxycyclohexyl phenyl ketone, and azides such as N-azidosulfonyl phenyl maleimide.
Further, a polymerizable photopolymerization initiator such as a maleimide-based compound can be used.

When the photopolymerization initiator is mixed and used in the composition (B), the amount of the nonpolymerizable photopolymerization initiator is preferably 0.005 to 20% in terms of mass percentage, and 0.1 to 5%. %
Is particularly preferred. Photopolymerization initiator is polymerizable,
For example, a polyfunctional or monofunctional maleimide-based monomer exemplified as the active energy ray-polymerizable active energy ray-curable compound may be used. The amount used in this case is not limited to the above.

Examples of the polymerization retarder or polymerization inhibitor that can be contained in the composition (B) include α-methylstyrene,
Examples of the active energy ray-polymerizable compound such as 2,4-diphenyl-4-methyl-1-pentene include a vinyl monomer having a low polymerization rate and a hindant phenol such as tert-butylphenol. When a light beam is used as the active energy ray, it is preferable to use a polymerization retarder and / or a polymerization inhibitor together with a photopolymerization initiator in order to improve patterning accuracy.

Examples of the thickener which can be mixed and used in the composition (B) as needed include, for example, chain polymers such as polystyrene. The modifier which can be mixed and used as needed in the composition (B) includes, for example, hydrophobic compounds such as silicone oil and fluorine-substituted hydrocarbon which function as a water repellent and a release agent; Water-soluble polymers such as polyvinylpyrrolidone and polyethylene glycol functioning as an adsorption inhibitor are exemplified. Examples of the colorant that can be mixed and used in the composition (B) as needed include arbitrary dyes and pigments, fluorescent dyes, and ultraviolet absorbers.

[0111] The present invention also provides a manufacturing method capable of preferably manufacturing the micronozzle of the present invention.
The first method for manufacturing a micro nozzle according to the present invention includes: a member (A) having four or more independent capillary flow paths penetrating the member and a discharge port of each flow path; A flow path in a member connected to the discharge port, or a member (B) having a defective portion forming a flow path with the member (A) and being made of a semi-cured active energy ray-curable composition is laminated. Then, the member (B) is cured by irradiating with an active energy ray, and the member (A) and the member (B) are bonded together. Hereinafter, for simplification of description, unless otherwise specified, coating includes casting. Also,
The coating shall include the casting.

In the first production method of the present invention, first, an active energy ray-curable composition (composition (B)) for forming a member (B) on a temporary support is applied, Preferably, an uncured coating is formed.

The temporary support used in the production method of the present invention is capable of coating or casting the composition (B) thereon and curing the composition (B). After that, it can be removed by any method such as peeling, dissolving, and decomposing. The shape of the temporary support does not need to be particularly limited, and can take a shape according to the purpose of use.

For example, the composition (B) may be in the form of a sheet (including a film, a ribbon, or a belt), a plate, a coating, a roll, or a molded article having a complicated shape. It is easy to apply or cast on the surface, and from the viewpoint of easily irradiating the active energy ray, the surface to be adhered is a flat surface, or a secondary curved surface shape obtained by bending a flat surface,
It is particularly preferable that the sheet is a flexible sheet.

The temporary support may be a composite, such as a coating formed on any support. The temporary support may also be printed with squares, drawings, alignment symbols, and the like. The material of the temporary support is not particularly limited as long as the above conditions are satisfied, and examples thereof include polymers (polymers), metals, glasses, crystals such as quartz, ceramics, and semiconductors such as silicon. Among these, polymers and metals are particularly preferred.

The polymer used for the temporary support may be a homopolymer or a copolymer, and may be a thermoplastic polymer or a thermosetting polymer. May be. From the viewpoint of productivity, it is preferably a thermoplastic polymer or an active energy ray-curable crosslinked polymer.

In the case where the temporary removal of the support is due to peeling, polyolefin is considered to be difficult to dissolve in many types of compositions (B) and to be easily peeled from the cured product. Polymers, chlorine-containing polymers, fluorine-containing polymers, polythioether-based polymers, polyetherketone-based polymers, and polyester-based polymers are preferably used.

When the temporary removal of the support is due to dissolution, for example, a water-soluble resin such as polyvinylpyrrolidone or polyethylene glycol, a resin soluble in alkali such as a carboxyl group-containing resin, an amino group or the like. An acid-soluble resin such as a quaternary ammonium salt-containing resin is preferably used.

The temporary support may be composed of a polymer blend or a polymer alloy, may be a laminate or other composite, or may be a surface-treated material. Further, the temporary support may contain additives such as modifiers, colorants, fillers, reinforcements, and the like. The surface treatment is intended for preventing dissolution by the composition (B), for facilitating the separation of the composition (B) from the cured product, and for improving the wettability of the composition (B). And so on.

The surface treatment method is optional, and examples thereof include a corona treatment, a plasma treatment, an ultraviolet ray treatment, an electron beam treatment, a sulfonation treatment, a fluorination treatment, a primer treatment with a silane coupling agent, a surface graft polymerization, and a rubbing. Physical processing and the like.

When the composition (B) is thinly coated thereon, the temporary support may be wet with the composition (B) or have a low repelling force. preferable. That is, the contact angle with the composition (B) used is 90.
Degrees or less, more preferably 45 degrees or less, and most preferably 25 degrees or less.

When the temporary support is made of a material having a low surface energy, for example, polyolefin, fluorine-based polymer, polyphenylene sulfide, polyether ether ketone, etc., the temporary support is treated by surface treatment. It is preferable to reduce the contact angle with the composition (B) to be used.

However, it is necessary to select the degree of the treatment so that the composition (B) cured by the surface treatment does not adhere so strongly that the composition (B) cannot be peeled off. As these surface treatment methods, for example, corona discharge treatment, plasma treatment, ultraviolet treatment, primer treatment and the like are preferable. The control of the wettability can be carried out by selecting a modifier to be blended with the temporary support in addition to the surface treatment.

Examples of the modifier that can be contained in the temporary support include hydrophobic agents (water repellents) such as silicone oil and fluorine-substituted hydrocarbons, water-soluble polymers, surfactants, and silica gels. And a hydrophilic agent such as an inorganic powder. Examples of the coloring agent that can be contained in the temporary support include arbitrary dyes and pigments, fluorescent dyes and pigments, and ultraviolet absorbers. Reinforcing materials that can be included in the temporary support include, for example, inorganic powders such as clay, and organic and inorganic fibers and fabrics.

Although the thickness of the uncured coating film to be applied to the temporary support slightly changes due to shrinkage at the time of curing, the thickness of the uncured coating film is approximately the thickness of the cured product layer. It is almost the same as the thickness of the member (B) in the micro nozzle of the invention. Further, the composition (B) to be applied is composed of the member (A)
May be the same or different from the composition (A).

As a method for applying the composition (B) to the temporary support, any coating method that can be applied on the support can be used. For example, a spin coating method, a roller coating method , A casting method, a dipping method, a spray method, a bar coater method, an XY applicator method, a screen printing method, a letterpress printing method, a gravure printing method, extrusion from a nozzle and casting. When the composition (B) is applied particularly thinly, a method in which a solvent is added to the composition (B) and then the solvent is volatilized may be adopted.

A part of the uncured coating film of the composition (B) applied on the temporary support, which is to be a flow path in the member (B) connected to the discharge port of the member (A), A portion serving as a defective portion forming a flow path on a surface laminated with the other member (B) (the member B2 or the member B2 ′) constituting the member (A) and the member (B), or an inlet. The active energy ray is irradiated except for the portions (ie, these portions that are defective portions) to semi-cure the irradiated portion of the composition (B), while the active energy ray of the composition (B) is not cured. The irradiated portion is left as an uncured portion (hereinafter, this operation may be referred to as “patterning exposure” or simply “exposure”).

The term "semi-cured" as used herein means that the composition (B) is cured to such an extent that the composition becomes non-flowable or hardly flowable and that unreacted active energy ray-polymerizable functional groups remain. Say Such a semi-cured state can be obtained by irradiating an active energy ray in an amount insufficient for complete curing. If the irradiation amount of the active energy ray is too small and the degree of curing is insufficient, the selectivity of removing the uncured portion becomes insufficient, so that a resin-defected portion having a desired shape is not formed, and the member (A In the step of fixing the composition (B), the composition (B) enters the defective portion of the member (A) or the member (B), thereby blocking the formed flow path or causing a change in the flow path cross-sectional area.

On the other hand, if the irradiation amount is excessive and the degree of curing is excessive, the semi-cured coating film loses flexibility and decreases in adhesiveness, resulting in incomplete adhesion. A suitable degree of semi-curing can be determined by simple experiments in the system used.

The shape of the pattern in the patterning exposure, that is, the shape of the portion to be a defect is determined by the flow path in the member (B) connected to the discharge port of the member (A), the member (A) and the member (B). It is a shape that becomes a defective portion or an injection port that forms a flow path on a surface laminated with another member (B) to be configured.
The defective portion can be formed not only with the discharge port and the flow path, but also with another structure, for example, an injection port, if necessary, at the same time.

Examples of the active energy rays that can be used in the present invention include light rays such as ultraviolet rays, visible light rays, infrared rays, laser rays, and radiated lights; ionizing radiation rays such as X-rays, gamma rays, and radiated lights; Examples include particle beams such as beta rays and heavy particle beams. Among these, ultraviolet light and visible light are preferred in terms of handleability and curing speed, and ultraviolet light is particularly preferred.

For the purpose of accelerating the curing speed and performing the curing completely, it is preferable that the irradiation with the active energy ray is performed in a low oxygen concentration atmosphere. The low oxygen concentration atmosphere is preferably a nitrogen stream, a carbon dioxide stream, an argon stream, a vacuum or a reduced pressure atmosphere.

An exposure method, that is, a method of irradiating a portion other than a portion to be a defective portion with an active energy ray is arbitrary. For example, masking and irradiating an unnecessary portion or irradiation with an active energy beam such as a laser beam Photolithography techniques such as scanning can be used.

In the first method for manufacturing a micro nozzle of the present invention, after exposure, the uncured portion of the uncured composition (B) is removed to form a defective portion (hereinafter, this operation is referred to as “development”). In some cases). The development method is optional, and examples thereof include a method of blowing off with compressed air or the like, absorption with a filter paper or the like, flushing with a non-solvent liquid flow such as water, and dissolution, volatilization or decomposition with a solvent. Of these, flushing with a non-solvent liquid stream or dissolution with a solvent is preferred. Also, flushing and dissolving are performed by ultrasonic cleaning,
It can be arbitrarily selected, for example, shaking in a liquid, washing with a discharged liquid or a spray liquid.

The size of the defect formed by patterning exposure and development is not always the same as the size of the non-irradiated portion of the active energy ray (non-exposed portion), and may be larger than the size of the portion of the non-irradiated active energy ray. Sometimes it becomes smaller. That is, the type and irradiation amount of the active energy ray,
It can vary depending on the reactivity of the active energy ray-curable compound, the type and amount of the active energy ray polymerization initiator, the amount of the polymerization inhibitor and the retarder added, and the developing method. For example, when the amount of irradiation light is large, the size of the defective portion tends to be smaller than the size of the non-exposed portion.

Composition (B) Coated on Temporary Support
After the development, the semi-cured coating film is brought into contact with the member (A), and further irradiated with an active energy ray in that state to obtain the composition (A)
Is further cured and adhered to the member (A). However, to further cure the semi-cured coating film of the composition (B) means that the cured coating film of the composition (B) is bonded to the member (A) with sufficient strength, and the cured material layer of the composition (B) Means that the temporary support is cured to the extent that it can be removed. Therefore, it is not always necessary to cure until the polymerizable reactive groups have completely disappeared.

The active energy ray irradiation in this step was performed to such an extent that the temporary support could be removed but the polymerizable reactive groups in the composition (B) were not completely eliminated, and the surface of the member (B) was exposed. It is also preferable to increase the strength with which other members are fixed to the substrate. For example, there is a case where a structure such as a spacer is fixedly formed on the surface of the member (B) in the same manner as the formation of the member (B) after the temporary support is removed.

As the active energy ray that can be used for curing for fixing in this step, the active energy ray used in the step of semi-curing the composition (B) can be used. It doesn't have to be the same.

After bonding the member (B) to the member (A), the member (B) is transferred to the member (A) by removing the temporary support from the member (B). The method of removing the temporary support is arbitrary, and may be peeling, dissolving, decomposing, melting, or volatilizing, but in terms of high productivity, peeling is preferred.
Peeling in a liquid such as water is also preferred.

When the member (B) comprises a plurality of members, a member is formed from the composition (B) in the same manner as described above, and the composition (B) is further formed on the member in the same manner as described above. It can be manufactured by repeatedly forming another member constituting the member (B) from B). That is, after forming the member (B1) from the composition (B),
On the member (B1), a member (B
A member (B) made of the same or different composition (B) as in 1)
2) The method of forming and laminating is mentioned. After the member (B1 ′) is formed from the composition (B), a member made of the same or different composition (B) from the member (B1 ′) is further formed on the member (B1 ′) in the same manner as described above. (B3 ') is repeatedly formed at least once, and a member (B2') made of the same or different composition (B) from member (B1 ') or (B3') is formed on the member (B3 '). There is a method of laminating.

At this time, when the member (B) is composed of a plurality of members, the cut-off portions serving as the flow paths of the members are arranged so that the positions do not overlap when viewed from above, so that a linear shape independent of each member is formed. A flow path can be formed, but when the positions overlap, an independent two-stage flow path is formed by sandwiching a member having a hole-shaped flow path serving as a vertical flow path between the members. be able to. The member to be transferred and bonded may not have a defective portion. In this case, the defective portion can be formed by laser ablation or the like after lamination and bonding.

When the member (B) is composed of a plurality of members, the order of forming the members is arbitrary, and may be from the side in contact with the member (A) or from the side opposite to the member (A). . Further, after the member (A) is laminated with the member (B2) or the member (B2 ′) that is a part of the member (B), the member (A) is further laminated on the member (B2) or the member (B2 ′). The member (B1) or the member (B3 ′) may be stacked.

The second method for producing a micro nozzle according to the present invention is characterized in that the active energy ray-curable composition has four or more independent capillary channels penetrating the member and a discharge port of each channel. A member (A) made of a semi-cured product of (a) and a member (B) having a flow path in a member connected to the discharge port of the member (A), or a member (B) having a defect formed by the member (A). And then irradiating active energy rays to cure the member (A) and adhere the member (A) to the member (B) to produce the micro nozzle of the present invention.

The second method for producing the micro nozzle of the present invention is the same as that of the member (A) except that the composition (A) was used instead of the composition (B) explained in the first production method. )
To form a semi-cured coating film, and laminate it to the member (B).
The member (A) and the member (B) are bonded by further irradiating an active energy ray to cure the member (A).

In the second method for manufacturing a micro nozzle according to the present invention, the defective portion formed as the non-irradiated portion of the active energy ray is a defective portion serving as a flow path or a defective portion serving as an injection port. The defective portion serving as a flow path may be a linear defective portion forming a flow path flowing in a direction parallel to the resin layer, and a hole-shaped penetrating through the resin layer flowing in a direction perpendicular to the resin layer. It may be a defect. In the development, the uncured composition (A) in the unexposed portion may not be completely removed, and the bottom of the defective portion may have a groove shape that does not reach the surface of the support. Although it is possible to form such a groove-shaped defective portion and provide a through hole by laser drilling or the like at a necessary portion, it is preferable to form a flow path penetrating the front and back by development.

Next, the spotting method of the present invention will be described. The spotting method of the present invention is a method of applying (spotting) a coating solution to an application target in a dot-like manner using the micro nozzle of the present invention.
Preferably 10 to 10000, more preferably 30 to 3
000, most preferably 50-1000 different solutions are spotted simultaneously. Of course, as a plurality of different solutions, coating solutions having the same components and compositions can be used. Note that, in the spotting method of the present invention, the contact between the micro nozzle and the application target includes a contact via a spacer, and the contact between the discharge port and the application target includes a contact via the spacer. Make it not exist.

The arrangement of spots to be spotted at the same time is arbitrary, but is preferably arranged in rows or in a matrix. According to the microarray manufacturing method of the present invention, one microarray can be manufactured by one spotting operation. However, when the number of spots to be formed is particularly large, one microarray is manufactured by a plurality of spotting operations. You may. In this case, it is preferable to use a plurality of micro nozzles and spot them on a substrate sequentially or in an arbitrary order.

The spotting method of the present invention is a method in which a coating liquid is simultaneously discharged from each discharge port using the micro-nozzle according to the present invention so as to apply (spot) to an object to be coated in a dot-like manner. Simultaneous ejection enables high-speed spotting, and simplifies the device for ejecting the application liquid.

In the spotting method of the present invention, it is preferable that the application liquid is applied by bringing the application object close to or in contact with the nozzle surface in a direction substantially perpendicular to the nozzle surface, and thereafter, the application liquid is separated again in a direction substantially perpendicular to the nozzle surface. By applying by this method, it is possible to apply such that the dots are uniform in shape and size, particularly the shape of the dots is circular. The control of the distance between the micro nozzle and the object to be coated may be performed by moving the micro nozzle or by moving the object to be coated.

The spotting method of the present invention can employ a method of stamping, contacting, pressing or non-contacting the micro nozzle to the object to be coated. In the case of stamping, contacting and pressing, when the micro nozzle has a spacer on the nozzle surface or when other spacers are used, the discharge port does not contact the application target and must be close to the specific interval become. By providing a spacer,
The distance between the ejection port and the object to be coated can be easily kept constant, and even if the spotting speed is increased, the spot size can be made uniform and the reproducibility can be improved, thereby improving the spotting speed.

The vertical and horizontal positions of the micro nozzle and the object to be coated can be arbitrarily determined. However, when spotting is stamping or pressing, and supply of a liquid to be described later is by gravity, the nozzle is It is preferable to move from top to bottom and stamp or press.

From the discharge port, for example, a hemispherical shape (hereinafter, a shape obtained by cutting a part of a sphere by a plane is referred to as a “hemispherical shape”)
When attaching the extruded liquid to the application target,
The ejected liquid may be extruded after approaching the object to be applied, or may be approached after extruding the ejected liquid, or simultaneously. When a pump is used, it is preferable to use a method of extruding at a constant speed and approaching the application object at regular time intervals to perform quantitative spotting.

The distance between the discharge port and the object to be coated during spotting is preferably 0.2 to 10 times the diameter of the discharge port, and more preferably 0.5 to 3 times the diameter of the discharge port. With this range, the spot shape, position, and spot interval can be accurately controlled, and the spotting speed can be improved.

However, in the case where the supply of the discharge liquid described later is caused by gravity or capillary action, and when the supply speed is reduced, it is preferably 0 to 3 times the diameter of the discharge port, more preferably the discharge port. 0 to 1 times the diameter of That is, the method of contacting the ejection port with the application target without providing a spacer is also available.
Although the spotting speed is low, it is preferable because a small spot can be formed. In any case, in the spotting method of the present invention, the distance between the discharge port and the application target is preferably smaller than the diameter when the amount of the application liquid to be spotted is spherical. That is, there is a moment when the coating liquid does not fly in the air and adhere to the application target, but adheres to both the micro nozzle and the application target.

The method of supplying the discharge liquid to the discharge port in the present coating method is arbitrary, but is preferably a spontaneous supply by gravity or capillary action. This can be performed, for example, by injecting the discharge liquid into an inlet in the form of a liquid storage tank. Attach a pipe filled with application liquid or other liquid to the inlet,
The supply speed of the coating liquid may be increased by the liquid column pressure, or the discharge liquid may be extruded from the discharge port into a hemisphere. Around the time when an appropriate liquid column height is selected, it is possible to stabilize the state in which the discharged liquid is extruded from the discharge port in a hemispherical shape. Further, by adjusting the liquid column opening, the amount of the hemispherical ejection liquid can be adjusted, and the size of the spot can be adjusted. This supply method is preferable because a device for spotting can be simplified, and even when a large number of spots are formed at the same time, it is not necessary to connect a pipe to each inlet.

The supply of the discharge liquid to the discharge port may be performed by a pump or the like. This makes it possible to adopt a method in which the liquid is extruded in a hemispherical shape from the ejection port and adheres to the application target placed close to the ejection port. In this method, a pump such as a syringe pump, a gear pump, an ironing pump, a diaphragm pump, a piezo element,
It can be used for pushing by pulse-shaped compression in the middle of a diaphragm or a flexible pipe by an electromagnetic actuator, a pneumatic actuator, or the like, opening and closing of a valve, and pressurization of a compressed air.

In order to prevent the spot from spreading due to bleeding after the spotting operation, or especially when the method for producing a microarray of the present invention is a stamp method, that is, a method in which the nozzle surface is in contact with the object to be coated. It is also preferred to adjust the viscosity of the liquid to be spotted to control the amount. The viscosity is 5-500
mPa · s (cps), preferably 10 to 1
More preferably, it is 00 mPa · s.

The method of adjusting the viscosity is arbitrary, but a method in which a water-soluble polymer or oligomer is added to and dissolved in a coating solution is preferable. The water-soluble polymer or oligomer is arbitrary, and a polymer or oligomer having a nonionic, cationic, or anionic hydrophilic group can be used. However, the compound having a nonionic hydrophilic group is not compatible with a biochemical substance to be plotted. Preferable because of little action, for example, polyethylene glycol, polyvinylpyrrolidone, poly (N-substituted) acrylamide, polyvinyl alcohol,
Polyhydroxymethylstyrene and the like can be preferably used.

The diameter of the applied spot changes greatly depending on the surface characteristics of the object to be applied, such as bleeding after spotting, but also depends on the size and shape of the discharge port of the micro nozzle. Therefore, it is preferable that the diameter of the micro nozzle discharge port is 1/10 to 1/2 of the diameter of the target spot. The distance between the centers of the spots is determined by the distance between the centers of the discharge ports of the micro nozzle. It is preferable to dry immediately after spotting for the purpose of preventing deformation of spots due to bleeding and contamination with adjacent spots. The drying method is optional,
Hot air drying, infrared drying, and vacuum drying are preferred.

When it takes time and temperature to dry, for example, by chemically binding the components in the coating solution to the object to be coated, it is preferable to keep moisturized or heated. The spotting method of the present invention enables one microarray to be manufactured by one spotting operation. However, when the number of spots to be formed is particularly large, a plurality of micro nozzles can be used to apply to a coating object. It is also preferable to perform spotting in an arbitrary order to produce one microarray.

The spotter of the present invention (apparatus for applying a coating solution to a coating object in a dot-like manner) has the above-mentioned micro nozzle. It is an apparatus having a mechanism for spotting according to the sequence of the spotting method according to the present invention. The spotter of the present invention is optional except that it has a mechanism for mounting a micro nozzle, a mechanism for holding an object to be coated, and a mechanism for discharging a coating liquid from the micro nozzle.

As a mechanism for discharging the coating liquid from the micro nozzle, a mechanism for contacting, pressing, or stamping the micro nozzle with the object to be coated, or a mechanism for applying an impact while the micro nozzle is in contact with the object to be coated. Or piezo element,
Heating elements, electromagnetic actuators, pneumatic actuators, open / close valves, mechanisms for pushing out the coating liquid in a pulsed manner by the impact of flexible pipes, and pumps and pneumatics such as syringe pumps, gear pumps, and ironing pumps A pressure mechanism can be used.

It is preferable that the spotter of the present invention has a mechanism capable of changing the distance between the micro nozzle and the object to be coated, and setting the contact or the predetermined distance.

The spotter of the present invention preferably has a drying device. The method of the drying device is arbitrary, but hot air drying, infrared drying and vacuum drying are preferred. When time and temperature are required until drying, such as when components in the coating solution are chemically bonded to the application target, the spotter of the present invention also preferably has a moisturizing mechanism or a heating mechanism.

The spotter of the present invention can manufacture one microarray by one spotting operation. However, when the number of spots to be formed is particularly large, a plurality of micronozzles are mounted. It is also preferable to use an apparatus for spotting an application object in an arbitrary order and manufacturing one microarray. Alternatively, it is also preferable that the device is equipped with a plurality of micro nozzles, spotted on a plurality of substrates simultaneously, and simultaneously manufacturing a plurality of micro arrays.

[0166]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to examples, but the present invention is not limited to the scope of these examples. In the following examples, "part"
Represents "parts by mass" unless otherwise specified, and "%" represents percent by mass.

<Active Energy Ray> Using a Multilight 200 type light source unit manufactured by Ushio Inc.
Ultraviolet rays having an intensity in nm of 50 mW / cm ² were irradiated in a nitrogen atmosphere.

<Measurement Method> The measurement in the examples was performed by the following method. [Measurement of Tensile Modulus and Elongation at Break] The sheet sample was cut into a strip having a width of 10 mm and a length of 100 mm to obtain a sample for measurement. These samples were 24 ± 1 ° C., 55 ± 5 humidity.
% Was left in the room for 16 hours or more before measurement. "Strograph V1" manufactured by Toyo Seiki Seisakusho as a tensile tester
-C "in an atmosphere of 24 ± 1 ° C. and 55 ± 5% humidity with a distance between grippers of 80 mm and a tensile speed of 20 mm / min.

[Measurement of Solubility of Polymerizable Compound in Water] A mixed solution of 0.5 part of the polymerizable compound (b) and 99.5 parts of water at 0 ° C. was prepared, vigorously stirred, and stirred at 0 ° C. for 24 hours. After standing for a while, the presence or absence of phase separation was visually determined.

[Measurement of Solubility of Polymerizable Compound in Hydrophobic Solvent] 62.5 parts of cyclohexane and 1 part of toluene
A mixed solvent of 2.5 parts of cyclohexane and toluene was prepared, and 25 parts of the polymerizable compound (b) and 75 parts of a mixed solvent of cyclohexane and toluene were mixed and vigorously stirred at 25 ° C. After standing for a while, the presence or absence of phase separation was visually determined.

[Measurement of contact angle with water]
After allowing to stand at 1 ° C. and a humidity of 55 ± 5% for 24 hours, measurement was carried out using a contact angle meter CA-X manufactured by Kyowa Interface Science at the same temperature and humidity as above, with a stabilization time of 3 minutes.

<Preparation of active energy ray-curable composition>
The preparation method of the active energy ray-curable composition used in the examples is shown below. [Preparation of Composition A1] As an active energy ray-curable compound, a trifunctional urethane acrylate oligomer (“Unidick V426” manufactured by Dainippon Ink and Chemicals, Inc.)
3 ") 10 parts, dicyclopentanyl diacrylate (" R-684 "manufactured by Nippon Kayaku Co., Ltd.) 90 parts, 2,4-diphenyl-4-methyl-1-pentene (Kanto Chemical And 1-hydroxycyclohexyl phenyl ketone (“Irgacure 184” manufactured by Ciba Geigy) as an ultraviolet polymerization initiator.
The components were mixed to prepare composition A1.

[Composition B1] As a crosslinkable polymerizable active energy ray-curable compound, 60 parts of a trifunctional urethane acrylate oligomer (“Unidick V4263” manufactured by Dainippon Ink and Chemicals, Inc.), and 1,6- 20 parts of hexanediol diacrylate (“New Frontier HDDA” manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) and nonylphenoxy polyethylene glycol (n = 17) acrylate (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) as an amphiphilic polymerizable compound "N-177E", HLB value = 14.64, soluble in water or a mixed solvent of cyclohexane and toluene), and 20 parts of 2,4-diphenyl-
0.5% of 4-methyl-1-pentene (manufactured by Kanto Chemical Co., Ltd.)
Parts B and 1 part of 1-hydroxycyclohexylphenyl ketone (“Irgacure 184” manufactured by Ciba Geigy) as a photopolymerization initiator were uniformly mixed to prepare composition B1.

Example 1 (Preparation of Member) As a temporary support, a polypropylene biaxially stretched sheet (“FOR” manufactured by Nimura Chemical Co., Ltd., thickness: 30)
The composition A1 was applied to a corona-treated surface of a [μm, one-sided corona-treated] (hereinafter referred to as an OPP sheet) (not shown) using a 50 μm bar coater, and a photomask was used. Ultraviolet rays are irradiated for 2 seconds to a portion other than the portion formed with the discharge port (2) and the flow path (A) (13) of the member (A) to form a semi-cured coating film having lost fluidity. Then, the uncured composition A1 in the non-irradiated portion was immersed in a 50% aqueous solution of ethanol and removed by an ultrasonic line for 5 seconds, and a 4 × 4 matrix having a diameter of 100 μm and a center distance of 300 μm was arranged in a matrix. Outlet (2) and channel (A) (1
3) was formed to form a 35-μm-thick member A1 (1) formed on a temporary support.

250 bar instead of 50 μm bar coater
2 except that a μm bar coater was used, composition B1 was used in place of composition A1, and the pattern of the photomask was to form a defect having the shape shown in FIG. Similarly, the first layer (3) of the member (B) having a thickness of about 185 μm and formed of the cured product of the composition B1 using the OPP sheet as a temporary support (not shown) Was formed. The first layer (3) of the member (B) is provided at a position where the distance between the outer rows is 10 mm from the position (4) corresponding to the outer two rows of the discharge ports (2) of the member A1 (1). A linear defect (6) having a line width of 150 μm and serving as a lateral flow path leading to the 4 × 2 rows of hole-shaped defects (1) having a diameter of 1 mm is formed. Also, the member A1
A hole-shaped defective portion (7) having a diameter of 200 μm is provided at a position corresponding to 4 × 2 rows inside the discharge port (2) of (1).

Separately, similarly to the first layer (3) of the member (B), the first member (B) has the same shape as that shown in FIG. Similar to the layer (3), a hole-shaped defective portion (4 ′) provided at a position corresponding to 4 × 2 rows outside the discharge port (2) of the member A1 (1), the member A1
A hole-shaped defective portion (4 ') provided at a position corresponding to the outer 4 × 2 rows of the discharge port (2) of (1), a hole provided at a position corresponding to the inner 4 × 2 rows 4 × 2 rows of hole-shaped defects having a diameter of 1 mm provided at positions corresponding to the hole-shaped defects (7 ′) and the hole-shaped defects (5) of the first layer (3) of the member (B). Part (5 ') of the shape shown in FIG.
The second layer (8) of the member (B) was formed.

Separately, similarly to the first layer (3) of the member (B), a position (7 ") corresponding to the two rows of ejection openings on the center side of the member A1 having the shape shown in FIG. , 4 × 2 rows of 1 m in diameter provided at a position where the distance between the centers of the rows is 6 mm
150 μm line width to each of the hole-shaped defects (9 ″)
4 mm × 4 rows of 1 mm in diameter provided at positions corresponding to the linear defect portion (10) of m and the hole-shaped defect portion (5 ′) of the second layer (8) of the member (B). The third layer (11) of the member (B) having the shape shown in FIG. 4 and having the hole-shaped defective portion (5 ″) was formed.

Separately, the coating thickness of the composition (B) is 2 m
m and the irradiation of the ultraviolet rays for 10 seconds, in the same manner as the other layers of the member (B), in the same manner as the other layers of the member (B), and the hole-shaped defect (5 ″) of the third layer (11) of the member (B) and At a position corresponding to (9 ″), a layer provided with a hole-shaped defective portion (5 ′ ″) and (9 ′ ″) having a diameter of 1 mm is formed, and 12 mm × 12 m
The periphery was cut off together with the temporary support except for the area of m to form a fourth layer (12) of the member (B) having the shape shown in FIG.

(Adhesion of Members) The fourth layer (1) of the member (B)
2) and the third layer (11) of the member (B) are brought into close contact with each other by aligning the positions of the hole-shaped defects, and the member (B) is placed in a nitrogen atmosphere.
The composition (B) forming these layers was irradiated with ultraviolet rays for 3 seconds from the side of the third layer (11) to advance curing of the two members. Then, the temporary support (not shown) is peeled off from the third layer (11) of the member (B), and the 12 mm × 12 mm portion in contact with the fourth layer (12) of the member (B) is removed. The periphery was excised, leaving behind.

Further, similarly, the second layer (8) constituting the member (B), the first layer (3) constituting the member (B), and the member A1 (1) are sequentially adhered thereon. Member (B)
The temporary support (not shown) of the fourth layer (12) constituting the layer is also peeled off, the peripheral portion is cut off, and the whole is irradiated with ultraviolet rays for 60 seconds to be completely cured, so that FIGS. A micro nozzle [D1] having the shape shown in FIG. 7 was produced.

That is, this micro nozzle is formed by the member (A)
A channel (6) extending in a horizontal direction (that is, a direction parallel to the nozzle surface) between the member (B) and the member (B).
There are also flow paths (10) extending in the horizontal direction, and the flow paths (4 ′) and (7, 7 ′) extending in the vertical direction in the member (B) and the member (B). ), (5, 5 ′, 5 ″, 5 ′ ″) and (9 ″, 9 ′ ″), and the flow path (A) (13) in the member (A). ), The discharge port (2) and the injection ports (5 ′ ″, 9 ′ ″) are connected to each other. Also, the flow paths (5, 5 ', 5 ", 5"') and (9 ", 9 '") have a well shape.

Further, a brass rod (not shown) having a diameter of 2 mm was placed on the part of the member (B) opposite to the area where the central discharge port (2) was formed on the micro nozzle by an epoxy adhesive. Vertically bonded.

(Material property test) Separately, the OPP film used for preparing the above member was used as a temporary support,
The composition (A) 1 or B1 is applied thereon, cured by irradiating the same ultraviolet ray as above for 60 seconds, and the coating film is peeled off from the temporary support to form a sheet-shaped molded product having a thickness of 185 μm. It was manufactured and subjected to a tensile test and measurement of a contact angle. As a result, the cured product of composition (A) 1 had a tensile modulus of 1.6 GPa, a breaking elongation of 2.8%, and a contact angle with water of 81 degrees. Further, the properties of the composition (B) cured product are as follows:
Tensile modulus is 580 MPa, elongation at break is 7.2%,
The contact angle with water was 13 degrees.

(Spotting test) 0.01% of fluorescin (manufactured by Wako Pure Chemical Industries) and an average molecular weight of about 2,000
Aqueous solution containing 1% of polyethylene glycol (manufactured by Soka Chemical Co., Ltd.) was fully filled into 16 wells (5 ′ ″) and (9 ′ ″) of the manufactured micro nozzle using a syringe. The solution spontaneously entered the flow channel and reached the nozzle surface, but did not drip from the discharge port (2) or wet the nozzle surface.

The micro nozzle [D1] was pressed in a stamping manner onto an OHP sheet for ink-jet printing with a brass bar, and the OHP sheet was immediately dried with hot air using a hair dryer. Irradiation with a black light under a microscope revealed fluorescence of 16 spots.

Example 2 (Preparation of Micro Nozzle) Discharge ports were arranged in a matrix of 10 rows × 10 columns, the number of resin layers having a linear flow path, and the number of holes formed between them. Example 1 was the same as Example 1 except that the number of the resin layers having the flow path was 5, and that the micro nozzle was formed into a shape that was a part of a cylinder having a diameter of about 1 m, with the member (A) side being convex. Similarly,
The discharge port is 100 μm in diameter, the center-to-center distance is 300 μm, the linear flow path in the layer is 150 μm in width, the height is about 185 μm, the vertical flow path penetrating the layer is 200 μm in diameter, and the diameter of the injection port used as a well is 1 mm. Dimensions 26 mm x
A 26 mm 100-hole micro nozzle [D2] was prepared. Further, a portion having a diameter of 4 m is provided on a portion of the micro nozzle [D2] opposite to the area where the discharge port at the center is formed.
An mx 4 mm brass square bar (not shown) was vertically bonded with an epoxy adhesive.

(Spotting test) Spotting was performed in the same manner as in Example 1 except that spotting was performed by rolling the nozzle surface on an OHP sheet. As a result, fluorescence of 100 spots was observed.

Example 3 (Production of Micro Nozzle) 100 discharge ports were formed in one row, and a resin layer having a linear flow path was provided with 20 flow paths each. 5 layers, 5 layers of resin layers having hole-shaped flow paths provided between the layers, 20 holes × 5 rows of injection ports used as wells, and In the same manner as in Example 1 except that the nozzle surface of the micro nozzle is a part of a cylinder having a diameter of about 30 cm (however, the direction in which the discharge port is in the same plane), the discharge port has a diameter of 100 μm, and the center-to-center distance. 300 μm
The linear flow path in the layer has a width of 150 μm and a height of about 185 μm.
m, the vertical channel passing through the layer is 200 μm in diameter, the diameter of the well is 1 mm, and the external dimensions are 15 mm × 50 mm.
A 00-hole micro nozzle [D3] was prepared.

Further, an acrylic plate (not shown) having a width of 50 mm, a thickness of 2 mm, and a height of 30 mm was applied to a portion of the nozzle member (B) opposite to the area where the discharge port was formed using an epoxy adhesive. Glued vertically.

(Spotting Test) When spotting was performed in the same manner as in Example 1, fluorescence of 100 spots was observed. In addition, 500 spotting operations
When the measurement was performed 100 times with the distance between the centers of μm, 10,000 spots were formed.

Example 4 (Preparation of Micro Nozzle) Except that the distance between the centers of the discharge port and the injection port, the dimension of the flow path, and the thickness of each layer were different,
In the same manner as in Example 1, the outlet has a diameter of about 10 μm, the center-to-center distance is 30 μm, and the linear flow path in the layer has a height of about 20 μm near the connection with the outlet and about 100 μm in the other part. About 35 μm, a vertical flow path penetrating the layer has a diameter of about 20 μm near the connection with the discharge port, and the other part has a diameter of 100 μm.
Outer dimensions 5 mm x 5 mm with well diameter of 1 mm
No. 16 hole micro nozzle [D4] was manufactured. Further, a stainless rod having a diameter of 1 mm was vertically bonded to a portion of the micro nozzle, which faced the area where the discharge port was formed, with an epoxy adhesive.

(Spotting Test) When spotting was performed in the same manner as in Example 1, fluorescence was observed at 16 spots.

Example 5 (Preparation of Micro Nozzle) Six discharge ports were formed in one row, and a resin layer having a linear flow path was provided with six flow paths. A discharge port having a diameter of 200 μm and a center-to-center distance of 500 μm was formed in the resin layer in the same manner as in Example 1 except that the injection port used as a well was provided in 3 holes × 2 rows. Is 150 μm wide,
A micronozzle precursor having a height of about 185 μm and a well diameter of 1.6 mm was prepared.

On the member (B) side of this micro-nozzle precursor, holes each serving as six wells having a diameter of 1.6 mm were formed at the position of the injection port, and the external dimensions were 25 mm × 75 mm × 3 mm.
(Available from Dainippon Ink and Chemicals, Inc.) was bonded to the composition A1 using ultraviolet light.

Further, as a temporary support, Example 1 was used.
The composition A1 was applied to the corona-treated surface of the same OPP sheet (not shown) as used in the above using a 50 μm bar coater, and a portion formed as a spacer was irradiated with ultraviolet rays for 2 seconds using a photomask. A semi-cured coating film having lost fluidity, and a non-irradiated portion of the uncured composition A1,
The semi-cured spacer is cured by being blown off with compressed air, being brought into close contact with the discharge port forming surface of the micro-nozzle precursor, and being irradiated with ultraviolet rays for 30 seconds to be simultaneously fixed to the member (A). Then, the OPP sheet was peeled off. By the above operation, 500 μm × 500 μ
m, a rectangular spacer having a thickness of about 25 μm is provided on both sides of the row of discharge ports at a distance of 1 m from a line passing through the center of each discharge port.
A 6-hole nozzle [D5] having an outer dimension of 25 mm × 75 mm was prepared in which each of 7 pieces was arranged in two rows with m and the interval between the rectangles was arranged at 500 μm.

(Spotting test) The micro nozzle [D5] was used, and 25 mm ×
75 mm, 1 mm thick aldehyde-based fixed glass slide [Telechem International
Organoaldehyde SMA, manufactured by Rnational Inc.), and a fluorescent-labeled DNA fragment having an amino group [Espec Oligo Service, 5'-
C6 amino group-3'-FITC-26 base oligonucleotide) and microspotting solution [Telechem International
Inc.) was used in the same manner as in Example 1 except that a 1/1 mixed solution was used. The object to be coated was held at 50 ° C. for 1 hour, washed with water, dried with hot air, and observed with a fluorescence microscope (Olympus).
Six 00 μm fluorescent spots were observed.

Example 6 (Preparation of Micro Nozzle) Each well of the inlet of the micro nozzle [D5] prepared in Example 5 had an outer diameter of 1.6 m.
A polyethylene tube having an inner diameter of 0.5 mm and an inner diameter of 0.5 mm was bonded with a cyanoacrylate-based adhesive (Aron Alpha +, manufactured by Toa Gosei Chemical Co., Ltd.) to form a micro nozzle [D6].

(Preparation of Spotter) A vertically movable pedestal equipped with a mechanism for fixing an object to be applied at a fixed position by a positioning pin and a vacuum, and a spot to be applied through a hole fixed to the pedestal and provided in the pedestal. A television camera (manufactured by Sony) for observing the forming section, an image monitor for projecting an image picked up by the television camera, a micro-nozzle mounting mechanism for holding the micro-nozzle [D6] at a fixed position with a positioning pin and a vacuum, and 6 stations A spotter having a macro syringe pump was manufactured, and a micro nozzle [D
6] The other end of each tube is filled with the same solution containing a fluorescent soldier-labeled DNA fragment as that used in Example 5, and a 6-micro syringe pump (manufactured by KD Scientific,
(IC-3260 type).

(Spotting test) The same aldehyde go-fixed slide glass as that used in Example 5 was used as an object to be applied, and the slide glass was placed horizontally above the pedestal, and the spacer of the micro nozzle [D6] was the slide glass of the object to be applied. The pedestal was raised until contact was made. Then, the above 6
Fluorescent label D from each syringe of the micro-syringe pump
When the NA fragment-containing solution was introduced into the micro-nozzle at a rate of 1 μL / min (set value), the DNA solution was slowly discharged from the discharge port of the micro-nozzle and swelled in a hemispherical shape.
It adhered to the surface of the application object. At that point, the syringe pump was stopped and the pedestal was lowered to separate it from the micro nozzle. The object to be coated was treated in the same manner as in Example 5 and observed with a fluorescence microscope. As a result, six fluorescent spots having a diameter equal to that of Example 5 and having a diameter of about 500 μm were observed.

[0200]

According to the present invention, a plurality of spots can be formed simultaneously and easily with a large number of spots being discharged simultaneously from a plurality of discharge ports through respective individual flow paths without contamination between the solutions. A nozzle, a manufacturing method thereof, a spotting method using the micro nozzle, and a spotter equipped with the micro nozzle can be provided. ADVANTAGE OF THE INVENTION The micro nozzle of this invention can perform spotting of many different types of solutions at high speed, and it is easy to supply different application liquids to each discharge port.

[0201]

[Brief description of the drawings]

FIG. 1 is a schematic plan view of a member (A) of a micro nozzle manufactured in Examples 1 and 4.

FIG. 2 is a schematic plan view of a first layer constituting a member (B) of a micronozzle manufactured in Examples 1 and 4.

FIG. 3 is a schematic plan view of a second layer constituting a member (B) of a micro nozzle manufactured in Examples 1 and 4.

FIG. 4 is a schematic plan view of a third layer constituting a member (B) of a micro nozzle manufactured in Examples 1 and 4.

FIG. 5 is a schematic plan view of a fourth layer constituting a member (B) of the micro nozzle manufactured in Examples 1 and 4.

FIG. 6 is a schematic diagram of a plan view of a micro nozzle manufactured in Examples 1 and 4.

FIG. 7 is a schematic view of an elevation view of the micro nozzle manufactured in Examples 1 and 4. In the figure, continuous cavities serving as discharge ports, flow paths (A), flow paths, wells, and injection ports are shown in white.

FIG. 8 is a schematic plan view of a micro nozzle used in the description of the present invention.

FIG. 9 is a schematic view of an elevation view of a micro nozzle used for describing the present invention.

[Explanation of symbols]

1: Member (A) 2: Discharge port 3: Member (B) first layer 4: Position corresponding to discharge port in outer row of member (A) 4 ': Hole-shaped defective portion, flow path 4 ": Perforated defect, flow path 5: Perforated defect, flow path, well 5 ': Perforated defect, flow path, well 5 ": Perforated defect, flow path, well 5''' : Porous defect, flow path, well, inlet 6: Linear defect 7: Porous defect 7 ′: Porous defect 7 ″: Position corresponding to defect (7 ′) 8 : Member (B) second layer 9 ″: Porous defect, flow path, well 9 ′ ″: Porous defect, flow path, well, injection port 10: Linear defect 11: Member ( B) Third layer 12: Member (B) fourth layer 13: Channel (A) 21: Member (A) 22: Member (B) first layer 23: Member (B) second layer 24, 24 ', 24 ″, 24 ′ ″: discharge ports 25, 25 ′, 25 , 25 ''': linear defect,
Grooves, channels 26, 26 ', 26 ", 26"': hole-shaped defects, channels, wells 27, 27 ', 27 ", 27'": inlets 28, 28 ', 28 ", 28 ''': Channel (A)

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Atsushi Teramae 11-67 Fari-term, Karimaru, Yachimata-shi, Chiba 2G042 BD19 CB03 EA20 FB05 HA02 2G058 AA09 EA05 EA11 ED12 ED19

Claims (17)

[Claims] 1. A micro-nozzle having four or more capillary channels independent of each other, and a discharge port and an injection port of each flow path, wherein the distance between the centers of adjacent discharge ports is equal to or smaller than that of the discharge port. A micro nozzle having a diameter of 4 to 10000 times the diameter, wherein the distance between centers of adjacent inlets is larger than the distance between centers of adjacent outlets, and the diameter of the inlet is larger than the diameter of the outlet. . 2. The micro-nozzle according to claim 1, wherein the micro-nozzle is made of an active energy ray-curable composition. 3. The micro-nozzle is formed by laminating a member (A) and a member (B), and the member (A) has four or more independent capillary tubes penetrating the member (A). The member (B) having a flow path in the shape of an arrow and a discharge port of each flow path, wherein the member (B) is made of a cured product of the active energy ray-curable composition, and is connected to the discharge port of the member (A). The micronozzle according to claim 1, further comprising a defective portion that forms a flow path on a surface laminated with the flow path or the member (A). 4. The micro-nozzle is formed by laminating a member (A) and a member (B), and the member (A) has four or more independent capillary tubes penetrating the member (A). Member (B) having a flow path in the shape of an arrow and a discharge port of each flow path, wherein the member (B) is made of a cured product of the active energy ray-curable composition, and is connected to the discharge port of the member (A). The micronozzle according to claim 1, further comprising: a defective portion that forms a flow path and an injection port on a surface where the flow path and the member (A) are stacked. 5. A member (B1) having an inlet and a flow path in a member connected to the inlet, and a surface on which the member (A) and the member (B1) are laminated. The micronozzle according to claim 4, further comprising a defective portion forming a flow path or a member (B2) having a flow path in the member. 6. The member (B) includes a member (B1) having an inlet and a flow path in a member connected to the inlet, and a defective portion forming a flow path on a surface where the members are stacked. A member (B3) having a flow path in the member, a member (A) and a member (B
The micronozzle according to claim 4, further comprising a member (B2) having a flow path in the member or a defective portion forming a flow path with the surface laminated with (3). 7. The capillary channel has a contact angle of 4 with water.
The micronozzle according to claim 1, wherein the micronozzle is formed of a material having a degree of less than 5 degrees. 8. The micro nozzle according to claim 1, wherein the surface of the member (A) provided with the discharge port has a contact angle with water of 45 degrees or more. 9. The micro nozzle according to claim 1, wherein a spacer having a thickness of 1 to 100 μm is formed on a surface of the member (A) provided with the discharge port. 10. The method for manufacturing a micro nozzle according to claim 1, wherein four or more independent capillary flow paths penetrating the member and a member (A) having a discharge port of each flow path are provided. A member having a flow path in a member connected to a discharge port of the member (A) or a defective portion forming a flow path with the member (A), and made of a semi-cured active energy ray-curable composition (B), and then irradiating an active energy ray to cure the member (B) and adhere the member (A) to the member (B). 11. The method of manufacturing a micro nozzle according to claim 1, comprising: four or more independent capillary flow paths penetrating the member and discharge ports of each flow path; Member (A) consisting of semi-cured product of curable composition
And a member (B) having a deficient portion forming a flow path with the flow path or the member (A) in the member connected to the discharge port of the member (A), and then irradiating active energy rays. A member (A) and a member (A) and a member (B) are adhered to each other by curing the member (A). 12. The member (B2) according to claim 10, wherein the member (B) is a member (B2) having a defective portion forming a flow path with the surface on which the member (A) is laminated and a flow path in the member. A manufacturing method of the micro nozzle according to the above. 13. A spotting method using the micro-nozzle according to claim 1 to apply an application liquid to an application target in a dot-like manner. 14. The spotting method according to claim 13, wherein the application liquid is supplied to the discharge port by capillary action. 15. The coating liquid having a viscosity of 5 to 500 mPa · s.
The spotting method according to claim 14, wherein 16. The spotting method according to claim 15, wherein a water-soluble polymer is added to the coating solution. 17. A spotter having the micro nozzle according to claim 1.